Alcoholic liver disease. An update

The prevalence and incidence of alcoholic liver disease are constantly evolving. Alcoholic liver disease has a wide clinical spectrum. It may progress to cirrhosis and to end-stage liver disease requiring liver transplantation. The histological manifestations range from steatosis without inflammation to liver cell injury and ultimately to fibrosis and cirrhosis. In some cases, the histological manifestation is steatohepatitis, morphologically characterized by inflammation and necrosis. Currently, although there are no specific tests to establish a diagnosis of steatohepatitis, some serological, radiological, or laboratory tests may be useful. Liver biopsy is useful in confirming a suspected diagnosis and in assessing the extent of parenchymal damage. This review synthesizes the main aspects of the epidemiology, pathogenesis, morphological characteristics, diagnosis, treatment, and prognosis of alcoholic liver disease.     

Histological characteristics and prognosis in patients with fatty liver

OBJECTIVE: The clinical-pathological spectrum of fatty liver ranges from simple steatosis to end-stage fibrotic liver disease. However, no histological characteristics have been identified that can predict progression from pure steatosis to fibrotic liver disease in non-alcoholic fatty liver disease. The objective of this study was to investigate whether histological characteristics in patients with fatty liver without inflammation could predict mortality or development of cirrhosis. MATERIAL AND METHODS: A total of 417 patients had a liver biopsy performed, which showed fatty liver without inflammation. The population consisted of 170 non-alcoholic and 247 alcoholic fatty liver patients. The study cohort was linked through their unique personal identification number to The National Registry of Patients and the nationwide Registry of Causes of Death. RESULTS: Median follow-up time was 19.9 years in the non-alcoholic group and 12.8 years in the alcoholic group. Overall mortality in the non-alcoholic group was not related to morphological findings in the index liver biopsy. Mortality was significantly (p < 0.05) higher in alcoholic patients with severe steatosis. One non-alcoholic patient (0.6%) developed cirrhosis versus 54 alcoholic patients (22%) during the follow-up period. CONCLUSIONS: In patients with non-alcoholic fatty liver without inflammation, patients at risk for premature death cannot be identified by histological characteristics in the index liver biopsy. Patients with alcoholic fatty liver have a high risk for development of cirrhosis and increased mortality with the severity of steatosis in the index liver biopsy.     

Investigation of alcoholic liver disease

In heavy drinkers with clinical evidence of liver disease, routine investigations should exclude the possibility of other chronic liver diseases of non-alcoholic aetiology requiring specific therapy-these include chronic viral hepatitis, autoimmune diseases of the liver, Wilson's disease and genetic haemochromatosis. If abnormalities in liver biochemistry persist despite abstinence, or if the diagnosis of alcoholic liver disease is in doubt, a liver biopsy should be carried out. Studies evaluating the role of liver biopsy in alcoholic liver disease suggest that without histological confirmation the diagnosis will be inaccurate in 10–20% of patients.Serum biochemistry and the currently available imaging modalities have severe limitations in determining the relative contributions of fatty liver, alcoholic hepatitis and cirrhosis to the overall picture in alcoholic liver disease. Histological examination is therefore of additional value in determining the prognosis, which is worst in patients with a combination of alcoholic hepatitis and cirrhosis.There area number of indices available, based on clinical and laboratory information, for evaluating the short-term prognosis, but these can only be used with accuracy if the histological pattern of damage has initially been evaluated.     

Histological characteristics and prognosis in patients with fatty liver

Objective The clinical-pathological spectrum of fatty liver ranges from simple steatosis to end-stage fibrotic liver disease. However, no histological characteristics have been identified that can predict progression from pure steatosis to fibrotic liver disease in non-alcoholic fatty liver disease. The objective of this study was to investigate whether histological characteristics in patients with fatty liver without inflammation could predict mortality or development of cirrhosis. Material and methods A total of 417 patients had a liver biopsy performed, which showed fatty liver without inflammation. The population consisted of 170 non-alcoholic and 247 alcoholic fatty liver patients. The study cohort was linked through their unique personal identification number to The National Registry of Patients and the nationwide Registry of Causes of Death. Results Median follow-up time was 19.9 years in the non-alcoholic group and 12.8 years in the alcoholic group. Overall mortality in the non-alcoholic group was not related to morphological findings in the index liver biopsy. Mortality was significantly (p<0.05) higher in alcoholic patients with severe steatosis. One non-alcoholic patient (0.6%) developed cirrhosis versus 54 alcoholic patients (22%) during the follow-up period. Conclusions In patients with non-alcoholic fatty liver without inflammation, patients at risk for premature death cannot be identified by histological characteristics in the index liver biopsy. Patients with alcoholic fatty liver have a high risk for development of cirrhosis and increased mortality with the severity of steatosis in the index liver biopsy.     

