International therapeutic guidelines for patients with HCV-related extrahepatic disorders. A multidisciplinary expert statement

Abstract

Hepatitis C virus (HCV) is both hepatotrophic and lymphotropic virus that causes liver as well extrahepatic manifestations including cryoglobulinemic vasculitis, the most frequent and studied condition, lymphoma, and neurologic, cardiovascular, endocrine-metabolic or renal diseases. HCV-extrahepatic manifestations (HCV-EHMs) may severely affect the overall prognosis, while viral eradication significantly reduces non-liver related deaths. Different clinical manifestations may coexist in the same patient. Due to the variety of HCV clinical manifestations, a multidisciplinary approach along with appropriate therapeutic strategies are required. In the era of interferon-free anti-HCV treatments, international recommendations for the therapeutic management of HCV-EHMs are needed. This implies the need to define the best criteria to use antivirals and/or other therapeutic approaches. The present recommendations, based on qualified expert experience and specific literature, will focus on etiological (antiviral) therapies and/or traditional pathogenetic treatments that still maintain their therapeutic utility.

Impact of sustained virological response on the extrahepatic manifestations of chronic hepatitis C: a meta-analysis

“…Since the development of direct-acting, non-interferon, antiviral regimens, the main international guidelines support the treatment of all patients HCV-infected patients, with the exception of those with a short life expectancy (reviewed in Zignego  et al 13). Although these recommendations do not account for economic criteria, Younossi et al estimated the direct medical costs for the extrahepatic manifestation of HCV, in the USA alone, to be US$1506 million (range US$922 to 2208 million) 29.…”

“…Altogether, these findings highlight the public health burden of extrahepatic manifestations associated with HCV infection. Treatment of HCV-infected patients therefore demands complex multidisciplinary management 13. Alternatively, a curative panoptic approach of viral eradication has been reported to reduce extrahepatic mortality 11 12 14 15.…”

Direct medical costs associated with the extrahepatic manifestations of hepatitis C infection in Europe

“…Retrospective and prospective studies in several countries have shown that the achievement of SVR may protect against the development of mixed cryoglobulinemia, malignant lymphoma, end‐stage renal disease (ESRD) and type 2 diabetes . Clinical guidelines in Europe, therefore, recommend that HCV patients with clinically significant EHMs be prioritized for DAA treatment . A recent study from France has estimated that DAA treatment may reduce the economic burden of EHMs by up to 13% .…”

Thyroid Involvement in Hepatitis C Virus-Infected Patients with/without Mixed Cryoglobulinemia

“…The standard hormone replacement therapy is indicated in symptomatic HCV-associated AT with/without MC syndrome. HCV eradication is an important therapeutical/preemptive approach to several manifestations of HCV syndrome (30), including thyroid involvement, in particular the rare HCV-related papillary thyroid cancer.…”