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Nakahara H, Ono A, Hayes CN, Shirane Y, Miura R, Fujii Y, Tamura Y, Uchikawa S, Fujino H, Nakahara T, Murakami E, Yamauchi M, Kawaoka T, Miki D, Tsuge M, Kobayashi T, Ohdan H, Arihiro K, Oka S. Multiomics Analysis of Liver Molecular Dysregulation Leading to Nonviral-Related Hepatocellular Carcinoma Development. J Proteome Res 2025; 24:1102-1117. [PMID: 39982271 PMCID: PMC11894656 DOI: 10.1021/acs.jproteome.4c00729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Revised: 12/26/2024] [Accepted: 02/10/2025] [Indexed: 02/22/2025]
Abstract
Chronic liver diseases exhibit diverse backgrounds, and it is believed that numerous factors contribute to progression to cancer. To achieve effective prevention of nonviral hepatocellular carcinoma, it is imperative to identify fundamental molecular abnormalities at the patient level. Utilizing cancer-adjacent liver tissues obtained from hepatocellular carcinoma patients (chronic liver disease), we conducted RNA-Seq and metabolome analyses. In the chronic liver disease cohort, upregulation of inflammation-associated signals was observed, concomitant with accumulation of acylcarnitine and fatty acid and depletion of NADP+, gamma-tocopherol, and dehydroisoandrosterone-3-sulfate-1 (DHEAS). To minimize heterogeneity, we performed multiomics clustering, successfully categorizing the chronic liver disease cases into two distinct subtypes. Subtype 1 demonstrated elevated inflammatory levels, whereas Subtype 2 included a disproportionately high proportion of elderly cases. Furthermore, RNA-Seq analysis revealed upregulation of inflammatory signals in Subtype 1, while both subtypes exhibited downregulation of fatty acid metabolism. Metabolome analysis indicated a tendency of increased acylcarnitine levels in Subtype 1 and augmented fatty acid accumulation in Subtype 2. Validation of differentially expressed genes using the Gene Expression Omnibus (GEO) data set revealed the potential for amelioration through supplementation with antioxidants such as epigallocatechin gallate (EGCG).
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Affiliation(s)
- Hikaru Nakahara
- Department
of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Department
of Clinical and Molecular Genetics, Hiroshima
University, Hiroshima 734-8551, Japan
| | - Atsushi Ono
- Department
of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - C. Nelson Hayes
- Department
of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Yuki Shirane
- Department
of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Ryoichi Miura
- Department
of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Yasutoshi Fujii
- Department
of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Department
of Clinical Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Yosuke Tamura
- Department
of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Shinsuke Uchikawa
- Department
of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Hatsue Fujino
- Department
of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Takashi Nakahara
- Hiroshima
Prefectural Hospital Gastroenterology & Hepatology, Hiroshima 734-8530, Japan
| | - Eisuke Murakami
- Department
of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Masami Yamauchi
- Department
of Clinical Oncology, Hiroshima Prefectural
Hospital, Hiroshima 734-8530, Japan
| | - Tomokazu Kawaoka
- Department
of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Daiki Miki
- Department
of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Masataka Tsuge
- Department
of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Liver center, Hiroshima University Hospital, Hiroshima 734-8551, Japan
| | - Tsuyoshi Kobayashi
- Department
of Gastroenterological and Transplant Surgery, Graduate School of
Biomedical and Health Sciences, Hiroshima
University, Hiroshima 734-8551, Japan
| | - Hideki Ohdan
- Department
of Gastroenterological and Transplant Surgery, Graduate School of
Biomedical and Health Sciences, Hiroshima
University, Hiroshima 734-8551, Japan
| | - Koji Arihiro
- Department
of Anatomical Pathology, Hiroshima University
Hospital, Hiroshima 734-8551, Japan
| | - Shiro Oka
- Department
of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
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Watanabe Y, Aikawa M, Oshima Y, Kato T, Takase K, Watanabe Y, Okada K, Okamoto K, Koyama I. Outcomes after laparoscopic or open liver resection for nonalcoholic fatty liver disease-associated hepatocellular carcinoma: a propensity score-matching study. Surg Endosc 2024; 38:3887-3904. [PMID: 38831217 DOI: 10.1007/s00464-024-10937-1] [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: 03/16/2024] [Accepted: 05/17/2024] [Indexed: 06/05/2024]
Abstract
BACKGROUND Laparoscopic liver resection (LLR) is rapidly gaining popularity; however, its efficacy for nonalcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) (NAFLD-HCC) has been not evaluated. The purpose of this study was to compare short- and long-term outcomes between LLR and open liver resection (OLR) among patients with NAFLD-HCC. METHODS We used a single-institution database to analyze data for patients who underwent LLR or OLR for NAFLD-HCC from January 2007 to December 2022. We performed propensity score-matching analyses to compare overall postoperative complications, major morbidities, duration of surgery, blood loss, transfusion, length of stay, recurrence, and survival between the two groups. RESULTS Among 210 eligible patients, 46 pairs were created by propensity score matching. Complication rates were 28% for OLR and 11% for LLR (p = 0.036). There were no significant differences in major morbidities (15% vs. 8.7%, p = 0.522) or duration of surgery (199 min vs. 189 min, p = 0.785). LLR was associated with a lower incidence of blood transfusion (22% vs. 4.4%, p = 0.013), less blood loss (415 vs. 54 mL, p < 0.001), and shorter postoperative hospital stay (9 vs. 6 days, p < 0.001). Differences in recurrence-free survival and overall survival between the two groups were not statistically significant (p = 0.222 and 0.301, respectively). CONCLUSIONS LLR was superior to OLR for NAFLD-HCC in terms of overall postoperative complications, blood loss, blood transfusion, and postoperative length of stay. Moreover, recurrence-free survival and overall survival were comparable between LLR and OLR. Although there is a need for careful LLR candidate selection according to tumor size and location, LLR can be regarded as a preferred treatment for NAFLD-HCC over OLR.
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Affiliation(s)
- Yukihiro Watanabe
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan.
| | - Masayasu Aikawa
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan
| | - Yuhei Oshima
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan
| | - Tomotaka Kato
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan
| | - Kenichiro Takase
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan
| | - Yuichiro Watanabe
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan
| | - Katsuya Okada
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan
| | - Kojun Okamoto
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan
| | - Isamu Koyama
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan
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Mazeaud S, Zupo R, Couret A, Panza F, Sardone R, Castellana F. Prevalence of Sarcopenia in Liver Cirrhosis: A Systematic Review and Meta-Analysis. Clin Transl Gastroenterol 2023; 14:e00584. [PMID: 37011140 PMCID: PMC10371322 DOI: 10.14309/ctg.0000000000000584] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 02/24/2023] [Indexed: 04/05/2023] Open
Abstract
INTRODUCTION Chronic liver disease is often combined with a morbidity burden that strongly affects the functional domain. In liver cirrhosis (LC), qualitative and quantitative muscle wasting, known as sarcopenia, poses an added clinical burden, together with comorbidities and a poor quality of life. METHODS We conducted a systematic review and meta-analysis of the prevalence of sarcopenia in LC. The literature was screened through 6 electronic databases from the study's inception to January 2023. No exclusion criteria were applied to language, operative tools for diagnosing sarcopenia, population age, general health status, country, and study setting (cohort or cross-sectional). Two independent researchers applied the inclusion criteria in parallel to evaluate the eligibility of the 44 retrieved articles; only 36 met the eligibility requirements. RESULTS The total sample (N = 8,821) was slightly dominated by men (N = 4,941). The cross-sectional design predominated over the longitudinal, and the hospital setting was prevalent. The pooled prevalence of sarcopenia across the selected studies was 33% (95% confidence interval [CI] 0.32-0.34), with high heterogeneity ( I2 = 96%). A further meta-analysis using the Child-Pugh (CP) score to stage LC was conducted on 24 entries, and the results showed that for the LC populations classified with the CP-A, CP-B, and CP-C staging, respectively, the overall mean prevalence was 33% (95% CI 0.31-0.35), 36% (95% CI 0.34-0.39) and 46% (95% CI 0.43-0.50). The risk of bias was moderate. In LC, 1 in 3 patients suffers sarcopenia. DISCUSSION Poor management of muscle mass loss plays a role in the prognosis of death and quality of life of patients with LC. Clinicians in the field are recommended, when screening for sarcopenia, to pay close attention by carefully assessing body composition as part of the monitoring scheme.
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Affiliation(s)
- Simon Mazeaud
- Clermont Auvergne University, CRNH, AME2P, Clermont-Ferrand, France
| | - Roberta Zupo
- Department of Interdisciplinary Medicine, University “Aldo Moro”, Bari, Italy
| | - Alexis Couret
- Clermont Auvergne University, CRNH, AME2P, Clermont-Ferrand, France
- Department of Digestive and Hepatobiliary Medicine, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Francesco Panza
- Department of Translational Biomedicine and Neuroscience (DiBrain), University “Aldo Moro,” Bari, Italy
| | | | - Fabio Castellana
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology IRCCS Saverio De Bellis, Research Hospital, Bari, Italy
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Lingas EC. Hematological Abnormalities in Cirrhosis: A Narrative Review. Cureus 2023; 15:e39239. [PMID: 37337504 PMCID: PMC10277171 DOI: 10.7759/cureus.39239] [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: 05/18/2023] [Indexed: 06/21/2023] Open
Abstract
Liver cirrhosis remains a major public health issue. Liver fibrosis leading to cirrhosis is the terminal stage of various chronic liver diseases. Inflammatory cytokines are involved in the pathogenesis. Patients with cirrhosis often have hematological abnormalities, such as anemia and thrombocytopenia, which have multifactorial etiologies. Anemia in cirrhosis could be related to bleeding leading to iron deficiency anemia or other nutritional anemia such as vitamin B12 and folate deficiency. The pathophysiology of thrombocytopenia in liver cirrhosis has been postulated to range from splenic sequestration to bone marrow suppression from toxic agents, such as alcohol. It often complicates management due to the risk of bleeding with severely low platelets. This review aimed to highlight pathogenesis of liver cirrhosis, hematological abnormalities in liver cirrhosis, and their clinical significance.
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Ye Y, Zhang Q, Lu ZH, Tan YW. Clinicopathological features of 11 cases of chronic hepatitis B infection complicated with primary biliary cholangitis. World J Hepatol 2023; 15:577-584. [PMID: 37206657 PMCID: PMC10190695 DOI: 10.4254/wjh.v15.i4.577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Revised: 03/09/2023] [Accepted: 03/29/2023] [Indexed: 04/20/2023] Open
Abstract
BACKGROUND Only a few cases of chronic hepatitis B (CHB) with primary biliary cholangitis (PBC) have been reported based on histological evidence from liver biopsies.
AIM To observe the clinicopathological features and outcomes of 11 patients with CHB infection complicated by PBC.
METHODS Eleven patients with CHB and PBC who underwent liver biopsy at the Zhenjiang Third Hospital, affiliated with Jiangsu University, and Wuxi Fifth People’s Hospital, from January 2005 to September 2020, were selected. All patients initially visited our hospital with CHB and were pathologically diagnosed with CHB and PBC.
RESULTS Only five had elevated alkaline phosphatase levels, nine were positive for anti-mitochondrial antibody (AMA)-M2, and two were negative for AMA-M2. Two had jaundice and pruritus symptoms, 10 had mildly abnormal liver function, and one had severely elevated bilirubin and liver enzyme levels. The pathological characteristics of CHB complicated by PBC overlapped with those of PBC-autoimmune hepatitis (AIH). When necroinflammation of the portal area is not obvious, the pathological features of PBC are predominant, similar to the features of PBC alone. When the interface is severe, biliangitis will occur, with a large number of ductular reactions in zone 3. Unlike the PBC-AIH overlap pathology, this pathology is characterized by a small amount of plasma cell infiltration. Unlike PBC, lobulitis is often observed.
CONCLUSION This is the first large case series to show that the rare pathological features of CHB with PBC are similar to those of PBC-AIH and small duct injury was observed.
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Affiliation(s)
- Yun Ye
- Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang 212003, Jiangsu Province, China
| | - Qian Zhang
- Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang 212003, Jiangsu Province, China
| | - Zhong-Hua Lu
- Department of Liver Disease, Wuxi No. 5 People’s Hospital Affiliated to Jiangnan University, Wuxi 214000, Jiangsu Province, China
| | - You-Wen Tan
- Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang 212003, Jiangsu Province, China
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Muacevic A, Adler JR, Hong J. Spontaneous Retroperitoneal Hematoma: A Deadly Complication for Patients Awaiting Liver Transplant. Cureus 2022; 14:e32522. [PMID: 36654646 PMCID: PMC9838682 DOI: 10.7759/cureus.32522] [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: 12/14/2022] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Patients with end-stage liver disease (ESLD) are at increased risk for hemorrhage and spontaneous retroperitoneal hematoma (sRPH) and also carry a high mortality rate. We sought to review the natural history of sRPH in patients with ESLD at a single center. METHODS All patients admitted to a single transplantation intensive care unit (TICU) at Froedtert and the Medical College of Wisconsin Transplant Center between June 2016 and August 2018 were retrospectively reviewed. Six ESLD patients with sRPH were studied. Clinical outcome measures were liver disease severity, sRPH treatment, and patient survival. RESULTS Six patients were included, four male and two female patients, with a median age of 56.5 years (range 30-67 years). All had alcohol-induced liver cirrhosis. The median Model for End-Stage Liver Disease (MELD) score at the time of sRPH diagnosis was 40 (range 30-43). The most commonly identified source of bleeding was from lumbar arteries. One patient had recurrent bleeding after embolization and underwent repeat embolization. Five patients died. The median time to death from the diagnosis of sRPH was 7.2 days (range 2-12 days). The patient who survived following embolization had the lowest MELD score. CONCLUSION Critically ill cirrhotic patients with sRPH have a significant mortality rate. Embolization is successful, albeit seldom. This is the largest retrospective series of sRPH in cirrhotic patients in the literature.
