Search

Cure of chronic hepatitis C (CHC) can lead to improvement of health-related quality of life and other patient-reported outcomes (PROs). While extensive PRO data for CHC patients who were enrolled in clinical trials are available, similar data for patients seen in real-world practices are scarce. Our aim was to assess PROs of CHC patients enrolled from real-world practices from different regions and to compare them with those enrolled in clinical trials. CHC patients seen in clinical practices and not receiving treatment were enrolled in the Global Liver Registry (GLR). Clinical and PRO (FACIT-F, CLDQ-HCV, WPAI) data were collected and compared with the baseline data from CHC patients enrolled in clinical trials. N = 12,171 CHC patients were included (GLR n = 3146, clinical trial subjects n = 9025). Patients were from 30 countries from 6 out of 7 Global Burden of Disease (GBD) super-regions. Compared with clinical trial enrollees, patients from GLR were less commonly enrolled from High-Income GBD super-region, older, more commonly female, less employed, had more type 2 diabetes, anxiety and clinically overt fatigue but less cirrhosis (all p 0.05). In conclusion, hepatitis C patients seen in the real-world practices have PRO impairment driven by fatigue and psychiatric comorbidities.

There are limited data to provide better understanding of the knowledge/awareness of general population towards liver health in Asia. We sought to identify the knowledge gaps and attitudes towards liver health and liver diseases as well as evaluate associated individual-level and macro-level factors based on contextual analysis. An online survey assessing knowledge, awareness and attitudes towards liver health and disease was conducted among 7500 respondents across 11 countries/territories in Asia. A liver index was created to measure the respondents' knowledge level and the degree of awareness and attitudes. Multilevel logistic regression was performed to identify individual factors and contextual effects that were associated with liver index. The overall liver index (0-100-point scale) was 62.4 with 6 countries/territories' liver indices greater than this. In the multilevel model, the inclusion of geographical information could explain for 9.6% of the variation. Residing in a country/territory with higher HBV prevalence (80% IOR: 1.20-2.79) or higher HCV death rate (80% IOR: 1.35-3.13) increased the individual probability of obtaining a high overall liver index. Individual factors like age, gender, education, household income, disease history and health screening behaviour were also associated with liver index (all p-values0.001). The overall liver index was positively associated with the two macro-level factors viz. HBV prevalence and HCV death rate. There is a need to formulate policies especially in regions of lower HBV prevalence and HCV death rate to further improve the knowledge, awareness and attitudes of the general public towards liver diseases.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide.1,2 It is believed that about one fourth of the world population may have NAFLD.3 The Global Burden of Disease data suggest that NAFLD and nonalcoholic steatohepatitis (NASH) are the main drivers of liver disease burden in most regions of the world, including that of hepatocellular carcinoma (HCC).4,5.

[Background & Aims] Globally, nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. We assessed the clinical presentation and patient-reported outcomes (PROs) among NAFLD patients from different countries., [Methods] Clinical, laboratory, and PRO data (Chronic Liver Disease Questionnaire–nonalcoholic steatohepatitis [NASH], Functional Assessment of Chronic Illness Therapy–Fatigue, and the Work Productivity and Activity Index) were collected from NAFLD patients seen in real-world practices and enrolled in the Global NAFLD/NASH Registry encompassing 18 countries in 6 global burden of disease super-regions., [Results] Across the global burden of disease super-regions, NAFLD patients (n = 5691) were oldest in Latin America and Eastern Europe and youngest in South Asia. Most men were enrolled at the Southeast and South Asia sites. Latin America and South Asia had the highest employment rates (>60%). Rates of cirrhosis varied (12%–21%), and were highest in North Africa/Middle East and Eastern Europe. Rates of metabolic syndrome components varied: 20% to 25% in South Asia and 60% to 80% in Eastern Europe. Chronic Liver Disease Questionnaire–NASH and Functional Assessment of Chronic Illness Therapy–Fatigue PRO scores were lower in NAFLD patients than general population norms (all P < .001). Across the super-regions, the lowest PRO scores were seen in Eastern Europe and North Africa/Middle East. In multivariate analysis adjusted for enrollment region, independent predictors of lower PRO scores included younger age, women, and nonhepatic comorbidities including fatigue (P < .01). Patients whose fatigue scores improved over time experienced a substantial PRO improvement. Nearly 8% of Global NAFLD/NASH Registry patients had a lean body mass index, with fewer metabolic syndrome components, fewer comorbidities, less cirrhosis, and significantly better PRO scores (P < .01)., [Conclusions] NAFLD patients seen in real-world practices in different countries experience a high comorbidity burden and impaired quality of life. Future research using global data will enable more precise management and treatment strategies for these patients.

