Objective: Little clinical data are available regarding the optimal treatment of patients who harbour entecavir (ETV)-resistant HBV. Design: In this multicentre randomised trial, patients who had HBV with ETV resistance-associated mutations and serum HBV DNA concentrations >60 IU/mL were randomised to receive tenofovir disoproxil fumarate (TDF, 300 mg/day) monotherapy (n=45) or TDF and ETV (1 mg/day) combination therapy (n=45) for 48 weeks. Results: Baseline characteristics were comparable between groups, including HBV DNA levels (median, 4.02 log ₁₀ IU/mL) and hepatitis B e antigen-positivity (89%). All patients had at least one ETV-resistance mutation: rtT184A/C/F/G/I/L/S (n=49), rtS202G (n=43) and rtM250L/V (n=7), in addition to rtM204V/I (n=90). All except one patient in the TDF group completed 48 weeks of treatment. At week 48, the proportion of patients with HBV DNA 0.99). The mean change in HBV DNA levels from baseline was not significantly different between groups (−3.66 vs −3.74 log ₁₀ IU/mL; p=0.81). Virological breakthrough occurred in one patient on TDF, which was attributed to poor drug adherence. At week 48, six and three patients in the TDF and TDF+ETV groups, respectively, retained their baseline resistance mutations (p>0.99). None developed additional resistance mutations. Safety profiles were comparable in the two groups. Conclusions: TDF monotherapy for 48 weeks provided a virological response comparable to that of TDF and ETV combination therapy in patients infected with ETV-resistant HBV. Trial registration number: ClinicalTrials.gov ID NCT01639092 .

Han Ah Lee, Joon Young Jung, Young-Sun Lee, Young Kul Jung, Ji Hoon Kim, Hyonggin An, Hyung Joon Yim, Yoon Tae Jeen, Jong Eun Yeon, Kwan Soo Byun, Soon Ho Um, and Yeon Seok Seo. Gut and Liver 2021;15:599-605. https://doi.org/10.5009/gnl20171

Sorafenib is the first approved systemic treatment for advanced hepatocellular carcinoma (HCC). However, its clinical utility is limited, especially in Asian countries. Several reports have suggested the survival benefits of hepatic arterial infusion chemotherapy (HAIC) for advanced HCC with main portal vein tumor thrombosis (PVTT). This study aimed to compare the efficacy of sorafenib-based therapy with that of HAIC-based therapy for advanced HCC with main PVTT. Advanced HCC patients with main PVTT treated with sorafenib or HAIC between 2008 and 2016 at Korea University Medical Center were included. We evaluated overall survival (OS), time-to-progression (TTP), and the disease control rate (DCR). Seventy-three patients were treated with sorafenib (n=35) or HAIC (n=38). Baseline characteristics were not significantly different between groups, except the presence of solid organ metastasis (46% vs 5.3%, p<0.001). The median OS time was not significantly different between the groups (6.4 months vs 10.0 months, p=0.139). TTP was longer in the HAIC group than in the sorafenib group (2.1 months vs 6.2 months, p=0.006). The DCR was also better in the HAIC group than in the sorafenib group (37% vs 76%, p=0.001). Subgroup analysis, which excluded patients with extrahepatic solid organ metastasis, showed the same trends for the median OS time (8.8 months vs 11.1 months, p=0.097), TTP (1.9 months vs 6.0 months, p<0.001), and DCR (53% vs 81%, p=0.030). HAIC-based therapy may be an alternative to sorafenib for advanced HCC with main PVTT by providing longer TTP and a better DCR.

Han Ah Lee, Young-Sun Lee, Beom Kyung Kim, Young Kul Jung, Seung Up Kim, Jun Yong Park, Ji Hoon Kim, Hyunggin An, Do Young Kim, Hyung Joon Yim, Sang Hoon Ahn, Jong Eun Yeon, Kwan Soo Byun, Kwang-Hyub Han, Soon Ho Um, and Yeon Seok Seo. Gut and Liver 2021;15:420-9. https://doi.org/10.5009/gnl20101

Yoon EL, et al. J Korean Med Sci. 2017 Feb;32(2):212-220. https://doi.org/10.3346/jkms.2017.32.2.212

Background: Genetic variations in interleukin 28B (IL28B) have been strongly associated with a sustained virological response (SVR) in European and African-American patients. Genetic variation of IL28B was investigated in healthy controls and chronic hepatitis C (CHC) patients, and the treatment response in the CHC patients was analyzed according to IL28B polymorphism in the Korean population. Methods: IL28B polymorphisms (rs12979860 and rs8099917) were studied in 200 healthy controls and in 167 CHC patients who were treated with peginterferon-α and ribavirin. Results: The prevalence of rs12979860 in healthy controls is as follows: the CC-genotype was 88.5%, the CT-genotype was 11.5%, and the TT-genotype was not found. The prevalence of rs8099917 in healthy controls is as follows: the TT-genotype was 89.5%, the TG-genotype was 10.5%, and the GG-genotype was not found. The CC-genotype of rs12979860 and the TT-genotype of rs8099917 were found to be closely related (linkage disequilibrium; D′=1.0, χ²=0.9082). In 106 CHC patients treated with peginterferon and ribavirin, the SVR was 67.2% (n=58) for 1b, 91.6% (n=47) for 2a. In hepatitis C virus (HCV) genotype 1b with respect to rs12979860, the SVR in CC-genotype was 72.9% and that in CT-genotype was 40.0%. On investigating predictive factors for SVR, pretreatment low-HCV RNA levels, HCV genotype non-1, early virological response, and also the IL28B CC-genotype for rs12979860 were good indicators of an SVR. Conclusions: In Korea, genetic variation of IL28B is different from that in western countries in view of high prevalence of rs12979860 CC-genotype. It seems likely that a high SVR in Korean patients with genotype 1 CHC patients is due to the genetic polymorphism in IL28B.