Janus Ong‡

Purpose Selective internal radiation therapy or radioembolization (RE) shows efficacy in unresectable hepatocellular carcinoma (HCC) limited to the liver. This study compared the safety and efficacy of RE and sorafenib in patients with locally advanced HCC. Patients and Methods SIRveNIB (selective internal radiation therapy v sorafenib), an open-label, investigator-initiated, phase III trial, compared yttrium-90 (Y) resin microspheres RE with sorafenib 800 mg/d in patients with locally advanced HCC in a two-tailed study designed for superiority/detriment. Patients were randomly assigned 1:1 and stratified by center and presence of portal vein thrombosis. Primary end point was overall survival (OS). Efficacy analyses were performed in the intention-to-treat population and safety analyses in the treated population. Results A total of 360 patients were randomly assigned (RE, 182; sorafenib, 178) from 11 countries in the Asia-Pacific region. In the RE and sorafenib groups, 28.6% and 9.0...

To determine the prevalence of hepatitis B surface antigen (HBsAg) seropositivity among adult Filipinos. Testing for HBsAg was performed on serum samples from persons aged ≥ 20 years old who participated in the National Nutrition and Health Survey (NNHeS) conducted in 2003. Information on age, sex, marital status, educational attainment, employment status, and income were collected. For this study, marital status was classified as never married or otherwise (i.e., married, divorced, separated, widowed); educational attainment was classified as high school graduate or below or at least some tertiary education; and employment status was classified as currently employed or currently unemployed. Annual income was divided into 4 quartiles in Philippine pesos (PhP): Q1, ≤ PhP 53064; Q2, PhP 53065-92192; Q3, PhP 92193-173387; and Q4, ≥ PhP 173388. Prevalence estimates were weighted so that they represented the general population. Social and demographic factors were correlated with HBsAg se...

Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. Most patients with cryptogenic cirrhosis are considered to have had "burned out NAFLD." Although the recurrence and progression of NAFLD after liver transplantation (LT) have been shown previously, the incidence of de novo NAFLD after LT has not been extensively reported. In this issue of the American Journal of Gastroenterology, Dumortier et al. report the incidence of de novo post-LT NAFLD. Although most of the risk factors for post-LT NAFLD are similar to those for primary NAFLD, hepatic steatosis in the donor livers and a pre-transplant diagnosis of alcoholic liver disease remain independent risk factors. Although there are some limitations, this study provides the largest cohort of patients for whom post-LT NAFLD is reported.

ABSTRACT Ascites is one of the most prevalent complications of cirrhosis. Ascites can hamper the patients’ quality of life as well as predispose them to develop spontaneous bacterial peritonitis. Paracentesis is often used for diagnostic as well as therapeutic purposes in the management of cirrhotics with ascites. It is often performed as an outpatient procedure with or without the aid of ultrasound marking and the preferred site is the left lower quadrant. Diagnostic paracentesis is needed to ascertain the etiology of ascites as well as to exclude spontaneous bacterial peritonitis. Therapeutic paracentesis, total or large volume, is employed to relieve patient discomfort in cases refractory or resistant to diuretics. While coagulopathy is common in cirrhosis, it is not a contraindication to paracentesis, unless there is evidence of hyperfibrinolysis. Post-paracentesis circulatory dysfunction can occur in 20% of patients after therapeutic paracentesis and should be prevented by using albumin infusion during the procedure. Paracentesis, both diagnostic and therapeutic, is an essential and safe procedure for the management of end-stage liver disease and cirrhosis.Copyright © 2011 S. Karger AG, Basel

Severe recurrent cholestatic hepatitis C after liver transplantation has a poor prognosis and no standard therapy is currently available. Four cases of severe recurrent cholestatic hepatitis C treated with a combination of interferon alpha 2b and ribavirin are described. All four patients were transplanted for hepatitis C-related cirrhosis. The mean age at transplantation was 45 years (range 41-51 years). Three of the patients were male and one was female. All four patients had hepatitis C virus viremia before and after liver transplantation. At 2 to 23 months after liver transplantation, all four patients developed jaundice, cholestatic elevation of liver enzymes, and histopathology consistent with severe recurrent cholestatic hepatitis C. Combination of interferon and ribavirin was given with prompt virological suppression. Despite this rapid viral suppression, all four patients developed progressive graft failure with three deaths.

