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Stasi C, Brillanti S. Liver Stiffness Evaluation in Chronic Hepatitis C Patients with Cirrhosis before and after Direct-Acting Antivirals. Microorganisms 2024; 12:1418. [PMID: 39065186 PMCID: PMC11279336 DOI: 10.3390/microorganisms12071418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 07/02/2024] [Accepted: 07/09/2024] [Indexed: 07/28/2024] Open
Abstract
After the introduction of direct-acting antivirals, parallel significant clinical progress has been achieved in the assessment of liver fibrosis progression/regression before treatment and during the follow-up of the cirrhotic patients with chronic hepatitis C virus (HCV) infection. The evolution of chronic hepatitis C into liver cirrhosis is correlated with an extensive accumulation of the extracellular matrix, leading to the formation of large amounts of fibrotic tissues that, initially, are concentrated in periportal areas and, in the later stages, surround the nodules of regenerating hepatocytes. The progressive increase in the fibrotic matrix contributes to vascular disturbances (favoring the development of portal hypertension) and to microenvironmental changes. The four clinical stages of liver cirrhosis are predictors for different clinical scenarios. The wide-ranging functions of the liver require different methods for their assessment. The non-invasive evaluation using transient elastography is useful in determining the longitudinal modifications of fibrosis during and after treatment with direct-acting antivirals. The liver stiffness evaluation, known to have a wide range of values in cirrhotic patients, can offer different prognostic implications after sustained virological response. This review discusses the different time points of liver stiffness evaluation that appear to show a more well-defined propensity to identify adequate monitoring schedules for these patients.
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Affiliation(s)
- Cristina Stasi
- Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy
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Xu S, Qiu L, Xu L, Liu Y, Zhang J. Development and validation of a nomogram for assessing hepatocellular carcinoma risk after SVR in hepatitis C patients with advanced fibrosis and cirrhosis. Infect Agent Cancer 2024; 19:17. [PMID: 38664813 PMCID: PMC11046761 DOI: 10.1186/s13027-024-00578-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 04/11/2024] [Indexed: 04/28/2024] Open
Abstract
BACKGROUND Hepatitis C patients with advanced fibrosis or cirrhosis are at high risk of developing hepatocellular carcinoma (HCC), even after sustained virological response (SVR). Clinical recommendations impose a significant burden on patients by recommending lifelong screening for HCC every six months. The goals of this study were to develop a nomogram that accurately stratifies risk of HCC and improve the screening approach that is currently in use. METHOD Risk factors for HCC were identified using univariate and multivariate analyses in this prospective study. We developed and validated a nomogram for assessing hepatocellular carcinoma risk after SVR in patients with advanced fibrosis and cirrhosis. RESULTS During the median follow-up period of 61.00 (57.00-66.00) months in the derivation cohort, 37 patients (9.61%) developed HCC. Older age (HR = 1.08, 95% CI 1.02-1.14, p = 0.009), male gender (HR = 2.38, 95% CI 1.10-5.13, p = 0.027), low serum albumin levels (HR = 0.92, 95% CI 0.86-1.00, p = 0.037), and high liver stiffness measurement (LSM) (HR = 1.03, 95% CI 1.01-1.06, p = 0.001) were found to be independent predictors of HCC development. Harrell's C-index for the derivation cohort was 0.81. The nomogram's 3-, 5- and 7-years time-dependent AUROCSs were 0.84 (95% CI 0.80-0.88), 0.83 (95% CI 0.79-0.87), and 0.81 (95% CI 0.77-0.85), respectively (all p > 0.05). According to the nomogram, patients are categorized as having low, intermediate, or high risk. The annual incidence rates of HCC in the three groups were 0.18%, 1.29%, and 4.45%, respectively (all p < 0.05). CONCLUSIONS Older age, male gender, low serum albumin levels, and high LSM were risk factors for HCC after SVR in hepatitis C patients with advanced fibrosis and cirrhosis. We used these risk factors to establish a nomogram. The nomogram can identify a suitable screening plan by classifying hepatitis C patients according to their risk of HCC.
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Affiliation(s)
- Shanshan Xu
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People's Republic of China
| | - Lixia Qiu
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People's Republic of China
| | - Liang Xu
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin Research Institute of Liver Diseases, Tianjin, 300192, People's Republic of China
| | - Yali Liu
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People's Republic of China
| | - Jing Zhang
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People's Republic of China.
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Isfordink CJ, van Erpecum KJ, Fischer K, van der Valk PR, van Vulpen LFD, Schutgens REG, Arends JE, Mauser‐Bunschoten EP. Liver-related complications before and after successful treatment of chronic hepatitis C virus infection in people with inherited bleeding disorders. Haemophilia 2023; 29:106-114. [PMID: 36184751 PMCID: PMC10092673 DOI: 10.1111/hae.14668] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 09/11/2022] [Accepted: 09/18/2022] [Indexed: 11/04/2022]
Abstract
INTRODUCTION With availability of direct-acting antivirals (DAA), most persons with inherited bleeding disorders are currently cured of hepatitis C virus (HCV) infection. The risk of liver-related complications following HCV cure has not been reported for this population. AIM Reporting liver-related complications during long-term chronic HCV infection and following sustained virological response (SVR) in this population. METHODS Retrospective follow-up of a prospective single-centre cohort of HCV antibody-positive persons with inherited bleeding disorders. Primary endpoint was liver-related complications [hepatocellular carcinoma (HCC), decompensated cirrhosis, bleeding gastroesophageal varices]. Liver-related complications were reported separately during chronic HCV and following SVR, stratified for interferon-based and DAA-based SVR. RESULTS In total 309/381 (81%) HCV antibody-positive individuals developed chronic HCV infection. Median follow-up was 44 years [interquartile range (IQR): 34-50]. Liver-related complications occurred in 36/309 (12%) of individuals with chronic HCV infection after median 31 years of chronic infection. Of 199 individuals with SVR, 97 were cured with interferon-based regimens and 102 with DAA after median infection durations of 29 and 45 years, respectively. At end of follow-up, respectively, 21% and 42% had advanced fibrosis or cirrhosis. Post-SVR, seven (4%) individuals had a liver-related complication, mainly HCC (n = 4). Incidence of liver-related complications per 100 patient-years post-SVR follow-up was .2 for interferon-cured and 1.0 for DAA-cured individuals (p = .01). CONCLUSION Successful HCV treatment does not eliminate the risk of liver-related complications in persons with inherited bleeding disorders. Due to higher baseline risk, incidence was higher after DAA than interferon-based SVR. We advise continuing HCC surveillance post-SVR in all with advanced fibrosis or cirrhosis.
