Chronic infection by the HCV is responsible for a systemic disease combining liver disease, cryoglobulinemic vasculitis and various extrahepatic manifestations (EHM) related to chronic inflammation (diabetes, neurocognitive disorders including asthenia, cardiovascular, renovascular and cerebrovascular pathologies, extrahepatic cancer including non-Hodgkin lymphoma (NHL) and intrahepatic cholangiocarcinoma) (1-2).
Figure 1: HCV infection is a systemic disease with the consequences of its hepatotropism, lymphotropism and of chronic inflammation.
As well as being responsible for a hepatic mortality rate that is around ten times higher than that in subjects with no active infection, the active infection is also responsible for an extrahepatic mortality rate that is around twice as high in the Taiwanese Reveal-HCV registry study (3). Given the remarkable efficacy of oral antiviral treatments, we were therefore hoping to see the same reduction in extrahepatic morbidity and mortality as that observed for hepatic morbidity and mortality.
The brief industrial post-therapeutic follow-up studies were unable to capture these variations extensively. Real-life studies, some of which presented at the American conference of the AASLD (8-13.11.2018, San Francisco, USA), unanimously confirm the benefits associated with virologic cure (4), which is defined as an undetectable viral RNA for 12 weeks after the end of antiviral treatment lasting 8 to 12 weeks.
In addition to a reduction in hepatic complications (cirrhosis and hepatocellular carcinoma), numerous studies unanimously show a rapid improvement in manifestations of cryoglobulinaemic vasculitis (5): The purpura or the necrotising acrodermatitis repairs itself during treatment, as do the glomerulopathy and the nephrotic syndrome; two thirds of NHL patients are placed in remission; the reduction in symptoms of peripheral neuropathy is slower.
Regarding the EHM related to inflammation, an improvement in glycoregulation together with a decrease in oral antidiabetic dosages, or even a diabetes cure, can be observed sometime after the treatment. A reduction in the risk of extrahepatic cancer in the event of a cure is not demonstrated. The two main improvements are as follows:
improvements in the physical and mental quality of life indexes during treatment and beyond, which are magnified by the initial neuropsychiatric disorder; an improvement in vascular accidents (myocardial infarction, stroke, peripheral artery disease), which are reduced by 50% in 3 years, not only in cirrhotic patients in the Cirvir cohort but also in non-cirrhotic patients (6). A reduction in intimal carotid plaque, which is more frequent in subjects with fibrosis, is reported during treatment (7).
Professor Stanislas Pol