Background & Aims The profile of chronic liver disease (CLD) in the United States has changed due to obesity trends and advances in treatment of viral hepatitis. We assessed liver transplant listing trends by CLD etiology. Methods Adult candidates for liver transplantation were selected from the Scientific Registry of Transplant Recipients (2002 through 2019). We calculated proportion trends for common CLD etiologies at time of placement on the wait list, including chronic infection with hepatitis B virus, chronic infection with hepatitis C virus (HCV), nonalcoholic steatohepatitis (NASH, including cryptogenic cirrhosis), alcohol-related liver disease (ALD) without or with chronic HCV infection, autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis, in patients with and without hepatocellular carcinoma (HCC). Results From the 168,441 patients with known etiology and non-acute liver failure on the liver transplant waitlist, 27,799 patients (16.5%) had HCC. In 2002, the most common etiologies in patients without HCC were chronic HCV infection (37%) and ALD (16%), whereas only 5% had NASH. Among patients with HCC, 58% had chronic HCV infection and 10% had ALD and only 1% had NASH. In 2019, among patients without HCC, NASH was the second leading indication for liver transplantation (28% of patients), after ALD (38% of patients). Among patients with HCC, chronic HCV infection remained the leading indication (40% of patients) but NASH (24% of patients) surpassed ALD (16% of patients) to become the second leading indication. NASH was the leading indication in women without HCC (34%), in patients older than 54 years (36%), and in patients on Medicare (41%). In trend analysis, NASH was the most rapidly increasing indication for liver transplantation in patients without HCC (Kendall tau=0.97; P Conclusions In an analysis of data from the Scientific Registry of Transplant Recipients (2002 through 2019), we found NASH to be the second most common indication for liver transplant in 2019, and the fastest increasing indication. In 2019, NASH was the leading indication for liver transplantation among women without HCC.

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 (90Y) 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%, respectively, failed to receive assigned therapy without significant cross-over to either group. Median OS was 8.8 and 10.0 months with RE and sorafenib, respectively (hazard ratio, 1.1; 95% CI, 0.9 to 1.4; P = .36). A total of 1,468 treatment-emergent adverse events (AEs) were reported (RE, 437; sorafenib, 1,031). Significantly fewer patients in the RE than sorafenib group had grade ≥ 3 AEs (36 of 130 [27.7%]) v 82 of 162 [50.6%]; P < .001). The most common grade ≥ 3 AEs were ascites (five of 130 [3.8%] v four of 162 [2.5%] patients), abdominal pain (three [2.3%] v two [1.2%] patients), anemia (zero v four [2.5%] patients), and radiation hepatitis (two [1.5%] v zero [0%] patients). Fewer patients in the RE group (27 of 130 [20.8%]) than in the sorafenib group (57 of 162 [35.2%]) had serious AEs. Conclusion In patients with locally advanced HCC, OS did not differ significantly between RE and sorafenib. The improved toxicity profile of RE may inform treatment choice in selected patients.

Multiple studies have shown a high prevalence of chronic hepatitis B (CHB) infection in the Philippines, not only in high-risk populations but also in the general population. The most recent national study estimated HBsAg seroprevalence to be 16.7%, corresponding to an estimated 7.3 million CHB adults. The factors underlying the high prevalence of CHB and its sequelae include the inadequate use of vaccination for prevention and the lack of treatment for many Filipinos. Because without medical monitoring and treatment of CHB the risk of progression to liver failure and death is 25-30%, the ultimate medical and societal costs will be very high if the Philippines fails to properly address hepatitis B infection. It will be very important to move forward with programs that can help to ensure universal vaccination of newborns, screening and vaccination nationwide, and monitoring and treatment for CHB persons. It will also be crucial to address transmission of HBV in the health-care setting (via contaminated needles and syringes and inadequately sterilized hospital equipment) and via injection drug use and tattooing. Because of the relatively low average per capita income and the lack of coverage by PhilHealth of outpatient visits and medications, there is an urgent need to move forward with a nationally supported program that includes education for both the general public and health-care workers on liver disease and screening for hepatitis viruses, followed by, as appropriate, vaccination or treatment, with expanded government coverage for these for all those who could not otherwise afford it.