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Enomoto H, Takashima T, Nishimura T, Aizawa N, Ikeda N, Yuri Y, Okamoto M, Yoshihara K, Yoshioka R, Kawata S, Ota S, Nakano R, Shiomi H, Iijima H. Liver cirrhosis in Japan: Future global trends in the era of progressive antiviral therapy. PORTAL HYPERTENSION & CIRRHOSIS 2022; 1:178-183. [DOI: 10.1002/poh2.30] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Accepted: 09/04/2022] [Indexed: 01/03/2025]
Abstract
AbstractIn Japan, viral hepatitis is the main cause of chronic liver diseases, including liver cirrhosis. Due to the availability of highly effective antiviral drugs in combination with antihepatitis measures, Japan has become one of the most successful countries in the world with regard to hepatitis virus elimination. In Japan, there are many elderly patients who have been infected with hepatitis C virus for a long time, and antihepatitis measures have been in place since the 2000s. Thus, the medical situation in Japan is expected to reflect the future situation in other countries where hepatitis countermeasures have been recently initiated and the infected population is aging. Our nationwide survey clarified the changes in the etiologies of liver cirrhosis in Japan. Although viral hepatitis remains a major cause of liver cirrhosis in Japan, nonviral cirrhosis is suggested to increasingly contribute to the etiologies of liver cirrhosis, as opposed to viral hepatitis‐related liver cirrhosis. The changing etiology of liver cirrhosis in Japan may help to predict future global trends in chronic liver diseases.
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Affiliation(s)
- Hirayuki Enomoto
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Tomoyuki Takashima
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Takashi Nishimura
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Nobuhiro Aizawa
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Naoto Ikeda
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Yukihisa Yuri
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Mamiko Okamoto
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Kohei Yoshihara
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Ryota Yoshioka
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Shoki Kawata
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Shogo Ota
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Ryota Nakano
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Hideyuki Shiomi
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
| | - Hiroko Iijima
- Department of Internal Medicine, Division of Hepatobiliary and Pancreatic Disease Hyogo Medical University Hyogo Japan
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Cavalcante LN, Dezan MGF, Paz CLDSL, Lyra AC. RISK FACTORS FOR HEPATOCELLULAR CARCINOMA IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE. ARQUIVOS DE GASTROENTEROLOGIA 2022; 59:540-548. [PMID: 36515349 DOI: 10.1590/s0004-2803.202204000-93] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 08/29/2022] [Indexed: 11/16/2022]
Abstract
Non-alcoholic fatty liver disease is growing in worldwide prevalence and thus, is expected to have a higher number of NAFLD-related hepatocellular carcinoma (HCC) in the following years. This review describes the risk factors associated with HCC in NAFLD-patients. The presence of liver cirrhosis is the preponderant one. Male gender, PNPLA3 variants, diabetes, and obesity also appear to predispose to the development of HCC, even in non-cirrhotic subjects. Thus far, intensive lifestyle modifications, including glycemic control, and obesity treatment, are effective therapies for NAFLD/ non-alcoholic steatohepatitis and, therefore, probably, also for HCC. Some drugs that aimed at decreasing inflammatory activity and fibrosis, as well as obesity, were studied. Other data have suggested the possibility of HCC chemoprevention. So far, however, there is no definitive evidence for the routine utilization of these drugs. We hope, in the future, to be able to profile patients at higher risk of NAFLD-HCC and outline strategies for early diagnosis and prevention.
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Affiliation(s)
- Lourianne Nascimento Cavalcante
- Universidade Federal da Bahia, Salvador, BA, Brasil.,Hospital São Rafael, Serviço de Gastro-Hepatologia, Salvador, BA, Brasil
| | | | | | - André Castro Lyra
- Universidade Federal da Bahia, Salvador, BA, Brasil.,Hospital São Rafael, Serviço de Gastro-Hepatologia, Salvador, BA, Brasil
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Ye F, Zhai M, Long J, Gong Y, Ren C, Zhang D, Lin X, Liu S. The burden of liver cirrhosis in mortality: Results from the global burden of disease study. Front Public Health 2022; 10:909455. [PMID: 36033800 PMCID: PMC9403789 DOI: 10.3389/fpubh.2022.909455] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 07/12/2022] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND Liver cirrhosis-related death is a serious threat worldwide. The number of studies exploring the mortality trend of cirrhosis caused by specific etiologies was limited. This study aimed to demonstrate the pattern and trend based on the data of global burden of disease (GBD). METHODS The data of cirrhosis mortality were collected from the GBD 2017. The Age standardized mortality rate (ASR) and estimated annual percentage changes (EAPC) were used to estimate the temporal trend of liver cirrhosis mortality by etiologies, regions, sociodemographic index (SDI), and sexes. RESULTS Globally, mortality cases of cirrhosis increased by 47.15%. Although the global ASR of cirrhosis mortality remained stable during this period, the temporal trend varied in etiologies. The ASR of mortality caused by hepatitis C virus (HCV), alcohol consumption, and non-alcoholic steatohepatitis (NASH) increased with an EAPC of 0.17 (95% CI, 0.14-0.20), 0.20 (95% CI, 0.16-0.24), 1.00 (95% CI, 0.97-1.04), respectively. A decreasing trend of ASR was found among the causes of hepatitis B virus (BV) and other causes. The increased pattern was heterogeneous worldwide. The most pronounced increase trend was found in middle-high SDI regions and Eastern Europe. Contrarily, the most pronounced decrease trend was found in low SDI regions and Western Sub-Saharan Africa. CONCLUSION Cirrhosis is still a public health problem. The growth trend of cirrhosis mortality caused by HCV was slowed by promoting direct-acting antiviral therapy. Unfortunately, we observed an unfavorable trend in etiologies for alcohol consumption and NASH, which indicated that more targeted and specific strategies should be established to limit alcohol consumption and promote healthy lifestyles in high-risk countries, especially in middle-high SDI regions and Eastern Europe.
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Affiliation(s)
- Fei Ye
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Mimi Zhai
- Xiangya Nursing School, Central South University, Changsha, China
| | - Jianhai Long
- Department of Respiratory, Beijing Tiantan Hospital, Capital Medicine University, Beijing, China
| | - Yi Gong
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Chutong Ren
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Dan Zhang
- Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Xiang Lin
- Department of General Surgery, The Huaihua Second People's Hospital, Huaihua, China
| | - Sushun Liu
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
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Comparison of Risk Factors for Cholangiocarcinoma and Hepatocellular Carcinoma: A Prospective Cohort Study in Korean Adults. Cancers (Basel) 2022; 14:cancers14071709. [PMID: 35406481 PMCID: PMC8997058 DOI: 10.3390/cancers14071709] [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: 02/11/2022] [Revised: 03/24/2022] [Accepted: 03/26/2022] [Indexed: 01/06/2023] Open
Abstract
Cholangiocarcinoma (CCA), especially intrahepatic CCA, is known to share several risk factors with hepatocellular carcinoma (HCC) and liver cirrhosis has been proposed as a common pathogenic factor. We aimed to identify the risk factors of CCA and to examine differences in risk factors between CCA and HCC. We followed 510,217 Korean adults who underwent health checkups during 2002−2003 until 2013 via linkage to national hospital discharge records. Hazard ratios (HRs) were calculated after adjustment for confounders. During the mean follow-up of 10.5 years, 1388 and 2920 individuals were diagnosed with CCA and HCC, respectively. Choledocholithiasis (HR = 13.7; 95% confidence interval (CI) = 7.58−24.88) was the strongest risk factor for CCA, followed by cholelithiasis (HR = 2.94) and hepatitis B virus (HBV) infection (HR = 2.71). Two of the strongest risk factors for HCC—liver cirrhosis (HR = 1.29; 95% CI = 0.48−3.45) and hepatitis C virus infection (HR = 1.89; 95% CI = 0.49−7.63)—were not significantly associated with the risk of CCA. HBV infection and diabetes increased the risk of both HCC and CCA, but the HRs were lower for CCA than for HCC (Pheterogeneity < 0.001 for HBV; Pheterogeneity = 0.001 for diabetes). The magnitudes of the effects of age, sex, obesity, alcohol consumption, and smoking on the development of both cancers were different (Pheterogeneity < 0.05 for each variable). In conclusion, choledocholithiasis, cholelithiasis, HBV, older age, male sex, diabetes, smoking, alcohol drinking, and obesity were found to be potential risk factors of CCA. Liver cirrhosis did not increase the risk of CCA. The magnitudes of the potential effects of common risk factors were generally different between CCA and HCC.
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Pal P, Palui R, Ray S. Heterogeneity of non-alcoholic fatty liver disease: Implications for clinical practice and research activity. World J Hepatol 2021; 13:1584-1610. [PMID: 34904031 PMCID: PMC8637673 DOI: 10.4254/wjh.v13.i11.1584] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 07/29/2021] [Accepted: 10/14/2021] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a heterogeneous condition with a wide spectrum of clinical presentations and natural history and disease severity. There is also substantial inter-individual variation and variable response to a different therapy. This heterogeneity of NAFLD is in turn influenced by various factors primarily demographic/dietary factors, metabolic status, gut microbiome, genetic predisposition together with epigenetic factors. The differential impact of these factors over a variable period of time influences the clinical phenotype and natural history. Failure to address heterogeneity partly explains the sub-optimal response to current and emerging therapies for fatty liver disease. Consequently, leading experts across the globe have recently suggested a change in nomenclature of NAFLD to metabolic-associated fatty liver disease (MAFLD) which can better reflect current knowledge of heterogeneity and does not exclude concomitant factors for fatty liver disease (e.g. alcohol, viral hepatitis, etc.). Precise identification of disease phenotypes is likely to facilitate clinical trial recruitment and expedite translational research for the development of novel and effective therapies for NAFLD/MAFLD.
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Affiliation(s)
- Partha Pal
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad 500082, India
| | - Rajan Palui
- Department of Endocrinology, The Mission Hospital, Durgapur 713212, West Bengal, India
| | - Sayantan Ray
- Department of Endocrinology, Jagannath Gupta Institute of Medical Sciences and Hospital, Kolkata 700137, West Bengal, India
- Diabetes and Endocrinology, Apollo Clinic, Ballygunge, Kolkata 700019, West Bengal, India.
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12
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Chaudhari R, Fouda S, Sainu A, Pappachan JM. Metabolic complications of hepatitis C virus infection. World J Gastroenterol 2021; 27:1267-1282. [PMID: 33833481 PMCID: PMC8015302 DOI: 10.3748/wjg.v27.i13.1267] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Revised: 02/10/2021] [Accepted: 03/12/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection is a systemic disease that is implicated in multiple extrahepatic organ dysfunction contributing to its protean manifestations. HCV is associated with diverse extrahepatic disorders including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases over and above the traditional liver manifestations of cirrhosis and hepatocellular carcinoma. The orchestration between HCV major proteins and the liver-muscle-adipose axis, poses a major burden on the global health of human body organs, if not adequately addressed. The close and inseparable associations between chronic HCV infection, metabolic disease, and cardiovascular disorders are specifically important considering the increasing prevalence of obesity and metabolic syndrome, and their economic burden to patients, the healthcare systems, and society. Cellular and molecular mechanisms governing the interplay of these organs and tissues in health and disease are therefore of significant interest. The coexistence of metabolic disorders and chronic hepatitis C infection also enhances the progression to liver fibrosis and hepatocellular carcinoma. The presence of metabolic disorders is believed to influence the chronicity and virulence of HCV leading to liver disease progression. This comprehensive review highlights current knowledge on the metabolic manifestations of hepatitis C and the potential pathways in which these metabolic changes can influence the natural history of the disease.
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Affiliation(s)
- Rahul Chaudhari
- Department of Medicine, Pennsylvania Hospital of the University of Pennsylvania, Pennsylvania, PA 19104, United States
| | - Sherouk Fouda
- School of Health and Biomedical Sciences, RMIT University, Melbourne VIC 3000, Australia
| | - Ashik Sainu
- Department of Gastroenterology and Hepatology, Aster Oman Hospital, Al Ghubra, Muscat OM 133, Oman
| | - Joseph M Pappachan
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Preston PR2 9HT, United Kingdom
- Faculty of Science, Manchester Metropolitan University, Manchester M15 6BH, United Kingdom
- Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, United Kingdom
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13
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Enomoto H, Ueno Y, Hiasa Y, Nishikawa H, Hige S, Takikawa Y, Taniai M, Ishikawa T, Yasui K, Takaki A, Takaguchi K, Ido A, Kurosaki M, Kanto T, Nishiguchi S. The transition in the etiologies of hepatocellular carcinoma-complicated liver cirrhosis in a nationwide survey of Japan. J Gastroenterol 2021; 56:158-167. [PMID: 33219410 PMCID: PMC7862502 DOI: 10.1007/s00535-020-01748-x] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Accepted: 10/31/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND We recently reported the real-world changes in the etiologies of liver cirrhosis (LC) based on nationwide survey data and assessed the etiologies of LC with hepatocellular carcinoma (HCC). METHODS Fifty-five participants from 68 institutions provided data on 23,637 patients with HCC-complicated LC. The changing trends in etiologies were assessed. We further analyzed the data from 29 hospitals that provided the annual number of newly identified HCC-complicated LC patients from 2008 to 2016 (N = 9362) without any missing years and assessed the transition in the real number of newly identified HCC-complicated LC cases. RESULTS In the overall cohort, hepatitis C virus (HCV) infection (60.3%) and hepatitis B virus (HBV) infection (12.9%) were the leading and third-most common causes of HCC-complicated LC in Japan, respectively. HCV infection was found to be the leading cause throughout Japan. The rate of viral hepatitis-related HCC decreased from 85.3 to 64.4%. Among non-viral etiologies, notable increases were observed in nonalcoholic steatohepatitis (NASH)-related HCC (from 1.5 to 7.2%) and alcoholic liver disease (ALD)-related HCC (from 8.5 to 18.6%). Regarding the real number of newly diagnosed patients, the number of patients with viral hepatitis-related HCC decreased, while the number of patients with non-viral HCC, particularly NASH-related HCC, increased. CONCLUSIONS Viral hepatitis has remained the main cause of HCC in Japan. However, the decrease in viral hepatitis-related HCC, particularly HCV-related HCC highly contributed to the etiological changes. In addition, the increased incidence of non-viral HCC, particularly NASH-related HCC, was involved in the changing etiologies of HCC-complicated LC in Japan.
