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Resistant starch (RS) has been reported to improve steatosis as well as obesity. Type 4 resistant starch (RS4), a chemically modified starch, is particularly hard to digest and suggesting higher efficacy. However, because the effects of RS4 on steatosis are not yet fully understood, the effects of RS4 on steatosis were examined using a murine high-fat diet model. Seven-week-old male mice were divided into three groups and fed a normal diet, a high-fat diet (HFD), or a high-fat diet with added RS (HFD + RS). Amylofiber SH® produced from acid-treated corn starch was used as the dietary RS. At 22 weeks old, hepatic steatosis and short chain fatty acid (SCFA) content and gut microbiota in cecum stool samples were analyzed. The ratio of body weight to 7 weeks was significantly suppressed in the HFD + RS group compared to the HFD group (132.2 ± 1.4% vs. 167.2 ± 3.9%, p = 0.0076). Macroscopic and microscopic steatosis was also suppressed in the HFD + RS group. Analysis of cecum stool samples revealed elevated SCFA levels in the HFD + RS group compared with the HFD group. Metagenome analysis revealed that Bifidobacterium (17.9 ± 1.9% vs. 3.6 ± 0.7%, p = 0.0019) and Lactobacillus (14.8 ± 3.4% vs. 0.72 ± 0.23%, p = 0.0045), which degrade RS to SCFA, were more prevalent in the HFD + RS group than the HFD group. In conclusion, RS4 suppressed steatosis, and increased Bifidobacterium and Lactobacillus, and SCFAs. RS4 may prevent steatosis by modulating the intestinal environment.

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Purpose: Posthepatectomy liver failure (PHLF) is a major complication of hepatectomy. Although the extent of liver resection and fibrosis stages were previously identified as predictors of the development of PHLF, fibrosis stages were diagnosed using samples from resected livers. We evaluated the association between preoperative/intraoperative liver biopsies and final fibrosis stages.Methods: We included 272 patients who underwent an initial hepatectomy at our facility between January 2014 and December 2018.Results: PHLF occurred in 70 patients (25.7%) and decreased their overall survival (p = 0.0001). Preoperative/intraoperative liver biopsies showed a significant correlation with final fibrosis stages (p < 0.0001). The underestimation rates of preoperative and intraoperative F0/F1/F2 were 16.9% and 28.2%, respectively. Among the preoperative factors, 99mTc-GSA scintigraphy LHL < 0.91 was significantly associated with the resected liver fibrosis stages (hazard ratio [HR], 2.38; 95% confidence interval [CI]: 1.37–4.21; p = 0.0022). The underestimation rates of preoperative F0/F1/F2 with 99mTc-GSA scintigraphy LHL > 0.91 and Conclusions: The fibrosis stages of the resected livers were associated with preoperative and intraoperative liver biopsies. Successful hepatectomies could be performed in accordance with findings from preoperative liver biopsies, 99mTc-GSA scintigraphy, and intraoperative liver biopsies without the incidence of PHLF.

Background/aim While there is increasing evidence supporting the role of several first- and second-line treatment regimens for advanced hepatocellular carcinomas (HCC), the clinical relevance of rechallenge treatment with previously administered drugs, however, remains to be explored. Patients and methods Five consecutive patients with advanced HCC who received lenvatinib rechallenge treatment after ramucirumab were assessed. Results All patients were clinically diagnosed with failure after ramucirumab treatment, and the frequencies of ramucirumab administration before lenvatinib re-administration ranged from 3 to 11. The alfa-fetoprotein level in four of five patients decreased 1 month after the lenvatinib rechallenge. Radiological findings via the modified Response Evaluation Criteria in Solid Tumors showed stable diseases in four patients and a partial response in one. Conclusion Rechallenge treatment with lenvatinib after ramucirumab can be effective, and may be a treatment option for HCC in cases wherein the disease progressed after an initial response to lenvatinib treatment.

