Alcoholic Liver Disease Mortality Research Articles

United States-Mexico Border Disparities in Alcoholic Liver Disease Mortality: A Cross-Sectional Analysis 1999-2020.

US-Mexico (US-MX) border regions are impacted by socioeconomic disadvantages. Alcohol use disorder remains widely prevalent in US-MX border regions, which may increase the risk of alcoholic liver disease (ALD). We aimed to characterize ALD mortality trends in border regions compared to non-border regions from 1999 to 2020 in the United States (US). We performed a cross-sectional analysis using the CDC repository. We queried death certificates to find ALD-related deaths from 1999 to 2020, which included demographic information such as gender, race/ethnicity, and area of residence. We estimated age-adjusted mortality rates (AAMR) per 100,000 population and compared the AAMRs across border and non-border regions. We also explored yearly mortality shifts using log-linear regression models and calculated the average annual percentage change (AAPC) using the Monte Carlo permutation test. In all, 11,779 ALD-related deaths were identified in border regions (AAMR 7.29) compared with 361,523 in non-border regions (AAMR 5.03). Border male (AAMR 11.21) and female (AAMR 3.77) populations were higher compared with non-border male (AAMR 7.42) and female (2.85) populations, respectively. Border non-Hispanic populations (AAMR 7.53) had higher mortality compared with non-border non-Hispanic populations (4.79), while both populations experienced increasing mortality shifts (AAPC +1.7, P<0.001 and +3.1, P<0.001, respectively). Border metropolitan (AAMR 7.35) and non-metropolitan (AAMR 6.76) regions had higher mortality rates compared with non-border metropolitan (AAMR 4.96) and non-metropolitan (AAMR 5.44) regions. Mortality related to ALD was higher in border regions compared with non-border regions. Border regions face significant health disparities when comparing ALD-related mortality.

Incidence Trends and Risk Factors of Alcohol-Specific Deaths

A simple but questionable view holds that alcohol-related mortality is directly and closely related to the total consumption of alcohol in a country. To study how uniform this relationship is, trends and changes by age and diagnosis in alcohol-specific deaths were studied in Finland between the years 2007-2022, a period when both alcohol consumption and alcohol-specific mortality showed a decreasing trend. Alcoholic liver disease mortality trends deviated markedly from those for the other diagnoses. Among those aged 64 years or less, there was a consistent decreasing trend for the other categories while liver disease showed a slight increase after the initial decrease. Among the population aged 65 years or more both liver disease and other groups showed an increasing trend. Alcohol poisoning decreased in both age groups. Mortality in all other diagnostic groups decreased in the younger age group and increased in the older group. Age-adjustment or gender did not explain differences. The different mortality trends were not consistent with the assumed uniform effect of alcohol consumption on alcohol-related harms. Other risk factors than alcohol may play a significant role. These are discussed and need to be considered to yield better estimates than the simplistic assumption of a 100 % attributable fraction of alcohol in these diagnoses.

Neoplastic Effects of Endogenous Alcohol in Carcinogenesis Process of Hepatocarcinoma

Introduction: Based on the grim statistics, the mortality of alcoholic liver disease was in last years the high in the undeveloped countries but and in developed countries in the statistic compared with last years.&#x0D; Aim: Scope of this work was to discover the patients diagnosed with alcoholic cirrhosis which in time was transformed in Hepatocellular Carcinoma, (HCT) by continue abuse alcohol and which presented, at a previous medical control, with the diagnosis of steatohepatitis after the chronic abuse of alcohol.&#x0D; Methodology: The retrospective study consisted of 180 patients, adult men (mean age 55 years) and females (mean age = 48) hospitalized and investigated for alcoholic liver diseases. From total cases investigated, 54 cases (30% from of cases admitted in hospital, meaning 27 men and 17 women), which were diagnosed with alcoholic liver cirrhosis in last 5-7 years but in next medical controls were discovered liver cancers in the 6.1% percent.&#x0D; Results: The majority of patients with uncompensated liver cirrhosis, (70%), have had elevated AST in average 66 U/L value, (N= 5-38U/L). Also, they have had an AST/ALT ratio 1.36, (N = 1.33) and ratio TGP/TGO = 0.95. In the liver carcinogenesis process the report AST/ALT increased in 2.64 value and ratio TGP/TGO decreased in 0.67 value.&#x0D; Conclusions: The active and rational lifestyle is an essential element in preventing the process of carcinogenesis. Liver disease it's not just how much you drink, but how and when you drink. The treatment of severe alcoholic hepatitis will be necessary in all alcoholic liver diseases centers to prevent hepatic cancer disease.