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Affiliation(s)
- Hirayuki Enomoto
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Yoshiyuki Ueno
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Hiroki Nishikawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
- Center for Clinical Research and Education, Hyogo College of Medicine, Nishinomiya, Japan
| | - Shuhei Hige
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Yasuhiro Takikawa
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Makiko Taniai
- Internal Medicine, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Toru Ishikawa
- Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata, Japan
| | - Kohichiroh Yasui
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Akinobu Takaki
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Akio Ido
- Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan
| | - Tatsuya Kanto
- Hepatitis Information Center, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Tokyo, Japan
| | - Shuhei Nishiguchi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
- Department of Gastroenterology, Kano General Hospital, 7-5-15, Tenjin-bashi, Kita-ku, Osaka, 531-0041, Japan.
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14
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Eguchi Y, Wong G, Lee IH, Akhtar O, Lopes R, Sumida Y. Hepatocellular carcinoma and other complications of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in Japan: A structured review of published works. Hepatol Res 2021; 51:19-30. [PMID: 33091191 DOI: 10.1111/hepr.13583] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 08/27/2020] [Accepted: 09/08/2020] [Indexed: 02/08/2023]
Abstract
AIMS Hepatocellular carcinoma (HCC) is a significant cause of morbidity and mortality in Japan. As the treatment of viral hepatitis improves, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are rapidly becoming leading causes of HCC in Japan. This structured review aims to characterize the morbidity and mortality of HCC and other malignant and non-malignant complications among Japanese NAFLD and NASH patients. METHODS An English and Japanese structured search of published works was undertaken in PubMed, Embase, and Ichushi Web databases, identifying 6553 studies, 34 of which met predefined inclusion criteria. RESULTS Hepatocellular carcinoma was the most common incident malignancy among NAFLD/NASH patients, with higher incidence in patients with advanced/severe fibrosis (F3/F4) of 10.5%-20.0%. Although NASH results in a lower HCC cumulative incidence than hepatitis C virus (HCV) (11.3% vs. 30.5%), they have similar impacts on health outcomes, including overall mortality. Among Japanese NASH patients, HCC was found to be the main driver of mortality (40.0% in 2.7 years in NASH-HCC). With longer follow-up, higher mortality rates are observed in F3/4 patients: 25.0% in NASH F3/F4 versus 0.0% in NASH F0/2 over 7.7 years. The NASH-HCC patients also have a higher post-operative mortality than HCV-HCC patients. Additionally, NAFLD/NASH patients had higher rates of cardiovascular disease than non-NAFLD/NASH controls, and slightly higher rates of gastric cancer than HCV patients. CONCLUSION Hepatocellular carcinoma is the most common malignancy and cause of death among NAFLD/NASH patients in Japan, with higher mortality observed among those with advanced disease and complications. Early identification and effective treatments are needed.
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Affiliation(s)
- Yuichiro Eguchi
- Liver Center, Saga University Hospital, Saga, Japan.,Department of Internal Medicine, Saga University, Japan
| | | | - I-Heng Lee
- Gilead Sciences Inc, Foster City, CA, USA
| | | | | | - Yoshio Sumida
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Japan
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15
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Baek KW, Gim JA, Park JJ. Regular moderate aerobic exercise improves high-fat diet-induced nonalcoholic fatty liver disease via monoacylglycerol O-acyltransferase 1 pathway suppression. JOURNAL OF SPORT AND HEALTH SCIENCE 2020; 9:472-478. [PMID: 32928450 PMCID: PMC7498633 DOI: 10.1016/j.jshs.2018.09.001] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/05/2018] [Revised: 03/16/2018] [Accepted: 04/26/2018] [Indexed: 06/11/2023]
Abstract
PURPOSE Monoacylglycerol O-acyltransferase 1 (MGAT1) is reported to play a key role in the development of diet-induced nonalcoholic fatty liver disease (NAFLD). Thus, this study investigated the effect of exercise on suppression of the MGAT1 pathway in NAFLD tissue of high-fat diet (HFD)-induced obese rats. METHODS Male Sprague-Dawley rats were fed an HFD containing 45% fat for 6 weeks. Upon confirmation that NAFLD had been induced in the obese animals, they were divided into HFD-fed groups provided with exercise (HFD + EXE) or without exercise (HFD) and a group given dietary adjustment (DA) only, for a further 6 weeks of intervention treatment. The 6-week regular moderate aerobic exercise consisted of an accommodation phase with increasing exercise. Lipid accumulation in the liver tissue was determined by Oil Red O staining. The MGAT1 and liver lipogenic gene mRNA levels were measured by qPCR, and their protein levels by western blot assay. RESULTS Oil Red O staining showed that NAFLD was successfully induced by HFD-fed. The gene expression of MGAT1 was significantly lower in HFD + EXE than HFD. However, there was no significant difference between HFD + EXE and DA. The protein expression of MGAT1 was significantly lower in HFD + EXE than both HFD and DA. Messenger RNA and protein expression of other lipogenic genes were not different among groups. These data indicate that exercise suppresses MGAT1 pathway regardless of HFD feeding; in part, this effect could be greater than DA. CONCLUSION Our data suggest that exercise can improve NAFLD, which is probably due to suppression of MGAT1 pathway.
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Affiliation(s)
- Kyung-Wan Baek
- Division of Sport Science, Pusan National University, Busan 46241, Korea
| | - Jeong-An Gim
- Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 46241, Korea
| | - Jung-Jun Park
- Division of Sport Science, Pusan National University, Busan 46241, Korea.
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16
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Hester CA, Rich NE, Singal AG, Yopp AC. Comparative Analysis of Nonalcoholic Steatohepatitis- Versus Viral Hepatitis- and Alcohol-Related Liver Disease-Related Hepatocellular Carcinoma. J Natl Compr Canc Netw 2020; 17:322-329. [PMID: 30959469 DOI: 10.6004/jnccn.2018.7105] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Accepted: 11/21/2018] [Indexed: 01/23/2023]
Abstract
BACKGROUND Despite an increasing burden of nonalcoholic steatohepatitis (NASH), limited data are available comparing outcomes of NASH-related hepatocellular carcinoma (HCC) versus other etiologies. METHODS Patient demographic and tumor characteristics were collected for 1,051 patients diagnosed with NASH-, alcohol-related liver disease (ALD)-, hepatitis C virus (HCV)-, and hepatitis B virus (HBV)-related HCC at 2 large health systems from January 2008 through December 2016. Patient demographics, clinical characteristics, and survival were compared. Risk-adjusted treatment receipt and overall survival (OS) were examined using multivariable analysis. RESULTS A total of 92 patients with NASH-related HCC were compared with 153 patients with ALD-, 719 with HCV-, and 87 with HBV-related HCC. Patients with NASH were older, more likely female, and more likely Hispanic white. Patients with NASH and HBV had more compensated liver disease than those with ALD or HCV, including significantly higher proportions having noncirrhotic HCC. Despite similar surveillance receipt and Barcelona Clinic Liver Cancer (BCLC) tumor stage at diagnosis, patients with NASH had higher rates of curative-intent therapy than those with other diseases. Unadjusted median OS was 16 months for NASH, 15 months for ALD, 14 months for HCV, and 8 months for HBV. In multivariable analysis, NASH was associated with worse OS compared with ALD (hazard ratio, 1.92; 95% CI, 1.3-2.5), but there was no difference between NASH- and HCV- or HBV-related HCC. CONCLUSIONS Patients with NASH-related HCC present with more preserved liver function, including a higher proportion having noncirrhotic HCC, than other diseases. Despite patients having similar tumor stage at diagnosis, NASH is independently associated with worse survival compared with ALD, but similar survival compared with HCV and HBV.
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Affiliation(s)
- Caitlin A Hester
- aDepartment of Surgery, Division of Surgical Oncology, Department of Medicine, and
| | - Nicole E Rich
- bDivision of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Amit G Singal
- bDivision of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Adam C Yopp
- aDepartment of Surgery, Division of Surgical Oncology, Department of Medicine, and
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17
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Miyatake D, Shibata T, Toyoshima J, Kaneko Y, Oda K, Nishimura T, Katashima M, Sakaki M, Inoue K, Ito T, Uchida N, Furihata K, Urae A. Pharmacokinetics and Safety of a Single Oral Dose of Peficitinib (ASP015K) in Japanese Subjects With Normal and Impaired Hepatic Function. Clin Pharmacol Drug Dev 2020; 9:699-708. [PMID: 31833184 PMCID: PMC7496893 DOI: 10.1002/cpdd.751] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 10/14/2019] [Indexed: 01/06/2023]
Abstract
Peficitinib (ASP015K) is a novel Janus kinase inhibitor developed for the treatment of rheumatoid arthritis (RA). The impact of hepatic impairment on the peficitinib pharmacokinetic (PK) and safety profile was investigated in non-RA subjects (n = 24) in an open-label, parallel-group, multicenter comparative study in Japan. Subjects received a single, clinically relevant, oral dose of a peficitinib 150 mg tablet under fasting conditions. Plasma PK parameters were measured for peficitinib and its metabolites H1 (sulfate and methylated metabolite), H2 (sulfate metabolite), and H4 (methylated metabolite) in subjects with normal hepatic function, mild hepatic impairment, or moderate hepatic impairment. The peficitinib area under the plasma-concentration-time curve from time 0 to infinity (AUCinf ) and maximum observed concentration (Cmax ) were not markedly different in subjects with mild hepatic impairment versus normal hepatic function. In subjects with moderate hepatic impairment versus normal hepatic function, the geometric mean ratios for peficitinib AUCinf and Cmax , were 1.92 (90% CI: 1.39, 2.66) and 1.82 (90% CI: 1.24, 2.69), respectively. Five treatment-emergent adverse events (TEAEs) were experienced by 3 subjects, 1 in each group. There were no deaths, no serious TEAEs, and no TEAEs leading to withdrawal. In summary, the PK profile was unaltered in subjects with mild hepatic impairment after a single clinically relevant dose of peficitinib, but exposure almost doubled in subjects with moderate hepatic impairment. Peficitinib dose reduction may be considered in RA patients with moderate hepatic impairment.
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Affiliation(s)
| | | | | | | | - Kazuo Oda
- Astellas Research Institute of America LLCNorthbrookIllinoisUSA
| | | | | | | | | | | | - Naoki Uchida
- Clinical Research Institute of Clinical Pharmacology and TherapeuticsShowa UniversityTokyoJapan
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18
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Survival advantage associated with metformin usage in hepatocellular carcinoma patients with diabetes mellitus receiving radical resection: a propensity score matching analysis. Eur J Gastroenterol Hepatol 2020; 32:1030-1035. [PMID: 31764404 PMCID: PMC7337117 DOI: 10.1097/meg.0000000000001610] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Metformin is associated with improved survival among hepatocellular carcinoma (HCC) patients with diabetes mellitus. However, the role of metformin in the survival of hepatitis B virus (HBV)-related HCC patients with diabetes mellitus after radical resection is unclear, so this study aimed to assess the effects of metformin on the clinical outcomes of patients who received radical resection for HCC. PATIENTS AND METHODS A total of 250 HCC patients (30-78 years old) diagnosed with diabetes mellitus were selected between 2000 and 2013 from the First Affiliated Hospital of Nanchang University and the Eastern Hepatobiliary Surgery Hospital in China. Patients were divided into the metformin group (n = 66) and the nonmetformin group (n = 184). A propensity score matching analysis was performed to evaluate the effect of metformin in patients receiving radical resection for HCC. RESULTS In the propensity score-matched cohort (n = 176), the overall survival (OS) in the metformin group at 1, 3, and 5 years was significantly higher than in the nonmetformin group (P = 0.002), and a similar treatment effect was observed for disease-free survival (DFS) (P = 0.030). The adjusted Cox proportional hazards model showed that metformin usage significantly improved OS [hazard ratio: 0.558, 95% confidence interval (CI): 0.385-0.810]. CONCLUSIONS Metformin is associated with satisfactory clinical outcomes among HBV-related HCC patients with diabetes mellitus after radical resection. The use of metformin could significantly improve the OS and reduce the risk of HCC recurrence in patients after radical resection. A prospective controlled study is recommended to verify the metformin effect and explore its possible mechanisms.