BACKGROUND: Cigarette smoking is known to be a significant risk factor associated with nonalcoholic fatty liver disease (NAFLD). We aimed to examine the association between smoking status and the severity of fatty liver with regard to sex and smoking cessation. METHODS: In total, 13,466 subjects (6,642 males and 6,824 females) who had undergone abdominal ultrasonography for health check-up, multivariable logistic regression analysis was retrospectively conducted to assess the association between smoking status and the prevalence of NAFLD stratified by sex after adjusting for other potential confounders. RESULTS: Male sex (odds ratio [OR] 3.27, 95% confidence interval [CI] 3.00–3.57) and smoking history (former smoker: OR 1.23, 95% CI 1.10–1.38, current smoker: OR 1.31, 95% CI 1.17–1.47) were significantly associated with NAFLD. In males with a smoking history, an increased pack-year was strongly associated with the prevalence and severity of NAFLD (prevalence of moderate to severe fatty liver: Pack-year from 0.01 to 9.99, 21.3%; Pack-year from 10.00 to 19.99, 27.2%; Pack-year ≥20.00, 33.7%; P

A 72-year-old man underwent transarterial chemoembolization (TACE) for solitary hepatocellular carcinoma (HCC) located on the S6 segment. He had a history of anti-viral therapy for hepatitis C virus and was being treated for diabetes mellitus with inadequate control. On day 28 after TACE, he visited our hospital again, with complaints of fever and abdominal pain in the right upper quadrant. Blood examination showed elevated levels of white blood cells and C-reactive protein. Computed tomography showed a poorly marginated, low-density lesion measuring 9.5 x 8.0 x 4.0 cm, forming multiple small gas bubbles, located superiorly, and in contact with HCC treated by TACE. Ultrasound-guided puncture revealed whiffy and muddy pus. Gram staining of the pus showed the presence of numerous gram-positive rods, which were identified as Cutibacterium namnetense. He underwent percutaneous trans-hepatic abscess drainage and received antibiotics treatment. The abscess was successfully treated, and he was discharged on day 19. The incidence of liver abscess after TACE is rare, and intestinal microbiota have been reported to be the common pathogens. To the best of our knowledge, this is the first case of liver abscess caused by Cutibacterium namnetense.

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Background & Aims: To eliminate hepatitis B virus (HBV) infection, scale-up of testing and treatment in resource-limited countries is crucial. However, access to nucleic acid testing to quantify HBV DNA, an essential test to examine treatment eligibility, remains severely limited. We assessed the performance of a novel immunoassay, HBV core-related antigen (HBcrAg), as a low-cost (less than US $15/assay) alternative to nucleic acid testing to indicate clinically important high viremia in chronic HBV patients infected with different genotypes. Methods: We searched Medline, Embase, Scopus, and Web of Science databases through June 27, 2018. Three reviewers independently selected studies measuring HBV DNA and HBcrAg in the same blood samples. We contacted authors to provide individual participant data (IPD). We randomly allocated each IPD to a derivation or validation cohort. We applied optimal HBcrAg cut-off values derived from the derivation set to the validation set to estimate sensitivity/specificity. Results: Of 74 eligible studies, IPD were obtained successfully for 60 studies (81%). Meta-analysis included 5591 IPD without antiviral therapy and 4806 treated with antivirals. In untreated patients, the pooled area under the receiver operating characteristic curve and optimal cut-off values were as follows: 0.88 (95% CI, 0.83–0.94) and 3.6 log U/mL to diagnose HBV DNA level of 2000 IU/mL or greater; and 0.96 (95% CI, 0.94–0.98) and 5.3 log U/mL for 200,000 IU/mL or greater, respectively. In the validation set, the sensitivity and specificity were 85.2% and 84.7% to diagnose HBV DNA level of 2000 IU/mL or greater, and 91.8% and 90.5% for 200,000 IU/mL or greater, respectively. The performance did not vary by HBV genotypes. In patients treated with anti-HBV therapy the correlation between HBcrAg and HBV DNA was poor. Conclusions: HBcrAg might be a useful serologic marker to indicate clinically important high viremia in treatment-naïve, HBV-infected patients.

