Treatment of HBV/HCV Coinfection By Dr. Shahriar Alian 2016/09/01 Associated professor , Antimicrobial Resistance Research Center, Mazandaran University of Medical Sciences, Sari, Iran

Introduction Mono infection with either hepatitis B (HBV) or C virus (HCV) represents one of the major causes of chronic liver disease globally. In endemic areas a of patients are infected with both viruses mainly as a result of the common routes of transmission.

Introduction HBV/HCV coinfection occurs with complex virological patterns that may be dynamic and change over time. HCV is the dominant virus in about half of patients, while HBV is dominant in 25% of patients. HBV/HCV coinfection is associated with more severe liver disease, with an increased risk for hepatic decompensation and more rapid development of hepatocellular carcinoma. HBV/HCV coinfection is associated with a higher mortality rate compared with HBV or HCV mono-infection.

Clinical presentation of HBV/HCV coinfected patients Simultaneous acute infection with HBV and HCV Superinfection of chronic HBV carriers with HCV HBV superinfection of chronic HCV

Viral interaction Treatment of HBV/HCV coinfected patients can be a challenge owing to the sometimes complex dynamic patterns of viral dominances. HCV and HBV seem to inhibit each other’s replication.

Viral interaction A variety of viral profiles has been documented in patients with HBV/HCV coinfection. Viral dominance can be defined as one virus showing significant viral replication (HCV RNA > 50,000 IU/ml; HBV DNA > 2000 IU/ml) with the other virus being suppressed (HCV RNA negative or HBV DNA negative or < 2000 IU/ml).

Treatment issue Very limited data regarding therapy of HBV/HCV coinfected patients are available, there are no established specific treatment guidelines for these patients Treatment must be individualized based on patient variables such as hepatitis virology, patient’s previous exposure to antiviral treatment, the presence of other similarly transmitted viruses such as hepatitis D virus and human immunodeficiency virus (HIV), stage and grade of liver disease and comorbidities

Treatment issues HBV dominance, which means high HBV DNA levels and low HCV RNA levels HCV dominance defined by the high HCV RNA levels and absent HBV DNA The first step in the treatment of HBV/HCV-coinfected patients is to determine which is the dominant virus that should be eradicated. Careful longitudinal follow up of serum HBV DNA and HCV RNA levels is essential before the diagnosis of the viral dominance These viral interactions will very likely influence the therapeutic strategies in dually infected patients

Treatment issues Treatment of HCV in dual HCV/HBV patients with active HCV infection Patients should be treated with the same regimens, following the same rules as HCV monoinfected patients Treatment of HBV in dual HCV/HBV patients with active HBV infection If HBV replicates at significant levels before, during or after HCV clearance, concurrent HBV nucleoside/ nucleotide analogue therapy is indicated Simeprevir increases exposure to tenofovir Thus, in patients receiving tenofovir as anti-HBV treatment, the eGFR and tubular function should be monitored frequently during treatment and tenofovir doses should be consequently adjusted

Treatment issues Patients with fulminant hepatic failure are not likely to respond to antiviral agents and are candidates for liver transplantation Initiation of antiviral treatment is recommended in patients with significant fibrosis, cirrhosis or risk of developing HCC