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Hatia RI, Hwang LY, Li R, Troisi C, Jalal PK, Amos CI, Gomez HF, Chun YS, Rashid A, Kaseb AO, Scheet PA, Hassan MM. Risk and Prognosis of Hepatocellular Carcinoma in Mexican Americans with Type 2 Diabetes Mellitus. J Hepatocell Carcinoma 2025; 12:93-106. [PMID: 39867264 PMCID: PMC11762437 DOI: 10.2147/jhc.s477141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 09/26/2024] [Indexed: 01/28/2025] Open
Abstract
Introduction Hepatocellular carcinoma (HCC) disproportionately affects Hispanic persons with higher age-specific incidence and increased mortality rates compared to non-Hispanic Whites. These high rates of incidence and mortality may be explained by the variation in risk factors. Given the high prevalence of type 2 diabetes mellitus (DM) among the Hispanic population, we aimed to assess the risk and prognosis of HCC in Mexican Americans with type 2 DM with consideration of treatment for DM. Methods A case-control study of 241 Mexican American HCC patients and 500 healthy controls in Texas was conducted. Multivariable logistic regression analysis was performed to determine the association between type 2 DM and HCC risk while adjusting for other risk factors. Also, a restricted analysis of patients with type 2 DM was conducted to determine the effects of age at onset and duration of DM on HCC risk. Interactions among DM, heavy alcohol consumption, and viral hepatitis infection were examined. Overall survival was examined, and multivariable Cox proportional hazards regression analysis was performed for HCC patients with type 2 DM. Results The adjusted odds ratio (AOR) for DM was 2.74 (P < 0.01). Compared with patients who had DM for 2-10 years, those who had it for at least 20 years had an AOR of 4.60 (P = 0.04). Metformin use was associated with a reduced risk of death in HCC cases with type 2 DM, with a hazard ratio of 0.72 (P = 0.01) as compared with non-users. Conclusion Our results demonstrate that type 2 DM was independently associated with increased risk of HCC among Mexican Americans. Metformin use was associated with improved survival among HCC patients with type 2 DM. Type 2 DM significantly increased the risk of HCC alone and in conjunction with other parameters of metabolic syndrome in the Mexican American population after adjusting for other risk factors.
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Affiliation(s)
- Rikita I Hatia
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Lu-Yu Hwang
- Department of Epidemiology, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Ruosha Li
- Department of Biostatistics and Data Science, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Catherine Troisi
- Department of Management, Policy & Community Health, School of Public Health, The University of Health Science Center at Houston, Houston, TX, USA
| | - Prasun K Jalal
- Department of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX, USA
| | - Christopher I Amos
- Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA
| | - Henry F Gomez
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Yun Shin Chun
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Asif Rashid
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ahmed O Kaseb
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Paul A Scheet
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Manal M Hassan
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Maezawa Y, Kodama Y, Ariga H, Kashimura J, Irie T. Hepatocellular Carcinoma Developing in a Patient 29 Years After Achieving Sustained Virologic Response for Hepatitis C With Interferon Therapy: A Case Report. Cureus 2024; 16:e74330. [PMID: 39720368 PMCID: PMC11667130 DOI: 10.7759/cureus.74330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/23/2024] [Indexed: 12/26/2024] Open
Abstract
We report a case of an 87-year-old female with a ruptured hepatocellular carcinoma (HCC). She presented with sudden epigastric and right upper abdominal pain. The physical examination revealed mild tenderness in the right upper abdomen, a positive Murphy's sign, and no jaundice. Laboratory tests showed mild anemia and elevated PIVKA-II (prothrombin induced by vitamin K absence II) levels. Abdominal ultrasound and CT revealed a large hypervascular mass in the liver, along with ascites and portal vein thrombosis. The patient had received interferon therapy for hepatitis C virus (HCV) 29 years before her presentation and blood tests and imaging examinations had confirmed sustained undetectability for HCV ribonucleic acid (RNA) and the absence of HCC for five years following treatment. HCV RNA remained undetectable at the time of her admission, and it was presumed that it had been negative for 29 years post-treatment, with no evidence of re-exposure. The patient had not attended any follow-up appointments. While there have been no reported cases of a patient developing HCC 29 years after achieving sustained virologic response (SVR), our case suggests that the absence of HCC risk is not guaranteed, even after a prolonged period post-SVR. Therefore, periodic imaging tests such as abdominal ultrasound or CT may be beneficial in detecting potential HCC, even long after achieving SVR.
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Affiliation(s)
- Yosuke Maezawa
- Department of Internal Medicine, Mito Kyodo General Hospital, Mito, JPN
| | - Yukiko Kodama
- Department of Internal Medicine, Mito Kyodo General Hospital, Mito, JPN
| | - Hiroyuki Ariga
- Department of Gastroenterology, Mito Kyodo General Hospital, Mito, JPN
| | - Junya Kashimura
- Department of Gastroenterology, Mito Kyodo General Hospital, Mito, JPN
| | - Toshiyuki Irie
- Department of Radiology, Mito Kyodo General Hospital, Mito, JPN
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Ohama H, Hiraoka A, Tada T, Kariyama K, Itobayashi E, Tsuji K, Ishikawa T, Toyoda H, Hatanaka T, Kakizaki S, Naganuma A, Tada F, Tanaka H, Nakamura S, Nouso K, Tanaka K, Kumada T. Changes in clinical outcomes in Japanese patients with hepatocellular carcinoma due to hepatitis C virus following the development of direct-acting antiviral agents. J Gastroenterol Hepatol 2024; 39:1394-1402. [PMID: 38602340 DOI: 10.1111/jgh.16553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Revised: 03/11/2024] [Accepted: 03/20/2024] [Indexed: 04/12/2024]
Abstract
BACKGROUND AND AIM Direct-acting antivirals (DAAs) have been accessible in Japan since 2014. The aim of this study is to compare how the prognosis of patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCV-HCC) changed before and after DAA development. METHODS A retrospective analysis of 1949 Japanese HCV-HCC patients from January 2000 to January 2023 categorized them into pre-DAA (before 2013, n = 1169) and post-DAA (after 2014, n = 780) groups. Changes in clinical features and prognosis were assessed. RESULTS Despite no significant differences in BCLC stage between groups, the post-DAA group exhibited higher rates of sustained virological response (SVR) (45.6% vs. 9.8%), older age (73 vs 69 years), lower levels of AST (40 vs 56 IU/L), ALT (31 vs 46 IU/L), and AFP (11.7 vs 23.6 ng/mL), higher platelet count (13.5 vs 10.8 × 104/μL), better prothrombin time (88.0% vs 81.9%), and better ALBI score (-2.54 vs -2.36) (all P < 0.001). The post-DAA group also showed higher rates of curative treatments (74.1% vs 65.2%) and significantly improved recurrence-free survival (median 2.8 vs 2.1 years). Adjusted for inverse probability weighting, overall survival was superior in the post-DAA group (median 7.4 vs 5.6 years, P < 0.001). Subanalysis within the post-DAA group revealed significantly shorter overall survival for patients without SVR (median 4.8 years vs NA vs NA) compared to pre-SVR or post-SVR patients (both P < 0.001). No significant difference in OS was observed between the pre-SVR and post-SVR groups (P = 1.0). CONCLUSION The development of DAA therapy has dramatically improved the prognosis of HCV-HCC patients.
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Affiliation(s)
- Hideko Ohama
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
- Department of Gastroenterology, Takarazuka City Hospital, Hyogo, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Toshifumi Tada
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan
| | - Kazuya Kariyama
- Department of Hepatology, Okayama City Hospital, Okayama, Japan
| | - Ei Itobayashi
- Department of Gastroenterology, Asahi General Hospital, Asahi, Japan
| | - Kunihiko Tsuji
- Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Toru Ishikawa
- Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takeshi Hatanaka
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Gunma, Japan
| | - Satoru Kakizaki
- Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan
| | - Atsushi Naganuma
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan
| | - Fujimasa Tada
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Hironori Tanaka
- Department of Gastroenterology, Takarazuka City Hospital, Hyogo, Japan
| | - Shinichiro Nakamura
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan
| | - Kazuhiro Nouso
- Department of Hepatology, Okayama City Hospital, Okayama, Japan
| | - Kazunari Tanaka
- Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Takashi Kumada
- Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan
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Suzuki T, Matsuura K, Nagura Y, Kawamura H, Fujiwara K, Ogawa S, Nagaoka K, Iio E, Watanabe T, Kataoka H, Tanaka Y. Serum Angiopoietin-2 Levels Predict the Development of Hepatocellular Carcinoma following Hepatitis C Virus Eradication Using Direct-Acting Antiviral Agents. Oncology 2024; 102:611-620. [PMID: 38211572 DOI: 10.1159/000536154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Accepted: 12/31/2023] [Indexed: 01/13/2024]
Abstract
INTRODUCTION Our previous studies showed that serum angiopoietin-2 (Ang-2) and C-X-C motif chemokine ligand 10 (CXCL10) levels predicted improvement in liver fibrosis following sustained virological response (SVR) of hepatitis C virus (HCV) obtained with administration of with direct-acting antiviral agents (DAAs). These levels were evaluated retrospectively as predictive indicators of hepatocellular carcinoma (HCC) development following SVR. METHODS We enrolled individuals from a historical cohort of 89 chronic HCV patients without history of HCC at baseline and with SVR following DAA therapy and had baseline serum levels of Mac-2 binding protein glycosylation isomer ≥2.0 cut-off index (C.O.I.). RESULTS Multivariate analyses revealed that only the Ang-2 level at 24 weeks following the end of treatment (EOT24W) was significantly related to HCC development (hazard ratio 2.27; p = 0.003). This result was reproduced in individuals without history of HCC and with advanced liver fibrosis (M2BPGi level ≥3.3 C.O.I. at baseline). Time-dependent receiver operating characteristic curve analyses for the future risk of developing HCC within 5 years of follow-up (5y-HCC) showed the best cut-off Ang-2 level at the EOT24W was 2,780 pg/mL, and significantly stratified the cumulative incidence of HCC (≥2,780 vs. < 2,780 pg/mL, 5y-HCC: 45.5 vs. 8.2%, p < 0.001). CONCLUSIONS At the EOT24W, serum Ang-2 level predicts the likelihood of developing HCC following SVR to DAA therapy.
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Affiliation(s)
- Takanori Suzuki
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kentaro Matsuura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yoshihito Nagura
- Department of Gastroenterology, Kasugai Municipal Hospital, Kasugai, Japan
| | - Hayato Kawamura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kei Fujiwara
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Shintaro Ogawa
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Katsuya Nagaoka
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Etsuko Iio
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Takehisa Watanabe
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hiromi Kataoka
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
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Sacco M, Ribaldone DG, Saracco GM. Metformin and Hepatocellular Carcinoma Risk Reduction in Diabetic Patients with Chronic Hepatitis C: Fact or Fiction? Viruses 2023; 15:2451. [PMID: 38140692 PMCID: PMC10748230 DOI: 10.3390/v15122451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Revised: 12/07/2023] [Accepted: 12/15/2023] [Indexed: 12/24/2023] Open
Abstract
BACKGROUND Patients with chronic hepatitis C (CHC) and concomitant type 2 diabetes mellitus (DM) show a higher risk of developing hepatocellular carcinoma (HCC). Successful antiviral therapy has reduced the incidence of post-therapy HCC, but the presence of DM still represents an unfavourable predictive factor even in cured patients. Metformin (MET) is recommended as a first-line therapy for DM, and its use is associated with a significant reduction in HCC among diabetic patients with chronic liver disease of different etiology, but very few studies specifically address this issue in patients with CHC. AIM the aim of this review is to evaluate whether the use of MET induces a significant decrease in HCC in diabetic patients with CHC, treated or untreated with antiviral therapy. METHODS A search of PubMed, Medline, Web of Sciences and Embase was conducted for publications evaluating the role of MET in reducing the risk of HCC in patients with DM and CHC, with no language and study type restrictions up to 30 June 2023. Only studies fulfilling the following inclusion criteria were considered: (1) data on the incidence of HCC in the follow-up of diabetic patients with CHC only; (2) follow-up ≥24 months; (3) sufficient data to establish the rate of diabetic patients with CHC treated with metformin or other antidiabetic medications; and (4) data on the type of antiviral treatment and the clinical outcome. RESULTS Three studies met the inclusion criteria. A prospective cohort study considering only patients with DM and untreated advanced CHC, or non-responders to interferon (IFN) therapy, showed that the use of MET was associated with a significant decrease in HCC incidence, liver-related death and liver transplants. A recent retrospective study focusing on a large-scale nationwide cohort of patients with CHC in Taiwan successfully treated with IFN-based therapy stratified patients into 3 groups: non-MET users, MET users and non-diabetic patients, with 5-year cumulative rates of HCC of 10.9%, 2.6% and 3.0%, respectively, showing a significantly higher HCC risk in non-MET users compared with MET users and with non-diabetic patients, while it was not significantly different between MET users and non-diabetic patients. In a recent Italian cohort study focusing on 7007 patients with CHC treated and cured with direct-acting antiviral agents (DAAs), a combined effect of DM and MET therapy was found, showing a higher incidence of HCC in diabetic patients not taking MET compared with those without DM and those with DM taking MET. CONCLUSION according to the current evidence, the use of MET should be encouraged in diabetic patients with CHC in order to reduce the risk of HCC; however, a well-designed randomized controlled trial is needed to establish the generalizability of the beneficial effects of MET in this particular subset of patients.
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Affiliation(s)
| | | | - Giorgio Maria Saracco
- Gastro-Hepatoloy Unit, Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (M.S.); (D.G.R.)
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Yoshida Y, Atsukawa M, Kondo C, Kitamura M, Shioda-Koyano K, Kawano T, Ono H, Hayama K, Okubo T, Arai T, Itokawa N, Iwakiri K. A novel formula used for predicting hepatocellular carcinoma after the achievement of sustained virologic response by direct-acting antivirals in patients with chronic hepatitis C. PLoS One 2023; 18:e0292019. [PMID: 37733802 PMCID: PMC10513247 DOI: 10.1371/journal.pone.0292019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 09/08/2023] [Indexed: 09/23/2023] Open
Abstract
Although eliminating HCV can prevent hepatocellular carcinoma (HCC), some patients develop HCC even after obtaining sustained virologic response (SVR). Previously, we developed a new formula to predict advanced liver fibrosis. This study aimed to clarify the usefulness of this formula for predicting HCC after achieving SVR. Among 351 consecutive patients who had been treated with direct-acting antivirals, 299 were included in this study. New formula scores were used as a marker for predicting liver fibrosis and as a predictive model for HCC incidence. The participants were 172 men and 127 women with a median age of 68 years. The median new formula score was -1.291. The cumulative HCC incidence rates were 4.3%, 9.7%, and 12.5% at 1, 3, and 5 years, respectively. The cumulative incidence of HCC was significantly higher in patients with a history of HCC than in those without treatment history of HCC (P = 2.52×10-26). Multivariate analysis revealed that male (HR = 6.584, 95% CI = 1.291-33.573, P = 0.023) and new formula score (HR = 1.741, 95% CI = 1.041-2.911, P = 0.035) were independent factors associated with the development of HCC in patients without a treatment history of HCC. The optimal cutoff value for predicting the development of HCC was -0.214. The cumulative incidence rates of HCC in patients with new formula scores ≥-0.214 were 5.4%, 15.3%, and 15.3% at 1, 3, and 5 years, respectively, whereas the incidence rates of HCC in patients with new formula scores <-0.214 were 0.0%, 0.6%, and 4.8%, respectively (P = 2.12×10-4). In conclusion, this study demonstrated the usefulness of new formula scores as a predictor of HCC after achieving SVR, especially in patients without past treatment history of treatment for HCC.
