Fatty liver indices in the multiethnic United States National Health and Nutrition Examination Survey.

BACKGROUND: Validated non-invasive measures of fatty liver are needed that can be applied across populations and over time. A fatty liver index (FLI) including body mass index, waist circumference, triglycerides and gamma glutamyltransferase (GGT) activity was developed in an Italian municipality, but has not been validated widely or examined in a multiethnic population. AIMS: We evaluated this FLI in the multiethnic U.S. National Health and Nutrition Examination Survey (NHANES) and also to explore whether an improved index for the U.S. population (US FLI) could be derived. The US FLI would then used to examine U.S. time trends in fatty liver prevalence. METHODS: We studied 5869 fasted, viral hepatitis negative adult participants with abdominal ultrasound data on fatty liver in the 1988-1994 NHANES. Time trend analyses included 21 712 NHANES 1988-1994 and 1999-2012 participants. RESULTS: The prevalence of fatty liver was 20%. For the FLI, the area under the receiver operating characteristic curve [AUC; 95% confidence interval (CI)] was 0.78 (0.74-0.81). The US FLI included age, race-ethnicity, waist circumference, GGT activity, fasting insulin and fasting glucose and had an AUC (95% CI) of 0.80 (0.77-0.83). Defining fatty liver as a US FLI ≥ 30, the prevalence increased from 18% in 1988-1991 to 29% in 1999-2000 to 31% in 2011-2012. CONCLUSIONS: For predicting fatty liver, the US FLI was a modest improvement over the FLI in the multiethnic U.S. population. Using this measure, the fatty liver prevalence in the U.S. population increased substantially over two decades.

Outcomes of living and deceased donor liver transplant recipients with hepatocellular carcinoma: results of the A2ALL cohort.

Hepatocellular carcinoma (HCC) represents an increasing fraction of liver transplant indications; the role of living donor liver transplant (LDLT) remains unclear. In the Adult-to-Adult Living Donor Liver Transplantation Cohort Study, patients with HCC and an LDLT or deceased donor liver transplant (DDLT) for which at least one potential living donor had been evaluated were compared for recurrence and posttransplant mortality rates. Mortality from date of evaluation of each recipient's first potential living donor was also analyzed. Unadjusted 5-year HCC recurrence was significantly higher after LDLT (38%) than DDLT (11%), (p = 0.0004). After adjustment for tumor characteristics, HCC recurrence remained significantly different between LDLT and DDLT recipients (hazard ratio (HR) = 2.35; p = 0.04) for the overall cohort but not for recipients transplanted following the introduction of MELD prioritization. Five-year posttransplant survival was similar in LDLT and DDLT recipients from time of transplant (HR = 1.32; p = 0.27) and from date of LDLT evaluation (HR = 0.73; p = 0.36). We conclude that the higher recurrence observed after LDLT is likely due to differences in tumor characteristics, pretransplant HCC management and waiting time.

Silymarin use and liver disease progression in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis trial.

BACKGROUND: Silymarin is the most commonly used herbal product for chronic liver disease; yet, whether silymarin protects against liver disease progression remains unclear. AIM: To assess the effects of silymarin use on subsequent liver disease progression in 1049 patients of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial who had advanced fibrosis or cirrhosis and had failed prior peginterferon plus ribavirin treatment. METHODS: Patients recorded their use of silymarin at baseline and were followed up for liver disease progression (two point increase in Ishak fibrosis score across baseline, year 1.5, and year 3.5 biopsies) and over 8.65 years for clinical outcomes. RESULTS: At baseline, 34% of patients had used silymarin, half of whom were current users. Use of silymarin was associated (P < 0.05) with male gender; oesophageal varices; higher ALT and albumin; and lower AST/ALT ratio, among other features. Baseline users had less hepatic collagen content on study biopsies and had less histological progression (HR: 0.57, 95% CI: 0.33-1.00; P-trend for longer duration of use=0.026). No effect was seen for clinical outcomes. CONCLUSIONS: Silymarin use among patients with advanced hepatitis C-related liver disease is associated with reduced progression from fibrosis to cirrhosis, but has no impact on clinical outcomes (Clinicaltrials.gov #NCT00006164).

