Epidemiologic research and the action plan for liver disease research.
Explore the source record for details and available documents.
Epidemiologic Research Design↗
Biomedical subjects
James E Everhart
Publications and source records attributed to James E Everhart.
Daily activity energy expenditure and mortality among older adults.
CONTEXT: Exercise is associated with mortality benefits but simply expending energy through any activity in an individual's free-living environment may confer survival advantages. OBJECTIVE: To determine whether free-living activity energy expenditure is associated with all-cause mortality among older adults. DESIGN, SETTING, AND PARTICIPANTS: Free-living activity energy expenditure was assessed in 302 high-functioning, community-dwelling older adults (aged 70-82 years). Total energy expenditure was assessed over 2 weeks using doubly labeled water. Resting metabolic rate was measured using indirect calorimetry and the thermic effect of meals was estimated at 10% of total energy expenditure. Free-living activity energy expenditure was calculated as: (total energy expenditure x 0.90) - resting metabolic rate. Participants were followed up over a mean of 6.15 years (1998-2006). MAIN OUTCOME MEASURES: Free-living activity energy expenditure (3 tertiles: low, <521 kcal/d; middle, 521-770 kcal/d; high, >770 kcal/d) and all-cause mortality. RESULTS: Fifty-five participants (18.2%) died during follow-up. As a continuous risk factor, an SD increase in free-living activity energy expenditure (287 kcal/d) was associated with a 32% lower risk of mortality after adjusting for age, sex, race, study site, weight, height, percentage of body fat, and sleep duration (hazard ratio, 0.68; 95% confidence interval, 0.48-0.96). Using the same adjustments, individuals in the highest tertile of free-living activity energy expenditure were at a significantly lower mortality risk compared with the lowest tertile (hazard ratio, 0.31; 95% confidence interval, 0.14-0.69). Absolute risk of death was 12.1% in the highest tertile of activity energy expenditure vs 24.7% in the lowest tertile; absolute risks were similar to these for tertiles of physical activity level. The effect of free-living activity energy expenditure changed little after further adjustment for self-rated health, education, prevalent health conditions, and smoking behavior. According to self-reports, individuals expending higher levels of free-living activity energy were more likely to work for pay (P = .004) and climb stairs (P = .01) but self-reported high-intensity exercise, walking for exercise, walking other than for exercise, volunteering, and caregiving did not differ significantly across the activity energy expenditure tertiles. CONCLUSIONS: Objectively measured free-living activity energy expenditure was strongly associated with lower risk of mortality in healthy older adults. Simply expending energy through any activity may influence survival in older adults.
Activities of Daily Living↗
HCV RNA detection by TMA during the hepatitis C antiviral long-term treatment against cirrhosis (Halt-C) trial.
For making treatment decisions related to chronic hepatitis C, the utility of HCV RNA tests with increased sensitivity has not been defined. Prior interferon nonresponders with advanced fibrosis (n = 1,145) were retreated with peginterferon alpha-2a and ribavirin. Patients who were HCV RNA-negative by a polymerase chain reaction (PCR)-based assay (Roche COBAS Amplicor HCV Test, v. 2.0; lower limit of detection [LOD] 100 IU/mL) at week 20 (W20) received treatment for 48 weeks. Stored specimens were tested using the Bayer VERSANT HCV RNA Qualitative (TMA) Assay (LOD 9.6 IU/mL) and compared to PCR results for the ability to predict sustained virological response (SVR; defined as undetectable HCV RNA by PCR at W72). Nearly all PCR-positive samples (1006/1007, 99.9%) were positive as assessed by TMA. Among 1,294 PCR-negative samples, 22% were TMA-positive. Negative TMA results were more predictive of SVR than were negative PCR results at W12 (82% vs. 64%, P < .001) and at W20 (66% vs. 52%, P = 0.001). SVR was more likely the earlier TMA had become negative during treatment (82% at W12, 44% at W20, 20% at W24). Among 45 patients who were TMA-positive but were PCR-negative at W20 and W24, none achieved SVR (95% CI: 0%-8%). Approximately 10% of patients with a single positive TMA result at the end of treatment still achieved SVR. In conclusion, negative TMA results at or after W12 were superior to negative PCR results for predicting SVR. In patients with negative PCR results during treatment, a single positive TMA test did not exclude SVR, although persistently positive tests did.