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Affiliation(s)
- Yuji Yoshida
- Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Masanori Atsukawa
- Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Chisa Kondo
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Michika Kitamura
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Kaori Shioda-Koyano
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Tadamichi Kawano
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Hiroki Ono
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Korenobu Hayama
- Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Tomomi Okubo
- Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Taeang Arai
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Norio Itokawa
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Katsuhiko Iwakiri
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
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Wang Y, Deng B. Hepatocellular carcinoma: molecular mechanism, targeted therapy, and biomarkers. Cancer Metastasis Rev 2023; 42:629-652. [PMID: 36729264 DOI: 10.1007/s10555-023-10084-4] [Citation(s) in RCA: 145] [Impact Index Per Article: 72.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 01/16/2023] [Indexed: 02/03/2023]
Abstract
Hepatocellular carcinoma (HCC) is a common malignancy and one of the leading causes of cancer-related death. The biological process of HCC is complex, with multiple factors leading to the broken of the balance of inactivation and activation of tumor suppressor genes and oncogenes, the abnormal activation of molecular signaling pathways, the differentiation of HCC cells, and the regulation of angiogenesis. Due to the insidious onset of HCC, at the time of first diagnosis, less than 30% of HCC patients are candidates for radical treatment. Systematic antitumor therapy is the hope for the treatment of patients with middle-advanced HCC. Despite the emergence of new systemic therapies, survival rates for advanced HCC patients remain low. The complex pathogenesis of HCC has inspired researchers to explore a variety of biomolecular targeted therapeutics targeting specific targets. Correct understanding of the molecular mechanism of HCC occurrence is key to seeking effective targeted therapy. Research on biomarkers for HCC treatment is also advancing. Here, we explore the molecular mechanism that are associated with HCC development, summarize targeted therapies for HCC, and discuss potential biomarkers that may drive therapies.
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Affiliation(s)
- Yu Wang
- Department of Infectious Diseases, The First Hospital of China Medical University, 155 Nanjing North Street, Shenyang, 110001, Liaoning Province, China
| | - Baocheng Deng
- Department of Infectious Diseases, The First Hospital of China Medical University, 155 Nanjing North Street, Shenyang, 110001, Liaoning Province, China.
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Konishi F, Miyake T, Watanabe T, Tokumoto Y, Furukawa S, Matsuura B, Yoshida O, Miyazaki M, Shiomi A, Kanzaki S, Nakaguchi H, Nakamura Y, Imai Y, Koizumi M, Yamamoto Y, Koizumi Y, Hirooka M, Takeshita E, Kumagi T, Ikeda Y, Abe M, Hiasa Y. Association of abnormal glucose tolerance with liver-related disease and cardiovascular diseases in patients with chronic hepatitis C. Hepatol Res 2023; 53:806-814. [PMID: 37183992 DOI: 10.1111/hepr.13925] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 05/06/2023] [Accepted: 05/08/2023] [Indexed: 05/16/2023]
Abstract
AIM Hepatitis C complicated by diabetes mellitus (DM) is considered a risk factor for the progression of fibrosis and development of hepatocellular carcinoma (HCC) and cardiovascular diseases. However, several studies may have lacked appropriate diagnosis of glucose intolerance. We aimed to examine the risk associated with abnormal glucose intolerance in the development of liver-related diseases, including HCC and complications of liver cirrhosis, such as ascites, esophageal and gastric varices, and hepatic encephalopathy, and cardiovascular diseases in patients with hepatitis C accurately diagnosed with impaired glucose tolerance. METHODS This longitudinal retrospective study included 365 patients with chronic hepatitis C admitted to Ehime University Hospital for anti-hepatitis C therapy between September 1991 and January 2015. Patients were classified into normal glucose tolerance (NGT), prediabetes, and DM groups based on 75-g oral glucose tolerance test results. RESULTS Both univariate and multivariate (adjusted for potential confounders) analyses revealed a significantly higher risk of developing HCC and cardiovascular events in the DM group than in the NGT group. However, in multivariate analysis, liver-related events, particularly liver cirrhosis complications, revealed no significant association. In addition, the prediabetes group had no significant risk of any outcome. CONCLUSIONS Patients with hepatitis C complicated by DM, compared with patients with hepatitis C with NGT or complicated with prediabetes, have a higher risk of HCC and cardiovascular disease events, but not liver-related events, particularly in not developing liver cirrhosis complications. Therefore, appropriate follow-up is required for patients with hepatitis C based on their glucose tolerance status.
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Affiliation(s)
| | - Teruki Miyake
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Takao Watanabe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Yoshio Tokumoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Shinya Furukawa
- Health Services Center, Ehime University, Matsuyama, Ehime, Japan
| | - Bunzo Matsuura
- Department of Lifestyle-related Medicine and Endocrinology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Osamu Yoshida
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Masumi Miyazaki
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Akihito Shiomi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Sayaka Kanzaki
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Hironobu Nakaguchi
- Department of Lifestyle-related Medicine and Endocrinology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Yoshiko Nakamura
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Yusuke Imai
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Mitsuhito Koizumi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Yasunori Yamamoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Yohei Koizumi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Eiji Takeshita
- Department of Inflammatory Bowel Diseases and Therapeutics, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Teru Kumagi
- Postgraduate Medical Education Center, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Yoshio Ikeda
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Masanori Abe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
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Hsu CC, Gopalakrishna H, Mironova M, Lee MH, Chen CJ, Yang HI, Wiese M, Chang KM, Wright EC, Abijo T, Feld JJ, Kaplan DE. Risk of Hepatocellular Carcinoma After Spontaneous Clearance of Hepatitis C Virus and in Noncirrhosis Chronic Hepatitis C Patients With Sustained Virological Response: A Systematic Review. Clin Infect Dis 2023; 77:S245-S256. [PMID: 37579210 PMCID: PMC10425144 DOI: 10.1093/cid/ciad380] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/16/2023] Open
Abstract
In a hepatitis C virus (HCV)-controlled human infection model (CHIM), healthy volunteers are inoculated with HCV and then treated. Residual hepatocellular carcinoma (HCC) risk after viral clearance is an important consideration when evaluating the CHIM. We estimate HCC risk in spontaneously cleared HCV and in noncirrhosis after sustained virological response (SVR) to HCV treatment in a systematic review and using data from 3 cohorts: German anti-D, Taiwan, and US Veterans Affairs (VA). For noncirrhosis SVR, the overall HCC rate is 0.33 per 100 patient-years in meta-analysis. HCC rates for the German, Taiwan, and US Veterans Affairs cohorts are 0, 0.14, and 0.02 per 100 patient-years, respectively. Past hepatitis B virus exposure was not accounted for in the Taiwan cohort, while VA patients were likely tested based on liver disease/risk factors, which may confound HCC outcomes. The German cohort with no HCC after 44 years is most comparable to the CHIM participants. Although it is difficult to precisely estimate HCC risk from an HCV CHIM, the data suggest the risk to be very low or negligible.
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Affiliation(s)
- Christine C Hsu
- Liver Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA
| | - Harish Gopalakrishna
- Liver Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA
| | - Maria Mironova
- Liver Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA
| | - Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - Chien-Jen Chen
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Hwai-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Manfred Wiese
- Department of Hepatology, University Hospital Leipzig, East German HCV Study Group, Leipzig, Germany
| | - Kyong-Mi Chang
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Division of Gastroenterology and Hepatology, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
| | - Elizabeth C Wright
- Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA
| | - Tomilowo Abijo
- Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA
| | - Jordan J Feld
- Department of Medicine, Division of Gastroenterology, Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada
- Toronto Viral Hepatitis Care Network, Toronto, Canada
| | - David E Kaplan
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Division of Gastroenterology and Hepatology, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
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10
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Watanabe T, Tokumoto Y, Joko K, Michitaka K, Horiike N, Tanaka Y, Hiraoka A, Tada F, Ochi H, Kisaka Y, Nakanishi S, Yagi S, Yamauchi K, Higashino M, Hirooka K, Morita M, Okazaki Y, Yukimoto A, Hirooka M, Abe M, Hiasa Y. Simple new clinical score to predict hepatocellular carcinoma after sustained viral response with direct-acting antivirals. Sci Rep 2023; 13:8992. [PMID: 37268672 DOI: 10.1038/s41598-023-36052-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 05/28/2023] [Indexed: 06/04/2023] Open
Abstract
The time point of the most precise predictor of hepatocellular carcinoma (HCC) development after viral eradication with direct-acting antiviral (DAA) therapy is unclear. In this study we developed a scoring system that can accurately predict the occurrence of HCC using data from the optimal time point. A total of 1683 chronic hepatitis C patients without HCC who achieved sustained virological response (SVR) with DAA therapy were split into a training set (999 patients) and a validation set (684 patients). The most accurate predictive scoring system to estimate HCC incidence was developed using each of the factors at baseline, end of treatment, and SVR at 12 weeks (SVR12). Multivariate analysis identified diabetes, the fibrosis-4 (FIB-4) index, and the α-fetoprotein level as independent factors at SVR12 that contributed to HCC development. A prediction model was constructed with these factors that ranged from 0 to 6 points. No HCC was observed in the low-risk group. Five-year cumulative incidence rates of HCC were 1.9% in the intermediate-risk group and 15.3% in the high-risk group. The prediction model at SVR12 most accurately predicted HCC development compared with other time points. This simple scoring system combining factors at SVR12 can accurately evaluate HCC risk after DAA treatment.
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Affiliation(s)
- Takao Watanabe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
| | - Yoshio Tokumoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.
| | - Kouji Joko
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, 1 Bunkyocho, Matsuyama, Ehime, 790-8524, Japan
| | - Kojiro Michitaka
- Department of Gastroenterology, Ehime Prefectural Central Hospital, 83 Kasugamachi, Matsuyama, Ehime, 790-0024, Japan
| | - Norio Horiike
- Department of Gastroenterology, Saiseikai Imabari Hospital, 7-1-6 Kitamura, Imabari, Ehime, 799-1502, Japan
| | - Yoshinori Tanaka
- Department of Gastroenterology, Matsuyama Shimin Hospital, 2-6-5 Ootemachi, Matsuyama, Ehime, 790-0067, Japan
| | - Atsushi Hiraoka
- Department of Gastroenterology, Ehime Prefectural Central Hospital, 83 Kasugamachi, Matsuyama, Ehime, 790-0024, Japan
| | - Fujimasa Tada
- Department of Internal Medicine, Saiseikai Matsuyama Hospital, 880-2 Yamanishicho, Matsuyama, Ehime, 791-8026, Japan
| | - Hironori Ochi
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, 1 Bunkyocho, Matsuyama, Ehime, 790-8524, Japan
| | - Yoshiyasu Kisaka
- Department of Gastroenterology, Uwajima City Hospital, 1-1 Gotenmachi, Uwajima, Ehime, 798-8510, Japan
| | - Seiji Nakanishi
- Department of Gastroenterology, Ehime Prefectural Imabari Hospital, 4-5-5 Ishiicho, Imabari, Ehime, 794-0006, Japan
| | - Sen Yagi
- Department of Internal Medicine, Saiseikai Matsuyama Hospital, 880-2 Yamanishicho, Matsuyama, Ehime, 791-8026, Japan
| | - Kazuhiko Yamauchi
- Department of Gastroenterology, National Hospital Organization Ehime Medical Center, 366 Yokogawara, Toon, Ehime, 791-0203, Japan
| | - Makoto Higashino
- Department of Internal Medicine, Saiseikai Matsuyama Hospital, 880-2 Yamanishicho, Matsuyama, Ehime, 791-8026, Japan
| | - Kana Hirooka
- Department of Gastroenterology, National Hospital Organization Ehime Medical Center, 366 Yokogawara, Toon, Ehime, 791-0203, Japan
| | - Makoto Morita
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
| | - Yuki Okazaki
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
| | - Atsushi Yukimoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
| | - Masanori Abe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
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11
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Yamagiwa Y, Tanaka K, Matsuo K, Wada K, Lin Y, Sugawara Y, Mizoue T, Sawada N, Takimoto H, Ito H, Kitamura T, Sakata R, Kimura T, Tanaka S, Inoue M. Response to antiviral therapy for chronic hepatitis C and risk of hepatocellular carcinoma occurrence in Japan: a systematic review and meta-analysis of observational studies. Sci Rep 2023; 13:3445. [PMID: 36859564 PMCID: PMC9977913 DOI: 10.1038/s41598-023-30467-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Accepted: 02/23/2023] [Indexed: 03/03/2023] Open
Abstract
In Japan, hepatocellular carcinoma (HCC) is a leading cause of cancer mortality and hepatitis C virus infection is a major cause of HCC. We conducted a systematic review and meta-analysis of published studies evaluating patient response to antiviral therapy for chronic hepatitis C on the risk of HCC occurrence in Japan. Articles were searched using terms determined a priori through PubMed, screened by title and abstract, and selected by full-text assessment according to criteria determined a priori, including HCC occurrence in response to interferon (IFN)-based or IFN-free therapy, Japanese study, and 2 or more years of follow-up. We excluded studies on HCC recurrence. We calculated the pooled estimate of the crude incidence rate ratio with data from the selected studies using the person-years method with Poisson regression model and pooled estimate of the hazard ratio adjusted for potential confounders reported by the studies using a random effects model. A total of 26 studies were identified, all of which examined only IFN-based therapy as a result of the selection process. The pooled estimate (95% confidence interval [CI]) of 25 studies was 0.37 (0.33-0.43) for sustained virologic response (SVR) and 1.70 (1.61-1.80) for non-SVR for the HCC incidence rate per 100 person-years, and 0.22 (0.19-0.26) for the incidence rate ratio (SVR vs. non-SVR). The pooled estimate of the hazard ratio (95% CI) of HCC incidence adjusted for potential confounders of 8 studies was 0.25 (0.19-0.34). SVR to interferon therapy for chronic hepatitis C reduces the risk of HCC occurrence.
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Affiliation(s)
- Yoko Yamagiwa
- Division of Prevention, National Cancer Center Institute for Cancer Control, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
- Clinical Research Centers for Medicine, International University of Health and Welfare, Tokyo, Japan
| | - Keitaro Tanaka
- Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga, Japan
| | - Keitaro Matsuo
- Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
| | - Keiko Wada
- Department of Epidemiology and Preventive Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Yingsong Lin
- Department of Public Health, Aichi Medical University School of Medicine, Aichi, Japan
| | - Yumi Sugawara
- Division of Epidemiology, Department of Public Health and Forensic Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Tetsuya Mizoue
- Department of Epidemiology and Prevention, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan
| | - Norie Sawada
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan
| | - Hidemi Takimoto
- Department of Nutritional Epidemiology, National Institute of Health and Nutrition, National Institute of Biomedical Innovation, Health and Nutrition, Tokyo, Japan
| | - Hidemi Ito
- Division of Cancer Information and Control, Department of Preventive Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan
| | - Tetsuhisa Kitamura
- Department of Social Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Ritsu Sakata
- Department of Epidemiology, Radiation Effects Research Foundation, Hiroshima, Japan
| | - Takashi Kimura
- Department of Public Health, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Shiori Tanaka
- Division of Prevention, National Cancer Center Institute for Cancer Control, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Manami Inoue
- Division of Prevention, National Cancer Center Institute for Cancer Control, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan.
