Global survey of stigma among physicians and patients with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Patients with fatty liver disease may experience stigma from the disease or comorbidities. In this cross-sectional study, we aimed to understand stigma among patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and healthcare providers. METHODS: Members of the Global NASH Council created two surveys about experiences/attitudes toward NAFLD and related diagnostic terms: a 68-item patient and a 41-item provider survey. RESULTS: Surveys were completed by 1,976 patients with NAFLD across 23 countries (51% Middle East/North Africa [MENA], 19% Europe, 17% USA, 8% Southeast Asia, 5% South Asia) and 825 healthcare providers (67% gastroenterologists/hepatologists) across 25 countries (39% MENA, 28% Southeast Asia, 22% USA, 6% South Asia, 3% Europe). Of all patients, 48% ever disclosed having NAFLD/NASH to family/friends; the most commonly used term was "fatty liver" (88% at least sometimes); "metabolic disease" or "MAFLD" were rarely used (never by >84%). Regarding various perceptions of diagnostic terms by patients, there were no substantial differences between "NAFLD", "fatty liver disease (FLD)", "NASH", or "MAFLD". The most popular response was being neither comfortable nor uncomfortable with either term (56%-71%), with slightly greater discomfort with "FLD" among the US and South Asian patients (47-52% uncomfortable). Although 26% of patients reported stigma related to overweight/obesity, only 8% reported a history of stigmatization or discrimination due to NAFLD. Among providers, 38% believed that the term "fatty" was stigmatizing, while 34% believed that "nonalcoholic" was stigmatizing, more commonly in MENA (43%); 42% providers (gastroenterologists/hepatologists 45% vs. 37% other specialties, p = 0.03) believed that the name change to metabolic dysfunction-associated steatotic liver disease (or MASLD) might reduce stigma. Regarding the new nomenclature, the percentage of providers reporting "steatotic liver disease" as stigmatizing was low (14%). CONCLUSIONS: The perception of NAFLD stigma varies among patients, providers, geographic locations and sub-specialties. IMPACT AND IMPLICATIONS: Over the past decades, efforts have been made to change the nomenclature of nonalcoholic fatty liver disease (NAFLD) to better align with its underlying pathogenetic pathways and remove any potential stigma associated with the name. Given the paucity of data related to stigma in NAFLD, we undertook this global comprehensive survey to assess stigma in NAFLD among patients and providers from around the world. We found there is a disconnect between physicians and patients related to stigma and related nomenclature. With this knowledge, educational programs can be developed to better target stigma in NAFLD among all stakeholders and to provide a better opportunity for the new nomenclature to address the issues of stigma.

Liver diseases: Perspective from the Philippines.

Liver diseases are a major cause of morbidity and mortality globally. In the Philippines, a lower middle-income country in Southeast Asia, liver diseases accounted for 27.3 cases per 1000 deaths. In this review, we discussed the prevalence, risk factors, and management of hepatitis B, hepatitis C and other viral hepatitis, non-alcoholic fatty liver disease, alcohol-associated liver disease, liver cirrhosis, and hepatocellular carcinoma. The true burden of liver disease in the Philippines is likely underestimated due to limited epidemiological studies. Thus, surveillance of liver disease should be strengthened. Clinical practice guidelines tailored to the local needs of the country have been developed for important liver diseases. Multisectoral cooperation among different stakeholders is needed to manage the burden of liver disease in the Philippines.

Severe impairment of patient-reported outcomes in patients with chronic hepatitis C virus infection seen in real-world practices across the world: Data from the global liver registry.

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 < 0.001). Out of 15 PRO domain and summary scores, 12 were lower in GLR patients than in subjects enrolled in clinical trials (p < 0.001). In multiple regression models, anxiety, depression, and fatigue were associated with significant PRO impairment in CHC patients (p < 0.05). After adjustment for the clinico-demographic confounders, the association of PRO scores of CHC patients with enrolment settings was no longer significant (all p > 0.05). In conclusion, hepatitis C patients seen in the real-world practices have PRO impairment driven by fatigue and psychiatric comorbidities.

The Impact of NASH to Liver Transplantations With Hepatocellular Carcinoma in the United States.

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.

Dietary Risks for Liver Mortality in NAFLD: Global Burden of Disease Data.