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Affiliation(s)
- Cas J. Isfordink
- Van Creveldkliniek, Department of Benign HematologyUniversity Medical Center Utrecht, Utrecht UniversityUtrechtThe Netherlands
- Department of Gastroenterology and HepatologyUniversity Medical Center UtrechtUtrecht UniversityUtrechtThe Netherlands
| | - Karel J. van Erpecum
- Department of Gastroenterology and HepatologyUniversity Medical Center UtrechtUtrecht UniversityUtrechtThe Netherlands
| | - Kathelijn Fischer
- Van Creveldkliniek, Department of Benign HematologyUniversity Medical Center Utrecht, Utrecht UniversityUtrechtThe Netherlands
| | - Paul R. van der Valk
- Van Creveldkliniek, Department of Benign HematologyUniversity Medical Center Utrecht, Utrecht UniversityUtrechtThe Netherlands
| | - Lize F. D. van Vulpen
- Van Creveldkliniek, Department of Benign HematologyUniversity Medical Center Utrecht, Utrecht UniversityUtrechtThe Netherlands
| | - Roger E. G. Schutgens
- Van Creveldkliniek, Department of Benign HematologyUniversity Medical Center Utrecht, Utrecht UniversityUtrechtThe Netherlands
| | - Joop E. Arends
- Department of Internal Medicine and Infectious DiseasesUniversity Medical Center Utrecht, Utrecht UniversityUtrechtThe Netherlands
| | - Evelien P. Mauser‐Bunschoten
- Van Creveldkliniek, Department of Benign HematologyUniversity Medical Center Utrecht, Utrecht UniversityUtrechtThe Netherlands
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Kouroumalis E, Voumvouraki A. Hepatitis C virus: A critical approach to who really needs treatment. World J Hepatol 2022; 14:1-44. [PMID: 35126838 PMCID: PMC8790391 DOI: 10.4254/wjh.v14.i1.1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 04/14/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023] Open
Abstract
Introduction of effective drugs in the treatment of hepatitis C virus (HCV) infection has prompted the World Health Organization to declare a global eradication target by 2030. Propositions have been made to screen the general population and treat all HCV carriers irrespective of the disease status. A year ago the new severe acute respiratory syndrome coronavirus 2 virus appeared causing a worldwide pandemic of coronavirus disease 2019 disease. Huge financial resources were redirected, and the pandemic became the first priority in every country. In this review, we examined the feasibility of the World Health Organization elimination program and the actual natural course of HCV infection. We also identified and analyzed certain comorbidity factors that may aggravate the progress of HCV and some marginalized subpopulations with characteristics favoring HCV dissemination. Alcohol consumption, HIV coinfection and the presence of components of metabolic syndrome including obesity, hyperuricemia and overt diabetes were comorbidities mostly responsible for increased liver-related morbidity and mortality of HCV. We also examined the significance of special subpopulations like people who inject drugs and males having sex with males. Finally, we proposed a different micro-elimination screening and treatment program that can be implemented in all countries irrespective of income. We suggest that screening and treatment of HCV carriers should be limited only in these particular groups.
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Affiliation(s)
- Elias Kouroumalis
- Department of Gastroenterology, University of Crete Medical School, Heraklion 71500, Crete, Greece
| | - Argyro Voumvouraki
- First Department of Internal Medicine, AHEPA University Hospital, Thessaloniki 54621, Greece
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Isfordink CJ, Maan R, de Man RA, van Erpecum KJ, van der Meer AJ. Should we continue surveillance for hepatocellular carcinoma and gastroesophageal varices in patients with cirrhosis and cured HCV infection? Eur J Intern Med 2021; 94:6-14. [PMID: 34563447 DOI: 10.1016/j.ejim.2021.08.023] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 08/02/2021] [Accepted: 08/27/2021] [Indexed: 12/13/2022]
Abstract
Hepatocellular carcinoma (HCC) and variceal bleeding are among the most common causes of liver-related mortality in patients with hepatitis C virus (HCV)-induced cirrhosis. Current guidelines recommend HCC and gastroesophageal varices (GEV) surveillance in patients with HCV infection and cirrhosis. However, since the recent introduction of direct-acting antivirals, most patients with cirrhosis are now cured of their chronic HCV infection. As virological cure is considered to substantially reduce the risk of cirrhosis-related complications, this review discusses the current literature concerning the surveillance of HCC and GEV in patients with HCV-induced cirrhosis with a focus on the setting following sustained virological response.
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Affiliation(s)
- Cas J Isfordink
- Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, the Netherlands; Division of Infectious Diseases, Amsterdam Infection & Immunity Institute Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Raoel Maan
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Robert A de Man
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Karel J van Erpecum
- Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, the Netherlands
| | - Adriaan J van der Meer
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.
