Search

Background & Aims: Body mass index (BMI) and alcohol use are risk factors for hepatocellular carcinoma (HCC). We performed a prospective study to determine if these factors have synergistic effects on HCC risk., Methods: Over 14 years, we followed up 2260 Taiwanese men from the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus (REVEAL-HBV) Study Cohort who tested positive for the hepatitis B surface antigen (mean age, 46 ± 10 y; mean BMI, 24 ± 3 kg/m(2)); 20% reported alcohol use. Incident HCC cases were identified via linkage to the national cancer registry. Multivariate-adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated using Cox-proportional hazards models., Results: In univariate analysis, the interaction between BMI and alcohol predicted incident HCC (P = .029). Alcohol use and extreme obesity (BMI ≥30 kg/m(2)) had synergistic effects on the risk of incident HCC in analyses adjusted for age (HR, 3.41; 95% CI, 1.25-9.27; P < .025) and multivariables (HR, 3.40; 95% CI, 1.24-9.34; P < .025). The relative risk estimate for the interaction and the attributable proportion from the interaction and synergy index were 1.59, 0.52, and 4.40, respectively; these indicate a multiplicative interaction between alcohol use and extreme obesity. In an analysis stratified into 4 World Health Organization categories of BMI and alcohol use, the risk of incident HCC increased in overweight (HR, 2.4; 95% CI, 1.3-4.4), obese (HR, 2.0; 95% CI, 1.1-3.7), and extremely obese (HR, 2.9; 95% CI, 1.0-8.0) users of alcohol (P for trend = .046)., Conclusions: Obesity and alcohol have synergistic effects to increase the risk of incident HCC in hepatitis B surface antigen-positive men. Lifestyle interventions might reduce the incidence of HCC., (Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Plasma levels of gamma-glutamyl transpeptidase (GGT) are associated with risk factors for nonalcoholic fatty liver disease (NAFLD), such as dyslipidemia, insulin resistance (IR), and hypertension. Limited data exist on whether there is genetic covariance between plasma levels of GGT and NAFLD risk factors. Variants of beta2-adrenergic receptor gene (ADRB2) have been associated with dyslipidemia, IR, and hypertension, but its effect on GGT secretion is not known. We estimated the heritability of GGT using a twin-study design and examined the genetic covariance between GGT levels, IR, hypertension, levels of low-density lipoproteins and triglycerides, and ADRB2 variants., Methods: We studied phenotypes of 362 twins; the heritabilities of increased GGT activity and genetic covariance with NAFLD risk factors were estimated by variance-component methodology. ADRB2 genotype associations with plasma GGT activity were examined using generalized estimating equations to account for intra-twinship correlations., Results: GGT activity was heritable at 49% +/- 8% of the twin cohort and had significant covariance with IR; insulin, triglyceride, and uric acid levels; and diastolic blood pressure. In generalized estimating equation models, the most common haplotype of ADRB2 was significantly associated with plasma GGT activity. Five single nucleotide polymorphisms in ADRB2 were associated with levels of GGT; ADRB2 haplotypes displayed pleiotropic effects on GGT and triglyceride levels., Conclusions: In a twin study, GGT shared genetic codetermination with traits of metabolic syndrome. The ADRB2 gene had pleiotropic effects on plasma levels of GGT and triglycerides, indicating linked pathways (eg, adrenergic) between genetic susceptibility to NAFLD and metabolic syndrome., (Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Chronic infection with hepatitis C, genotype 2/3, responds better than other genotypes to peginterferon and ribavirin treatment. We hypothesized that a lower dose of peginterferon would be as effective, but less toxic than standard doses., Aim: To test the hypothesis that a lower dose of peginterferon would be as effective as, but less toxic than, standard doses., Methods: A total of 30 patients were treated with low-dose peginterferon alfa-2a (90 microg/week) and 27 patients with standard doses (180 microg/week) for 24 weeks in combination with 800 mg/day of ribavirin. Patients who failed treatment were offered 48 weeks of standard-dose treatment. Viral and serum inducible protein 10 (IP-10) levels were measured and early viral kinetic parameters were calculated., Results: Sustained virological response was achieved in 68% of the low-dose and 87% of the standard-dose patients (per protocol, P = 0.79 for non-inferiority). Re-treatment was successful in all patients who tolerated full dose and duration. The standard-dose group had greater first-phase declines of viral levels and faster time to negativity. The second-phase slope was not dose-dependent. IP-10 induction was significantly greater with the standard dose. Although fatigue and general feeling during treatment were worse for standard dose, haematological toxicity and depression did not differ between groups., Conclusion: A lower dose of peginterferon is associated with some symptomatic benefit, but the response is not equivalent to standard dosing.