Nonalcoholic fatty liver disease (NAFLD) is a common but complex chronic liver disease, driven by environmental and genetic factors. We assessed metabolic and dietary risk factor associations with NAFLD liver mortality using the Global Burden of Disease (GBD) 2017 data. NAFLD liver deaths were calculated (per 100,000) as age-standardized rates (ASRs) from 195 countries and territories (21 GBD regions; 7 GBD superregions). Dietary risks included low intake of fruits, vegetables, legumes, whole grains, nuts/seeds, milk, fiber, calcium, seafood omega-3 fatty acids, and polyunsaturated fatty acids, and high intake of red meat, processed meat, sugar-sweetened beverages, trans fatty acids, and sodium. Metabolic risks included high low-density lipoprotein cholesterol, systolic blood pressure (BP), fasting glucose (FG), body mass index (BMI), as well as low bone mineral density and impaired kidney function (IKF). Socio-demographic index (SDI)-adjusted partial Spearman correlation coefficients and multivariable generalized linear regression models/bidirectional stepwise selection (significance level for entry, 0.2; for stay, 0.05) determined the associations. The ASR for NAFLD liver deaths was 2.3 per 100,000 (2017) and correlated with dietary risk factors (0.131, -0.010-0.267) and metabolic risk factors (SDI-adjusted = 0.225, 95% CI 0.086-0.354). High intake of sugar-sweetened beverages and red meat (0.358, 0.229-0.475; 0.162, 0.022-0.296), and low intake of nuts/seed and milk (0.154, 0.014-0.289; 0.145, 0.004-0.280) was significant for NAFLD liver deaths. Other risk factors for liver death included IKF (0.402, 0.276-0.514), increased BMI (0.353, 0.223-0.407), FG (0.248, 0.111-0.376), and BP (0.163, 0.022-0.297). High intake of trans fatty acids (2.84% increase [1.65%-4.03%]) was the largest associated risk of NAFLD liver deaths. In addition to metabolic risks, dietary risks independently drive the global burden of NAFLD-related liver mortality. Conclusion: These data provide additional support for policies to improve dietary environment for NAFLD burden reduction.

A Global Survey of Physicians Knowledge About Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Despite rapidly increasing nonalcoholic fatty liver disease (NAFLD) prevalence, providers' knowledge may be limited. We assessed NAFLD knowledge and associated factors among physicians of different specialties globally. METHODS: NAFLD knowledge surveys containing 54 and 59 questions covering 3 domains (epidemiology/pathogenesis, diagnostics, and treatment) were completed electronically by hepatologists, gastroenterologists (GEs), endocrinologists (ENDOs), and primary care physicians (PCPs) from 40 countries comprising 5 Global Burden of Disease super-regions. Over 24 months, 2202 surveys were completed (488 hepatologists, 758 GEs, 148 ENDOs, and 808 PCPs; 50% high-income Global Burden of Disease super-region, 27% from North Africa and Middle East, 12% Southeast Asia, and 5% South Asian and Latin America). RESULTS: Hepatologists saw the greatest number of NAFLD patients annually: median 150 (interquartile range, 60-300) vs 100 (interquartile range, 35-200) for GEs, 100 (interquartile range, 30-200) for ENDOs, and 10 (interquartile range, 4-50) for PCPs (all P < .0001). The primary sources of NAFLD knowledge acquisition for hepatologists were international conferences (33% vs 8%-26%) and practice guidelines for others (39%-44%). The Internet was the second most common source of NAFLD knowledge for PCPs (28%). NAFLD knowledge scores were higher for hepatologists than GEs: epidemiology, 62% vs 53%; diagnostics, 80% vs 73%; and treatment, 61% vs 58% (P < .0001), and ENDOs scores were higher than PCPs: epidemiology, 70% vs 60%; diagnostics, 71% vs 64%; and treatment, 79% vs 68% (P < .0001). Being a hepatologist or ENDO was associated with higher knowledge scores than a GE or PCP, respectively (P < .05). Higher NAFLD knowledge scores were associated independently with a greater number of NAFLD patients seen (P < .05). CONCLUSIONS: Despite the growing burden of NAFLD, a significant knowledge gap remains for the identification, diagnosis, and management of NAFLD.

Clinical and Patient-Reported Outcomes From Patients With Nonalcoholic Fatty Liver Disease Across the World: Data From the Global Non-Alcoholic Steatohepatitis (NASH)/ Non-Alcoholic Fatty Liver Disease (NAFLD) Registry.

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.

Contextual and individual factors associated with knowledge, awareness and attitude on liver diseases: A large-scale Asian study.

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-values<0.001). 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 Steatohepatitis Is the Fastest Growing Cause of Hepatocellular Carcinoma in Liver Transplant Candidates.