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12
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Zhang W, Zhang J, Tang S, Liu Y, Du X, Qiu L, Liu M, Yu H, Pan CQ. Efficacy and Safety of Sofosbuvir-based Regimens in Hepatitis C Patients With Decompensated Cirrhosis: A Systematic Review and Meta-analysis. J Clin Transl Hepatol 2023; 11:144-155. [PMID: 36406321 PMCID: PMC9647115 DOI: 10.14218/jcth.2022.00006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 05/04/2022] [Accepted: 05/13/2022] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND AND AIMS Decompensated cirrhotic patients with hepatitis C (HCV) are often under-represented in clinical trials. We aimed to evaluate pooled data on the efficacy and safety of sofosbuvir (SOF)-based regimens in these patients. METHODS We conducted a systemic review and meta-analysis by searching multiple databases for studies published from October 2010 to October 2020. Outcomes of interest were sustained virologic response (SVR) and safety of SOF-based regimens in decompensated HCV patients. Two reviewers independently performed the study selection and data extraction. RESULTS We included 33 studies that enrolled 5,302 HCV patients. The pooled SVR rate in decompensated patients with SOF-based regimens was 85.1% (95% CI: 82.8-87.3). Patients on SOF/velpatasvir±ribavirin achieved a significantly higher SVR (91.0%, 95% CI: 87.7-93.9) than that of SOF/ledipasvir±ribavirin [(86.3%, 95% CI: 84.6-87.8); p=0.004)], or on SOF/daclatasvir±ribavirin (82.4%, 95% CI: 78.2-86.2%; p<0.001). Adding ribavirin to SOF-based regimens (pooled SVR 84.9%, 95% CI: 81.7-87.9) did not significantly increase the SVR [(83.8% (95% CI: 76.8-89.8%; p=0.76)] in decompensated patients, which was also true in subgroup analyses for each regimen within the same treatment duration. However, adding ribavirin significantly increased the frequency of adverse events from 52.9% (95% CI: 28.0-77.1) to 89.2% (95% CI: 68.1-99.9) and frequency of severe events. The pooled incidence of hepatocellular carcinoma and case-fatality of decompensated patients were 3.1% (95% CI: 1.5-5.0) and 4.6% (95% CI: 3.1-6.3), respectively. The overall heterogeneity was high. There was no publication bias. CONCLUSIONS The analysis found that 12 weeks of SOF/velpatasvir without ribavirin is the preferred therapy, with a significantly higher SVR compared with other SOF-based regimens in decompensated HCV patients.
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Affiliation(s)
- Wenyan Zhang
- Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jing Zhang
- Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Shan Tang
- Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Yali Liu
- Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Xiaofei Du
- Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Lixia Qiu
- Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Menglu Liu
- Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Haibin Yu
- Beijing Youan Hospital, Capital Medical University, Beijing, China
- Correspondence to: Haibin Yu, The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China. ORCID: https://orcid.org/0000-0002-2123-7790. Tel: +86-13811669802, Fax: +86-10-63056962, E-mail: ; Calvin Q Pan, Tisch Hospital of NYU Langone Health, NYU School of Medicine, NY, USA. ORCID: https://orcid.org/0000-0002-3723-6688. Tel: +1-7188887728, Fax: +1-7183536901, E-mail:
| | - Calvin Q. Pan
- Division of Gastroenterology and Hepatology, Department of Medicine, NYU Langone Health, NYU Grossman School of Medicine, New York, USA
- Correspondence to: Haibin Yu, The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China. ORCID: https://orcid.org/0000-0002-2123-7790. Tel: +86-13811669802, Fax: +86-10-63056962, E-mail: ; Calvin Q Pan, Tisch Hospital of NYU Langone Health, NYU School of Medicine, NY, USA. ORCID: https://orcid.org/0000-0002-3723-6688. Tel: +1-7188887728, Fax: +1-7183536901, E-mail:
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13
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Nakatsuka T, Tateishi R. Development and prognosis of hepatocellular carcinoma in patients with diabetes. Clin Mol Hepatol 2023; 29:51-64. [PMID: 35903020 PMCID: PMC9845683 DOI: 10.3350/cmh.2022.0095] [Citation(s) in RCA: 36] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 07/03/2022] [Indexed: 02/02/2023] Open
Abstract
The incidence of diabetes mellitus and hepatocellular carcinoma (HCC) has been increasing worldwide during the last few decades, in the context of an increasing prevalence of obesity and non-alcoholic fatty liver disease (NAFLD). Epidemiologic studies have revealed that patients with diabetes have a 2- to 3-fold increased risk of developing HCC, independent of the severity and cause of the underlying liver disease. A bidirectional relationship exists between diabetes and liver disease: advanced liver disease promotes the onset of diabetes, and HCC is an important cause of death in patients with diabetes; conversely, diabetes is a risk factor for liver fibrosis progression and HCC development, and may worsen the long-term prognosis of patients with HCC. The existence of close interconnections among diabetes, obesity, and NAFLD causes insulin resistance-related hyperinsulinemia, increased oxidative stress, and chronic inflammation, which are assumed to be the underlying causes of hepatocarcinogenesis in patients with diabetes. No appropriate surveillance methods for HCC development in patients with diabetes have been established, and liver diseases, including HCC, are often overlooked as complications of diabetes. Although some antidiabetic drugs are expected to prevent HCC development, further research on the optimal use of antidiabetic drugs aimed at hepatoprotection is warranted. Given the increasing medical and socioeconomic impact of diabetes on HCC development, diabetologists and hepatologists need to work together to develop strategies to address this emerging health issue. This article reviews the current knowledge on the impact of diabetes on the development and progression of HCC.
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Affiliation(s)
- Takuma Nakatsuka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryosuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan,Corresponding author : Ryosuke Tateishi Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan Tel: +81-3-3815-5411, Fax: +81-3-3814-0021, E-mail:
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14
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Wu SY, Chen WM, Chen YC, Chiang MF, Lee MC, Soong RS. Effects of H1-Antihistamines on hepatocellular carcinoma risk in patients with type 2 diabetes mellitus. DIABETES & METABOLISM 2023; 49:101393. [PMID: 36170945 DOI: 10.1016/j.diabet.2022.101393] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 09/18/2022] [Accepted: 09/19/2022] [Indexed: 01/28/2023]
Abstract
PURPOSE H1-antihistamines (AHs) may exert protective effects against cancer. We investigated the association of AH use with hepatocellular carcinoma (HCC) risk in type 2 diabetes mellitus (T2DM) patients without hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. METHODS The data of patients with T2DM enrolled from Taiwan's National Health Insurance Research Database were examined for the period of January 1, 2008, to December 31, 2018. We used the Kaplan-Meier method and Cox proportional hazards regression to evaluate the AH use-HCC risk association. RESULTS After 1:1 propensity score matching was performed, the two cohorts were each divided into AH users (n = 47,990) and nonusers (n = 47,990). The risk of HCC was significantly lower in AH users than in AH nonusers (adjusted hazard ratio [aHR]: 0.55 95% confidence interval [95% CI], 0.46 to 0.67; IRR: 0.70; 95% CI, 0.60 to 0.84), respectively. The dose-response relationship between AH use and HCC risk was also observed (aHRs: 0.58, 0.56, 0.50, and 0.41 for 28-35, 36-49, 50-77, and >77 cumulative defined daily doses of AH, respectively). CONCLUSION AH use can reduce HCC risk in T2DM patients without HBV or HCV infection in a dose-dependent manner.
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Affiliation(s)
- Szu-Yuan Wu
- 1Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, New Taipei City, Taiwan; Artificial Intelligence Development Center, Fu Jen Catholic University, New Taipei City, Taiwan; Department of Food Nutrition and Health Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan; Big Data Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan; Division of Radiation Oncology, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan; Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan; Centers for Regional Anesthesia and Pain Medicine, Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Wan-Ming Chen
- 1Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, New Taipei City, Taiwan; Artificial Intelligence Development Center, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Yi-Chan Chen
- Department of General Surgery, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Ming-Feng Chiang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan 265, Taiwan
| | - Ming-Che Lee
- Department of Surgery, Taipei Municipal Wanfang Hospital, Taipei, Taiwan; College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Ruey-Shyang Soong
- Department of Surgery, Taipei Municipal Wanfang Hospital, Taipei, Taiwan; College of Medicine, Taipei Medical University, Taipei, Taiwan.
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15
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Shin HS, Jun BG, Yi SW. Impact of diabetes, obesity, and dyslipidemia on the risk of hepatocellular carcinoma in patients with chronic liver diseases. Clin Mol Hepatol 2022; 28:773-789. [PMID: 35934813 PMCID: PMC9597232 DOI: 10.3350/cmh.2021.0383] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 04/20/2022] [Indexed: 01/05/2023] Open
Abstract
Despite the increasing prevalence of metabolic disorders, the potential effects of metabolic factors on hepatocellular carcinoma (HCC) development in individuals with chronic liver diseases (CLDs) are not well understood. For a metabolic factor to be identified as a risk factor for HCC in patients with CLDs, such as hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, there should be a strong synergistic interaction between the carcinogenic mechanisms of the metabolic factor and the CLD itself. This review aims to comprehensively summarize the published data on the relationship between metabolic factors such as diabetes mellitus (DM), obesity, and blood lipids and the risk of HCC in patients with CLDs. DM consistently increases the risk of HCC in patients with CLD. When associated with DM, the risk of HCC seems to be highest in HCV and non-alcoholic fatty liver disease (NAFLD), followed by alcoholic liver disease (ALD) and HBV. Obesity may increase the risk of HCC. Among CLDs, the evidence is relatively consistent and clear for ALD, while clear evidence is limited in other CLDs including HBV, HCV, and NAFLD. Total cholesterol, potentially low-density lipoprotein cholesterol and triglyceride, seems to have strong inverse associations with HCC in individuals with CLDs. Despite evidence from observational studies, statins had no effect in preventing HCC in randomized controlled trials. Whether statins have a preventive effect against HCC is unclear. A better understanding and management of metabolic factors may be beneficial to reduce the risk of HCC in patients with CLDs.
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Affiliation(s)
- Hwang Sik Shin
- Department of Family Medicine, Soonchunhyang University Hospital Cheonan, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Baek Gyu Jun
- Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea,Corresponding author : Baek Gyu Jun Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, 1342 Dongil-ro, Nowon-gu, Seoul 01757, Korea Tel: +82-2-950-8889, Fax: +82-2-950-1955, E-mail:
| | - Sang-Wook Yi
- Department of Preventive Medicine and Public Health, College of Medicine, Catholic Kwandong University, Gangneung, Korea,Sang-Wook Yi Department of Preventive Medicine and Public Health, College of Medicine, Catholic Kwandong University, 24 Beomil-ro 579beon-gil, Gangneung 25601, Korea Tel: +82-33-649-7468, Fax: +82-33-641-1074, E-mail:
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16
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Chang SS, Hu HY, Chen YC, Yen YF, Huang N. Late hepatitis C virus diagnosis among patients with newly diagnosed hepatocellular carcinoma: a case–control study. BMC Gastroenterol 2022; 22:425. [PMID: 36115934 PMCID: PMC9482748 DOI: 10.1186/s12876-022-02504-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 09/13/2022] [Indexed: 12/09/2022] Open
Abstract
Abstract
Background
New direct-acting antiviral therapies have revolutionized hepatitis C virus (HCV) infection therapy. Nonetheless, once liver cirrhosis is established, the risk of hepatocellular carcinoma (HCC) still exists despite virus eradication. Late HCV diagnosis hinders timely access to HCV treatment. Thus, we determined trends and risk factors associated with late HCV among patients with a diagnosis of HCC in Taiwan.
Methods
We conducted a population-based unmatched case–control study. 2008–2018 Claims data were derived from the Taiwan National Health Insurance Research Database. Individuals with an initial occurrence of liver cancer between 2012 and 2018 were included. The late HCV group were referred as individuals who were diagnosed with HCC within 3 years after HCV diagnosis. The control group were referred as individuals who were diagnosed more than 3 years after the index date. We used multivariable logistic models to explore individual- and provider-level risk factors associated with a late HCV diagnosis.
Results
A decreasing trend was observed in the prevalence of late HCV-related HCC diagnosis between 2012 and 2018 in Taiwan. On an individual level, male, elderly patients, patients with diabetes mellitus (DM), and patients with alcohol-related disease had significantly higher risks of late HCV-related HCC diagnosis. On a provider level, patients who were mainly cared for by male physicians, internists and family medicine physicians had a significantly lower risk of late diagnosis.
Conclusions
Elderly and patients who have DM and alcohol related disease should receive early HCV screening. In addition to comorbidities, physician factors also matter. HCV screening strategies shall take these higher risk patients and physician factors into consideration to avoid missing opportunities for early intervention.
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Tada T, Kumada T, Matono T, Nakamura S, Sue M, Matsuo Y, Takatani M, Iijima H, Tanaka J. Characteristics of hepatocellular carcinoma in patients with hepatitis C virus who received direct‐acting antiviral therapy and achieved sustained virological response: The impact of a hepatologist on surveillance. JGH Open 2022; 6:462-469. [PMID: 35822120 PMCID: PMC9260217 DOI: 10.1002/jgh3.12774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2022] [Revised: 05/08/2022] [Accepted: 05/14/2022] [Indexed: 11/28/2022]
Abstract
Background and Aim The relationship between the characteristics of hepatocellular carcinoma (HCC) diagnosed after sustained virological response (SVR) with direct‐acting antiviral (DAA) therapy and surveillance status has not been sufficiently investigated. This study investigated the clinical risk factors for HCC development and HCC characteristics according to which type of physician performed follow‐up after SVR. Methods A total of 1070 patients in whom hepatitis C virus (HCV) was eradicated with DAA therapy were evaluated. Results There were 458 patients followed by hepatologists (specialist group) and 612 followed by non‐hepatologists (non‐specialist group) after SVR. During the follow‐up period, 54 patients developed HCC. The 1‐, 2‐, 3‐, 4‐, and 5‐year cumulative incidence rates of HCC were 1.8, 4.1, 6.9, 10.5, and 17.2%, respectively. Multivariate Cox proportional hazards analysis showed that male sex (hazard ratio [HR], 3.139; 95% confidence interval [CI], 1.732–5.690), α‐fetoprotein level (HR, 1.056; 95% CI, 1.035–1.077), and fibrosis‐4 (FIB‐4) index (HR, 1.051; 95% CI, 1.017–1.085) were significantly associated with HCC development, while the follow‐up physician type after SVR was not. There were 25 patients with stage I HCC, 17 with stage II, 9 with stage III, and 3 with stage IV. Multivariate ordinal logistic regression showed that follow‐up physician type (non‐specialist) (HR, 39.100; 95% CI, 9.350–224.00) was independently associated with HCC stage, while α‐fetoprotein level and FIB‐4 index were not. Conclusion When patients have more risk factors for HCC development after SVR (i.e., male sex, elevated α‐fetoprotein, or elevated FIB‐4 index), they should be followed by a hepatologist for HCC surveillance.
