Unmet need in chronic hepatitis B management

Abstract

Despite all these exciting developments, there remain some unmet needs in the management for patients with chronic hepatitis B (CHB). As majority of CHB patients are going to use oral nucleos(t)ide analogues (NAs) for decades, Safety profile of NAs is of no doubt an important issue. The newest nucleotide analogue tenofovir alafenamide is potent in terms of viral suppression, together with favourable renal and bone safety profile. Biochemical response as reflected by alanine aminotransferase (ALT) normalization is recently found to be prognostically important. Patients who achieved ALT normalization have reduced the risk of hepatic events by 49%. Functional cure as reflected by hepatitis B surface antigen seroclearance not only implies patients may stop NA treatment, it also confers to a reduced risk of hepatocellular carcinoma and other hepatic events. Hence functional cure should be the ultimate treatment goal in CHB patients. Preemptive antiviral treatment may reduce mother-to-child transmission of hepatitis B virus, especially if birth dose of vaccination cannot be given in the first two hours after delivery. Lastly, despite the currently first-line NAs have high-genetic barrier to drug resistance mutations, there are still are many patients who were previously treated with low barrier of resistance including lamivudine, telbivudine or adefovir dipivoxil which could lead to antiviral resistance and affecting the choice of NAs.

Keywords: Cirrhosis; Hepatitis B; Hepatocellular carcinoma; Mortality; Tenofovir alafenamide.

Figure 1.

Dose-response of on-treatment alanine aminotransferase (ALT) levels and hepatocellular carcinoma (HCC). There was a dose response in terms of ALT level at 12 months and risk of HCC. Kaplan-Meier analysis estimated the cumulative incidence (95% confidence interval) of composite endpoint at 6 years in of different ALT levels at 12 months: P<0.001 for trend). Adopted from Wong et al. [23]. ULN, upper limit of normal.

Figure 2.

Impact of age and gender on risk of hepatocellular carcinoma (HCC) after hepatitis B surface antigen (HBsAg) seroclearance. The cumulative incidence rates of HCC at 1, 3 and 5 years after HBsAg seroclearance were 0.8% (0.4% to 1.6%), 1.0% (0.5% to 1.8%) and 1.0% (0.5% to 1.8%), respectively in female >50 subgroup; the corresponding rates were 0.5% (0.2% to 1.4%), 0.7% (0.3% to 1.6%) and 0.7% (0.3% to 1.6%) in male ≤50 years old subgroup. Adopted from Yip et al. [33].