Database comparison of the adult-to-adult living donor liver transplantation cohort study (A2ALL) and the SRTR U.S. Transplant Registry.

Data submitted by transplant programs to the Organ Procurement and Transplantation Network (OPTN) are used by the Scientific Registry of Transplant Recipients (SRTR) for policy development, performance evaluation and research. This study compared OPTN/SRTR data with data extracted from medical records by research coordinators from the nine-center A2ALL study. A2ALL data were collected independently of OPTN data submission (48 data elements among 785 liver transplant candidates/recipients; 12 data elements among 386 donors). At least 90% agreement occurred between OPTN/SRTR and A2ALL for 11/29 baseline recipient elements, 4/19 recipient transplant or follow-up elements and 6/12 donor elements. For the remaining recipient and donor elements, >10% of values were missing in OPTN/SRTR but present in A2ALL, confirming that missing data were largely avoidable. Other than variables required for allocation, the percentage missing varied widely by center. These findings support an expanded focus on data quality control by OPTN/SRTR for a broader variable set than those used for allocation. Center-specific monitoring of missing values could substantially improve the data.

Recipient morbidity after living and deceased donor liver transplantation: findings from the A2ALL Retrospective Cohort Study.

Patients considering living donor liver transplantation (LDLT) need to know the risk and severity of complications compared to deceased donor liver transplantation (DDLT). One aim of the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) was to examine recipient complications following these procedures. Medical records of DDLT or LDLT recipients who had a living donor evaluated at the nine A2ALL centers between 1998 and 2003 were reviewed. Among 384 LDLT and 216 DDLT, at least one complication occurred after 82.8% of LDLT and 78.2% of DDLT (p = 0.17). There was a median of two complications after DDLT and three after LDLT. Complications that occurred at a higher rate (p < 0.05) after LDLT included biliary leak (31.8% vs. 10.2%), unplanned reexploration (26.2% vs. 17.1%), hepatic artery thrombosis (6.5% vs. 2.3%) and portal vein thrombosis (2.9% vs. 0.0%). There were more complications leading to retransplantation or death (Clavien grade 4) after LDLT versus DDLT (15.9% vs. 9.3%, p = 0.023). Many complications occurred more commonly during early center experience; the odds of grade 4 complications were more than two-fold higher when centers had performed 40). In summary, complication rates were higher after LDLT versus DDLT, but declined with center experience to levels comparable to DDLT.

Relationship of serum leptin concentration and other measures of adiposity with gallbladder disease.

Obesity increases the risk of gallstones, especially in women. Most gallbladder disease studies have used body mass index (BMI) as a measure of overall adiposity, although BMI does not distinguish between fat and lean body mass. Central adiposity may also increase gallstone risk, although this is less well studied. Leptin is a peptide whose serum concentration is highly correlated with total body fat mass. We examined the relationship of gallbladder disease with anthropometric measures and serum leptin concentration in a large, national, population-based study. A total of 13,962 adult participants in the Third National Health and Nutrition Examination Survey underwent gallbladder ultrasonography and anthropometric measurements of BMI, body circumferences, and skinfold thicknesses, and a random subgroup of 5,568 had measures of fasting serum leptin concentrations. Gallstone-associated gallbladder disease was defined as ultrasound-documented gallstones or evidence of cholecystectomy. When controlling for BMI and other gallbladder disease risk factors in multivariate analysis, a test for trend for increasing waist-to-hip circumference ratio and risk of gallbladder disease was statistically significant among women (P =.043) and men (P =.007). BMI remained strongly associated with gallbladder disease among women (P <.001), but was unrelated among men (P =.46). Leptin concentration was associated with gallbladder disease in both sexes (P <.001), but not after controlling for BMI and waist-to-hip circumference in either women (P =.29) or men (P =.65). In conclusion, waist-to-hip circumference ratio was related to gallbladder disease among women and men. Serum leptin concentration was not a better predictor of gallbladder disease than anthropometry.