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Computed Tomography-Measured Liver Volume Predicts the Risk of Hepatocellular Carcinoma Development in Chronic Hepatitis C Patients. Dig Dis Sci 2021; 66:4536-4544. [PMID: 33630218 DOI: 10.1007/s10620-020-06762-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Accepted: 12/06/2020] [Indexed: 01/10/2023]
Abstract
AIM In this retrospective cohort study, we evaluated the significance of liver volume in the prediction of hepatocellular carcinoma (HCC) in 277 chronic hepatitis C (CHC) patients who received dynamic computed tomography (CT) during surveillance. METHODS Liver volumes were measured on portal venous phase of CT images by using ImageJ software. Liver volume index, a ratio of the standard liver volume expected by weight and height to the measured liver volume, was calculated to adjust for normal variations. The cohort was randomly divided to derivation (n = 100) and validation sets (n = 177) for the generation of a liver volume-based Cox prediction model and validation of a liver volume-based nomogram, respectively. RESULTS The liver volume index was independent of weight or height, and it predicted further development of HCC (hazard ratio [HR] 16.30, 95% CI 6.70-39.62; p < 0.001). Liver cirrhosis, gamma-glutamyl transferase, and liver volume index were independent predictors of HCC, and nomogram-based prediction score from these three parameters identified high-risk patients at the cutoff of 110 in both derivation (p < 0.001) and validation cohort (p < 0.001). CONCLUSION Liver volume-based prediction model stratifies the risk of developing HCC in CHC patients whose initial dynamic CT study gave negative results.
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7
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Zhang X, Guan L, Tian H, Zeng Z, Chen J, Huang D, Sun J, Guo J, Cui H, Li Y. Risk Factors and Prevention of Viral Hepatitis-Related Hepatocellular Carcinoma. Front Oncol 2021; 11:686962. [PMID: 34568017 PMCID: PMC8458967 DOI: 10.3389/fonc.2021.686962] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Accepted: 08/20/2021] [Indexed: 12/11/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a common cancer in the world, and its incidence is increasing yearly. Hepatitis B virus (HBV) infection and hepatitis C virus (HCV) infection are important causes of HCC. Liver cirrhosis, age, sex, smoking and drinking, and metabolic risk factors will increase the risk of cancer in HBV/HCV patients. And viral load, APRI, FIB-4, and liver stiffness can all predict the risk of HCC in patients with viral infection. In addition, effective prevention strategies are essential in reducing the risk of HCC. The prevention of HCC involves mainly tertiary prevention strategies, while the primary prevention is based on standardized vaccine injections to prevent the occurrence of HBV/HCV. Eliminating the route of transmission and vaccination will lead to a decrease in the incidence of HCC. Secondary prevention involves effective antiviral treatment of HBV/HCV to prevent the disease from progressing to HCC, and tertiary prevention is actively treating HCC to prevent its recurrence.
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Affiliation(s)
- Xinhe Zhang
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Lin Guan
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Haoyu Tian
- The 3rd Clinical Department of China Medical University, Shenyang, China
| | - Zilu Zeng
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Jiayu Chen
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Die Huang
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Ji Sun
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Jiaqi Guo
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Huipeng Cui
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Yiling Li
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
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8
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Isfordink CJ, van Erpecum KJ, van der Valk M, Mauser-Bunschoten EP, Makris M. Viral hepatitis in haemophilia: historical perspective and current management. Br J Haematol 2021; 195:174-185. [PMID: 33955555 DOI: 10.1111/bjh.17438] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The introduction of clotting factor concentrates has substantially improved the lives of people with clotting factor deficiencies. Unfortunately, the transmission of blood-borne viral infections through these plasma-derived products led to a huge epidemic of human immunodeficiency virus and viral hepatitis in people with haemophilia (PWH). In a significant proportion of PWH exposed to these viruses, the ensuing decades-long chronic infection resulted in excess morbidity and mortality. Fortunately, developments in the safety of blood products, as well as vaccination and highly effective antiviral treatments have improved the prospects of PWH. The present article reviews the background of the viral hepatitis epidemic in PWH, the natural history of hepatitis B and C infections and their long-term management.
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Affiliation(s)
- Cas J Isfordink
- Van Creveldkliniek, Department of Benign Haematology, University Medical Center Utrecht, Utrecht, the Netherlands.,Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands.,Department of Internal Medicine, Division of Infectious Diseases, Amsterdam Institute for Infection and Immunity, University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
| | - Karel J van Erpecum
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Marc van der Valk
- Department of Internal Medicine, Division of Infectious Diseases, Amsterdam Institute for Infection and Immunity, University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
| | - Evelien P Mauser-Bunschoten
- Van Creveldkliniek, Department of Benign Haematology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Michael Makris
- Sheffield Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital, Sheffield, UK.,Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
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You MW, Kim KW, Shim JJ, Pyo J. Impact of liver-stiffness measurement on hepatocellular carcinoma development in chronic hepatitis C patients treated with direct-acting antivirals: A systematic review and time-to-event meta-analysis. J Gastroenterol Hepatol 2021; 36:601-608. [PMID: 32875681 DOI: 10.1111/jgh.15243] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 08/17/2020] [Accepted: 08/25/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Patients with chronic hepatitis C (CHC) treated with direct-acting antivirals (DAAs) are still at risk for developing hepatocellular carcinoma (HCC) even after achieving sustained virologic response (SVR). Liver-stiffness measurement (LSM) on imaging has been investigated as a predictor of HCC occurrence. OBJECTIVES To provide systematic summary of the predictive value of LSM in predicting HCC occurrence in HCV patients treated with DAA. METHODS A comprehensive literature search of the PubMed-MEDLINE and EMBASE databases was performed to identify studies that evaluated the predictive value of LSM in CHC patients treated with DAAs. Pooled hazard ratio (HR) comparing HCC occurrence between patients with positive and negative results on LSM was calculated for all studies and various subgroups. Subgroup analyses and meta-regression were performed. RESULTS A review of 135 candidate articles identified eight eligible articles with a total of 3398patients for qualitative review and meta-analysis. The pooled HR for HCC occurrence determined by LSM was 3.43 (95% confidence interval [CI], 1.63-7.19) with heterogeneity (I2 = 81.87%, P < 0.001), thus indicating that LSM might be helpful for predicting HCC occurrence. In subgroup analyses, pooled HRs were different according to the study design (2.29; [95% CI, 0.96-5.45] for retrospective studies; 4.61 [95% CI, 2.44-8.71] for prospective studies), study population (4.00 [95% CI, 2.00-7.99] for CHC; 2.64 [0.99-7.00] for CHC with liver cirrhosis) and LSM parameter (3.17 [95% CI, 1.35-7.41] for baseline LSM; 4.19 [95% CI, 1.89-9.29] for others). In multivariate meta-regression, study design was the only influencing factor for pooled HR for HCC occurrence (P < 0.05). CONCLUSIONS Consistent evidence demonstrated the predictive value of LSM for HCC occurrence in CHC patients treated with DAA. The significant influencing factor for risk of HCC occurrence indicated by LSM was study design.
