Abstract
Reducing the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) is the key ultimate goal set in essentially all treatment guidelines. There has been solid evidence supporting the relationship between serum hepatitis B virus (HBV) DNA level and risk of HCC. Antiviral treatment with oral nucleos(t)ide analogues (NAs) leads to sustained viral suppression and hence is often adopted as the secondary prevention for HCC in CHB patients. The first-generation NA, lamivudine, reduced the risk of HCC at 3 years compared to placebo; yet, its high emergence of antiviral resistance has made it no longer recommended in the international guidelines. Recent heated debate is about the two current first-line NAs—entecavir and tenofovir disoproxil fumarate (TDF)—Are they just as good to reduce HCC risk in CHB patients? A handful of cohort studies show two different kinds of observations—TDF is better than entecavir in lowering HCC risk, or these two NAs have led to similarly low risk of HCC. Tenofovir alafenamide (TAF), a modified version of TDF higher rate of ALT normalization, would be another potent nucleotide analogue is the treatment of choice for secondary prevention for HCC.
Highlights
Hepatocellular carcinoma (HCC) is a major global health problem because of its high incidence rate and unfavorable clinical course [1]
Recent heated debate is about the two current first-line nucleos(t)ide analogues (NAs)—entecavir and tenofovir disoproxil fumarate (TDF)—Are they just as good to reduce hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) patients? A handful of cohort studies show two different kinds of observations—TDF is better than entecavir in lowering HCC risk, or these two NAs have led to low risk of HCC
The vaccine has dramatically reduced the prevalence rates of chronic hepatitis B virus (HBV) infection and the incidence of HCC at younger ages in high-risk countries in East Asia, where universal vaccination was first introduced [5]. While such primary prevention for HCC has benefited children and young adults, patients who were born before the availability of HBV vaccination and chronically infected with HBV cannot benefit from such primary prevention and remain at risk of developing HCC [6]
Summary
Hepatocellular carcinoma (HCC) is a major global health problem because of its high incidence rate and unfavorable clinical course [1]. The current international treatment guidelines for patients with chronic hepatitis B (CHB) recommend entecavir, tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) as the first-line nucleos(t)ide analogues (NA) treatment They have high antiviral effects and a high genetic barrier to drug resistance [8, 10]. All three international guidelines have recommended the use of entecavir and two formulations of tenofovir (TDF and TAF) as treatment of choice regardless of the severity of liver disease, given their high resistance barrier with predictable high long-term antiviral efficacy leading to undetectable HBV DNA, as well as favorable safety profile, in the majority of compliant patients. Kim et al reported their results of a cohort of 2897 CHB patients from four academic, tertiary hospitals They showed by propensity score-matched analysis that there was no statistically significant difference between TDF and entecavir treatment on HCC risk, with an HR of 1.02. The focus on comparison on drug effectiveness and chemoprevention may switch from TDF to TAF when more long-term data are available
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