Background & Aims Non-alcoholic and alcohol-related fatty liver disease are overlapping diseases in which metabolic syndrome and alcohol consumption each contribute to progressive liver disease. We aimed to assess the effects of alcohol consumption and metabolic syndrome on mortality in individuals with fatty liver. Methods We searched the National Health and Nutrition and Examination Survey III for adults (20–74 years old) with hepatic steatosis, detected by ultrasound, for whom mortality and follow-up data were available. We collected data from the alcohol use questionnaire (self-reported number of days a participant drank alcohol; the number of drinks [10 g alcohol] per day on a drinking day; the number of days the participant had 5 or more drinks) and calculated the average amount of alcohol consumption in drinks/day for each participant during the year preceding enrollment. Excessive alcohol consumption for men was >3 drinks/day and for women was >1.5 drinks/day. We also collected clinical data, and mortality data were obtained from the National Death Index. Demographic and clinical parameters were compared among consumption groups using the χ2 test for independence or survey regression models. We used Cox proportional hazard models to identify independent predictors of all-cause and cause-specific mortality. Results The study cohort included 4264 individuals with hepatic steatosis (mean age, 45.9 years; 51% male; 76% white; 46% with metabolic syndrome; 6.2% with excessive alcohol use). There was no significant difference in mean age between individuals with vs without excessive alcohol consumption (P=.65). However, overall mortality was significantly higher among participants with excessive alcohol consumption (32.2%) vs participants with non-excessive alcohol use (22.2%) after mean 20 years of follow up (P=.003), as well as after 5 years of follow up. In multivariate analysis, the presence of metabolic syndrome (adjusted hazard ratio [aHR], 1.43; 95% CI, 1.12–1.83) and excessive alcohol consumption (aHR, 1.79; 95% CI, 1.21–2.66) were independently associated with an increased risk of death in individuals with hepatic steatosis; any lower average amount of alcohol consumption was not associated with mortality (all P>.60). In a subgroup analysis, the association of excessive alcohol use with mortality was significant in individuals with metabolic syndrome (aHR, 2.46; 95% CI, 1.40–4.32) but not without it (P=.74). Conclusion In review of data from the National Health and Nutrition and Examination Survey III, we associated alcohol consumption with increased mortality in participants with fatty liver and metabolic syndrome. These findings indicate an overlap between non-alcoholic and alcohol-related fatty liver disease.

Background and Objective: Hepatic encephalopathy (HE) is a serious complication of cirrhosis. Clinical trials have consistently shown that L-ornithine-L-aspartate significantly improves HE symptoms. Health-related quality of life (HR-QOL) is impaired in HE patients and represents an important outcome measure for therapeutic intervention. The present study aimed to assess the impact of L-ornithine-L-aspartate on HR-QOL and safety in patients with HE in a clinical practice setting. Methods: This was an open-label, prospective, multicentre observational study in clinical practice (general practitioners in Germany) that included 191 cirrhotic patients with HE. Patients were administered three sachets daily of L-ornithine-L-aspartate 6 g (Hepa-Merz®, Merz Pharmaceuticals GmbH, Frankfurt/Main, Germany) dissolved in water taken during or after meals. L-ornithine-L-aspartate was administered over a period of 8 weeks. The main outcome variable was the mean change in HR-QOL over the observation period as assessed by the patients using the German-validated version of the Chronic Liver Disease Questionnaire (CLDQ-D). Further assessments included mean changes in the severity of cirrhosis/HE-related symptoms, changes in disease severity (measured on the modified Clinical Global Impression-Severity [CGI-S] scale), and changes in disease status (measured on the modified CGI-Improvement [CGI-I] scale). Results: Treatment with L-ornithine-L-aspartate for 8 weeks markedly improved all HR-QOL domains, in particular fatigue (67.5% improvement), resulting in a mean ± SD CLDQ-D sum score improvement from 3.53 ± 1.03 at baseline to 5.04 ± 0.93 at the end of treatment. Symptom severity also improved, with particular benefits seen in fatigue, sleep quality and concentration deficits. Patient self-assessment correlated well with the physicians’ clinical evaluation. Physicians rated 70.0% of the patients very much or much improved at the end of treatment. Very good or good tolerability was observed in 97.8% of patients. No drug-related adverse events were reported. Conclusion: Treatment of HE with oral L-ornithine-L-aspartate in cirrhotic patients markedly improved HR-QOL and was well tolerated by 97.8% of patients.

Background/Aims 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. Methods 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. Results 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 P P Conclusions 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.

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.

Multiple studies have shown a high prevalence of chronic hepatitis B (CHB) infection in the Philippines, not only in high-risk populations but also in the general population. The most recent national study estimated HBsAg seroprevalence to be 16.7%, corresponding to an estimated 7.3 million CHB adults. The factors underlying the high prevalence of CHB and its sequelae include the inadequate use of vaccination for prevention and the lack of treatment for many Filipinos. Because without medical monitoring and treatment of CHB the risk of progression to liver failure and death is 25-30%, the ultimate medical and societal costs will be very high if the Philippines fails to properly address hepatitis B infection. It will be very important to move forward with programs that can help to ensure universal vaccination of newborns, screening and vaccination nationwide, and monitoring and treatment for CHB persons. It will also be crucial to address transmission of HBV in the health-care setting (via contaminated needles and syringes and inadequately sterilized hospital equipment) and via injection drug use and tattooing. Because of the relatively low average per capita income and the lack of coverage by PhilHealth of outpatient visits and medications, there is an urgent need to move forward with a nationally supported program that includes education for both the general public and health-care workers on liver disease and screening for hepatitis viruses, followed by, as appropriate, vaccination or treatment, with expanded government coverage for these for all those who could not otherwise afford it.