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Affiliation(s)
- Myung-Won You
- Department of Radiology, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, South Korea
| | - Kyung Won Kim
- Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jae-Jun Shim
- Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, South Korea
| | - Junhee Pyo
- WHO Collaborating Center for Pharmaceutical Policy and Regulation, Department of Pharmaceutical Science, Utrecht University, Utrecht, The Netherlands
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Zhu H, Guo H, Yin X, Yang J, Yin Q, Xiao J, Wang Y, Zhang M, Han H, Zhuge Y, Zhang F. Spleen Stiffness Predicts Survival after Transjugular Intrahepatic Portosystemic Shunt in Cirrhotic Patients. BIOMED RESEARCH INTERNATIONAL 2020; 2020:3860390. [PMID: 33282945 PMCID: PMC7685811 DOI: 10.1155/2020/3860390] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 10/19/2020] [Accepted: 10/29/2020] [Indexed: 12/21/2022]
Abstract
OBJECTIVES Transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention for portal hypertensive complications. Little is known about the ability of spleen stiffness (SS) for predicting the survival of cirrhotic patients undergoing TIPS. This study is to evaluate the influence of SS detected by point shear wave elastography (pSWE) in predicting survival after TIPS. METHODS This retrospective cohort study screened consecutive patients who underwent TIPS and reliable pSWE measurement between October 2014 and September 2017 from our prospectively maintained database. SS values were measured before TIPS. The primary endpoint was the overall survival after TIPS. The Cox regression analysis model was used for univariate and multivariate analyses. A receiver operating characteristic (ROC) curve analysis was performed to calculate the sensitivity, specificity, and positive and negative predictive values. RESULTS A total of 89 patients were involved in the final analysis. 24 patients (27.0%) died during a median follow-up time of 31 m. Multivariable Cox regression analysis confirmed that higher SS value (P < 0.001), LS value (P = 0.008), diameter of shunt (P = 0.001), and older age (P < 0.001) were independent prognostic factors of survival after TIPS. The risk of death rose 57.440-fold for each SS unit (m/s) increase. SS was also correlated with liver failure after TIPS. ROC analysis showed that the best SS cutoff value was 3.60 m/s for predicting survival, with a sensitivity of 54.2% and specificity of 90.8%. CONCLUSIONS The SS value determined by pSWE in cirrhotic patients was an independent predictive factor for survival after TIPS.
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Affiliation(s)
- Hao Zhu
- Department of Gastroenterology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Huiwen Guo
- Department of Gastroenterology, Affiliated Drum Tower Clinical Medical School of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Xiaochun Yin
- Department of Gastroenterology, Affiliated Drum Tower Clinical Medical School of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jian Yang
- Department of Ultrasound, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Qin Yin
- Department of Gastroenterology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Jiangqiang Xiao
- Department of Gastroenterology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Yi Wang
- Department of Gastroenterology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Ming Zhang
- Department of Gastroenterology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Hao Han
- Department of Ultrasound, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Yuzheng Zhuge
- Department of Gastroenterology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Feng Zhang
- Department of Gastroenterology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
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Llamosas-Falcón L, Shield KD, Gelovany M, Manthey J, Rehm J. Alcohol use disorders and the risk of progression of liver disease in people with hepatitis C virus infection - a systematic review. SUBSTANCE ABUSE TREATMENT PREVENTION AND POLICY 2020; 15:45. [PMID: 32605584 PMCID: PMC7325038 DOI: 10.1186/s13011-020-00287-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Accepted: 06/23/2020] [Indexed: 02/08/2023]
Abstract
Liver cirrhosis and other chronic liver diseases are usually compartmentalized into separate categories based on etiology (e.g., due to alcohol, virus infection, etc.), but it is important to study the intersection of, and possible interactions between, risk factors. The aim of this study is to summarize evidence on the association between alcohol use disorders (AUDs) and decompensated liver cirrhosis and other complications in patients with chronic Hepatitis C virus (HCV) infection. A systematic search of epidemiological studies was conducted using Ovid Medline databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Relative Risk estimates were combined using random-effects meta-analyses. The proportion of cases with liver disease progression that could be avoided if no person with a chronic HCV infection had an AUD was estimated using an attributable fraction methodology. A total of 11 studies fulfilled the inclusion criteria, providing data from 286,641 people with chronic HCV infections, of whom 63,931 (22.3%) qualified as having an AUD. Using decompensated liver cirrhosis as the outcome for the main meta-analysis (n = 7 unique studies), an AUD diagnosis was associated with a 3.3-fold risk for progression of liver disease among people with a chronic HCV infection (95% Confidence Interval (CI): 1.8–4.8). In terms of population-attributable fractions, slightly less than 4 out of 10 decompensated liver cirrhosis cases were attributable to an AUD: 35.2% (95% CI: 16.2–47.1%). For a secondary analyses, all outcomes related to liver disease progression were pooled (i.e., liver deaths or cirrhosis in addition to decompensated liver cirrhosis), which yielded a similar overall effect (n = 13 estimates; OR = 3.7; 95% CI: 2.2–5.3) and a similar attributable fraction (39.3%; 95% CI: 21.9–50.4%). In conclusion, AUDs were frequent in people with chronic HCV infections and contributed to worsening the course of liver disease. Alcohol use and AUDs should be assessed in patients who have liver disease of any etiology, and interventions should be implemented to achieve abstinence or to reduce consumption to the greatest possible extent.