Introduction: In our local setting, medical management of hepatic encephalopathy predominates due to various medical or social problems e.g. low economic profile, comorbidities associated with advancing age, etc. In view of the widespread importance of zinc and its role in the pathophysiologic mechanism of hepatic encephalopathy, this study aims to investigate the effect of oral zinc supplementation in improving the course of hepatic encephalopathy in chronic liver disease. Methods: All published randomized controlled trials regarding the use of zinc in hepatic encephalopathy were included in this study. Participants were adult patients (>18 y/o) identified with hepatic encephalopathy from chronic liver disease. Primary outcome was an improvement of mental status and secondary outcome was an increase in blood urea nitrogen and/or a decrease in serum ammonia levels. A systematic search of local and international electronic databases was done: (PubMed (January 1950-June 2012), Coch...

Background: Use of DA and FL for anemia and neutropenia of combination therapy for CHC may improve patients’ quality of life (HRQL) and adherence. Methods: Open label study of CHC patients treated with Pegylated Interferon α-2b (1.5 mcg/kg/wk) and Ribavirin (800-1400 mg/d). Patients who developed severe anemia [hemoglobin (Hgb) ≤ 10.5 g/dL] received DA [3 mcg/kg once every-two-wks] titrated to Hgb of 12 g/dL. Patients with significant neutropenia [absolute neutrophil count (ANC) ≤ 0.75 x109/L] received FL, dose titrated from 150 mcg SQ once a week to 300 mcg SQ thrice weekly, to keep ANC ≥ 0.75 X 109/L and < 10 x109/L. Clinical and HRQL data [Short-Form 36 (SF-36) and Chronic Liver Disease Questionnaire (CLDQ)] were assessed. Results: 60 patients were enrolled [Age 47.6± 8.9; 60% male; 60% Caucasians; 100% treatment-naïve, 55% HCV Genotype 1; HCV RNA 3.68 ± 5.54 million IU/ml, Hgb 14.7± 1.3 g/dL; ANC 3.77± 1.59 x 109/L]. By treatment week 12, 61.7% of patients experienced mild (H...

Case: A 33 year-old female with UC presented with severe abdominal pain, bloating, bloody diarrhea, and abnormal liver enzymes. A CT scan of the abdomen showed hepatomegaly, ascites, small bowel edema, and thrombosis of the hepatic, portal, superior mesenteric, ...

Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease in the United States. It describes several clinicopathologic entities from simple hepatic steatosis to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. This article describes the epidemiology, clinical features, natural history, and pathogenesis of NAFLD.

... pediatric patients with chronic liver disease, hemodialysis, homosexuals, parenteral drug users and blood donors, respectively.3 Mappala reported a ... Mechanism of carcinogenesis of HCV remains unclear because HCV does not incorporate its genome into the host genetic ...

Adipose tissue is an active endocrine organ that secretes a variety of metabolically important substances including adipokines. These factors affect insulin sensitivity and may represent a link between obesity, insulin resistance, type 2 diabetes (DM), and nonalcoholic fatty liver disease (NAFLD). This study uses real-time polymerase chain reaction (PCR) quantification of mRNAs encoding adiponectin, leptin, and resistin on snap-frozen samples of intra-abdominal adipose tissue of morbidly obese patients undergoing bariatric surgery. Morbidly obese patients undergoing bariatric surgery were studied. Patients were classified into two groups: Group A (with insulin resistance) (N=11; glucose 149.84 +/- 40.56 mg/dL; serum insulin 8.28 +/- 3.52 microU/mL), and Group B (without insulin resistance) (N=10; glucose 102.2 +/- 8.43 mg/dL; serum insulin 3.431 +/- 1.162 microU/mL). Adiponectin mRNA in intra-abdominal adipose tissue and serum adiponectin levels were significantly lower in Group A compared to Group B patients (P<0.016 and P<0.03, respectively). Although serum resistin was higher in Group A than in Group B patients (P<0.005), resistin gene expression was not different between the two groups. Finally, for leptin, neither serum level nor gene expression was different between the two groups. Serum adiponectin level was the only predictor of nonalcoholic steatohepatitis (NASH) in this study (P=0.024). Obese patients with insulin resistance have decreased serum adiponectin and increased serum resistin. Additionally, adiponectin gene expression is also decreased in the adipose tissue of these patients. This low level of adiponectin expression may predispose patients to the progressive form of NAFLD or NASH.