Chronic hepatitis B virus (HBV) infection can lead to liver cirrhosis and hepatocellular carcinoma. Current therapeutic drugs for chronic hepatitis B using pegylated interferons and nucleos(t)ide analogs have limited efficacy. Therefore, the development of novel and safe antivirals is required. Natural products including medicinal plants produce complex and structurally diverse compounds, some of which offer suitable targets for antiviral screening studies. In the present study, we screened various crude extracts from Indonesian plants for anti-HBV activity by determining their effects on the production of extracellular HBV DNA in Hep38.7-Tet cells and HBV entry onto a HBV-susceptible cell line, HepG2-NTCP, with the following results: (1) In Hep38.7-Tet cells, Cananga odorata exhibited the highest anti-HBV activity with a 50% inhibitory concentration (IC(50)) of 56.5 μg/ml and 50% cytotoxic concentration (CC(50)) of 540.2 μg/ml (Selectivity Index: 9.6). (2) The treatment of HepG2-NTCP cells with Cassia fistula, C. odorata, and Melastoma malabathricum at concentrations of 100 μg/ml lowered the levels of HBsAg production to 51.2%, 58.0%, and 40.1%, respectively, compared to untreated controls, and IC(50) and CC(50) values of C. odorata were 142.9 μg/ml and >400 μg/ml. In conclusion, the C. odorata extract could be a good candidate for the development of anti-HBV drugs.

Nucleos(t)ide analog (NA) therapy has proven effective in treating chronic hepatitis B. However, NAs frequently result in viral relapse after the cessation of therapy. This is because NAs cannot fully eliminate the viral episomal covalently closed circular DNA (cccDNA) in the nucleus. In this study, we identified small molecular compounds that control host factors related to viral replication using in silico screening with simulated annealing based on bioinformatics for protein-ligand flexible docking. Twelve chemical compound candidates for alpha-glucosidase (AG) inhibitors were identified from a library of chemical compounds and used to treat fresh human hepatocytes infected with HBV. They were then monitored for their anti-viral effects. HBV replication was inhibited by one candidate (1-[3-(4-tert-butylcyclohexyl)oxy-2-hydroxypropyl]-2,2,6,6-tetramethylpiperidin-4-ol) in a dose-dependent manner. This compound significantly reduced ccc DNA production, compared to Entecavir (p

Background A large-scale Japanese study showed that low skeletal muscle index (SMI) and intramuscular fat (IMF) deposition are associated with hepatocellular carcinoma (HCC) survival. Here, we evaluated the effects of SMI and IMF on the survival of Indonesian HCC patients, whose characteristics differ from those of Japanese patients. Methods SMI and mean muscle attenuation (MA) were evaluated using computed tomography images of the third lumbar vertebra (L3) in a prospective cohort of 100 Indonesian HCC patients. Clinical, laboratory and body composition data were analysed using the Kaplan–Meier method and Cox regression model to investigate which factors are associated with prognosis. Results Of 100 patients, 31 were diagnosed with sarcopenia (L3 SMI value ≤36.2 cm2/m2 for men and ≤ 29.6 cm2/m2 for women), and 65 had IMF deposition (MA value ≤44.4 HU for men and ≤ 39.3 HU for women). These groups had shorter median survival than the reference groups (both P P = 0.016), IMF deposition (HR, 3.580; P P P P = 0.020), and male gender (HR: 3.211, P Conclusion Sarcopenia and IMF deposition showed superior value in combination with BCLC stage and JIS score for predicting the survival of Indonesian HCC patients. Increased awareness and strategies to prevent or reverse these factors might improve patient outcomes. (Electric word counts: 249).

Objective Supraventricular arrhythmias are commonly detected in patients with anti-mitochondrial antibody M2 (AMA-M2)-associated myopathy. However, the prevalence of supraventricular arrhythmias in unselected AMA-M2-positive patients and the impact of AMA-M2 on supraventricular arrhythmias have yet to be fully investigated. Methods We analyzed 384 patients (116 men; age, 60 [48-69] years), who underwent AMA-M2 testing following the detection of elevated hepatobiliary enzymes. Supraventricular arrhythmias involving atrial fibrillation, atrial flutter, atrial tachycardia, sick sinus syndrome, and atrial standstill were confirmed by a 12-lead electrocardiogram, 24-hour ambulatory monitoring, and physician-assigned diagnoses within the three years before and two years after the AMA-M2 test. Results Seventy-seven (20%) patients were positive for AMA-M2. The prevalence of supraventricular arrhythmias among AMA-M2-positive patients was higher than that among AMA-M2-negative patients (14% vs. 6%, p=0.008). A univariate analysis showed that supraventricular arrhythmias were associated with AMA-M2 positivity, aging, congestive heart failure, and the CHADS2 score. The multivariate analysis determined that AMA-M2 positivity was an independent risk factor for supraventricular arrhythmias (odds ratio 3.52, p=0.011). Among the AMA-M2-positive patients, the AMA-M2 titer did not differ to a statistically significant extent, regardless of the presence or absence of supraventricular arrhythmias. Multiple supraventricular arrhythmias with extremely low atrial deflections was a characteristic finding in AMA-M2-positive patients with supraventricular arrhythmias. Conclusion AMA-M2 enhances the risk of supraventricular arrhythmias, indicating the possible involvement of the atrial myocardium and the formation of an arrhythmogenic substrate. The results highlight the need for clinical attention to supraventricular arrhythmias in AMA-M2-positive patients.

