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We examined the frequency and significance of mutations in the core promoter and precore region in 103 Japanese patients with chronic hepatitis B virus (HBV) infection. HBV DNAs from the patients' sera were amplified by polymerase chain reaction and were directly sequenced. A double mutation (T1762 A1764) in the core promoter was frequently observed in the patients regardless of HBeAg status except for asymptomatic carriers with HBeAg. Furthermore, a mutation at nucleotide 1753 from T to C or G was frequently found in anti-HBe positive patients and was often accompanied by the double mutation. The A1896 mutation was found in only about one fourth of the patients with anti-HBe. These data suggest that the patients with chronic liver diseases frequently had a double mutation regardless of HBeAg status and a mutation at nucleotide 1753 might be associated with HBeAg-negative chronic hepatitis B virus infection. [ABSTRACT FROM AUTHOR]

Abstract Background A recent genome-wide association study (GWAS) using chronic HBV (hepatitis B virus) carriers with and without hepatocellular carcinoma (HCC) in five independent Chinese populations found that one SNP (rs17401966) in KIF1B was associated with susceptibility to HCC. In the present study, a total of 580 HBV-derived HCC cases and 1351 individuals with chronic hepatitis B (CHB) or asymptomatic carrier (ASC) were used for replication studies in order to evaluate the reported association with HBV-derived HCC in other East Asian populations. Results We did not detect any associations between rs17401966 and HCC in the Japanese cohorts (replication 1: OR = 1.09, 95 % CI = 0.82-1.43; replication 2: OR = 0.79, 95 % CI = 0.54-1.15), in the Korean cohort (replication 3: OR = 0.95, 95 % CI = 0.66-1.36), or in the Hong Kong Chinese cohort (replication 4: OR = 1.17, 95 % CI = 0.79-1.75). Meta-analysis using these cohorts also did not show any associations with P = 0.97. Conclusions None of the replication cohorts showed associations between rs17401966 and HBV-derived HCC. This may be due to differences in the genetic diversity among the Japanese, Korean and Chinese populations. Other reasons could be the high complexity of multivariate interactions between the genomic information and the phenotype that is manifesting. A much wider range of investigations is needed in order to elucidate the differences in HCC susceptibility among these Asian populations.

Tenofovir alafenamide (TAF), a prodrug of tenofovir, delivers high levels of active drug to hepatocytes and is given in a lower dose than tenofovir disoproxil fumarate (TDF). TAF reduces viral replication in patients with chronic hepatitis B (CHB) similar to TDF and has shown a lower risk of the renal and bone toxicities associated with TDF use. This post-marketing surveillance study examined the safety and effectiveness of TAF in treatment-naïve and -experienced CHB patients who received TAF for 144 weeks at real-world clinical sites in Japan. Safety assessments included the incidence of adverse drug reactions (ADRs), renal and bone events, and changes in selected laboratory parameters. Effectiveness was based on the proportion of patients with HBV DNA levels below the lower limit of quantitation or <29 IU/mL. This analysis included 580 patients; 18.4% of whom were treatment-naïve. The cumulative incidence of ADRs was 0.21 per 100 person-months, and the incidence of serious ADRs was 0.01 (95% CI, 0.00-0.04) per 100 person-months. There were no ADRs of declines in estimated glomerular filtration rates, renal failure or proximal tubulopathy. The most common ADR was hypophosphataemia in seven (1.2%) patients. Two (0.4%) patients each had decreased blood phosphorus, bone mineral density decreased, dizziness and alopecia. Overall, the proportion of virologically suppressed patients increased from 68.8% at baseline to 97.5% at Week 144. These results confirm the real-world safety and effectiveness of TAF in Japanese patients with CHB and are consistent with the findings of other evaluations of the safety and efficacy of TAF in CHB., (© 2023 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

Aim: Cell-free and concentrated ascites reinfusion therapy (CART) and large-volume paracentesis (LVP) with albumin infusion are useful for managing refractory ascites (RA). However, it remains unclear which therapy is more effective in patients with cirrhosis with RA., Methods: From June 2018 to March 2022, 25 patients with RA treated with CART or LVP with albumin infusion were enrolled in this multicenter prospective observational study to investigate the number of abdominal paracenteses, albumin preparations used, and drainage volume during an 8-week observation period., Results: Among all patients at entry (median age, 63 years; 52% men; 60% Child-Pugh B and 40% Child-Pugh C), 92% were treated with furosemide (median, 20 mg/day), 92% with spironolactone (25 mg/day), and all with tolvaptan (7.5 mg/day). Patients with RA had a poor health-related quality of life (HRQOL) and prominent ascites-related symptoms. Four of the 20 eligible patients were treated with CART, 11 with LVP with albumin infusion, and five with their combination. The median number of paracenteses, total drainage volume, and albumin infusions were 1.5, 7.4 L, and 0, respectively, in the CART group; 5.0, 22.0 L, and 5.0, respectively, in the LVP group; and 5.0, 30.0 L, and 5.0, respectively in their combination group. The treatment effects did not differ significantly among the three groups regarding weight loss, liver function, renal function, electrolytes, and HRQOL. However, patients treated with CART had fewer paracenteses and albumin infusions than those treated with LVP., Conclusions: CART and LVP have comparable therapeutic efficacy for RA in patients with cirrhosis., (© 2022 Japan Society of Hepatology.)