Antiviral Agents↗
The prevalence and risk factors associated with esophageal varices in subjects with hepatitis C and advanced fibrosis.
BACKGROUND: The factors predictive of the presence or the absence of esophageal varices in hepatitis C virus (HCV) and advanced fibrosis have not been defined. OBJECTIVES: To define the prevalence of esophageal varices and the factors that are positively and negatively with such varices in hepatitis C and advanced fibrosis. DESIGN: A prospective study of esophageal varices and associated risk factors in subjects with hepatitis C and advanced fibrosis. SETTING: Prerandomization data from the HALT-C (hepatitis C long-term antiviral treatment against cirrhosis) clinical trial. PATIENTS AND INTERVENTION: Subjects with bridging fibrosis or cirrhosis, who were virologic nonresponders to treatment with pegylated interferon alpha 2a and ribavirin, underwent endoscopy. RESULTS: Sixteen percent of subjects with bridging fibrosis (95/598) and 39% of subjects with cirrhosis (164/418) had varices (P < .0001); 2% of subjects with bridging fibrosis (13/598) and 11% of those with cirrhosis (48/418) had medium or large varices. Subjects with bridging fibrosis and varices had a significantly lower platelet count and higher bilirubin and international normalized ratio (INR) compared with those without varices, suggesting that the biopsy may have underestimated the severity of fibrosis. A platelet count >150,000/mm(3) was associated with a negative predictive value of 99% for esophageal varices. By logistic regression modeling, African American race and female sex were protective, whereas a lower platelet count and higher bilirubin and INR predicted varices (c statistic, 0.758). CONCLUSIONS: The risk of having varices increases with decreasing platelet counts, increasing bilirubin, and INR. The probability of having medium or large varices at platelet counts >150,000/mm(3) is negligible in this population.
Antiviral Agents↗
Modifiable environmental and behavioral determinants of overweight among children and adolescents: report of a workshop.
The number of children at risk for overweight and the number of overweight children are increasing and have become a serious public health concern. Interventions that could be applied at the population level have not been proven effective. The development of effective strategies is thought to be hampered by the lack of understanding of which behavioral and environmental factors need to be modified. On June 14 and 15, 2004, the NIH held a meeting of experts to discuss the issue of modifiable determinants of obesity in children and adolescents. Included were presentations on interventions among children that have been proven effective, dietary and physical activity behavioral determinants, physical, social, and family environmental determinants, and the quality of measures of determinants and correlates of overweight.
Adolescent↗
Alcohol and hepatitis C: do we have a drinking problem?
Explore the source record for details and available documents.
Alcohol Drinking↗
Predicting cirrhosis in patients with hepatitis C based on standard laboratory tests: results of the HALT-C cohort.
Knowledge of the presence of cirrhosis is important for the management of patients with chronic hepatitis C (CHC). Most models for predicting cirrhosis were derived from small numbers of patients and included subjective variables or laboratory tests that are not readily available. The aim of this study was to develop a predictive model of cirrhosis in patients with CHC based on standard laboratory tests. Data from 1,141 CHC patients including 429 with cirrhosis were analyzed. All biopsies were read by a panel of pathologists (blinded to clinical features), and fibrosis stage was determined by consensus. The cohort was divided into a training set (n = 783) and a validation set (n = 358). Variables that were significantly different between patients with and without cirrhosis in univariate analysis were entered into logistic regression models, and the performance of each model was compared. The area under the receiver-operating characteristic curve of the final model comprising platelet count, AST/ALT ratio, and INR in the training and validation sets was 0.78 and 0.81, respectively. A cutoff of less than 0.2 to exclude cirrhosis would misclassify only 7.8% of patients with cirrhosis, while a cutoff of greater than 0.5 to confirm cirrhosis would misclassify 14.8% of patients without cirrhosis. The model performed equally well in fragmented and nonfragmented biopsies and in biopsies of varying lengths. Use of this model might obviate the requirement for a liver biopsy in 50% of patients with CHC. In conclusion, a model based on standard laboratory test results can be used to predict histological cirrhosis with a high degree of accuracy in 50% of patients with CHC.