Background The present study aimed to assess the clinical features of patients who received lenvatinib treatment for unresectable hepatocellular carcinoma (HCC). Methods The clinical characteristics, adverse events, and radiological responses were evaluated for 51 consecutive patients. Results Of the study subjects, 37 patients had Child–Pugh class A (CPA) liver function, and 14 patients had Child–Pugh class B (CPB) liver function. The overall response rates in the CPA and CPB groups were 42.9% and 25.0%, respectively, and disease control rates were 82.9% and 83.3%, respectively, without significant difference (p = 0.2621 and 0.9697). There was no significant difference between CPA and CPB groups regarding the incidence of adverse events, except for hepatic coma. No significant difference was observed in the relative dose intensity between the CPA and CPB groups, for the first month, 1–2 months, or 2–3 months (p = 0.2368, 0.9368, and 0.9293). Conclusion The comparable outcomes between the CPA and CPB groups suggest the acceptability of lenvatinib treatment in patients with impaired liver function, at least in the acute phase. With careful follow-up, the dose can be relatively intensified, even in patients with impaired liver function and this may contribute to offering comparable treatment.

Background A large-scale Japanese retrospective study showed that low skeletal muscle index (SMI) and intramuscular fat (IMF) deposition are associated with hepatocellular carcinoma (HCC) survival. Here, we evaluated the effects of SMI and IMF on the survival of Indonesian HCC patients, whose characteristics differ from those of Japanese patients.Methods SMI and mean muscle attenuation (MA) were evaluated using computed tomography images of the third lumbar vertebra (L3) in a prospective cohort of 100 Indonesian HCC patients. Clinical, laboratory and body composition data were analysed using the Kaplan–Meier method and Cox regression model to investigate which factors are associated with prognosis.Results Of 100 patients, 31 were diagnosed with sarcopenia (L3 SMI value ≤36.2 cm 2 /m 2 for men and ≤29.6 cm 2 /m 2 for women), and 65 had IMF deposition (MA value ≤44.4 HU for men and ≤39.3 HU for women). These groups had shorter median survival than the reference groups (both P

A universal hepatitis B vaccination program for infants was adopted in Indonesia in 1997. Before its implementation, the prevalence of hepatitis B surface antigen (HBsAg)–positive individuals in the general population was approximately 5–10%. The study aimed to investigate the hepatitis B virus (HBV) serological status and molecular profile among children, 15 years after adoption of a universal infant vaccination program in Indonesia. According to the Local Health Office data in five areas, the percentages of children receiving three doses of hepatitis B vaccine are high (73.9–94.1%), whereas the birth dose coverage is less than 50%. Among 967 children in those areas, the seropositive rate of HBsAg in preschool- and school-aged children ranged from 2.1% to 4.2% and 0% to 5.9%, respectively. Of the 61 HBV DNA–positive samples, the predominant genotype/subtype was B/adw2. Subtype adw3 was identified in genotype C for the first time in this population. Six samples (11.5%) had an amino acid substitution within the a determinant of the S gene region, and one sample had T140I that was suggested as a vaccine-escape mutant type. The low birth dose coverage and the presence of a vaccine-escape mutant might contribute to the endemicity of HBV infection among children in Indonesia.