Background: The association between body-mass-index (BMI), alcohol consumption and their joint effect in increasing the risk of elevated serum alanine (ALT) and aspartate (AST) is unclear in older community-dwelling adults., Aim: To determine the association between alcohol, BMI, and their combined effect with serum ALT and AST in older community-dwelling adults in the United States., Methods: A cross-sectional, population-based study in participants (n = 2364) from the Rancho Bernardo Study (54% women; mean age: 70 years, BMI: 25 kg/m(2), alcohol users: 63%) who attended a research visit in 1984-87. BMI was recorded by a trained nurse and alcohol use ascertained by a validated questionnaire. Odds-ratio (OR) and 95% confidence intervals (CI) of elevated serum ALT and AST (defined as > or =30 U/L in men and > or =19 U/L in women) were calculated for alcohol and BMI separately and their joint exposure using logistic regression models., Results: In multivariate logistic regression models adjusted for age, alcohol use, total cholesterol, serum triglycerides, fasting plasma glucose, systolic blood pressure, and diabetes mellitus, obesity independently increased the odds of elevated ALT in this cohort of older men and women by 3.0 (95% CI, 1.7-5.3) and 1.8 (95% CI, 1.1-2.7) respectively. Joint effects of consuming >3 alcoholic drinks/day and obesity raised the odds of elevated ALT by 8.9 (95% CI, 2.4-33.1) and AST by 21-fold (95% CI, 2.6-170.1), demonstrating synergism. Obese participants had higher odds of elevated ALT even at 0 < or = 1 drink/day., Conclusions: In older men and women, the combination of obesity with alcohol is synergistic in increasing the risk of liver injury.

Nonalcoholic fatty liver disease (NAFLD), first described in 1980, is now recognized as one of the most common causes of elevated liver enzymes and chronic liver disease in Western countries. The incidence of NAFLD in both adults and children is rising, in conjunction with the burgeoning epidemics of obesity and type 2 diabetes mellitus. NAFLD often coexists with other sequelae of the metabolic syndrome: central obesity, type 2 diabetes, hypertension, and hyperlipidemia. NAFLD encompasses a spectrum of pathologic liver diseases ranging from simple hepatic steatosis to a predominant lobular necro-inflammation, with or without centrilobular fibrosis (called nonalcoholic steatohepatitis or NASH). NASH can progress to cirrhosis, decompensated liver disease, and hepatocellular carcinoma. Though the natural history of NASH is still not clearly defined, it has been observed to progress to cirrhosis in 15%-220% of those affected. Insulin resistance is nearly universal in NASH and is thought to play an important role in its pathogenesis leading to dysregulated lipid metabolism. The prevalence of insulin resistance is reported in the general population to be approaching 45%, suggesting that NAFLD and NASH will contin nue to be an important public health concern. To date, NASH has proven to be a difficult disease to treat. Front-line therapy with lifestyle modifications resulting in weight loss through decreased caloric intake and moderate exercise is generally believed to be beneficial in patients with NASH, but is often difficult to maintain long term. Given that insulin resistance plays a dominant role in the pathogenesis, many studies have examined the use of insulin sensitizers: the biguanides (metformin), thiazolidinediones (pioglitazone, troglitazone, and rosiglitazone), glucagon-like peptide-1-receptor agonists, or incretins (exenatide)in NASH. This review will provide an overview of insulin resistance in NAFLD and provide a detailed summary on the clinical data regarding the use of insulin sensitizers in NASH.

Unlabelled: Nonalcoholic fatty liver disease (NAFLD) has emerged as the leading cause of chronic liver disease in children and adolescents in the United States. A two- to three-fold rise in the rates of obesity and overweight in children over the last two decades is probably responsible for the NAFLD epidemic. Emerging data suggest that children with nonalcoholic steatohepatitis (NASH) progress to cirrhosis, which may ultimately increase liver-related mortality. More worrisome is the recognition that cardiovascular risk and morbidity in children and adolescents are associated with fatty liver. Pediatric fatty liver disease often displays a histologic pattern distinct from that found in adults. Liver biopsy remains the gold standard for diagnosis of NASH. Noninvasive biomarkers are needed to identify individuals with progressive liver injury. Targeted therapies to improve liver histology and metabolic abnormalities associated with fatty liver are needed. Currently, randomized-controlled trials are underway in the pediatric population to define pharmacologic therapy for NAFLD., Conclusion: Public health awareness and intervention are needed to promote healthy diet, exercise, and lifestyle modifications to prevent and reduce the burden of disease in the community.

