Kathleen E. Corey

Does a Surgical Antireflux Procedure Decrease the Incidence of Esophageal Adenocarcinoma in Barrett's Esophagus? A Meta-Analysis

OBJECTIVE:The risk of adenocarcinoma of the esophagus is increased among those with Barretts esophagus (BE). Whether the risk of cancer in the setting of BE can be decreased by a surgical antireflux procedure (SARP) is unclear. This study compared the reported incidence of esophageal adenocarcinoma in subjects with BE who underwent SARP with those with BE who had medical management.METHODS:We used MEDLINE to perform a meta-analysis of the English language literature published from 1966 through October 2001. We reviewed abstracts found with the search term “Barretts esophagus” and the following: “adenocarcinoma,”“esophageal neoplasm,”“proton pump inhibitor,”“fundoplication,” or “antireflux procedure.” Study entry criteria included 1) trial or cohort study with a report of cancer risk expressible in cancers per patient-year, 2) histologic confirmation of BE and any adenocarcinomas, and 3) adequate description of intervention (medical vs SARP). Data were abstracted by two reviewers using standardized forms. Subgroup comparisons were made using only medical management studies published in the last 5 yr. Multivariable regression controlling for subject age, country of origin, and BE length was performed.RESULTS:We reviewed 1247 abstracts, and 34 met the inclusion criteria. There were a cumulative 4678 patient-years of follow-up in the SARP group and 4906 patient-years in the medical group. The cancer incidence rate in the SARP group was 3.8 cancers/1000 patient-years, compared with 5.3 in the medical group (p = 0.29). Similarly, there was no significant difference between cancer rates when comparing SARP with medical series reported in the last 5 yr (3.8/1000 patient-years vs 4.2/1000 patient-years, p = 0.33). Multivariate analysis controlling for subject age, country of origin, and BE length did not alter these findings.CONCLUSION:The reported risk of adenocarcinoma in subjects with BE is low and not significantly decreased by a surgical antireflux procedure. Antireflux surgery in the setting of BE should not be recommended as an antineoplastic measure.

Hepatitis C virus infection and its clearance alter circulating lipids: implications for long-term follow-up.

Hepatitis C associated hypolipidemia has been demonstrated in studies from Europe and Africa. In two linked studies, we evaluated the relationship between hepatitis C infection and treatment with lipid levels in an American cohort and determined the frequency of clinically significant posttreatment hyperlipidemia. First, a case‐control analysis of patients with and without hepatitis C was performed. The HCV Group consisted of 179 infected patients. The Uninfected Control Group consisted of 180 age‐matched controls. Fasting cholesterol, low density lipoprotein (LDL), high density lipoprotein and triglycerides were compared. Next was a retrospective cohort study (Treated Hepatitis C Group) of 87 treated hepatitis C patients with lipid data before and after therapy was performed. In the case‐control analysis, the HCV Group had significantly lower LDL and cholesterol than the Uninfected Control Group. In the retrospective cohort, patients in the Treated Hepatitis C Group who achieved viral clearance had increased LDL and cholesterol from baseline compared to patients without viral clearance. These results persisted when adjusted for age, sex, and genotype. 13% of patients with viral clearance had increased LDL and 33% experienced increases in cholesterol to levels warranting lipid lowering therapy. Conclusion: Hepatitis C is associated with decreased cholesterol and LDL levels. This hypolipidemia resolves with successful hepatitis C treatment but persists in nonresponders. A significant portion of successfully treated patients experience LDL and cholesterol rebound to levels associated with increased coronary disease risk. Lipids should be carefully monitored in persons receiving antiviral therapy. (HEPATOLOGY 2009;50:1030–1037.)