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19
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Effects of Child-Pugh B Cirrhosis on Pharmacokinetics of Tofogliflozin, a New Sodium-Glucose Co-Transporter (SGLT2) Inhibitor. Drug Res (Stuttg) 2020; 70:401-409. [PMID: 32707593 DOI: 10.1055/a-1202-0818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
BACKGROUND Tofogliflozin is a highly selective sodium-glucose co-transporter 2 (SGLT2) inhibitor. A mass balance study with combinations of microdoses revealed that tofogliflozin has high oral bioavailability (97.5%) and that tofogliflozin in circulation is eliminated primarily by metabolic pathways, with the liver playing a prominent role in elimination. OBJECTIVES This study aimed to evaluate the effect of moderate hepatic impairment on the pharmacokinetics of tofogliflozin and on the pharmacodynamics (urinary glucose excretion [UGE]). METHODS In an open-label, parallel-group study, 17 subjects (9 with moderate hepatic impairment [Child-Pugh Class B, score 7-9] and 8 healthy) received a single oral dose of 40 mg tofogliflozin. Plasma and urine concentrations of tofogliflozin were determined. Accumulated UGE, adverse events, and physiological and laboratory test data were monitored. RESULTS Geometric mean ratio (GMR; geometric mean value for subjects with moderate hepatic impairment / geometric mean value for healthy subjects) of Cmax was 1.47 and GMR of AUCinf was 1.70. Moderate hepatic impairment had only a little effect on tmax and CLR but it prolonged MRT. The levels of cumulative UGE were similar between the 2 groups. No clinically significant adverse events, laboratory test values, or physiological test values were observed in any subject. CONCLUSIONS Moderate hepatic impairment increased Cmax and AUCinf of tofogliflozin by 47% and 70%, respectively. This increase in tofogliflozin exposure did not increase UGE in hepatically impaired subjects. A single oral dose of 40 mg tofogliflozin was well tolerated, supporting dose adjustment is unnecessary even in moderately hepatically impaired subjects.
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20
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Mohagheghi S, Khajehahmadi Z, Nikeghbalian S, Alavian SM, Doosti-Irani A, Khodadadi I, Karimi J, Sharafi H, Tavilani H. Changes in the distribution of etiologies of cirrhosis among patients referred for liver transplantation over 11 years in Iran. Eur J Gastroenterol Hepatol 2020; 32:844-850. [PMID: 31688307 DOI: 10.1097/meg.0000000000001590] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND AND AIM Cirrhosis is a major public health problem worldwide. The prevalence of cirrhosis is various in different geographical regions. The aim of the present study was to determine the distribution of the etiologies of cirrhosis and their proportional changes through recent 11 years in Iran. METHODS In this retrospective, observational study, the data of cirrhotic patients who have been listed for liver transplantation in the Namazi Transplant Center (Shiraz, Iran) between January 2006 and December 2016 were analyzed. Demographic and clinical data of the patients including model for end-stage liver disease score, year of registration, and the etiologic diagnosis for each patient were retrieved. RESULTS The ratio of males to females was the highest (2.6:1) in patients with age over 50 years. Of 4891 patients, hepatitis B virus cirrhosis had the highest frequency (23.53%) and alcoholic cirrhosis had the lowest frequency (1.70%). The percentages of waiting list patients with hepatitis B virus (34.48%-17.48%) (P < 0.001), autoimmune hepatitis (12.64%-8.50%) (P = 0.037), and alcoholic cirrhosis (2.30%-1.10%) were decreased (P = 0.008) and the percentages of waiting list patients with cholestatic (12.64%-25.20%) and nonalcoholic steatohepatitis cirrhosis (0.77%-8.82%) were increased over 11 years (both P < 0.001). Hepatitis B virus and autoimmune hepatitis cirrhosis were the most prevalent in male and female patients, respectively. CONCLUSION The results of the present study showed an increase in the frequency of cholestasis and nonalcoholic steatohepatitis cirrhosis and therefore it should be considered in the health policy implementation.
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Affiliation(s)
- Sina Mohagheghi
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran.,Department of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan
| | - Zohreh Khajehahmadi
- Department of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan
| | - Saman Nikeghbalian
- Shiraz Transplant Center, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz
| | - Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran.,Middle East Liver Diseases (MELD) Center, Tehran
| | - Amin Doosti-Irani
- Department of Epidemiology, Research Center of Modeling of Non-Communicable Disease, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Iraj Khodadadi
- Department of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan
| | - Jamshid Karimi
- Department of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan
| | | | - Heidar Tavilani
- Department of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan
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21
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Eguchi Y, Wong G, Lee EIH, Akhtar O, Lopes R, Sumida Y. Epidemiology of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in Japan: A focused literature review. JGH OPEN 2020; 4:808-817. [PMID: 33102749 PMCID: PMC7578337 DOI: 10.1002/jgh3.12349] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Revised: 04/07/2020] [Accepted: 04/18/2020] [Indexed: 12/13/2022]
Abstract
Non‐alcoholic fatty liver disease (NAFLD) and non‐alcoholic steatohepatitis (NASH) represent a growing unmet medical need and an increasingly prevalent cause of cirrhosis, hepatocellular carcinoma (HCC), and death in Japan. The aim of this review was to characterize the epidemiology of NAFLD and NASH in Japan. An English and Japanese literature search was conducted in PubMed, Embase, and ICHUSHI Web, identifying 6553 studies, 67 of which were included. Prevalence of NAFLD in the Japanese population rose from the early 1990s (12.6–12.9%) to the early 2000s (24.6–34.7% of the population). Japanese NASH prevalence is estimated to be 1.9–2.7%. NAFLD and NASH are more common among males than females; however, females experience more severe disease than males. While obese patients had higher prevalence of NAFLD/NASH, nonobese individuals (body mass index [BMI] <25 kg/m2) consistently comprised 20% to >35% of NAFLD and NASH patients. The evidence shows that, despite obesity being linked with worse disease stages, “lean‐NASH” also plays an important role in NASH epidemiology. Besides obesity, diabetes and metabolic syndrome appeared to be reliably associated with disease severity. The prevalence of advanced fibrosis or cirrhotic disease was the highest in patients with NASH‐HCC (44–80% with stage F3/F4 disease), while 21–50% of patients with NASH had F3/F4 disease. NAFLD/NASH is common in the Japanese population, and the prevalence of these conditions has tripled in the last two decades. Furthermore, these NAFLD/NASH patients have a high comorbidity burden. Early and efficient identification of safe and effective treatments for NAFLD/NASH patients is urgently needed.
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Affiliation(s)
- Yuichiro Eguchi
- Liver Center, Saga University Hospital, Saga University Saga Japan
| | - Gabriel Wong
- Gilead Sciences, Inc. Foster City California USA
| | | | | | | | - Yoshio Sumida
- Division of Hepatology and Pancreatology, Department of Internal Medicine Aichi Medical University Nagakute Japan
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Nagai K, Ide K, Kawasaki Y, Tanaka-Mizuno S, Seto K, Iwane S, Eguchi Y, Kawakami K. Estimating the cost-effectiveness of screening for hepatitis C virus infection in Japan. Hepatol Res 2020; 50:542-556. [PMID: 31899841 DOI: 10.1111/hepr.13478] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Revised: 11/28/2019] [Accepted: 12/04/2019] [Indexed: 01/15/2023]
Abstract
AIM The management of hepatitis C virus (HCV) has changed with the advent of interferon (IFN)-free treatment and the declining prevalence of HCV infection, which may impact the cost-effectiveness of the screening. We aimed to compare the cost-effectiveness and clinical outcomes of three screening strategies in the Japanese general population: no screening, screening plus IFN-based therapy, and screening plus IFN-free therapy. METHODS We developed a decision analytic Markov model for screening intervention and natural history of HCV. Model parameters were derived from published literature. A lifetime horizon and the healthcare payer perspective were taken. Subanalyses included high screening scenario with improved rates of screening and attending referral, in addition to heterogeneity analysis by age subgroup. RESULTS In the base case, the incremental cost-effectiveness ratio in the Japanese general population aged 40-89 years was ¥1 124 482 and ¥1 085 183 per quality-adjusted life year gained for screening plus IFN-free therapy compared with no screening and screening plus IFN-based therapy, respectively. Screening plus IFN-free therapy remained cost-effective below ¥5 000 000 per quality-adjusted life year gained in sensitivity analyses. Incremental cost-effectiveness ratios were lower in the younger population. Nearly 0.2% of HCV-related deaths were avoided by 1.5% of the general population screened followed by IFN-free therapy relative to no screening; the impact was greater with improved rates of screening and attending referral. CONCLUSIONS Screening and subsequent IFN-free therapy for HCV appears to be cost-effective. Early diagnosis and treatment would produce a favorable incremental cost-effectiveness ratio. Improved rates of screening and attending referral would result in further reduction of disease progression.
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Affiliation(s)
- Kota Nagai
- Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan.,Eisai Co., Ltd., Tokyo, Japan
| | - Kazuki Ide
- Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan.,Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan
| | - Yohei Kawasaki
- Biostatistics Section, Clinical Research Center, Chiba University Hospital, Chiba, Japan
| | | | - Kahori Seto
- Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan
| | - Shinji Iwane
- Liver Center, Saga University Hospital, Saga, Japan
| | | | - Koji Kawakami
- Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan.,Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan
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23
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Enomoto H, Ueno Y, Hiasa Y, Nishikawa H, Hige S, Takikawa Y, Taniai M, Ishikawa T, Yasui K, Takaki A, Takaguchi K, Ido A, Kurosaki M, Kanto T, Nishiguchi S. Transition in the etiology of liver cirrhosis in Japan: a nationwide survey. J Gastroenterol 2020; 55:353-362. [PMID: 31768801 PMCID: PMC7026312 DOI: 10.1007/s00535-019-01645-y] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Accepted: 11/14/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND To assess the recent real-world changes in the etiologies of liver cirrhosis (LC) in Japan, we conducted a nationwide survey in the annual meeting of the Japan Society of Hepatology (JSH). METHODS We investigated the etiologies of LC patients accumulated from 68 participants in 79 institutions (N = 48,621). We next assessed changing trends in the etiologies of LC by analyzing cases in which the year of diagnosis was available (N = 45,834). We further evaluated the transition in the real number of newly identified LC patients by assessing data from 36 hospitals with complete datasets for 2008-2016 (N = 18,358). RESULTS In the overall data, HCV infection (48.2%) was the leading cause of LC in Japan, and HBV infection (11.5%) was the third-most common cause. Regarding the transition in the etiologies of LC, the contribution of viral hepatitis-related LC dropped from 73.4 to 49.7%. Among the non-viral etiologies, alcoholic-related disease (ALD) and nonalcoholic steatohepatitis (NASH)-related LC showed a notable increase (from 13.7 to 24.9% and from 2.0 to 9.1%, respectively). Regarding the real numbers of newly diagnosed patients from 2008 to 2016, the numbers of patients with viral hepatitis-related LC decreased, while the numbers of patients with non-viral LC increased. CONCLUSIONS HCV has remained the main cause of LC in Japan; however, the contribution of viral hepatitis as an etiology of LC is suggested to have been decreasing. In addition, non-viral LC, such as ALD-related LC and NASH-related LC, is suggested to have increased as etiologies of LC in Japan.
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Affiliation(s)
- Hirayuki Enomoto
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo, 663-8501, Japan
| | - Yoshiyuki Ueno
- Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Hiroki Nishikawa
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo, 663-8501, Japan
- Center for Clinical Research and Education, Hyogo College of Medicine, Nishinomiya, Japan
| | - Shuhei Hige
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Yasuhiro Takikawa
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Makiko Taniai
- Internal Medicine, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Toru Ishikawa
- Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata, Japan
| | - Kohichiroh Yasui
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Akinobu Takaki
- Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Akio Ido
- Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan
| | - Tatsuya Kanto
- Hepatitis Information Center, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Tokyo, Japan
| | - Shuhei Nishiguchi
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo, 663-8501, Japan.
- Center for Clinical Research and Education, Hyogo College of Medicine, Nishinomiya, Japan.
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24
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Ujiie N, Nakano T, Yamada M, Sato C, Nakanishi C, Fujishima F, Ito K, Shindo T, Shimokawa H, Kamei T. Low-energy extracorporeal shock wave therapy for a model of liver cirrhosis ameliorates liver fibrosis and liver function. Sci Rep 2020; 10:2405. [PMID: 32051434 PMCID: PMC7016168 DOI: 10.1038/s41598-020-58369-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Accepted: 01/06/2020] [Indexed: 12/02/2022] Open
Abstract
Low-energy extracorporeal shock waves (LESW) have been studied as a new treatment for angina pectoris and several ischemic diseases because of its effect on angiogenesis and inhibition of fibrosis of the heart. The effect of LESW on fibrosis in liver cirrhosis has not been studied. The aim of this study was to verify the amelioration of liver fibrosis by LESW and elucidate its mechanisms in a rat model of drug-induced liver cirrhosis. Male Wistar rats aged 7 weeks were injected with carbon tetrachloride intraperitoneally twice a week for 12 weeks. Eight rats underwent LESW therapy (0.25 mJ/mm2, 4 Hz, 1000 shots) under general anesthesia (shock wave group). Seven rats only underwent general anesthesia (control group). Quantitative analysis showed that the area of fibrosis in the shock wave group was significantly reduced compared with the control group (11,899.9 vs. 23,525.3 pixels per field, p < 0.001). In the shock wave group, the mRNA expression of transforming growth factor (TGF)-β1 was significantly suppressed (0.40-fold, p = 0.018) and vascular endothelial growth factor-B was significantly increased (1.77-fold, p = 0.006) compared with the control group. Serum albumin was significantly higher in the shock wave group than in the control group (3.0 vs. 2.4 g/dl, p = 0.025). Aspartate aminotransferase/alanine aminotransferase ratio decreased by LESW compared with the control group (1.49 vs. 2.04, p = 0.013). These results suggest that LESW therapy ameliorates liver fibrosis by reducing the expression of TGF-β1 and increasing the expression of angiogenic factors, and improves hepatic function.