The accuracy of the clinical diagnosis in acute hepatitis and alcoholic liver disease. Clinical versus morphological diagnosis

Microfilms were prepared from the case histories of 357 consecutive patients submitted to liver biopsy for the first time so that all information after the time of the liver biopsy was erased. The microfilms were assessed by four clinicians, and the pre-biopsy diagnostic proposals were graded according to the degree of certainty and were compared with the results of the liver biopsies. Out of 357 patients, 200 had a history of alcoholism, of whom 172 had alcohol-induced changes in the liver biopsies: 80 cases of alcoholic cirrhosis, 84 cases of steatosis, and 8 cases of alcoholic hepatitis without cirrhosis. In 65 of the 80 patients with biopsy-verified alcoholic cirrhosis the clinical pre-biopsy diagnosis was in agreement with the histological findings. In 51 cases in which the clinical diagnosis of alcoholic cirrhosis was given as moderately certain or very certain, 4 clinically incorrect diagnoses occurred. No incorrect diagnoses occurred in the 35 cases in which the clinicians claimed the greatest diagnostic accuracy. In the 84 patients with steatosis in the liver biopsies the clinicians felt uncertain or moderately certain about all but 2 patients, and 14 incorrect diagnoses occurred. In none of the 8 patients with histological alcoholic hepatitis without cirrhosis was a correct clinical diagnosis made. The clinical pre-biopsy diagnosis of acute hepatitis was in agreement with the results of the liver biopsies in 52 out of 57 patients. In 51 cases in which the clinical diagnosis of acute hepatitis was given as moderately certain or very certain, 1 clinically incorrect diagnosis occurred.(ABSTRACT TRUNCATED AT 250 WORDS)     

Non-invasive assessment of liver fibrosis in patients with alcoholic liver disease

Alcoholic liver disease(ALD) consists of a broad spectrum of disorders, ranging from simple steatosisto alcoholic steatohepatitis and cirrhosis. Fatty liver develops in more than 90% of heavy drinkers, however only 30%-35% of them develop more advanced forms of ALD. Therefore, even if the current "gold standard" for the assessment of the stage of alcohol-related liver injury is histology, liver biopsy is not reasonable in all patients who present with ALD. Currently, although several non-invasive fibrosis markers have been suggested as alternatives to liver biopsy in patients with ALD, none has been sufficiently validated. As described in other liver disease, the diagnostic accuracy of such tests in ALD is acceptable for the diagnosis of significant fibrosis or cirrhosis but not for lesser fibrosis stages. Existing data suggest that the use of noninvasive tests could be tailored to first tier screening of patients at risk, in order to diagnose early patients with progressive liver disease and offer targeted interventions for the prevention of decompensation. We review these tests and critically appraise the existing evidence.     

Histological features after liver transplantation in alcoholic cirrhotics.

