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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: The platelet-to-white blood cell ratio (PWR) is a hematologic marker of the systemic inflammatory response. Recently, the PWR was revealed to have a role as an independent prognostic factor for mortality in patients with hepatitis B virus (HBV)-related acute-on-chronic failure (ACLF) and HBV-related liver cirrhosis (LC) with acute decompensation (AD). However, the prognostic role of the PWR still needs to be investigated in LC patients with AD. In this study, we analyzed whether the PWR could stratify the risk of adverse outcomes (death or liver transplantation (LT)) in these patients. Methods: A prospective cohort of 1670 patients with AD of liver cirrhosis ((age: 55.2 ± 7.8, male = 1226 (73.4%)) was enrolled and evaluated for 28-day and overall adverse outcomes. Results: During a median follow-up of 8.0 months (range, 1.9–15.5 months), 424 (25.4%) patients had adverse outcomes (death = 377, LT = 47). The most common etiology of LC was alcohol use (69.7%). The adverse outcome rate was higher for patients with a PWR ≤ 12.1 than for those with a PWR > 12.1. A lower PWR level was a prognostic factor for 28-day adverse outcomes (PWR: hazard ratio 1.707, p = 0.034) when adjusted for the etiology of cirrhosis, infection, ACLF, and the MELD score. In the subgroup analysis, the PWR level stratified the risk of 28-day adverse outcomes regardless of the presence of ACLF or the main form of AD but not for those with bacterial infection. Conclusions: A lower PWR level was associated with 28-day adverse outcomes, indicating that the PWR level can be a useful and simple tool for stratifying the risk of 28-day adverse outcomes in LC patients with AD. [ABSTRACT FROM AUTHOR]

Antiviral therapy improves survival in patients with hepatitis B virus (HBV)‐induced hepatocellular carcinoma (HCC). However, the effect of antiviral therapy in patients with low‐level viremia HBV‐HCC receiving non‐curative therapy remains unclear. We aimed to evaluate the role of antiviral therapy in patients with low‐level viremia and treated with transarterial chemoembolization (TACE). This retrospective study evaluated 206 patients with HBV‐HCC who underwent TACE as an initial treatment. Of those, 135 patients received antiviral therapy (antiviral group), and 71 did not (non‐antiviral group). The definition of low‐level viremia was an HBV DNA level <2000 IU/ml. Kaplan‐Meier curves, log‐rank tests and Cox regression analysis were used for statistical analyses. The median follow‐up duration was 39 months (1–174 months). Overall survival (OS) did not differ between groups (P =.227). Barcelona Clinic Liver Cancer stage (BCLC), Child‐Pugh (CP) class and α‐fetoprotein level were independent prognostic factors for OS. Antiviral therapy (hazard ratio [HR], 0.503, P =.022) was a prognostic factor for 2‐year survival. On subgroup analysis, antiviral therapy improved short‐term survival in patients with BCLC stage 0 and A (P =.037) and CP class A (P =.04). In patients with low‐level viremia, antiviral therapy yielded short‐term survival benefits, particularly in patients with early‐stage HCC. [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]

Convincing data that support routine use of preventive therapy against hepatitis B virus (HBV) reactivation in radiotherapy (RT) for hepatocellular carcinoma (HCC) are lacking. The aim of this study was to investigate the incidence, clinical significance, and risk factors of HBV reactivation after RT. Medical records of 133 HBsAg (+) HCC patients who received radiotherapy from March 2009 to February 2016 were reviewed. Patients were divided into two groups: 1) non-antiviral group, those who did not receive antiviral therapy before RT (n = 27); and antiviral group (those who underwent antiviral therapy before RT) (n = 106). Factors related to HBV reactivation in HCC patients were evaluated. 17 (12.7%) of 133 patients developed HBV reactivation after RT. Patients in the antiviral group had significantly lower rates of HBV reactivation than those in the non-antiviral group (7.5% vs. 33.3%, p<0.001). HBV related hepatitis was also lower in the antiviral group (3.8% vs. 14.8%, p = 0.031). In multivariate analysis, absence of antiviral treatment (OR: 8.339, 95% CI: 2.532–27.470, p<0.001) and combined treatment of RT with transarterial chemoembolizatoin (TACE) (OR: 5.313, 95% CI: 1.548–18.232, p = 0.008) were risk factors for HBV reactivation. HBV reactivation can occur after radiotherapy. Combination treatment of RT with TACE and non-antiviral treatment are major risk factors for HBV reactivation during or after RT. Therefore, preventive antiviral therapy should be recommended for patients with HCC who are scheduled to receive RT. [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]

Abstract: Vaccination against hepatitis B virus (HBV) is recommended for health care workers (HCWs), but it is not clear whether HBV vaccination is required for HCWs who have isolated antibody to hepatitis B core antigen (anti-HBc), or whether prevaccination screening for anti-HBc is needed in HCWs. Among 1812 HCWs, subjects with isolated anti-HBc and those with no HBV markers (control) were screened. The anamnestic response (antibody to hepatitis B surface antigen over 50mIU/mL after the first vaccine injection) was compared prospectively between the two groups. The prevalence of isolated anti-HBc was 2.3%. Their anamnestic response was lower than that of controls (27.5% vs. 46.9%, P =0.020). The subjects who had isolated anti-HBc were older and predominantly male, compared with the controls. Multivariate analysis revealed that age (odds ratio [OR], 0.67; confidence interval [CI], 0.51–0.90) and prior vaccination (OR, 3.36; CI, 2.04–5.54) were independent predictors of the anamnestic response, regardless of the anti-HBc status. Serum HBV DNA was not detected in any subject. Anti-HBs seroconversion was achieved in most of the anti-HBc-positive subjects after full vaccination, and the rate was comparable with controls (89.5% vs. 96.6%, P =0.067). Isolated anti-HBc-positive HCWs are rare and most of them respond to vaccination. Anti-HBc testing is not a prerequisite for vaccination. This serology suggests a loss of acquired anti-HBs rather than occult HBV infection. Their reduced immunity to vaccination may be related to old age. [Copyright &y& Elsevier]