Is it better to treat chronic hepatitis B as early as possible?—Con

Ideally, treatment of chronic hepatitis B in its early stage prior to irreversible liver damage should be most effective in preventing adverse clinical outcome. However, currently available treatments have low efficacy in achieving sustained response among patients in the early phase of chronic hepatitis B infection when the immune response to hepatitis B virus is weak. This review will provide evidence why a ‘wait and monitor’ approach is appropriate for chronic hepatitis B patients who are in the immune tolerant phase.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73513/1/j.1440-1746.2004.03660.x.pd

Hepatitis B and Renal Disease

Glomerulonephritis is an important extrahepatic manifestation of chronic hepatitis B virus (HBV) infection. The uncommon occurrence, variability in renal histopathology, and heterogeneity in clinical course present challenges in clinical studies and have resulted in a relative paucity of data and uncertainty with regard to the optimal management of HBV-related glomerular diseases. The advent of nucleos(t)ide analogue medications that effectively suppress HBV replication has markedly altered the clinical outcomes of kidney transplant recipients with HBV infection, but the emergence of drug resistance is an escalating problem. This article reviews the recent knowledge of the pathogenesis and treatment of HBV-related membranous nephropathy, and discusses the management of hepatitis B in kidney transplant recipients, which is continuously evolving

The importance of baseline viral load when assessing relative efficacy in treatment-naïve HBeAg-positive chronic hepatitis B: a systematic review and network meta-analysis.

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

The Role of Interferon in Hepatitis B Therapy

Despite the introduction of new nucleos(t)ide analogues in recent years, peginterferon is still recommended as a potential first-line treatment option by current practice guidelines for the management of chronic hepatitis B. Peginterferon offers the advantage of higher sustained off-treatment response rates compared to nucleos(t)ide analogues because of its immunomodulatory effects. Sustained transition to the inactive hepatitis B surface antigen (HBsAg) carrier state can be achieved in about 30% of hepatitis B e antigen (HBeAg)–positive patients and 20% of HBeAg-negative patients. Recent studies have focused on identification of pretreatment and on-treatment factors that allow the selection of patients who are likely to achieve a sustained response to peginterferon therapy in order to avoid the side-effects and costs associated with unnecessary treatment. Future studies need to address whether specific virologic benchmarks can guide individualized decisions concerning therapy continuation and whether peginterferon combined with new potent nucleos(t)ide analogues improves treatment outcomes

Effect of Ethanol and Dietary-Protein Concentration On Whole-Body Protein-Synthesis Rates in Rats

The effect of ethanol intake in whole body protein synthesis in rats fed diets low in protein concentration (4% of calories) or nutritionally adequate (13% of calories) was studied. Protein synthesis was decreased significantly by alcohol intake in rats fed the low protein diet or the nutritionally adequate diet when compared with appropriate controls. The inclusion of ethanol in the diet decreased plasma nitrogen flux and the proportion of flux nitrogen recycled for protein synthesis. The proportion of flux nitrogen arising from dietary nitrogen was increased, although dietary nitrogen intake was similar, indicating a decrease in protein catabolism when alcohol is included in the diet