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Affiliation(s)
- Toshifumi Tada
- Department of Internal medicine Japanese Red Cross Society Himeji Hospital Himeji Japan
- Department of Internal Medicine, Division of Gastroenterology and Hepatology Hyogo Medical University Nishinomiya Japan
| | | | - Tomomitsu Matono
- Department of Internal Medicine, Division of Gastroenterology and Hepatology Hyogo Medical University Nishinomiya Japan
- Department of Internal medicine Himeji St. Mary's Hospital Himeji Japan
| | - Shinichiro Nakamura
- Department of Internal medicine Japanese Red Cross Society Himeji Hospital Himeji Japan
| | - Masahiko Sue
- Department of Internal medicine Japanese Red Cross Society Himeji Hospital Himeji Japan
| | - Yu Matsuo
- Department of Internal medicine Japanese Red Cross Society Himeji Hospital Himeji Japan
| | - Masahiro Takatani
- Department of Internal medicine Japanese Red Cross Society Himeji Hospital Himeji Japan
| | - Hiroko Iijima
- Department of Internal Medicine, Division of Gastroenterology and Hepatology Hyogo Medical University Nishinomiya Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan
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Nakamura Y, Miyaaki H, Miuma S, Akazawa Y, Fukusima M, Sasaki R, Haraguchi M, Soyama A, Hidaka M, Eguchi S, Nakao K. Automated fibrosis phenotyping of liver tissue from non-tumor lesions of patients with and without hepatocellular carcinoma after liver transplantation for non-alcoholic fatty liver disease. Hepatol Int 2022; 16:555-561. [PMID: 35553006 DOI: 10.1007/s12072-022-10340-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 04/09/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND Fibrosis is the most important pathological feature in predicting development of Hepatocellular carcinoma (HCC). However, the incidence rate of HCC in patients with non-alcoholic fatty liver disease (NAFLD) is relatively low. We evaluated phenotypic histological features to differentiate HCC from non-HCC in patients with non-tumor lesions of cirrhotic livers. METHODS Seventeen patients with NAFLD who underwent liver transplantation were enrolled. FibroNest was used to quantify histological phenotypes of non-tumor fibrosis lesions. Quantification included collagen content and structure traits, fiber morphometric traits, and fibrosis architecture traits. Each trait was described by up to seven quantitative fibrosis traits (qFTs). Among the qFTs measured in each specimen, those that described most of the variability between consecutive groups were automatically detected and combined into a normalized Phenotypic Composite Fibrosis Score (Ph-CFS). We trained FibroNest to identify the principal traits that differentiate HCC from non-HCC. RESULTS HCC was found in 8 cases and non-HCC in 9 cases. The Ph-CFS significantly differentiated HCC from non-HCC (4.6 vs. 5.9, p < 0.05). Individual qFTs for morphometric features including collagen fiber length, width, perimeter, and area denoted significant differences between HCC and non-HCC. The Ph-CFS could be used to distinguish HCC (Ph-FCS < 5.0) from non-HCC (Ph-FCS ≥ 5.0) with 75% sensitivity and 100% specificity. CONCLUSION In patients who underwent liver transplantation, fibrotic histological phenotypes in non-tumor lesions appeared to be different between HCC and non-HCC. Phenotypic analysis of collagen in non-tumor lesions might be an effective and automated method to distinguish HCC from non-HCC on histopathology imaging.
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Affiliation(s)
- Yutaka Nakamura
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Hisamitsu Miyaaki
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
| | - Satoshi Miuma
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Yuko Akazawa
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Masanori Fukusima
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Ryu Sasaki
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Masafumi Haraguchi
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Akihiko Soyama
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Masaaki Hidaka
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
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Hagiwara H, Ito Y, Ohta T, Nozaki Y, Iwamoto T, Hosui A, Hiramatsu N, Tahata Y, Sakamori R, Hikita H, Hayashi N. Incidence and risk factors of hepatocellular carcinoma in patients with hepatitis C who achieved a sustained virological response through direct‐acting antiviral agents among the working population in Japan. JGH Open 2022; 6:395-401. [PMID: 35774345 PMCID: PMC9218520 DOI: 10.1002/jgh3.12745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Revised: 04/08/2022] [Accepted: 04/11/2022] [Indexed: 11/18/2022]
Abstract
Background and Aim The development of hepatocarcinogenesis after a sustained virological response (SVR) remains an important issue affecting the balance between treatment and occupational life of workers with chronic hepatitis C virus (HCV) infection in Japan. Here, we aimed to evaluate the hepatocellular carcinoma (HCC) reducing effect and risk factors for developing HCC after SVR in patients treated with direct‐acting antiviral agents (DAAs) among the working population. Methods We studied 2579 working patients with chronic HCV infection who achieved SVR after antiviral treatment. We compared the difference in the cumulative incidence of post‐SVR HCC between the interferon (IFN)‐based n = 1615 and DAA (n = 964) groups. The risk factors for post‐SVR HCC development were determined in the DAA group. Results After propensity score matching (n = 644 in each group), the HCC development rates were not significantly different between the groups (P = 0.186). Multivariate Cox regression and the cutoff values determined by the receiver operating characteristic curve analyses revealed that age ≥61 years, diabetes, lower serum albumin levels <4.0 g/dL at 24 weeks after the end of treatment (EOT), and higher serum α‐fetoprotein levels ≥4.1 ng/mL at 24 weeks after the EOT were associated with the development of HCC. Conclusion The HCC suppressing effect after SVR through DAA treatment is equivalent to that of IFN treatment in patients in the working population. Intensive follow‐up is required after SVR with DAA treatment in Japanese workers with these risk factors to ensure the promotion of health and employment support.
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Affiliation(s)
- Hideki Hagiwara
- Department of Gastroenterology and Hepatology Kansai Rosai Hospital Amagasaki Hyogo Japan
| | - Yoshiki Ito
- Department of Gastroenterology and Hepatology Kansai Rosai Hospital Amagasaki Hyogo Japan
| | - Takashi Ohta
- Department of Gastroenterology and Hepatology Kansai Rosai Hospital Amagasaki Hyogo Japan
| | - Yasutoshi Nozaki
- Department of Gastroenterology and Hepatology Kansai Rosai Hospital Amagasaki Hyogo Japan
| | - Takayuki Iwamoto
- Department of Gastroenterology and Hepatology Kansai Rosai Hospital Amagasaki Hyogo Japan
| | - Atsushi Hosui
- Department of Gastroenterology and Hepatology Osaka Rosai Hospital Sakai Osaka Japan
| | - Naoki Hiramatsu
- Department of Gastroenterology and Hepatology Osaka Rosai Hospital Sakai Osaka Japan
| | - Yuki Tahata
- Department of Gastroenterology and Hepatology Osaka University Graduate School of Medicine Suita Osaka Japan
| | - Ryotaro Sakamori
- Department of Gastroenterology and Hepatology Osaka University Graduate School of Medicine Suita Osaka Japan
| | - Hayato Hikita
- Department of Gastroenterology and Hepatology Osaka University Graduate School of Medicine Suita Osaka Japan
| | - Norio Hayashi
- Department of Gastroenterology and Hepatology Kansai Rosai Hospital Amagasaki Hyogo Japan
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20
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Manoharan SA, Hess RS. The odds of neoplasia in dogs with and without diabetes mellitus. J Vet Intern Med 2022; 36:726-732. [PMID: 35081271 PMCID: PMC8965209 DOI: 10.1111/jvim.16370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 01/12/2022] [Accepted: 01/13/2022] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND Increased risk of neoplasia in humans with diabetes mellitus (DM) is well documented. It is unknown if dogs with DM have increased risk of neoplasia. OBJECTIVE Determine if dogs with DM have an overall increased risk of neoplasia and risk for specific forms of neoplasia compared to dogs without DM. ANIMALS Seven hundred dogs with DM and 700 breed, age, and sex-matched dogs without DM, examined during the same years. METHODS Retrospective case-control study. Odds ratios (OR), corresponding 95% confidence intervals (CI), and P-values were calculated using conditional logistic regression to determine if dogs with DM had increased odds of developing neoplasia compared to dogs without DM. RESULTS The overall odds of developing neoplasia were not significantly different in dogs with and without DM. However, dogs with DM had significantly higher odds of developing an adrenal mass (OR, 4; 95% CI, 1.1-14.2; P = .03) compared to dogs without DM. The odds of developing a splenic mass in dogs with DM (OR, 1.2; 95% CI, 0.99-1.39) were increased compared to dogs without DM, but this difference was not significant (P = .07). CONCLUSIONS AND CLINICAL IMPORTANCE Dogs with DM may be at increased risk for adrenal neoplasia. Awareness of this risk can facilitate early diagnosis of this life-threatening comorbidity. Larger studies are needed to confirm these findings.
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Affiliation(s)
- Sindumani A. Manoharan
- Department of Clinical Sciences and Advanced MedicineSchool of Veterinary Medicine, University of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | - Rebecka S. Hess
- Department of Clinical Sciences and Advanced MedicineSchool of Veterinary Medicine, University of PennsylvaniaPhiladelphiaPennsylvaniaUSA
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21
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Yang C, Wan M, Lu Y, Yang X, Yang L, Wang S, Sun G. Associations between diabetes mellitus and the risk of hepatocellular carcinoma in Asian individuals with hepatitis B and C infection: systematic review and a meta-analysis of cohort studies. Eur J Cancer Prev 2022; 31:107-116. [PMID: 35103624 DOI: 10.1097/cej.0000000000000669] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
We aim to further analyze and compare associations between diabetes mellitus and the risk of hepatocellular carcinoma (HCC) in Asian individuals with hepatitis B or C virus infection by conducting an updated meta-analysis of cohort studies. Literature search was conducted in PubMed, Scopus, Web of Science, and Cochrane Library from the beginning of indexing for each database to January 1, 2020. A total of 22 articles met the inclusion criteria, in which 18 were cohort studies and 4 were case-control studies. We identified eight cohort studies and three case-control studies that presented results on diabetes mellitus and the risk of HCC in Asian subjects with hepatitis B virus (HBV) infection: the cumulative relative risk (RR) with 95% confidence interval (CI) was 1.37 (95% CI: 1.24 to 1.51; I2 = 27.8%) for cohort studies and cumulative odds ratio (OR) with 95% CI was 1.99 (95% CI: 0.73 to 5.48; I2 = 88.4%) for case-control studies. Thirteen cohort studies and two case-control studies presented results on the association between diabetes mellitus and the risk of HCC in Asian subjects with hepatitis C virus (HCV) infection: the RR with 95% CI was 1.76 (95% CI: 1.42 to 2.17; I2 = 62.8%) for cohort studies and OR with 95% CI was 1.77 (95% CI: 1.18 to 2.64; I2 = 0.0%) for case-control studies. In summary, our meta-analysis strongly supports the association between coexistent HCV and diabetes with the increasing risk of HCC; although the results equally support diabetes mellitus being significantly associated with increased risk of HCC among patients with HBV infection, this correlation is weaker than the former.
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Affiliation(s)
- Chao Yang
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing, P.R. China
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22
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Di Ciaula A, Bonfrate L, Krawczyk M, Frühbeck G, Portincasa P. Synergistic and Detrimental Effects of Alcohol Intake on Progression of Liver Steatosis. Int J Mol Sci 2022; 23:2636. [PMID: 35269779 PMCID: PMC8910376 DOI: 10.3390/ijms23052636] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 02/24/2022] [Accepted: 02/25/2022] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are the most common liver disorders worldwide and the major causes of non-viral liver cirrhosis in the general population. In NAFLD, metabolic abnormalities, obesity, and metabolic syndrome are the driving factors for liver damage with no or minimal alcohol consumption. ALD refers to liver damage caused by excess alcohol intake in individuals drinking more than 5 to 10 daily units for years. Although NAFLD and ALD are nosologically considered two distinct entities, they show a continuum and exert synergistic effects on the progression toward liver cirrhosis. The current view is that low alcohol use might also increase the risk of advanced clinical liver disease in NAFLD, whereas metabolic factors increase the risk of cirrhosis among alcohol risk drinkers. Therefore, special interest is now addressed to individuals with metabolic abnormalities who consume small amounts of alcohol or who binge drink, for the role of light-to-moderate alcohol use in fibrosis progression and clinical severity of the liver disease. Evidence shows that in the presence of NAFLD, there is no liver-safe limit of alcohol intake. We discuss the epidemiological and clinical features of NAFLD/ALD, aspects of alcohol metabolism, and mechanisms of damage concerning steatosis, fibrosis, cumulative effects, and deleterious consequences which include hepatocellular carcinoma.
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Affiliation(s)
- Agostino Di Ciaula
- Clinica Medica “Augusto Murri”, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School—Piazza Giulio Cesare 11, 70124 Bari, Italy; (A.D.C.); (L.B.)
| | - Leonilde Bonfrate
- Clinica Medica “Augusto Murri”, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School—Piazza Giulio Cesare 11, 70124 Bari, Italy; (A.D.C.); (L.B.)
| | - Marcin Krawczyk
- Department of Medicine II Saarland University Medical Center, Saarland University, 66424 Homburg, Germany;
- Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Centre for Preclinical Research, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Gema Frühbeck
- Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, 31008 Pamplona, Spain;
- Metabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), ISCIII, 31009 Pamplona, Spain
- Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31009 Pamplona, Spain
| | - Piero Portincasa
- Clinica Medica “Augusto Murri”, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School—Piazza Giulio Cesare 11, 70124 Bari, Italy; (A.D.C.); (L.B.)
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23
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Nakai M, Yamamoto Y, Baba M, Suda G, Kubo A, Tokuchi Y, Kitagataya T, Yamada R, Shigesawa T, Suzuki K, Nakamura A, Sho T, Morikawa K, Ogawa K, Furuya K, Sakamoto N. Prediction of hepatocellular carcinoma using age and liver stiffness on transient elastography after hepatitis C virus eradication. Sci Rep 2022; 12:1449. [PMID: 35087141 PMCID: PMC8795443 DOI: 10.1038/s41598-022-05492-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 01/12/2022] [Indexed: 12/27/2022] Open
Abstract
Liver stiffness measurement (LSM) is a useful tool for assessing advanced liver fibrosis, an important risk factor for hepatocellular carcinoma (HCC) following hepatitis C (HCV) eradication. This study aimed to clarify the non-invasive factors associated with HCC following sustained virological response (SVR) and to identify the low-risk group. 567 patients without history of HCC who achieved SVR at 24 weeks (SVR24) after IFN-free treatment were retrospectively analyzed. The cumulative incidence of HCC and the risk factors were examined using pre-treatment and SVR24 data. The median observation period was 50.2 months. Thirty cases of HCC were observed, and the 4-year cumulative incidence of HCC was 5.9%. In multivariate analysis, significant pre-treatment factors were age ≥ 71 years (hazard ratio [HR]: 3.402) and LSM ≥ 9.2 kPa (HR: 6.328); SVR24 factors were age ≥ 71 years (HR: 2.689) and LSM ≥ 8.4 kPa (HR: 6.642). In cases with age < 71 years and LSM < 8.4 kPa at the time of SVR24, the 4-year cumulative incidence of HCC was as low as 1.1%. Both pre-treatment LSM (≥ 9.2 kPa) and SVR24 LSM (≥ 8.4 kPa) and age (≥ 71 years) are useful in predicting the risk of HCC after SVR with IFN-free treatment. Identification of low-risk individuals may improve the efficiency of follow-up.