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Affiliation(s)
- Naoto Ujiie
- Division of Advanced Surgical Science and Technology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Toru Nakano
- Division of Advanced Surgical Science and Technology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. .,Division of Gastroenterologic and Hepatobiliarypancreatic Surgery, Tohoku Medical and Pharmaceutical University Hospital, Sendai, Miyagi, Japan.
| | - Masato Yamada
- Division of Advanced Surgical Science and Technology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Chiaki Sato
- Division of Advanced Surgical Science and Technology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Chikashi Nakanishi
- Division of Advanced Surgical Science and Technology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Fumiyoshi Fujishima
- Department of Anatomic Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Kenta Ito
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Tomohiko Shindo
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Hiroaki Shimokawa
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Takashi Kamei
- Division of Advanced Surgical Science and Technology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
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25
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Shimizu Y, Mizuno S, Fujinami N, Suzuki T, Saito K, Konishi M, Takahashi S, Gotohda N, Tada T, Toyoda H, Kumada T, Miura M, Suto K, Yamaji T, Matsuda T, Endo I, Nakatsura T. Plasma and tumoral glypican-3 levels are correlated in patients with hepatitis C virus-related hepatocellular carcinoma. Cancer Sci 2020; 111:334-342. [PMID: 31774932 PMCID: PMC7004540 DOI: 10.1111/cas.14251] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Revised: 11/12/2019] [Accepted: 11/17/2019] [Indexed: 12/24/2022] Open
Abstract
Glypican-3 (GPC3) is a cancer antigen expressed in approximately 80% of hepatocellular carcinomas (HCC) and is secreted into the blood. To confirm the effectiveness of GPC3 as a biomarker in HCC, we analyzed the relationship between GPC3 expression levels in cancer cells and in blood in 56 patients with HCC. Preoperative plasma GPC3 levels were determined with an immunoassay, and expression of GPC3 in resected tumors was analyzed by immunohistochemical staining. Median plasma GPC3 level in all HCC cases was 4.6 pg/mL, and tended to be higher in patients with hepatitis C virus (HCV)-related HCC (HCV group) (9.9 pg/mL) than in patients with hepatitis B virus (HBV)-related HCC (HBV group) (2.6 pg/mL) or in those without virus infection (None group) (3.0 pg/mL), suggesting that the virus type most likely influences GPC3 secretion. Median percentage of GPC3+ cells in tumors was also higher in the HCV (26.2%) and HBV (11.1%) groups than in the None group (4.2%). In the HCV group, there was a positive correlation between the two parameters (r = 0.66, P < .01). Moreover, receiver operating characteristic analysis predicted >10% GPC3+ cells in a tumor if the cut-off value was 6.8 pg/mL (sensitivity 80%, specificity 100%; area under the curve 0.875, 95% confidence interval 0.726-1) in the HCV group. Plasma concentration of GPC3 could be a predictive marker of tumoral GPC3 expression in patients with HCV-related HCC, suggesting a useful biomarker for immunotherapies targeting GPC3, although larger-scale validations are needed.
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Affiliation(s)
- Yasuhiro Shimizu
- Division of Cancer ImmunotherapyExploratory Oncology Research and Clinical Trial CenterNational Cancer CenterKashiwaJapan
- Department of Gastroenterological SurgeryYokohama City University Graduate School of MedicineYokohamaJapan
| | - Shoichi Mizuno
- Division of Cancer ImmunotherapyExploratory Oncology Research and Clinical Trial CenterNational Cancer CenterKashiwaJapan
| | - Norihiro Fujinami
- Division of Cancer ImmunotherapyExploratory Oncology Research and Clinical Trial CenterNational Cancer CenterKashiwaJapan
| | - Toshihiro Suzuki
- Division of Cancer ImmunotherapyExploratory Oncology Research and Clinical Trial CenterNational Cancer CenterKashiwaJapan
- General Medical Education and Research CenterTeikyo UniversityTokyoJapan
| | - Keigo Saito
- Division of Cancer ImmunotherapyExploratory Oncology Research and Clinical Trial CenterNational Cancer CenterKashiwaJapan
| | - Masaru Konishi
- Department of Hepatobiliary and Pancreatic SurgeryNational Cancer Center Hospital EastKashiwaJapan
| | - Shinichiro Takahashi
- Department of Hepatobiliary and Pancreatic SurgeryNational Cancer Center Hospital EastKashiwaJapan
| | - Naoto Gotohda
- Department of Hepatobiliary and Pancreatic SurgeryNational Cancer Center Hospital EastKashiwaJapan
| | - Toshifumi Tada
- Department of Gastroenterology and HepatologyOgaki Municipal HospitalOgakiJapan
| | - Hidenori Toyoda
- Department of Gastroenterology and HepatologyOgaki Municipal HospitalOgakiJapan
| | - Takashi Kumada
- Department of Gastroenterology and HepatologyOgaki Municipal HospitalOgakiJapan
| | - Masahiro Miura
- Central Research LaboratoriesSysmex CorporationHyogoJapan
| | - Kouzou Suto
- Central Research LaboratoriesSysmex CorporationHyogoJapan
| | - Taiki Yamaji
- Epidemiology and Prevention GroupCenter for Public Health SciencesNational Cancer CenterTokyoJapan
| | - Takahisa Matsuda
- Division of Screening TechnologyCenter for Public Health SciencesNational Cancer CenterTokyoJapan
| | - Itaru Endo
- Department of Gastroenterological SurgeryYokohama City University Graduate School of MedicineYokohamaJapan
| | - Tetsuya Nakatsura
- Division of Cancer ImmunotherapyExploratory Oncology Research and Clinical Trial CenterNational Cancer CenterKashiwaJapan
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26
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Suoh M, Tamori A, Amano-Teranishi Y, Nakai T, Enomoto M, Kawasaki Y, Kioka K, Kawada N. The Administration of Tenofovir Disoproxil Fumarate for Pregnant Japanese Women with Chronic Hepatitis B. Intern Med 2020; 59:205-210. [PMID: 31941870 PMCID: PMC7008036 DOI: 10.2169/internalmedicine.3504-19] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Accepted: 07/29/2019] [Indexed: 12/16/2022] Open
Abstract
The appropriate management of hepatitis B virus (HBV) infection during pregnancy has not been established in Japan. We herein report five HBV-infected pregnant Japanese women who received tenofovir disoproxil fumarate (TDF). Two of them had been born after the introduction of nationwide immunoprophylaxis and were vertically infected with HBV, highlighting the need to address mother-to-child transmission further. In both entecavir-experienced and nucleoside/nucleotide analog-naïve mothers, TDF suppressed HBV replication without serious adverse events. All five children were free from congenital disorders, growth impairment, and HBV infection. TDF showed safety and efficacy for pregnant woman with chronic hepatitis B and might have helped prevent mother-to-child transmission.
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Affiliation(s)
- Maito Suoh
- Department of Hepatology, Osaka City General Hospital, Japan
- Department of Hepatology, Osaka City University Graduate School of Medicine, Japan
| | - Akihiro Tamori
- Department of Hepatology, Osaka City University Graduate School of Medicine, Japan
| | | | - Takashi Nakai
- Department of Hepatology, Osaka City General Hospital, Japan
| | - Masaru Enomoto
- Department of Hepatology, Osaka City University Graduate School of Medicine, Japan
| | - Yasuko Kawasaki
- Department of Hepatology, Osaka City General Hospital, Japan
| | - Kiyohide Kioka
- Department of Hepatology, Osaka City General Hospital, Japan
| | - Norifumi Kawada
- Department of Hepatology, Osaka City University Graduate School of Medicine, Japan
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27
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Sasaki R, Shiino C, Imawari M, Bentley R, Cai B, Yoshida M, Afdhal N. Safety and effectiveness of lusutrombopag in Japanese chronic liver disease patients with thrombocytopenia undergoing invasive procedures: Interim results of a postmarketing surveillance. Hepatol Res 2019; 49:1169-1181. [PMID: 31228221 PMCID: PMC6899664 DOI: 10.1111/hepr.13392] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Revised: 06/14/2019] [Accepted: 06/14/2019] [Indexed: 01/10/2023]
Abstract
AIM Lusutrombopag is approved for the treatment of thrombocytopenia in chronic liver disease patients undergoing invasive procedures. This real-world surveillance assesses the safety and effectiveness of lusutrombopag in Japan. METHODS This ongoing, multicenter, prospective, real-world surveillance is collecting data from case report forms between October 2016 and May 2021. Interim data up to September 2018 were used to evaluate safety (adverse events and adverse drug reactions [ADRs]) and effectiveness (proportion of patients avoiding preoperative platelet transfusion and change in platelet count from baseline). RESULTS The safety analysis set included 331 patients. The mean baseline platelet count was 46.2 ± 13.7 × 109 /L. Of 377 invasive procedures, radiofrequency ablation (110 procedures, 29.2%) was the most frequent. The mean time from starting lusutrombopag treatment to invasive procedure was 12.3 days. Incidences of serious adverse events and ADRs were 8.76% and 3.32%, respectively. Six cases (1.81%) of portal vein thrombosis were considered serious adverse events; of these, four cases (1.21%) were classified as serious ADRs. Of 300 patients who underwent an invasive procedure (excluding those with platelet transfusion refractoriness), 282 (94.0%) avoided preoperative platelet transfusion. In patients with platelet measurements before and after lusutrombopag administration who did not undergo platelet transfusion, the mean maximum change in platelet count from baseline was 41.7 ± 31.4 × 109 /L (range, -6 to 276; n = 286). All patients receiving second (n = 20) and third (n = 1) treatments avoided preoperative platelet transfusion without developing any ADRs. CONCLUSIONS This real-world surveillance further supports the safety and effectiveness of lusutrombopag in patients with chronic liver disease undergoing invasive procedures.
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Affiliation(s)
| | - Chikako Shiino
- Postmarketing Surveillance & Pharmacoepidemiology Department, Shionogi Pharmacovigilance CenterOsakaJapan
| | - Michio Imawari
- Institute for Gastrointestinal and Liver Diseases, Shin‐Yurigaoka General HospitalKawasakiJapan
| | - Roy Bentley
- Global Market Access, ShionogiFlorham ParkNew JerseyUSA
| | - Bin Cai
- Global Observational Research, Epidemiology and Health Outcomes, ShionogiFlorham ParkNew JerseyUSA
| | | | - Nezam Afdhal
- Liver Center, Beth Israel Deaconess Medical CenterBostonMassachusettsUSA
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28
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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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Zaki M, Hazem M, Elsamman M. Shear wave elastography in assessment of liver stiffness and prediction of gastro-esophageal varices in patients with liver cirrhosis. THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2019. [DOI: 10.1186/s43055-019-0015-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
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Chueiri Neto F, Emídio LA, Perales SR, Stucchi RSB, Dragosavac D, Falcao ALE, Osni Leão Perin P, Boin IDFSF, de Ataide EC. Bloodstream Infections in Early Postsurgery Liver Transplant: An Analysis of 401 Patients Over 10 Years. Transplant Proc 2019; 51:1972-1977. [PMID: 31399179 DOI: 10.1016/j.transproceed.2019.03.040] [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: 10/24/2018] [Revised: 01/23/2019] [Accepted: 03/13/2019] [Indexed: 11/18/2022]
Abstract
Bloodstream infections are a major factor contributing to morbidity and mortality following liver transplantation. The increasing occurrence of multidrug-resistant bloodstream infections represents a challenge for the prevention and treatment of those infections. The aim of this study was to evaluate the occurrence and microbiological profile of bloodstream infections during the early postoperative period (from day 0 to day 60) in patients undergoing liver transplantation from January 2005 to June 2016 at the State University of Campinas General Hospital. A total of 401 patients who underwent liver transplantation during this period were included in the study. The most common cause of liver disease was hepatitis C virus cirrhosis (34.01%), followed by alcoholic disease (16.24%). A total of 103 patients had 139 microbiologically proven bloodstream infections. Gram-negative bacteria were isolated in 63.31% of the cases, gram-positive bacteria in 28.78%, and fungi in 7.91%. Fifty-six infections (43.75%) were multidrug-resistant bacteria, and 72 (56.25%) were not. There was no linear trend concerning the occurrence of multidrug-resistant organisms throughout the study period. Patients with multidrug-resistant bloodstream infections had a significantly lower survival rate than those with no bloodstream infections and those with non-multidrug-resistant bloodstream infections. In conclusion, the occurrence of bloodstream infections during the early postoperative period was still high compared with other profile patients, as well as the rates of multidrug-resistant organisms. Even though the occurrence of multidrug resistance has been stable for the past decade, the lower survival rates associated with that condition and the challenge related to its treatment are of major concern.