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Affiliation(s)
- Laura Llamosas-Falcón
- Preventive Medicine and Public Health, Preventive Medicine, Universitary Hospital "12 de Octubre", Avda de Córdoba s/n 28041, Madrid, Spain.,Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, 33 Russell Street, Room T420, Toronto, Ontario, M5S 2S1, Canada
| | - Kevin D Shield
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, 33 Russell Street, Room T420, Toronto, Ontario, M5S 2S1, Canada.,Dalla Lana School of Public Health, University of Toronto, 155 College Street, Toronto, Ontario, M5T 1P8, Canada
| | - Maya Gelovany
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, 33 Russell Street, Room T420, Toronto, Ontario, M5S 2S1, Canada
| | - Jakob Manthey
- Center for Interdisciplinary Addiction Research (ZIS), Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf (UKE), Martinistraße 52, 20246, Hamburg, Germany.,Institute of Clinical Psychology and Psychotherapy & Center of Clinical Epidemiology and Longitudinal Studies (CELOS), Technische Universität Dresden, Chemnitzer Str. 46, 01187, Dresden, Germany
| | - Jürgen Rehm
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, 33 Russell Street, Room T420, Toronto, Ontario, M5S 2S1, Canada. .,Dalla Lana School of Public Health, University of Toronto, 155 College Street, Toronto, Ontario, M5T 1P8, Canada. .,Institute of Clinical Psychology and Psychotherapy & Center of Clinical Epidemiology and Longitudinal Studies (CELOS), Technische Universität Dresden, Chemnitzer Str. 46, 01187, Dresden, Germany. .,Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, M5T 2S1, Canada. .,Faculty of Medicine, Institute of Medical Science, University of Toronto, Medical Sciences Building, 1 King's College Circle, Room 2374, Toronto, Ontario, M5S 1A8, Canada. .,Department of Psychiatry, University of Toronto, 250 College Street, 8th floor, Toronto, Ontario, M5T 1R8, Canada. .,Department of International Health Projects, Institute for Leadership and Health Management, I.M. Sechenov First Moscow State Medical University, Trubetskaya str., 8, b. 2, Moscow, Russian Federation, 119992.
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12
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Nahon P, Ganne-Carrié N. Management of patients with pre-therapeutic advanced liver fibrosis following HCV eradication. JHEP Rep 2019; 1:480-489. [PMID: 32039400 PMCID: PMC7005771 DOI: 10.1016/j.jhepr.2019.11.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Revised: 10/30/2019] [Accepted: 11/06/2019] [Indexed: 12/19/2022] Open
Abstract
Patients with HCV-related bridging fibrosis or cirrhosis remain at risk of developing life-threatening complications even after achieving a sustained virological response. Although it is reduced, the risk of liver-related events in these patients justifies their inclusion in surveillance programmes dedicated to the early detection of hepatocellular carcinoma and the screening for portal hypertension. Biochemical parameters or non-invasive tests might indicate the potential progression of liver injury despite viral clearance. Specific attention must be focused on the management of comorbidities, while dedicated educational programmes must be encouraged to increase compliance and commitment to surveillance. Better knowledge of the long-term evolution of these patients, who now live longer, is essential to improve risk stratification and refine screening strategies in this growing population.
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Key Words
- AFP, alpha-fetoprotein
- ALT, alanine aminotransferase
- APRI, AST-to-platelet ratio index
- AST, aspartate aminotransferase
- DAAs, direct-acting antivirals
- EHC, extrahepatic cancer
- FIB-4, fibrosis-4
- HCC, hepatocellular carcinoma
- HCV
- HR, hazard ratio
- Hepatocellular carcinoma
- LSM, liver stiffness measurement
- Liver failure
- MACEs, major adverse cardiovascular events
- PHT, portal hypertension
- Portal hypertension
- SMR, standardised mortality ratio
- SVR
- SVR, sustained virological response
- surveillance
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Affiliation(s)
- Pierre Nahon
- AP-HP, Hôpital Jean Verdier, Liver Unit, Bondy, France
- University Paris 13, Sorbonne Paris Cité, “équipe labellisée Ligue Contre le Cancer”, F-93000 Bobigny, France
- INSERM UMR-1162: Functional Genomics of Solid Tumours, F-75010, Paris, France
| | - Nathalie Ganne-Carrié
- AP-HP, Hôpital Jean Verdier, Liver Unit, Bondy, France
- University Paris 13, Sorbonne Paris Cité, “équipe labellisée Ligue Contre le Cancer”, F-93000 Bobigny, France
- INSERM UMR-1162: Functional Genomics of Solid Tumours, F-75010, Paris, France
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13
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Liang LY, Wong VWS, Tse YK, Yip TCF, Lui GCY, Chan HLY, Wong GLH. Improvement in enhanced liver fibrosis score and liver stiffness measurement reflects lower risk of hepatocellular carcinoma. Aliment Pharmacol Ther 2019; 49:1509-1517. [PMID: 31025388 DOI: 10.1111/apt.15269] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Revised: 02/06/2019] [Accepted: 03/28/2019] [Indexed: 12/19/2022]
Abstract
BACKGROUND The Liver stiffness measurement hepatocellular carcinoma (LSM-HCC) score predicts HCC accurately in patients with chronic hepatitis B (CHB). AIM To assess the ability of LSM-HCC combined with enhanced liver fibrosis (ELF) score to predict HCC in CHB patients who received anti-viral treatment. METHODS CHB patients who had transient elastography examinations in 2006-2013 with intermediate and high risk of HCC by LSM-HCC score (ie 11 or above) were assessed by repeat transient elastography at least 3 years later. ELF score was assessed by retrieving the stored serum samples 4 weeks within transient elastography examination. The primary endpoint was the cumulative incidence of HCC. RESULTS A total of 453 CHB patients (mean age 51.7 ± 10.3 years; male 74.4%) were recruited, 45 patients (9.9%) developed HCC during the mean follow-up of 56 months. Regarding LSM-HCC score, 71.4%, 24.3% and 4.3% of patients had LSM-HCC score improved, remained static and deteriorated respectively; whereas 36.9%, 57.8% and 5.3% of patients had ELF score improved, remained static and deteriorated respectively. The sensitivity (86.7%) and negative predictive value (NPV) (95.3%) of combined LSM-HCC and ELF score were higher than that of each score alone. Kaplan-Meier analysis showed that ELF score would help further differentiate the HCC risk in patients with intermediate risk by LSM-HCC score (P = 0.026), but not in patients with high risk by LSM-HCC score (P = 0.770). CONCLUSIONS The two-step algorithm combining LSM-HCC score and ELF score could improve the accuracy of predicting HCC of CHB patients receiving anti-viral treatment.
