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The effect of sustained virological response on the risk of extrahepatic manifestations of hepatitis C virus infection.

ABSTRACT: BACKGROUND AND AIM:Chronic HCV infection is associated with several extrahepatic manifestations (EHMs). Data on the effect of sustained virological response (SVR) on the risk of EHMs are limited. METHODS:We conducted a retrospective cohort study using data of patients from the US Veterans Affairs HCV Clinical Case Registry who had a positive HCV RNA test (10/1999-08/2009). Patients receiving interferon-based antiviral therapy (AVT) were identified. SVR was defined as negative HCV RNA at least 12 weeks after end of AVT. Risks of eight incident EHMs were evaluated in Cox regression models. RESULTS:Of the 160 875 HCV-infected veterans, 31?143 (19.4%) received AVT, of whom 10?575 (33.9%) experienced SVR. EHM risk was reduced in the SVR group compared with untreated patients for mixed cryoglobulinaemia (adjusted HR (aHR)=0.61; 95% CI 0.39 to 0.94), glomerulonephritis (aHR=0.62; 95% CI 0.48 to 0.79), porphyria cutanea tarda (PCT) (aHR=0.41; 95% CI 0.20 to 0.83), non-Hodgkin's lymphoma (NHL) (aHR=0.64; 95% CI 0.43 to 0.95), diabetes (aHR=0.82; 95% CI 0.76 to 0.88) and stroke (aHR=0.84; 95% CI 0.74 to 0.94), but not for lichen planus (aHR=1.11; 95% CI 0.78 to 1.56) or coronary heart disease (aHR=1.12; 95% CI 0.81 to 1.56). Risk reductions were also observed when patients with SVR were compared with treated patients without SVR for mixed cryoglobulinaemia, glomerulonephritis, PCT and diabetes. Significant reductions in the magnitude of aHRs towards the null with increasing time to initiation of AVT after HCV diagnosis were observed for glomerulonephritis, NHL and stroke. CONCLUSIONS:Risks of several EHMs of HCV infection are reduced after AVT with SVR. However, early initiation of AVT may be required to reduce the risk of glomerulonephritis, NHL and stroke.

SUBMITTER: Mahale P

PROVIDER: S-EPMC6292199 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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The effect of sustained virological response on the risk of extrahepatic manifestations of hepatitis C virus infection.

Mahale Parag P Engels Eric A EA Li Ruosha R Torres Harrys A HA Hwang Lu-Yu LY Brown Eric L EL Kramer Jennifer R JR

Gut 20170620 3

<h4>Background and aim</h4>Chronic HCV infection is associated with several extrahepatic manifestations (EHMs). Data on the effect of sustained virological response (SVR) on the risk of EHMs are limited.<h4>Methods</h4>We conducted a retrospective cohort study using data of patients from the US Veterans Affairs HCV Clinical Case Registry who had a positive HCV RNA test (10/1999-08/2009). Patients receiving interferon-based antiviral therapy (AVT) were identified. SVR was defined as negative HCV ...[more]

PMID: 28634198

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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.

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The effect of sustained virological response on the risk of extrahepatic manifestations of hepatitis C virus infection.

Publications

The effect of sustained virological response on the risk of extrahepatic manifestations of hepatitis C virus infection.

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