Neoplastic Effects of Endogenous Alcohol in Carcinogenesis Process of Hepatocarcinoma

Introduce: Based on the grim statistics, the mortality of alcoholic liver disease was in last years the high in the undeveloped countries but and in developed countries in the statistic compared with last years. Aim: Scope of this work was to discover the patients diagnosed with alcoholic cirrhosis which in time was transformed in Hepatocellular Carcinoma, (HCT) by continue abuse alcohol and which presented, at a previous medical control, with the diagnosis of steatohepatitis after the chronic abuse of alcohol. Methodology: The retrospective study consisted of 180 patients, adult men (mean age 55 years) and females (mean age = 48) hospitalized and investigated for alcoholic liver diseases. From total cases investigated, 54 cases (30% from of cases admitted in hospital, meaning 27 men and 17 women), which were diagnosed with alcoholic liver cirrhosis in last 5-7 years but in next medical controls were discovered liver cancers in the 6.1% percent. Results: The majority of patients with uncompensated liver cirrhosis, (70%), have had elevated AST in average 66 U/L value, (N= 5-38U/L). Also, they have had an AST/ALT ratio 1.36, (N = 1.33) and ratio TGP/TGO = 0.95. In the liver carcinogenesis process the report AST/ALT increased in 2.64 value and ratio TGP/TGO decreased in 0.67 value. Conclusions: The active and rational lifestyle is an essential element in preventing the process of carcinogenesis. Liver disease it’s not just how much you drink, but how and when you drink. The treatment of severe alcoholic hepatitis will be necessary in all alcoholic liver diseases centers to prevent hepatic cancer disease.

Trends in Premature Deaths From Alcoholic Liver Disease in the U.S., 1999–2018

So-called deaths of despair-those involving drug overdoses, alcohol-related liver disease, and suicide-have been rising in the U.S. among middle-aged white, non-Hispanic adults without a college degree. Premature deaths (ages 25-69) from alcoholic liver disease were examined specifically in this study from 1999 to 2018, by sex, race/Hispanic origin, and age group. Data were drawn from the 1999-2018 Multiple Cause of Death database and bridged-race estimates of the U.S. resident population, including 281,243 alcoholic liver disease deaths or an average of 8 deaths per 100,000 population. Analyses examined alcoholic liver disease death rates for sex differences among 3 age groups (25-49, 50-59, and 60-69 years), by race and Hispanic origin, from 1999 to 2018; age-adjusted and age-specific annual percentage changes (accounted for cohorts); years of potential life lost; and age of death for sociodemographic backgrounds, alcoholic liver disease clinical courses, and comortalities. White non-Hispanics increasingly experienced greater alcoholic liver disease mortality than black non-Hispanics and Hispanics, confirming the racial and ethnic crossover observed in previous studies. Although men consistently had higher rates of mortality, male-to-female ratios decreased in the past 2 decades and were the lowest among ages 25-49 years and especially among ages 25-34 years. Although women generally had longer life expectancies, women died of alcoholic liver disease on average about 2-3 years earlier than men. Prevention and intervention efforts are imperative to address the narrowing sex gap and widening racial disparities in alcoholic liver disease premature deaths.

