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The effects of sustained virological response to direct-acting anti-viral therapy on the risk of extrahepatic manifestations of hepatitis C infection.

ABSTRACT: BACKGROUND:Direct-acting anti-viral (DAA) therapy may have a beneficial role in extrahepatic manifestations of hepatitis C virus (HCV) infection. However, the available data are limited. AIM:To examine the effects of DAA treatment on the risk of several extrahepatic manifestations of HCV. METHODS:We conducted a retrospective cohort study of patients from the US Department of Veterans Affairs Corporate Data Warehouse who had a positive HCV RNA test and received first course of DAAs between 2012 and 2016. We calculated incidence rates by sustained virological response (SVR) status for six extrahepatic manifestations, and effect of SVR on these conditions was evaluated in adjusted Cox regression models. RESULTS:Of the 45 260 patients treated with DAA with mean follow-up of 2.01 years, 41 711 (92.2%) experienced SVR. Incidence rates ranged from 0.17/1000 PY for porphyria cutanea tarda to 21.04/1000 PY for diabetes in the SVR group and 0.51/1000 PY for porphyria cutanea tarda to 23.11/1000 PY for diabetes in the no SVR group. The risk was reduced with SVR for mixed cryoglobulinaemia (adjusted HR (aHR) = 0.23; 95% CI 0.10-0.56), glomerulonephritis (aHR = 0.61; 95% CI 0.41-0.90) and lichen planus (aHR = 0.46; 95% CI 0.30-0.70), but not for non-Hodgkin's lymphoma (aHR = 0.86; 95% CI 0.52-1.43) or diabetes (aHR = 0.98; 95% CI 0.81-1.19). Non significant risk reduction was seen for porphyria cutanea tarda (aHR = 0.33; 95% CI 0.11-1.03). CONCLUSIONS:Successful DAA treatment resulting in SVR was associated with significant reductions in the risk of mixed cryoglobulinaemia, glomerulonephritis, lichen planus and possibly porphyria cutanea tarda, but not non-Hodgkin's lymphoma or diabetes.

SUBMITTER: El-Serag HB

PROVIDER: S-EPMC6510621 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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The effects of sustained virological response to direct-acting anti-viral therapy on the risk of extrahepatic manifestations of hepatitis C infection.

El-Serag Hashem B HB Christie Israel C IC Puenpatom Amy A Castillo Diana D Kanwal Fasiha F Kramer Jennifer R JR

Alimentary pharmacology & therapeutics 20190401 11

<h4>Background</h4>Direct-acting anti-viral (DAA) therapy may have a beneficial role in extrahepatic manifestations of hepatitis C virus (HCV) infection. However, the available data are limited.<h4>Aim</h4>To examine the effects of DAA treatment on the risk of several extrahepatic manifestations of HCV.<h4>Methods</h4>We conducted a retrospective cohort study of patients from the US Department of Veterans Affairs Corporate Data Warehouse who had a positive HCV RNA test and received first course ...[more]

PMID: 30932218

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Project description:Hepatitis C virus (HCV) is a common cause of liver disease and is associated with various extrahepatic manifestations (EHMs). This mini-review outlines the currently available treatments for HCV infection and their prognostic effect on hepatic manifestations and EHMs. Direct-acting antiviral (DAA) regimens are considered pan-genotypic as they achieve a sustained virological response (SVR) > 85% after 12 wk through all the major HCV genotypes, with high percentages of SVR even in advanced fibrosis and cirrhosis. The risk factors for DAA failure include old males, cirrhosis, and the presence of resistance-associated substitutions (RAS) in the region targeted by the received DAAs. The effectiveness of DAA regimens is reduced in HCV genotype 3 with baseline RAS like A30K, Y93H, and P53del. Moreover, the European Association for the Study of the Liver recommended the identification of baseline RAS for HCV genotype 1a. The higher rate of hepatocellular carcinoma (HCC) after DAA therapy may be related to the fact that DAA regimens are offered to patients with advanced liver fibrosis and cirrhosis, where interferon was contraindicated to those patients. The change in the growth of pre-existing subclinical, undetectable HCC upon DAA treatment might be also a cause. Furthermore, after DAA therapy, the T cell-dependent immune response is much weaker upon HCV clearance, and the down-regulation of TNF-α or the elevated neutrophil to lymphocyte ratio might increase the risk of HCC. DAAs can result in reactivation of hepatitis B virus (HBV) in HCV co-infected patients. DAAs are effective in treating HCV-associated mixed cryoglobulinemia, with clinical and immunological responses, and have rapid and high effectiveness in thrombocytopenia. DAAs improve insulin resistance in 90% of patients, increase glomerular filtration rate, and decrease proteinuria, hematuria and articular manifestations. HCV clearance by DAAs allows a significant improvement in atherosclerosis and metabolic and immunological conditions, with a reduction of major cardiovascular events. They also improve physical function, fatigue, cognitive impairment, and quality of life. Early therapeutic approach with DAAs is recommended as it cure many of the EHMs that are still in a reversible stage and can prevent others that can develop due to delayed treatment.

Dataset Information

The effects of sustained virological response to direct-acting anti-viral therapy on the risk of extrahepatic manifestations of hepatitis C infection.

Publications

The effects of sustained virological response to direct-acting anti-viral therapy on the risk of extrahepatic manifestations of hepatitis C infection.

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