Adult↗
Serum alpha-fetoprotein levels in patients with advanced hepatitis C: results from the HALT-C Trial.
BACKGROUND/AIMS: Alpha-fetoprotein (AFP) has been useful in the diagnosis of hepatocellular carcinoma (HCC) but lacks specificity. We assessed serum AFP among patients with chronic hepatitis C and advanced fibrosis to establish predictors of AFP elevations and changes with antiviral therapy. METHODS: Serum AFP was measured at baseline and on therapy in patients in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C). AFP levels were correlated with patient demographic and clinical features. RESULTS: Baseline AFP was > or = 20 ng/mL in 191 of 1145 patients (16.6%). Mean AFP values were significantly higher in patients with cirrhosis than in those with bridging fibrosis (22.5 vs. 11.4 ng/mL, P < 0.0001). Factors independently associated with raised serum AFP in patients with cirrhosis were female gender, black race, decreased platelet count, increased serum AST/ALT ratio, serum ferritin, and Mallory bodies in liver biopsies. Serum AFP levels decreased significantly during therapy with pegylated interferon alpha-2a and ribavirin. HCC was identified in six subjects, only three of whom had AFP > 20 ng/mL. CONCLUSIONS: Among patients with advanced chronic hepatitis C, serum AFP values are frequently elevated, even in the absence of HCC. Factors associated with raised AFP include severity of liver disease, female gender and black race. Serum AFP levels decline during antiviral therapy.
Alanine Transaminase↗
Is cirrhosis an inevitable consequence of chronic hepatitis C virus infection?
Explore the source record for details and available documents.
Asian People↗
Joint effects of body weight and alcohol on elevated serum alanine aminotransferase in the United States population.
BACKGROUND & AIMS: Both alcohol and obesity are associated with hepatic steatosis. However, little is known about whether the toxicity of alcohol to the liver is influenced by adiposity. We examined the relationship of alcohol drinking and binge drinking with abnormal serum aminotransferase activity in normal weight, overweight, and obese persons in a national, population-based study. METHODS: Data were analyzed from 13,580 adult participants in the third US National Health and Nutrition Examination Survey, 1988-1994, after excluding participants with hepatitis B or C or iron overload. Abnormal aminotransferase levels were defined by using sex-specific cutoffs for ALT and AST. Analyses were adjusted for other liver injury risk factors. RESULTS: The prevalence of abnormal aminotransferase activity was elevated with consumption of >2 drinks per day or with overweight and obesity. In multivariate analysis, there was no association of alcohol intake with a higher prevalence of elevated aminotransferase levels among normal weight persons. In contrast, among overweight persons, consumption of >2 drinks per day increased the risk of elevated aminotransferase levels, and among the obese, > or = 1 drink per day was associated with a higher risk. Results were similar with elevated ALT alone as the outcome. With elevated AST alone as the outcome, intake of >2 drinks per day increased the risk, even among normal weight persons. Binge drinking was associated with aminotransferase elevation among obese consumers of 1-2 drinks per day. CONCLUSIONS: In this large, national, population-based study, overweight and obesity increased the risk of alcohol-related abnormal aminotransferase activity.
Adult↗
Coffee and caffeine consumption reduce the risk of elevated serum alanine aminotransferase activity in the United States.
