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Simple Summary: Further information is necessary regarding the influence of besifovir (BSV), a new nucleotide analogue, on the occurrence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). When we compared the HCC incidence in non-cirrhotic CHB patients receiving BSV with the predicted number derived from the REACH-B (risk estimation for HCC in CHB) model, the standardized incidence ratio (SIR) was significantly reduced to 0.128 at 7 years. The incidence of HCC in patients with cirrhosis was compared using the GAG-HCC (guide with age, gender, HBV DNA, core promotor mutation, and cirrhosis) model, and the SIR was significantly decreased to 0.371 at 7.5 years. HCC prediction was available for BSV-treated patients using existing models. We concluded that BSV decreases the risk of HCC in patients with CHB, and HCC risk prediction models are applicable. No information is available regarding the influence of besifovir (BSV), a new nucleotide analogue, on the occurrence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This study evaluated the reduced risk of HCC in patients undergoing BSV treatment. A total of 188 patients with CHB were treated with BSV for up to 8 years. We prospectively assessed the incidence of HCC compared with the risk from prediction models. During the follow-up, 5 patients developed HCC: 1 of 139 patients with non-cirrhotic CHB, and 4 of 49 patients with liver cirrhosis. We compared the HCC incidence in non-cirrhotic and cirrhotic patients with the predicted number derived from the REACH-B (risk estimation for HCC in CHB) model and GAG-HCC (guide with age, gender, HBV DNA, core promotor mutation, and cirrhosis) model, respectively. The standardized incidence ratio (SIR) was 0.128 (p = 0.039) at 7 years in non-cirrhotic CHB patients, and the SIR was 0.371 (p = 0.047) at 7.5 years in cirrhotic patients, suggesting a significantly decreased HCC incidence in both groups. HCC prediction was available for BSV-treated patients using existing models. In conclusion, BSV decreased the risk of HCC in patients with CHB, and prediction models were applicable. Clinical trial registry website and trial number: ClinicalTrials.gov no: NCT01937806. [ABSTRACT FROM AUTHOR]

Background and Aim: Besifovir dipivoxil maleate (BSV) was reported to have comparable antiviral efficacy and superior renal and bone safety to tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients. The present study aims to evaluate changes of liver histology and intrahepatic covalently closed circular DNA (cccDNA) levels by BSV treatment in comparison with TDF therapy. Methods: This is a subset study of the phase 3 trial comparing BSV with TDF. Among them, only CHB patients willing to participate in a histologic evaluation study were enrolled. Liver histologic examination and intrahepatic cccDNA quantification were performed. Results: A total of 46 CHB patients received liver biopsies (BSV, n = 29; TDF, n = 17). After 48 weeks of treatment, virological response rate was comparable between the groups (P = 0.707). Follow‐up liver biopsies showed that necroinflammation was significantly improved in the both groups. However, the histological response rate defined as the proportion of subjects whose modified histologic activity index score decreased by ≥ 2 without deterioration in fibrosis was higher in the BSV group than in the TDF group (77.8% vs 36.4%, P = 0.048). The proportion of subjects with Ishak fibrosis score 3 or more decreased from 77.7% to 55.5% in the BSV and that decreased from 72.7% to 45.4% in the TDF group. The intrahepatic cccDNA significantly decreased from baseline after 48 weeks of BSV or TDF treatment (P < 0.001) without intergroup differences (P = 0.349). Conclusions: The BSV therapy improves hepatic histology and decreases intrahepatic cccDNA in CHB patients. [ABSTRACT FROM AUTHOR]