Human leukocyte antigen (HLA) DPA1/DPB1 variants have been reported to influence Hepatitis B virus (HBV) infection. HLA-DPA1/DPB1 plays a pivotal role in antigen presentation to CD4(+) helper T cells and influences the outcome of HBV infection. To investigate the influence of HLA-DP variants on the outcome of HBV infection in an Indonesian population where it has the third-highest prevalence of HBV infection worldwide, we performed a case-control study of 686 participants, including patients with HBV-related advanced or nonadvanced liver disease, patients with spontaneously resolved HBV, and healthy controls. Single-nucleotide polymorphisms in HLA-DPA1 (rs3077) and HLA-DPB1 (rs3135021, rs9277535, and rs228388) were genotyped using real-time TaqMan® genotyping assays. Because rs2281388 deviated from Hardy-Weinberg equilibrium, it was excluded from subsequent analyses. The results of logistic regression analyses showed that the HLA-DPB1 rs9277535 variants were associated with a reduced risk of persistent HBV infection (odds ratio [OR] 0.70, 95% confidence interval [95% CI] 0.52-0.96, P=0.026, additive genetic model; OR 0.60, 95% CI 0.38-0.96, P=0.033, dominant genetic model). The HLA-DPA1 rs3077 variant was associated with a protective effect increasing the spontaneously resolved HBV infection (OR 0.64, 95% CI 0.41-0.98, P=0.039, dominant genetic model). By contrast, the HLA-DPB1 rs3135021 variant was not associated with the outcome of HBV infection, including susceptibility, spontaneously resolved, or disease progression. Combinations of haplotype markers were also associated with HBV susceptibility (CA for rs3077-rs9277535, OR 0.57, 95% CI 0.36-0.92, P=0.021; GA for rs3135021-rs9277535, OR 0.56, 95% CI 0.36-0.86, P=0.0087). In conclusion, these findings confirm that HLA-DPA1/DPB1 variants were associated with the outcomes of HBV infection in an Indonesian population.

Liver cirrhosis (LC) and hepatocellular carcinoma (HCC) are life-threatening conditions frequently associated with chronic hepatitis B virus (HBV) infection in Asian countries, including Indonesia. HBV genotypes and several specific mutations are associated with disease progression. To clarify the geographical variation in viral characteristics, HBV genotypes and gene mutations were investigated in patients with advanced liver disease (ALD) in Samarinda, East Kalimantan, Indonesia. Sera were collected from 41 patients with ALD at Abdul Wahab Sjahranie Hospital and HBV carriers from Red Cross Center blood bank in Samarinda, and screened for hepatitis B surface antigen and hepatitis B e-antigen. Liver function data were obtained from the medical records from each patient. HBV genotype and gene mutations were determined by polymerase chain reaction sequencing. Analysis of HBV isolates indicated that genotype B was the most frequent genotype, at 85.4 and 97.8%, followed by C, at 14.6 and 2.2%, in patients with ALD and in HBV carriers, respectively. The C1505A mutation in X region, T1753V and A1762T/G1764A mutations in the basal core promoter region and C1858T in precore (PC) region were frequent and only detected in patients with ALD (28.9, 40, 73.5 and 17.6%, respectively), whereas the G1896A mutation in the PC region was frequently detected in HBV carriers. The presence of HBV genotype B and certain HBV gene mutations were characteristic of patients with ALD in East Kalimantan.

Background Body composition components (Sarcopenia and intramuscular fat [IMF] deposition) were proven as risk factors predicting poor survival among HCC patients in the Japanese population. Since HCC characteristics were peculiar in Indonesia: advanced-stage at presentation; early-age onset; and HBV endemicity; our objective was to demonstrate key determinants of HCC prognosis in Indonesia. Methods Skeletal muscle index (SMI) and mean muscle attenuation (MA) were measured from transverse Computed Tomography (CT) images at the third lumbar vertebra (L3) in a prospective cohort of 49 Indonesia patients with different stages of HCC. Images were analysed using SliceOmatic V5.0 (Tomovision, QC Canada), which enables specific tissue demarcation using Hounsfield unit (HU) thresholds. Clinical, laboratory and body composition assessments are comprehensively analysed using Kaplan-Meier procedure and Cox’s regression model to investigate critical features associated with prognosis. Results Patients with low MA (called intramuscular fat [IMF] deposition) had shorter median survival than non-IMF deposition (73 11.61 vs. 252 26.56 days, p=0.008) as also observed shorter in patients with alpha-fetoprotein (AFP) level ≥200 ng/ml than AFP Conclusions Muscle Attenuation and BCLC stage were significant independent predictors of survival in HCC Indonesian patients. External validation of these prognostic factors in larger cohorts of HCC patients is warranted.

