Aim: Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease resulting in cognitive impairment, physical disabilities, and neurological symptoms. Ocrelizumab is an effective drug used in MS treatment. However, it causes a risk of hepatitis B reactivation in anti-HBc positive patients. We describe the impact of entecavir and tenofovir on HBV reactivation during treatment with ocrelizumab.

Materials and methods: Our study included eight patients (aged 18-70 years) with positive anti-HBc antibodies who were diagnosed with MS based on the 2017 McDonald criteria. The subjects were treated with ocrelizumab and were given anti-HBV prophylaxis with nucleoside analogs. The mean time from the beginning of therapy with nucleoside analogs to the initiation of ocrelizumab treatment was 27.5 days. Patients were administered ocrelizumab and none of them was diagnosed with HBV reactivation.

Results: None of the laboratory parameters worsened. No severe adverse effects were observed. These results suggest that entecavir and tenofovir are effective in HBV reactivation prophylaxis. Additionally, positive anti-HBc antibodies do not rule out treatment with ocrelizumab.

Conclusions: In patients with positive anti-HBc antibodies, nucleoside analogs, such as entecavir or tenofovir, should be administered before ocrelizumab administration to reduce the risk of viral reactivation. Further studies on simultaneous treatment with ocrelizumab and nucleoside analogs are required to confirm our findings.

Whether the efficacies of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) in treating liver-related outcomes of decompensated chronic hepatitis B (CHB) patients are comparable remained inconclusive.

An 8-year cohort study of 736 decompensated CHB patients was conducted, and 65 TDF-treated patients were sex, age and model for end-stage liver disease (MELD) scores-1:4 matched with 260 ETV-treated patients through propensity score-matching method.

Of 736 patients, 574 (78%) were male, with a mean age of 54.3 years, 438 (59.5%) had cirrhosis, 147 (20%) were positive for HBeAg, and 84 (11.6%) and 652 (88.4%) were treated with TDF and ETV, respectively. The 652 ETV-treated patients were older, had higher baseline MELD score and rates of encephalopathy, but lower ALT levels than the 84 TDF-treated patients. No significant differences were observed in the cumulative incidences of liver-related mortality or liver transplantation (1-month, 18.45 vs. 14.01%, p = 0.368; 8-year, 39.74 vs. 34.24%, p = 0.298), and hepatocellular carcinoma development (5-year, 7.21 vs.13.17%, p = 0.994; 8-year, 11.60 vs.13.17%, p = 0.857) between the matched 260 ETV- and 65 TDF-treated patients, regardless of time points. Baseline MELD score (subdistribution hazard ratio (sHR): 1.063; 95% confidence interval (CI) of sHR: 1.016-1.112) and hepatic encephalopathy (sHR: 5.127; 95% CI sHR: 3.032-8.669) were independently associated with liver-related mortality or liver transplantation in the matched patients.

ETV and TDF had comparable efficacy in the short- and long-term liver-related outcomes of decompensated CHB patients, and baseline liver reserve was associated with the outcomes.

Hepatitis B e antigen (HBeAg) is a soluble viral protein in plasma of patients with hepatitis B virus infection. HBeAg loss is an important first stage of viral antigen clearance. We determined the rate and predictors of HBeAg loss in a North American cohort with chronic hepatitis B viral infection (CHB). Among children and adults with CHB and without HIV, HCV or HDV co-infection enrolled in the Hepatitis B Research Network prospective cohort studies, 819 were HBeAg positive at their first assessment (treatment naïve or >24 weeks since treatment). Of these, 577 (200 children, 377 adults) were followed every 24-48 weeks. HBeAg loss was defined as first HBeAg-negative value; sustained HBeAg loss was defined as ≥2 consecutive HBeAg-negative values ≥24 weeks apart. During a median follow-up of 1.8 years, 164 participants experienced HBeAg loss, a rate of 11.4 (95% CI, 9.8-13.3) per 100 person-years. After adjustment for confounders, HBeAg loss rate was significantly higher in males than females, in older than younger individuals, in Whites or Blacks than Asians, in those with genotype A2 or B versus C, and in those with basal core promoter/pre-core mutations versus wild type. Additionally, during follow-up, an ALT flare and a lower quantitative HBsAg, quantitative HBeAg or HBV DNA level predicted higher rates of HBeAg loss. The majority (88%) with HBeAg loss had sustained HBeAg loss. In conclusion, a number of specific demographic, clinical and viral characteristics impacted rate of HBeAg loss and may prove useful in design and interpretation of future therapeutic studies.