Rapid weight loss increases risk for gallstone formation. Prophylactic cholecystectomy is difficult. Several small trials have shown that ursodeoxycholic acid (UDCA) may prevent gallstone formation after bariatric surgery. The aim of this study is to assess the efficacy and safety of UDCA in the prevention of gallstone formation after bariatric surgery. Electronic databases, including the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Australasian Medical Index, LILACS, and HERDIN, were searched. Reference lists of trials selected by the above electronic searching were also searched. Authors of the retrieved trials and pharmaceutical companies were also contacted for other trials, published and unpublished. A meta-analysis of all randomized, double-blind, placebo-controlled prospective trials comparing UDCA and placebo was performed. Five RCTs including 521 patients were assessed. Random effects meta-analysis showed a significant reduction of gallstone formation (RR 0.43, 95% confidence interval 0.22-0.83), with 8.8% of those taking UDCA developing gallstones compared to 27.7% for placebo. Although this meta-analysis is heterogeneous with I(2) of 61.9%, the directions of the effect are all consistently in favor of UDCA (p=0.01). A meta-analysis on the adverse effects could not be performed because the studies did not report them in a way to make the analysis possible. UDCA can prevent gallstone formation after bariatric surgery.

Non-alcoholic fatty liver disease (NAFLD) is among the most common causes of chronic liver disease. NAFLD includes a spectrum of clinicopathologic syndromes that includes non-alcoholic steatohepatitis (NASH) that has potential for progression. The pathogenesis of NASH is poorly characterized. This study was designed to identify differences in hepatic gene expression in patients with NASH and to relate such differences to their clinical characteristics. Consecutive patients undergoing bariatric surgery were prospectively recruited. Extensive clinical data and two liver biopsy specimens were obtained at the time of enrollment. A single hepatopathologist reviewed and classified the liver biopsies. Patients with excessive alcohol use and other causes of liver disease were excluded. A group of 29 NASH patients, 12 with steatosis alone, seven obese controls and six non-obese controls were selected for further investigation. Customized cDNA microarrays containing 5220 relevant genes were designed specifically for this study. Microarray experiments were run in triplicate for each sample and a selected group of genes were confirmed using real-time PCR. Differential hepatic gene expressions in patients with NASH as compared with controls. Thirty-four genes with significant differential expression were identified in patients with NASH when compared with non-obese controls. Moreover, 19 of these genes showed no significant expression differences in obese vs. non-obese controls, suggesting a stronger association of these genes to NASH. Several differentially expressed genes in patients with NASH are related to lipid metabolism and extracellular matrix remodeling. Additionally, genes related to liver regeneration, apoptosis, and the detoxification process were differentially expressed. These findings may help clarify the molecular pathogenesis of NASH and identify potential targets for therapeutic intervention.

The natural history of non-alcoholic fatty liver disease (NAFLD) remains to be defined. We conducted a study to determine the overall and liver-related mortality of NAFLD in the general US population. In this study, the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES III-Linked Mortality File were used. Adjusted hazard ratios (HR) for overall and liver-related mortality were calculated for NAFLD using persons without liver disease as reference. Causes of death were determined. After a median follow-up of 8.7 years, 80 persons with NAFLD and 1453 without liver disease died. Older age, male gender, non-Hispanic white race, lower educational level, lower income, higher BMI, presence of hypertension, diabetes mellitus, or metabolic syndrome were significantly (p<0.05) associated with overall mortality. Persons with NAFLD had higher overall mortality [HR 1.038 (95% CI 1.036-1.041), P<0.0001] and liver-related mortality [HR 9.32 (95% CI 9.21-9.43), P<0.0001]. Liver disease was the third leading cause of death among persons with NAFLD after cardiovascular disease and malignancy. NAFLD is associated with higher overall and liver-related mortality in the general US population. Liver disease is a significant cause of death among persons with NAFLD.