Hospitalization with respiratory disease following hiatal hernia and reflux esophagitis in a prospective, population-based study.

PURPOSE: Hiatal hernia and reflux esophagitis have been associated with respiratory manifestations, though the temporal sequence of this relationship is uncertain. This study examined prospectively the relationship of hiatal hernia and reflux esophagitis with respiratory outcomes in a representative sample of the United States population. METHODS: 6928 participants in the first National Health and Nutrition Examination Survey, a population-based sample initially examined in 1971-1975, who were hospitalized during follow-up through 1992-1993 composed the study population. The relationship between hiatal hernia and reflux esophagitis hospitalization and a subsequent hospitalization with respiratory outcomes was measured in persons free of respiratory disease at baseline and at first hospitalization. RESULTS: Multivariable survival analysis showed higher rates of hospitalization with any respiratory diagnosis [rate ratio (RR) = 1.4, 95% confidence interval (CI) 1.2-1.7] in persons with preceding hiatal hernia or reflux esophagitis hospitalization. Individually, rate ratios of pharyngitis (RR = 5.6, CI 2.0-15.7), tonsillitis (RR = 8.0, CI 2.5-25.8), bronchitis (RR = 1.8, CI 1.2-2.7), pneumonia (RR = 1.3, CI 1.0-1.7), emphysema (RR = 2.9, CI 1.5-5.5), asthma (RR = 2.1, CI 1.1-4.2), bronchiectasis (RR = 6.2, CI 1.1-34.3), and empyema or abscess (RR = 7.4, CI 1.3-42.3) were all higher following hiatal hernia and reflux esophagitis. Rate ratios were similar when reflux esophagitis and hiatal hernia were examined separately. CONCLUSIONS: A prior hiatal hernia or reflux esophagitis hospitalization increased risk of respiratory disease hospitalization.

The role of diabetes in hepatocellular carcinoma: a case-control study among United States Veterans.

OBJECTIVE: Diabetes mellitus (DM) has been reported to increase the risk of hepatocellular carcinoma (HCC). We carried out a case-control study to examine the role of DM while controlling for several known risk factors of HCC. METHODS: All hospitalized patients with primary liver cancer (PLC) during 1997-1999 were identified in the computerized database of the Department of Veterans Affairs, the Patient Treatment File. Controls without cancer were randomly assigned from the Patient Treatment File during the same time period. The inpatient and outpatient files were searched for several conditions including DM, hepatitis C virus (HCV), hepatitis B virus (HBV), alcoholic cirrhosis, autoimmune hepatitis, hemochromatosis, and nonspecific cirrhosis. Adjusted odds ratios (OR) were calculated in a multivariable logistic regression model. RESULTS: We identified 823 patients with PLC and 3459 controls. The case group was older (62 yr [+/-10] vs 60 [+/-11], p < 0.0001), had more men (99% vs 97%, 0.0004), and a greater frequency of nonwhites (66% vs 71%, 0.0009) compared with controls. However, HCV- and HBV-infected patients were younger among cases than controls. Risk factors that were significantly more frequent among PLC cases included HCV (34% vs 5%, p < 0.0001), HBV (11% vs 2%, p < 0.0001), alcoholic cirrhosis (47% vs 6%, p < 0.0001), hemochromatosis (2% vs 0.3%, p < 0.0001), autoimmune hepatitis (5% vs 0.5%, p < 0.0001), and diabetes (33% vs 30%, p = 0.059). In the multivariable logistic regression, diabetes was associated with a significant increase in the adjusted OR of PLC (1.57, 1.08-2.28, p = 0.02) in the presence of HCV, HBV, or alcoholic cirrhosis. Without markers of chronic liver disease, the adjusted OR for diabetes and PLC was not significantly increased (1.08, 0.86-1.18, p = 0.4). There was an increase in the HCV adjusted OR (17.27, 95% Cl = 11.98-24.89) and HBV (9.22, 95% CI = 4.52-18.80) after adjusting for the younger age of HCV- and HBV-infected cases. The combined presence of HCV and alcoholic cirrhosis further increases the risk with an adjusted OR of 79.21 (60.29-103.41). The population attributable fraction for HCV among hospitalized veterans was 44.8%, whereas that of alcoholic cirrhosis was 51%. CONCLUSION: DM increased the risk of PLC only in the presence of other risk factors such as hepatitis C or B or alcoholic cirrhosis. Hepatitis C infection and alcoholic cirrhosis account for most of PLC among veterans.