Chronic Hepatitis B (CHB) is a global health problem affecting around 400 million of people worldwide. Two available first-line antiviral drugs are tenofovir disoproxil fumarate (TDF) and Entecavir (ETV). Till date,there are few published reports from India comparing efficacy of TDF and ETV in CHB cases. Therefore, this present study was carried out with an aim to compare the efficacy of ETV and TDF in patients with nucleos(t)ide naïve CHB.

This retrospective cohort study was carried out in 192 treatment naïve CHB cases, who completed 24 months of treatment with either TDF or ETV between March 2015 and August 2017. The primary end point of the study was undetectable hepatitis B virus DNA after 24 months of therapy.

Of total 192 patients with CHB, 38 hepatitis B e-antigen (HBeAg)-positive and 53 HBeAg-negative patients were treated with tenofovir, whereas 40 HBeAg-positive and 61 HBeAg-negative patients were treated with ETV. Pretreatment characteristics at baseline were not statistically different between the TDF and ETV groups. Patients treated with TDF achieved significantly higher complete viral suppression as compared with ETV-treated patients (Log rank: 7.04, P = 0.008) in HBeAg-positive CHB during the 24 months follow-up time; whereas no significant difference in viral suppression rate could be noticed in HBeAg-negative patients (Log rank: 0.98, P = 0.38). Both univariate and multivariate analysis by cox proportional hazard model confirmed that tenofovir had significant rate of complete viral suppression in comparison with ETV in HBeAg-positive patients (P < 0.05); whereas complete viral suppression rates were similar in HBeAg-negative patients.

In our study, tenofovir had more effective antiviral suppressive effect compared with ETV in HBeAg-positive, nucleos(t)ide-naïve CHB cases.

Not all treatment-naïve patients receiving entecavir (ETV) or tenofovir disoproxil fumarate (TDF) therapy can achieve complete virological response, and many factors may be related with the outcome of partial virological response. This study aimed to determine whether the manner of drug administration affects the antiviral efficacy of ETV/TDF monotherapy. All eligible patients were divided into complete or partial response cohorts based on their virological response following 24-week therapy. Factors related with partial response were evaluated. Patients with partial response were further grouped depending on whether they later adjusted the manner of drug administration, and the antiviral efficacy was compared between the two groups during prolonged treatment. A total of 518 patients were enrolled. Suboptimal drug administration (OR 77.511, P = .000), positive-HBeAg (OR 3.191, P = .000) and ETV treatment (OR 2.537, P = .001) were identified as independent risk factors for partial response. Among patients with partial response, 213 were in the adjusted group and 76 were in the unadjusted group. The percentages of patients with undetectable serum HBV DNA (78.9% vs 31.6%, P < .001) and with normal alanine aminotransferase (ALT) (88.7% vs 68.4%, P < .001) were both higher in the adjusted group than that in unadjusted group following a further 6-month therapy. In conclusion, the manner of drug administration is an important factor influencing the efficacy of ETV/TDF therapy, and optimal drug administration manner can help to increase antiviral efficacy and rescue patients with partial response.

HBeAg seroconversion is an important intermediate outcome in HBeAg-positive chronic hepatitis B (CHB) patients. This study aimed to compare the effect of nucleos(t)ide analogs (NAs) on HBeAg seroconversion in treating CHB with lamivudine, adefovir, telbivudine, entecavir, and tenofovir.

