Tuesday

Hepatic enzymes have a role in the diagnosis of hepatic injury after blunt abdominal trauma

Injury, Volume 40, Issue 9, Pages 978-983
K. Tan, S. Bang, A. Vijayan, M. Chiu

Introduction: Delayed diagnosis of patients with severe liver injuries is associated with an adverse outcome. As computed tomographic (CT) scan is not always available in the management of blunt abdominal trauma worldwide, the present study was undertaken to determine the accuracy of selected haematological markers in predicting the presence of hepatic injury and its severity after blunt abdominal trauma.

Methods: A retrospective review of all patients with blunt abdominal trauma presented to our institution over a 3-year period was performed. Patients were excluded if they suffered penetrating injuries, died in the emergency department or if the required blood tests were not performed within 24h of the accident. The grading of the hepatic injury was verified using CT scans or surgical findings.

ResultsNinety-nine patients with blunt abdominal trauma had the required blood tests performed and were included in the study. The median injury severity score was 24 (range 4–75). Fifty-five patients had hepatic injuries, of which 47.3% were minor (Grades I and II) while 52.7% had major hepatic injuries (Grades III–V). There were no patients with Grade VI injuries.

A raised Alanine Transaminase (ALT)(sGPT) was strongly associated with presence of hepatic injuries (OR, 109.8; 95% CI, 25.81–466.9). This relation was also seen in patients with raised AST>2 times (OR, 21.33; 95% CI, 7.27–62.65). This difference was not seen in both bilirubin and ALP.

Alanine Transaminase ALT>2 times normal was associated with major hepatic injuries (OR, 7.15; 95% CI, 1.38–37.14; p=0.012) while patients with simultaneous raised AST>2 times and ALT>2 times had a stronger association for major hepatic injuries (OR, 8.44; 95% CI, 1.64–43.47).

Conclusion: Abnormal transaminases levels are associated with hepatic injuries after blunt abdominal trauma. Patients with (GPT) ALT and (GOT) AST>2 times normal should be assumed to possess major hepatic trauma and managed accordingly. Patients with normal ALT, AST and LDH are unlikely to have major liver injuries.

Thursday

Alanine aminotransferase, gamma-glutamyltransferase (GGT) and all-cause mortality: results from a population-based Danish twins study alanine aminotra

Fraser A, Thinggaard M, Christensen K, Lawlor DA.
Department of Social Medicine, MRC Centre for Causal Analysis in Translational Epidemiology, University of Bristol, Bristol BS8 2BN, UK.

Alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) are widely used markers of liver disease. Several population-based cohort studies have found associations of these liver enzymes with all-cause mortality. None of these studies controlled for genetic variation as well as fetal and early life exposure, whether environmental or genetic. Methods: We studied the associations of ALT and GGT with all-cause mortality using data for 686 twins (73-94 years old) included in the Longitudinal Study of Aging Danish Twins.

Results: An increase in 1 logged U/L of GGT was associated with a 15% increase in the hazard ratio (HR) for mortality [95% confidence interval (CI) 0.99, 1.32] but there was no strong evidence of an association of ALT with all-cause mortality (HR=1.07, 95% CI 0.82, 1.40) when controlling for potential confounders. In this analysis, the study population was treated as individuals, with similarities between twins accounted for by using robust standard errors.

However, an intrapair analysis in which the proportion of twin pairs in which the twin with the higher level of ALT or GGT died first was compared with 50% (expected under the null hypothesis), found no strong evidence that higher ALT or GGT was associated with earlier death within twin pairs; the results were consistent in both monozygotic and dizygotic twins.

Conclusions: gamma-glutamyltransferase but not ALT predicts mortality among older Danish twins when using traditional methods for controlling for potential confounders and existing diabetes and cardiovascular disease. Environmental developmental origins may explain the association, but larger twin studies are required to replicate our findings

Monday

New approaches in the therapy of hepatitis C in dialysis patients

Patients with renal disease are at increased risk of acquiring hepatitis C virus (HCV) infection because of their frequent exposure to blood from transfusions or exposure to HCV-contaminated medical equipment during hemodialysis.

The prevalence of anti-HCV antibodies among hemodialysis patients varies between 5-10% in the developed world, and 10-70% in developing countries. Acute hepatitis C is often mild and associated with few, if any symptoms. The major complication of acute HCV infection is chronic hepatitis, which occurs in up to 80% of the cases, the long-term outcome being cirrhosis, portal hypertension, hepatic failure, and hepatocellular carcinoma.