Background & Aims: HBV infection may reactivate in the setting of immunosuppression, although the frequency and consequences of HBV reactivation are not well known. We report 6 patients who experienced loss of serologic markers of hepatitis B immunity and reappearance of HBsAg in the serum as a result of a variety of acquired immune deficiencies., Methods: Between 2000 and 2005, six patients with reactivation of hepatitis B were seen in consultation by the Liver Diseases Branch at the Clinical Center, National Institutes of Health. The course and outcome of these 6 patients were reviewed., Results: All 6 patients developed reappearance of HBsAg and evidence of active liver disease after stem cell transplantation (n = 4), immunosuppressive therapy (n = 1), or change in human immunodeficiency virus antiretroviral regimen (n = 1), despite having antibody to HBsAg (anti-HBs) or antibody to hepatitis B core antigen (anti-HBc) without HBsAg before. All 6 patients developed chronic hepatitis B, 2 patients transmitted hepatitis B to their spouses, and 1 patient developed cirrhosis. The diagnosis of hepatitis B reactivation was frequently missed or delayed and often required interruption of the therapy for the underlying condition. None of the patients received antiviral prophylaxis against HBV reactivation., Conclusions: Serologic evidence of recovery from hepatitis B infection does not preclude its reactivation after immunosuppression. Screening for serologic evidence of hepatitis B and prophylaxis of those with positive results by using nucleoside analogue antiviral therapy should be provided to individuals in whom immunosuppressive therapy is planned.

Background & Aims: The use of antibiotics in the primary prophylaxis for spontaneous bacterial peritonitis (SBP) in patients with cirrhosis is controversial. Our purpose was to determine the beneficial effect of fluoroquinolones as compared with placebo in primary prophylaxis of SBP in high-risk patients with cirrhosis by using meta-analysis., Methods: Medline, Embase, Cochrane, and Web of Science databases were searched in all languages until August 2008 for randomized placebo-controlled studies evaluating the role of fluoroquinolones in primary prevention of SBP in patients with low protein ascites (total ascitic protein, <1.5 g/dL) and without history of SBP. Two investigators independently performed literature search and data extraction, and then another investigator independently reviewed whether the studies met prespecified criteria and rechecked data extraction. Odds ratios (Peto method) for the risk reduction with fluoroquinolones were calculated for each study and combined by using a random-effects model., Results: Four randomized controlled studies met predefined criteria. The odds ratios for developing first episode of SBP, serious infections, and mortality with fluoroquinolone prophylaxis (n = 194) versus placebo (n = 190) were 0.18 (95% confidence interval [CI], 0.09-0.35), 0.18 (95% CI, 0.10-0.32), and 0.60 (95% CI, 0.37-0.97), respectively. All studies were unidirectional in showing the beneficial effect of fluoroquinolone prophylaxis. We were limited by finding few studies with relatively small sample sizes., Conclusions: Daily oral fluoroquinolone prophylaxis reduces the risk of development of first episode of SBP and mortality in cirrhotic patients with low total protein in the ascitic fluid. Fluoroquinolones might be advisable for the primary prophylaxis of SBP in selected high-risk patients with cirrhosis.

Hepatitis B virus infection (HBV) is a significant global health problem. Despite the success of universal hepatitis B vaccination in many countries, more than 350 million individuals worldwide are chronically infected and 15- 40% of those will develop cirrhosis and/or hepatocellular carcinoma if left untreated. Available therapies for chronic hepatitis B (CHB) infection are effective at decreasing viremia and improving measured clinical outcomes, however, no single therapy is optimal. As such, alternative drug therapies and the investigation of their role in the management of CHB are warranted. Significant improvements in the understanding of the HBV life cycle, viral genomics, and virus-host interactions continue to lead to the development of novel viral targets and immune modulators. Currently, two major classes of agents are utilized in CHB: the interferons and the nucleos(t)ide analogues. Each agent has individual advantages and drawbacks. The development of specific antiviral therapy has led to the emergence of HBV drug-resistant strains that has limited the long-term therapeutic potential of available agents. This necessitates the development of new agents that target both wild-type and drug-resistant strains. Further understanding of the basic mechanisms and clinical nuances of drug therapy is warranted. As most novel therapies are in the earliest stages of clinical development and testing, in the near future, treatment will continue to be long-term and likely involve the use of combination therapies to prevent viral resistance. In this review, we will highlight the HBV life cycle and genome, focusing in on current and potential novel antiviral drug targets as well as the benefits and clinical challenges with these therapies.