Early Treatment Improves Outcomes in Acute Hepatitis C Virus Infection: A Meta-Analysis

Summary.  Acute hepatitis C virus infection is associated with high rates of spontaneous clearance and variable rates of treatment‐induced clearance. The benefit of early treatment versus awaiting spontaneous clearance is unknown, as is the optimal timing of treatment.We performed a MEDLINE and EMBASE search for the time period 1950 to October 2008. All English language abstracts using the search terms acute hepatitis C, hepatitis C and acute and hepatitis C and acute disease or acute infection were reviewed. Bibliographies were reviewed.Twenty‐two studies including 1075 patients met the inclusion criteria. The sustained virologic response (SVR) rate for treated patients was 78%, significantly higher than 55.1% in untreated patients (OR = 3.08, 95% CI: 1.8–4.8 P value <0.0001). Mean time from diagnosis to spontaneous clearance was 9.7 weeks (SD 6.5). SVR rates varied inversely with time from acute HCV diagnosis. SVR rates for treatment within 12 weeks was 82.5% (95% CI: 75.6–89.3), significantly better than the clearance rates in untreated patients (P < 0.001). Response rates fell to 66.9% for treatment between 12 and 24 weeks, and decreased further to 62.5% for treatment beyond 24 weeks. Rates of viral clearance in treated patients with acute hepatitis C virus infection were significantly higher than that in untreated patients. Treatment rates were highest when treatment was initiated within 12 weeks of diagnosis. Based on these findings, we would advocate a 12 week period of observation for spontaneous clearance before treatment initiation. If no clearance has occurred by 12 weeks, treatment should be initiated.

Secondary causes of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is becoming the most common cause of chronic liver disease in the developing world, found in 17-30% of the population in Western countries and 2-4% worldwide. Defined as the accumulation of fatty acid content greater than 5% of liver weight, NAFLD is a spectrum of disease ranging from simple steatosis to nonalcoholic steatohepatitis. The pathophysiology of NAFLD involves increased de novo synthesis of fatty acids in hepatocytes, the retention of lipids due to impaired hepatocyte apolipoprotein secretion or beta-oxidation. The well-known primary causes of NAFLD are obesity, type II diabetes, dyslipidemia, and insulin resistance. However, other less common conditions can cause a similar clinical and histologic picture, and should be considered in patients who present with NAFLD but do not have traditional risk factors. In this review, we discuss uncommon but important causes of NAFLD, including inborn errors of metabolism, iatrogenic causes, viral hepatitis, and nutritional disorders to provide practicing clinicians with an understanding of the less well recognized causes of NAFLD.

Human monoclonal antibody MBL-HCV1 delays HCV viral rebound following liver transplantation: a randomized controlled study.

Rapid allograft infection complicates liver transplantation (LT) in patients with hepatitis C virus (HCV). Pegylated interferon‐α and ribavirin therapy after LT has significant toxicity and limited efficacy. The effect of a human monoclonal antibody targeting the HCV E2 glycoprotein (MBL‐HCV1) on viral clearance was examined in a randomized, double‐blind, placebo‐controlled pilot study in patients infected with HCV genotype 1a undergoing LT. Subjects received 11 infusions of 50 mg/kg MBL‐HCV1 (n = 6) or placebo (n = 5) intravenously with three infusions on day of transplant, a single infusion on days 1 through 7 and one infusion on day 14 after LT. MBL‐HCV1 was well‐tolerated and reduced viral load for a period ranging from 7 to 28 days. Median change in viral load (log10 IU/mL) from baseline was significantly greater (p = 0.02) for the antibody‐treated group (range −3.07 to −3.34) compared to placebo group (range −0.331 to −1.01) on days 3 through 6 posttransplant. MBL‐HCV1 treatment significantly delayed median time to viral rebound compared to placebo treatment (18.7 days vs. 2.4 days, p < 0.001). As with other HCV monotherapies, antibody‐treated subjects had resistance‐associated variants at the time of viral rebound. A combination study of MBL‐HCV1 with a direct‐acting antiviral is underway.