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31
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Koganebuchi K, Kimura R. Biomedical and genetic characteristics of the Ryukyuans: demographic history, diseases and physical and physiological traits. Ann Hum Biol 2019; 46:354-366. [PMID: 31116031 DOI: 10.1080/03014460.2019.1582699] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Context: The Ryukyu Islands stretch across a southwestern area of the Japanese Archipelago. Because of their unique geographical and historical backgrounds, Ryukyuans have their own genetic and phenotypic characteristics, which have been disclosed in previous anthropological and biomedical studies. Objective: The history, peopling and biomedical and genetic characteristics of Ryukyuans are reviewed and future research directions are discussed. Conclusion: Morphological and genetic studies have suggested the complex demographic history of Ryukyuans and their relationships with other Asian populations. Knowledge of population formation processes is important to understand the distribution of pathogens. In viral infectious diseases, some strains that may be associated with disease symptoms are specific to Ryukyuans. Dramatic changes in diet have played an important role among Ryukyuans in terms of increases in lifestyle-related diseases and mortality risks. To achieve a better understanding of pathogenic disease factors, further integration of findings regarding the genetic and biomedical characteristics of the Ryukyuans is needed.
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Affiliation(s)
- Kae Koganebuchi
- Department of Human Biology and Anatomy, Graduate School of Medicine, University of the Ryukyus , Okinawa , Japan
| | - Ryosuke Kimura
- Department of Human Biology and Anatomy, Graduate School of Medicine, University of the Ryukyus , Okinawa , Japan
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Moayedi J, Moini M, Geramizadeh B, Malekhosseini SA, Yaghobi R. Seropositive Form of Occult Hepatitis B Virus Infection in Iranian Patients with Cryptogenic Liver Cirrhosis. HEPATITIS MONTHLY 2019; In Press. [DOI: 10.5812/hepatmon.84806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Fujiya Y, Hayakawa K, Gu Y, Yamamoto K, Mawatari M, Kutsuna S, Takeshita N, Kato Y, Kanagawa S, Ohmagari N. Age-related differences in clinical characteristics of invasive group G streptococcal infection: Comparison with group A and group B streptococcal infections. PLoS One 2019; 14:e0211786. [PMID: 30845149 PMCID: PMC6405256 DOI: 10.1371/journal.pone.0211786] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Accepted: 01/22/2019] [Indexed: 12/22/2022] Open
Abstract
Purpose Invasive Group G streptococcal infection (iGGS) has increasingly been recognized as a cause of severe disease, mainly among elderly people with chronic illnesses. This study aimed to examine age-related differences in clinical characteristics of iGGS and describe its characteristics among very elderly individuals (≥80 years). Methods Fifty-four iGGS patients for whom detailed clinical information was available were identified from 2002 to 2014 in a tertiary care hospital in Japan. iGGS (n = 54) was compared with invasive Group A (iGAS; n = 17) and B streptococcal infection patients (iGBS; n = 52) based on patient age. Results The incidence of iGGS in our catchment area significantly increased during the study period. The prevalence of iGGS in the very elderly population was higher than that of iGAS or iGBS (p<0.001). Among iGGS patients, cardiovascular disease, chronic kidney disease, oxygen demand, and bacteremia with unknown focus of infection were more frequent in the very elderly population (p = 0.009, p = 0.02, p = 0.04, and p = 0.04, respectively). Altered mental status was present in half of iGGS patients aged ≥60 years (p = 0.03). In contrast, alcohol drinking and liver cirrhosis were significantly more frequent in patients with iGGS aged <60 years than in other age groups (p<0.001, p = 0.001, respectively). Levofloxacin resistance in GBS isolates was significantly more frequent among very elderly patients than among other age groups (p<0.001). Conclusions The burden of iGGS has been increasing in our catchment area. Different iGGS-associated clinical characteristics were found in each age group. Unclear and atypical clinical manifestations and syndromes were likely to be observed in very elderly patients. Alcohol drinking and liver cirrhosis may contribute to iGGS even in patients aged <60 years. Understanding these age-related differences could be helpful for optimal diagnosis and treatment.
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Affiliation(s)
- Yoshihiro Fujiya
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan
- * E-mail:
| | - Kayoko Hayakawa
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan
| | - Yoshiaki Gu
- AMR Clinical Reference Center, National Center for Global Health and Medicine Hospital, Shinjuku-ku, Tokyo, Japan
| | - Kei Yamamoto
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan
| | - Momoko Mawatari
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan
| | - Satoshi Kutsuna
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan
| | - Nozomi Takeshita
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan
| | - Yasuyuki Kato
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan
| | - Shuzo Kanagawa
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan
| | - Norio Ohmagari
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan
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Wong MCS, Huang JLW, George J, Huang J, Leung C, Eslam M, Chan HLY, Ng SC. The changing epidemiology of liver diseases in the Asia-Pacific region. Nat Rev Gastroenterol Hepatol 2019; 16:57-73. [PMID: 30158570 DOI: 10.1038/s41575-018-0055-0] [Citation(s) in RCA: 233] [Impact Index Per Article: 38.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
This Review presents current epidemiological trends of the most common liver diseases in Asia-Pacific countries. Hepatitis B virus (HBV) remains the primary cause of cirrhosis; despite declining prevalence in most Asian nations, this virus still poses a severe threat in some territories and regions. Mortality resulting from HBV infection is declining as a result of preventive measures and antiviral treatments. The epidemiological transition of hepatitis C virus (HCV) infection has varied in the region in the past few decades, but the medical burden of infection and the prevalence of its related cancers are increasing. The lack of licensed HCV vaccines highlights the need for novel treatment strategies. The prevalence of nonalcoholic fatty liver disease (NAFLD) has risen in the past decade, mostly owing to increasingly urbanized lifestyles and dietary changes. Alternative herbal medicine and dietary supplements are major causes of drug-induced liver injury (DILI) in some countries. Complications arising from these chronic liver diseases, including cirrhosis and liver cancer, are therefore emerging threats in the Asia-Pacific region. Key strategies to control these liver diseases include monitoring of at-risk populations, implementation of national guidelines and increasing public and physician awareness, in concert with improving access to health care.
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Affiliation(s)
- Martin C S Wong
- Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
- State Key Laboratory for Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
- J.C. School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Jason L W Huang
- J.C. School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Jacob George
- Storr Liver Centre, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia
| | - Junjie Huang
- J.C. School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Colette Leung
- J.C. School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia
| | - Henry L Y Chan
- Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
- State Key Laboratory for Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Siew C Ng
- Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong.
- State Key Laboratory for Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong.
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong.
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Méndez-Sánchez N, Zamarripa-Dorsey F, Panduro A, Purón-González E, Coronado-Alejandro EU, Cortez-Hernández CA, Higuera de la Tijera F, Pérez-Hernández JL, Cerda-Reyes E, Rodríguez-Hernández H, Cruz-Ramón VC, Ramírez-Pérez OL, Aguilar-Olivos NE, Rodríguez-Martínez OF, Cabrera-Palma S, Cabrera-Álvarez G. Current trends of liver cirrhosis in Mexico: Similitudes and differences with other world regions. World J Clin Cases 2018; 6:922-930. [PMID: 30568947 PMCID: PMC6288506 DOI: 10.12998/wjcc.v6.i15.922] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2018] [Revised: 10/19/2018] [Accepted: 11/14/2018] [Indexed: 02/05/2023] Open
Abstract
AIM To investigate the main current etiologies of cirrhosis in Mexico. METHODS We performed a cross-sectional retrospective multicenter study that included eight hospitals in different areas of Mexico. These hospitals provide health care to people of diverse social classes. The inclusion criteria were a histological, clinical, biochemical, endoscopic, or imaging diagnosis of liver cirrhosis. Data were obtained during a 5-year period (January 2012-December 2017). RESULTS A total of 1210 patients were included. The mean age was 62.5 years (SD = 12.1), and the percentages of men and women were similar (52.0% vs 48.0%). The most frequent causes of liver cirrhosis were hepatitis C virus (HCV) (36.2%), alcoholic liver disease (ALD) (31.2%), and nonalcoholic steatohepatitis (23.2%), and the least frequent were hepatitis B virus (1.1%), autoimmune disorders (7.3%), and other conditions (1.0%). CONCLUSION HCV and ALD are the most frequent causes of cirrhosis in Mexico. However, we note that non-alcoholic fatty liver disease (NAFLD) as an etiology of cirrhosis increased by 100% compared with the rate noted previously. We conclude that NAFLD will soon become one of the most frequent etiologies of liver cirrhosis in Mexico.
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Affiliation(s)
- Nahum Méndez-Sánchez
- Liver Research Unit, Medica Sur Clinic and Foundation, Mexico City 14050, Mexico
| | | | - Arturo Panduro
- Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara “Fray Antonio Alcalde”, Guadalajara 44280, Jalisco, Mexico
| | - Emma Purón-González
- Department of Internal Medicine, “Christus Muguerza “Super Specialty” Hospital” Monterrey, Monterrey 64060, Nuevo León, Mexico
| | - Edgar Ulises Coronado-Alejandro
- Department of Internal Medicine, “Christus Muguerza “Super Specialty” Hospital” Monterrey, Monterrey 64060, Nuevo León, Mexico
| | | | - Fátima Higuera de la Tijera
- Department of Gastroenterology, “General Hospital of Mexico “Dr. Eduardo Liceaga”, Mexico City 06720, Mexico
| | - José Luis Pérez-Hernández
- Department of Gastroenterology, “General Hospital of Mexico “Dr. Eduardo Liceaga”, Mexico City 06720, Mexico
| | - Eira Cerda-Reyes
- Department of Gastroenterology, “Central Military Hospital”, Mexico City 11200, Mexico
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IL-1β/ATF3-mediated induction of Ski2 expression enhances hepatitis B virus x mRNA degradation. Biochem Biophys Res Commun 2018; 503:1854-1860. [PMID: 30055801 DOI: 10.1016/j.bbrc.2018.07.126] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Accepted: 07/24/2018] [Indexed: 12/17/2022]
Abstract
Hepatitis B virus (HBV) -x protein is a transcriptional regulator required for the HBV life cycle. HBx also induces complications in the host such as hepatocellular carcinoma. We previously showed that HBx mRNA is degraded by the Ski2/RNA exosome complex. In the present study, we report the regulation of this system through the control of Ski2 expression. We identified interleukin (IL) -1β as an inducer of expression from the Ski2 promoter. IL-1β induced the expression of ATF3 transcription factor, which in turn binds to cyclic AMP-responsive element sequence in the Ski2 promoter and is responsible for Ski2 promoter induction by IL-1β. We previously reported that Ski2 expression increases HBx mRNA degradation; consistent with those data, we showed here that HBx mRNA is degraded in response to IL-1β treatment. Interestingly, HBx also significantly induced Ski2 expression. To our knowledge, this is the first report to show activation of the Ski2/RNA exosome complex by both the host and HBV. Understanding the regulation of the Ski2/RNA exosome system is expected to facilitate prevention of HBx-mediated complications through targeting the posttranscriptional degradation of HBx mRNA; and will also help shedding a light on the role of RNA decay systems in inflammation.
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Li B, Zhang C, Zhan YT. Nonalcoholic Fatty Liver Disease Cirrhosis: A Review of Its Epidemiology, Risk Factors, Clinical Presentation, Diagnosis, Management, and Prognosis. Can J Gastroenterol Hepatol 2018; 2018:2784537. [PMID: 30065915 PMCID: PMC6051295 DOI: 10.1155/2018/2784537] [Citation(s) in RCA: 75] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2018] [Revised: 05/31/2018] [Accepted: 06/13/2018] [Indexed: 12/11/2022] Open
Abstract
Cirrhosis is the common end stage of a number of chronic liver conditions and a significant cause of morbidity and mortality. With the growing epidemic of obesity and metabolic syndrome, nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide and will become one of the leading causes of cirrhosis. Increased awareness and understanding of NAFLD cirrhosis are essential. To date, there has been no published systematic review on NAFLD cirrhosis. Thus, this article reviews recent studies on the epidemiology, risk factors, clinical presentation, diagnosis, management, and prognosis of NAFLD cirrhosis.
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Affiliation(s)
- Bei Li
- Department of Gastroenterology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
| | - Chuan Zhang
- Department of Gastroenterology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
| | - Yu-Tao Zhan
- Department of Gastroenterology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
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Mochida S, Nakayama N, Ido A, Inoue K, Genda T, Takikawa Y, Sakaida I, Terai S, Yokosuka O, Shimizu M, Takikawa H. Proposed diagnostic criteria for acute-on-chronic liver failure in Japan. Hepatol Res 2018; 48:219-224. [PMID: 29361652 DOI: 10.1111/hepr.13066] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2017] [Revised: 01/19/2018] [Accepted: 01/20/2018] [Indexed: 12/22/2022]
Abstract
To establish diagnostic criteria for acute-on-chronic liver failure (ACLF) in Japan, the Intractable Hepato-Biliary Disease Study Group of Japan undertook a multicenter pilot survey for patients fulfilling the Asian Pacific Association for the Study of the Liver (APASL), Association for the Study of the Liver-Chronic Liver Failure (EASL-Clif) Consortium, or Chinese Medical Association (CMA) diagnostic criteria for ACLF. The APASL criteria were suitable for screening Japanese patients with ACLF when patients whose conditions were triggered by gastrointestinal bleeding were included within the disease entity, and the EASL-Clif Consortium criteria were useful for classifying the severity of the patients' conditions. Based on these observations, the Study Group proposed the following diagnostic criteria for ACLF in Japan: patients with cirrhosis and a Child-Pugh score of 5-9 should be diagnosed as having ACLF when a deterioration of liver function (serum bilirubin level ≥5.0 mg/dL and prothrombin time value ≤40% of the standardized values and/or international normalization rate ≥1.5) caused by severe liver damage develops within 28 days after acute insults, such as alcohol abuse, bacterial infection, gastrointestinal bleeding, or the exacerbation of underlying liver diseases. The severities of the patients can be classified into four grades depending on the extent of the deterioration in organ functions, including kidney, cerebral, blood coagulation, circulatory and respiratory functions, as well as liver function. The usefulness of these novel criteria should be validated prospectively in a large-scale cohort in the future.