Leptin concentrations in the United States: relations with demographic and anthropometric measures.

BACKGROUND: Leptin is a peptide that is strongly correlated with adiposity and is a potential determinant of obesity and its complications. OBJECTIVE: Leptin concentrations from a representative sample of the US population were examined in relation to demographic and anthropometric measures. DESIGN: Fasting serum leptin concentrations were measured in 6303 women and men aged > or =20 y in the third National Health and Nutrition Examination Survey. Anthropometric measures included body mass index, 4 skinfold thicknesses, and 4 body circumferences. Ethnic groups included non-Hispanic whites and blacks and Mexican Americans. RESULTS: The mean serum leptin concentration was much higher in women (12.7 microg/L) than in men (4.6 microg/L). In a multivariate analysis, leptin concentrations were associated with the sum of 4 skinfold thicknesses, waist and hip circumferences, ethnicity, and age. These measures explained most of the variance in leptin concentrations in women (R2 = 0.69) and in men (R2 = 0.67). Triceps skinfold thickness, when substituted for the sum of skinfold thicknesses, performed nearly as well in women (R2 = 0.68) and men (R2 = 0.67). Leptin concentrations were slightly but significantly higher in non-Hispanic blacks than in non-Hispanic whites of both sexes when these anthropometric measures and age were controlled for; Mexican Americans had concentrations that were intermediate compared with the concentrations of non-Hispanic whites and blacks. CONCLUSIONS: In this large, representative sample of the US population, demographic and anthropometric measures predicted serum leptin concentrations in women and men.

Relationship of iron-deficiency anemia with esophagitis and hiatal hernia: hospital findings from a prospective, population-based study.

OBJECTIVE: Iron-deficiency anemia is sometimes attributed to esophagitis and hiatal hernia; however, because these GI conditions are so common, such an association could be coincidental. We examined prospectively whether esophagitis and hiatal hernia increased the risk of iron-deficiency anemia in a national, population-based study. METHODS: The study population comprised 5069 adult participants in the first National Health and Nutrition Examination Survey, who were free of GI hemorrhage and anemia at baseline examination in 1971-1975 and who were hospitalized at some point during nearly 20 yr of follow-up. Rates of hospitalization with iron-deficiency or unspecified anemia were compared between patients with a hospital diagnosis of esophagitis or hiatal hernia and those who had not yet had a diagnosis of these disorders. Adjusted rate ratios were calculated using time-dependent, multivariable, proportional hazards analysis. RESULTS: During follow-up, 59 patients were hospitalized with esophagitis alone, 140 with hiatal hernia alone, and 70 with both diagnoses. A total of 102 participants were hospitalized with iron-deficiency anemia and 256 with unspecified anemia. Compared to those without a diagnosis of esophagitis or hiatal hernia, patients with a diagnosis of hiatal hernia had higher rates of subsequent hospitalization with iron-deficiency anemia. The hazard rate ratio (HRR) for hiatal hernia was 2.9 (95% confidence interval, 1.5-5.5). A trend was found for esophagitis with a HRR of 2.2 (95% confidence interval, 0.79-6.0). Results were similar with unspecified anemia as the outcome. CONCLUSIONS: Hiatal hernia should be considered as a possible cause of iron-deficiency anemia. The relationship of esophagitis with iron-deficiency anemia requires further study.