National Trends and Outcomes of Nonautoimmune Hemolytic Anemia in Alcoholic Liver Disease: Analysis of the Nationwide Inpatient Sample.

The aim of this study was to determine the burden of nonautoimmune hemolytic anemia (NAHA) in hospitalized patients with coexisting alcoholic liver disease (ALD), identify risk factors for NAHA in ALD and describe the hospitalization outcomes. ALD can result in structural and metabolic alterations in the red-blood cell membrane leading to premature destruction of erythrocytes and hemolytic anemia of varying severity. Hospitalized ALD patients with concomitant NAHA were identified in the Nationwide Inpatient Sample database using International Classification of Diseases-9 codes from 2009 to 2014. The primary outcome was to determine the nationwide prevalence and risk factors of NAHA in patients hospitalized with ALD. The prevalence of NAHA was 0.17% (n=3585) among all ALD patients (n=2,125,311) that were hospitalized. Multivariate analysis indicated higher odds of NAHA in ALD patients in the following groups: female gender [adjusted odds ratio (AOR) AOR 1.80, P<0.0001]; highest quartile of median household income (AOR 1.88, P<0.0001); increasing Charlson-Deyo Comorbidity Index (3 to 4 vs. 0, AOR 2.16, P=0.0042) and cirrhosis (AOR 2.74, P<0.0001). Discharges of ALD with anemia had a significantly longer average length of stay (8.8 vs. 6.0 d, P<0.0001), increased hospital charges ($38,961 vs. $25,244, P<0.0001) and higher mortality (9.0% vs. 5.6%, P<0.0001) when compared with ALD with no anemia. NAHA in patients with ALD is an important prognostic marker, predicting a longer, costlier hospitalization and increased inpatient mortality in ALD.

Coffee and wine consumption is associated with reduced mortality from alcoholic liver disease: follow-up of 219,279 Norwegian men and women aged 30–67 years

PurposeTo study the association between coffee and alcoholic beverage consumption and alcoholic liver disease mortality. MethodsIn total, 219,279 men and women aged 30–67 years attended cardiovascular screening in Norway from 1994 to 2003. Linkage to the Cause of Death Registry identified 93 deaths from alcoholic liver disease. Coffee consumption was categorized into four levels: 0, 1–4, 5–8, and greater than or equal to 9 cups/d and alcohol consumption as 0, greater than 0 to less than 1.0, 1.0 to less than 2.0, and greater than or equal to 2.0 units/d, for beer, wine, liquor, and total alcohol consumption. ResultsThe hazard ratios per one category of consumption were 2.06 (95% confidence interval 1.62–2.61), 0.68 (0.46–1.00), and 2.54 (1.92–3.36) for beer, wine, and liquor, respectively. Stratification at 5 cups/d (the mean) revealed a stronger association between alcohol consumption and alcoholic liver disease at less than 5 versus 5 or more cups/d. With less than 5 cups/d, 0 alcohol units/d as reference, the hazard ratio reached to 25.5 (9.2–70.5) for greater than or equal to 2 units/d, whereas with greater than or equal to 5 cups/d, it reached 5.8 (1.9–17.9) for greater than or equal to 2 units/d. A test for interaction was significant (P = .01). ConclusionsCoffee and wine consumption were inversely associated with alcoholic liver disease death. Total alcohol consumption was adversely associated with alcoholic liver disease mortality and the strength of the association varied with the level of coffee consumption.