Non-alcoholic fatty liver disease (NAFL) includes a spectrum of clinicopathological conditions with increasing prevalence in the developed world. Although steatosis alone seems to have a benign course, those patients with the diagnosis of non-alcoholic steatohepatitis (NASH) can have a progressive course. Additionally, there is now evolving, indirect evidence that some of the patients with cryptogenic cirrhosis may be the result of 'burned-out' NASH. Although NAFL and NASH are associated with insulin-resistance syndrome, some patients with NAFL may have no obvious risk factors. Despite preliminary data from a number of pilot studies, no established therapies can be offered to patients with NASH. Over the next few years, a number of exciting research projects dealing with the epidemiology as well as the pathogenesis of NAFL are expected to be completed. It is anticipated that, through a better understanding of NAFL, more effective treatment protocols can be developed targeting only those patients with NASH that are at the highest risk for progression to cirrhosis and liver failure.

There are no published data on the health insurance status of Hepatitis C virus (HCV)-positive individuals. To address this issue, we analyzed data from the Third National Health and Nutrition Examination Survey (NHANES III). Individuals 18 years of age and older who participated in NHANES III were included in the study. We determined the rates of health insurance coverage according to HCV status. We also determined healthcare status and health service utilization according to health insurance status among HCV-positive persons. HCV-positive individuals were more likely to be uninsured compared with those who were HCV-negative (29.6% vs. 12.2%, P = 0.0002). Among those with health insurance, HCV-positive individuals were more likely to have government insurance compared with those who were HCV-negative (42.9% vs. 27.6%, P < 0.005). Among HCV-positive individuals, being uninsured was associated with younger age, being unmarried, living in the South, Mexican-American race/ethnicity, and not graduating from high school. Additionally, the uninsured were less likely than their insured counterparts to identify a healthcare facility for sick or routine care, and less likely to have regular contact with a healthcare professional. A high proportion of HCV-positive individuals are uninsured, and many HCV-positive individuals with health insurance have publicly funded insurance. This finding may have implications for access to health care and for liver-related disease outcomes in HCV-positive persons.

Superimposed non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) may affect HCV-related fibrosis. We performed a study to determine the relationship between NAFLD and chronic hepatitis C. One hundred and twenty patients with chronic hepatitis C and available liver biopsies were included. Baseline liver biopsies were read by 1 hepatopathologist using Metavir, as well as a fatty liver pathology protocol. Patients' baseline clinical, demographic, and virologic data were associated with the extent of steatosis (>33% vs. < or =33%), the type of fatty liver (no steatosis vs. steatosis only vs. NASH), and the stage of fibrosis seen on the liver biopsy. Seventy percent of patients were men and 80% were white. The mean age was 47.48+/-5.70 years, mean BMI was 29.01 +/-5.01 kg/m, and mean waist to hip ratio (W/H) was 0.90+/-0.08. Patients with higher grade of steatosis had higher BMI (32.83+/-6.26 vs. 28.49+/-4.62, P = 0.034), more likely to have genotype 3 (21.4% vs. 5.7%, P = 0.037) and advanced fibrosis (92.9% vs. 62.3%, P = 0.033) than those with lower grade of steatosis. Of these, only HCV-genotype 3 remained independently associated with higher grade of steatosis. When patients with superimposed NASH (n = 22) were compared with those with only steatosis (n = 49) and those without steatosis (n = 49), patients with superimposed NASH had more evidence of obesity (BMI: 30.64+/-5.23 vs. 29.90+/-5.35 vs. 27.33+/-4.07, P = 0.008; W/H: 0.97+/-0.06 vs. 0.91+/-0.08 vs. 0.87+/-0.07, P < 0.001), more commonly infected with HCV genotype 3 (14% vs. 12% vs. 0%, P = 0.036) and had more advanced fibrosis (95.5% vs. 75.5% vs. 42.9%, P < 0.001). Race, gender, and age did not affect extent of steatosis or presence of superimposed NASH. In conclusion, markers of obesity (BMI and W/H) and HCV genotype 3 are associated with the extent of steatosis and type of fatty liver. Higher grade of steatosis and presence of superimposed NASH are both associated with advanced hepatic fibrosis.

