Abstract/Text
BACKGROUND/AIMS: The significance of abnormal liver function tests in the absence of diagnostic serology is unclear. The aim of this study was to report liver biopsy findings in a large group of patients with unexplained abnormal liver biochemistry.
METHODS: Histological findings were examined in 354 patients who underwent liver biopsy to investigate abnormal liver function tests.
RESULTS: Six percent of patients had a normal liver biopsy while 26% were found to have some degree of fibrosis and 6% were cirrhotic. Thirty four and 32% of biopsies suggested non-alcoholic steatohepatits or fatty liver respectively. Other diagnoses included cryptogenic hepatitis, drug toxicity, primary and secondary biliary cirrhosis, autoimmune hepatits, alcohol-related liver disease, primary sclerosing cholangitis, haemochromatosis, amyloid and glycogen storage disease. Patient management was directly altered in 18% of patients due to liver biopsy findings and three families were entered into screening programmes for inheritable liver disease.
CONCLUSIONS: The finding of abnormal liver function tests in the absence of diagnostic serology may indicate significant liver disease. Liver biopsy yields a range of liver diseases of diverse nature and extent. Liver diseases may be uncovered for which specific treatment is indicated.
Abstract/Text
OBJECTIVES: It is currently recommend to perform a liver biopsy for patients with chronically elevated liver function tests (LFT) of unknown etiology (marker negative). The necessity and benefits of these recommendations are unknown. The aims of this study were to determine the prevalence of marker-negative LFT in patients referred for evaluation of chronically elevated LFT; to determine the prevalence of diseases that may be associated with marker-negative abnormal LFT; and to assess whether a liver biopsy alters the management of such patients.
METHODS: We conducted a prospective observational study of 1124 adults referred for evaluation of chronically elevated LFT. Patients who consented to a liver biopsy were eligible. Marker-negative abnormal LFT was defined as the absence of accepted serum markers for infectious, metabolic, autoimmune, or hereditary liver disease, the absence of a history of alcohol or hepatotoxic drug use, and the absence of signs of chronic liver disease.
RESULTS: Eighty-one of 1124 eligible patients were marker-negative. Liver biopsies in the 81 marker-negative patients revealed: normal histology (eight), steatosis (41), steatohepatitis (26), fibrosis (four), and cirrhosis (two). All 73 abnormal liver biopsies had some degree of steatosis. There were no significant associations between histological findings and the presence of obesity (p = 0.13), hyperlipidemia (p = 0.4), or diabetes (p = 0.9). There were no significant associations when classifying patients by gender or by symptoms.
CONCLUSION: In the setting of marker-negative elevated LFT, the most likely histological diagnosis is fatty metamorphosis of the liver with occasional associated fibrosis.
Abstract/Text
Non-alcoholic fatty liver disease (NAFLD) in non-obese individuals is inadequately elucidated. We aim to investigate the impact of known genetic polymorphisms on NAFLD and the interaction between genetic risks and weight gain on NAFLD in obese and non-obese Japanese individuals. A total of 1164 participants who received health checkups were included. Participants with excessive alcohol consumption, with viral hepatitis or other inappropriate cases were excluded. Fatty liver was diagnosed by ultrasonography. Participants with a body mass index (BMI) of <18.5 kg/m2, 18.5-22.9 kg/m2, 23.0-24.9 kg/m2 and ≥25 kg/m2 were classified underweight, normal weight, overweight and obese, respectively. Self-administered questionnaire for lifestyle was assessed and a total of 8 previously reported genetic polymorphisms were chosen and examined. In all, 824 subjects were enrolled. The overall prevalence of NAFLD was 33.0%: 0% in underweight, 15.3% in normal weight, 41.1% in overweight and 71.7% in obese individuals. The prevalence of NAFLD is more affected by the G allele of patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 in normal weight (odds ratio (OR) 3.52; 95%-CI: 1.42-8.71; P = 0.0063) and in overweight individuals (OR 2.60; 95%-CI: 1.14-5.91; P = 0.0225) than in obese individuals (not significant). Moreover, the G allele of PNPLA3 rs738409 and weight gain ≥10 kg after age 20 had a joint effect on the risk of NAFLD in the normal weight (OR 12.00; 95% CI: 3.71-38.79; P = 3.3×10-5) and the overweight individuals (OR 13.40; 95% CI: 2.92-61.36; P = 0.0008). The G allele of PNPLA3 rs738409 is a prominent risk factor for NAFLD and the interaction between the PNPLA3 rs738409 and weight gain ≥10 kg after age 20 plays a crucial role in the pathogenesis of NAFLD, especially in non-obese Japanese individuals.