Misconceptions, preferences and barriers to alcohol use disorder treatment in alcohol-related cirrhosis

BackgroundWhile alcohol cessation improves mortality in alcoholic liver disease (ALD), many patients struggle to achieve abstinence. Our aim was to characterize ALD patients' preferences, misconceptions, and barriers to alcohol use treatment options. MethodsThis mixed-methods study included outpatients with a history of alcohol-related cirrhosis or alcoholic hepatitis recruited from a hepatology clinic for a survey or an in-depth semi-structured interview. We purposefully sampled men and women, compensated and decompensated patients to ensure adequate representation of gender and severity of liver disease for the qualitative interviews. Results123 patients completed surveys among which 50% reported having at least one drink within the past year while only 20 patients were in any form of current alcohol treatment. Of the 23 patients reporting drinking within 3 months, only 3 were in AUD treatment currently. 17% had at least one misconception about alcohol use or treatment. An additional 22 ALD patients (10 women, 12 men) completed phone interviews of which two-third self-reported alcohol abstinence. All 22 interview participants had awareness of some form of alcohol treatment, but 13 felt that they did not need treatment with several characterizing it as ineffective or a “waste of time.” Misconceptions included inaccurate perceptions of relapse medication side effects, beliefs that the presence of advanced liver disease symptoms means it is too late to treat alcohol use, and a lack of understanding about the chronicity of alcohol use disorders. The most common barriers to treatment included unwillingness to be in treatment, financial/insurance and transportation barriers. ConclusionsAlcohol use treatment was underutilized in many ALD patients, despite active drinking in many. Tailored education and preference sensitive treatment engagement may overcome barriers to alcohol use treatment and promote abstinence.

Incidence, survival and cause-specific mortality in alcoholic liver disease: a population-based cohort study

Objective: We studied the incidence of severe ALD requiring hospitalization in Finland, and survival and causes of death among the ALD patients.Methods: A cohort of 11,873 persons (8796 men and 3077 women) with diagnosis of ALD during the years 1996–2012 was identified from Finnish national Inpatient Register. The annual incidence of alcoholic hepatitis (AH) and alcoholic liver cirrhosis was calculated. The cohort was combined with the data from national Cause of Death Register of Statistics Finland.Results: The incidence of alcoholic liver cirrhosis increased from 8.8/100,000 in year 2001 to 14.6/100,000 in year 2012 among men and from 2.4 to 4.2/100,000 among women. The incidence of AH increased from 3.7 to 6.5/100,000 among men and from 1.3 to 2.7/100,000 among women. The relative 5-year survival ratios of patients with alcoholic liver cirrhosis and AH were 29 and 50% among men and 38 and 52% among women, respectively. Out of 8440 deaths, 65% were due to alcoholic-related causes. The risk of death among ALD patients was increased in malignancies (SMR 6.82; 95% CI: 6.35–7.29), cardiovascular diseases (6.13; 5.74–6.52), respiratory diseases (7.86; 6.70–9.10), dementia (3.31; 2.41–4.44) and accidents and violence (11.12; 10.13–12.15).Conclusions: The incidence of AH and alcoholic liver cirrhosis is increasing. The survival is poor. Most deaths are alcohol-related and other common causes of excess deaths are cancers especially in the upper aerodigestive tract and cardiovascular, digestive and respiratory diseases as well as violence and accidents.

Age-period-cohort effects in alcoholic liver disease mortality in France from 1968 to 2010

BackgroundPer capita alcohol consumption in France has historically been among the highest levels in Europe. In more recent history, however, consumption (mostly wine) has substantially decreased as has alcohol-related mortality. The present study characterizes age, period, and cohort (APC) trends in liver disease in France for the past four decades.MethodsData were drawn from overall French death certificates records covering the years 1968 to 2010. Liver disease mortality was defined from underlying cause ICD 8, 9, and 10 codes. We estimated age, period, and cohort effects, by sex, using Poisson modeling estimation and Clayton & Shiffler’s approach to model identification for APC modeling.ResultsLiver disease mortality exhibited significant age, period and cohort effects. The overall mortality rates were 25/100,000 for men and 9/100,000 for women over the period of data collection, with mortality increasing across age and peaking around age 70. Among males, there was no cohort effect and a clear and significant period effect; the risk of liver cirrhosis mortality in men has been steadily decreasing for all age groups across time. Conversely among women, there was a similar decreasing period effect but a strong and significant cohort effect as well. Specifically, there was a positive cohort effect for cirrhosis mortality for women born before around 1960 with the risk of liver cirrhosis for those cohorts between 4.0 and 5.0 times higher than the risks for those born after 1970, controlling for age and period effect.ConclusionLiver disease mortality has been decreasing in France for the past four decades, across all age groups and across men and women. Women born in older cohorts have much higher risks of dying from liver disease compared with women in younger cohorts, controlled for age, which may be a function of different beverage consumption patterns.