BACKGROUND & AIMS: Based on experimental and epidemiologic studies, we investigated whether coffee and caffeine consumption reduced the risk of elevated alanine aminotransferase (ALT) activity in persons at high risk for liver injury in a national, population-based study. METHODS: Participants were 5944 adults in the Third US National Health and Nutrition Examination Survey, 1988-1994, with excessive alcohol consumption, viral hepatitis, iron overload, overweight, or impaired glucose metabolism. Liver injury was indicated by abnormal serum ALT activity (>43 U/L). RESULTS: Elevated ALT activity was found in 8.7% of this high-risk population. In unadjusted analysis, lower ALT activity was associated with increasing consumption of coffee ( P = .001) and caffeine ( P = .001). Multivariate logistic regression analyses showed that the risk of elevated ALT activity declined with increasing intake of coffee ( P for trend = .034) and caffeine ( P < .001). Comparing persons who drank more than 2 cups per day with noncoffee drinkers, the odds ratio was .56 (95% confidence interval, .31-1.0). Comparing persons in the highest caffeine quintile with the lowest, the odds ratio was .31 (95% confidence interval, .16-.61). These relationships were consistent across subgroups at risk for liver injury and were relatively unchanged when analyses included the entire population or when limited to persons without impaired liver function or right upper quadrant pain. Fasting insulin concentrations did not mediate the effects. CONCLUSIONS: In this large, national, population-based study, among persons at high risk for liver injury, consumption of coffee and especially caffeine was associated with lower risk of elevated ALT activity.
Alanine Transaminase↗
Coffee and tea consumption are associated with a lower incidence of chronic liver disease in the United States.
BACKGROUND & AIMS: Coffee drinking has been suggested to protect against liver injury, but it is uncertain whether this is of clinical significance. We examined the relationship of coffee and tea consumption with the incidence of hospitalization or death from chronic liver disease (CLD). METHODS: Participants in the population-based, first National Health and Nutrition Examination Survey, 1971-1975, were asked about coffee and tea consumption, which was categorized as <1 cup (mean, 0.2 cups), 1 to 2 cups, and >2 cups per day (mean, 4.0 cups). A second analysis included persons who, in 1982-1984, were asked more detailed questions on coffee and tea drinking. Participants were followed through 1992-1993 for a hospital or death certificate diagnosis of CLD or cirrhosis (ICD-9-CM 571). Hazard rate ratios for CLD according to coffee and tea intake were calculated using Cox proportional hazards analysis. RESULTS: Among 9849 persons followed for a median of 19.0 years (range, 0.02-22.1), the cumulative incidence of CLD was 1.4%. In multivariate analysis, participants who drank >2 cups per day had less than half the rate of CLD as those who drank <1 cup per day (hazard ratio, 0.43, 95% confidence interval: 0.24-0.78). Protection by coffee and tea was limited to persons at higher risk for liver diseases from heavier alcohol intake, overweight, diabetes, or high iron saturation. Among 9650 participants who provided detailed drink information in 1982-1984, intake of regular ground coffee and of caffeine was associated with lower incidence of CLD. CONCLUSIONS: Coffee and tea drinking decreases the risk of clinically significant CLD.
Adult↗
Outcomes of 385 adult-to-adult living donor liver transplant recipients: a report from the A2ALL Consortium.