Background/Aims Hepatitis C (HCV) infected patients have significant health-related quality of life (HRQL) impairment which worsens during anti-viral therapy. Our aim was to examine the association of HRQL with treatment-induced depression and anemia. Methods Two hundred and seventy-one HCV patients who received pegylated interferon alfa 2b and ribavirin were included. Data on HRQL, depressive symptoms, laboratory values and socio-demographic characteristics were collected. Results Mean age was 47.1±6.5, 69% were male, and 73% were White. HCV patients' HRQL declined during anti-viral therapy but returned to or exceeded baseline levels within 24 weeks of completion. Anemia and depression were both associated with HRQL impairment. The effects of depression on HRQL were strong; once depression scores were included other factors were no longer significant. Patients' depressive symptoms tended to increase during the initial half of treatment regimen. Those with higher body mass index (BMI), cirrhosis, and women reported more HRQL impairments. HRQL scales were generally not associated with alcohol abuse, age, race, ALT and HCV RNA levels. Conclusions Anti-viral therapy for HCV is associated with diminished HRQL. Although anemia and depression were associated with this impairment, depression was the most consistent predictor. Future studies are needed to see whether proactive management of these side effects can improve patients' HRQL and the efficacy of antiviral therapy for hepatitis C.

Background and Goals: 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). Study: 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. Results: 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. Conclusions: 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.

Background: 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. Aim: This study was designed to identify differences in hepatic gene expression in patients with NASH and to relate such differences to their clinical characteristics. Design: 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. Outcome Measure: Differential hepatic gene expressions in patients with NASH as compared with controls. Results: 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. Conclusions: 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.

In an attempt to improve the efficacy of antiviral therapy for chronic hepatitis C, a three-drug combination of pegylated interferon alpha-2b, ribavirin, and amantadine has been suggested. Despite the initial enthusiasm, the role of amantadine in the treatment of chronic hepatitis C remains controversial. In a multi-center, open-label clinical trial, the potential efficacy and safety of this triple combination regimen were assessed. In this open-label pilot study, two separate patient populations with chronic hepatitis C and viremia were enrolled: treatment-naive and those who had failed a previous course of treatment. Patients were started on pegylated interferon alpha-2b at a dose of 1.5 microg/kg weekly with ribavirin, 1000-1200 mg/day, and amantadine, 200 mg/day, for 4 weeks, followed by pegylated interferon alpha-2b, 0.5 microg/kg weekly, ribavirin, 1000-1200 mg/day, and amantadine, 200 mg/day, for another 20 weeks. Patients with undetectable HCV RNA at week 24 continued this regimen for a total of 48 weeks and were followed for another 24 weeks. Patients with undetectable virus (50 IU/mL) after 24 weeks of follow-up were considered to have SVR. Health-related quality of life and safety data were also collected. Sixty-nine treatment-naive and 99 nonresponder patients with chronic hepatitis C were enrolled in the study. Of all patients enrolled, 74% were male, aged 47.27+/-5.76 years; their body mass index (BMI) was 28.87+/-5.05 kg/m2, 79.4% were white, 85% had HCV genotypes 1 and 4, and 36% had cirrhosis. Their baseline HCV RNA was 689,242+/-698,030 IU/mL, with a baseline ALT of 107.25+/-79.08. Of the entire cohort, 35 (21%) discontinued early due to side effects or loss to follow-up. Significant anemia (hemoglobin,10 g/dL) occurred in 11% (19/168), while severe anemia (hemoglobin,8.5 g/dL) occurred in 0.6% (1/168). In the treatment-naive group, sustained virologic response (SVR) was 34.3%, versus 19.4% for the group who had previously failed to respond to a course of treatment (P = 0.01). For both groups combined, virologic response after 24 weeks of therapy was 40.5%, with an end-of-treatment virologic response of 35.7% and a SVR of 26.2%. Patients with genotypes 1 and 4 had lower response rates than those with genotypes 2 and 3 (SVR, 21 vs. 46%; P = 0.001). Patients with advanced fibrosis (Metavir stages 3 and 4) tended to have lower response rates than those with minimal or mild fibrosis (Metavir stages 0-2) (SVR, 10 vs. 30%; P = 0.08). African-American patients with HCV had lower response rates than Caucasians or other ethnic groups (SVR, 4 vs. 29 vs. 20%; P = 0.04). Age, gender, and BMI did not affect SVR. The addition of amantadine to pegylated interferon alpha-2b and ribavirin does not seem to increase the efficicacy of this regimen.