BACKGROUND & AIMS: Although hepatitis B and C have been the main drivers of hepatocellular carcinoma (HCC), nonalcoholic steatohepatitis (NASH) has recently become an important cause of HCC. The aim of this study was to assess the causes of HCC among liver transplant (LT) candidates in the United States. METHODS: The Scientific Registry of Transplant Recipients (2002-2016) was used to estimate the trends in prevalence of HCC in LT candidates with the most common types of chronic liver disease: alcoholic liver disease (ALD), chronic hepatitis B (CHB), chronic hepatitis C, and NASH. RESULTS: 158,347 adult LT candidates were included. Of these, 26,121 (16.5%) had HCC; this proportion increased from 6.4% (2002) to 23.0% (2016) (trend P < .0001). Over the study period, CHC remained the most common etiology for HCC (65%). The proportions of HCC accounted for by CHC and ALD remained stable (both trend P > .10), the proportion of CHB decreased 3.1-fold (P < .0001), while the proportion of NASH in HCC increased 7.7-fold (from 2.1% to 16.2%; P < .0001). Furthermore, since 2002, the prevalence of HCC in LT candidates with NASH increased 11.8-fold, while this rate increased 6.0-fold in CHB, 3.4-fold in ALD, and 2.3-fold in CHC (all P < .0001); the increasing trend in NASH was steeper than that for any other etiology (P < .0001 in a trend regression model). The proportion of LT candidates with HCC who ultimately received a transplant or died while waiting did not differ between etiologies (P > .05). CONCLUSIONS: Nonalcoholic steatohepatitis is the most rapidly growing cause of HCC among US patients listed for liver transplantation.

Chronic hepatitis B virus in the Philippines.

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.

The 2014 Hepatology Society of the Philippines consensus statements on the management of chronic hepatitis B

Chorinic hepatitis B virus (CHB) infection is a serious problem that affects over 300 million people worldwide and is highly prevalent in the Asia Pacific region. In the Philippines an estimate 7.3 million Filipinos or 16.7% of adults are chronically infected with HBV, more than twice the average prevalence in the Western Pacific region. In view of the above, the Hepatology Society of the Philippines (HSP) embarked on the development of consensus statements on the management of hepatitis B with the primary objectives of standardizing approach to management, empowering other physicians involved in the management of hepatitis B and advancing treatment subsidy by the Philippine Health Insurance Corporation (PhilHealth). The local guidelines include screening and vaccination general management, indications for assessment of fibrosis in those who did not meet treatment criteria. indications for treatment, on-treatment and post-treatment monitoring and duration of antiviral treatment. Recommendations on the management of antiviral drug resistance, management of special populations including patients with concurrent HIV or hepatitis C infection, women of child-bearing age (pregnancy and breastfeeding), patients with decompensated liver disease, patients receiving immunosuppressive medications or chemotherapy and patients in the setting of hepatocellular carcinoma are also included. However, the guidelines did not include management for patients with liver and other solid organ transplantation, patients on renal replacement therapy, and children. The consensus statements will be amended accordingly as new therapies become available.

The 2014 Hepatology Society of the Philippines consensus statements on the diagnosis and treatment of hepatitis C

Hepatitis C virus (HCV) infection is a devastating disease that is increasingly being diagnosed among Filipinos, especially in at-risk populations. There are disease-specific nuances in the evaluation and management of this infection. Furthermore, advances in the field brought about by clinical research are rapidly moulding the way we evaluate and manage HCV patients. Evidently, consensus statements formulated by experts in the field are needed in order to serve as a guide to physicians who see HCV patients in the clinic. With this in mind, the Hepatology Society of the Philippines spearheaded the formation of these statements which aimed to address issues in the diagnosis, evaluation, treatment, and follow-up care of patients with HCV infection.Recommendations on the specific tests to perform in the evaluation of HCV patients before, during and after treatment, and first-line treatment of patients with acute and chronic HCV infection were provided. Treatment algorithms for chronic HCV infection, divided according to viral genotype, were also devised. We acknowledge the limitations brought about by the local inavailability of some drugs/treatment regimens in the local setting at the time of the formulation of these statements. As such, these statements will be revised as soon as new data become locally applicable.  