Network meta-analysis of NA treatment-induced HBeAg seroconversion after 1-2 years of treatment was performed. In addition, NA treatment-induced HBeAg seroconversion after 3-5 years of treatment was systematically evaluated.

A total of 31 articles were included in this study. Nine and five studies respectively reporting on 1- and 2-year treatment were included in our network meta-analysis. In addition, 6, 5, and 5 studies, respectively reporting on 3-, 4-, and 5-year treatment were included in our systematic evaluation. Telbivudine showed a significantly higher HBeAg seroconversion rate after a 1 year treatment period compared to the other NAs (odds ratio (OR) = 3.99, 95% CI 0.68-23.6). This was followed by tenofovir (OR = 3.36, 95% CI 0.70-16.75). Telbivudine also showed a higher seroconversion rate compared to the other NAs after a 2 year treatment period, (OR = 1.38, 95% CI 0.92-2.22). This was followed by entecavir (OR = 1.14, 95% CI 0.72-1.72). No significant difference was observed between spontaneous induction and long-term telbivudine treatment-induced HBeAg seroconversion. However, entecavir and tenofovir treatment-induced HBeAg seroconversions were significantly lower than spontaneous seroconversion.

Long-term treatment with potent anti-HBV drugs, especially tenofovir and entecavir, may reduce HBeAg seroconversion compared with spontaneous HBeAg seroconversion rate. Telbivudine treatment, whether short term or long term, is associated with higher HBeAg seroconversion compared with the other NAs. However, the high rates of drug resistance likely limit the application of telbivudine.

A comprehensive and up-to-date network meta-analysis (NMA) helps to determine the comparative efficacies of nucleos(t)ide analogs (NAs) in patients with chronic hepatitis B (CHB). The aim of this NMA was to assess the efficacy of telbivudine versus adefovir, entecavir, lamivudine, and tenofovir in nucleos(t)ide-naïve hepatitis B e antigen (HBeAg)-positive patients with CHB.

A systematic review was conducted to search Medline, Medline-In Process, EMBASE, and the Cochrane Central Register of Controlled Trials databases for publications of randomized controlled trials (RCTs). NMA was performed to compare the efficacy outcomes of telbivudine versus other approved NAs at 1- and 2-year time points.

A total of 75 RCTs were included in the systematic review. At the 1-year time point, telbivudine was associated with significantly higher rates of: (1) HBeAg seroconversion than adefovir [odds ratio (OR) 1.99 (95% credible interval (CrI): 1.05, 3.45)], entecavir [OR 2.00 (95% CrI: 1.44, 2.82)] and lamivudine [OR 1.49 (95% CrI: 1.10, 2.03)]; (2) HBeAg loss than entecavir [OR 1.85 (95% CrI: 1.28, 2.76)] and lamivudine [OR 1.62 (95% CrI: 1.20, 2.24)]; (3) alanine aminotransferase (ALT) normalization than lamivudine [OR 1.50 (95% CrI: 1.05, 2.21)]; and (4) hepatitis B virus (HBV) DNA suppression than adefovir [OR 2.77 (95% CrI: 1.28, 5.45)] and lamivudine [OR 2.97 (95% CrI: 1.99, 4.53)]. At the 2-year time point, the relative efficacy outcomes were not statistically significant.

At 1 year, telbivudine was superior to adefovir, entecavir and lamivudine in HBeAg seroconversion, and to entecavir and lamivudine in HBeAg loss. Telbivudine was also superior to lamivudine in ALT normalization and to adefovir and lamivudine in suppressing HBV DNA levels.

Novartis Pharma AG.