BACKGROUND/AIMS: Though alcoholic cirrhosis is a common indication for liver transplantation, it carries the risk of alcohol recidivism and consequent graft failure. This study aims to evaluate the effect of alcohol recidivism on survival rates and histological parameters in patients transplanted for alcoholic cirrhosis, with and without hepatitis C virus (HCV) infection. METHODS: Fifty-one out of 189 consecutive transplanted patients underwent psychosocial evaluation and liver biopsy at 6 and 12 months, then yearly after transplantation. RESULTS: The cumulative 84 month survival rate was identical in patients transplanted for alcoholic (51%) and non-alcoholic cirrhosis (52%). No difference emerged between anti-HCV negative vs. positive alcoholic cirrhosis patients. Psycho-social evaluation revealed alcohol recidivism in 11/34 long-term survivors, but this did not affect overall survival rate in patients with or without HCV. In anti-HCV negative cases, fatty changes and pericellular fibrosis were significantly more common in heavy drinkers than in occasional drinkers and abstainers. When HCV status was considered regardless of alcohol intake, fibrosis was significantly more frequent in patients with HCV. CONCLUSION: Alcohol recidivism after transplantation in alcoholic cirrhosis patients does not affect survival, irrespective of HCV status. Fatty changes and pericellular fibrosis are the most relevant histological signs of heavy alcohol intake.     

Prothrombin index is an indirect marker of severe liver fibrosis

OBJECTIVE: The non-invasive diagnosis of liver fibrosis is based mainly on biochemical markers. The main aim was to validate whether the prothrombin index is an indirect marker of the severity of liver fibrosis. PATIENTS AND METHODS: The predictive value of the prothrombin index for liver fibrosis was first assessed in 243 patients with chronic liver disease, then validated in 193 other patients with chronic liver disease. The reproducibility of measurement of the prothrombin index in different laboratories was evaluated in 82 other patients. RESULTS: In the first group, the prothrombin index was predicted accurately by serum hyaluronate (R(2)= 0.67 at the first step by multiple regression). The relationship between the prothrombin index and the area of fibrosis was not influenced significantly by non-fibrotic pathological lesions. The prothrombin index began to decrease when the Metavir fibrosis score was 2 versus 3 for albumin. In the second group, the prothrombin index and the histological fibrosis score were well correlated (r= -0.70, P< 10(-4)). Prothrombin index < or =80% or < or =70% diagnosed severe fibrosis or cirrhosis, respectively, and prothrombin index > or =105% or > or =100% excluded a diagnosis of severe fibrosis or cirrhosis, respectively, at the 95% probability level. The prothrombin indices measured in different laboratories were similar (78+/-18% v. 78+/-14%) and well correlated (r= 0.91, P< 10(-4)). CONCLUSIONS: The prothrombin index was well correlated with pathological liver fibrosis score, had a high diagnostic accuracy for severe fibrosis or cirrhosis especially due to alcohol, and was not influenced by other pathological lesions. The prothrombin index was reproducible. Thus, the prothrombin index expressed as a percentage is an accurate, reproducible, inexpensive and easily available marker of severe liver fibrosis.     

原因不明肝功能异常88例临床及病理分析

目的 探讨不明原因肝功能异常患者的临床和肝穿刺活检病理学特点,并对其诊断和鉴别诊断进行分析.方法 收集2008年1月-2009年12月以"肝功能异常原因待查"入院并行肝穿刺活检的患者,剔除病毒性肝炎、酒精性肝病、肝占位病变、结石所致胆管梗阻及抗线粒体抗体(AMA)和(或)抗线粒体抗体M2亚型(AMA-M2)阳性的原发性胆汁性肝硬化等比较容易诊断的疾病后,对最后诊断出的疾病种类及特点进行总结分析.结果 共88例符合上述入选标准,诊断共涉及15种疾病,居前3位的是药物性肝损害(DILI)[34.09%(30/88)]、自身免疫性肝病[22.73%(20/88)]和非酒精性脂肪性肝病(NAFLD)[12.50%(11/88)].结论 在原因不明的肝病中,DILI、自身免疫性肝病及NAFLD最常见,而遗传代谢性肝病等以前不被重视或未认识到的疾病也占相当的比例,应引起临床医师的重视.