Trends in the epidemiological aspects and mortality of alcoholic liver disease in Korea in the decade between 2000 and 2009.

BackgroundAlcohol consumption and related alcohol liver disease (ALD) have substantially increased in Korea during the last decade. The objective of this study was to evaluate the trends in the epidemiological aspects and mortality rate (MR) of Korea in the decade between 2000 and 2009.MethodsThe raw data analyzed in this study were obtained from the website of “the ALD” managed by Korea Center for Disease Control and Prevention (KCDC), Korea Public Health Association (KPHA), and statistics website of Statistics Korea. The data analyses were performed using Excel 2007 statistical software (Microsoft Corp., USA).ResultsThe amount of alcohol-consumption-per-capita-per-year (ACCY) in Korea was 8.38 L in 2000 and 8.54 L in 2009. The most taken alcoholic beverage was soju, followed by beer. There were a total of 1,403 case-fatalities (CF) with an MR of 2.98 per 100,000 populations of ALD in 2000, while a total of 3,588 CF with an MR of 7.21 in 2009 (P < 0.01). The CF and MR of ALD in males were significantly higher than those in females (P < 0.01). In over 40-year-old age groups, the CF and MR were significantly increased (P < 0.01). Moreover, occupational classification revealed that the mistress/students/jobless (MSJ) were the most risky group. The comparison of overall CF and MR of ALD by six key classifications (International Classification of Diseases (ICD)) showed that alcoholic cirrhosis (229 CF and 16.3%) in 2000 tended to be increased in 2009 (2,803 CF and 78.1%), while alcoholic fibrosis and sclerosis (607 CF and 43.3%) in 2000 significantly decreased in 2009 (120 CF and 3.3%), respectively.ConclusionALD is one of the most severe diseases in Korea, as indicated by its high CF and MR in this study. As over-consumption of alcoholic beverages is relatively common in Korea, more efforts should be made toward prevention of ALD by raising awareness of the risk factors of ALD by public health education.

Parallel 20: Mechanisms and Mortality in Alcoholic Liver Disease

Parallel 20: Mechanisms and Mortality in Alcoholic Liver Disease

S07 * NONINVASIVE SCREENING TOOLS FOR LIVER CIRRHOSIS IN ADDICTED PATIENTS

S07 * NONINVASIVE SCREENING TOOLS FOR LIVER CIRRHOSIS IN ADDICTED PATIENTS

Marked 25-hydroxyvitamin D deficiency is associated with poor prognosis in patients with alcoholic liver disease

Vitamin D deficiency has been frequently reported in advanced liver disease. However, its influence on alcoholic liver disease (ALD) has been poorly elucidated. We investigated the association of vitamin D with clinical, biological, and histological parameters and survival in ALD patients. Furthermore, we explored the effect of vitamin D treatment on ALD patient peripheral blood mononuclear cells (PBMCs), and in a murine experimental model of ALD. Serum levels of 25-hydroxyvitamin D [25(OH)D] were determined in 324 Caucasian ALD patients and 201 healthy controls. In vitro experiments on vitamin D pre-treated PBMCs evaluated TNFα production by ELISA in culture supernatants. Mice were submitted to an ethanol-fed diet and some of them were orally supplemented three times per week with 1,25(OH)2D. Severe deficiency in 25(OH)D (<10 ng/ml) was significantly associated with higher aspartate aminotransferase levels (p=1.00 × 10(-3)), increased hepatic venous pressure gradient (p=5.80 × 10(-6)), MELD (p=2.50 × 10(-4)), and Child-Pugh scores (p=8.50 × 10(-7)). Furthermore, in multivariable analysis, a low 25(OH)D concentration was associated with cirrhosis (OR=2.13, 95% CI=1.18-3.84, p=0.013) and mortality (HR=4.33, 95% CI=1.47-12.78, p=7.94 × 10(-3)) at one year. In addition, in vitro, 1,25(OH)2D pretreatment decreased TNFα production by stimulated PBMCs of ALD patients (p=3.00 × 10(-3)), while in vivo, it decreased hepatic TNFα expression in ethanol-fed mice (p=0.04). Low 25(OH)D levels are associated with increased liver damage and mortality in ALD. Our results suggest that vitamin D might be both a biomarker of severity and a potential therapeutic target in ALD.