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Affiliation(s)
- Masato Nakai
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Yoshiya Yamamoto
- Department of Gastroenterology, Hakodate Municipal Hospital, Hakodate, Hokkaido, Japan
| | - Masaru Baba
- Department of Gastroenterology, JCHO Hokkaido Hospital, Sapporo, Hokkaido, Japan
| | - Goki Suda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Akinori Kubo
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Yoshimasa Tokuchi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Takashi Kitagataya
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Ren Yamada
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Taku Shigesawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Kazuharu Suzuki
- Department of Gastroenterology, Hakodate Municipal Hospital, Hakodate, Hokkaido, Japan
| | - Akihisa Nakamura
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Takuya Sho
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Kenichi Morikawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Koji Ogawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Ken Furuya
- Department of Gastroenterology, JCHO Hokkaido Hospital, Sapporo, Hokkaido, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
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Kouroumalis E, Voumvouraki A. Hepatitis C virus: A critical approach to who really needs treatment. World J Hepatol 2022; 14:1-44. [PMID: 35126838 PMCID: PMC8790391 DOI: 10.4254/wjh.v14.i1.1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 04/14/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023] Open
Abstract
Introduction of effective drugs in the treatment of hepatitis C virus (HCV) infection has prompted the World Health Organization to declare a global eradication target by 2030. Propositions have been made to screen the general population and treat all HCV carriers irrespective of the disease status. A year ago the new severe acute respiratory syndrome coronavirus 2 virus appeared causing a worldwide pandemic of coronavirus disease 2019 disease. Huge financial resources were redirected, and the pandemic became the first priority in every country. In this review, we examined the feasibility of the World Health Organization elimination program and the actual natural course of HCV infection. We also identified and analyzed certain comorbidity factors that may aggravate the progress of HCV and some marginalized subpopulations with characteristics favoring HCV dissemination. Alcohol consumption, HIV coinfection and the presence of components of metabolic syndrome including obesity, hyperuricemia and overt diabetes were comorbidities mostly responsible for increased liver-related morbidity and mortality of HCV. We also examined the significance of special subpopulations like people who inject drugs and males having sex with males. Finally, we proposed a different micro-elimination screening and treatment program that can be implemented in all countries irrespective of income. We suggest that screening and treatment of HCV carriers should be limited only in these particular groups.
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Affiliation(s)
- Elias Kouroumalis
- Department of Gastroenterology, University of Crete Medical School, Heraklion 71500, Crete, Greece
| | - Argyro Voumvouraki
- First Department of Internal Medicine, AHEPA University Hospital, Thessaloniki 54621, Greece
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25
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Mori Y, Matsuda S, Sato M, Muraoka M, Suzuki Y, Tatsumi A, Nakayama Y, Inoue T, Maekawa S, Enomoto N. The Impact of Antiviral Therapy for Hepatitis C Virus on the Survival of Patients after Hepatocellular Carcinoma Treatment. Intern Med 2022; 61:2721-2729. [PMID: 36104175 PMCID: PMC9556239 DOI: 10.2169/internalmedicine.8456-21] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Objective Owing to advances in direct-acting antiviral (DAA) therapy, a considerable number of patients with hepatitis C virus (HCV)-positive hepatocellular carcinoma (HCC) are now able to achieve a sustained viral response (SVR) after curative treatment of HCC. However, the beneficial effect of a DAA-SVR on the survival remains unclear. Methods A total of 205 patients with HCC who were HCV-positive with Child-Pugh A at the onset from 2008 to 2018 were categorized into 2 groups: 140 patients untreated for HCV throughout the entire course after HCC development (untreated group) and 65 patients treated for HCV with DAAs following HCC treatment who achieved an SVR (SVR group). After propensity score matching, 63 patients from each group were selected. Using these patients, the survival and maintenance of Child-Pugh A after HCC treatment were compared between the untreated group and SVR group. Results There was a significant difference in the overall survival (p<0.001) and the rate of maintaining Child-Pugh A (p<0.001) between the groups. The 5-year survival rates were 96% (SVR group) and 60% (untreated group), and the proportions of patients with Child-Pugh A at 5 years after HCC treatment were 96% (SVR group) and 38% (untreated group). Conclusion In patients with HCV-positive HCC, achieving a DAA-SVR after HCC treatment significantly improved the overall survival rate compared with HCV-untreated patients. The contribution of DAA-SVR during the course of HCC treatment to a longer survival is mainly due to the prevention of the progression of Child-Pugh A to B/C. Further research is needed to determine whether aggressive antiviral therapy is also effective for HCC patients with Child-Pugh B/C.
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Affiliation(s)
- Yuki Mori
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Japan
| | - Shuya Matsuda
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Japan
| | - Mitsuaki Sato
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Japan
| | - Masaru Muraoka
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Japan
| | - Yuichiro Suzuki
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Japan
| | - Akihisa Tatsumi
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Japan
| | - Yasuhiro Nakayama
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Japan
| | - Taisuke Inoue
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Japan
| | - Shinya Maekawa
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Japan
| | - Nobuyuki Enomoto
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Japan
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Azit NA, Sahran S, Voon Meng L, Subramaniam M, Mokhtar S, Mohammed Nawi A. Risk factors of hepatocellular carcinoma in type 2 diabetes patients: A two-centre study in a developing country. PLoS One 2021; 16:e0260675. [PMID: 34882716 PMCID: PMC8659343 DOI: 10.1371/journal.pone.0260675] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Accepted: 11/13/2021] [Indexed: 12/24/2022] Open
Abstract
Type 2 diabetes mellitus (T2DM) is increasingly known as a risk factor of hepatocellular carcinoma (HCC). In this study, we determined the risk factors associated with HCC in T2DM patients. This was a matched case-control study conducted at two hepatobiliary referral centres in a developing country. Patients' sociodemographic, clinical, and biochemical characteristics between 1 January 2012 and 30 June 2018 were extracted from the electronic medical records and analysed using multivariate logistic regression analysis. A total of 212 case-control pairs were included. Significant risk factors included Chinese and Malay ethnicities that interacted with viral hepatitis (adjusted odds ratio [AOR] = 11.77, 95% confidence interval [CI]: 1.39-99.79) and (AOR = 37.94, 95% CI: 3.92-367.61) respectively, weight loss (AOR = 5.28, 95% CI: 2.29-12.19), abdominal pain/ discomfort (AOR = 6.73, 95% CI: 3.34-13.34), alcohol (AOR = 4.08, 95% CI: 1.81-9.22), fatty liver (AOR = 3.29, 95% CI: 1.40-7.76), low platelet (AOR = 4.03, 95% CI:1.90-8.55), raised alanine transaminase (AOR = 2.11, 95% CI: 1.16-3.86). and alkaline phosphatase (ALP) levels (AOR = 2.17, 95% CI: 1.17-4.00). Statins reduced the risk of HCC by 63% (AOR = 0.37, 95% CI: 0.21-0.65). The identification of these factors aids the risk stratification for HCC among T2DM patients for early detection and decision-making in patient management in the primary care setting.
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Affiliation(s)
- Noor Atika Azit
- Department of Community Health, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Shahnorbanun Sahran
- Faculty of Information Science and Technology, National University of Malaysia, Bangi, Selangor, Malaysia
| | - Leow Voon Meng
- Advanced Medical and Dental Institute (AMDI), USM, Kepala Batas, Penang, Malaysia
- Hepato-Pancreato-Biliary Unit, Department of Surgery, Hospital Sultanah Bahiyah, Ministry of Health Malaysia, Alor Setar, Kedah, Malaysia
| | - Manisekar Subramaniam
- Hepato-Pancreato-Biliary Unit, Department of Surgery, Hospital Sultanah Bahiyah, Ministry of Health Malaysia, Alor Setar, Kedah, Malaysia
| | - Suryati Mokhtar
- Hepato-Pancreato-Biliary Unit, Department of Surgery, Hospital Selayang, Ministry of Health Malaysia, Batu Caves, Selangor, Malaysia
| | - Azmawati Mohammed Nawi
- Department of Community Health, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
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Miyasaka A, Yoshida Y, Suzuki A, Sawara K, Takikawa Y. A Novel Standard for Hepatocellular Carcinoma Screening Intensity After Hepatitis C Elimination. Int J Gen Med 2021; 14:8935-8943. [PMID: 34866934 PMCID: PMC8636695 DOI: 10.2147/ijgm.s344492] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 11/12/2021] [Indexed: 12/22/2022] Open
Abstract
Purpose To investigate long-term incidence of hepatocellular carcinoma (HCC) and the factors associated with HCC occurrence after achieving sustained virological response (SVR) by direct-acting antiviral agent (DAA) treatment for hepatitis C virus (HCV). Methods A total of 476 patients (male 227, female 249; median age 68) with chronic HCV infection who were treated with DAAs and achieved SVR were analyzed. The incidence of HCC and factors related to the development of HCC after HCV elimination were evaluated. Results The median observation period was 46.4 months. During this period, 40 patients developed HCC. The incidence rates of HCC were 3.7%, 6.0%, 7.1%, 9.3%, and 10.6% at 1, 2, 3, 4, and 5 years post-SVR12, respectively. Multivariate analysis with pre-treatment factors revealed that platelet count, α-fetoprotein, fibrosis-4 (Fib-4) index, and previous HCC history were independent factors that contributed to development of HCC post-SVR following DAA treatment. Of these factors, previous HCC history was the most significant, followed by Fib-4 index. Using these two factors, a novel scoring system was established. The presence of previous HCC history was scored as 2, and then, the absence of previous HCC history was stratified by Fib-4 index (≥3.07, 1; <3.07, 0). The HCC occurrence rate at 5 years was 0.4% in the 0-point group, 6.8% in the 1-point group, and 55.6% in the 2-point group, respectively. Conclusion Fib-4 index and previous HCC history were independent predictors for development of HCC after DAA treatment. Patients with these risk factors require careful observation.
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Affiliation(s)
- Akio Miyasaka
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Shiwa-gun, Iwate, Japan.,Department of Gastroenterology, Iwate Prefectural Ninohe Hospital, Ninohe, Iwate, Japan
| | - Yuichi Yoshida
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Shiwa-gun, Iwate, Japan.,Department of Gastroenterology, Iwate Prefectural Ninohe Hospital, Ninohe, Iwate, Japan
| | - Akiko Suzuki
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Shiwa-gun, Iwate, Japan
| | - Kei Sawara
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Shiwa-gun, Iwate, Japan.,Department of Gastroenterology, Iwate Prefectural Kamaishi Hospital, Kamaishi, Iwate, Japan
| | - Yasuhiro Takikawa
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Shiwa-gun, Iwate, Japan
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28
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Cerrito L, Ainora ME, Nicoletti A, Garcovich M, Riccardi L, Pompili M, Gasbarrini A, Zocco MA. Elastography as a predictor of liver cirrhosis complications after hepatitis C virus eradication in the era of direct-acting antivirals. World J Hepatol 2021; 13:1663-1676. [PMID: 34904036 PMCID: PMC8637667 DOI: 10.4254/wjh.v13.i11.1663] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 07/08/2021] [Accepted: 08/17/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic inflammation due to hepatitis C virus (HCV) infection leads to liver fibrosis and rearrangement of liver tissue, which is responsible for the development of portal hypertension (PH) and hepatocellular carcinoma (HCC). The advent of direct-acting antiviral drugs has revolutionized the natural history of HCV infection, providing an overall eradication rate of over 90%. Despite a significant decrease after sustained virological response (SVR), the rate of HCC and liver-related complications is not completely eliminated in patients with advanced liver disease. Although the reasons are still unclear, cirrhosis itself has a residual risk for the development of HCC and other PH-related complications. Ultrasound elastography is a recently developed non-invasive technique for the assessment of liver fibrosis. Following the achievement of SVR, liver stiffness (LS) usually decreases, as a consequence of reduced inflammation and, possibly, fibrosis. Recent studies emphasized the application of LS assessment in the management of patients with SVR in order to define the risk for developing the complications of chronic liver disease (functional decompensation, gastrointestinal bleeding, HCC) and to optimize long-term prognostic outcomes in clinical practice.
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Affiliation(s)
- Lucia Cerrito
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Maria Elena Ainora
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Alberto Nicoletti
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Matteo Garcovich
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Laura Riccardi
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Maurizio Pompili
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Antonio Gasbarrini
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Maria Assunta Zocco
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168,
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Clinical Presentation of Hepatocellular Carcinoma in African Americans vs. Caucasians: A Retrospective Analysis. PATHOPHYSIOLOGY 2021; 28:387-399. [PMID: 35366282 PMCID: PMC8830457 DOI: 10.3390/pathophysiology28030026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 08/10/2021] [Accepted: 08/19/2021] [Indexed: 12/27/2022] Open
Abstract
Hepatocellular carcinoma (HCC) remains an important form of cancer-related morbidity and mortality in the U.S. and worldwide. Previous U.S.-based studies on survival suggest ethnic disparities in HCC patients, but the complex interplay of multiple factors that contribute are still incompletely understood. Here we considered the influences of risk factors contributing towards HCC survival, including ethnic background, over ten years at a premier academic medical center with a majority (57.20%) African American (AA) population. Retrospective HCC data were collected from 2008–2018 at LSUHSC-Shreveport, an urban tertiary medical center. Data included demographics, comorbidities, liver disease characteristics, and tumor parameters. Statistical analysis was performed using Chi Square and one-way ANOVA. Results: 229 HCC patients were identified (male 78.6%). The mean HCC age at diagnosis was 61 years (SD = 7.3). Compared to non-Hispanic Caucasians (42.7%), AA patients (57.2% of total) were older at presentation, had more frequent diabetes/dyslipidemia/NAFLD (45 (34.3%) compared with 19 (19.3%) in non-Hispanic Caucasians, p = 0.02), and had a larger HCC burden at diagnosis. We conclude that compared to white patients, despite having similar BMI and MELD scores and rates of portal vein thrombosis, AA patients with HCC in our cohort were older at presentation, had a significantly increased incidence of modifiable metabolic risk factors including diabetes, higher AFP values, increased incidence of gallstones, and larger sized HCCs, and were more likely to be outside Milan criteria. These findings have important prognostic and diagnostic implications for developing a more targeted HCC surveillance program.
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Watanabe T, Tokumoto Y, Joko K, Michitaka K, Horiike N, Tanaka Y, Tada F, Kisaka Y, Nakanishi S, Yamauchi K, Ochi H, Hiraoka A, Yagi S, Yukimoto A, Hirooka M, Abe M, Hiasa Y. AFP and eGFR are related to early and late recurrence of HCC following antiviral therapy. BMC Cancer 2021; 21:699. [PMID: 34126947 PMCID: PMC8201700 DOI: 10.1186/s12885-021-08401-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Accepted: 05/24/2021] [Indexed: 01/05/2023] Open
Abstract
Background An unexpected recurrence of hepatocellular carcinoma (HCC) sometimes occurs in patients with hepatitis C virus (HCV) after treatment with direct-acting antivirals (DAAs). However, the characteristics of patients with HCC recurrence may differ depending on time after DAA treatment. We aimed to identify risk factors related to HCC recurrence according to time after DAA treatment. Methods Of 1663 patients with HCV treated with a DAA, 199 patients had a previous history of HCC. We defined HCC recurrence within 1 year after DAA treatment as ‘early recurrence’, and recurrence more than 1 year after as ‘late recurrence’. The different risk factors between the early and late phases of HCC recurrence after the end of DAA therapy were investigated. Results Ninety-seven patients experienced HCC recurrence during the study period. Incidences of recurrence were 29.8, 41.0, and 53.4% at 1, 2, and 3 years, respectively, after the end of DAA therapy. Multivariate analysis identified post-treatment α-fetoprotein (AFP) as an independent factor contributing to HCC recurrence in the early phase (hazard ratio, 1.056; 95% confidence interval, 1.026–1.087, p < 0.001) and post-treatment estimated glomerular filtration rate (eGFR) (hazard ratio, 0.98; 95% confidence interval, 0.96–0.99, p = 0.032) as a predictor of HCC recurrence in the late phase. Conclusion Patients with higher post-treatment AFP in the early phase and those with lower post-treatment eGFR in the late phase had a high risk of HCC recurrence. The risk factors associated with HCC recurrence after DAA treatment were different between the early and late phases. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-08401-7.