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Affiliation(s)
- Lilian Yan Liang
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong
| | - Vincent Wai-Sun Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong
| | - Yee-Kit Tse
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong
| | - Terry Cheuk-Fung Yip
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong
| | - Grace Chung-Yan Lui
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong
| | - Henry Lik-Yuen Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong
| | - Grace Lai-Hung Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong
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14
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Ren H, Wang J, Gao Y, Yang F, Huang W. Metabolic syndrome and liver-related events: a systematic review and meta-analysis. BMC Endocr Disord 2019; 19:40. [PMID: 31023282 PMCID: PMC6485158 DOI: 10.1186/s12902-019-0366-3] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2019] [Accepted: 04/08/2019] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Previous studies have suggested that metabolic syndrome (MetS) and its component conditions are linked to the development of many benign or malignant diseases. Some studies have described relationships among metabolic syndrome or diabetes and liver cancer, but not many articles described the relationships between MetS and cirrhosis, acute hepatic failure, end-stage liver disease, and even death. However, liver cancers, cirrhosis, acute hepatic failure, end-stage liver disease, and liver-related mortality-collectively described as liver-related events (LREs)-may have different relationships with MetS. We undertook this meta-analysis to examine the association between MetS and LREs, and to determine whether geographic region or hepatitis B virus (HBV) positivity might influence the association. METHODS Relevant studies were identified from PubMed, EMBASE, and the Cochrane database. Two reviewers independently searched records from January 1980 to December 2017. The search terms included 'metabolic syndrome', 'diabetes mellitus', 'insulin resistance syndrome', and 'metabolic abnormalities', combined with 'cirrhosis', 'hepatic fibrosis ', 'hepatocellular carcinoma', 'complication', 'LRE', 'HCC', 'liver-related events', and 'liver cancer'. No language restriction was applied to the search. We chose the studies reporting an association between MetS and LREs. We used Begg's and Egger's tests and visually examined a funnel plot to assess publication bias. All analyses were conducted in Stata 14.0 software. RESULTS There were 19 studies (18 cohort and 1 case-control) included in the analysis, with a total of 1,561,457 participants. The subjects' ages ranged from 18 to 84 years. The combined analysis showed an overall 86% increase risk of LREs in cases with MetS (RR: 1.86,95% CI: 1.56-2.23). The funnel plot was asymmetrical, and the Egger's test p values showed a publication bias in this meta analysis. However, through the trim and fill method, we obtained a new RR value for LREs with MetS of 1.49 (95% CI: 1.40-1.58, p = 0.000). There was no obvious difference with the two answers, so we concluded that the results were robust. For hepatitis B positive patients, the RR for MetS and LREs was 2.15 (95% CI:1.02-4.53, p = 0.038), but for the hepatitis B negative patients, the RR was 1.85 (95% CI:1.53-2.24, p = 0.000). And for non-Asians, the RR for MetS and LREs was 2.21 (95% CI: 1.66-2.69, p = 0.000), while for Asians, the RR was 1.73 (95% CI: 1.35-2.22, p = 0.000). CONCLUSIONS This meta-analysis showed that MetS is associated with a moderately increased risk of LREs prevalence. Patients with MetS together with hepatitis B are more likely to develop hepatic events. For non-Asians, MetS is more likely to increase the incidence of LREs.
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Affiliation(s)
- Huina Ren
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016 China
| | - Junna Wang
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016 China
| | - Yue Gao
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016 China
| | - Fuwei Yang
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016 China
| | - Wenxiang Huang
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016 China
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15
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Kim W, Jeong D, Chung J, Lee D, Joo S, Jang ES, Choi YJ, Yoon H, Shin CM, Park YS, Jeong SH, Kim N, Lee DH, Kim JW. Development of colorectal cancer predicts increased risk of subsequent hepatocellular carcinoma in patients with alcoholic liver disease: case-control and cohort study. Sci Rep 2019; 9:3236. [PMID: 30824851 PMCID: PMC6397178 DOI: 10.1038/s41598-019-39573-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Accepted: 01/24/2019] [Indexed: 11/09/2022] Open
Abstract
Alcohol increases the risk of both hepatocellular carcinoma (HCC) and colorectal neoplasia. In this hospital-based case-control and retrospective cohort study, we sought to determine whether development of colorectal neoplasia increases the risk of HCC in patients with alcoholic liver disease (ALD). In the phase I case-control analysis, the association between history of colorectal cancer (CRC) and HCC development was assessed in patients with ALD by logistic regression modeling (n = 1,659). In the phase II retrospective cohort analysis, the relative risk of HCC development was compared in ALD patients with respect to the history of CRC by a Cox model (n = 1,184). The history of CRC was significantly associated with HCC in the case-control analysis (adjusted odds ratio, 1.82; 95% CI, 1.06-3.15; P < 0.05). ALD patients with CRC had higher risk of developing HCC compared to those without CRC (adjusted hazards ratio [HR], 5.48; 95% CI, 1.63-18.36; P = 0.006) in the cohort analysis. Presence of CRC, liver cirrhosis, elevated baseline alpha-fetoprotein level, and low platelet counts were independent predictors of HCC development in ALD patients. Patients with history of CRC had an increased risk of HCC in both cirrhotic (HR, 3.76; 95% CI, 1.05-13.34, P = 0.041) and non-cirrhotic (HR, 23.46; 95% CI, 2.81-195.83, P = 0.004) ALD patients. In conclusion, ALD patients with CRC are at increased risk of developing HCC.