Background: Nonalcoholic fatty liver disease (NAFLD) is a common form of chronic liver disease in the United States. It is commonly associated with the components of the metabolic syndrome including obesity. From the spectrum of NAFLD, only patients with nonalcoholic steatohepatitis (NASH) have been convincingly shown to have a potential for progression to cirrhosis. We report the prevalence of NAFLD and NASH as well as predictors of NASH and advanced fibrosis in morbidly obese patients. Methods: 212 consecutive patients who underwent bariatric surgery were enrolled in the study. A liver biopsy was performed at the time of the surgery. Causes of chronic liver disease other than NAFLD were excluded by clinical and laboratory evaluation. Results: The prevalence of NAFLD was 93%. Of those with NAFLD, 26% had NASH. 17 patients (9%) had advanced fibrosis (i.e., bridging fibrosis or cirrhosis). Male gender, AST, and type 2 diabetes mellitus were independently associated with NASH. Waistto-hip ratio, AST, and focal hepatocyte necrosis on liver biopsy were independently associated with advanced fibrosis. Interestingly, while AST was associated with NASH and advanced fibrosis, the majority of the patients with either NASH or advanced fibrosis had normal AST. Conclusions: NAFLD and NASH are very common in morbidly obese patients undergoing bariatric surgery. Features associated with the metabolic syndrome and liver cell injury are independently associated with either NASH or advanced fibrosis.

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, P0.001), 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%, P0.001). 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.

Background & Aims: This prospective study evaluates the role of radiological modalities in establishing the diagnosis of nonalcoholic steatohepatitis (NASH). Methods: Consecutive patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) were enrolled (2000–2001). Patients with other liver diseases and significant alcohol consumption (>20 g/day) were excluded. Clinicodemographic data were gathered at the time of liver biopsy. Each biopsy specimen was assessed by a hepatopathologist. Each patient underwent a limited abdominal ultrasonography (US), computerized tomography (CT), and magnetic resonance imaging (MRI). Films were interpreted by a radiologist who used a predetermined radiological protocol. Each radiological study was reread by the same radiologist and a second radiologist. Results: Patients with NASH had greater aspartate aminotransferase levels ( P = 0.03), greater ferritin levels ( P = 0.05), more hepatocyte ballooning ( P P = 0.002). None of the radiological features distinguished between NASH and other types of NAFLD. No radiological modality detected the presence of hepatocyte ballooning, Mallory's hyaline, or fibrosis, which are important features in the diagnosis of NASH. The presence of >33% fat on liver biopsy was optimal for detecting steatosis on radiological imaging. Conclusions: Differences between NASH and nonprogressive NAFLD were not apparent with any radiological modality. Of the pathologic features important for establishing the diagnosis of NASH, only the severity of steatosis was reflected in these radiological modalities. Good intraobserver agreement was evident for each modality (US, CT, and MRI) that was superior to interobserver agreement. GASTROENTEROLOGY 2002;123:745-750

Background/Aims: Hepatitis C and nonalcoholic fatty liver disease (NAFL) are the two most common forms of liver disease in the United States. Recently, obesity and its associated risk factors have been suggested to enhance HCV-related fibrosis. The aim of this study was to assess the impact of hepatic steatosis, steatohepatitis, and its associated risk factors on HCV-related fibrosis. Methods: Patients with untreated, biopsy-proven, chronic hepatitis C (6/97–3/99) were included. Clinical and demographic data at the time of liver biopsy were obtained from chart review and verified by telephone survey. One hepatopathologist reviewed all pathologic specimens, using the modified histological activity index score and the Ishak staging for fibrosis and a NAFL pathologic protocol. Results: One hundred and seventy patients with hepatitis C were included [age: 48.7±9.33 (years), body mass index (BMI): 28.1±5.7 (kg/m2) and type 2 diabetes mellitus (DM): 14%]. Of these, 77 (45.3%) had no or mild fibrosis and 93 (54.7%) had advanced fibrosis. Hepatic steatosis was seen in 90 (52.9%) patients. The grade of steatosis was associated with markers of obesity only. Age (p=0.002), type 2 DM (p=0.04), and superimposed steatohepatitis (p=0.047) were independently associated with advanced fibrosis. Superimposed nonalcoholic steatohepatitis (NASH) was seen in 17 (10%) patients. Patients with superimposed NASH were mostly obese (76.5%), males (62%) with 16% having type 2 diabetes and a BMI 33.8±7.12. Conclusion: In patients with chronic hepatitis C, type 2 DM and superimposed steatohepatitis are independently associated with advanced fibrosis.

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.