Background Hepatocellular carcinoma (HCC) can develop in patients who are negative for the hepatitis B surface antigen (HBsAg) in serum but positive for hepatitis B virus (HBV) DNA in the liver, referred to as occult HBV infection (OBI). Previous reports showed that HBV variants in OBI-related HCC are different from those in HBsAg-positive HCC. In the present study, HBV quasispecies based on the pre-S/S gene in OBI-related HCC patients were examined by high throughput sequencing and compared with those in HBsAg-positive HCC. Methods Nineteen tissue samples (9 OBI-related and 10 HBsAg-positive non-cancerous tissues) were collected at the time of surgery at Kobe University Hospital. The quasispecies with more than 1% variation in the pre-S/S region were isolated and analysed by ultra-deep sequencing. Results There were no significant differences in the major HBV populations, which exhibit more than 20% variation within the entire pre-S/S region, between OBI-related HCC and HBsAg-positive HCC. However, the prevalences of major populations with pre-S2 region mutations and of minor populations with polymerized human serum albumin-binding domain mutations were significantly higher in OBI-related HCC than in HBsAg-positive HCC. Moreover, the major variant populations associated with the B-cell epitope, located within the pre-S1 region, and the a determinant domain, located in the S region, were detected frequently in HBsAg-positive HCC. The minor populations of variants harbouring the W4R, L30S, Q118R/Stop, N123D and S124F/P mutations in the pre-S region and the L21F/S and L42F/S mutations in the S region were detected more frequently in OBI-related HCC than in HBsAg-positive HCC. Conclusions Ultra-deep sequencing revealed that the B-cell epitope domain in the pre-S1 region and alpha determinant domain in the S region were variable in HBsAg-positive HCC, although the quasispecies associated with the pre-S2 region were highly prevalent in OBI-related HCC. Trial registration Ref: R000034382/UMIN000030113; Retrospectively registered 25 November 2017.

Quasispecies of hepatitis B virus (HBV) with variations in the major hydrophilic region (MHR) of the HBV surface antigen (HBsAg) can evolve during infection, allowing HBV to evade neutralizing antibodies. These escape variants may contribute to chronic infections. In this study, we looked for MHR variants in HBV quasispecies using ultradeep sequencing and evaluated the relationship between these variants and clinical manifestations in infected patients. We enrolled 30 Indonesian patients with hepatitis B infection (11 with chronic hepatitis and 19 with advanced liver disease). The most common subgenotype/subtype of HBV was B3/adw (97%). The HBsAg titer was lower in patients with advanced liver disease than that in patients with chronic hepatitis. The MHR variants were grouped based on the percentage of the viral population affected: major, ≥20% of the total population; intermediate, 5% to

Aim: Transcatheter arterial chemoembolization (TACE) is thought to be a safe and effective treatment for hepatocellular carcinoma (HCC). However, in some HCC patients, it potentially shortens survival due to liver damage. We aimed to identify independent factors to predict overall survival of HCC after TACE. Methods: We included a total of 96 consecutive HCC patients who underwent TACE at Kobe University Hospital. Areas of skeletal muscle and fat tissue were measured by computed tomography (CT) scan before TACE. We divided the patients into two groups in terms of the presence or absence of 1-year mortality after TACE. Factors associated with 1-year mortality after TACE were assessed by multivariate analyses, and the optimal cut-off values were evaluated using a propensity score. Results: Multivariate analyses showed that visceral fat accumulation on CT was an independent factor associated with 1-year mortality after TACE (p = 0.033). There were no differences in skeletal muscle area and subcutaneous and intermuscular fat area between the two groups. Cut-off values for visceral fat area associated with 1-year mortality after TACE were defined as 33.3 cm 2 /m 2 for males and 24.4 cm 2 /m 2 for females. Conclusions: High visceral fat area was a prognostic factor associated with increased mortality rate in HCC patients undergoing TACE. Using this value, 1-year mortality risk after TACE would be better estimated before the day TACE was performed. * Corresponding author.