The treatment of multidrug‐resistant (MDR) chronic hepatitis B (CHB) is challenging. Herein, we report a multicenter prospective cohort study for the evaluation of tenofovir disoproxil fumarate (TDF)‐based therapy for MDR CHB in a real‐life setting. The inclusion criteria comprised patients with resistance to more than two nucleos(t)ide analogue (NA) classes and hepatitis B virus (HBV) DNA level of ≥200 IU/mL. The primary end‐point was virologic response (VR), defined as undetectable HBV DNA (<20 IU/mL) after 60 months. A total of 236 patients met the inclusion criteria. The mean HBV DNA level was 4.16 ± 1.44 log IU/mL; 26.7% of patients had liver cirrhosis. Before the initiation of TDF, 33.5%, 44.9% and 21.6% of patients had mutations resistant to L‐NA + adefovir, L‐NA + entecavir (ETV) and L‐NA + adefovir + ETV, respectively. A total of 184 patients received TDF‐based combination therapy [TDF + ETV (n = 178) or TDF + L‐NA (n = 6)], and 52 patients received TDF monotherapy. In the entire cohort, the VR rates were 77.2%, 89.9% and 92.2% at 12, 36 and 60 months, respectively. The VR rates were not significantly different between the combination therapy and the monotherapy group after 12 (76.2% vs 80.4%, P =.533), 36 (89.8% vs 90.3%, P = 1.000) or 60 (92.9% vs 87.5%, P =.499) months. Also, there was no significant difference in the cumulative VR rates for 5 years between the treatment groups (P =.910). Newly developed antiviral resistance was not observed. TDF‐based therapy was effective for the treatment of MDR CHB. The efficacy of TDF monotherapy was not different from that of the TDF‐based combination therapy. [ABSTRACT FROM AUTHOR]

Background/Aims Transient elastography ( TE) has become an alternative to liver biopsy ( LB). This study investigated the diagnostic performance of liver stiffness ( LS) measurement using TE in Korean patients with chronic hepatitis B and C ( CHB and CHC). Methods From April 2006 to June 2014, 916 patients (567 CHB and 349 CHC) who underwent LB and TE at 15 centres were analyzed. The Batts and Ludwig scoring system was used for histologic assessment. Aspartate aminotransferase ( AST)-to-platelet ratio indexes ( APRI) were calculated. Area under the receiver operating characteristic curve ( AUROC) was used. Results The median age, LS value, and APRI score were 45 years, 8.8 kPa, and 0.61, respectively, in CHB patients vs. 51 years, 6.8 kPa and 0.55, respectively, in CHC patients. TE was significantly superior to APRI in CHB patients (AUROC 0.774 vs. 0.72 for ≥F2, 0.849 vs. 0.812 for ≥F3, and 0.902 vs. 0.707 for F4, respectively; all P < 0.05). Furthermore, TE was significantly superior for predicting ≥ F3 stage (AUROC 0.865 vs. 0.840, P = 0.009) whereas it was similar for predicting ≥ F2 and F4 stage (AUROC 0.822 vs. 0.796; 0.910 vs. 0.884; all P > 0.05) in CHC patients. In CHB patients, optimal cut-off LS values were 7.8 kPa for ≥F2, 8.2 kPa for ≥ F3, and 11.6 kPa for F4, vs. 6.8 kPa, 8.6 kPa, and 14.5 kPa, respectively, in CHC patients. Conclusions TE can accurately assess the degree of liver fibrosis in Korean patients with CVH. TE was superior to APRI for predicting each fibrosis stage. [ABSTRACT FROM AUTHOR]

