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Background: Many people living with chronic HBV infection remain undiagnosed until later stages of disease. Increasing testing and treatment rates form part of the strategy to respond to the WHO goal of eliminating viral hepatitis as a public health threat by 2030. However, achieving these ambitious targets is dependent on finding effective and cost-effective methods of scale up strategies. The aim of this study was to undertake a narrative review of the literature on economic evaluations of testing and treatment for HBV infection, to help inform the development of the 2017 WHO Hepatitis Testing Guidelines.Methods: We undertook a focussed literature review for economic evaluations on testing for HBV accompanied by antiviral treatment. The search was carried out in Pubmed and included only articles published after 2000 and written in English. We narratively synthesise the results and discuss the key drivers of cost-effectiveness and their applicability to low and middle-income countries (LMICs).Results: Nine published studies were included in this review, only one of which was performed in a low or middle-income setting in West Africa. Eight studies were performed in high-income settings, seven among high risk groups and one among the general population. The studies were heterogeneous in many respects including the population and testing strategy under consideration, model structure and baselines parameters, willingness to pay thresholds and outcome measures used. However, most studies found HBV testing and treatment to be cost-effective, even at low HBsAg prevalence levels.Conclusions: Currently economic evaluations of HBV testing and treatment strategies in LMICs is lacking, therefore limiting the ability to provide formal recommendations on the basis of cost-effectiveness alone. Further implementation research is needed in order to help guide national policy planning. [ABSTRACT FROM AUTHOR]

Background Variants of the interferon-lambda3 (IFNL3) gene have been associated with both spontaneous and treatment induced clearance of HCV infection. Attempts to link polymorphisms of the IFNL3 gene with variation in the level of IFNL3 expression have been inconclusive. This is partially due to the difficulty to design assays distinguishing IFNL3 from IFNL2. Methods In this study an allele specific real-time PCR (RT-PCR) assay was developed which allows the relative quantification of the two IFNL3 transcripts in cells heterozygous for SNPIFNL3.rs4803217 in the 3'UTR of the IFNL3 gene. This SNP is in strong linkage disequilibrium (LD) with the predictive marker rs12979860. Results Raji cells showed two-fold increased levels of IFNL3.rs4803217 C-allele expression. In peripheral blood mononuclear cells (PBMCs) of eight uninfected donors, two donors showed increased IFNL3.rs4803217 C-allele expression. Conclusion This indicates that allele specific differences in IFNL3 expression vary between individuals and might contribute to the varying outcomes of HCV infection in infected patients. [ABSTRACT FROM AUTHOR]

Background: Alcoholic hepatitis is the most florid presentation of alcohol-related liver disease. In its severe form, defined by a Maddrey's discriminant function (DF) ⩾32, the 28-day mortality rate is approximately 35%. A number of potential treatments have been subjected to clinical trials, of which two, corticosteroids and pentoxifylline, may have therapeutic benefit. The role of corticosteroids is controversial as trial results have been inconsistent, whereas the role of pentoxifylline requires confirmation as only one previous placebo-controlled trial has been published. Methods/design: STOPAH is a multicentre, double-blind, factorial (2 × 2) trial in which patients are randomised to one of four groups: 1. Group A: placebo / placebo 2. Group B: placebo / prednisolone 3. Group C: pentoxifylline / placebo 4. Group D: pentoxifylline / prednisolone The trial aims to randomise 1,200 patients with severe alcoholic hepatitis, in order to provide sufficient power to determine whether either of the two interventions is effective. The primary endpoint of the study is mortality at 28 days, with secondary endpoints being mortality at 90 days and 1 year. Discussion: STOPAH aims to be a definitive study to resolve controversy around the existing treatments for alcoholic hepatitis. Eligibility criteria are based on clinical parameters rather than liver biopsy, which are aligned with standard clinical practice in most hospitals. The use of a factorial design will allow two treatments to be evaluated in parallel, with efficient use of patient numbers to achieve high statistical power. Trial registration: EudraCT reference number: 2009-013897-42 ISRCTN reference number: ISRCTN88782125 [ABSTRACT FROM AUTHOR]

Background: Variants of the interferon-lambda3 (IFNL3) gene have been associated with both spontaneous and treatment induced clearance of HCV infection. Attempts to link polymorphisms of the IFNL3 gene with variation in the level of IFNL3 expression have been inconclusive. This is partially due to the difficulty to design assays distinguishing IFNL3 from IFNL2., Methods: In this study an allele specific real-time PCR (RT-PCR) assay was developed which allows the relative quantification of the two IFNL3 transcripts in cells heterozygous for SNP IFNL3.rs4803217 in the 3'UTR of the IFNL3 gene. This SNP is in strong linkage disequilibrium (LD) with the predictive marker rs12979860., Results: Raji cells showed two-fold increased levels of IFNL3.rs4803217 C-allele expression. In peripheral blood mononuclear cells (PBMCs) of eight uninfected donors, two donors showed increased IFNL3.rs4803217 C-allele expression., Conclusion: This indicates that allele specific differences in IFNL3 expression vary between individuals and might contribute to the variety of outcomes in HCV infected patients.

Background: 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., Methods: 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., Results: 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., Conclusions: 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.