Nucleotide/nucleoside analogues (antiviral therapy) are used in the therapy of HBeAg positive and HBeAg negative chronic hepatitis B. We analyzed ten selected randomized controlled with 2557 patients to estimate the effect of antiviral drugs in chronic hepatitis B with compared to placebo. Virological response, biochemical response, histological response, seroconversion of HBeAg, and loss of HBeAg were estimated as primary efficacy measures. The included studies were subjected for heterogeneity and publication bias. The heterogeneity was assessed with χ2 and I(2) statistics. Publication bias was assessed by funnel plot. Greater rates of improvement obtained in antiviral group for virological response [43.96 % vs. 3.15 %, RR = 0.57, 95 % CI = 0.54-0.61, p-value <0.00001], biochemical response [58.37 % vs. 21.87 %, RR = 0.52, 95 % CI = 0.48-0.56, p-value <0.00001], histological response [58.99 % vs. 27.13 %, RR = 0.56, 95 % CI = 0.50-0.63, p-value <0.0001], seroconversion of HBeAg [10.66 % vs. 5.56 %, RR = 0.94, 95 % CI = 0.91-0.97, p-value = 0.0005], and HBeAg loss [14.59 % vs. 9.64 %, RR = 0.92, 95 % CI = 0.88-0.96, p-value = 0.0002]. The safety analysis were carried out for adverse events such as headache [17.22 % vs. 17.34 %, OR = 1.09, 95 % CI = 0.81-1.46, p-value = 0.58], abdominal pain [16.46 % vs. 14.34 %, OR = 1.24, 95 % CI = 0.90-1.72, p-value = 0.19], and pharyngitis [22.22 % vs. 18.23 %, OR = 1.12, 95 % CI = 0.86-1.45, p-value = 0.40]. Excluding adverse events, all primary efficacy measures shown statistical significant result for chronic hepatitis treatment (p-value <0.05). Antiviral therapy provided significant benefit for the treatment of chronic hepatitis B with no measurable adverse effects.

Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts' personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.

Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is a major route of HBV transmission worldwide despite an existing immunoprophylaxis regimen. The implementation of immunoprophylaxis has been challenging, especially in low-income and middle-income countries, where MTCT is common, because of difficulty obtaining and delivering the monovalent HBV vaccine and the HBV immunoglobulin. Global control of the HBV epidemic will need improved prevention of MTCT. We discuss research gaps that hinder development of new options for the elimination of MTCT as well as policy changes that may help the current vaccine-based strategy to live up to its full potential. We propose that decreasing hepatitis B viral concentrations before delivery, along with HBV vaccine use, could provide an alternative strategy that would decrease MTCT of HBV.

Little is known about the factors associated with patient compliance with nucleos(t)ide analog (NUC) treatment for chronic hepatitis B (CHB). The purpose of this study was to examine the association between sociodemographic and clinical characteristics and adherence to NUCs among patients with CHB. A total of 211 CHB patients receiving NUC monotherapy were asked to report the number of prescribed doses of medication they had taken during the last 90 days. A total of four 3-month adherence scores were averaged to obtain a combined rate of NUC adherence during a 1-year follow up period. The mean age of the patients was 29.6 years, 79% were men, and 68% had no prior NUC treatment for CHB. Females, patients without a previous NUC treatment, and those who had NUC drug resistance showed better adherence to NUC treatment, and compliance was better with telbivudine than with lamivudine and entecavir.

Chronic hepatitis B (CHB) virus infection is a global public health problem, affecting more than 400 million people worldwide. The clinical spectrum is wide, ranging from a subclinical inactive carrier state, to progressive chronic hepatitis, cirrhosis, decompensation, and hepatocellular carcinoma. However, complications of hepatitis B virus (HBV)-related chronic liver disease may be reduced by viral suppression. Current international guidelines recommend first-line treatment of CHB infection with pegylated interferon, entecavir, or tenofovir, but the optimal treatment for an individual patient is controversial. The indications for treatment are contentious, and increasing evidence suggests that HBV genotyping, as well as serial on-treatment measurements of hepatitis B surface antigen and HBV DNA kinetics should be used to predict antiviral treatment response. The likelihood of achieving a sustained virological response is also increased by extending treatment duration, and using combination therapy. Hence the paradigm for treatment of CHB is constantly evolving. This article summarizes the different indications for treatment, and systematically reviews the evidence for the efficacy of various antiviral agents. It further discusses the shortcomings of current guidelines, use of rescue therapy in drug-resistant strains of HBV, and highlights the promising clinical trials for emerging therapies in the pipeline. This concise overview presents an updated practical approach to guide the clinical management of CHB.