Abstract：

Objective To evaluate the clinical and histological features of patients with abnormal liver tests of unknown etiology, and then to investigate the diagnosis and differential diagnosis. Methods Patients with abnormal liver function test hospitalized and had liver biopsies during 2008-2009 constituted this retrospective study cohort. After excluding those patients diagnosed with hepatotropic viral hepatitis,space occupying lesions of the liver, alcoholic liver disease and obstruction of bile duct caused by stone or malignancy and AMA/AMA-M2 positive of primary biliary cirrhosis ( PBC ), the clinical and histological characteristics were evaluated. Results Out of the 180 patients who underwent liver biopsy, 88 patients were included in the present analysis. The final diagnosis involved 15 categories of diseases, with druginduced liver injury ( DILI ) [34. 09% ( 30/88 )], autoimmune liver diseases [22.73% ( 20/88 )], and nonalcoholic fatty liver disease (NAFLD) [12. 50% ( 11/88 )] being the most common causes, following by genetic and other rare diseases. Conclusion DILI, autoimmune liver disease and NAFLD were the most common causes of abnormal liver tests in these non-viral liver diseases. Some rare diseases such as hereditary metalbolic liver disease also represent a considerable proportion in patients with abnormal liver function test.     

Liver fibrosis in overweight patients

BACKGROUND & AIMS: A common clinical issue is whether overweight patients with abnormal liver function test results should undergo liver biopsy. Although serious liver injury can occur, its prevalence and risk factors are not well known. METHODS: Ninety-three consecutive patients with abnormal liver function tests (but without overt liver disease), body mass index (BMI) > 25 kg/m(2), and no alcoholic, viral, autoimmune, drug-induced, or genetic liver disease were retrospectively studied. Clinical, biological, and histological variables were tested for association with septal fibrosis or cirrhosis. RESULTS: Septal fibrosis was present in 28 patients (30%) including cirrhosis in 10 (11%). Age >/= 50 years (odds ratio [OR], 14.1), BMI >/= 28 kg/m(2) (OR, 5.7), triglycerides >/= 1.7 mmol/L (OR, 5), and alanine aminotransferase (ALT) >/= 2N (OR, 4.6) were independently associated with septal fibrosis. Among histological features, septal fibrosis was strongly associated with necroinflammatory activity (OR, 44). A score combining age, BMI, triglycerides, and ALT had 100% negative predictive value for septal fibrosis when scoring 0 or 1 (100% sensitivity for a specificity of 47%). CONCLUSIONS: Septal fibrosis occurs frequently in overweight patients with abnormal liver function tests. A clinicobiological score combining BMI, age, ALT, and triglycerides could improve selection of patients for liver biopsy.     

Serum hyaluronate correlates with histological progression in alcoholic liver disease

OBJECTIVES: Chronic alcohol consumption may lead to the development of liver cirrhosis. Serum concentrations of hyaluronate were suggested as a predictor in chronic liver disease, but its power to distinguish between severity of fibrosis and inflammation had not been assessed. In order to evaluate hyaluronate as a marker to detect early stages of alcoholic liver disease and to establish a possible correlation with hepatic histology, serum concentrations were measured by radioimmunoassay in 87 patients with biopsy-proven fatty liver, fatty liver and mild fibrosis, fatty liver and inflammation, severe fibrosis and inflammation, and cirrhosis, and in 12 non-alcoholic control subjects. In addition, serum hyaluronate was determined in 40 non-cirrhotic alcoholic patients with either a normal serum aspartate aminotransferase (AST) or an AST elevated at least two-fold. RESULTS: Serum hyaluronate increased significantly with advanced stages of alcoholic liver disease, while levels in patients with fatty liver were elevated only slightly without reaching significance. Hyaluronate correlated well with histological stage and was highly sensitive for detecting fibrosis in general and perivenular fibrosis as an indicator of progression to cirrhosis. Hyaluronate levels were not influenced by AST levels. CONCLUSION: Serum hyaluronate is a good predictor of the presence of even moderate hepatic fibrosis in alcoholic liver disease, justifying its clinical use to assess morphological alterations of the liver in alcoholics.     