Interferon alpha (IFN-alpha) has shown activity against HCV. Twenty four to 48 week course of therapy with interferon could lead to a sustained loss of HCV RNA, normalization of alanine aminotrasferase (ALT) levels, and resolution of the liver disease. Sustained viral response was achieved in approximately half of the treated patients. Therapy with interferon was associated with a number of adverse events such as: "flu-like" symptoms, neurological, gastrointestinal symptoms, anemia, fatigue, thrombocytopenia, leucopenia. A major advance in therapy came with the addition of ribavirin to interferon therapy. Peginterferon-alpha-2a (40KD) is a new 'pegylated' subcutaneous formulation of interferon-alpha-2a, that was developed to improve the pharmacokinetic profile and therapeutic efficacy of interferon-alpha-2a. In our study, fourteen hemodialysis patients with chronic hepatitis C received 135 microg PEG-IFN alpha-2a subcutaneously, once a week, after dialysis session for a period of 48 weeks.

In the intention-to-treat analysis, sustained viral response was present in 36% of the patients (five out of fourteen patients) at the end of the follow up period. The biochemical response with normalization of serum ALT levels during the treatment was observed in all treated patients (83 +/- 20.1 U/L at base line vs. 23.4 +/- 4.6 U/L after the 48 weeks; p < 0.01). At present, therapy for hepatitis C should be considered in hemodialysis patients with significant liver disease, minimal other co morbidities, and a reasonable likelihood of prolonged survival or if renal transplantation is planned.

Sikole A, Dzekova P, Asani A, Amitov V, Selim G, Gelev S, Polenakovic M.
University Clinic of Nephrology, Skopje, R. Macedonia

Tuesday

Identifying hepatitis C virus: Prevalence of ALT

To evaluate the validity of predicting the prevalence of antibodies to hepatitis C virus (anti-HCV) based on the prevalence of alanine transaminase (ALT) elevation (>40IU/l), we conducted a community-based study. In total, 56698 individuals underwent health examinations in 2004.

Another 43738 subjects in 2005 were the validation set. It should be valid to predict the prevalence of anti-HCV in villages (>25 participants) by the prevalence of ALT elevation. The equation was anti-HCV (%)=(% of ALT elevation - 6%)/65% (n=487 villages, R(2)=0.58). Villages with prevalence of ALT elevation >13% had a high probability of being HCV-endemic (anti-HCV >10%). The sensitivity and specificity were 73.6 and 74.6%, respectively.

By the validation set, the positive and negative predictive values were 52.0% and 79.4%, respectively. Clinical and epidemiological deductions of the equation were that baseline of ALT elevation was 6% and two-thirds of anti-HCV-positive subjects had elevated ALT.

Department of Family Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan; Department of Occupational Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan; Graduate Institute of Environmental and Occupational Health, Medical College, National Cheng Kung University, Tainan, Taiwan.

Saturday

Age- and Ethnic-Specific Elevation of ALT Among Obese Children at Risk for Nonalcoholic Steatohepatitis

The objectives are to: (1) characterize ethnic-specific differences in alanine aminotransferase (ALT) elevation among obese children, (2) investigate the earliest ages at which significant ALT elevation occurs, and (3) determine associations between ALT and biochemical parameters. A cohort of 134 multiethnic obese children and adolescents was analyzed retrospectively. ALT levels 45 U/L or <45 U/L, denoting high or normal risk, were used to categorize obese children's risk for developing nonalcoholic steatohepatitis. In all, 60% of Hispanics had high-risk ALT levels compared with 12% of whites and 8% of blacks. A significantly higher proportion of boys had ALT 45 U/L (49.4%, vs 37.9% for girls, P = .002); 17.5% were Hispanic boys less than 7 years old. Obese Hispanic children, particularly boys, not only have higher ALT/GPT levels but present alarmingly young with high-risk levels. This study highlights a discrete subgroup of children who may present with fatty liver at a younger age and should be screened earlier.

Daniel H. Leung, MD Children's Hospital of Philadelphia, Pennsylvania, leungd@email.chop.edu

Kent Williams, MD Vanderbilt University School of Medicine, Nashville, Tennessee

J. Kennard Fraley, MS, BS Baylor College of Medicine, Texas Children's Hospital, Houston, Texas

William J. Klish, MD Baylor College of Medicine, Texas Children's Hospital, Houston, Texas