US Mortality from Liver Cirrhosis and Alcoholic Liver Disease in 1999–2004: Regional and State Variation in Relation to Per Capita Alcohol Consumption

Apparent per-capita alcohol consumption in 2001 in four US regions (West, Northeast, South, and Midwest), and in 50 states was examined in relation to mortality rates (1999–2004) from liver cirrhosis and for the subcategory alcoholic liver disease. Alcohol consumption and mortality rates were highest in the west. The alcoholic liver disease mortality rate by state was strongly correlated with alcohol consumption, but several outlier or mismatch states were identified. Per-capita alcohol consumption should be useful for US public health policy, as suggested for Europe and Canada, but outlier states require further study.

Mortality rate of alcoholic liver disease and risk of hospitalization for alcoholic liver cirrhosis, alcoholic hepatitis and alcoholic liver failure in Australia between 1993 and 2005

Alcoholic liver disease (ALD) is an important contributor to the total burden of alcohol-related harm; however, the morbidity of different types of ALD in Australia has not been described. The aim of this study was to investigate recent trends in hospital admission rates among alcoholic liver cirrhosis, alcoholic hepatic failure and alcoholic hepatitis in Australia, as well as the mortality of ALD. This is a population-based cohort study including the total 15+ years Australian population. Data were obtained from the Australian Bureau of Statistics and the Australian Institute of Health and Welfare. (i) trend of standardized mortality rates and trend of standardized hospital admission rates for males and females for 1993/1994-2004/2005 (fiscal year), (ii) relative risk of alcoholic liver cirrhosis, alcoholic hepatic failure and alcoholic hepatitis hospital admissions for 1999/2000-2004/2005. The mortality rate of ALD decreased significantly. Significant increases in hospital admissions for alcoholic hepatic failure among older adults and alcoholic hepatitis among younger age groups were observed. There is a significant 10-fold increase in the risk of hospital admissions of alcoholic cirrhosis in 2002/2003 for the 20-29 years population. Reductions in overall ALD mortality observed are likely the result of advances in disease management. Significant increase in hospital admissions suggests an increase in the prevalence of ALD among the Australian population. Dramatic increases in hospital admissions for alcoholic cirrhosis in 2002/2003 for the 20-29 years population may have been due to an increase in screening of alcohol-related harms in primary care settings.

Chronic Liver Disease--An Increasing Problem: A Study of Hospital Admission and Mortality Rates in England, 1979-2005, with Particular Reference to Alcoholic Liver Disease