Gallstones and ethnicity in the Americas.

Information on ethnicity as related to gallstones has been limited by insufficient or inaccurate characterization of ethnicity. Nevertheless, in recent years, ultrasonography has allowed limited examination of ethnic differences in the risk of gallbladder disease, defined by a history of cholecystectomy or ultrasonographic detection of gallstones. Among women, the risk of gallbladder disease is highest among American Indians, followed by Hispanics, non-Hispanic whites, and non-Hispanic blacks. Men differ from women by having lower risk in all ethnic groups and by having a similar prevalence between Hispanics and non-Hispanic whites. It does not appear that the type of stone differs much according to ethnic group in the United States. Well-known risks for gallbladder disease, such as obesity, weight loss, pregnancy, and low alcohol use do not explain differences in ethnic risk. As yet, genetic markers have not been identified that would explain differences in risk among ethnic groups. Higher case fatality rates among non-Hispanic blacks than non-Hispanic whites suggest that blacks may have inadequate access to medical care for gallbladder disease.

Association of coffee consumption with gallbladder disease.

Coffee consumption was recently shown to protect against symptomatic gallbladder disease in men. The authors examined the relation of ultrasound-documented gallbladder disease with coffee drinking in 13,938 adult participants in the Third National Health and Nutrition Examination Survey, 1988-1994. The prevalence of total gallbladder disease was unrelated to coffee consumption in either men or women. However, among women a decreased prevalence of previously diagnosed gallbladder disease was found with increasing coffee drinking (p = 0.027). These findings do not support a protective effect of coffee consumption on total gallbladder disease, although coffee may decrease the risk of symptomatic gallstones in women.

Recent developments in the epidemiology of Helicobacter pylori.

Prevalence determinations have been performed around the world, and regardless of how exotic a location, H. pylori is found in a substantial proportion of the population. H. pylori remains among the most universal of infections. Understanding of some features of infection has changed. Infection can be gained and lost at rates higher than previously realized. Oral-oral and oral-fecal transmission account for most, if not nearly all, cases of infection. H. pylori infection has declined rapidly in developed countries, which probably has contributed to declines in duodenal ulcer disease and gastric cancer. The full health implications of the potential elimination of infection are unknown.

Food intake patterns and gallbladder disease in Mexican Americans.

OBJECTIVE: Results of previous studies on diet and gallbladder disease (GBD), defined as having gallstones or having had surgery for gallstones, have been inconsistent. This research examined patterns of food intake in Mexican Americans and their associations with GBD. DESIGN: Cross-sectional. SUBJECTS: The study population included 4641 Mexican Americans aged 20-74 years who participated in the 1988-94 third National Health and Nutrition Examination Survey (NHANES III). GBD was diagnosed by ultrasound. Food intake patterns were identified by principal components analysis based on food frequency questionnaire responses. Component scores representing the level of intake of each pattern were categorized into quartiles, and prevalence odds ratios (POR) were estimated relative to the lowest quartile along with 95% confidence intervals (CI). RESULTS: There were four distinct patterns in women (vegetable, high calorie, traditional, fruit) and three in men (vegetable, high calorie, traditional). After age adjustment, none were associated with GBD in women. However, men in the third (POR = 0.42, 95%CI 0.21-0.85) and fourth (POR = 0.53, 95%CI 0.28-1.01) quartiles of the traditional intake pattern were half as likely to have GBD as those in the lowest quartile. CONCLUSIONS: These findings add to a growing literature suggesting dietary intake patterns can provide potentially useful and relevant information on diet-disease associations. Nevertheless, methods to do so require further development and validation.

