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.

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.

Duration of obesity increases the incidence of NIDDM.

The effect of duration of obesity on incidence of non-insulin-dependent diabetes mellitus (NIDDM) was determined among Pima Indians. Duration of obesity was defined as the time since body mass index (BMI) was first known to be at least 30 kg/m2. Among 1057 participants eligible for study, there were 224 incident cases of NIDDM in 5975 person-yr of follow-up. The association of duration of obesity with incidence of diabetes adjusted for age, sex, and current BMI was highly significant (P less than 0.0001). This adjusted incidence of diabetes in cases/1000 person-yr of obesity was 24.8 for people with less less than 5 yr of obesity, 35.2 for people with 5-10 yr of obesity, and 59.8 for people with at least 10 yr of obesity. There was no apparent excess risk of diabetes for people who had a BMI of at least 30 kg/m2 and then lost weight. They had a slightly nonsignificantly higher rate than people who had not attained a BMI of at least 30 kg/m2 and a lower rate than people whose BMI remained 30-35 kg/m2. The relationship of duration of obesity with serum insulin concentrations among nondiabetic people was determined controlling for sex and age, BMI, and plasma glucose concentrations at the time of a glucose tolerance test. Duration of obesity was inversely associated with fasting serum insulin concentration through most of the range of fasting plasma glucose concentrations (P less than 0.001) and tended to be inversely associated with 2-h postload serum insulin concentration through the entire range of postload plasma glucose concentrations (P = 0.058).

Lower-extremity amputations in NIDDM. 12-yr follow-up study in Pima Indians.

The incidence of lower-extremity amputations was estimated in the Pima Indians of the Gila River Indian Community in Arizona, a population with a high prevalence of non-insulin-dependent diabetes mellitus (NIDDM). Between 1972 and 1984, from a study population of 4399 subjects, lower-extremity amputations were performed on 84 patients, 80 (95%) of whom had NIDDM. Among diabetic subjects, the incidence rate of first lower-extremity amputations was higher in men than in women. Rates increased significantly with increasing duration of diabetes. Presence of medial arterial calcification, retinopathy, or nephropathy; absence of patellar tendon reflexes; impaired great toe vibration-perception threshold; and degree of fasting and 2-h postload hyperglycemia were significant risk factors for amputations. Serum cholesterol concentration, blood pressure, age, and absence of Achilles tendon reflexes were not predictive of amputations. The death rate was greater in diabetic amputees than in diabetic nonamputees of similar age, sex, and duration of diabetes, and a significant increase in cardiovascular deaths was observed in diabetic subjects with amputations. The incidence rate of lower-extremity amputations in diabetic Pima Indians is higher than that reported in other diabetic populations. This may reflect differences in risk or a more complete case ascertainment than was possible in previous studies. If the latter is true, the rate of amputations in diabetic individuals may be higher than has been previously appreciated.

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.

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.

Increased waiting time for liver transplantation results in higher mortality.

BACKGROUND: Waiting time to liver transplantation (LTx) has dramatically lengthened, but the proportion of candidates who die awaiting transplantation has not increased. We evaluated whether longer waiting time for LTx candidates increases mortality. METHODS: A cohort of candidates listed for LTx between 1990 and 1993 by three large transplantation programs was followed for 2 years. The exposure measure was ABO blood type, which is not inherently related to outcome, but is a major determinant of waiting time. The main outcome measure was 2-year mortality, as evaluated by logistic regression analysis that controlled for differences in clinical status at the time of evaluation for LTx. RESULTS: The 308 candidates with type O blood waited longer for LTx (median 109 days) than the 399 candidates with other blood types (median 58 days) (P=0.001). Candidates listed for LTx with type O blood had better clinical status at evaluation, but then had higher pretransplantation mortality (13.3%) than other candidates (7.0%) (P=0.005). Blood group O candidates had higher 2-year mortality (26.6%) than other candidates (22.1%), which on multivariate analysis resulted in a mortality odds ratio at 2 years of 1.52 (95% confidence interval=1.04-2.23). With the difference in median waiting time between blood groups increasing from 44 days in the first year to 108 days in the third year, the 2-year mortality odds ratio also rose from 0.94 to 1.97. CONCLUSIONS: When compared with LTx candidates with other blood types, blood type O candidates have longer waiting times and higher pretransplantation mortality, which results in higher 2-year mortality.

Overweight, but not high dietary fat intake, increases risk of gastroesophageal reflux disease hospitalization: the NHANES I Epidemiologic Followup Study. First National Health and Nutrition Examination Survey.