Since the introduction of transjugular intrahepatic portosystemic shunt (TIPS) 10 years ago, it has been used increasingly in the management of portal hypertension and its complications. TIPS is now considered the procedure of choice for management of refractory variceal bleeding. Its role in the management of refractory ascites, hepatic hydrothorax, hepatorenal syndrome, and hepatopulmonary syndrome still awaits further prospective studies. The two main complications of TIPS are hepatic encephalopathy and shunt malfunction. Generally, TIPS stenosis or occlusion is a major drawback requiring routine surveillance of TIPS with doppler ultrasound. Venography with balloon dilation of the stent or placement of serial or parallel stents may be required in some cases. Promising modalities of preventing TIPS malfunction (e.g., brachy-therapy, covered stents, or anti-platelet derived growth factor) are currently being investigated.

The outcome of de novo hepatitis C virus (HCV) infection in heart transplant recipients of HCV-antibody positive organs is not known. The aim of the study was to determine the short-term outcome of de novo HCV infection in recipients of HCV-positive donor organs. HCV-antibody negative recipients of HCV-antibody positive hearts were identified from January 1, 1991 to February 28, 1998. Control patients matched for year of transplantation were also identified. Twenty-eight patients (22 males, mean age of 56 +/- 11 SD) received hearts from HCV-antibody-positive donors. The control group was similar to the patients in all clinical and demographic aspects. Twenty-three patients had detectable viremia by reverse-transcription polymerase chain reaction (RT-PCR). Of these 23 patients with de novo HCV infection, 7 (30%) developed HCV-related liver disease. Three patients (13%) had chronic hepatitis and 4 patients (17%) developed severe acute cholestatic hepatitis (ACH). Mycophenolate mofetil (MMF) use (P =.04) and high viral load at onset of acute liver disease (P =.02) were associated with ACH. Overall survival was similar between patients with de novo HCV infection and controls (P =.20). Development of ACH (P =.02) and MMF use (P =.0009) were associated with decreased survival in patients with de novo HCV infection. The present study showed that survival of patients with de novo HCV infection was similar to a matched control group. HCV-related severe ACH is associated with a poor short-term outcome in patients with de novo HCV infection. MMF use may be associated with a higher incidence of HCV-related severe ACH and a poor short-term outcome.

Selective digestive decontamination (SDD) involves the use of antibiotics to enhance the colonisation resistance of the gastrointestinal (GI) tract. This eradicates the Gram-negative organisms and fungi, if antifungals are used, which colonise the GI tract and subsequently cause infections in susceptible hosts. It has been used in patients who are critically ill and in intensive care units, in those who have multiple trauma or neutropenia and in bone marrow transplant recipients.

Nonalcoholic fatty liver disease (NAFLD) two decades later: are we smarter about its natural history?

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.

Objective: To describe the clinical characteristics of patients diagnosed with hepatocellular cancer admitted at the Philippine General Hospital from January 2001 to December 2006 Background: Hepatocellular carcinoma (HCC) is the third leading site of cancer in the Philippines. Although risk factors for HCC are already established, significance of risk factors may vary among regions. Diabetes has also not been examined as a risk factor among Filipinos. Methodology: This is a descriptive study with data collection done through chart review. All charts with the diagnosis of hepatocellular carcinoma admitted from 2001 to 2006 were retrieved from the Medical Records Section. Participants included all adult hepatocellular carcinoma patients, diagnosed with HCC either by: (1) biopsy or (2) mass > 2cm and elevated ?-fetoprotein >200. Demographic data, risk factors, and laboratory exams were collated. Descriptive statistics were generated using SPSS 15.0. Results: Two hundred twenty two patients were included in the study. Males outnumbered females (3.5:1). Majority were older than 50 years old. The most common symptom is abdominal pain. Two thirds had a history of drinking alcohol. Almost half were smokers. Thirty eight patients (40.0%) had previous hepatitis B and 66 patients (52.3%) had chronic Hepatitis B. Only 3 (6.2%) patients had hepatitis C infection. Two thirds had no evidence of cirrhosis. Thirteen percent of the population had diabetes mellitus while 20% of the HBsAg-negative patients had diabetes mellitus. Eighty seven percent were in the advanced stage and 11.7% were terminal stage. Conclusion: The most common risk factors for HCC are still hepatitis B infection and alcohol drinking. Diabetes mellitus deserves to be investigated as an important contributing factor to the development of HCC, especially in HBsAg-negative patients. Most patients belonged to late stages of the disease but a selection bias is recognized. Our study indicates the need for screening patients at risk so early-stage disease can be detected. Keywords : Hepatocellular carcinoma, ?-fetoprotein, risk factors, hepatitis, cirrhosis