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Affiliation(s)
- Won Kim
- Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.,Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Dongjae Jeong
- Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jungwha Chung
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Donghyeon Lee
- Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.,Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Saekyoung Joo
- Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.,Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Eun Sun Jang
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Yoon Jin Choi
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Hyuk Yoon
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Cheol Min Shin
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Young Soo Park
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Sook-Hyang Jeong
- Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.,Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Nayoung Kim
- Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Dong Ho Lee
- Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.,Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Jin-Wook Kim
- Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. .,Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
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16
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Hedenstierna M, Nangarhari A, El-Sabini A, Weiland O, Aleman S. Cirrhosis, high age and high body mass index are risk factors for persisting advanced fibrosis after sustained virological response in chronic hepatitis C. J Viral Hepat 2018; 25:802-810. [PMID: 29406590 DOI: 10.1111/jvh.12879] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2017] [Accepted: 01/02/2018] [Indexed: 12/11/2022]
Abstract
We aimed to assess fibrosis with liver stiffness measurement long-term after sustained virological response of chronic hepatitis C and to identify risk factors associated with persisting fibrosis. In this cross-sectional study, patients with chronic hepatitis C and pretreatment advanced fibrosis or cirrhosis treated successfully at Karolinska University Hospital with an interferon-containing regimen underwent liver stiffness measurement with FibroScan. The impact of potential risk factors for persisting fibrosis was estimated. We included 269 patients with a median follow-up time of 7.7 years (range 0-20), 84 with a follow-up time of ≥10 years. Patients with pretreatment cirrhosis had a significantly higher median liver stiffness level (8.5 kPa 95% CI 7-9.1) at follow-up, than patients with advanced fibrosis (6 kPa 95% CI 5.5-6.4). A majority improved their fibrosis stage after sustained virological response, but 24% had persisting advanced fibrosis with a liver stiffness level of ≥ 9.5 kPa. Among patients with pretreatment cirrhosis, the proportion with persisting advanced fibrosis diminished with longer follow-up time, from 48% after <5 years to 21% after >10 years. The main risk factors for persisting advanced fibrosis were pretreatment cirrhosis, high age and body mass index. In conclusion, fibrosis improves substantially during long-term follow-up after sustained virological response in hepatitis C patients with pretreatment advanced liver fibrosis. Lifestyle intervention to decrease weight in obese persons and treatment before establishment of cirrhosis should therefore be recommended to avoid persistence of advanced fibrosis after virological cure.
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Affiliation(s)
- M Hedenstierna
- Department of Infectious Diseases, Danderyd Hospital, Stockholm, Sweden
- Division of Infectious Diseases, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | - A Nangarhari
- Division of Infectious Diseases, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | - A El-Sabini
- Division of Infectious Diseases, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | - O Weiland
- Division of Infectious Diseases, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
- Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - S Aleman
- Division of Infectious Diseases, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
- Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
- Department of Gastroenterology and Hepatology, Karolinska University Hospital, Stockholm, Sweden
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17
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Facciorusso A, Del Prete V, Turco A, Buccino RV, Nacchiero MC, Muscatiello N. Long-term liver stiffness assessment in hepatitis C virus patients undergoing antiviral therapy: Results from a 5-year cohort study. J Gastroenterol Hepatol 2018; 33:942-949. [PMID: 28976021 DOI: 10.1111/jgh.14008] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2017] [Revised: 09/12/2017] [Accepted: 09/25/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Observational studies showed significant liver stiffness regression after sustained virological response, but long-term effects of antiviral therapy are still unknown. The aim of this study was to assess the magnitude of change in stiffness up to 5 years after therapy in hepatitis C patients undergoing antiviral treatment. METHODS Data of 153 patients were retrieved. Stiffness was assessed by Fibroscan at baseline, end of treatment, 6 months after treatment, and every year hereafter up to 5 years. RESULTS Seventy patients were treated with interferon-based regimens and 83 with direct antiviral agents. Baseline cirrhosis was diagnosed in 53 (34.6%) patients. Sustained virological response was achieved in 112 patients, whereas 41 were non-responders. In responders, stiffness decreased from 12.3 kPa (9-17.8) to 6.6 kPa (5.3-7.4) at 5 years. A sharper decline was observed immediately after treatment (-2.5 kPa at the end of treatment and -3.7 kPa at 6 months), while from 1 year onwards, the magnitude of stiffness decrease was progressively lower. In non-responders, stiffness showed a slight decrease at the end of treatment (from 19.2 to 18.1 kPa), then returned to baseline levels at 6 months (19.4 kPa), and finally increased over time up to 23.7 kPa (15-32.5) at 5 years. The proportion of cirrhotic patients decreased by 50% at 6 months and finally fell < 5% at 4 years after treatment. CONCLUSIONS Stiffness declines significantly after achieving response, and the magnitude of decline is greater in the first year after treatment, while it tends to plateau from 1 year onwards.
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Affiliation(s)
| | | | - Antonio Turco
- Gastroenterology Unit, University of Foggia, Foggia, Italy
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18
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Liver stiffness measurement predicts liver-related events in patients with chronic hepatitis C: A retrospective study. PLoS One 2017; 12:e0184404. [PMID: 28880930 PMCID: PMC5589221 DOI: 10.1371/journal.pone.0184404] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Accepted: 08/23/2017] [Indexed: 12/20/2022] Open
Abstract
The management of patients with chronic hepatitis C (CHC) depends on their clinical stage. Thus, noninvasive early recognition of patients with CHC at high risk for developing liver-related events (LREs) is important because it ensures optimal preventative management strategies may be employed that can affect the course of CHC disease. Our aim was to determine whether liver stiffness measurement (LSM) in hepatitis C virus (HCV)-infected patients is associated with a risk of LREs, particularly in cirrhotic patients. We carried out a retrospective study on 343 HCV-infected patients stratified according to cirrhosis (LSM<12.5 kPa vs. LSM≥12.5 kPa), and the cirrhotic patient group (LSM≥12.5 kPa) was divided according to risk of esophageal varices (LSM <25 kPa vs. LSM≥25 kPa). For all patients, each incremental unit in the natural logarithm (Ln) of LSM was associated with 14.76 times higher risk of developing LREs (p<0.001). Patients with cirrhosis (LSM≥12.5 kPa) had a higher risk of LREs than patients without cirrhosis (LSM<12.5 kPa) [adjusted hazard ratio (aHR) = 30.97; p<0.001]. When only cirrhotic patients were analyzed (n = 60), each incremental unit in the Ln of LSM was associated with 10.56 times higher risk of developing LREs (p = 0.010). Patients with LSM≥25 kPa had a greater risk for LRE development compared to those with LSM<25 kPa (aHR = 3.65; p = 0.045). The AUROC for predicting the onset of LREs was 0.876 in all patients and 0.729 in cirrhotic patients. In conclusion, LSM was associated with an increased risk of developing LREs in HCV-infected patients, even within the group of cirrhotic patients.