To date no network meta-analysis (NMA) has accounted for baseline variations in viral load when assessing the relative efficacy of interventions for chronic hepatitis B (CHB). We undertook baseline-adjusted and unadjusted analyses using the same data to explore the impact of baseline viral load (BVL) on CHB treatment response.

We searched Embase, Medline, Medline in Process and the Cochrane CENTRAL databases for randomised clinical trials (RCTs) of monotherapy interventions at licensed doses for use in CHB. Search strategies comprised CHB disease and drug terms (a combination of controlled vocabulary and free text terms) and also a bespoke RCT filter.The NMA was undertaken in WinBUGs using fixed and random effects methods, using data obtained from a systematic review. Individual patient data (IPD) from an entecavir clinical trial were used to quantify the impact of different baseline characteristics (in particular undetectable viral load (UVL) at 1 year) on relative treatment effect. Study level mean baseline values from all identified studies were used. Results were generated for UVL and presented as relative risks (RRs) and 95% credible intervals (CrIs) using entecavir as reference treatment.

Overall, for all eight relevant interventions we identified 3,000 abstracts. Following full text review a total of 35 (including the contents of six clinical study reports) met the inclusion critera; 19 were in hepatitis B e antigen (HBeAg)-positive patients and 14 of the 19 contained outcome information of relevance to the NMA.Entecavir and tenofovir studies had heterogeneous patient populations in terms of BVL (mean values 9.29 and 8.65 log10 copies/ml respectively). After adjusting UVL for BVL using an informative prior based on the IPD analysis, the difference between entecavir and tenofovir was not statistically significant (RR 1.27, 95% CrI 0.96 to 1.47-fixed effects). A similar conclusion was found in all sensitivity analyses. Adjusted tenofovir results were more consistent with observed clinical trial response rates.

This study demonstrates the importance of adjusting for BVL when assessing the relative efficacy of CHB interventions in achieving UVL. This has implications for both clinical and economic decision making.

Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are the two first-line anti-viral therapies for chronic hepatitis B (CHB); however, there are limited studies directly comparing their effectiveness.

To compare the effectiveness of ETV and TDF in nucleos(t)ide-naïve CHB patients with high hepatitis B virus (HBV) DNA levels, defined as serum HBV DNA greater than 6 log10  IU/mL.

We performed a retrospective multicentre cohort study of adult CHB patients who were seen between 2009 and 2012 at four Northern California community gastroenterology and hepatology clinics.

We identified 59 consecutive patients treated with TDF and 216 patients treated with ETV. Pre-treatment characteristics were similar between the two groups. Among HBeAg-negative patients, there was no significant difference in viral suppression rates between ETV and TDF (P = 0.72). In contrast, among HBeAg-positive patients, those treated with TDF achieved viral suppression significantly more rapidly than those treated with ETV (P < 0.0001); the Kaplan-Meier estimated probability of complete suppression was 18% vs. 11% at 6 months, 51% vs. 28% at 12 months and 72% vs. 39% at 18 months respectively. Multivariate Cox proportional hazards analysis indicated that treatment with TDF compared to ETV was a significant predictor of viral suppression, but only for HBeAg-positive patients (HR = 2.59; 95% CI 1.58-4.22; P < 0.001).

Tenofovir is significantly more effective than entecavir for achieving complete viral suppression in HBeAg-positive, nucleos(t)ide-naïve chronic hepatitis B patients with HBV DNA greater than 6 log10  IU/mL.