Gagan Sood

Effect of Bariatric Surgery on Nonalcoholic Fatty Liver Disease: Systematic Review and Meta-Analysis

BACKGROUND & AIMS Weight loss in overweight or obese individuals results in marked improvement or resolution of hypertension, diabetes mellitus, and hyperlipidemia. However, the overall effect of weight loss on nonalcoholic fatty liver disease (NAFLD) remains unclear. This systematic review and meta-analysis is an effort to explore the effect of weight loss after bariatric surgical procedures on NAFLD. METHODS We performed an electronic literature search of published articles on bariatric surgery and liver histology since inception to September of 2007. Primary outcome measures were improvement and/or resolution in the 3 components of NAFLD (steatosis, steatohepatitis, and fibrosis) after bariatric surgery-induced weight loss. A pooled proportion of patients with improvement or resolution was calculated for steatosis, steatohepatitis, and fibrosis using a random effects model. Heterogeneity among the studies was assessed using the I(2) (inconsistency) statistic and subgroup analyses. RESULTS A total of 15 studies (766 paired liver biopsies) were selected for final data extraction. The percentage reduction in mean body mass index after bariatric surgeries ranged from 19.11 to 41.76. The pooled proportion of patients with improvement or resolution in steatosis was 91.6% (95% confidence interval [CI], 82.4%-97.6%), in steatohepatitis was 81.3% (95% CI, 61.9%-94.9%), in fibrosis was 65.5% (95% CI, 38.2%-88.1%), and for complete resolution of nonalcoholic steatohepatitis was 69.5 (95% CI, 42.4%-90.8%). CONCLUSIONS Steatosis, steatohepatitis, and fibrosis appear to improve or completely resolve in the majority of patients after bariatric surgery-induced weight loss.

Hepatic outflow obstruction (Budd-Chiari syndrome). Experience with 177 patients and a review of the literature.

Budd-Chiari syndrome (BCS) may not be as uncommon as was once believed. Our study has substantiated the existence of 2 major clinical forms. The acute syndrome is invariably associated with extensive blockage of the major hepatic veins, resulting in congestive liver cell necrosis. In a small, but significant, number of patients the inferior vena cava (IVC) is also occluded. The important etiologic factors are related to hypercoagulability of blood. Immediate placement of a shunt improves survival. The chronic syndrome is characterized by portal hypertension and is associated with a variable abnormal vascular anatomy. The causes of the chronic syndrome are not clear, but a substantial number of cases are related to the presence of an IVC membrane. Shunt surgery is effective but procedures aimed at the primary pathology are likely to be even more so. The natural history of BCS should be viewed over a long period of time. The very long survival of several patients urges a more cautious approach to surgical remedies. Budd-Chiari syndrome probably represents a spectrum of disease caused primarily by a hypercoagulable state and having a varied presentation depending on the balance between rate of formation and the extent of the thrombosis and the bodys own rate of thrombolysis and recanalization. The extent and efficacy of the individuals collateral circulation and the rate of development of liver fibrosis are other determinants. It is thus possible to view BCS as a continuum of a single pathogenetic spectrum. Pregnancy-related BCS in India probably has strong social determinants, and is usually acute and fulminant. We have, however, documented a chronic form not described earlier. Children usually do not have acute BCS, but chronic BCS in children and adolescents is similar to that in adults. Membranous obstruction of the inferior vena cava (MOVC) is common and was found even at a young age. The association of MOVC with hepatocellular carcinoma, however, did not appear to be as clear as was previously believed. There has been a wide geographical variability in the causes and manifestations of BCS. Our study has clearly shown that--Kiplings categorical statement to the contrary--East and West do meet in India, in the Budd-Chiari syndrome.

Predictors of large esophageal varices in patients with cirrhosis.

Abstract OBJECTIVE: Recent guidelines recommend that all cirrhotics undergo screening upper endoscopy to identify those patients at risk for bleeding from varices. However, this practice may not be cost effective as large esophageal varices are seen only in 9–36% of these patients. The aim of this study was to determine whether clinical variables were predictive of the presence of large esophageal varices. METHODS: This is a retrospective analysis of cirrhotics who had a screening upper endoscopy during an evaluation for liver transplantation at three different centers and who had not previously bled from varices. A multivariate model was derived on the combined cohort using logistic regression. Three hundred forty-six patients were eligible for the study. RESULTS: The prevalence of large esophageal varices was 20%. On multivariate analysis, splenomegaly detected by computed tomographic scan (odds ratio: 4.3; 95% confidence interval: 1.6–11.5) or by physical examination (odds ratio: 2.0; 95% confidence interval: 1.1–3.8), and low platelet count were independent predictors of large esophageal varices. On the basis of these variables, cirrhotics were stratified into high- and low-risk groups for the presence of large esophageal varices. Patients with a platelet count of ≥88,000/mm3 (median value) and no splenomegaly by physical examination had a risk of large esophageal varices of 7.2%. Those with splenomegaly or platelet count CONCLUSIONS: Our data show that clinical predictors could be used to stratify cirrhotic patients for the risk of large esophageal varices and such stratification could be used to improve the cost effectiveness of screening endoscopy.

