Secondary prevention for hepatocellular carcinoma in patients with chronic hepatitis B: are all the nucleos(t)ide analogues the same?

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.

Novel machine learning models outperform risk scores in predicting hepatocellular carcinoma in patients with chronic viral hepatitis

“… 23 Furthermore, recent studies suggest that tenofovir may further reduce HCC risk in patients with CHB. 24 , 25 DAAs are also increasingly used in patients with CHC. 26 With increasing and changing use of these antiviral therapies, the machine learning models should be continuously optimised.…”

Risk factors for hepatocellular carcinoma at baseline and 1 year after initiation of nucleos(t)ide analog therapy for chronic hepatitis B

“…NA therapy has been shown to significantly reduce the cumulative incidence of HCC. 32 ; however, the increased risk of HCC conferred by HBV infection is not completely eliminated.…”

Unique Features of Hepatitis B Virus-Related Hepatocellular Carcinoma in Pathogenesis and Clinical Significance

“…Clinical use of antiviral nucleotide and nucleot(s)tide analogs (NUCs) at the first line efficiently represses HBV replication and reduces inflammation [ 11 , 12 ]. Subsequently, the HCC risk in these NUCs-treated patients is significantly lowered [ 13 , 14 ]. Therefore, long-term antiviral therapies by NUCs become the standard of care for CHB.…”

“…Therefore, long-term antiviral therapies by NUCs become the standard of care for CHB. However, the residual HCC risk in these treated patients is not negligible since the five-year cumulative incidence of HCC in the noncirrhotic population remains up to 6.9%, which is still above the threshold of surveillance [ 14 , 15 ]. One of the reasons is probably due to the unique feature of HBV DNA integration that happens during early infection periods in the majority of HBV-related HCC [ 16 ].…”