PURPOSE: Gastroesophageal reflux disease is an important and increasingly common condition. Both overweight and high fat food consumption have been implicated as causes of reflux disease. We examined the relationship of overweight, high dietary fat intake, and other factors with reflux disease hospitalization. METHODS: We studied participants in the first National Health and Nutrition Examination Survey, a population-based sample examined in 1971-75 and followed through 1992-93. Persons with a physician-diagnosed hiatal hernia at baseline or reflux disease hospitalization within the first five years of study were excluded. A second analysis included follow-up of 9851 participants free of reflux disease in 1982-84. Ninety-six percent of the baseline cohort were recontacted. Reflux disease cases were persons hospitalized with a diagnosis of esophagitis or uncomplicated hiatal hernia. Hazard rate ratios for reflux disease hospitalization according to body mass index (BMI) (kg/m2), total daily servings of high fat foods and other factors were calculated using Cox proportional hazards analysis. RESULTS: A total of 12,349 persons were followed for a median of 18.5 years (range 5.0-22.1). Cumulative incidence of reflux disease hospitalization was 5.2% at 20 years. Multivariate survival analysis revealed higher reflux disease hospitalization rates with higher BMI (5 kg/m2) [hazard ratio (HR) = 1.22, 95% confidence interval (CI) = 1.13-1.32]. No relationship was found between higher fat intake and reflux disease hospitalization. Other factors associated with reflux disease hospitalization included age, low recreational activity, and history of doctor-diagnosed arthritis. CONCLUSIONS: Overweight, but not high dietary fat intake, increases risk of gastroesophageal reflux disease hospitalization.

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.

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.

Incidence, prevalence and risk factors for non-insulin-dependent diabetes mellitus.

Non-insulin-dependent diabetes is a worldwide disease. In the United States nearly 10 million persons are affected and the prevalence is increasing. Considerable advances in the understanding of the pathogenesis and determinants of non-insulin-dependent diabetes have occurred in recent years. Genetic and environmental determinants are associated with the development of diabetes, but the mode of inheritance of the genetic determinants is unknown. Obesity, particularly if it is centrally distributed and of long duration, is the most prominent environmental risk factor for non-insulin-dependent diabetes. Although it has long been suspected as an etiological factor, evidence that physical activity is a predictor of the disease is now emerging. The adoption of a western lifestyle and improvements in socioeconomic conditions are at least partially responsible for the very high rates of diabetes among several ethnic and racial groups, although the specific components of these changes that contribute to development of non-insulin-dependent diabetes are still uncertain. Other factors that worsen insulin resistance are likewise predictive of the development of disease. An understanding of the risk factors for non-insulin-dependent diabetes may lead to more specific intervention, and possibly to prevention of this disease.

Geographical patterns of proportionate mortality for the most common causes of death in Brazil.

Mortality due to chronic diseases has been increasing in all regions of Brazil with corresponding decreases in mortality from infectious diseases. The geographical variation in proportionate mortality for chronic diseases for 17 Brazilian state capitals for the year 1985 and their association with socio-economic variables and infectious disease was studied. Calculations were made of correlation coefficients of proportionate mortality for adults of 30 years or above due to ischaemic heart disease, stroke and cancer of the lung, the breast and stomach with 3 socio-economic variables, race, and mortality due to infectious disease. Linear regression analysis included as independent variables the % of illiteracy, % of whites, % of houses with piped water, mean income, age group, sex, and % of deaths caused by infectious disease. The dependent variables were the % of deaths due to each one of the chronic diseases studied by age-sex group. Chronic diseases were an important cause of death in all regions of Brazil. Ischaemic heart diseases, stroke and malignant neoplasms accounted for more than 34% of the mortality in each of the 17 capitals studied. Proportionate cause-specific mortality varied markedly among state capitals. Ranges were 6.3-19.5% for ischaemic heart diseases, 8.3-25.4% for stroke, 2.3-10.4% for infections and 12.2-21.5% for malignant neoplasm. Infectious disease mortality had the highest (p < 0.001) correlation with all the four socio-economic variables studied and ischaemic heart disease showed the second highest correlation (p < 0.05). Higher socio-economic level was related to a lower % of infectious diseases and a higher % of ischaemic heart diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

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).

Contributions of obesity and weight loss to gallstone disease.

OBJECTIVE: To examine the relation of obesity and weight loss to the formation of gallstones according to pertinent clinical and research issues. DATA SOURCES AND EXTRACTION: Original reports obtained through a MEDLINE search from 1966 to 1992 on gallstones plus obesity or reducing diets, supplemented by a manual search of bibliographies, a Current Contents title search from 1991 to 1992 on gallstones and gallbladder, and expert opinion. Only studies of humans were cited. DATA SYNTHESIS: For women, but less so for men, obesity is a strong risk factor for gallstones, and this risk is increased during weight loss. Between 10% and 25% of obese men and women may develop gallstones within a few months of beginning a very low calorie diet, and perhaps one third of these will develop symptoms of gallstones. Persons with the highest body mass index before weight loss and those who lose weight most rapidly appear to be at the greatest risk for gallstones. Treatment with ursodeoxycholic acid (ursodiol) during weight loss dieting is the only proven prevention for the formation of gallstones. Issues to be resolved include how different diets affect the risk for developing gallstones, the identification of other risk factors for gallstone formation during weight loss, the effect of weight loss among people with preexisting gallstones, and the optimum means of preventing gallstones during weight loss. CONCLUSIONS: During weight loss, particularly among the obese, an increased risk exists for symptomatic gallstone formation. This acute risk offers the opportunity to investigate the cause of gallstones and possibly to prevent them.

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.

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.