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Affiliation(s)
- Satoshi Mochida
- Department of Gastroenterology and Hepatology, Saitama Medical University, Moroyama, Japan
| | - Nobuaki Nakayama
- Department of Gastroenterology and Hepatology, Saitama Medical University, Moroyama, Japan
| | - Akio Ido
- Department of Digestive and Life-Style Related Disease, Health Research Course, Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Kazuaki Inoue
- Department of Gastroenterology, Showa University Fujigaoka Hospital, Yokohama, Japan
| | - Takuya Genda
- Department of Gastroenterology, Juntendo University Shizuoka Hospital, Izunokuni, Japan
| | - Yasuhiro Takikawa
- Department of Gastroenterology and Hepatology, School of Medicine, Iwate Medical University, Morioka, Japan
| | - Isao Sakaida
- Department of Gastroenterology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Shuji Terai
- Division of Gastroenterology & Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | | | - Masahito Shimizu
- Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Hajime Takikawa
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
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Nakayama N, Uemura H, Uchida Y, Tomiya T, Ido A, Inoue K, Genda T, Takikawa Y, Sakaida I, Terai S, Yokosuka O, Shimizu M, Takikawa H, Mochida S. A multicenter pilot survey to clarify the clinical features of patients with acute-on-chronic liver failure in Japan. Hepatol Res 2018; 48:303-312. [PMID: 29341357 DOI: 10.1111/hepr.13064] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2017] [Revised: 01/06/2018] [Accepted: 01/14/2018] [Indexed: 12/11/2022]
Abstract
AIM To establish diagnostic criteria for acute-on-chronic liver failure (ACLF) in Japan, a multicenter pilot survey was carried out to examine the usefulness of overseas criteria in patients with chronic liver diseases manifesting acute decompensation. METHODS Patients fulfilling the Asian-Pacific Association for the Study of the Liver (APASL), European Association for the Study of the Liver (EASL), or Chinese Medical Association (CMA) criteria for decompensation were enrolled from eight institutions in Japan, and the clinical features were evaluated. RESULTS Among 112 patients, 109 patients (97.3%) fulfilled the APASL criteria for decompensation; 7 patients were excluded because the decompensation had been provoked by gastrointestinal bleeding. Consequently, 102 patients (91.1%) were diagnosed as having ACLF according to the APASL definition. Among the patients who fulfilled the APASL criteria for decompensation, the etiologies of the underlying liver diseases were alcohol abuse in 59 cases (54.1%) and hepatitis B or hepatitis C virus infection in 24 (22.0%). The acute insults were alcohol abuse in 50 (45.9%), bacterial infection in 26 (23.9%), and exacerbation of underlying liver disease in 14 (12.8%). Fifty-four patients (49.5%) satisfied the CMA criteria, but the survival rates were similar between patients who did and those who did not meet the criteria. When 84 patients with underlying cirrhosis were classified according to the EASL-Chronic Liver Failure (Clif) Consortium criteria, the survival rates differed according to grade: 67.6% (23/34) for patients without ACLF, and 41.2% (14/34) and 18.8% (3/16) for those with grade 1/2 and grade 3 ACLF, respectively. CONCLUSION The APASL definition was suitable for screening Japanese patients with ACLF, including those whose conditions were triggered by gastrointestinal bleeding, and the EASL-Clif Consortium criteria were useful for predicting outcome.
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Affiliation(s)
- Nobuaki Nakayama
- Department of Gastroenterology and Hepatology, Saitama Medical University, Saitama, Japan
| | - Hayato Uemura
- Department of Gastroenterology and Hepatology, Saitama Medical University, Saitama, Japan
| | - Yoshihito Uchida
- Department of Gastroenterology and Hepatology, Saitama Medical University, Saitama, Japan
| | - Tomoaki Tomiya
- Department of Gastroenterology and Hepatology, Saitama Medical University, Saitama, Japan
| | - Akio Ido
- Department of Digestive and Life-Style Related Disease, Health Research Course, Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Kazuaki Inoue
- Department of Gastroenterology, Showa University Fujigaoka Hospital, Yokohama, Japan
| | - Takuya Genda
- Department of Gastroenterology, Juntendo University Shizuoka Hospital, Izunokuni, Japan
| | - Yasuhiro Takikawa
- Department of Gastroenterology and Hepatology, School of Medicine, Iwate Medical University, Morioka, Japan
| | - Isao Sakaida
- Department of Gastroenterology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Shuji Terai
- Division of Gastroenterology & Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | | | - Masahito Shimizu
- Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Hajime Takikawa
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Satoshi Mochida
- Department of Gastroenterology and Hepatology, Saitama Medical University, Saitama, Japan
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Kitazawa T, Matsumoto K, Fujita S, Seto K, Wu Y, Hirao T, Hasegawa T. Cost of illness of non-alcoholic liver cirrhosis in Japan: A time trend analysis and future projections. Hepatol Res 2018; 48:176-183. [PMID: 28497644 DOI: 10.1111/hepr.12913] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Revised: 04/25/2017] [Accepted: 05/09/2017] [Indexed: 12/29/2022]
Abstract
AIM Liver cirrhosis is a preneoplastic condition to hepatocellular carcinoma that is an important worldwide public health concern, and its economic burden has been estimated in some countries. The objective of this study was to estimate and predict the cost of illness (COI) associated with non-alcoholic liver cirrhosis in Japan. METHODS Using a COI method on available data from government statistics, we estimated the economic burden in 3-year intervals from 1996 to 2014. We then predicted the COI in 3-year intervals from 2017 to 2029 using fixed and variable model estimations. With fixed model estimation, only the estimated future population was used as a variable. Variable model estimation considered the time trends of health-related indicators throughout the past 18 years. RESULTS The estimated COI of non-alcoholic liver cirrhosis was ¥208.1bn in 2014. The COI of non-alcoholic liver cirrhosis had a downward trend from 1996 to 2014. The predicted future COI of non-alcoholic liver cirrhosis was ¥144.3-210.5bn, ¥106.0-213.8bn, ¥88.6-213.4bn, ¥76.7-215.5bn, and ¥66.4-214.3bn in 2017, 2020, 2023, 2026, and 2029, respectively. CONCLUSIONS The results of this study suggest that the COI of non-alcoholic liver cirrhosis in Japan has steadily decreased and will continue to decrease. Treatment of patients with hepatitis C virus infection with newly introduced technologies has high therapeutic effectiveness, which will affect the future prevalence of non-alcoholic liver cirrhosis. When interpreting the results of long-term estimation, it should be noted that the results of this study were based on present conditions.
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Affiliation(s)
- Takefumi Kitazawa
- Department of Social Medicine, Toho University School of Medicine, Tokyo, Japan
| | - Kunichika Matsumoto
- Department of Social Medicine, Toho University School of Medicine, Tokyo, Japan
| | - Shigeru Fujita
- Department of Social Medicine, Toho University School of Medicine, Tokyo, Japan
| | - Kanako Seto
- Department of Social Medicine, Toho University School of Medicine, Tokyo, Japan
| | - Yinghui Wu
- Shanghai Jiao Tong University School of Nursing, Shanghai, China
| | - Tomohiro Hirao
- Department of Public Health, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Tomonori Hasegawa
- Department of Social Medicine, Toho University School of Medicine, Tokyo, Japan
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Mochida S, Nakayama N, Ido A, Inoue K, Genda T, Takikawa Y, Sakaida I, Terai S, Yokosuka O, Shimizu M, Takikawa H. Proposal of Diagnostic Criteria for Acute-On-Chronic Liver Failure (ACLF) in Japan. KANZO 2018; 59:155-161. [DOI: 10.2957/kanzo.59.155] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2025]
Affiliation(s)
- Satoshi Mochida
- Department of Gastroenterology & Hepatology, Saitama Medical University
| | - Nobuaki Nakayama
- Department of Gastroenterology & Hepatology, Saitama Medical University
| | - Akio Ido
- Department of Digestive and Life-Style Related Disease, Health Research Course, Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences
| | - Kazuaki Inoue
- Department of Gastroenterology, Showa University Fujigaoka Hospital
| | - Takuya Genda
- Department of Gastroenterology, Juntendo University Shizuoka Hospital
| | - Yasuhiro Takikawa
- Department of Gastroenterology and Hepatology, School of Medicine, Iwate Medical University
| | - Isao Sakaida
- Department of Gastroenterology, Yamaguchi University Graduate School of Medicine
| | - Shuji Terai
- Division of Gastroenterology & Hepatology, Graduate School of Medical and Dental Sciences, Niigata University
| | | | - Masahito Shimizu
- Department of Gastroenterology, Gifu University Graduate School of Medicine
| | - Hajime Takikawa
- Department of Medicine, Teikyo University School of Medicine
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Hsieh PH, Huang JY, Nfor ON, Lung CC, Ho CC, Liaw YP. Association of type 2 diabetes with liver cirrhosis: a nationwide cohort study. Oncotarget 2017; 8:81321-81328. [PMID: 29113391 PMCID: PMC5655286 DOI: 10.18632/oncotarget.18466] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2017] [Accepted: 04/18/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The link between the subcategories of liver cirrhosis and type 2 diabetes is not well known. We investigated the association of type 2 diabetes mellitus with alcoholic cirrhosis and cirrhosis without alcohol. METHODS This nationwide cohort study used the Taiwan National Health Insurance Research Database. Cirrhotic individuals and their matched controls were identified from 2001-2008. In all, 9 313 cirrhotic patients aged 20 years or older were matched by age, sex, and index date with the non-cirrhotic individuals (n = 37 252). Cirrhosis was categorized into alcoholic cirrhosis and cirrhosis without alcohol. Type 2 diabetes mellitus was identified from January 2001- December 2011. RESULTS The incidence densities (per 1 000 person-months) of type 2 diabetes were as follows: 1.14 (95% CI: 1.09-1.20) in the non-cirrhotic group, 1.88 (CI 1.76-2.01) in patients with cirrhosis, 1.62 (CI 1.48-1.78) in patients with cirrhosis without alcohol, and 2.92 (CI 2.64-3.23) in patients with alcoholic cirrhosis. The adjusted hazards ratio (aHR) for type 2 diabetes mellitus among cirrhotic individuals was 0.774 (CI: 0.715-0.8934). Alcoholic cirrhotic men had a significantly higher risk of type 2 diabetes (aHR 1.182, CI: 1.046-1.335) compared with non-cirrhotic individuals. Increased risks were seen in men (aHR 1.690; CI: 1.455-1.963) and women (aHR 1.715; CI: 1.113-2.645) with alcoholic cirrhosis compared to those with cirrhosis without alcohol. CONCLUSIONS This study indicates that alcoholic cirrhosis is a significant risk factor for type 2 diabetes mellitus compared with cirrhosis without alcohol.
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Affiliation(s)
- Ping-Hsin Hsieh
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Chi-Mei Medical Center, Tainan, Taiwan
| | - Jing-Yang Huang
- Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, Taiwan
| | - Oswald Ndi Nfor
- Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, Taiwan
| | - Chia-Chi Lung
- Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, Taiwan
| | - Chien-Chang Ho
- Department of Physical Education, Fu-Jen Catholic University, New Taipei, Taiwan
| | - Yung-Po Liaw
- Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, Taiwan
- Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
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Genda T, Ichida T, Sakisaka S, Tanaka E, Mochida S, Ueno Y, Inui A, Egawa H, Umeshita K, Furukawa H, Kawasaki S, Inomata Y. Survival in patients with Child-Pugh class C cirrhosis: Analysis of the liver transplant registry in Japan. Hepatol Res 2017; 47:1155-1164. [PMID: 27995739 DOI: 10.1111/hepr.12855] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Revised: 12/06/2016] [Accepted: 12/18/2016] [Indexed: 12/30/2022]
Abstract
AIM To clarify the survival and prognostic factors in patients with Child-Turcotte-Pugh class C (CTP-C) cirrhosis. METHODS From all candidates for deceased donor liver transplantation in Japan between 2007 and 2015, 1014 adult patients with CTP-C cirrhosis were retrospectively enrolled in this study. The hazard ratio (HR) of factors associated with mortality was estimated by the Cox proportional hazard model. The survival probabilities were evaluated by Kaplan-Meier analysis and the log-rank test. RESULTS Median survival time of the entire cohort was 475 days. Univariate analysis identified age, CTP, Model for End-Stage Liver Disease (MELD) score, and primary biliary cholangitis (PBC) as significant variables associated with mortality and hepatitis B virus (HBV) infection as a close-to-significant variable. Multivariate analysis revealed that age-adjusted mortality risk increased by 59% and 12% per 1 score step up in CTP and MELD scores, respectively. The HRs for HBV infection and PBC were significant after adjustment for age and CTP score, and they showed a 26% lower risk and an 83% higher risk than hepatitis C virus (HCV) infection, respectively. After adjustment for age and MELD score, the HR was also significant for HBV infection, but lost statistical significance for PBC. The survival curves were well stratified by both CTP or MELD score and revealed significant difference in both HBV infection and PBC as compared to HCV infection. CONCLUSIONS In patients with CTP-C cirrhosis, CTP and MELD scores could well stratify the patients' survival, and HBV infection and PBC as etiologies have an impact on survival.