Long term prognosis of fatty liver: risk of chronic liver disease and death

BACKGROUND AND AIMS: Fatty liver is a common histological finding in human liver biopsy specimens. It affects 10-24% of the general population and is believed to be a marker of risk of later chronic liver disease. The present study examined the risk of development of cirrhotic liver disease and the risk of death in a cohort diagnosed with pure fatty liver without inflammation. METHODS: A total of 215 patients who had a liver biopsy performed during the period 1976-1987 were included in the study. The population consisted of 109 non-alcoholic and 106 alcoholic fatty liver patients. Median follow up time was 16.7 (0.2-21.9) years in the non-alcoholic and 9.2 (0.6-23.1) years in the alcoholic group. Systematic data collection was carried out by review of all medical records. All members of the study cohort were linked through their unique personal identification number to the National Registry of Patients and the nationwide Registry of Causes of Death, and all admissions, discharge diagnoses, and causes of death were obtained. RESULTS: In the non-alcoholic fatty liver group, one patient developed cirrhosis during the follow up period compared with 22 patients in the alcoholic group. Survival estimates were significantly (p<0.01) different between the two groups, for men as well as for women, with a higher death rate in the alcoholic fatty liver group. Survival estimates in the non-alcoholic fatty liver group were not different from the Danish population. CONCLUSIONS: This study revealed that patients with type 1 non-alcoholic fatty liver disease have a benign clinical course without excess mortality.     

Cirrhosis: diagnosis by liver surface analysis with high-frequency ultrasound.

To determine the sensitivity, specificity, and predictive values of the sonographic analysis of liver surface irregularities for the diagnosis of cirrhosis, the authors conducted a prospective and blinded study in 70 subjects with abnormal liver function tests. All patients included underwent liver biopsy within 15 days of the sonographic study. Twenty-three subjects with no signs or symptoms of liver disease were examined to assess the sonographic appearance of normal liver surface. Studies were performed with a small-parts probe, high-frequency transducer (7.5 MHz). Three basic patterns of liver surface were found: type I, normal; type II, focal abnormality; and type III, diffuse irregularity. Considering diffuse surface irregularity as an objective sonographic sign of cirrhosis, the study's sensitivity was 87.5%, specificity 81.5%, and positive and negative predictive values were 80% and 88.5%, respectively. Disease prevalence for cirrhosis was 45%. We conclude that sonographic analysis of the liver surface is a useful noninvasive test for the diagnosis of cirrhosis in the appropriate clinical setting.     

Hepatic collagen synthesis in patients with alcoholic and nonalcoholic liver disease

To examine the synthesis of hepatic collagen in patients with alcoholic and nonalcoholic liver disease, liver biopsy specimens were incubated in vitro with 14C-proline, and the radioactivity of the newly synthesized protein-bound 14C-hydroxyproline was measured. Mean hepatic collagen synthesis was 0.82 +/- 0.19 pmole of 14C-hydroxyproline/g liver/2 h in control subjects without histological liver fibrosis. Hepatic collagen synthesis was increased in patients with alcoholic and nonalcoholic liver diseases, especially in those with alcoholic fibrosis, alcoholic cirrhosis and chronic active hepatitis. The raised collagen synthesis in alcoholic liver disease rapidly decreased after withdrawal of alcohol. When alcoholic liver disease were compared with nonalcoholic liver disease, there was no significant difference in hepatic collagen synthesis.     

VA Cooperative Study on Alcoholic Hepatitis IV. The Significance of Clinically Mild Alcoholic Hepatitis—Describing the Population with Minimal Hyperhilirubinemia

As part of a large multicenter Veterans Administration Cooperative Study of Alcoholic Hepatitis, 89 patients with clinically mild biopsy-proven disease were followed for at least 30 months. Although clinical and laboratory abnormalities were minimal, cirrhosis was present in 38%, and mortality was 22% at 30 months. Clinical features suggesting more advanced disease (i.e., ascites and encephalopathy) and laboratory parameters for the diagnosis of alcoholic hepatitis and/or cirrhosis were imprecise and frequently misleading. The histologic diagnosis of cirrhosis correlated best with changes in immunoglobulin A, prothrombin time, and SGOT/SGPT. However, by using logistic discriminant analysis on 26 commonly available laboratory tests to diagnose cirrhosis, only a 72% sensitivity and 88% specificity could be obtained. Mortality in the patients with cirrhosis (10/34) was significantly higher at 1 and 2 yr compared with patients without cirrhosis (10/55, p less than 0.01). The high mortality in noncirrhotics may have resulted from progression to cirrhosis subsequent to the initial evaluation. Thus, liver biopsy in this population with minimal disease seems necessary to establish both an accurate diagnosis and the reversibility of the disease.     