Antiviral Therapy Reduces Risk of Hepatocellular Carcinoma in Patients With Hepatitis C Virus–Related Cirrhosis

BACKGROUND & AIMS The effects of antiviral therapy on prevention of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related cirrhosis are unclear. We performed a systematic review and meta-analysis to assess HCC risk reduction in patients with HCV-related cirrhosis who have received antiviral therapy. METHODS Twenty studies (4700 patients) were analyzed that compared untreated patients with those given interferon (IFN) alone or ribavirin. Risk ratios (RRs) determined effect size using a random effects model. RESULTS Pooled data showed reduced HCC risk in the treatment group (RR, 0.43; 95% confidence interval [CI], 0.33-0.56), although the data were heterogenous (chi(2) = 59.10). Meta-regression analysis showed that studies with follow-up durations of more than 5 years contributed to heterogeneity. Analysis of 14 studies (n = 3310) reporting sustained virologic response (SVR) rates with antiviral treatment showed reduced HCC risk in patients with an SVR, compared with nonresponders (RR, 0.35; 95% CI, 0.26-0.46); the maximum benefits were observed in patients treated with ribavirin-based regimens (RR, 0.25; 95% CI, 0.14-0.46). Meta-analysis of 4 studies assessing the role of maintenance IFN in nonresponders did not show HCC risk reduction (RR, 0.58; 95% CI, 0.33-1.03). No publication bias was detected by the Egger test analysis (P > 0.1). CONCLUSIONS The risk of HCC is reduced among patients with HCV who achieve an SVR with antiviral therapy. Maintenance therapy with IFN does not reduce HCC risk among patients who do not respond to initial therapy. View this articles video abstract atwww.cghjournal.org.

Occult hepatitis B virus infection: a covert operation.

Summary.  Detection of occult hepatitis B requires assays of the highest sensitivity and specificity with a lower limit of detection of less than 10 IU/mL for hepatitis B virus (HBV) DNA and <0.1 ng/mL for hepatitis B surface antigen (HBsAg). This covert condition is relatively common in patients with chronic hepatitis C virus (HCV) that seems to exert some influence on the replicative capacity and latency of HBV. Detection of virus‐specific nucleic acid does not always translate into infectivity, and the occurrence of primer‐generated HBV DNA that is of partial genomic length in immunocompetent individuals who have significant levels of hepatitis B surface antibody (anti‐HBs) may not be biologically relevant. Acute flares of alanine aminotransferase (ALT) that occur during the early phase of therapy for HCV or ALT levels that remain elevated at the end of therapy in biochemical nonresponders should prompt an assessment for occult hepatitis B. Similarly, the plasma from patients with chronic hepatitis C that is hepatitis B core antibody (anti‐HBc) positive (±anti‐HBs at levels of <100 mIU/mL) should be examined for HBV DNA with the most sensitive assay available. If a liver biopsy is available, immunostaining for hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) should be contemplated and a portion of the sample tested for HBV DNA. This is another reason for optimal collection of a specimen (e.g. two passes with a 16‐guage needle under ultrasound guidance). Transmission of HBV to immunosuppressed orthotopic liver transplant recipients by donors with occult hepatitis B (OHB) will continue to occupy the interests of the transplant hepatologist. As patients with OHB may have detectable HBV DNA in serum, peripheral blood mononuclear cells (PBMC) and/or liver that can be reactivated following immunosuppression or intensive cytotoxic chemotherapy, the patient needs to be either monitored or treated depending on the pretreatment serological results such as an isolated anti‐HBc reaction or a detectable HBV DNA.

Hepatocellular carcinoma review: Current treatment, and evidence-based medicine

Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide. Multiple treatment options are available for HCC including curative resection, liver transplantation, radiofrequency ablation, trans-arterial chemoembolization, radioembolization and systemic targeted agent like sorafenib. The treatment of HCC depends on the tumor stage, patient performance status and liver function reserve and requires a multidisciplinary approach. In the past few years with significant advances in surgical treatments and locoregional therapies, the short-term survival of HCC has improved but the recurrent disease remains a big problem. The pathogenesis of HCC is a multistep and complex process, wherein angiogenesis plays an important role. For patients with advanced disease, sorafenib is the only approved therapy, but novel systemic molecular targeted agents and their combinations are emerging. This article provides an overview of treatment of early and advanced stage HCC based on our extensive review of relevant literature.