Noradrenaline vs terlipressin for hepatorenal syndrome (no to hepatorenal syndrome): A meta-analysis

INTRODUCTION: Hepatorenal syndrome (HRS) is a functional renal impairment associated with advanced cirrhosis. The best treatment is liver transplantation; however, many patients die before this can be done. Terlipressin improves renal function in HRS, but recent studies have shown similar effects with the cheaper and more readily available norepinephrine. This review included randomized trials comparing noradrenaline to terlipressin for patients with type 1 HRS, as defined by the International Ascites Club. OBJECTIVE: To determine the safety and effectiveness of noradrenaline in the management of HRS in terms of 1) reducing mortality, 2) reversal and 3) occurrence of adverse events METHODOLOGY: For this meta-analysis paper, the researchers utilized an electronic search of databases and manual scanning of reference lists were performed. Standardized eligibility assessment was performed independently by three reviewers. Review Manager 5.0.23 was used to calculate odds ratios (OR) with 95% confidence intervals (CIs) as well as I2 values for inter-trial heterogeneity. Standardized eligibility assessment was performed independently by three reviewers. RESULTS: Thirty-six articles were found after electronic and manual searching. Three were assessed for validity and included in the final analysis. The total number of patients across all trials was 95. Noradrenaline was found not to differ from terlipressin in terms of 15-day survival rate (OR 01.17; 95% CI: 0.51-2.66), reversal of HRS (OR1.07; 95% CI: 0.47-2.44), and a post-hoc analysis on disease-free survival (OR 0.78; 95% CI: 0.34-1.79). Results of sensitivity analysis were consistent with the previous findings (15-day survival: OR=1.21 95% CI = 0.52-2.83; HRS reversal: OR= 1.33, 95% CI = 0.56-3.13; disease-free survival: 1.35, CI =0.56-3.25). Only transient adverse effects were noted with either drugs. CONCLUSION: There is inconclusive evidence that noradrenaline and terlipressin are significantly different in the reversal of HRS and reduction of mortality. Larger trials on noradrenaline or a non-inferiority trial may be needed to establish the equivalence of noradrenaline with terlipressin.

Demographic profile and treatment outcomes of Filipino patients with hepatocellular carcinoma in a liver tumor registry

BACKGROUND AND OBJECTIVES: Previous studies using older diagnostic criteria indicated chronic Hepatitis B and alcohol as the most common etiologies of HCC in the Philippines. No recent studies updated criteria for diagnosis have been published. This study used the diagnostic criteria from the latest APASL guidelines to describe the demographic profile of patients with HCC. METHODS: This is a cross-sectional study of adult HCC cases from a liver tumor registry in the Philippine General Hospital from 2009 to 2012. Demographics, AFP levels, BCLC stage, Child-Pugh Score, ECOG performance status, treatments received, and mortality were assessed. RESULTS: The HCC prevalence rate was 7.8%, mostly occurring between ages 40 to 65 years. It is more common in males (M:F=4:1). Most of the HCC cases were diagnosed at early stages, with less severity of liver functional impairment compared to older studies. Resection was the common treatment undertaken (50%) and overall mortality rate at the time of hospital discharge was 25%.  CONCLUSION: The profile of HCC patients in this study is similar to previous studies. More cases were recognized at earlier stages with better liver function, implying better treatment outcomes with surgery, although selection bias is recognized.

Hepatitis B infection among adults in the philippines: A national seroprevalence study.

AIM: To determine the prevalence of hepatitis B surface antigen (HBsAg) seropositivity among adult Filipinos. METHODS: 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 seropositivity. Multivariate analysis was used to determine independent predictors of HBsAg seropositivity. RESULTS: A total of 2150 randomly selected adults, 20 years and over, out of the 4753 adult participants of NNHeS were tested for HBsAg. The HBsAg seroprevalence was 16.7% (95%CI: 14.3%-19.1%), which corresponded to an estimated 7278968 persons infected with hepatitis B. There was no significant difference between males and females (17.5% vs 16.0%; P = 0.555). This corresponded to an estimated 3721775 men and 3557193 women infected with hepatitis B. The HBsAg seroprevalence peaked at age 20-39 years old, with declining prevalence in the older age groups. The only independent predictor of HBsAg seropositivity was the annual income, with persons in the highest income quartile being less likely to be HBsAg positive (age-adjusted OR = 0.51; 95%CI: 0.30-0.86) compared to subjects in the lowest income quartile. Sex, marital status, educational attainment, and employment status were not found to be independent predictors of HBsAg seropositivity. CONCLUSION: The high HBsAg seroprevalence among adults in the Philippines classifies the country as hyperendemic for HBV infection and appears unchanged over the last few decades.

Oral L-ornithine-L-aspartate improves health-related quality of life in cirrhotic patients with hepatic encephalopathy: an open-label, prospective, multicentre observational study.

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.

Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease.

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<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. 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.

Ursodeoxycholic acid in the prevention of gallstone formation after bariatric surgery: a meta-analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: UDCA can prevent gallstone formation after bariatric surgery.