Infection by the hepatitis B virus (HBV) represents a significant global socio-sanitary burden. While liver transplantation (LT) is an important therapeutic option, treatments that prevent HBV reinfection are necessary. The combination of anti-hepatitis B immunoglobulin (HBIG) and nucleoside/nucleotide analogs (NA) is the standard post-transplant treatment; however, there are limitations in using HBIG, particularly its cost. We present two illustrative clinical cases as examples of post-transplant management using dual NA therapy, unaccompanied by HBIG.

The first case involves a 42-year-old man with HBV-related cirrhosis, who, in the context of a diagnosis of hepatocellular carcinoma and hepatopulmonary syndrome, underwent LT without viremia at the time of transplantation. A lack of availability of HBIG led to the combined use of two NAs, entecavir, and tenofovir alafenamide-resulting in the negativization of hepatitis B surface antigen (HBsAg) and maintenance of a negative viral load in the post-transplant period. In the second case, a 63-year-old woman presented with acute hepatic failure due to HBV with viremia during transplantation. Combined therapy with entecavir and tenofovir alafenamide, again due to the unavailability of HBIG, ultimately led to the negativization of HBsAg and viral load.

These cases suggest the efficacy of dual NA therapy in post-transplant HBV management, emphasizing the need to reconsider traditional treatment approaches.

Vanitaracin A is an anti-hepatitis B virus (anti-HBV) compound isolated from the culture broth of the fungus Talaromyces sp. Vanitaracin A inhibits the entry of HBV into target cells with sub-micromolar IC₅₀ values. While a structure-activity relationship study is highly desirable, a synthetic approach still needs to be developed, which is difficult because the absolute configurations of the six stereogenic centers in the structure of vanitaracin A have not yet been determined. In the present study, we used the crystalline sponge method to clarify the configuration of the compound after determining the absolute configuration of the secondary alcohol using a modified Mosher ester method. Combining these analyses with the NOESY spectrum of vanitaracin A and NMR analyses of the crude side-chain carboxylic acid obtained by the alkaline hydrolysis of vanitaracin A revealed the absolute configurations of all stereogenic centers in this important compound.

Chronic hepatitis B (CHB) patients with higher hepatitis B virus (HBV) load (higher viral load [HVL], HBV DNA ≥1 × 10⁷ copies/mL) require antiviral therapy, but data for evaluating the long-term outcome of this therapy with antiviral agents remain limited. We comparatively evaluated the efficacy and the safety of nucleoside analogues in 179 noncirrhotic CHB patients with HVL over 5 years. The HBeAg-positive (n = 104) or HBeAg-negative (n = 75) patients were treated consecutively with telbivudine (LdT, n = 88) or entecavir (ETV, n = 91) and evaluated for viral response, drug resistance and safety. HBV DNA, viral serology, biochemistries, HBV mutation and off-therapy relapse were determined. The cumulative rates of HBV DNA negativity were 86.4% and 94.5% for LdT and ETV at year 5, respectively. The rates of early viral response (EVR, HBV DNA <10³ copies/mL at month 6) under LdT and ETV treatments were 58.0% and 34.1%, respectively (P < .05). Hepatitis B e antigen (HBeAg) and Hepatitis B surface antigen (HBsAg) loss-seroconversions were 47.7% and 18.2% on LdT and 16.5% and 2.2% on ETV (P < .01). Eighteen patients (age 28.2 ± 3.1) experienced HBsAg loss-seroconversion, followed by 33 ± 4.6 month off-therapy without a relapse. Viral mutations and serum creatine kinase elevation were 9.1% and 8.0% on LdT, but only 1.1% and 0% on ETV. Both LdT and ETV suppressed HBV replication in HVL CHB patients within 5 years. LdT therapy achieved a higher EVR, HBeAg and HBsAg seroconversion, especially in the younger patients, whereas ETV caused lower drug resistance and fewer adverse events. This finding might help to identify the optimal treatment for CHB patients with HVL.