Background and Aims: Analysis of alpha-fetoprotein (AFP) levels affords limited diagnostic accuracy because of the high false-positive rates, especially in those with active chronic hepatitis B (CHB). We measured AFP levels before and after commencement of oral antiviral therapy and explored the utility of these data in terms of early detection of hepatocellular carcinoma (HCC) in patients with CHB. Methods: A total of 207 patients with CHB who were treated with an oral antiviral agent were consecutively included. Dynamic changes in AFP levels and the diagnostic utility of such changes for HCC detection during the therapy were explored. Results: The proportions of patients showing elevated AFP levels (≥ 20 ng/mL) were 22.2%, 5.5%, and 1.3% at baseline; and at 6 and 12 months after commencement of antiviral therapy, respectively. All patients who did not suffer from HCC exhibited normalization of AFP levels at 12 months. The cumulative incidence of HCC was 9.5% during 36 months of follow-up. If AFP levels were over 20 ng/mL after 12 months of antiviral treatment, the probability of HCC development approached certainty. The positive predictive value for HCC development remained at 100% in patients prescribed long-term (≥ 12 months) antiviral therapy, if AFP levels persistently or abruptly elevated more than 12 ng/mL. Conclusions: In the era of oral antiviral agents, AFP might be a useful biomarker for HCC surveillance in patients with CHB. [ABSTRACT FROM AUTHOR]

Background and Aims Although prolonged lamivudine ( LAM) therapy is associated with the emergence of LAM-resistant mutations, it is still a commonly used therapy in many Asian countries because of its established long-term safety and low cost. The aim of our study was to assess the predictors of long-term LAM treatment response and to establish an individual prediction model ( IPM) for hepatitis B virus e antigen ( HBeAg) seroconversion in HBeAg-positive chronic hepatitis B ( CHB) patients. Methods This was a multicenter analysis of 838 patients treated with LAM between January 1999 and August 2004. Of these, 748 patients were followed up for at least 24 months. Results The median age was 43.0 years (range, 19-79 years) and the mean duration of LAM monotherapy was 34.2 ± 0.7 months. In the multivariate analysis, age (odds ratio [ OR] = 0.974, P < 0.001), baseline alanine aminotransferase level ( OR = 1.001, P = 0.014), and baseline hepatitis B virus DNA level ( OR = 0.749, P < 0.001) were independent factors for HBeAg seroconversion. Based on the predictors, an IPM was established. Patients were classified into high (> 50%), intermediate (30-50%), or low (≤ 30%) response groups based on their probability of HBeAg seroconversion according to the IPM. The cumulative HBeAg seroconversion rate at 6 years for the high, intermediate, and low response groups was 66.0%, 48.5%, and 21.8%, respectively ( P < 0.001). Conclusions An IPM was developed based on predictors of HBeAg seroconversion in HBeAg-positive CHB patients on LAM monotherapy. This model will allow screening of LAM responders prior to the commencement of antiviral treatment. [ABSTRACT FROM AUTHOR]

Background/Aim: We aimed to demonstrate the efficacy and safety of tenofovir disoproxilorotate (TDO) compared with that of tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B. Methods: This multicenter, open-label, prospective clinical trial (KCT0004185) was conducted to evaluate the efficacy and safety of TDO on switching from TDF for 24 weeks in virologically suppressed chronic hepatitis B patients. The primary efficacy endpoint was the maintenance of virologic response. Safety was assessed by evaluating major adverse events, changes in renal function, and occurrence of hepatocellular carcinoma (HCC). Results: TDO treatment was not inferior in terms of virological response when compared with that on TDF treatment, with a noninferiority margin of −10% (risk difference, −3.17%; 95% confidence interval, −7.5–1.15%). The biological response of TDO was also comparable to that of TDF, with no significant difference in the proportion of patients with normalized alanine transaminase levels. After 24 weeks of treatment, hepatitis B core-related antigen (HBcrAg) significantly decreased to a mean titer of 3.91 log U/mL from 4.15 log U/mL at baseline (p = 0.01). There were no cases of grade 3 or higher adverse events and HCC. The mean estimated glomerular filtration rate increased from 91.09 mL/min to 93.34 mL/min (p = 0.056), and the mean serum level of phosphorus increased from 3.33 mg/dL to 3.44 mg/dL (p = 0.045), suggesting improvement in renal function with TDO treatment. Conclusion: In patients with chronic hepatitis B, the efficacy of TDO was noninferior to that of TDF, with a significant decrease in the HBcrAg titer and improved renal function. [ABSTRACT FROM AUTHOR]