Abstract/Text
The purpose of this study was to determine the etiology of elevated alanine aminotransferase (ALT) in a population of asymptomatic volunteer blood donors. Subjects with an ALT value > 2.25 sd above norm (> 55 IU/liter) from the donated unit, were prospectively evaluated over a six-week interval. The subjects consisted of blood donors (78% male, 22% female) beginning basic military training at Lackland Air Force Base. Of 44,160 individuals screened, 19,877 (45%) voluntarily donated blood, 99 (0.5%) of which had confirmed ALT elevation. Of these (90 male/9 female), an associated condition or explanation was made in 12%: four with acute hepatitis B, four positive for anti-HCV, two with autoimmune disease, one with cholelithiasis and one associated with acute appendicitis. In 87 the ALT elevation could not be explained using available testing methods but may represent individual variation from a non-Gaussian distribution, be of nonhepatic origin (muscle), or of hepatic disease not detected by the diagnostic algorithm used. To increase the diagnostic yield, it is suggested that at least two elevated ALT values be established in this population over a period of time (yet undefined), before an extensive hepatic investigation is pursued.
Abstract/Text
The accidental finding of raised levels of serum aminotransferase levels may lead to extensive investigations of the liver in apparently healthy people. To identify diagnostic groups and their need for investigations, we have evaluated the results of all investigative procedures carried out in 149 asymptomatic patients with persistently raised serum levels of aminotransferases. Fatty liver was found in 64%. These patients often had a high body weight. A high alcohol intake and diabetes mellitus were also noted. Chronic active or persistent hepatitis was found in 20% of the patients. Six per cent had cirrhosis, 4% had alpha 1-antitrypsin deficiency, and 3.5% had hemochromatosis. Apart from ferritin, alpha 1-antitrypsin, and markers for hepatitis B, blood tests were of little value for distinguishing among different diagnostic groups. This was the case also for the imaging procedures, and neither liver scintigraphy nor ultrasonography was a reliable source of diagnostic information. The results of our study indicate that diagnosis in this group of patients cannot be made without liver biopsy.
Abstract/Text
Isolated alterations of biochemical markers of liver damage in a seemingly healthy patient can present a challenge for the clinician. In this review we provide a guide to interpreting alterations to liver enzyme levels. The functional anatomy of the liver and pathophysiology of liver enzyme alteration are briefly reviewed. Using a schematic approach that classifies enzyme alterations as predominantly hepatocellular or predominantly cholestatic, we review abnormal enzymatic activity within the 2 subgroups, the most common causes of enzyme alteration and suggested initial investigations.
Abstract/Text
Traditionally, the constellation of biochemistry tests including liver enzymes, total bilirubin, and hepatic synthetic measures (prothrombin time (PT) and serum albumin level) are referred to as liver function tests (LFTs). Abnormal LFTs can be encountered during primary health care visits, routine blood donation, and insurance screening. A reported 1% to 4% of asymptomatic patients exhibit abnormal LFTs, leading to a sizeable number of annual consultations to a gastroenterology and/or hepatology practice. A cost-effective and systematic approach is essential to the interpretation of abnormal LFTs. A review of pattern of abnormal LFTs, detailed medical history, and a comprehensive physical examination help establish a foundation for further individualized testing. Further investigation often involves biochemical testing for disease-specific markers, radiographic imaging, and even consideration of a liver biopsy. In the following account, markers of hepatic injury are reviewed followed by a discussion on an approach to various patterns of abnormal LFTs in an asymptomatic patient.
Abstract/Text
Mild elevations in liver chemistry tests such as alanine transaminase and aspartate transaminase can reveal serious underlying conditions or have transient and benign etiologies. Potential causes of liver transaminase elevations include viral hepatitis, alcohol use, medication use, steatosis or steatohepatitis, and cirrhosis. The history should be thorough, with special attention given to the use of medications, vitamins, herbs, drugs, and alcohol; family history; and any history of blood-product transfusions. Other common health conditions, such as diabetes, heart disease, and thyroid disease, can cause or augment liver transaminase elevations. The recent American Gastroenterological Association guideline regarding the evaluation and management of abnormal liver chemistry tests proposes a practical, algorithmic approach when the history and physical examination do not reveal the cause. In addition to liver chemistries, an initial serologic evaluation includes a prothrombin time; albumin; complete blood count with platelets; hepatitis A, B, and C serologies; and iron studies. Depending on the etiology, management strategies may include cessation of alcohol use, attention to medications, control of diabetes, and modification of lifestyle factors such as obesity. If elevations persist after an appropriate period of observation, further testing may include ultrasonography and other serum studies. In some cases, biopsy may be indicated.