Unlabelled: Cardiovascular disease remains a leading cause of mortality worldwide. As dyslipidemia increases cardiovascular disease risk, proper management of dyslipidemia is one means by which to decrease cardiovascular disease risk. This review focuses on dyslipidemia treatment utilizing fibrate therapy, which targets high trigylcerides, low HDL, and high small, dense LDL, while contrasting fibrate therapy with statin therapy and combined therapy. Studies were obtained using electronic search strategies, such as Medline and Cochrane Library. Sources selected were limited to those that discussed fibrates, statins, and combined therapy, with specific emphasis placed on sources that focused on fibrates. Selected studies were then assessed for quality via analysis of the study's methodology, results, and data., Results: of selected studies were then stratified using a rating system devised to determine the quality of results using the scientific evidence provided for them. Combination fibrate and statin therapy can be more effective in achieving optimal lipid levels than just fibrate or statin therapy alone without significant side effects as long as gemfibrozil is not used in therapy.

Background: Non-alcoholic steatohepatitis (NASH) is a form of progressive fatty liver disease that is strongly associated with insulin resistance, which suggests that insulin sensitizing agents such as metformin may be beneficial for NASH., Aim: To assess the effects of metformin on insulin sensitivity, body composition, serum alanine aminotransferase (ALT) levels and liver histology in patients with NASH., Methods: Patients underwent liver biopsy, metabolic profiling and imaging studies before and at the end 48 weeks of metformin (2000 mg/day) therapy. The primary endpoint was a three-point improvement in the histological NASH activity index., Results: Of 28 patients enrolled, 26 (13 females; average age 44 years) completed 48 weeks of treatment and underwent repeat metabolic studies, imaging and liver biopsy. Thirty per cent achieved a histological response. Most patients lost weight, the average being 6 kg. There was a marked association between weight loss and improvements in NASH activity index and ALT levels (both, P < 0.01). Insulin sensitivity also improved, but the degree of change did not correlate with histological improvement., Conclusion: Metformin leads to improvements in liver histology and ALT levels in 30% of patients with NASH, probably by its effects in causing weight loss.

Background & Aims: Changes in biochemical and histologic parameters related to nonalcoholic steatohepatitis (NASH) in placebo-treated patients may provide an insight into the natural history and help in defining treatment end points in NASH. The aim of our study was to assess the biochemical and histologic changes seen in the placebo arm of the randomized, placebo-controlled trials in adult patients with NASH., Methods: Medline was searched (through May 2008) for studies published in the English language. Randomized, placebo-controlled trials of at least 6 months' duration in patients with NASH that provided biochemical and/or histologic data of the placebo arm were included. One investigator performed the literature search and data extraction. Two investigators independently confirmed that the studies met prespecified criteria. Pooled estimates of biochemical and histologic parameters associated with NASH were calculated., Results: Five randomized controlled trials met the predefined criteria and included 162 placebo-treated and 189 active-treatment patients. The mean serum alanine and aspartate aminotransferase levels decreased on placebo. A 1-point improvement in steatosis, ballooning degeneration, lobular inflammation, NASH fibrosis, and combined inflammation scores was seen in 31%, 15%, 33%, 22%, and 32% of patients, respectively. A 2-point improvement in NASH histologic scores is rarely seen., Conclusions: Serum alanine aminotransferase levels may decrease on placebo and is not a reliable measure of treatment response. Although a 1-point improvement is seen in a third of patients, a 2-point improvement in histologic parameters is rarely seen in the placebo arm and may be more reliable in assessing treatment response. These data may have important implications in designing future clinical trials in NASH.