Terlipressin therapy for reversal of type 1 hepatorenal syndrome: A meta-analysis of randomized controlled trials

Background and Aim:  Hepatorenal syndrome (HRS) is a serious complication of advanced liver disease and carries a poor prognosis. Recent trials have indicated that terlipressin may be effective in reversing HRS. Our aim was to evaluate the efficacy of terlipressin therapy in reversing type 1 HRS defined as a serum creatinine <1.5 mg/dL during treatment.

Long term results of endoscopic dilatation for corrosive oesophageal strictures.

Although dilatation is the treatment of choice for most patients with benign oesophageal strictures, there is little information on its efficacy and safety in corrosive oesophageal strictures. Of 123 adults with benign oesophageal strictures treated by endoscopic dilatation, 52 (42.3%) had strictures after corrosive ingestion and 39 (31.7%) had peptic strictures. Treatment was considered adequate if the oesophageal lumen could be dilated to 15 mm and there was complete relief of dysphagia. If dysphagia recurred after adequate initial dilatation, the stricture was dilated again up to 15 mm. Initial dilatation was adequate in 93.6% of patients with corrosive strictures and this success rate was comparable with that of the peptic stricture group (100%, p > 0.05). Long term success after adequate initial dilatation was studied in 36 patients with corrosive strictures (mean follow up 32.36 (17.12) months, range 6-60) and 33 patients with peptic strictures (mean follow up 36.32 (17.9) months, range 6-60). The mean (SEM) number of symptomatic recurrences per patient month during the total follow up period in the corrosive group was significantly higher than that in the peptic group (0.27 (0.04) v 0.07 (0.02), p < 0.001). The recurrence rate in the corrosive group, however, decreased over time, and after 12 months it was significantly (p < 0.001) lower than the recurrence rate in the first six months. After 36 months, the difference in the recurrence rate in the two groups was not significant (p > 0.05). Only nine oesophageal perforations occurred during a total of 1373 dilatation treatments (procedure related incidence 0.66%), and eight of these were in the corrosive stricture group. These patients were managed conservatively and subsequently strictures were dilated adequately in all. Endoscopic dilatation is safe and effective for short and long term relief of dysphagia in patients with corrosive oesophageal strictures.

Hepatotoxicity Fears Contribute to Underutilization of Statin Medications by Primary Care Physicians

Introduction:The safety and efficacy of hydroxymethylglutaryl CoA reductase inhibitors (statins) have been extensively demonstrated, but in clinical practice, there remains significant underutilization of these medications. The authors hypothesized that this underutilization could stem in part from fear of liver damage caused by statins. The purpose was to determine whether concern about hepatotoxicity acts as a barrier among primary care physicians to prescribing statins for patients with elevated liver transaminase values and/or underlying liver disease. Method:The survey included 937 primary care physicians from 138 academic centers in the United States, and the following were measured: (1) comparison of statin prescribing for patients with clinical indications and (a) no mention of liver transaminase values, (b) elevated liver transaminase values and (c) underlying liver disease; (2) correlation between perception of statin hepatotoxicity and statin prescribing. Results:Seventy-one percent of respondents would prescribe statins in scenario 1, (45-year-old woman with low-density lipoprotein 240 mg/dL), whereas only 50% would prescribe statins if the baseline liver transaminase values were elevated to 1.5 times upper limit of normal (P < 0.001). This prescribing rate dropped even further to 40% in scenario 3 (55-year-old man with known coronary disease, low-density lipoprotein 250 mg/dL and hepatitis C). Thirty-seven percent of respondents had falsely elevated perceptions of statin hepatotoxicity risk, and these perceptions correlated inversely with statin prescribing. The method of survey administration prevented calculation of response rate, possibility of response bias exists. Conclusion:Despite extensive data documenting safety of statins, primary care physicians harbor significant hepatotoxicity concerns, and these concerns act as a barrier to statin utilization.

Tacrine: A cause of fatal hepatotoxicity?

Tacrine, an acetyl cholinesterase inhibitor used in the treatment of Alzheimers disease, often causes reversible abnormalities in liver enzymes, but significant hepatotoxicity is uncommon. We describe fatal hepatic failure associated with tacrine administration. A 75-year-old woman with Alzheimers disease, taking tacrine for 14 months, developed progressive jaundice. Liver function abnormalities developed during tacrine treatment and led to hepatic failure and death. An extensive evaluation for other etiologies of liver disease was negative. Other potentially hepatotoxic medicines had been administered for at least 2 years before beginning tacrine, and postmortem examination of the liver was consistent with drug-induced hepatotoxicity. Approximately half the patients treated with tacrine have liver enzyme abnormalities develop, primarily in the first 12 weeks of therapy, that resolve with discontinuation of drug or dosage adjustment. Our case of tacrine-associated hepatotoxicity 14 months after the initiation of treatment despite regular biochemical evaluation suggests the potential for delayed and fatal hepatotoxicity with tacrine.