Acute viral hepatitis is a term that is generally given to the disease condition attributed to a group of viruses that have the propensity to infect the liver and cause necroinflammation. Although these hepatotropic viruses share a common clinical presentation, they belong to different virus families, have different modes of transmission, and differ in their propensity to lead to chronic infection (Table 1.1). Evenas acute viral hepatitis remains an importantpublic healthproblem in the United States, it is noteworthy that there has been and continues to be a decline in the number of new infections of hepatitis A, B, and C (Table 1.2).1 It is important to keep in mind that there are a number of conditions that can have a clinical presentation consistent with an acute hepatitis – elevated serum aminotransferases with variable elevations in bilirubin levels. Aside from the hepatotropic viruses, other viruses such as the herpes viruses can also lead to acute hepatitis. The differential diagnoses for acute hepatitis include alcoholic hepatitis, acute Budd-Chiari syndrome, drug-induced liver injury, shock liver, autoimmune hepatitis, biliary obstruction, and Wilson’s disease (Table 1.3). A careful history and physical examination can usually point the clinician to the appropriate diagnostic evaluation to arrive at a correct diagnosis. This chapter will review the hepatotropic viruses – hepatitis A to E.

Understanding of the epidemiology and natural history of non-alcoholic fatty liver disease (NAFLD) has increased; it is the most common form of chronic liver disease in the Western world and increasing in importance in other parts of the world. Prevalence is expected to increase as obesity and diabetes epidemics evolve. The natural history of NAFLD depends on the histologic subtype. Those who have simple hepatic steatosis or nonspecific inflammation generally have a benign long-term prognosis, whereas non-alcoholic steatohepatitis (NASH) can progress to cirrhosis. NASH-related cirrhosis may have a similar prognosis as cirrhosis from other causes, leading to liver failure or hepatocellular carcinoma.

Background: 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. Methods: 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 μU/mL), and Group B (without insulin resistance) (N=10; glucose 102.2 ± 8.43 mg/dL; serum insulin 3.431 ± 1.162 μU/mL). Results: Adiponectin mRNA in intra-abdominal adipose tissue and serum adiponectin levels were significantly lower in Group A compared to Group B patients (P

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

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and some of its forms are progressive. This study describes the profiling of hepatic gene expression and serum protein content in patients with different subtypes of NAFLD. Liver biopsy specimens from 98 bariatric surgery patients were classified as normal, steatosis alone, steatosis with nonspecific inflammation, and nonalcoholic steatohepatitis (NASH). Microarray hybridizations were performed in triplicate and the microarray expression levels of a selected group of genes were confirmed using real-time quantitative reverse-transcriptase polymerase chain reaction. Serum protein profiles of the same patients were determined by SELDI-TOF mass spectrometry. Of 98 obese patients, 91 were diagnosed with NAFLD (12 steatosis alone, 52 steatosis with nonspecific inflammation, and 27 NASH), and 7 patients without NAFLD served as obese controls. Each group of NAFLD patients was compared with the obese controls, and 22 genes with more than twofold differences in expression levels were revealed. Proteomics analyses were performed for the same group comparisons and revealed twelve significantly different protein peaks. In conclusion, this genomic/proteomic analysis suggests differential expression of several genes and protein peaks in patients within and across the forms of NAFLD. These findings may help clarify the pathogenesis of NAFLD and identify potential targets for therapeutic intervention.

Background:This study investigates the expression patterns in human adipose tissue, and identifies genes that may be involved in the abnormal energy homeostasis. Methods: Subjects were prospectively recruited from morbidly obese patients undergoing bariatric surgery and from non-obese organ donors. Extensive clinical data and visceral fat specimens were obtained from each subject at the time of surgery. A group of 50 obese patients and 9 non-obese controls were selected for further study. Two custom two-color cDNA microarrays were produced with 40,173 human individual cDNA clones. Microarray experiments were performed for each sample, and a selected group of gene expression values were confirmed with real-time RT-PCR. Results: A comparison of gene expression profiles from obese and non-obese patients identified 1,208 genes with statistically significant differential expression between the 2 groups. Most prominent among these genes are multiple glycolysis enzyme encoding genes; others are involved in oxysterol biosynthesis and signaling, or are ATP-binding transporters and solute carriers. Conclusion: Differential gene expression in the adipose tissue of morbidly obese patients includes genes related to lipid and glucose metabolism, membrane transport, and genes promoting the cell cycle. These findings are a first step toward clarifying the molecular pathogenesis of obesity and identifying potential targets for therapeutic intervention.

Hematologic abnormalities such as anemia, neutropenia, and thrombocytopenia are common during combination therapy with pegylated (or standard) interferon and ribavirin for chronic hepatitis C. Ribavirin-induced hemolytic anemia is a common cause of dose reduction or discontinuation. Bone marrow suppression also contributes to the anemia and is the predominant mechanism for interferon-induced neutropenia and thrombocytopenia. Although dose reduction or discontinuation of combination therapy can reverse these abnormalities, they may reduce virologic response. Hematopoietic growth factors may provide a useful alternative for managing these hematologic side effects without reducing the optimal dose of the combination antiviral regimen. Treatment of anemia also may improve patients' health-related quality of life and their adherence to combination antiviral therapy. The impact of growth factors on sustained virologic response and their cost-effectiveness in patients with chronic hepatitis C need further assessment.