Background & Aims: HBV recurrence increases morbidity and mortality in HBsAg+ patients undergoing liver transplantation. We aimed to estimate the relative efficacy of combined therapy with hepatitis B immunoglobulin (HBIG) and lamivudine (LAM) versus HBIG monotherapy for preventing HBV-related morbidity and mortality in this setting., Methods: We performed a meta-analysis of clinical trials that met the prespecified criteria and provided data for risk estimation of HBV recurrence in HBsAg+ liver transplant patients receiving HBIG and LAM versus HBIG alone. Databases searched until May 2007 included MEDLINE (Ovid), PubMed, Embase, Toxnet, Scopus, and Web of Science. Literature search and data extraction were conducted independently by 2 study investigators; then 2 other investigators reviewed and screened eligible studies. Odds ratios (ORs) for the risk reduction with HBIG and LAM versus HBIG alone were calculated by using a random-effects model., Results: Two prospective and 4 retrospective studies were included in the meta-analysis. The OR showing risk reduction in HBV recurrence with HBIG and LAM (n = 193) versus HBIG alone (n = 124) was 0.08 (95% confidence interval [CI], 0.03-0.21). HBV-related death and all-cause mortality could only be assessed in 3 studies each. The ORs showing HBV-related death and all-cause mortality reduction with HBIG and LAM versus HBIG alone were 0.08 (95% CI, 0.02-0.33) and 0.02 (95% CI, 0.06-0.82), respectively., Conclusions: Although this meta-analysis was limited by small studies and varying levels of immunosuppression, it is apparent that adding LAM to HBIG improved HBV-related morbidity and mortality in HBsAg+ recipients of liver transplants.

Background: Lamivudine is increasingly being used to prevent hepatitis B reactivation in patients with cancer who test positive for hepatitis B surface antigen (HBsAg) and are undergoing chemotherapy., Purpose: To determine whether preventive lamivudine reduces chemotherapy-induced hepatitis B virus (HBV)-related morbidity and mortality in patients with cancer who test positive for HBsAg., Data Sources: MEDLINE, Ovid MEDLINE, TOXNET, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched in all languages until June 2007., Study Selection: Clinical trials and cohort studies that reported the efficacy of preventive lamivudine versus control on HBV reactivation in patients who tested positive for HBsAg and were receiving chemotherapy were included. Additional requirements included minimum sample size (>5 participants per treatment group) and reported HBV-related morbidity and mortality data., Data Extraction: Two investigators independently did literature searches and data extraction, and 2 other investigators independently confirmed study eligibility and data retrieval., Data Synthesis: Fourteen studies (2 randomized, controlled trials; 8 prospective cohort studies; and 4 retrospective cohort studies) met the predefined criteria for analysis. There were 275 patients in the preventive lamivudine group and 475 control participants for the primary end point of HBV reactivation. With preventive lamivudine, the relative risk for both HBV reactivation and HBV-related hepatitis ranged from 0.00 to 0.21. None of the patients in the preventive lamivudine group developed HBV-related hepatic failure (0 of 108 patients vs. 21 of 162 patients), and only 4 deaths were attributable to HBV (4 of 208 patients vs. 27 of 394 patients) in the preventive lamivudine group. Lamivudine was well tolerated, and no adverse effects were noted., Limitations: The studies included in the meta-analysis did not consistently report all of the outcomes of interest. Sample sizes were small and only 2 studies had a randomized, controlled design., Conclusion: Preventive therapy with lamivudine for patients who test positive for HBsAg and are undergoing chemotherapy may reduce the risk for HBV reactivation and HBV-associated morbidity and mortality.

Background & Aims: Obesity is an important correlate of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. We sought to examine the relations between parental obesity and the serum ALT and AST levels among offspring in a community-based sample., Methods: Participants (n = 1732) of the Framingham Offspring Study (50% women; mean age, 42 years) who had serum ALT and AST measurements and both parents in the original Framingham cohort were studied. Study participants were grouped into early-onset parental obesity (n = 193) (at least one parent obese), later-onset parental obesity (n = 460), and no parental obesity (n = 1079) subgroups. The association between elevated ALT or AST levels and parental obesity was tested using generalized estimating equations to account for familial correlations., Results: In multivariable analysis including adjustment for offspring obesity, significantly higher ALT levels were observed among individuals with paternal early-onset obesity as compared with those without paternal obesity (P = .02). Offspring with early-onset paternal obesity were more likely to have elevated ALT levels compared with those without paternal obesity (odds ratio, 1.75; 95% confidence interval, 1.06-2.89; P = .03). There was no association with elevated ALT levels among offspring with maternal early-onset obesity (odds ratio, 1.10; 95% confidence interval, 0.76-1.59; P = .61). There was no association between parental obesity and serum AST levels., Conclusions: Early-onset paternal obesity, but not maternal obesity, increases the odds of elevated serum ALT levels in offspring, suggesting a predisposition to developing elevated serum ALT levels that may be mediated through familial early-onset obesity.