OBJECTIVE: The objective of this study was to characterize the patient population with respect to patient selection, assess surgical morbidity and graft failures, and analyze the contribution of perioperative clinical factors to recipient outcome in adult living donor liver transplantation (ALDLT). SUMMARY BACKGROUND DATA: Previous reports have been center-specific or from large databases lacking detailed variables. The Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) represents the first detailed North American multicenter report of recipient risk and outcome aiming to characterize variables predictive of graft failure. METHODS: Three hundred eighty-five ALDLT recipients transplanted at 9 centers were studied with analysis of over 35 donor, recipient, intraoperative, and postoperative variables. Cox regression models were used to examine the relationship of variables to the risk of graft failure. RESULTS: Ninety-day and 1-year graft survival were 87% and 81%, respectively. Fifty-one (13.2%) grafts failed in the first 90 days. The most common causes of graft failure were vascular thrombosis, primary nonfunction, and sepsis. Biliary complications were common (30% early, 11% late). Older recipient age and length of cold ischemia were significant predictors of graft failure. Center experience greater than 20 ALDLT was associated with a significantly lower risk of graft failure. Recipient Model for End-stage Liver Disease score and graft size were not significant predictors. CONCLUSIONS: This multicenter A2ALL experience provides evidence that ALDLT is a viable option for liver replacement. Older recipient age and prolonged cold ischemia time increase the risk of graft failure. Outcomes improve with increasing center experience.
Adult↗
Evolution of the HALT-C Trial: pegylated interferon as maintenance therapy for chronic hepatitis C in previous interferon nonresponders.
The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial was designed to determine whether maintenance interferon therapy could slow disease progression in patients who had failed to eradicate hepatitis C virus (HCV) during prior interferon treatment (nonresponders). Ten clinical sites, a virological testing center, and a data coordinating center (DCC) were selected to collaborate in the design and implementation of the final protocol. Eligible patients had been treated previously with interferon for at least 12 weeks, with or without another antiviral, ribavirin, but still had persistent viremia. Because patients had received a variety of prior treatments, and as a perceived benefit of enrollment, we incorporated a Lead-in period of treatment with long-acting pegylated interferon alfa-2a plus ribavirin into the study design, a combination believed to be more effective but not approved by the Food and Drug Administration at the Trial's inception. If patients failed to achieve clearance of virus from the blood after 20 weeks of this Lead-in therapy, they were entered into the main trial at week 24 and randomized to receive either a lower dose of pegylated interferon weekly alone or no further therapy for an additional 3 1/2 years. The original protocol was amended later in three respects to improve enrollment and to adapt to Food and Drug Administration approval of the Lead-in therapy, including allowing patients to proceed directly to the randomized part of the study if treatment resembling the Lead-in had been completed. The protocol changes enhanced enrollment while upholding the original goals of the study and its integrity.
Antiviral Agents↗
Epidemiology of nonalcoholic fatty liver.
Nonalcoholic fatty liver (NAFL) is increasingly recognized as an important and common public health problem that can lead to cirrhosis and hepatic failure. Because it is often asymptomatic,many people may not know that they have it. NAFL is closely linked to obesity, which in the United States and other developed countries is becoming more common. Consequently, the proportion of the population affected by NAFL will likely increase. Despite the growing importance of this condition, knowledge of the epidemiology of NAFL is limited by the lack of an accurate,noninvasive measure for use in screening of the general population. This article reviews information available from studies with relatively unselected samples with regard to prevalence, demographics,and risk factors for NAFL.
Adult↗
Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma.
BACKGROUND & AIMS: An association between diabetes and chronic liver disease has been reported. However, the temporal relationship between these conditions remains unknown. METHODS: We identified all patients with a hospital discharge diagnosis of diabetes between 1985 and 1990 using the computerized records of the Department of Veterans Affairs. We randomly assigned 3 patients without diabetes for every patient with diabetes. We excluded patients with concomitant liver disease. The remaining cohort was followed through 2000 for the occurrence of chronic nonalcoholic liver disease (CNLD) and hepatocellular carcinoma (HCC). Hazard rate ratios (HRR) were determined in Cox proportional hazard survival analysis. RESULTS: The study cohort comprised 173,643 patients with diabetes and 650,620 patients without diabetes. Most were men (98%). Patients with diabetes were older (62 vs. 54 years) than patients without diabetes. The incidence of chronic nonalcoholic liver disease was significantly higher among patients with diabetes (incidence rate: 18.13 vs. 9.55 per 10,000 person-years, respectively, P < 0.0001). Similar results were obtained for HCC (incidence rate: 2.39 vs. 0.87 per 10,000 person-years, respectively, P < 0.0001). Diabetes was associated with an HRR of 1.98 (95% CI: 1.88 to 2.09, P < 0.0001) of CNLD and an HRR of 2.16 (1.86 to 2.52, P < 0.0001) of hepatocellular carcinoma. Diabetes carried the highest risk among patients with longer than 10 years of follow-up. CONCLUSIONS: Among men with diabetes, the risk of CNLD and HCC is doubled. This increase in risk is independent of alcoholic liver disease, viral hepatitis, or demographic features.