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Affiliation(s)
- Takao Watanabe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
| | - Yoshio Tokumoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.
| | - Kouji Joko
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, 1 Bunkyocho, Matsuyama, Ehime, 790-8524, Japan
| | - Kojiro Michitaka
- Department of Gastroenterology, Ehime Prefectural Central Hospital, 83 Kasugamachi, Matsuyama, Ehime, 790-0024, Japan
| | - Norio Horiike
- Department of Gastroenterology, Saiseikai Imabari Hospital, 7-1-6 Kitamura, Imabari, Ehime, 799-1502, Japan
| | - Yoshinori Tanaka
- Department of Gastroenterology, Matsuyama Shimin Hospital, 2-6-5 Ootemachi, Matsuyama, Ehime, 790-0067, Japan
| | - Fujimasa Tada
- Department of Internal Medicine, Saiseikai Matsuyama Hospital, 880-2 Yamanishicho, Matsuyama, Ehime, 791-8026, Japan
| | - Yoshiyasu Kisaka
- Department of Gastroenterology, Uwajima City Hospital, 1-1 Gotenmachi, Uwajima, Ehime, 798-8510, Japan
| | - Seiji Nakanishi
- Department of Gastroenterology, Ehime Prefectural Imabari Hospital, 4-5-5 Ishiicho, Imabari, Ehime, 794-0006, Japan
| | - Kazuhiko Yamauchi
- Department of Gastroenterology, National Hospital Organization Ehime Medical Center, 366 Yokogawara, Toon, Ehime, 791-0203, Japan
| | - Hironori Ochi
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, 1 Bunkyocho, Matsuyama, Ehime, 790-8524, Japan
| | - Atsushi Hiraoka
- Department of Gastroenterology, Ehime Prefectural Central Hospital, 83 Kasugamachi, Matsuyama, Ehime, 790-0024, Japan
| | - Sen Yagi
- Department of Internal Medicine, Saiseikai Matsuyama Hospital, 880-2 Yamanishicho, Matsuyama, Ehime, 791-8026, Japan
| | - Atsushi Yukimoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
| | - Masanori Abe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
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Sacco M, Saracco GM. The impact of direct-acting antiviral treatment on glycemic homeostasis in patients with chronic hepatitis C. Minerva Gastroenterol (Torino) 2021; 67:264-272. [PMID: 33856147 DOI: 10.23736/s2724-5985.21.02835-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND there is robust epidemiological evidence suggesting the link of chronic Hepatitis C Virus (HCV) infection with type 2 diabetes mellitus (DM). Viral clearance achieved by Direct Acting Antiviral Agents (DAAs) has been associated to significant improvements in glycometabolic control but data on the long-term effect of Sustained Virological Response on diabetic disease are limited. AIM the aim of this review is to evaluate the influence of SVR after DAA-based therapy on Insulin Resistance (IR) and DM incidence in non-diabetic patients, on the glycemic homeostasis in diabetic patients and on their long-term hepatic and metabolic outcomes. METHODS an electronic search of Embase, PubMed, MEDLINE, Ovid and the Cochrane Database of Systematic Reviews was performed for papers regarding the effect of DAAinduced SVR on the glycometabolic control and clinical outcomes of HCV-positive diabetic patients up to September 30, 2020. RESULTS among non-diabetic patients, a significant reduction in the risk of IR and DM was reported by the vast majority of the studies; the glycometabolic control significantly improved in diabetic patients during and immediately after the end of antiviral treatment. However, whether this beneficial effect is long lasting is still matter of debate. Furthermore, at variance with data obtained during the Interferon (IFN) era, DM does not seem to be an unfavourable predictive factor of Hepatocellular Carcinoma (HCC) in cured patients. CONCLUSIONS a favourable influence of DAA-induced SVR on IR and DM incidence and on glycemic control is reported by several studies. However, the long-term biochemical, metabolic and clinical impact of this endocrine benefit remains largely unknown.
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Affiliation(s)
- Marco Sacco
- Gastro-hepatoloy Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Giorgio M Saracco
- Gastro-hepatoloy Unit, Department of Medical Sciences, University of Turin, Turin, Italy -
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Cheng CH, Chu CY, Chen HL, Lin IT, Wu CH, Lee YK, Bair MJ. Virus Elimination by Direct-Acting Antiviral Agents Impacts Glucose Homeostasis in Chronic Hepatitis C Patients. Front Endocrinol (Lausanne) 2021; 12:799382. [PMID: 35095765 PMCID: PMC8792856 DOI: 10.3389/fendo.2021.799382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 12/20/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND AND AIMS Chronic hepatitis C virus (HCV) infection is associated with dysregulation of glucose homeostasis, including insulin resistance (IR) and type 2 diabetes. However, independent risk factors associated with IR in chronic HCV-infected patients have not been detailly elucidated. Previous data regarding the impact of HCV elimination by direct-acting antiviral agents (DAAs) on glucose homeostasis is insufficient and controversial. This study aimed to analyze the independent factors associated with IR and to evaluate the changes in glucose homeostasis in chronic HCV-infected patients treated with DAAs therapies. METHODS We screened 704 patients with chronic HCV infection who underwent treatment with interferon-free DAAs. Patients' baseline characteristics, biochemical and virological data were collected. The outcome measurements were their IR and β-cell function assessed by the homeostasis model assessment (HOMA) method at baseline and 12-weeks post-treatment. RESULTS High IR (HOMA-IR ≥ 2.5) was observed in 35.1% of the patients. Multivariable logistic regression analysis revealed that body mass index (BMI) >25 kg/m2, treatment experience, elevated baseline levels of alanine aminotransferase (ALT) and triglyceride, as well as Fibrosis-4 score >3.25 were independently associated with high IR. In patients who achieved sustained virological response (SVR), no significant change in mean HOMA-IR was observed from baseline to 12-weeks post-treatment (2.74 ± 2.78 to 2.54 ± 2.20, p = 0.128). We observed a significant improvement in β-cell secretion stress from 121.0 ± 110.1 to 107.6 ± 93.0 (p = 0.015). Subgroup analysis revealed that SVR was associated with a significant reduction in mean HOMA-IR in patients with baseline HOMA-IR ≥ 2.5 (5.31 ± 3.39 to 3.68 ± 2.57, p < 0.001), HCV genotype 1 (3.05 ± 3.11 to 2.62 ± 2.05, p = 0.027), and treatment experience (4.00 ± 3.37 to 3.01 ± 2.49, p = 0.039). CONCLUSIONS There were several independent factors associated with IR in patients with chronic HCV infection, including obesity, treatment experience, high serum ALT and triglyceride levels, as well as advanced hepatic fibrosis. After viral elimination by DAAs, we observed a significant reduction in mean HOMA-IR in patients with baseline high IR, HCV genotype 1, and treatment experience.
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Affiliation(s)
- Chun-Han Cheng
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
- Department of Medicine, Mackay Medical College, New Taipei, Taiwan
| | - Chia-Ying Chu
- Department of Pathology, Taitung Mackay Memorial Hospital, Taitung, Taiwan
| | - Huan-Lin Chen
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
- Department of Medicine, Mackay Medical College, New Taipei, Taiwan
| | - I-Tsung Lin
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
- Department of Medicine, Mackay Medical College, New Taipei, Taiwan
| | - Chia-Hsien Wu
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
- Department of Medicine, Mackay Medical College, New Taipei, Taiwan
| | - Yuan-Kai Lee
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
- Department of Medicine, Mackay Medical College, New Taipei, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
- Department of Medicine, Mackay Medical College, New Taipei, Taiwan
- *Correspondence: Ming-Jong Bair,
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Abe K, Wakabayashi H, Nakayama H, Suzuki T, Kuroda M, Yoshida N, Tojo J, Kogure A, Rai T, Saito H, Mukai S, Fujita M, Hayashi M, Takahashi A, Ohira H. Factors associated with hepatocellular carcinoma occurrence after HCV eradication in patients without cirrhosis or with compensated cirrhosis. PLoS One 2020; 15:e0243473. [PMID: 33284844 PMCID: PMC7721183 DOI: 10.1371/journal.pone.0243473] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2020] [Accepted: 11/21/2020] [Indexed: 02/08/2023] Open
Abstract
The present study aimed to investigate the incidence of hepatocellular carcinoma (HCC) and factors related to HCC occurrence after direct-acting antiviral (DAA) treatment in the Fukushima Liver Academic Group (FLAG). We conducted a multicenter retrospective cohort study of 1068 patients without cirrhosis (NC) or with compensated liver cirrhosis (LC) who achieved a sustained virologic response (SVR). First, we compared the cumulative HCC incidence and survival rates in NC (n = 880) and LC (n = 188) patients without a history of HCC treatment. Second, we performed multivariate analysis of factors related to HCC occurrence after DAA treatment. Overall, the average age was 65 years, and the male/female ratio was 511/557. Thirty-nine (4%) patients developed HCC. The cumulative 4-year HCC incidence and survival rates were 3.0% and 99.8% in NC patients and 11.5% and 98.5% in LC patients, respectively. The independent factors affecting HCC occurrence identified by multivariate analysis were the serum albumin (ALB) level before SVR for NC patients and the ALBI score, platelet count, and diabetes before SVR for LC patients. The factors related to HCC occurrence differed between NC and LC patients. Careful surveillance of post-SVR patients with these risk factors is needed.
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Affiliation(s)
- Kazumichi Abe
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
- Department of Internal Medicine, Hanawa Kosei Hospital, Higashishirakawa, Japan
- * E-mail:
| | - Hiroto Wakabayashi
- Department of Gastroenterology, Takeda General Hospital, Aizuwakamatsu, Japan
| | - Haruo Nakayama
- Department of Gastroenterology, Iwaki City Medical Center, Iwaki, Japan
| | - Tomohiro Suzuki
- Department of Gastroenterology, Fukushima Rosai Hospital, Iwaki, Japan
| | - Masahito Kuroda
- Department of Gastroenterology, Fukushima Red Cross Hospital, Fukushima, Japan
| | - Naoe Yoshida
- Department of Internal Medicine, Iwase General Hospital, Sukagawa, Japan
| | | | - Atsuko Kogure
- Department of Gastroenterology, Fujita General Hospital, Date, Japan
| | | | | | - Shinji Mukai
- Department of Gastroenterology, Ohta Nishinouchi Hospital, Koriyama, Japan
| | - Masashi Fujita
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Manabu Hayashi
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Atsushi Takahashi
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Hiromasa Ohira
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
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Pawlotsky JM, Negro F, Aghemo A, Berenguer M, Dalgard O, Dusheiko G, Marra F, Puoti M, Wedemeyer H. EASL recommendations on treatment of hepatitis C: Final update of the series ☆. J Hepatol 2020; 73:1170-1218. [PMID: 32956768 DOI: 10.1016/j.jhep.2020.08.018] [Citation(s) in RCA: 756] [Impact Index Per Article: 151.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 08/18/2020] [Indexed: 02/08/2023]
Abstract
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, with approximately 71 million chronically infected individuals worldwide. Clinical care for patients with HCV-related liver disease has advanced considerably thanks to an enhanced understanding of the pathophysiology of the disease, as well as developments in diagnostic procedures and improvements in therapy and prevention. These therapies make it possible to eliminate hepatitis C as a major public health threat, as per the World Health Organization target, although the timeline and feasibility vary from region to region. These European Association for the Study of the Liver recommendations on treatment of hepatitis C describe the optimal management of patients with recently acquired and chronic HCV infections in 2020 and onwards.
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Development of Hepatocellular Carcinoma in a Patient with Chronic Hepatitis C 21 Years after Achieving a Sustained Virological Response to Interferon Therapy. Case Reports Hepatol 2020; 2020:8824974. [PMID: 33123390 PMCID: PMC7582091 DOI: 10.1155/2020/8824974] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 09/30/2020] [Accepted: 10/06/2020] [Indexed: 12/04/2022] Open
Abstract
A 77-year-old man with chronic hepatitis C (CH-C) infection, who achieved a sustained virological response (SVR) to interferon (IFN) therapy, was followed up regularly. Before IFN therapy, he did not have metabolic diseases, and the histological diagnosis of his chronic hepatitis was stage-3 fibrosis. After achieving SVR, the fibrosis-4 (FIB-4) index level dropped once but gradually increased. 21 years after SVR, hepatocellular carcinoma (HCC) was diagnosed by dynamic computed tomography. The HCC was 12 mm in diameter. The HCC was treated with radiofrequency ablation. CH-C patients with advanced fibrosis require long-term follow-up, even after achieving SVR.
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Impaired insulin exocytosis in chronic hepatitis C infection: contributory role of p38δ MAPK-protein kinase D-golgi complex axis. Clin Sci (Lond) 2020; 134:1449-1456. [PMID: 32556178 DOI: 10.1042/cs20200686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Revised: 05/31/2020] [Accepted: 06/03/2020] [Indexed: 11/17/2022]
Abstract
Hepatitis C virus (HCV) infection and chronic hepatitis C (CHC) are associated with a measurable risk of insulin resistance (IR)/impaired glucose tolerance (IGT)/diabetes mellitus (DM). While loss of hepatic endocrine function contributes to liver cirrhosis in diabetic patients, onset and progression of IR/IGT to diabetes and exacerbation of incident hyperglycemia are ostensibly linked with chronic HCV infection. In this regard, the study by Chen J et al. appearing in Clinical Science (2020) (134(5) https://doi.org/10.1042/CS20190900) attempts to understand the mechanisms underlying the savaging effects of chronic HCV infection on insulin-producing pancreatic β-cells and hence diabetic onset. The study investigated the role of mitogen-activated protein kinase (MAPK) p38δ-protein kinase D (PKD)-golgi complex axis in impacting insulin exocytosis. It was inferred that an insulin secretory defect of pancreatic β-cells, owing to disrupted insulin exocytosis, to an extent explains β-cell dysfunction in HCV-infected or CHC milieu. HCV infection negatively regulates first-phase and second-phase insulin secretion by impinging on PKD-dependent insulin secretory granule fission at trans-golgi network and insulin secretory vesicle membrane fusion events. This commentary highlights the study in question, that deciphered the contribution of p38δ MAPK-PKD-golgi complex axis to β-cell dysfunction in CHC milieu. This pivotal axis proffers a formidable therapeutic opportunity for alleviation of double burden of glucose abnormalities/DM and CHC.
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Saleh P, Infectious and Tropical Disease Research Center, Department of Infectious and Tropical Disease, Tabriz University of Medical Sciences, Tabriz, Iran, Sheikholeslami A, Infectious and Tropical Disease Research Center, Department of Infectious and Tropical Disease, Tabriz University of Medical Sciences, Tabriz, Iran, Salman Mohajer A, Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran, Babapour S, Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran, Hosseini MS, Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. Association between Different Hepatitis C Virus Genotypes Infection and Type-2 Diabetes Mellitus: A Descriptive-Analytical Study from the Northwest of Iran. JOURNAL OF MEDICAL MICROBIOLOGY AND INFECTIOUS DISEASES 2020; 8:137-142. [DOI: 10.29252/jommid.8.4.137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
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Asahina Y. JSH Guidelines for the Management of Hepatitis C Virus Infection, 2019 Update; Protective Effect of Antiviral Therapy against Hepatocarcinogenesis. Hepatol Res 2020; 50:775-790. [PMID: 32298527 DOI: 10.1111/hepr.13501] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 03/04/2020] [Accepted: 04/05/2020] [Indexed: 02/08/2023]
Abstract
The Drafting Committee for Hepatitis Management Guidelines established by the Japan Society of Hepatology (JSH) drafted the first version of the clinical practice guidelines for the management of hepatitis C virus (HCV) infection in 2012. Since then, we have been publishing updates as new drugs for hepatitis C become available and new indications for existing drugs are added. The new approval of sofosbuvir/velpatasvir prompted us to publish the seventh version of the guidelines in Japanese in March 2019. We also published the first English-language version of the JSH guidelines in 2013 and English versions of updates made to the Japanese-language guidelines in 2014 and 2016. In 2020, the committee has decided to publish a new English version, covering general information about treatment for hepatitis C, drugs used, recommended treatments for chronic hepatitis and cirrhosis, and special populations, such as patients who have renal impairment, are on dialysis, or have developed recurrence of hepatitis C after liver transplantation. Furthermore, the committee has released a separate publication covering the protective effect of antiviral therapy against hepatocarcinogenesis.