To assess the efficacy and safety of maintenance therapy with ribavirin alone in chronic hepatitis C, 108 patients were treated with the combination of interferon alfa and ribavirin for 24 weeks; those who failed to have a virologic response were offered enrollment in a randomized, double-blind, controlled trial of ribavirin (1,000-1,200 mg daily) versus placebo for the subsequent 48 weeks. Patients were monitored at regular intervals with symptom questionnaires, serum aminotransferase levels, hepatitis C virus (HCV) RNA levels, and complete blood counts and underwent liver biopsy at the completion of therapy. Among 108 patients, 50 were still HCV RNA positive after 24 weeks of treatment, of whom 34 agreed to be randomized to continue either ribavirin monotherapy or placebo. Among 17 patients who received placebo, there was no overall improvement in symptoms, serum alanine aminotransferase (ALT) levels, HCV RNA levels, or hepatic histology. Among the 17 patients who received ribavirin, serum ALT levels and necroinflammatory features of liver histology were improved, whereas symptoms, HCV RNA levels, and hepatic fibrosis scores were not changed significantly from baseline. Responses to ribavirin seemed to be categorical, such that 8 patients (47%) had definite improvement in liver histology. Patients with improved histology had improvements in serum ALT levels both on combination therapy and after switching to ribavirin monotherapy. In conclusion, continuation of ribavirin monotherapy may maintain serum biochemical improvements that occur during interferon-ribavirin combination therapy in some patients and that these improvements are often associated with decreases in necroinflammatory changes in the liver. Whether these improvements will ultimately result in prevention of progression of hepatitis C requires further study.

ABSTRACT Recombivax-HB (REC) and Engerix-B (ENG) are FDA-approved vaccines for hepatitis B virus (HBV) in end-stage renal disease (ESRD). This study compares antibody response rates between them in routine clinical practice. Patients completing the recommended 40 mug dose of REC (3 doses) or ENG (4 doses) between January 1, 2000 to April 30, 2003 were eligible. Patients with prior positive HBV surface antigen (HBsAg) or antibody (HBsAb) test results were excluded. The conversion rate and persistence of protective titer (HBsAb titer>or=10 IU/mL) were tracked for 1 year. A supplemental analysis of a one-to-one matched patient sample was also performed. REC patients (N=885) were older, had longer dialysis vintage, and had a larger proportion of whites than ENG patients (N=13,661). Cumulative conversion response was greater in ENG (58%) than REC (40%) at 1 year (p<0.0001). The odds ratio for response to ENG compared with REC was 1.96 (95% limits: 1.56, 2.45; p<0.0001) adjusted for age, gender, race, diabetes, vintage, BSA, hemoglobin, and eKt/V. Persistent protective HBsAb after 1 year was 77% (ENG) vs. 53% (REC). HBsAg was positive in 208 ENG patients (1.5%) with all but 1 because of transient, vaccine-related antigenemia. The difference in conversion response favoring ENG persisted in a one-to-one sample matched for age, gender, race, modality, and dialysis vintage. The study found higher seroconversion response to ENG compared with REC at several time points up to 1 year. Protective HBsAb disappeared in 23-47% of patients 1 year later, validating CDC recommendations to re-test HBsAb yearly. The observed difference in response rates may be related to the extra ENG dose given at the second month (0, 1, 2, 6 regimen). The study raises a hypothesis that requires confirmation in a prospective clinical trial.