Nonalcoholic fatty liver disease (NAFLD) is common in patients with the metabolic syndrome, and it is expected to become more common in countries where obesity, one of the components of the metabolic syndrome, is increasing.

The organ allocation system for liver transplantation was recently changed to address criticisms that it was too subjective and relied too heavily on total waiting time. The new system, Model for End-Stage Liver Disease and Pediatric Model for End-Stage Liver Disease (MELD/PELD), stratifies patients based on the risk of 3-month pretransplant mortality, allocating livers thereby. There is concern that such a scheme gives priority to the sickest patients, who may not enjoy good posttransplant outcomes. The aim of the present study was to compare the outcomes of liver transplant recipients who had been admitted to the intensive care unit (ICU) to those who had not. Admission to the ICU is considered here to be another indicator of the severity of illness. Patients who underwent liver transplantation at the Cleveland Clinic between January 1, 1993 and October 31, 1998 and were at least 18 years of age were coded for liver transplantation as status 2, 2A, and 2B (n = 112). These patients fell into three groups: those who had been admitted to an ICU before transplantation (group A, n = 16), those who had been admitted to the hospital but not to an ICU (group B, n = 63), and those who were living at home and had undergone an elective transplant (group C, n = 33). Clinical and demographic information (age, sex, race, disease severity, disease etiology, and cold ischemia time) were associated with patient survival, patient/graft survival, and posttransplant resource utilization (hospital length of stay and hospital charges). Age, sex, race, etiology of disease, and cold ischemia time were similar among the three groups. Patient survival, patient/graft survival, and hospital charges were not statistically different between the three groups. The median length of stay was statistically different only between groups B and C (P = .006). Our data support the idea that if severely ill patients with end-stage liver disease are selected appropriately, liver transplant outcomes are similar to those observed among subjects who are less ill and are transplanted electively from home.

Background/Aims: The efficacy and safety of rifaximin in comparison with lactitol in the treatment of hepatic encephalopathy was assessed in a prospective randomized, double-blind, double-dummy, controlled trial. Methods: A total of 103 patients with grade I-III acute hepatic encephalopathy were randomized to receive rifaximin (50 patients, 1200 mg/day) or lactitol (53 patients, 60 g/day) for 5-10 days. Changes in portal-systemic encephalopathy (PSE) index on entry and at the end of the study were used to evaluate the efficacy of the two therapies. Results: Both groups were comparable before treatment with regard to demographic data and characteristics of the hepatic encephalopathy episode. The global efficacy of both therapies was similar: 81.6% in the rifaximin group and 80.4% in the lactitol group showed improvement or total regression of the episode. A significantly better evolution of the PSE index was observed in the rifaximin group, due to a greater effect of rifaximin in two components of the index: EEG abnormalities and ammonia levels. No serious events related to either treatment were found during the study. Conclusions: Rifaximin may be considered a useful and safe alternative therapy to lactitol in the treatment of acute hepatic encephalopathy in cirrhosis.

PURPOSE: Because the correlation between ammonia levels and the severity of hepatic encephalopathy remains controversial, we prospectively evaluated the correlation in 121 consecutive patients with cirrhosis. METHODS: The diagnosis of hepatic encephalopathy was based on clinical criteria, and the severity of hepatic encephalopathy was based on the West Haven Criteria for grading of mental status. Arterial and venous blood samples were obtained from each patient. Four types of ammonia measurements were analyzed: arterial and venous total ammonia, and arterial and venous partial pressure of ammonia. Spearman rank correlations (rs) were calculated. RESULTS: Of the 121 patients, 30 (25%) had grade 0 encephalopathy (no signs or symptoms), 27 (22%) had grade 1, 23 (19%) had grade 2, 28 (23%) had grade 3, and 13 (11%) had grade 4 (the most severe signs and symptoms). Each of the four measures of ammonia increased with the severity of hepatic encephalopathy: arterial total ammonia (rs 0.61, P 0.001), venous total ammonia (rs 0.56, P 0.001), arterial partial pressure of ammonia (rs 0.55, P 0.001), and venous partial pressure of ammonia (rs 0.52, P 0.001). CONCLUSION: Ammonia levels correlate with the severity of hepatic encephalopathy. Venous sampling is adequate for ammonia measurement. There appears to be no additional advantage of measuring the partial pressure of ammonia compared with total ammonia levels. Am J Med. 2003;114:188 –193. ©2003 by Excerpta Medica Inc.

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.