Influence of parental height and sociodemographic factors on adolescent height in Brazil.

OBJECTIVE: To analyze the influence of parental stature and environmental factors on the stature of adolescents from a national survey sample. METHODS: A nationwide survey was carried out in 1989 among a stratified, two-stage, probability cluster sample of 14,455 Brazilian households to provide estimates of anthropometric deficits for urban and rural populations from the five regions of the country. Stature was measured for 5681 boys and girls age 14-18 years, 78.9% of their fathers, and 93.8% of their mothers. Associations between explanatory variables and adolescent height in centimeters were assessed by fitting multiple linear models to the data. RESULTS: The predicted effects of parental stature and environmental conditions together sum to a total of 17 cm when comparing a boy born to parents with stature below the median and living in the underdeveloped rural Northeast region (1.56 m) with one born to parents with stature above the median and living in the partially industrialized urban South region (1.73 m). For girls, this estimated difference was 12 cm. For boys, the overall influence of parents' stature was 10 cm (R(2)= 0.40) and the sociodemographic factors had an overall influence of 7 cm (R(2) = 0.29). For girls, these values were 7 cm (R(2)= 0.35) for the parental influence and 5 cm (R(2) = 0.11) for the sociodemographic factors. CONCLUSIONS: Mother's stature had the same influence on adolescent's stature as father's stature. Independent of parental stature, environmental factors have a strong influence on adolescent stature, particularly among boys.

Country of birth and prevalence of gallbladder disease in Mexican Americans.

OBJECTIVES: This research sought to describe the association between country of birth and gallbladder disease (GBD) in Mexican Americans, identify subgroups at especially high risk, and identify risk factors that may mediate a birthplace-GBD association. DESIGN: Cross-sectional. METHODS: Our study population included 4157 Mexican Americans aged 20-74 who participated in the 1988-94 third National Health and Nutrition Examination Survey. GBD was diagnosed by ultrasound. Information on country of birth, education, income, and selected GBD risk factors was obtained from interviews. Prevalence odds ratios (POR) for GBD in Mexico- vs. US-born Mexican Americans were estimated by unconditional logistic regression, along with 95% confidence intervals (CI). To evaluate the extent to which GBD risk factors mediated the birthplace-GBD association, PORs for country of birth were compared in models with and without additional covariates. RESULTS: Age-adjusted GBD prevalence was lower in Mexico- than in US-born Mexican-American women (POR = 0.70, 95% CI 0.50, 0.98) and men (POR = 0.63, 95% CI 0.40, 0.97). The difference was especially pronounced among subjects of lower socioeconomic status. Despite substantial differences in GBD risk factor distributions by birthplace, none could completely explain the prevalence difference. CONCLUSIONS: The observation that GBD prevalence is higher among US-born Mexican Americans is consistent with research showing poorer health in this group. Further research is needed to identify strategies for reducing morbidity from GBD in Mexican Americans.

Seroprevalence and ethnic differences in Helicobacter pylori infection among adults in the United States.

The seroprevalence of Helicobacter pylori infection was examined in the adult US population and among different ethnic groups. Stored sera from 7465 adult participants in the first phase of the third National Health and Nutritional Examination Survey (1988-1991) were tested with a sensitive and specific IgG ELISA, to diagnose infection. Seroprevalence of H. pylori among all participants was 32. 5%. This increased with age, from 16.7% for persons 20-29 years old to 56.9% for those > or =70 years old. Age-adjusted prevalence was substantially higher among non-Hispanic blacks (52.7%) and Mexican Americans (61.6%) than among non-Hispanic whites (26.2%). After controlling for age and other associated factors, the odds ratios relative to non-Hispanic whites decreased for non-Hispanic blacks, from 3.9 (95% confidence interval [CI], 3.1-4.9) to 3.3 (95% CI, 2. 6-4.2), and for Mexican Americans, from 6.3 (95% CI, 4.8-8.3) to 2.3 (95% CI, 1.6-3.5). The high prevalence of H. pylori infection among non-Hispanic blacks and Mexican Americans is partially explained by other factors associated with infection.