Descriptive epidemiology of patients with alcoholic liver disease hospitalized in a hepato-gastroenterology service]

OBJECTIVE: To improve the detection of early stage alcoholic liver disease and to identify the importance of this disease, this study compared epidemiological characteristics, the reasons for and the duration of hospitalization, in-patient mortality and the frequency of multiple hospitalizations in alcoholic patients without cirrhosis and in patients with alcoholic cirrhosis hospitalized in the hepatogastroenterology department of Antoine-Beclere Hospital. MATERIAL AND METHODS: From January 1982 to December 1995, all patients with a daily alcohol intake in the previous year of at least 50 g per day and all patients with alcoholic cirrhosis whatever their drinking habits were studied. RESULTS: Three thousand three hundred and forty six patients were included. The daily alcohol intake in the previous five years was 118 +/- 81 g and the duration of alcohol abuse was 22 +/- 13 years. Two thousand one hundred eight patients had liver biopsy; 37% had histologically proven or probable cirrhosis. Forty one percent of the patients without cirrhosis who had liver biopsy already had steatofibrosis and/or acute alcoholic hepatitis. 32.5% of the patients had hepatitis B virus markers. 7.7% of the patients were positive for anti hepatitis C virus antibody. Thirty two percent of the patients with cirrhosis were women versus 22% of the patients without cirrhosis (P < 0.01). Alcoholism was the reason for the first hospitalization in sixty percent of the patients without cirrhosis and in twenty percent of the patients with cirrhosis (P < 0.01). On the other hand, ascites were the first reason for the first hospitalization in patients with cirrhosis (28%). The two main causes for multiple hospitalizations were also ascites and alcoholism. CONCLUSION: Two thirds of heavy drinkers did not have cirrhosis on admission since alcoholism was the first reason for multiple hospitalizations in these patients, therefore the management of alcoholism in out-patients must be improved.     

Non-invasive diagnosis of alcoholic liver disease

Alcoholic liver disease (ALD) is the most common liver disease in the Western world. For many reasons, it is underestimated and underdiagnosed. An early diagnosis is absolutely essential since it (1) helps to identify patients at genetic risk for ALD; (2) can trigger efficient abstinence namely in non-addicted patients; and (3) initiate screening programs to prevent life-threatening complications such as bleeding from varices, spontaneous bacterial peritonitis or hepatocellular cancer. The two major end points of ALD are alcoholic liver cirrhosis and the rare and clinically-defined alcoholic hepatitis (AH). The prediction and early diagnosis of both entities is still insufficiently solved and usually relies on a combination of laboratory, clinical and imaging findings. It is not widely conceived that conventional screening tools for ALD such as ultrasound imaging or routine laboratory testing can easily overlook ca. 40% of manifest alcoholic liver cirrhosis. Non-invasive methods such as transient elastography (Fibroscan), acoustic radiation force impulse imaging or shear wave elastography have significantly improved the early diagnosis of alcoholic cirrhosis. Present algorithms allow either the exclusion or the exact definition of advanced fibrosis stages in ca. 95% of patients. The correct interpretation of liver stiffness requires a timely abdominal ultrasound and actual transaminase levels. Other non-invasive methods such as controlled attenuation parameter, serum levels of M30 or M65, susceptometry or breath tests are under current evaluation to assess the degree of steatosis, apoptosis and iron overload in these patients. Liver biopsy still remains an important option to rule out comorbidities and to confirm the prognosis namely for patients with AH.     

CASE REPORT: Incomplete septal cirrhosis with liver cell dysplasia

A 60-year-old woman was transplanted for end-stage alcoholic cirrhosis. The diagnosis of cirrhosis was made 13 years earlier on the basis of features of portal hypertension and a wedge liver biopsy. Liver function tests were subnormal except for a low prothrombin time. Unproven possible alcohol abuse was the only aetiological factor. Her condition remained unchanged until transplantation, despite complete abstinence. Histological examination of the explant showed incomplete septal cirrhosis associated with distal obstructive portal venopathy, cirrhotic nodules predominantly in the subcapsular areas and nodular regenerative hyperplasia with septal fibrosis elsewhere. In addition, there were areas of large and small liver cell dysplasia. This observation shows the difficulty in making a diagnosis of incomplete septal cirrhosis and the hypothetical link between liver cell dysplasia (which has never been reported in incomplete septal cirrhosis but is well known to be associated with hepatocellular carcinoma in cirrhosis) and rare cases of liver adenomas and carcinomas reported in patients presenting with liver vascular disorders.     