Mutations in the reverse transcriptase (RT) region of the hepatitis B virus (HBV) genome are an important factor in low therapeutic effectiveness. Nonetheless, the prevalence of these mutations in HBV strains isolated previously in Indonesia has not been systematically examined. Therefore, in this study, we investigated the profile of mutations in the RT region and the associations of these mutations with amino acid changes in the surface protein in the virus of treatment-naive Indonesian HBV carriers. Overall, 96 sequences of the full-length Indonesian HBV genomes (genotype B, n = 54; genotype C, n = 42) were retrieved from the National Center for Biotechnology Information. Naturally occurring primary and/or compensatory drug resistance mutations were found in 6/54 (11.1%) genotype B strains and in 1/42 (2.4%) genotype C strains. The potential mutations underlying resistance to a nucleos(t)ide analog and/or pretreatment mutations were more frequent in both genotypes but more frequent in genotype C strains than in genotype B strains. The A-B interdomain region in the RT gene was more frequently mutated in genotype C than in genotype B (3.51 ± 2.53 vs. 1.08 ± 1.52, P ＜ 0.001). Knowledge about the mutational profiles of the RT gene and changes in the surface protein may help clinicians to select the most appropriate antiviral drug and vaccination or HBV immunoglobulin regimen for management of HBV infection in Indonesia.

Hepatitis B virus (HBV) polymerase gene is targeted by nucleos(t)ide analogues (NUC), but it is unclear how HBV quasispecies of whole genome changes during early period of NUC treatment. To understand the unknown region of drug sensitivity and treatment resistance, HBV quasispecies of whole genome during early period of NUC treatment was examined using ultra‑deep sequencing. Eleven patients with chronic HBV infection who received NUC treatment were enrolled in the current study. Viral DNA was extracted from serum samples before and early period of NUC treatment. Polymerase chain reaction analysis was subsequently performed on the DNA products. The viral quasispecies of the entire genome was analyzed by ultra‑deep sequencing. The regions and positions corresponding to the changes in the quasispecies were investigated before and early period of NUC treatment. The secondary structure changes were predicted by mutations/substitutions detected using Lasergene Protean v14.1 software. The frequency of quasispecies variants increased significantly in the polymerase domain from before to early period of NUC treatment (3.08±1.28 vs. 3.51±1.47%, P

The purpose of antiviral therapy in chronic hepatitis B (CHB) is generally to achieve a decrease and ultimately disappearance of HBs antigen (HBsAg). Interferon (IFN) therapy of CHB appears to be less effective in Asian countries than in European countries, and the advantage of IFN and nucleotide(s) analog (NA) combination therapy has yet to be fully investigated. The present study focused on the factors associated with a decrease in HBs antigen following IFN monotherapy or IFN + NA combination therapy. A total of 35 patients with CHB who received IFN-based therapy (mean ± standard deviation age 36.7±8.5 years; 27 males and 8 females) were enrolled in this study. Of the 35 patients, 21 patients received pegylated IFN monotherapy and 14 patients received IFN and adefovir (ADV) combination therapy. We examined the factors associated with reductions in the HBsAg titer of >1.0 log IU/ml from the initial HBsAg titer to the end of treatment and to 24 weeks after treatment. Although 13 patients (37%) had a reduction in HBsAg of >1.0 IU/ml at the end of treatment, it was only maintained to 24 weeks after treatment in 7 patients (20%). The HBV core-related antigen (HBcrAg) titer before treatment was significantly higher in patients with a decrease in HBsAg at the end of treatment than in patients without a decrease in HBsAg (6.56±0.78 vs. 5.30±1.66 log IU/ml, P2 times from baseline occurred significantly more frequently in patients with a decrease in HBsAg (62 vs. 14%, P

OBJECTIVE The supplementation of oral branched-chain amino acid (BCAA) granules is known to improve energy metabolism in cirrhotic patients, but not those with hepatocellular carcinoma (HCC). We aimed to clarify whether BCAA granules improve energy metabolism in HCC patients after radiofrequency ablation (RFA). METHODS We performed a prospective cohort study (UMIN000004624) involving 40 HCC patients who underwent RFA at Kobe University Hospital. Indirect calorimetry and urinary/blood biochemical examinations were performed before and seven days after RFA. Blood biochemical examinations were also conducted three months after RFA. The patients treated with and without BCAA supplementation were compared, and univariate factors were statistically examined. RESULTS The non-protein respiratory quotient (npRQ) and albumin levels before RFA were significantly lower in the BCAA group than in the control group (p=0.024 and 0.005). The npRQ ratio (seven days after/before RFA) was significantly higher in the BCAA group than in the control group (p=0.019). In addition, the albumin ratio (three months after/before RFA) was significantly higher in the BCAA group than in the control group (p=0.018). CONCLUSION Supplementation with BCAA granules improves energy metabolism in addition to the liver function after RFA. Improvements in the liver function may result in consistently adequate treatment for HCC recurrence after RFA.