Shear-Wave Elastography for the Estimation of Liver Fibrosis in Chronic Liver Disease: Determining Accuracy and Ideal Site for Measurement

PURPOSE To evaluate the accuracy of shear-wave elastography (SWE) for staging liver fibrosis in patients with diffuse liver disease (including patients with hepatitis C virus [HCV]) and to determine the relative accuracy of SWE measurements obtained from different hepatic acquisition sites for staging liver fibrosis. MATERIALS AND METHODS The institutional review board approved this single-institution prospective study, which was performed between January 2010 and March 2013 in 136 consecutive patients who underwent SWE before their scheduled liver biopsy (age range, 18-76 years; mean age, 49 years; 70 men, 66 women). Informed consent was obtained from all patients. SWE measurements were obtained at four sites in the liver. Biopsy specimens were reviewed in a blinded manner by a pathologist using METAVIR criteria. SWE measurements and biopsy results were compared by using the Spearman correlation and receiver operating characteristic (ROC) curve analysis. RESULTS SWE values obtained at the upper right lobe showed the highest correlation with estimation of fibrosis (r = 0.41, P < .001). Inflammation and steatosis did not show any correlation with SWE values except for values from the left lobe, which showed correlation with steatosis (r = 0.24, P = .004). The area under the ROC curve (AUC) in the differentiation of stage F2 fibrosis or greater, stage F3 fibrosis or greater, and stage F4 fibrosis was 0.77 (95% confidence interval [CI]: 0.68, 0.86), 0.82 (95% CI: 0.75, 0.91), and 0.82 (95% CI: 0.70, 0.95), respectively, for all subjects who underwent liver biopsy. The corresponding AUCs for the subset of patients with HCV were 0.80 (95% CI: 0.67, 0.92), 0.82 (95% CI: 0.70, 0.95), and 0.89 (95% CI: 0.73, 1.00). The adjusted AUCs for differentiating stage F2 or greater fibrosis in patients with chronic liver disease and those with HCV were 0.84 and 0.87, respectively. CONCLUSION SWE estimates of liver stiffness obtained from the right upper lobe showed the best correlation with liver fibrosis severity and can potentially be used as a noninvasive test to differentiate intermediate degrees of liver fibrosis in patients with liver disease.

The effect of angiotensin-blocking agents on liver fibrosis in patients with hepatitis C.

Background: Multiple studies implicate the renin–angiotensin system in hepatic fibrogenesis. Few studies have examined the effects of angiotensin blockade on liver fibrosis via human histology.

Obesity and Liver Disease: The Epidemic of the Twenty-First Century

Obesity is a rapidly growing health problem that is associated with more than 65 comorbidities and results in substantially increased all-cause mortality. The increase of obesity has played an important role in the increasing prevalence of nonalcoholic fatty liver disease (NAFLD), the most common cause of liver disease in the United States. Understanding the prevalence, comorbidities, and pathogenesis of obesity provides an essential foundation for clinicians who care for individuals with NAFLD.

Lipid metabolite profiling identifies desmosterol metabolism as a new antiviral target for hepatitis C virus

Hepatitis C virus (HCV) infection has been clinically associated with serum lipid abnormalities, yet our understanding of the effects of HCV on host lipid metabolism and conversely the function of individual lipids in HCV replication remains incomplete. Using liquid chromatography-mass spectrometry metabolite profiling of the HCV JFH1 cell culture infection model, we identified a significant steady-state accumulation of desmosterol, an immediate precursor to cholesterol. Pharmacological inhibition or RNAi-mediated depletion of DHCR7 significantly reduced steady-state HCV protein expression and viral genomic RNA. Moreover, this effect was reversed when cultures were supplemented with exogenous desmosterol. Together, these observations suggest an intimate connection between HCV replication and desmosterol homeostasis and that the enzymes responsible for synthesis of desmosterol may be novel targets for antiviral design.

Hepatitis B screening, prophylaxis and re-activation in the era of rituximab-based chemotherapy

Background: Hepatitis B re‐activation is a well‐described complication in patients with inactive chronic hepatitis B receiving chemotherapy. Screening for HBV and pre‐emptive therapy are recommended. However, the rates of HBV screening, prophylaxis and re‐activation during rituximab‐containing chemotherapy are unknown.