HCV infection and extra-hepatic manifestations
The existence of hepatitis C virus (HCV) infection in an individual is commonly associated with many extra-hepatic manifestations such as skin and auto-immune disorders.
Speaking at the recent Asia Pacific Association for the Study of the Liver (APASL) Single Topic Conference, held in Kuala Lumpur recently, Professor Dr Diana Alcantara Payawal, Fatima University Medical Center, said that extra-hepatic manifestations (EHM) of HCV cause significant morbidity and mortality. The increase in mortality is mostly due to renal, metabolic and cardiovascular complications.
HCV is strongly associated with cryoglobulinemia, diabetes and lymphoma, among others. HCV’s link to EHMs and poorer outcomes was established in the REVEAL-HCV Cohort study, where it was discovered that persons who were anti-HCV seropositive with detectable HCV RNA had significantly higher mortality from hepatic and extrahepatic diseases than those who were anti-HCV seropositive with undetectable HCV RNA. [J Infect Dis 2012;206(4):469–477]
In kidney disease, too, the presence of HCV leads to poorer outcomes as demonstrated by Nakayama and Lai. Both teams revealed a corresponding increase in mortality in patients with end-stage renal disease (ESRD) and those undergoing haemodialysis. [JASN 2000;11(10):1896–1902]
Other studies point to HCV’s link with autoimmune or lymphoproliferative disorders, from mixed cryoglobulinemia vasculitis to frank lymphomas. [Ther Adv Infect Dis 2016;3(1): 3–14]
The global nonprofit organization known as Kidney Disease: Improving Global Outcomes (KDIGO) recommends for HCV infected patients to be tested annually for proteinurea, haematuria and estimated glomerular filtration rate (eGFR) to detect possible HCV-associated kidney disease. Conversely, patients with chronic kidney disease should also be tested for HCV.
Treatment of HCV EHM
In light of all the possible collateral damage caused by HCV infection, the first target of etiologic therapy is HCV eradication and subsequently, the improvement of HCV EHM comorbidities. According to Payawal, first-line therapeutic measures for HCV EHM treatment should include interferon (IFN) and direct-acting antivirals (DAAs). This is true for those who do not need urgent or life-threatening measures.
In those with impaired kidney function, there are a few options for treatment with DAAs. Those with glomerular filtration rate (GFR) >30 mL/min can still access all therapeutic options. Those with GFR<30 mL/min or genotype 1b/1a/4 can undergo elbasvir/grazoprevir (EBV/GZP) combination or the 3D regimen for 12 weeks. Those with GFR <30 mL/min and GT1a will need to undergo GZP/EBV for 16 weeks or a 12-week treatment of 3D plus ribavirin. Testing for NS5A inhibitor resistance-associated variants (RAVs) should be done as these are associated with relapse.
The combination of IFN-free DAA and non-etiologic therapy can be considered in severe cases, noted Payawal. However, the choice of non-etiologic therapy should consider the degree of HCV-related liver damage and, should it be used together with DAAs, the possible drug-drug interactions. [Autoimmunity Reviews 2017;16:523–541]
Note: REVEAL-HCV was a prospective community based study carried out in Taiwan looking at hepatitis B status, anti-HCV status, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alpha-fetoprotein (AFP) among other things. Those who had HBsAg (positive for active hepatitis B infection) or anti-HCV, or family history of hepatocellular carcinoma were followed-up and subjected to abdominal ultrasound and blood tests until 2004.