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Affiliation(s)
- Takuya Genda
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Izunokuni, Japan
| | - Takafumi Ichida
- Department of Hepatology, East Shonan General Hospital, Kanagawa, Japan
| | - Shotaro Sakisaka
- Department of Gastroenterology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
| | - Eiji Tanaka
- Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan
| | - Satoshi Mochida
- Department of Gastroenterology and Hepatology, Saitama Medical University, Saitama, Japan
| | - Yoshiyuki Ueno
- Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan
| | - Ayano Inui
- Division of Hepatology and Gastroenterology, Department of Pediatrics, Eastern Yokohama Hospital, Yokohama, Japan
| | - Hiroto Egawa
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Koji Umeshita
- Department of Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Hiroyuki Furukawa
- Department of Gastroentrologic and General Surgery, Asahikawa Medical University, Asahikawa, Japan
| | - Seiji Kawasaki
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Yukihiro Inomata
- Department of Transplantation and Pediatric Surgery, Postgraduate School of Medical Science, Kumamoto University, Kumamoto, Japan
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Samukawa Y, Sata M, Furihata K, Ito T, Ueda N, Ochiai H, Sakai S, Kumagai Y. Luseogliflozin, an SGLT2 Inhibitor, in Japanese Patients With Mild/Moderate Hepatic Impairment: A Pharmacokinetic Study. Clin Pharmacol Drug Dev 2017; 6:439-447. [DOI: 10.1002/cpdd.364] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2016] [Accepted: 04/05/2017] [Indexed: 11/09/2022]
Affiliation(s)
| | - Michio Sata
- Kurume University School of Medicine; Fukuoka Japan
| | | | - Toshifumi Ito
- Japan Community Healthcare Organization Osaka Hospital; Osaka Japan
| | - Naohiko Ueda
- Medical Corporation Kyosoukai AMC Nishi Umeda Clinic; Osaka Japan
| | | | | | - Yuji Kumagai
- Kitasato University School of Medicine; Kanagawa Japan
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Okajima A, Sumida Y, Taketani H, Hara T, Seko Y, Ishiba H, Nishimura T, Umemura A, Nishikawa T, Yamaguchi K, Moriguchi M, Mitsuyoshi H, Yasui K, Minami M, Itoh Y. Liver stiffness measurement to platelet ratio index predicts the stage of liver fibrosis in non-alcoholic fatty liver disease. Hepatol Res 2017; 47:721-730. [PMID: 27539017 DOI: 10.1111/hepr.12793] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Revised: 08/08/2016] [Accepted: 08/10/2016] [Indexed: 12/18/2022]
Abstract
AIM Platelet count and liver stiffness measurement (LSM) using transient elastography could identify significant fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). We constructed a novel index combining LSM with platelet count for staging fibrosis in Japanese patients with NAFLD. METHODS We recruited 173 Japanese patients with liver biopsy-proven NAFLD. The areas under the receiver operating characteristic curves were calculated and compared with established parameters and scoring systems for staging liver fibrosis. RESULTS After excluding 10 patients in whom LSM failed, 163 patients with NAFLD were enrolled. The areas under the receiver operating characteristic curves of the LSM/platelet ratio (LPR) index for detecting fibrosis ≥stage 1, ≥stage 2, and ≥stage 3 were the greatest (0.835, 0.913, and 0.936, respectively) compared with those for various other parameters and established scoring systems, such as LSM, type IV collagen 7 s domain, platelet count, NAFIC score, fibrosis-4 index, NAFLD fibrosis score, aspartate aminotransferase/alanine aminotransferase ratio, and aspartate aminotransferase to platelet ratio index. The optimal cut-off, positive predictive, and negative predictive values of the LPR index for detecting ≥stage 3 fibrosis were 0.60, 48.9%, and 99.2%, whereas those of LSM were 10.0 kPa, 35.0%, and 99.0%, respectively. The novel LPR index helps avoid biopsies in a larger percentage of patients with NAFLD compared with that LSM alone. CONCLUSIONS The LPR index was the best predictor for staging fibrosis in patients with NAFLD. It represents a simple and non-invasive alternative to liver biopsy in clinical practice.
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Affiliation(s)
- Akira Okajima
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yoshio Sumida
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hiroyoshi Taketani
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Tasuku Hara
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yuya Seko
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hiroshi Ishiba
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takeshi Nishimura
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Atsushi Umemura
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Taichiro Nishikawa
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kanji Yamaguchi
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Michihisa Moriguchi
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hironori Mitsuyoshi
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kohichiroh Yasui
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Masahito Minami
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yoshito Itoh
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
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A Erdogan M, R Benli A, B Acmali S, Koroglu M, Atayan Y, Danalioglu A, Kayhan B. Predictive Value of Mean Platelet Volume in Variceal Bleeding due to Cirrhotic Portal Hypertension. Euroasian J Hepatogastroenterol 2017; 7:6-10. [PMID: 29201764 PMCID: PMC5663766 DOI: 10.5005/jp-journals-10018-1203] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2016] [Accepted: 08/25/2016] [Indexed: 12/22/2022] Open
Abstract
Aim: To investigate whether mean platelet volume (MPV) is a predictor of variceal bleeding in patients with cirrhotic portal hypertension. Materials and methods: This prospective cohort was performed in the internal medicine department of our tertiary care center. Cirrhotic patients were allocated into two groups: Group I consisted of 31 cases without a history of variceal bleeding, whereas group II was made up of 31 patients with a history of variceal bleeding. Data derived from medical history, physical examination, ultrasonography, gastrointestinal system endoscopy, complete blood count, hepatic, and renal function tests were recorded and compared between two groups. On physical examination, encephalopathy and ascites were evaluated and graded with respect to Child-Pugh-Turcotte classification. Results: There was no significant difference between the two groups in terms of age, duration of the disease, and gender of the patient. The only remarkable difference was that hemoglobin (p = 0.02) and hematocrit (p = 0.02) values were lower in group II. Neither the etiology of bleeding was different between groups nor did MPV seem to have a noteworthy impact on bleeding. Interestingly, risk of variceal bleeding increased in parallel to the higher grade of varices. Conclusion: Our results imply that there is a correlation between the grade of varices and esophageal vari-ceal bleeding in cirrhotic patients. However, association between MPV and variceal bleeding could not be demonstrated. Utilization of noninvasive tests as predictors in these patients necessitates further controlled trials on larger series. How to cite this article: Erdogan MA, Benli AR, Acmali SB, Koroglu M, Atayan Y, Danalioglu A, Kayhan B. Predictive Value of Mean Platelet Volume in Variceal Bleeding due to Cirrhotic Portal Hypertension. Euroasian J Hepato-Gastroenterol 2017;7(1):6-10.
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Affiliation(s)
- Mehmet A Erdogan
- Department of Gastroenterology, Karabük Education and Research Hospital, Karabük University, Karabük, Turkey
| | - Ali R Benli
- Department of Family Medicine, Karabük University, Karabük, Turkey
| | - Serap B Acmali
- Department of Family Medicine, Dudullu Aile Sağliği Merkezleri, Istanbul Turkey
| | - Mustafa Koroglu
- Department of Hematology, Karabük University, Karabük, Turkey
| | - Yahya Atayan
- Department of Gastroenterology, Gümüshane State Hospital Gümüşhane, Turkey
| | - Ahmet Danalioglu
- Department of Internal Medicine, Bezmiâlem Vakif University, Istanbul, Turkey
| | - Burcak Kayhan
- Department of Internal Medicine Karabük University, Karabük, Turkey
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Oza N, Isoda H, Ono T, Kanto T. Current activities and future directions of comprehensive hepatitis control measures in Japan: The supportive role of the Hepatitis Information Center in building a solid foundation. Hepatol Res 2017; 47:487-496. [PMID: 28326651 DOI: 10.1111/hepr.12897] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Revised: 03/13/2017] [Accepted: 03/17/2017] [Indexed: 12/12/2022]
Abstract
In Japan, hepatitis B or C virus infection has been a major health issue. For the prevention of liver-related deaths, multifaceted strategies have been taken against hepatitis virus. In fiscal year (FY) 2002, nationwide screening for hepatitis was started as a part of health examinations provided by municipal governments. From FY2007, the hepatitis treatment network has been strengthened by the nationwide establishment of regional government-based hepatitis treatment systems, comprising linked regional core centers, specialized institutions for hepatitis treatment, primary care physicians, and regional governments. Special subsidy program for patients with viral hepatitis was started at FY2008. The range of coverage has been expanding from patients treated with interferon to those on nucleotide analogs or interferon-free therapies, including drug prices and examination expenses. The Basic Act on Hepatitis Measures was established in 2009. The Basic Guidelines for Promotion of Control Measures for hepatitis was issued in 2011, comprising nine principles in order to promote measures for hepatitis B and C. The Hepatitis Information Center was established in 2008. Its mission is to provide up-to-date hepatitis-related information, supporting collaboration between regional core centers, and training medical personnel. The revision of the above-mentioned Basic Guidelines in 2016 set the target as the reduction of patients progressing to cirrhosis and/or liver cancer. Achieving this goal definitely requires active collaboration among the national and local governments, regional core centers, and the Hepatitis Information Center, and participation by medical personnel, patients, and people with awareness.
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Affiliation(s)
- Noriko Oza
- Hepatitis Information Center, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan
| | - Hiroshi Isoda
- Office for Promotion of Hepatitis Measures, Cancer and Disease Control Division, Health Service Bureau, Ministry of Health, Labour and Welfare, Tokyo, Japan
| | - Toshiki Ono
- Office for Promotion of Hepatitis Measures, Cancer and Disease Control Division, Health Service Bureau, Ministry of Health, Labour and Welfare, Tokyo, Japan
| | - Tatsuya Kanto
- Hepatitis Information Center, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan
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Hirata A, Hirata T, Takahashi Y, Nakayama T. Surveillance rates for hepatocellular carcinoma among patients with cirrhosis, chronic hepatitis B, and chronic hepatitis C based on Japanese claims database. Hepatol Res 2017; 47:283-292. [PMID: 27027417 DOI: 10.1111/hepr.12714] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2015] [Revised: 03/02/2016] [Accepted: 03/20/2016] [Indexed: 12/20/2022]
Abstract
AIM Surveillance is recommended for patients with risk of hepatocellular carcinoma (HCC) such as viral hepatitis and liver cirrhosis (LC). Although populations are at higher risk in Asia, surveillance rates have not been evaluated in those countries. Therefore, we aimed to examine surveillance rates for HCC and to compare predictors for surveillance among each type of liver disease in Japan. METHODS We carried out an observational study using the medical claims data of Japan. A total of 4713 patients who were diagnosed with LC, hepatitis B virus (HBV), or hepatitis C virus (HCV) infection were followed for 12 months. We described surveillance rates in patients with HBV or HCV infection or non-viral LC and evaluated potential predictors for follow-up surveillance among them by using multivariable logistic regression analysis, in which we set explanatory variables as sex, age, medical facility, HBV or HCV infection, and LC. RESULTS The HCC surveillance rate during follow-up was 42.3% among patients with chronic viral hepatitis, 56.5% with viral cirrhosis and 26.0%, with non-viral LC. Significant predictors for follow-up surveillance were presence of LC and hospital visits. Hepatitis B virus-infected patients aged <50 years and HCV-infected patients aged ≥50 years were more likely to undergo exams, that is, different tendencies between HBV and HCV patients were shown. CONCLUSIONS Follow-up surveillance for HCC was not adequately carried out among patients at risk for HCC in Japan, despite of recommendation in guidelines. In future, methodological research might be needed to increase surveillance rates for HCC in patients with chronic hepatitis or those who received treatment at a clinic.
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Affiliation(s)
- Aya Hirata
- Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan.,Department of Health Informatics, Kyoto University School of Public Health, Kyoto, Japan
| | - Takumi Hirata
- Center for Supercentenarian Medical Research, Keio University School of Medicine, Tokyo, Japan
| | - Yoshimitsu Takahashi
- Department of Health Informatics, Kyoto University School of Public Health, Kyoto, Japan
| | - Takeo Nakayama
- Department of Health Informatics, Kyoto University School of Public Health, Kyoto, Japan
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Nonalcoholic fatty liver disease in Asia: emerging perspectives. J Gastroenterol 2017; 52:164-174. [PMID: 27637587 DOI: 10.1007/s00535-016-1264-3] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Accepted: 09/06/2016] [Indexed: 02/07/2023]
Abstract
As in the West, nonalcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease in Asia, with a prevalence higher than 40 % in some countries. The risk factors for NAFLD development are similar to those in Western countries, including increased body mass index, diabetes, insulin resistance, and metabolic syndrome. NAFLD in Asians is associated with different extrahepatic manifestations involving the cardiovascular, gastrointestinal, and renal systems. A considerable proportion of Asians with NAFLD are described as having "lean" NAFLD. Present in approximately 20 % of the Asian population, lean NAFLD is closely linked with insulin resistance, diabetes, and other metabolic complications, but its association with disease progression to nonalcoholic steatohepatitis and cirrhosis remains to be defined. There is emerging evidence of the interactions of NAFLD with hepatitis B virus and hepatitis C virus infection in Asia. Unlike in Western countries, NAFLD constitutes only a minority of cirrhosis and hepatocellular carcinoma cases in Asia. Possible explanations are the lower prevalence of obesity and the overwhelming problem of viral hepatitis in Asia. With aging of the obesity cohort in Asia, NAFLD-related liver complications are expected to increase.
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Miyagi T, Takehara T. [linical Importance of Non-alcoholic Fatty Liver Diseases. Topics II Clinical impact of epidemiological studies]. ACTA ACUST UNITED AC 2016; 105:9-14. [PMID: 27266038 DOI: 10.2169/naika.105.9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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