BackgroundSerum alanine aminotransferase (ALT) is a marker of liver injury. The 2005 American Gastroenterology Association Future Trends Committee report states that serum ALT levels remain constant with age. This study examines the association between serum ALT and age in a community-dwelling cohort in the United States.MethodsA cross-sectional study of 2,364 (54% female) participants aged 30–93 years from the Rancho Bernardo Study cohort who attended a research clinic visit in 1984–87. Demographic, metabolic co-variates, ALT, bilirubin, gamma glutamyl transferase (GGT), albumin, and adiposity signaling biomarkers (leptin, IL-6, adiponectin, ghrelin) were measured. Participants were divided into four-groups based upon age quartile, and multivariable-adjusted least squares of means (LSM) were examined (p for trend <0.05).ResultsALT decreased with increasing age, with mean ALT levels (IU/L) of 23, 21, 20, and 17 for those between quartile ages 30–62, 63–71, 72–77, and 78–93 years (p<0.0001). Trends of decreasing LSM ALT with age and the decreasing prevalence of categorically defined elevated serum ALT with age remained robust after adjusting for sex, alcohol use, metabolic syndrome components, and biomarkers of adiposity (p-value <0.0001), and was not materially changed after adjusting for bilirubin, GGT, and albumin.ConclusionsALT levels decrease with age in both men and women independent of metabolic syndrome components, adiposity signaling biomarkers, and other commonly used liver function tests. Further studies are needed to understand the mechanisms responsible for a decline in ALT with age, and to establish the optimal cut-point of normal ALT in the elderly.

Nonalcoholic fatty liver disease (NAFLD), first described in 1980, is now recognized as one of the most common causes of elevated liver enzymes and chronic liver disease in Western countries. The incidence of NAFLD in both adults and children is rising, in conjunction with the burgeoning epidemics of obesity and type 2 diabetes mellitus. NAFLD often coexists with other sequelae of the metabolic syndrome: central obesity, type 2 diabetes, hypertension, and hyperlipidemia. NAFLD encompasses a spectrum of pathologic liver diseases ranging from simple hepatic steatosis to a predominant lobular necro-inflammation, with or without centrilobular fibrosis (called nonalcoholic steatohepatitis or NASH). NASH can progress to cirrhosis, decompensated liver disease, and hepatocellular carcinoma. Though the natural history of NASH is still not clearly defined, it has been observed to progress to cirrhosis in 15%-220% of those affected. Insulin resistance is nearly universal in NASH and is thought to play an important role in its pathogenesis leading to dysregulated lipid metabolism. The prevalence of insulin resistance is reported in the general population to be approaching 45%, suggesting that NAFLD and NASH will contin nue to be an important public health concern. To date, NASH has proven to be a difficult disease to treat. Front-line therapy with lifestyle modifications resulting in weight loss through decreased caloric intake and moderate exercise is generally believed to be beneficial in patients with NASH, but is often difficult to maintain long term. Given that insulin resistance plays a dominant role in the pathogenesis, many studies have examined the use of insulin sensitizers: the biguanides (metformin), thiazolidinediones (pioglitazone, troglitazone, and rosiglitazone), glucagon-like peptide-1-receptor agonists, or incretins (exenatide)in NASH. This review will provide an overview of insulin resistance in NAFLD and provide a detailed summary on the clinical data regarding the use of insulin sensitizers in NASH.

Background & Aims An increased level of alanine aminotransferase (ALT) is a marker of liver injury. The mean ALT level has been reported to decrease with age; we performed a longitudinal analysis to determine whether serum levels of ALT changes with age among community-dwelling, older adults in the US. Methods We analyzed clinical data from 2 cohorts of individuals who participated in the Rancho Bernardo Study, in Southern CA. The first cohort comprised 1073 community-dwelling participants (59% women); clinical data was collected from 1984 to 1987 and 1992 to 1997. The second cohort comprised 416 participants (64% women); data was collected from 1984 to 1987, 1992 to 1997, and 1997 to 1999. Demographic, metabolic covariates, ALT, bilirubin, and albumin were measured. Changes in individual ALT over time were examined in unadjusted and multivariable-adjusted linear and logistic regression analyses. Results At the baseline visit, the patients’ mean age was 65.7 years and body mass index was 24.9 kg/m2. In cohort 1, the mean levels of ALT decreased with age by 10% (from 21 to 19 IU/L) between the time periods of 1984–1987 and 1992–1997 (P<.0001). In cohort 2, they decreased by 20% (from 20 to 16 IU/L) between the time periods of 1984–1987 and 1997–1999 (P<.0001). Categorically-defined increases in ALT also decreased with age (P<.0001). Results remained consistent in sex-specific analyses and after adjusting for metabolic syndrome components, alcohol use, bilirubin, and serum levels of albumin (P<.0001). Conclusions In a longitudinal analysis, we observed that levels of ALT decrease with age, independent of sex, metabolic factors, alcohol use, and results from commonly used liver function tests (bilirubin and albumin). When interpreting serum levels of ALT, physicians should consider patients’ age especially in elderly.

