Reply
Authors: Manuel Mendizabal, Federico Piñero, Ezequiel Ridruejo
Journal: Clinical Gastroenterology and Hepatology (2020)

We appreciate the constructive comments provided by Allain Braillon on our study evaluating the incidence of disease progression in patients with hepatitis C virus (HCV) infection who underwent direct-acting antiviral (DAA) treatment.1Mendizabal M. Piñero F. Ridruejo E. et al.Clin Gastroenterol Hepatol. 2020; 18: 2554-2563Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar Essentially, he highlighted a relevant observation of our study and requested clarification on some issues related to the analysis of the Latin American Liver Research, Educational and Awareness Network cohort. First, our study not only evaluated the incidence of hepatocellular carcinoma (HCC) in patients with HCV after receiving DAA but also described the incidence of liver decompensation events and death. In this cohort we only included patients with no history of liver decompensation; thus patients with Child-Pugh score B or C were excluded. HCC screening was performed every 6 months as recommended by international guidelines.2Heimbach J. Kulik L.M. Finn R. et al.Hepatology. 2018; 67: 358-380Crossref PubMed Scopus (1302) Google Scholar As a consequence of the later introduction of DAAs in Latin America, the follow-up period of our study was relatively short (median, 26.2 months; interquartile range, 15.3–37.5), and 27.1% of the patients completed 3 or more years of follow-up. Second, Dr Braillon questioned the 13.6% human immunodeficiency virus prevalence in our study because we excluded patients with active intravenous drug addiction. We decided to exclude these patients because they are associated with a higher chance of missing follow-up, a key element of our study. We would like to add that the prevalence of intravenous drug abuse in Latin America is considerably lower than in Europe and the United States.3Dolan K. Wirtz A.L. Moazen B. et al.Lancet. 2016; 388: 1089-1102Abstract Full Text Full Text PDF PubMed Scopus (279) Google Scholar Furthermore, we performed a sensitivity analysis of baseline variables associated with disease progression excluding human immunodeficiency virus coinfected patients, and we found no significant differences. Third, we understand the importance of following the Strengthening the reporting of observational studies in epidemiology (STROBE) statement in observational studies. However, the authors reporting these guidelines underlined that their intention is solely to provide guidance on how to report observational research well, and they emphasize that the STROBE statement was not developed as a tool for assessing the quality of published observational research. Last, Dr. Braillon brings a substantial topic into discussion. Is HCV eradication with antiviral therapies enough to avoid future liver decompensation events? Achieving sustained virologic response with interferon-based therapies or DAAs is associated with a decreased adjusted risk of all-cause mortality (13 studies, n = 36,986; pooled hazard ratio, 0.40; 95% confidence interval, 0.28–0.56) and HCC (20 studies, n = 84,491; pooled hazard ratio, 0.29; 95% CI, 0.23–0.38) vs not achieving sustained virologic response.4Chou R. Dana T. Fu R. et al.JAMA. 2020; 323: 976-991Crossref Scopus (26) Google Scholar Despite these remarkable benefits obtained after HCV cure, the risk of developing liver decompensation events or death is not fully eliminated, especially in patients with advanced liver fibrosis. Dr Braillon mentioned a very interesting study by Innes et al5Innes H. McAuley A. Alavi M. et al.Hepatology. 2018; 67: 97-107Crossref PubMed Scopus (20) Google Scholar analyzing the contribution to excess mortality of health risk behaviors in individuals with chronic HCV. Well-known health risk behaviors such as alcohol use, cigarette smoking, physical inactivity, unhealthy diet, and illicit drug use are significantly associated with increased mortality risk in this group of patients. Our study was designed to evaluate the incidence of disease progression in individuals with HCV after treatment with DAAs and not the impact of lifestyle interventions. Nevertheless, no one can question the long-term impact of lifestyle interventions in overall mortality. In our study we made a relevant observation; patients with mild to moderate liver fibrosis who achieved sustained virologic response were still at risk of developing liver-related complications, albeit at a low risk. This could be the consequence of misdiagnosis of pretreatment hepatic fibrosis and, more importantly, the omission of some health risk behaviors during follow-up evaluation. However, we do not agree with Dr Braillon when he prioritizes lifestyle interventions over DAA therapies. There are no studies comparing the impact of lifestyle interventions vs HCV cure on the incidence of liver decompensation events and death; this would have been unethical. Nevertheless, physicians treating HCV should keep in mind that we are not treating only a viral infection; we are dealing with patients with a complex liver disease where HCV is the main risk factor but perhaps not the only one. Overweight, alcohol consumption, diabetes, and other comorbidities should also be considered. That is one of the reasons why hepatologists are essential to achieve the World Health Organization’s ambitious goal of a 65% decrease in HCV-related mortality by 2030. Efforts should be made to overcome multiple-layered barriers related to patient, provider, and structural factors that prevent linkage to HCV care.6Mendizabal M. Alonso C. Silva M.O. Overcoming barriers to hepatitis C elimination.Frontline Gastroenterol. 2019; 10: 207-209Crossref PubMed Scopus (12) Google Scholar We need to collaborate with primary care or non-liver specialists to make a positive impact on HCV disease burden. Screening for Cirrhosis in People With Fatty Liver?Clinical Gastroenterology and HepatologyVol. 19Issue 4PreviewThe complex and theoretical decision model by Vilar-Gomez et al1 to quantify the accuracy and costs of various strategies for detection of cirrhosis in patients with nonalcoholic fatty liver disease deserves clinical comments. Full-Text PDF