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19
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Torres HA, Shigle TL, Hammoudi N, Link JT, Samaniego F, Kaseb A, Mallet V. The oncologic burden of hepatitis C virus infection: A clinical perspective. CA Cancer J Clin 2017; 67:411-431. [PMID: 28683174 PMCID: PMC5591069 DOI: 10.3322/caac.21403] [Citation(s) in RCA: 75] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Revised: 05/09/2017] [Accepted: 05/10/2017] [Indexed: 12/18/2022] Open
Abstract
Answer questions and earn CME/CNE Chronic hepatitis C virus (HCV) infection affects millions of people worldwide and is associated with cancer. Direct-acting antivirals (DAAs) have changed HCV treatment paradigms, but little is known about the management of HCV infection in patients with cancer. The substantial burden of HCV infection and the inconclusive evidence regarding its detection and management in patients with cancer prompted the authors to review the literature and formulate recommendations. Patients for whom HCV screening is recommended included all patients with hematologic malignancies, hematopoietic cell transplantation candidates, and patients with liver cancer. There is a lack of consensus-based recommendations for the identification of HCV-infected patients with other types of cancer, but physicians may at least consider screening patients who belong to groups at heightened risk of HCV infection, including those born during 1945 through 1965 and those at high risk for infection. Patients with evidence of HCV infection should be assessed by an expert to evaluate liver disease severity, comorbidities associated with HCV infection, and treatment opportunities. DAA therapy should be tailored on the basis of patient prognosis, type of cancer, cancer treatment plan, and hepatic and virologic parameters. HCV-infected patients with cancer who have cirrhosis (or even advanced fibrosis) and those at risk for liver disease progression, especially patients with HCV-associated comorbidities, should have ongoing follow-up, regardless of whether there is a sustained virologic response, to ensure timely detection and treatment of hepatocellular carcinoma. HCV infection and its treatment should not be considered contraindications to cancer treatment and should not delay the initiation of an urgent cancer therapy. CA Cancer J Clin 2017. © 2017 American Cancer Society. CA Cancer J Clin 2017;67:411-431. © 2017 American Cancer Society.
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Affiliation(s)
- Harrys A. Torres
- H. A. Torres: Department of Infectious Diseases, Infection Control
and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX,
USA
| | - Terri Lynn Shigle
- T. L. Shigle: Division of Pharmacy, Section of Clinical Pharmacy
Services, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Nassim Hammoudi
- N. Hammoudi and V. Mallet: Université Paris
Descartes-Sorbonne Paris Cité; Assistance Publique-Hôpitaux de
Paris, Groupe Hospitalier Cochin Port Royal, Hepatology service; Institut National
de la Santé et de la Recherche Médicale unité 1223; Institut
Pasteur; all in Paris, France
| | - J. T. Link
- J. T. Link and A. Kaseb: Department of Gastrointestinal Medical
Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Felipe Samaniego
- F. Samaniego: Department of Lymphoma & Myeloma, The University
of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ahmed Kaseb
- J. T. Link and A. Kaseb: Department of Gastrointestinal Medical
Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Vincent Mallet
- N. Hammoudi and V. Mallet: Université Paris
Descartes-Sorbonne Paris Cité; Assistance Publique-Hôpitaux de
Paris, Groupe Hospitalier Cochin Port Royal, Hepatology service; Institut National
de la Santé et de la Recherche Médicale unité 1223; Institut
Pasteur; all in Paris, France
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20
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Jacobson IM, Lim JK, Fried MW. American Gastroenterological Association Institute Clinical Practice Update-Expert Review: Care of Patients Who Have Achieved a Sustained Virologic Response After Antiviral Therapy for Chronic Hepatitis C Infection. Gastroenterology 2017; 152:1578-1587. [PMID: 28344022 DOI: 10.1053/j.gastro.2017.03.018] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Chronic hepatitis C virus infection is well-recognized as a common blood-borne infection with global public health impact affecting 3 to 5 million persons in the United States and more than 170 million persons worldwide. Chronic hepatitis C virus infection is associated with significant morbidity and mortality due to complications of liver cirrhosis and hepatocellular carcinoma. Current therapies with all-oral direct-acting antiviral agents are associated with high rates of sustained virologic response (SVR), generally exceeding 90%. SVR is associated with a reduced risk of liver cirrhosis, hepatic decompensation, need for liver transplantation, and both liver-related and all-cause mortality. However, a subset of patients who achieve SVR will remain at long-term risk for progression to cirrhosis, liver failure, hepatocellular carcinoma, and liver-related mortality. Limited evidence is available to guide clinicians on which post-SVR patients should be monitored vs discharged, how to monitor and with which tests, how frequently should monitoring occur, and for how long. In this clinical practice update, available evidence and expert opinion are used to generate best practice recommendations on the care of patients with chronic hepatitis C virus who have achieved SVR.
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Affiliation(s)
- Ira M Jacobson
- Department of Medicine, Mount Sinai Beth Israel Medical Center, Icahn School of Medicine at Mount Sinai, New York, New York.
| | - Joseph K Lim
- Section of Digestive Diseases and Yale Liver Center, Yale University School of Medicine, New Haven, Connecticut
| | - Michael W Fried
- Division of Gastroenterology and Hepatology, UNC Liver Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina
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