Aged↗
Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment.
BACKGROUND & AIMS: The most effective therapy currently available for treatment of chronic hepatitis C virus (HCV) is the combination of peginterferon and ribavirin. This study evaluated the effectiveness of this treatment in patients who were nonresponders to previous interferon-based therapy. METHODS: The first 604 patients enrolled in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial were evaluated. All were HCV RNA positive, previous nonresponders to interferon, with or without ribavirin, and had bridging fibrosis or cirrhosis on liver biopsy (Ishak fibrosis stage 3-6). Patients were retreated with peginterferon alfa-2a 180 microg/wk plus ribavirin 1000-1200 mg/day. Those with no detectable HCV RNA in serum at week 20 continued treatment for a total of 48 weeks and were then followed for an additional 24 weeks. RESULTS: Thirty-five percent of patients had no detectable HCV RNA in serum at treatment week 20, and 18% achieved sustained virologic response (SVR). Factors associated with an SVR included previous treatment with interferon monotherapy, infection with genotypes 2 or 3, a lower AST:ALT ratio, and absence of cirrhosis. Reducing the dose of ribavirin from > or =80% to < or =60% of the starting dose during the first 20 weeks of treatment was associated with a decline in SVR from 21% to 11% (P < or = 0.05). In contrast, reducing the dose of peginterferon or reducing ribavirin after week 20, when HCV RNA was already undetectable, did not significantly affect SVR. CONCLUSIONS: Selected nonresponders to previous interferon-based therapy can achieve SVR following retreatment with peginterferon alfa-2a and ribavirin.
Adult↗
Energy requirements in the eighth decade of life.
BACKGROUND: Knowledge of energy requirements among relatively healthy elderly is limited. OBJECTIVES: The objectives of the study were to measure total energy expenditure (TEE)-derived energy requirements in a biracial population of older adults without limitations to daily life and to test these empirical measures against national and international recommendations. DESIGN: TEE (measured by the doubly labeled water method), resting metabolic rate (RMR), activity-related energy expenditure (AEE), and body composition were measured in 288 persons aged 70-79 y selected from the Health, Aging, and Body Composition Study. RESULTS: TEE was lower in women (approximately 530 kcal/d; P < 0.0001) than in men because of the women's lower RMR and AEE. Fat-free mass explained the sex difference in RMR, but body weight failed to account for the women's lower AEE (approximately 1 kcal x kg(-1) x d(-1); P = 0.007). Blacks had lower TEE than did whites (approximately 100 kcal/d, P = 0.03), and that was explained by blacks' lower RMR. Physical activity level (TEE/RMR) did not differ significantly between sexes and races (1.70 +/- 0.23). The World Health Organization (WHO) recommendations overestimated TEE by 10 +/- 15% (P < 0.0001) in women but not in men, and the dietary reference intakes (DRIs) were accurate to 0 +/- 14% (P = 0.1). Both WHO and DRI recommendations are based on an underestimated physical activity level, and WHO recommendations are based on overestimated RMR. CONCLUSIONS: This study of well-functioning older adults confirms the racial difference in energy metabolism and supports the use of the 2002 DRIs. Because the DRIs and WHO recommendations underestimated PAL, new predictive equations of energy requirements are proposed.
Aged↗