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Yang JD, Mara KC, Gores GJ, Roberts LR. REPLY. Hepatology 2020; 72:362-363. [PMID: 31901147 DOI: 10.1002/hep.31097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
Affiliation(s)
- Ju Dong Yang
- Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, CA.,Comprehensive Transplant Center, Cedars Sinai Medical Center, Los Angeles, CA.,Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center, Los Angeles, CA.,Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN
| | - Kristin C Mara
- Department of Health Science Research, Mayo Clinic College of Medicine and Science, Rochester, MN
| | - Gregory J Gores
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN
| | - Lewis R Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN
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Takemura K, Takizawa E, Tamori A, Nakamae M, Kubota H, Uchida-Kobayashi S, Enomoto M, Kawada N, Hino M. Post-Treatment M2BPGi Level and the Rate of Autotaxin Reduction are Predictive of Hepatocellular Carcinoma Development after Antiviral Therapy in Patients with Chronic Hepatitis C. Int J Mol Sci 2020; 21:4517. [PMID: 32630450 PMCID: PMC7350226 DOI: 10.3390/ijms21124517] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 06/22/2020] [Accepted: 06/23/2020] [Indexed: 01/10/2023] Open
Abstract
Patients with chronic hepatitis C virus (HCV) develop hepatocellular carcinoma (HCC) regardless of achieving a sustained viral response (SVR). Because advanced liver fibrosis is a powerful risk factor for HCC, we analyzed the association between autotaxin (ATX), a liver fibrosis marker, and post-SVR HCC development within 3 years after antiviral treatment. We included 670 patients with HCV who received direct-acting antivirals, achieved SVR and were followed up for at least 6 months (270 of them were followed up for 3 years or more). We measured serum ATX levels before treatment and 12/24 weeks after treatment. The diagnosis of HCC was based on imaging modalities, such as dynamic computed tomography and dynamic magnetic resonance imaging and/or liver biopsy. The present study revealed that high levels of serum ATX predicted post-SVR HCC development (area under the receiver operating characteristic: 0.70-0.76). However, Wisteria floribunda agglutinin positive Mac-2 binding protein (M2BPGi), another liver fibrosis marker, was a more useful predictive marker especially post-treatment according to a multivariate analysis. Patients with a high rate of ATX reduction before and after antiviral treatment did not develop HCC regardless of high pretreatment ATX levels. In conclusion, post-treatment M2BPGi level and the combination of pretreatment ATX levels and rate of ATX reduction were useful predictive markers for post-SVR HCC development in patients with chronic HCV infection.
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MESH Headings
- Aged
- Antigens, Neoplasm/blood
- Antigens, Neoplasm/genetics
- Antigens, Neoplasm/metabolism
- Antiviral Agents/therapeutic use
- Biomarkers/blood
- Biomarkers, Tumor/blood
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism
- Carcinoma, Hepatocellular/etiology
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/pathology
- Female
- Hepacivirus/pathogenicity
- Hepatitis C, Chronic/complications
- Hepatitis C, Chronic/drug therapy
- Hepatitis C, Chronic/metabolism
- Humans
- Liver Cirrhosis/complications
- Liver Neoplasms/etiology
- Liver Neoplasms/genetics
- Liver Neoplasms/pathology
- Male
- Membrane Glycoproteins/blood
- Middle Aged
- Phosphoric Diester Hydrolases/blood
- Phosphoric Diester Hydrolases/metabolism
- Phosphoric Diester Hydrolases/physiology
- Risk Factors
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Affiliation(s)
- Kazuya Takemura
- Department of Central Clinical Laboratory, Osaka City University Hospital, 1-5-7, Asahi-machi, Abeno-ku, Osaka-shi, Osaka 545-8586, Japan; (K.T.); (E.T.); (M.N.); (H.K.); (M.H.)
| | - Etsuko Takizawa
- Department of Central Clinical Laboratory, Osaka City University Hospital, 1-5-7, Asahi-machi, Abeno-ku, Osaka-shi, Osaka 545-8586, Japan; (K.T.); (E.T.); (M.N.); (H.K.); (M.H.)
| | - Akihiro Tamori
- Department of Hepatology, Graduate School of Medicine, Osaka City University, 1-4-3, Asahi-machi, Abeno-ku, Osaka-shi, Osaka 545-8585, Japan; (S.U.-K.); (M.E.); (N.K.)
| | - Mika Nakamae
- Department of Central Clinical Laboratory, Osaka City University Hospital, 1-5-7, Asahi-machi, Abeno-ku, Osaka-shi, Osaka 545-8586, Japan; (K.T.); (E.T.); (M.N.); (H.K.); (M.H.)
- Department of Hematology, Graduate School of Medicine, Osaka City University, 1-4-3, Asahi-machi, Abeno-ku, Osaka-shi, Osaka 545-8585, Japan
| | - Hiroshi Kubota
- Department of Central Clinical Laboratory, Osaka City University Hospital, 1-5-7, Asahi-machi, Abeno-ku, Osaka-shi, Osaka 545-8586, Japan; (K.T.); (E.T.); (M.N.); (H.K.); (M.H.)
| | - Sawako Uchida-Kobayashi
- Department of Hepatology, Graduate School of Medicine, Osaka City University, 1-4-3, Asahi-machi, Abeno-ku, Osaka-shi, Osaka 545-8585, Japan; (S.U.-K.); (M.E.); (N.K.)
| | - Masaru Enomoto
- Department of Hepatology, Graduate School of Medicine, Osaka City University, 1-4-3, Asahi-machi, Abeno-ku, Osaka-shi, Osaka 545-8585, Japan; (S.U.-K.); (M.E.); (N.K.)
| | - Norifumi Kawada
- Department of Hepatology, Graduate School of Medicine, Osaka City University, 1-4-3, Asahi-machi, Abeno-ku, Osaka-shi, Osaka 545-8585, Japan; (S.U.-K.); (M.E.); (N.K.)
| | - Masayuki Hino
- Department of Central Clinical Laboratory, Osaka City University Hospital, 1-5-7, Asahi-machi, Abeno-ku, Osaka-shi, Osaka 545-8586, Japan; (K.T.); (E.T.); (M.N.); (H.K.); (M.H.)
- Department of Hematology, Graduate School of Medicine, Osaka City University, 1-4-3, Asahi-machi, Abeno-ku, Osaka-shi, Osaka 545-8585, Japan
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Among Medicare Patients With Hepatocellular Carcinoma, Non-alcoholic Fatty Liver Disease is the Most Common Etiology and Cause of Mortality. J Clin Gastroenterol 2020; 54:459-467. [PMID: 30672817 DOI: 10.1097/mcg.0000000000001172] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
GOALS The main purpose of this study was to assess the recent trends in mortality and health care utilization of hepatocellular carcinoma (HCC) among Medicare population in the United States. BACKGROUND The incidence of HCC is increasing in the United States. MATERIALS AND METHODS Data were obtained for a sample of Medicare beneficiary from 2005 to 2014. Diagnosis of HCC and etiology of liver disease were based on ICD-9 codes. Temporal trends in HCC rates, clinical, demographical and utilization parameters were analyzed by joinpoint regression model. RESULTS Study cohort included 13,648 Medicare recipients with HCC (mean age: 70.0 y, 62.8% male and 76.0% white). Non-alcoholic fatty liver disease (NAFLD) was the most common cause of HCC in the inpatient (32.07%) and outpatient (20.22%) followed by hepatitis C virus (HCV) (19.2% and 9.75%, respectively). Between 2005 and 2014, HCC rate per 100,000 Medicare recipients increased from 46.3 to 62.8 [average annual percentage change (AAPC) =3.4%, P<0.001]. Rate of HCV-HCC increased from 6.18 to 16.54 (AAPC=11.8%, P<0.001) while the NAFLD-HCC increased from 9.32 to 13.61, P<0.001). Overall 1-year mortality decreased from 46.2% to 42.1% (AAPC=-1.7%, P=0.004). Total charges increased from $67,679 to $99,420 (AAPC=5.1%, P<0.001) for inpatients and from $11,933 to $32,084 (P<0.001) for outpatients. On comparison of patients with hepatitis B virus-HCC, those with NAFLD-HCC (odds ratio: 1.87, P<0.001) had higher risk of mortality. On comparison of patients with hepatitis B virus-HCC, those with HCV-HCC had higher charges (percent change: 24.33%, 95% confidence interval: 1.02%-53.02%, P=0.040). CONCLUSIONS Although HCC rates are increasing, the overall mortality is decreasing. NAFLD is the most important cause of HCC and an independent predictor of HCC in the outpatient setting for Medicare patients with HCC.
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The Effect of Viral Clearance Achieved by Direct-Acting Antiviral Agents on Hepatitis C Virus Positive Patients with Type 2 Diabetes Mellitus: A Word of Caution after the Initial Enthusiasm. J Clin Med 2020; 9:jcm9020563. [PMID: 32092892 PMCID: PMC7074145 DOI: 10.3390/jcm9020563] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2020] [Revised: 02/11/2020] [Accepted: 02/17/2020] [Indexed: 02/07/2023] Open
Abstract
The causal link between chronic hepatitis C and glycometabolic alterations has been confirmed by much biochemical, clinical, and epidemiological research work, but what is still controversial is the long-term clinical impact of sustained virologic response (SVR) achieved by direct-acting antiviral agents (DAAs) on patients with type 2 diabetes mellitus (DM). The aim of this paper is to summarize the biochemical and clinical consequences to DM of DAA-based therapy for hepatitis C virus (HCV) infection. An electronic search of Embase, PubMed, MEDLINE, Ovid, and the Cochrane Database of Systematic Reviews was conducted for publications assessing whether clearance of HCV achieved by interferon (IFN)-free antiviral therapy determines significant changes in glycometabolic control and clinical outcomes of diabetic patients. A beneficial effect of SVR obtained by DAA therapy on DM prevention and the short-term outcome of glycometabolic alterations are acknowledged by most of the studies. Whether this effect is maintained over the long term with a significant clinical impact on diabetic and liver disease is still a matter of debate.
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Tani J, Morishita A, Sakamoto T, Takuma K, Nakahara M, Fujita K, Oura K, Tadokoro T, Mimura S, Nomura T, Yoneyama H, Kobara H, Himoto T, Tsutsui A, Senoh T, Nagano T, Ogawa C, Moriya A, Deguchi A, Takaguchi K, Masaki T. Simple scoring system for prediction of hepatocellular carcinoma occurrence after hepatitis C virus eradication by direct-acting antiviral treatment: All Kagawa Liver Disease Group Study. Oncol Lett 2020; 19:2205-2212. [PMID: 32194718 PMCID: PMC7038998 DOI: 10.3892/ol.2020.11341] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2019] [Accepted: 12/12/2019] [Indexed: 02/06/2023] Open
Abstract
Direct acting antivirals (DAA) have recently been developed to treat patients with hepatitis C virus (HCV) infection, and interferon-free DAA treatment has improved the cure rate of patients. However, the occurrence rate of hepatocellular carcinoma (HCC) following HCV eradication remains unknown. Therefore, the present study aimed to identify predictors of HCC occurrence following DAA treatment. Among 1,454 patients infected with HCV, 1,088 patients who achieved sustained virologic response and who had no history of HCC treatment were recruited between September 2014 and November 2018. The incidence of HCC in patients infected with HCV following DAA treatment, and the predictors contributing to HCC occurrence were identified using clinicopathological characteristics and blood test results. During the present study, 26 patients developed HCC. The incidence of HCC was 0.61, 1.88, 2.82 and 3.71% at 6, 12, 18 and 24 months after treatment with DAA, respectively. The results of multivariate analysis identified age [hazard ratio (HR), 1.0729; P=0.0044] and α-fetoprotein (AFP) level after DAA treatment (HR, 1.0486; P=0.0486) as independent factors that may contribute to HCC occurrence following DAA treatment. By using these two factors, a novel scoring system (0-2 points) was established to predict HCC occurrence following HCV eradication by DAA treatment. The incidence of HCC at 2 years was 0.3% in the 0 points group, 6.27% in the 1 point group and 18.37% in the 2 points group. In conclusion, AFP level after DAA treatment and age at DAA administration were identified as independent predictors of HCC occurrence in patients that were treated with DAA. The scoring system that was established in the present study is simple and easy, and using pre-treatment factors may be a convenient tool to predict the risk of HCC occurrence in HCV-free patients following DAA treatment.
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Affiliation(s)
- Joji Tani
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan
| | - Asahiro Morishita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan
| | - Teppei Sakamoto
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan
| | - Kei Takuma
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan
| | - Mai Nakahara
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan
| | - Koji Fujita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan
| | - Kyoko Oura
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan
| | - Tomoko Tadokoro
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan
| | - Shima Mimura
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan
| | - Takako Nomura
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan
| | - Hirohito Yoneyama
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan
| | - Hideki Kobara
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan
| | - Takashi Himoto
- Department of Medical Technology, Kagawa Prefectural University of Health Sciences, Takamatsu, Kagawa 761-0123, Japan
| | - Akemi Tsutsui
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Kagawa 760-8557, Japan
| | - Tomonori Senoh
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Kagawa 760-8557, Japan
| | - Takuya Nagano
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Kagawa 760-8557, Japan
| | - Chikara Ogawa
- Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Kagawa 760-0017, Japan
| | - Akio Moriya
- Department of Gastroenterology, Mitoyo General Hospital, Kanonji, Kagawa 769-1695, Japan
| | - Akihiro Deguchi
- Department of Gastroenterology, Kagawa Rosai Hospital, Marugame, Kagawa 763-8502, Japan
| | - Kouichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Kagawa 760-8557, Japan
| | - Tsutomu Masaki
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan
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Yang WY, Rao PS, Luo YC, Lin HK, Huang SH, Yang JM, Yuh CH. Omics-based Investigation of Diet-induced Obesity Synergized with HBx, Src, and p53 Mutation Accelerating Hepatocarcinogenesis in Zebrafish Model. Cancers (Basel) 2019; 11:cancers11121899. [PMID: 31795276 PMCID: PMC6966430 DOI: 10.3390/cancers11121899] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 11/17/2019] [Accepted: 11/25/2019] [Indexed: 12/19/2022] Open
Abstract
The primary type of liver cancer, hepatocellular carcinoma (HCC), has been associated with nonalcoholic steatohepatitis, diabetes, and obesity. Previous studies have identified some genetic risk factors, such as hepatitis B virus X antigens, overexpression of SRC oncogene, and mutation of the p53 tumor suppressor gene; however, the synergism between diet and genetic risk factors is still unclear. To investigate the synergism between diet and genetic risk factors in hepatocarcinogenesis, we used zebrafish with four genetic backgrounds and overfeeding or high-fat-diet-induced obesity with an omics-based expression of genes and histopathological changes. The results show that overfeeding and high-fat diet can induce obesity and nonalcoholic steatohepatitis in wild-type fish. In HBx, Src (p53-) triple transgenic zebrafish, diet-induced obesity accelerated HCC formation at five months of age and increased the cancer incidence threefold. We developed a global omics data analysis method to investigate genes, pathways, and biological systems based on microarray and next-generation sequencing (NGS, RNA-seq) omics data of zebrafish with four diet and genetic risk factors. The results show that two Kyoto Encyclopedia of Genes and Genomes (KEGG) systems, metabolism and genetic information processing, as well as the pathways of fatty acid metabolism, steroid biosynthesis, and ribosome biogenesis, are activated during hepatocarcinogenesis. This study provides a systematic view of the synergism between genetic and diet factors in the dynamic liver cancer formation process, and indicate that overfeeding or a high-fat diet and the risk genes have a synergistic effect in causing liver cancer by affecting fatty acid metabolism and ribosome biogenesis.
