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Hepatitis C virus as a systemic disease: reaching beyond the liver.
K. Gill.
Hepatol Int 2016; 10:415–23.

Chronic hepatitis C (CHC) is associated with multiple extrahepatic manifestations that may impact infected patients. The mechanisms through which these develop include those which are immunological and those which are virological and related to the extrahepatic tropism of the virus to other tissues. It is estimated that 40–74 % of patients with CHC may develop at least one extrahepatic manifestation during the course of the disease. Extrahepatic syndromes may represent the first signal of hepatitis C infection in some patients.

Extrahepatic manifestations :

Although data are limited on the resolution of extrahepatic manifestations with the new direct acting antiviral medications, multiple studies over the course of the past few decades have shown marked improvement of extrahepatic manifestations upon eradication of HCV after treatment with previous therapies, primarily combination therapy with peg-IFN and ribavirin. With standard courses of peg-IFN/ribavirin the following have been seen:

Emerging data on treatment with the direct acting antivirals show similar effects. A recent study showed decreased fatigue at SVR 12 compared to baseline with treatment with ledipasvir and sofosbuvir. Viral eradication with sofosbuvir/ledipasvir has also been associated with improvement in health-related quality of life and work productivity.

Expert's Commentary

« Chronic HCV infection not only affects the liver but also leads to significant organs involvement outside the liver. Most organs are affected, with various consequences in terms of morbidity and mortality, from the most benign – dermatological, thyroid – to the most severe conditions including cardiovascular events, renal insufficiency associated with cryoglobulinemia, lymphoma. The extrahepatic effects of HCV are likely multifactorial and include HCV replication in extrahepatic cells, auto-immune and immune-mediated effects as well as endocrine effects.
Many studies, with pegylated interferon and ribavirine, have shown that SVR improves liver-related but also non-liver morbidity and mortality. Such improvement is with no doubt a consequence of HCV cure, and is independent of the treatment used to achieve such cure.
With availability of simpler, well tolerated, and more efficacious anti-HCV regimens, the extent of improvements in the extrahepatic manifestations of HCV will likely increase in the near future.
Given the burden and frequency of these extrahepatic manifestations of chronic HCV infection, more systematic treatment of HCV should be offered in patients presenting with pre-existing co-morbidities which could be worsened by chronic HCV infection. Also, extrahepatic manifestations of HCV should be considered as a major indication for treatment even in the absence of liver disease. »

Pr François Raffi, Nantes