To determine time trends in hospital admissions for chronic liver disease in England between 1989/1990 and 2002/2003, mortality rates in England and Wales between 1979 and 2005, and the influence of alcohol-related disease on these trends. Hospital episode statistics for admissions in England were obtained from the Information Center for Health and Social Care and mortality data for England and Wales from the Office for National Statistics. Hospital admission rates for chronic liver disease increased by 71% in males and 43% in females over the study period. This increase was largely due to alcoholic liver disease, admission rates for which more than doubled between 1989/1990 and 2002/2003. While there was a smaller rise for chronic viral hepatitis B and C, admission rates declined for hepatitis A, autoimmune hepatitis, and primary biliary cirrhosis. Mortality rates for chronic liver disease more than doubled between 1979 and 2005. Two thirds of these deaths were attributable to alcohol-related liver disease in 2005. The highest rate of alcoholic liver disease mortality was in the 45-64 age group, and the largest percentage increase between 1979 and 2005 occurred in the 25-34 age group. Hospital admissions and mortality in England from chronic liver disease are increasing. The underlying reasons are complex, but alcohol-induced liver disease makes a major contribution. There are clear social and health implications if the trend continues and addressing alcohol-related liver disease should be a public health priority.

Epidemiology of alcoholic liver disease.

Alcohol is one of the main causes of end-stage liver disease worldwide, and alcoholic liver disease is the second most common reason for liver transplantation in the United States. Beginning in the 1970s, there was a gradual decline in alcoholic cirrhosis-related mortality in many countries. However, in the past few years, alcoholic liver disease mortality rates in several countries have stabilized or started to increase. There are significant ethnic and gender differences in alcoholic cirrhosis-related mortality rates. Furthermore, alcohol use increases the risk for liver disease in those infected with hepatitis C. A better understanding of the epidemiology of alcoholic liver disease will allow for improved diagnosis and management of this common problem.

TGF-beta isoforms in alcoholic liver disease.

The increased deposition of extracellular matrix proteins in the liver is a key factor in the morbidity and mortality of alcoholic liver disease (ALD). This increased fibrosis may be due to a superabundance of profibrogenic factors such as transforming growth factor-beta (TGF-beta). The original peptide is now called TGF-beta 1, and two other isoforms have been recognized in humans (TGF-beta 2 and TGF-beta 3). It was the aim of the present study to determine the expression of the TGF-beta isoforms in different stages of ALD. Thirty patients with ALD had percutaneous liver biopsies performed for diagnostic purposes. They were grouped by clinical findings and by liver histology into four groups: I, steatosis; II, fibrosis; III, hepatitis; and IV, cirrhosis. An unused portion of each biopsy sample was used to evaluate the gene expression of TGF-beta 1, TGF-beta 2, and TGF-beta 3 by reverse transcription polymerase chain reaction (RT-PCR). The expression of all isoforms from patients was significantly greater than their expression in controls. No significant correlation was determined between TGF-beta isoform expression and liver function test results. When the different isoforms were grouped by histology, increased expression with more severe disease was found; however, differences existed among the isoforms. In ALD, all TGF-beta isoforms were increased and their expression was significantly greater in patients with more active and advanced disease. RT-PCR is an effective method for evaluating gene expression in clinical samples which often provide a limited amount of tissue.

Long-term treatment of alcoholic liver disease with propylthiouracil. Part 2: Influence of drop-out rates and of continued alcohol consumption in a clinical trial

Although propylthiouracil has previously been shown to reduce the risk of mortality in alcoholic liver disease by 60%, generalized use of propylthiouracil for this condition has not occurred. Additional data are therefore presented on four aspects to provide a better assessment of its therapeutic effectiveness. First, the characteristics and the prognosis of dropouts were virtually identical in both the drug and placebo groups. Also the methodology and analysis employed, were designed to control for dropouts, thus providing an accurate interpretation of the outcome. Secondly, since 97% of the patients continued to drink, abstinence was not a precondition for the beneficial effect of propylthiouracil. However, the beneficial effect was observed most clearly in those patients who continued to drink at lower levels, whereas lower level drinking per se did not afford protection in placebo patients. Thirdly, serious side effects or clinical hypothyroidism occurred extremely rarely in these patients, many of whom have now received propylthiouracil for over 4 years. Fourthly, we discuss why the outcome in long-term clinical trials in alcoholic liver disease cannot be compared with effects observed in clinical trials lasting only a few weeks. Journal of Hepatology.