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Early treatment of HCV reduces extrahepatic morbidity, mortality

AMSTERDAM — Dealing with hepatitis C virus as a systemic disease, and not just a complication of the liver, may aid clinicians in reducing extrahepatic manifestations of the infection, according to experts at the International Liver Congress.

Francesco Negro, MD, of the departments of clinical pathology, gastroenterology and hepatology at University Hospital in Geneva, Switzerland, suggested that there is strong evidence that people with HCV often die of non–liver-related causes. “Of course, the leading cause of death is from the liver, but a group in Hong Kong observed many other reasons for dying, including renal, metabolic and cardiovascular disease,” he said. “These complications are not linked to the viral infection.”

Negro added that this is not necessarily new information. “Historically, we knew from the early days that non-A, non-B hepatitis was associated with vasculitis,” he said. “It was very clear that those viruses were possibly also involved with triggering immune-mediated reactions outside the virus.”

Recent data describing this incidence have proliferated. Findings from Younossi and colleagues suggested that hyperbilirubinemia, Sjögren’s syndrome, diabetes and other costly complications may arise when a patient has HCV, according to Negro. He said that data from Arase and colleagues showed that curing HCV can reduce diabetes by about half over time, and that data from Hsu indicated that treatment of the virus may reduce ESLD, acute coronary disease and stroke.

“The HCV health burden deriving from extrahepatic manifestations of the disease can be staggering,” Negro said. “There has been a lack of analysis of indirect costs, which may be extremely significant, especially when it comes to fatigue and loss of time at work.”

Moreover, it is difficult to dissect true extrahepatic manifestations from other comorbidities, according to Negro. “There is anecdotal evidence of direct infection of non-hepatocytes causing central nervous system dysfunction,” he said, and added that the secretion of substances with endocrine effects may yield insulin resistance. “We also have seen abnormal autoimmune reactions.”

Renal complications, of course, were the first to be identified, according to Negro. “HCV patients should be tested annually for proteinuria, hematuria and EGFR to detect possible kidney disease,” he said. “HCV is a non-traditional risk factor for chronic kidney disease.”

Regarding diabetes and insulin resistance, historical data, particularly those from NHANES in 2000, have shown that diabetes incidence increases steadily in patients with HCV compared with patients without the virus, according to Negro. He suggested that this phenomenon accelerates between ages 40 to 49 years and 50 to 59 years. “HCV accelerates diabetes by 10 years,” Negro said. However, he acknowledged that NHANES data from 2014 showed that the association was lost.

For cardiovascular disease, Negro cited data from Petta and colleagues showing that carotid plaque was elevated among patients with HCV, but he suggested that smoking was also a factor in this incidence. “There was also an effect of the virus on cerebrovascular events, but other risk factors were present, as well,” he said.

More broadly, Negro said that the evidence is pointing toward a clear benefit of early treatment of HCV, but that more data are needed. “We don’t expect miracles from these new cures,” he said. – by Rob Volansky

Reference: Negro F. Joint Workshop EASL/Viral Hepatitis Group. Presented at: International Liver Congress; April 19-24, 2017; Amsterdam.

Disclosure: Negro reports associations with AbbVie, Merck and Gilead.