Background: Hepatitis B virus (HBV) is one of the most prevalent chronic viral infections that causes chronic hepatitis B (CHB). In Japan, genotypes B and C account for most of acute and chronic cases of hepatitis. However, previous studies showed that the prevalence of genotype A in CHB gradually increased every 5 years. Therefore, we have conducted a nationwide survey to comprehensively investigate the trends of HBV genotype distribution in CHB patients in Japan., Methods: 4421 CHB patients were recruited between 2015 and 2016. Clinical characteristics and distribution of CHB patients among different age groups and genotypes in 2015-2016 was compared with those in 2000-2001, 2005-2006, and 2010-2011., Results: The percentages of genotype A, B, C, and D were 4.0, 16.2, 79.1, and 0.7%, respectively. While the overall percentage of CHB patients with genotype A did not change in the past 5 years, CHB with genotype A increased in young adults. On the other hand, the peak distribution of CHB with genotypes B and C, two genotypes with the largest patient population, has shifted to an older age group., Conclusions: In Japan, the peak distribution for CHB with genotypes B and C advanced to an older age group while CHB with genotype A expanded in a younger age group. Given the universal HBV vaccination launch in Japan in 2016, these pre-vaccination survey data provide important baseline information for comparative studies of the impact of universal vaccination on HBV genotypes., (© 2022. Japanese Society of Gastroenterology.)

Background: Rifaximin is commonly used for hepatic encephalopathy (HE). However, the effects of long-term treatment for Japanese people are limited. Therefore, this study aimed to investigate the effects and safety of long-term treatment with rifaximin on HE. Methods: A total of 215 patients with cirrhosis administered with rifaximin developed overt or covert HE, which was diagnosed by an attending physician for >12 months. Laboratory data were extracted at pretreatment and 3, 6, and 12 months after rifaximin administration. The long-term effect of rifaximin was evaluated, and the incidence of overt HE during 12 months and adverse events was extracted. Results: Ammonia levels were significantly improved after 3 months of rifaximin administration and were continued until 12 months. There were no serious adverse events after rifaximin administration. The number of overt HE incidents was 9, 14, and 27 patients within 3, 6, and 12 months, respectively. Liver enzymes, renal function, and electrolytes did not change after rifaximin administration. Prothrombin activity is a significant risk factor for the occurrence of overt HE. The serum albumin, prothrombin activity, and albumin−bilirubin (ALBI) scores were statistically improved after 3 and 6 months of rifaximin administration. Moreover, the same results were obtained in patients with Child−Pugh C. Conclusions: The long-term rifaximin treatment was effective and safe for patients with HE, including Child−Pugh C.

Introduction and Objectives: Sustained virologic response (SVR) is achieved in most cases of C-type liver disease after direct-acting antiviral (DAA) therapy. Although liver fibrosis improves, the degree of improvement is different. This study aimed to analyze the factors involved in improving liver fibrosis using the fibrosis 4 (FIB-4) index., Material and Methods: Patients were monitored for >3 years after SVR. At the start of therapy (SOT), liver fibrosis was categorized as either mild (<1.45 n = 28), moderate (1.45-3.25 n = 139), or advanced (>3.25 n = 236) based on the FIB-4 index. The FIB-4 index in the advanced group decreased significantly compared to that of the other two, so we selected the advanced group as the analysis target. SOT and end of therapy (EOT) factors that contributed to the FIB-4 index ≤3.25 at 3 years after therapy were examined using a multivariate analysis., Results: Among the SOT factors, age (<72 years old), absence of liver cirrhosis (LC), alanine transferase (ALT) (≥50 U/L), platelet (PLT) (≥10.2 × 10 4 /mm 3 ), and total bilirubin (T.Bil) (<0.8 mg/dl) were the significant factors contributing to the improvement of the FIB-4 index. Among the EOT factors, age (<72 years), PLT (≥12.0 × 10 4 /mm3), and hemoglobin (Hb) (≥12.1 g/dl) were the significant factors contributing to the improvement of FIB-4 index., Conclusions: Factors involved in the improvement of liver fibrosis after SVR were young age, absence of LC, low T.Bil., high ALT, high PLT, and high Hb levels. The levels of T.Bil, PLT, and Hb were considered to be related to portal hypertension. Aging strongly impaired the improvement in liver fibrosis., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2021 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Objective This study evaluated the efficacy associated with switching to rifaximin in patients with hepatic cirrhosis receiving kanamycin sulfate for the treatment of hepatic encephalopathy and hyperammonemia. Methods We included 37 patients who switched from kanamycin sulfate to rifaximin at our institution from January 2017 to December 2018. The onset of hepatic encephalopathy and changes in blood ammonia values during a six-month period were retrospectively evaluated. Results There were 4 (11%) patients with hepatic encephalopathy at the time of switching from kanamycin sulfate to rifaximin. The cumulative incidence of hepatic encephalopathy was 3% and 16% at 3 and 6 months later, respectively. The blood ammonia levels at the time of switching to rifaximin and at 3 and 6 months later were 94 (range, 20-243) μg/dL, 95 (range, 33-176) μg/dL, and 81 (range, 32-209) μg/dL, respectively, and no significant changes were observed. However, in the 11 patients receiving an oral dose of <1,500 mg/day of kanamycin sulfate, the blood ammonia levels at the time of switching and at 3 and 6 months later were 136 (range, 35-243) μg/dL, 95 (range, 33-150) μg/dL, and 63 (range, 43-124) μg/dL, respectively. Furthermore, the blood ammonia levels significantly decreased at the time of the switching to rifaximin and at three and six months later (p=0.043 and p=0.011, respectively). Conclusion Switching to rifaximin in hepatic cirrhosis patients receiving kanamycin sulfate to treat hepatic encephalopathy and hyperammonemia showed effects that were equivalent to or greater than the original therapy, thereby demonstrating the clinical efficacy.