Background and aims Bilirubin, a breakdown product of heme metabolism, has been shown to be protective against cardiovascular mortality; however, it is also a marker of liver function. There are limited data on the longitudinal changes in bilirubin with aging in a population-based cohort of older adults. This study was designed to determine whether serum bilirubin changes with age in older adults, and to evaluate whether age attenuates the association between bilirubin and mortality. Methods This is a prospective cohort study of 2364 participants with a mean age of 70 years, who completed a research clinic visit from 1984 to 1987, and 1703 participants who returned for a second research visit approximately 8 years later. Cross-sectional and longitudinal multivariable-adjusted analyses were performed to examine the association between serum bilirubin, aging, and mortality. Results In cross-sectional analyses, when the cohort was divided into quartiles of age, higher baseline serum bilirubin levels were associated with older age in analyses adjusted for sex, body mass index (BMI), alanine aminotransferase (ALT), albumin, and metabolic traits (P-value <0.001). In longitudinal analyses, among the subset of participants who had two research visits, aging remained significantly associated with an increase in bilirubin in multivariable-adjusted models (P-value <0.0001). When the longitudinal cohort was divided into bilirubin quartiles, Kaplan–Meier analysis showed an incremental reduction in survival with higher bilirubin levels (P-value = 0.002); however, this association between bilirubin quartile and mortality was no longer significant after adjusting for age (P-value 0.30), suggesting higher bilirubin in older age does not confer survival advantage. Conclusions Serum bilirubin levels gradually increase with age in older adults. Elevated bilirubin in older individuals is not associated with improved survival as previously reported in middle-aged populations.

Hepatitis B reactivation is a major cause of morbidity and mortality in patients undergoing chemotherapy for lymphomas. These patients may experience direct liver-related complications or reduced cancer survival because of interruptions in chemotherapy. Our aim was to compare the costs and outcomes of 2 different chronic hepatitis B management strategies. In hepatitis B carriers undergoing chemotherapy, we pursued a decision analysis model to compare the costs and clinical outcomes of using lamivudine prophylaxis versus initiating lamivudine only when clinically overt hepatitis occurred. H epatitis B virus (HBV) infection is an important medical and public health concern, and it is a leading cause of cirrhosis and hepatocellular carcinoma. 1,2 Patients with hepatitis B are at risk of viral reactivation when undergoing cytotoxic or immunosuppressive chemotherapy for malignancies, particularly lymphomas. 3 The incidence of HBV reactivation may be as high as 50% and is associated with an overall liver-related mortality of 5%. 4,5 Even in patients who are able to recover from hepatitis B reactivation, their cancer survival may be impaired because of alterations or cessation of the initially intended chemotherapy course. 6,7 The pathogenesis of HBV reactivation during or after chemotherapy appears to be related to an increase in viral replication during immunosuppression with a resultant increase in hepatocyte destruction and inflammation upon immune reconstitution. [3][4][5] Lamivudine, a nucleoside analogue, has been shown to be effective in inhibiting viral replication and decreasing viral load. [8][9][10] Various strategies have been proposed in patients with hepatitis B undergoing chemotherapy to prevent viral replication. It has been suggested that the earlier use of lamivudine, before overt clinical hepatitis, is most efficacious. 11 The use of prophylactic lamivudine can decrease the incidence of HBV reactivation from 30%-80% to 0%-17%. [12][13][14][15][16][17] The aim of this study was to compare the efficacy and costs of 2 management strategies in patients with hepatitis B undergoing chemotherapy: (1) lamivudine prophylaxis and (2) lamivudine use only in patients with evidence of an HBV reactivation. Because lamivudine has been