Unlabelled: A pilot study of a 48-week course of pioglitazone demonstrated significant improvements in the biochemical and histological features of nonalcoholic steatohepatitis (NASH). The aim of the study was to assess the effects of stopping pioglitazone. Twenty-one patients with NASH were treated with pioglitazone (30 mg/day) for 48 weeks and underwent baseline and end-of-treatment evaluation including liver biopsy. Thirteen patients were followed for at least 48 weeks after stopping therapy and 9 underwent repeat liver biopsy. Statistical comparisons were made to evaluate whether discontinuation of pioglitazone resulted in a reversal of improvements seen on therapy. Stopping pioglitazone was associated with subsequent elevation in serum alanine aminotransferase levels (from 34 +/- 13 to 70 +/- 39 IU/l), decrease in adiponectin (from 9.7 +/- 9.1 to 5.1 +/- 4.5 microg/ml), worsening insulin sensitivity (HOMA Index: from 2.9 +/- 1.8 to 5.5 +/- 5.4), and increase in total hepatic fat (from 30% +/- 32% to 71% +/- 33%) despite no change in average body weight compared to the end of treatment. Repeat liver biopsy in 9 patients revealed significant worsening of parenchymal inflammation (from 1.2 +/- 0.7 to 2.9 +/- 1.1) and steatosis (from 0.9 +/- 0.6 to 2.1 +/- 1.3) but no change in fibrosis (from 1.1 +/- 1.2 to 1.2 +/- 1.3). NASH was again present on liver biopsy in 7 patients., Conclusion: These findings suggest that long-term therapy with pioglitazone may be necessary to maintain improvements in disease activity in patients with NASH, although weight gain during treatment may ultimately limit its beneficial effects.

Hepatitis B virus (HBV) infection is the leading cause of chronic liver disease and hepatocellular carcinoma worldwide. Approximately 350 million individuals are infected with HBV and >500,000 deaths per year can be attributed to HBV. Although universal vaccination has reduced HBV incidence in many countries, it still remains a major public health problem, especially in parts of Asia and Africa. Improved understanding of HBV virology and virus-host interactions has revolutionized chronic hepatitis B therapy in the past two decades. Development of oral nucleoside/nucleotide analogues heralds a new era of safe and effective treatment of this disease. On the basis of these advances, new guidelines for the treatment of chronic hepatitis B have been issued. Successful long-term treatment of chronic hepatitis B may rest on combination therapy that is based on molecular approaches targeting various stages of the HBV life-cycle. In this review, we summarize the current modalities and highlight important issues in the treatment of chronic hepatitis B monoinfection.

Hepatitis B is one of the most prevalent viral diseases in the world. It leads to chronic liver disease in 10% of infected individuals, putting them at an increased risk for liver-related morbidity and mortality from complications of cirrhosis and hepatocellular carcinoma. Despite the success of universal hepatitis B vaccination in many countries, this disease remains a major public health problem, resulting in more than 500,000 deaths per year. Although the current therapy for chronic hepatitis B (CHB) is effective, it is not optimal; novel approaches to the management of CHB are needed. An improved understanding of virus-host interactions, advances in gene therapy, the development of molecular therapies targeted at different stages of the hepatitis B virus life cycle, and new insights into various approaches of immune modulation will lead to the development of better therapeutic agents for the management of CHB. These advances herald a new era of combination therapy. In this review, we will discuss emerging therapies and potential mechanisms, and highlight the promises and pitfalls of these new treatment strategies.

We present 2 cases of lead poisoning, the first of a child playing with painted toys and the second of an adult on local medicine. The former presented with acute abdomen and the latter with peripheral muscle weakness. We propose that raised serum δ-amino leavulinic acid (δ-ALA) levels strongly point towards the possibility of lead poisoning.

With the advent of intra ocular lens implantation at the time of cataract extraction, especially by intracapsular method, it has become very important to prevent the loss of vitreous during surgery. This can be achieved by lowering the intraocular pressure by various methods. In order to find out the best method to achieve a soft & safe eye before surgery, a study was conducted on 90 patients, undergoing intracapsular cataract extraction. The patients were divided into 9 groups of 10 each, & different methods of lowering intraocular pressure were tried and results compared. It was observed that intravenous mannitol given preoperatively and pressure with mercury column together, formed the best combination to achieve the maximum tension lowering effect.