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Affiliation(s)
- Wan-Yu Yang
- Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan 35053, Miaoli, Taiwan; (W.-Y.Y.); (P.-S.R.); (H.-K.L.)
| | - Pei-Shu Rao
- Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan 35053, Miaoli, Taiwan; (W.-Y.Y.); (P.-S.R.); (H.-K.L.)
- Department of Life Science, National Tsing-Hua University, Hsinchu 30070, Taiwan
| | - Yong-Chun Luo
- Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu 30010, Taiwan; (Y.-C.L.); (S.-H.H.)
| | - Hua-Kuo Lin
- Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan 35053, Miaoli, Taiwan; (W.-Y.Y.); (P.-S.R.); (H.-K.L.)
| | - Sing-Han Huang
- Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu 30010, Taiwan; (Y.-C.L.); (S.-H.H.)
| | - Jinn-Moon Yang
- Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu 30010, Taiwan; (Y.-C.L.); (S.-H.H.)
- Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30010, Taiwan
- Center for Intelligent Drug Systems and Smart Bio-devices, National Chiao Tung University, Hsinchu 30010, Taiwan
- Correspondence: (J.-M.Y.); (C.-H.Y.); Tel.: +011-886-03-5712121*56942 (J.-M.Y.); +011-886-37-206166*35338 (C.-H.Y.)
| | - Chiou-Hwa Yuh
- Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan 35053, Miaoli, Taiwan; (W.-Y.Y.); (P.-S.R.); (H.-K.L.)
- Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30010, Taiwan
- Institute of Bioinformatics and Structural Biology, National Tsing-Hua University, Hsinchu 30070, Taiwan
- Program in Environmental and Occupational Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Correspondence: (J.-M.Y.); (C.-H.Y.); Tel.: +011-886-03-5712121*56942 (J.-M.Y.); +011-886-37-206166*35338 (C.-H.Y.)
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Muñoz Díaz HA, Lúquez Mindiola AJ, Gómez Aldana AJ. Fisiopatología de la hepatitis C y diabetes mellitus. Hacia la cura de dos epidemias en el siglo XXI. REVISTA COLOMBIANA DE GASTROENTEROLOGÍA 2019; 34:277-287. [DOI: 10.22516/25007440.322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/01/2024]
Abstract
La infección crónica por virus de la hepatitis C (VHC) y la diabetes mellitus (DM) son dos problemas de salud pública que impactan los sistemas de salud, con una alta carga económica global. La infección por VHC produce manifestaciones hepáticas tales como hepatitis, cirrosis y carcinoma hepatocelular; asimismo, se ha involucrado en la patogénesis de manifestaciones extrahepáticas, entre las cuales se ha asociado con alteraciones metabólicas como la DM. Estudios longitudinales y transversales han reportado mayor incidencia y prevalencia de DM en pacientes con infección crónica por VHC. La DM acelera la progresión histológica y clínica en pacientes con infección crónica por VHC y las complicaciones cardiovasculares. Recientemente se ha avanzado en el tratamiento y la introducción de nuevos medicamentos como los antivirales de acción directa, que mejoran el control glucémico en estos pacientes.
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Tan Y, Zhang X, Zhang W, Tang L, Yang H, Yan K, Jiang L, Yang J, Li C, Yang J, Wen T, Tang H, Yan L. The Influence of Metabolic Syndrome on the Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Infection in Mainland China. Cancer Epidemiol Biomarkers Prev 2019; 28:2038-2046. [PMID: 31533942 DOI: 10.1158/1055-9965.epi-19-0303] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Revised: 06/15/2019] [Accepted: 09/12/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The association between metabolic syndrome (MS), both in terms of its components and as a whole, and the risk of hepatocellular carcinoma (HCC) in subjects with hepatitis B virus (HBV) infection remains unclear, especially in mainland China. METHODS We prospectively included 6,564 individuals with HBV infection from an initial cohort of 105,397 civil servants. The multivariate-adjusted HR and 95% confidence interval (95% CI) were evaluated using Cox proportional hazards models to explore the potential connection between HCC risk and MS. Cumulative incidences were plotted using Kaplan-Meier curves. RESULTS After a 45,668.0 person-year follow-up (76.0 ± 30.8 months) of 6,564 subjects who were seropositive for hepatitis B surface antigen, 89 incident HCC cases were identified. MS as a whole was independently associated with a 2-fold increased HCC risk (HR, 2.25; 95% CI, 1.41-3.60) after adjusting for age (in 1-year increments), gender, cigarette smoking, alcohol consumption, liver cirrhosis, and elevated aspartate aminotransferase levels (≥40 U/L). Subjects with three or more factors and those with one or two factors had adjusted increased HCC risks of 2.12-fold (95% CI, 1.16-3.89) and 1.28-fold (95% CI, 0.74-2.22), respectively, in comparison with those without any metabolic factors. Central obesity and type 2 diabetes were associated with significantly increased HCC risk, whereas this association was not observed in obese subjects (body mass index ≥30 kg/m2; 95% CI, 0.73-3.44). CONCLUSIONS MS as a whole, central obesity, and type 2 diabetes were independently associated with increased HCC risk in a population with HBV infection in mainland China. IMPACT MS may be a risk factor for HCC.
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Affiliation(s)
- Yifei Tan
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Xiaoyun Zhang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Wei Zhang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Li Tang
- Department of Intense Care Unit, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Hanwei Yang
- Physical Examination Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Ke Yan
- West China School of Public Health, Sichuan University, Chengdu, Sichuan Province, China
| | - Li Jiang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Jian Yang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Chuan Li
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Jiayin Yang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.
| | - Tianfu Wen
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.
| | - Huairong Tang
- Physical Examination Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.
| | - Lunan Yan
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
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Sustained Improvement in Type 2 Diabetes Mellitus is Common After Treatment of Hepatitis C Virus With Direct-acting Antiviral Therapy. J Clin Gastroenterol 2019; 53:616-620. [PMID: 30614943 DOI: 10.1097/mcg.0000000000001168] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
GOALS To determine whether diabetic patients with hepatitis C virus (HCV) treated with direct-acting antiviral agents have improved diabetes, accounting for change in both hemoglobin A1c (HbA1c) and diabetes medications, and whether any improvement was sustained. BACKGROUND HCV infection is associated with an increased risk of diabetes, with improvement in glycemic control after eradication. There remains uncertainty about the durability and magnitude of this effect. STUDY HbA1c and diabetes medications were recorded at 6-month intervals for 1.5 years pretreatment and posttreatment for 122 patients. Subjects were classified as having improved diabetes if there was a decrease in HbA1c≥0.5% with no increase in diabetes medications or a decrease in diabetes medications with a stable HbA1c. RESULTS HbA1c at the nearest time point before treatment was 8.4%±1.9%, compared with 7.8%±1.7% after treatment, a mean difference of 0.6% [95% CI (0.2, 0.9), P<0.01]. A linear mixed effects model incorporating each subject's repeated measurements over time also demonstrated a reduction after treatment of 0.5% [95% CI, (0.3, 0.8), P<0.001]. Accounting for both HbA1c and diabetes medications, 42 of 122 (34%) had an improvement in diabetes after HCV treatment, and 20 of 28 (71%) of these subjects sustained improvement at 1.5 years follow-up. Prescription of insulin was associated with improved diabetes. CONCLUSIONS Treatment of HCV with direct-acting antiviral agents was associated with improved diabetes in a significant portion of patients with an average reduction in HbA1c of clinically significant magnitude. Among responders, this effect was sustained over 1.5 years of follow-up.
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Masarone M, Persico M. Hepatitis C virus infection and non-hepatocellular malignancies in the DAA era: A systematic review and meta-analysis. Liver Int 2019; 39:1292-1306. [PMID: 30983083 DOI: 10.1111/liv.14119] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Revised: 03/12/2019] [Accepted: 04/05/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Direct antiviral agents have greatly improved therapeutic options for chronic hepatitis C. Indeed, former "difficult-to-treat" patients can now be treated and can achieve sustained response. Hepatitis C virus (HCV) is associated with hepatocellular carcinoma and with B-cell non-Hodgkin lymphoma (B-NHL). Other malignancies have been reported to be associated with HCV infection albeit with various grades of evidence. Antineoplastic treatment is often reduced or suspended in HCV-positive cancer patients to avoid "HCV reactivation." In this setting, antiviral therapy combined with antineoplastic protocols may improve the outcome. For this reason, we conducted a systematic review and a meta-analysis to update the association between HCV infection and non-hepatocellular malignancies, and to shed light on the effects exerted by antiviral treatment on the natural history of oncological diseases. METHODS Relevant studies were identified by searching PUBMED, EMBASE and MEDLINE up to 1 August 2018. Pooled risk estimates were calculated with random-effects models according to PRISMA guidelines. RESULTS A total of 58 studies were included in the analysis: 27 studies of the association between HCV and B-NHL(OR 3.36; 95% CI 2.40-4.72;P < 0.00001);13 studies of the association between sustained virological response and progression-free survival (PFS) in B-NHL patients(OR 9.34; 95% CI 4.90-17.79; P < 0.00001); 13 studies of the association between HCV and intrahepatic-cholangio-carcinoma (OR 3.95;95% CI 2.25-6.94; P < 0.00001); and 5 studies of the association between HCV infection and pancreatic adeno-carcinoma(OR 1.60; 95% CI:1.25-2.04; P = 0.0002). CONCLUSIONS This study updates the strong association between B-NHL and HCV infection, confirms the association between HCV and non-hepatocellular tumours, and demonstrates a very strong association between viral eradication and a better outcome of HCV-positive B-NHL.
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Affiliation(s)
- Mario Masarone
- Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy
| | - Marcello Persico
- Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy
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Shchanitcyna SE, Burnevich EZ, Nikulkina EN, Filatova AL, Мoiseev SV, Мukhin NA. Risk factors of unfavorable prognosis of chronic hepatitis C. TERAPEVT ARKH 2019; 91:59-66. [PMID: 31094173 DOI: 10.26442/00403660.2019.02.000082] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
AIM To investigate risk factors of unfavorable prognosis in patients with chronic hepatitis C (CHC), including liver cirrhosis (LC), decompensated cirrhosis, hepatocellular carcinoma (HCC), cryoglobulinemic vasculitis (CryoVas) and B-cell non-Hodgkin's lymphoma. MATERIALS AND METHODS This was a retrospective study using data of 824 patients with CHC hospitalized between 2010 and 2016 in clinic named after E.M. Tareev. We used multivariate analysis including logistic regression to calculate odds ratios (ORs) for potential risk factors/predictors associated with unfavorable outcomes in patients with CHC. RESULTS The rate of LC, decompensated LC, HCC, serious CryoVas and B-cell lymphoma in patients with CHC was 39.1% (322/824), 14.0% (115/824), 2.8% (23/824), 5.2% (43/824) and 1.2% (10/824), respectively. After adjustment for sex and age the rate of LC, decompensated LC, HCC was 22.8, 8.0 and 1.5%, respectively. Annual rate of LC in patients with CHC was 1.5%; in cirrhotic patients annual rate of decompensated LC and HCC was 2.9 and 1%, respectively. Risk factors independently associated with development of LC were elevated body mass index (OR 1.43), immunosuppressive therapy (OR 1.67), diabetes type 2 (OR 2.03), absence of antiviral therapy (OR 2.15), alcohol abuse (OR 2.34), duration of infection ≥20 years (ОR 2.74) and an absence of sustained virological responce (SVR) (OR 2.98). Independent risk factors for decompensation in cirrhotic patients included diabetes type 2 (OR 1.47), alcohol abuse (OR 1.53), an absence of antiviral therapy (OR 2.36) and an absence of SVR (OR 1.94). An episode of decompensation was the independent predictor of HCC in cirrhotic patients (OR 3.99). Genotype 1b (OR 1.66) and an absence of antiviral therapy (OR 3.31) were independently associated with serious CryoVas. Two prognostic scales were offered for risk evaluation of LC and its complications. CONCLUSION Multivariate analysis showed several factors independently associated with higher risk for LC, decompensation of LC, HCC, serious CryoVas in patients with CHC. The rate of unfavorable outcomes of CHC is found, including rare extrahepatic manifestations.
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Affiliation(s)
- S E Shchanitcyna
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - E Z Burnevich
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia.,City Clinical Hospital №24, Moscow, Russia
| | - E N Nikulkina
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - A L Filatova
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - S V Мoiseev
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia.,M.V. Lomonosov Moscow State University, Moscow, Russia
| | - N A Мukhin
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia.,M.V. Lomonosov Moscow State University, Moscow, Russia
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Andreone P, Di Marco V, Gaeta GB, Fagiuoli S, Vukotic R, Craxì A. Current and forthcoming perspectives in linkage to care of hepatitis C virus infection: Assessment of an Italian focus group. Dig Liver Dis 2019; 51:915-921. [PMID: 31031174 DOI: 10.1016/j.dld.2019.03.033] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Revised: 03/06/2019] [Accepted: 03/28/2019] [Indexed: 02/06/2023]
Abstract
Hepatitis C virus (HCV) remains a significant public health problem and is one of the major causes of chronic liver disease worldwide. In recent years many new tools to facilitate widespread HCV screening and new therapeutic options with excellent efficacy and tolerability profiles and cost lowering policies have become available. To fully utilise these new tools, the link between local and specialist centres for the management of HCV infection must be reinforced. In order to GAIN further insight into these aspects, with a particular focus on the Italian scenario, a group of experts met to discuss relevant aspects and open issues on chronic HCV. As a summary of that meeting, the following aspects are here overviewed: (i) global situation of HCV; (ii) screening, diagnosis and indications for the treatment of HCV; (iii) the Italian situation of HCV referrals; (iv) 'hard to reach' patients; (v) treatment of HCV with extrahepatic manifestations; (vi) treatment of patients with advanced cirrhosis. It is the intention of the expert panel to further promote widespread screening and eradication policies that should be accompanied by greater interaction, by attempting to involve all healthcare providers in an organised process to facilitate linkage to care of patients with HCV infections.
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Affiliation(s)
- Pietro Andreone
- Department of Medical and Surgical Sciences, Bologna University, Bologna, Italy.
| | - Vito Di Marco
- Unit of Gastroenterology, PROMISE Department, University of Palermo, Palermo, Italy.
| | - Giovanni Battista Gaeta
- Department of Mental and Physical Health and Preventive Medicine, Infectious Diseases, Campania University "Luigi Vanvitelli", Napoli, Italy.
| | - Stefano Fagiuoli
- Department of Gastroenterology, Hepatology and Liver Transplantation, Papa Giovanni XXIII Hospital, Bergamo, Italy.
| | - Ranka Vukotic
- Department of Medical and Surgical Sciences, Bologna University, Bologna, Italy.
| | - Antonio Craxì
- Gastroenterology and Liver Unit, DiBiMIS, University of Palermo, Palermo, Italy.
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