Hepatitis C Extrahepatic Manifestations Reduced by Sustained Virologic Response

Patrice Cacoub, MD

Achieving sustained virological response (SVR) with treatment of hepatitis C virus (HCV) infection was found to be associated with a reduction of extrahepatic manifestations and the corresponding mortality in a new meta-analysis.

Although liver cirrhosis and hepatocellular carcinoma account for many of the 700,000 annual HCV-related deaths in the US, investigators from Sorbonne University in Paris, France, found that a substantial portion of this mortality can be attributed to the extrahepatic manifestations associated with HCV.

These are not limited to autoimmune and lymphoproliferative disorders, they note, but to a range of conditions including cardiovascular, neurological, metabolic and renal, which large cohort studies have found can emerge with or be exacerbated by HCV infection.

In their meta-analysis, Patrice Cacoub, MD, of the university’s Immunopathology-Biotherapy Department and colleagues found that SVR—which is attained in more than 90% of patients treated with direct-acting antivirals (DAAs)—is associated with an approximate 50% reduction in HCV-related extrahepatic mortality. This finding supports a curative, panoptic approach to viral eradication with DAAs over the more complex and costly multidisciplinary management of HCV-infected patients.

"Given adequate testing to identify chronically infected individuals, these potential savings reflect the compelling opportunity that such safe and highly effective treatments offer to diminish the healthcare burden caused by HCV morbidity and mortality," Cacoub and colleagues wrote.

In commentary accompanying the meta-analysis, Francesco Negro, MD, Divisions of Clinical Pathology, Gastroenterology and Hepatology, University Hospital, Geneva, Switzerland, commended the investigators for factoring in extrahepatic complications in weighing mortality and morbidity of untreated HCV against the cost of treatment with DAAs.

"The costs of untreated HCV are significant, although most studies have been focusing only on direct costs associated with the management of HCV-associated liver disease, that is, excluding indirect costs related to loss of productivity, which are estimated to be at least twofold the direct ones," Negro pointed out.

Cacoub and colleagues identified 48 publications that compared conditions in SVR and non-SVR patients for inclusion in the meta-analysis, including 4 studies involving over 7,000 patients which reported on extrahepatic mortality. They calculated a reduced extrahepatic-related mortality in SVR patients versus non-SVR, with an odds ratio (OR) of 0.44 (95% CI: 0.28-0.67).

In addition, SVR was associated with higher complete remissions in patients with cryoglobulinemia vasculitis (OR 20.76 [95% CI: 6.73-64.05]); and a higher objective response in those with malignant B-cell lymphoproliferative diseases (OR 6.49 [95% CI: 2.02-20.85]). There was also a reduction in insulin resistance in those achieving SVR (OR 0.42 [95% CI: 0.33-0.53]); and some protective effect on the incidence of diabetes (OR 0.34 [95% CI 0.21-0.56]).

The investigators acknowledge that the lack of randomized data comparing SVR versus non-SVR patients in the trials limited the strength of their findings. They also pointed out that rapid achievement of SVR with successful DAA treatments necessarily limited the available timeframe to follow patients, requiring longer surveillance studies to evaluate their findings.

Negro agreed with their assessment.

"One must concur with the authors that in spite of the large amount of published evidence, there is need of better quality data gathered over long periods of follow-up to assess the genuine impact of antiviral therapy on some HCV-associated extrahepatic manifestations," he observed.

The study, “Impact of sustained virological response on the extrahepatic manifestations of chronic hepatitis C: a meta-analysis,” was published online in the BMJ Journal Gut.