Association of diabetes, serum insulin, and C-peptide with gallbladder disease.

An inconsistent association has been found between gallbladder disease and diabetes mellitus. We hypothesized that insulin resistance rather than diabetes status may be a primary factor involved in gallstone formation. A total of 5,653 adult participants in the third United States National Health and Nutrition Examination Survey without known diabetes underwent gallbladder ultrasonography and phlebotomy after an overnight fast for measurement of serum insulin, C-peptide, and glucose. Gallbladder disease was defined as ultrasound-documented gallstones or evidence of cholecystectomy. Subjects were characterized as having normal fasting glucose (<110 mg/dL), impaired fasting glucose (110 to <126 mg/dL), or undiagnosed diabetes (>/=126 mg/dL). After controlling for other known gallbladder disease risk factors, among women, undiagnosed diabetes was associated with increased risk of gallbladder disease (prevalence ratio [PR] = 1.91, 95% confidence interval [CI] = 1.29-2. 83); whereas impaired fasting glucose was unassociated. Gallbladder disease risk in women increased with levels of fasting insulin (PR = 1.63, 95% CI = 1.11-2.40) and C-peptide (PR = 2.07, 95% CI = 1.32-3. 25) comparing highest to lowest quintiles. However, the association of gallbladder disease with undiagnosed diabetes was not diminished when the model included fasting insulin (PR = 1.85, 95% CI = 1.24-2. 77). In men, there was a statistically nonsignificant association with undiagnosed diabetes (PR = 2.11, 95% CI = 0.76-5.85), but no association of gallbladder disease with insulin or C-peptide. Among women higher fasting serum insulin levels increased the risk of gallbladder disease, but did not account for the increased risk in persons with diabetes.

Improved survival after variceal hemorrhage over an 11-year period in the Department of Veterans Affairs.

OBJECTIVES: Over the past two decades, several modalities have become widely used in the management of esophageal variceal hemorrhage. The effectiveness of these measures on the outcome of patients with this type of hemorrhage remains unknown. METHODS: Using the Department of Veterans Affairs (VA) Patient Treatment File, we identified two cohorts of patients diagnosed with an initial variceal hemorrhage: an early cohort during 1981-1982 (1339 patients), and a late cohort during 1988-1991 (3636 patients). Each cohort was followed for 6 yr for rebleeding and death. Analyses were performed with proportional hazards survival analysis controlling for confounding factors. RESULTS: On presentation, patients in the late cohort were older (57 yr vs 55 yr, p < 0.0001) and had more ascites (25% vs 13%, p < 0.0001), more peritonitis (4% vs 2%, p < 0.0001), and more encephalopathy (14% vs 9%, p = 0.0003). The late cohort experienced a significant decline in mortality at 30 days (20.8% vs 29.6%, p = 0.0001) and at 6 yr (69.7% vs 74.5%, p = 0.0001). This improvement was accentuated in multivariate survival analysis when controlling for the more severe illness in the late cohort. For patients who survived the first 30 days, no significant difference in 6-yr mortality was found on univariate analysis between the early cohort (63.7%) and late cohort (61.8%) (p = 0.25), but survival was slightly better in the late cohort on multivariate analysis (p = 0.01). In the late cohort, patients with sclerotherapy during the initial hospitalization had better 30-day (17%) and 6-yr mortality (68%) than did the rest of the late cohort. CONCLUSIONS: Between the years 1981-1982 and 1988-1991, improvements in long-term survival after an initial episode of esophageal variceal hemorrhage resulted primarily from better short-term mortality. Sclerotherapy offers a partial explanation for improved survival.