Antiviral treatment to prevent chronic hepatitis B or C-related hepatocellular carcinoma

Abstract

Antiviral treatment is the only option to prevent or defer the occurrence of hepatocellular carcinoma (HCC) in patients chronically infected with hepatitis B virus (HBV) or hepatitis C virus (HCV). The approved medication for the treatment of chronic HBV infection is interferon-α (IFNα) and nucleos(t)ide analogues (NAs), including lamivudine, adefovir dipivoxil, telbivudine, entecavir and tenofovir disoproxil fumarate. IFNα is the most suitable for young patients with less advanced liver diseases and those infected with HBV genotype A. IFNα treatment significantly decreases the overall incidence of HBV-related HCC in sustained responders. However, side effects may limit its long-term clinical application. Orally administered NAs are typically implemented for patients with more advanced liver diseases. NA treatment significantly reduces disease progression of cirrhosis and therefore HCC incidence, especially in HBV e antigen-positive patients. NA-resistance due to the mutations in HBV polymerase is a major limiting factor. Of the NA resistance-associated mutants, A181T mutant significantly increases the risk of HCC development during the subsequent course of NA therapy. It is important to initiate treatment with NAs that have a high genetic barrier to resistance, to counsel patients on medication adherence and to monitor virological breakthroughs. The recommended treatment for patients with chronic HCV infection is peg-IFN plus ribavirin that can decrease the occurrence of HCC in those who achieve a sustained virological response and have not yet progressed to cirrhosis. IFN-based treatment is reserved for patients with decompensated cirrhosis who are under evaluation of liver transplantation to reduce post-transplant recurrence of HCV. More effective therapeutic options such as direct acting antiviral agents will hopefully increase the response rate in difficult-totreat patients with HCV genotype 1. However, the risk of HCC remains in cirrhotic patients (both chronic HBV and HCV infection) if treatment is initiated after cirrhosis is established. Future research should focus on investigating new agents, especially for those patients with hepatic decompensation or post-transplantation.

The progress and prospects of routine prophylactic antiviral treatment in hepatitis B-related hepatocellular carcinoma

“…Although the relationship between HBV infection and HCC has not been fully described, antiviral treatments for HBV infections have been proven to reduce HCC risk in patients with chronic HBV infection, with or without the presence of cirrhosis [12]. It was reported that antiviral treatments using oral nucleoside analogs can result in up to a 78% decrease in HCC incidence, especially in HBeAg-positive patients, but long-term continuous treatment with nucleoside or nucleotide analogs (NAs) can cause drug resistance due to the mutations in HBV polymerase [13][14][15]. Lai et al pointed out that antiviral treatments using nucleoside analogs appear to be more effective in reducing the risk of HCC development, while the effect of interferon-α (IFN-α) antiviral treatment is likely to be limited to patients with cirrhosis [16].…”

Dysregulation of Retinoic Acid Receptor Diminishes Hepatocyte Permissiveness to Hepatitis B Virus Infection through Modulation of Sodium Taurocholate Cotransporting Polypeptide (NTCP) Expression

“…However, the antiviral efficacy of IFN-based drugs is restricted to less than 40% (9,10). Second, nucleos(t)ide analogs, including lamivudine (LMV), adefovir, entecavir (ETV), tenofovir, and telbivudine suppress HBV by inhibiting the viral reverse transcriptase (11,12). Although they can provide significant clinical improvement, long term therapy with nucleos(t)ide analogs often results in the selection of drug-resistant mutations in the target gene, which limits the treatment outcome.…”

The Distribution Clinical and Demographic Features of HBsAg Positive Patients in Şanlıurfa Region

“…Potent antiviral agents are medicines which may provide long-term HBV DNA suppression and improvement of cirrhosis with quite low resistance rates. Additionally, their long-term use may decrease the risk of HCC development (19). The most commonly given drugs in our patient group were tenofovir and entecavir.…”