13C-galactose breath test and 13C-aminopyrine breath test for the study of liver function in chronic liver disease.

BACKGROUND AND AIMS: Liver biopsy examination is the gold standard to diagnose the presence of cirrhosis. The aim of this study was to evaluate the accuracy of both 13 C-aminopyrine breath test ( 13 C-ABT) and 13 C-galactose breath test ( 13 C-GBT) in the noninvasive assessment of the presence of cirrhosis in patients with chronic liver disease. METHODS: We evaluated 61 patients with chronic liver disease of diverse etiologies (21 compensated cirrhosis). All patients underwent 13 C-GBT and 13 C-ABT, and the results were expressed as a percentage of the administered dose of 13 C recovered per hour (%dose/h) and as the cumulative percentage of administered dose of 13 C recovered over time (%dose cumulative). Results were analyzed according to absence vs presence of cirrhosis. RESULTS: On average, 13 C-GBT %dose/h and %dose cumulative were decreased significantly in patients with compensated cirrhosis, and the same finding was observed for 13 C-ABT results from 30 to 120 minutes. 13 C-GBT %dose/h at 120 minutes had 71.4% sensitivity, 85.0% specificity, and 83.7% accuracy, whereas 13 C-ABT %dose cumulative at 30 minutes had 85.7% sensitivity, 67.5% specificity, and 77.1% accuracy for distinguishing between the 2 subgroups of patients. Combined assessment of 13 C-GBT and 13 C-ABT increased the diagnostic accuracy (80% positive predictive value) of either test alone and reached 92.5% specificity and 100% sensitivity for the diagnosis of cirrhosis. CONCLUSIONS: In patients with chronic liver disease, both 13 C-GBT and 13 C-ABT are useful for the diagnosis of cirrhosis. Combination of the tests increases the diagnostic yield of each test alone.     

Plasma endotoxin concentrations in patients with alcoholic and non-alcoholic liver disease: reevaluation with an improved chromogenic assay

Plasma endotoxin concentration was measured in 85 patients with alcoholic liver disease (alcoholic cirrhosis (n = 64), alcoholic hepatitis without cirrhosis (n = 11), fatty liver (n = 10), and in patients with non-alcoholic cirrhosis (n = 15]. Endotoxin concentration was determined with an improved chromogenic substrate assay, using individual standard curves for each plasma sample. In patients with alcoholic cirrhosis the mean endotoxin concentration was significantly higher than in patients with non-alcoholic cirrhosis (p less than 0.05). In addition, distinctly higher endotoxin concentrations (greater than 20 pg/ml) were more frequently observed in patients with alcoholic cirrhosis than in non-alcoholic cirrhosis (34.4 vs. 14.3%, p less than 0.05). Mean endotoxin concentration was not significantly higher in cirrhotics with ascites or esophageal varices as compared with the subgroup without ascites or esophageal varices. The endotoxin concentration did not correlate with serum bilirubin, prothrombin concentration or serum enzyme activities. In patients with alcoholic liver disease, however, endotoxin concentration revealed a negative correlation (p less than 0.05) with the concentration of high density lipoprotein cholesterol. On admission endotoxin concentrations in alcoholics with fatty liver were similarly elevated as observed in alcoholic cirrhosis. In six out of 12 patients with fatty liver or alcoholic hepatitis, in whom a second sample of plasma was investigated after 6 to 8 days, endotoxemia was no longer detectable; in the remaining patients, the endotoxin concentration decreased markedly. The results indicate that, irrespective of the stage of liver disease, alcohol abuse favours the development of endotoxemia. They support the hypothesis that gut-derived endotoxins might play a role in the initiation and aggravation of alcohol-induced liver disease.