Non invasive prediction of severe fibrosis in patients with alcoholic liver disease

OBJECTIVES: The aim of this study was to assess the diagnostic accuracy of noninvasive markers of liver fibrosis in alcoholic liver disease. PATIENTS AND METHODS: Fifty-four clinical and biochemical parameters including serum fibrosis markers (hyaluronate and transforming growth factor beta1) were analyzed in 146 consecutive heavy drinkers (106 men, 40 women; mean age 49.2 years). Following liver biopsy, fibrosis was evaluated using a semi-quantitative scoring system (no fibrosis (0) to severe fibrosis (3 + )). Multivariate analysis was performed to determine the markers that were best correlated with the fibrosis score. RESULTS: Fifty-nine patients (40.4 %) had severe fibrosis (3 +) while 87 (59.6 %) had no fibrosis or moderate fibrosis (0 to 2 +). In multivariate analysis, serum hyaluronate and the prothrombin index were the best markers for the prediction of severe fibrosis. Hyaluronate and the prothrombin index had a diagnostic accuracy of 91.1 % and 89.7 %, respectively in the whole population. Finally, a significant negative correlation was found between hyaluronate and the prothrombin index (r =- 0.86, P <0.0001). CONCLUSIONS: Using only hyaluronate and the prothrombin index, 9 out of 10 alcoholic patients can be correctly classified according to the severity of liver fibrosis.     

Which patients with primary biliary cirrhosis or primary sclerosing cholangitis should undergo endoscopic screening for oesophageal varices detection?

BACKGROUND: Recent guidelines from an AASLD Single Topic Symposium suggest that patients with cirrhosis, including those with primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC), should be screened for oesophageal varices when the platelet count is <140,000/mm3. AIM: To determine the validity of these guidelines in clinical practice in patients with PBC or PSC. METHODS: Retrospective review of individuals undergoing screening upper endoscopy for oesophageal varices at a single centre. Oesophageal varices were reported as being present or absent. RESULTS: A total of 235 patients with chronic liver disease, including 86 patients with PBC (n=79) or PSC (n=7), 104 patients with chronic viral hepatitis, and 45 with non-alcoholic cirrhosis of differing aetiologies, underwent a single screening endoscopy between 1996 and 2001. Oesophageal varices were detected in 26 (30%) of the PBC/PSC group, 38 (37%) of the viral hepatitis group, and 21 (47%) of the "other" group. Applying multiple logistic regression analysis to the data in the group with PBC/PSC, platelets <200,000/mm3 (odds ratio (OR) 5.85 (95% confidence interval (CI) 1.79-19.23)), albumin <40 g/l (OR 6.02 (95% CI 1.78-20.41)), and serum bilirubin >20 micromol/l (OR 3.66 (95% CI 1.07-12.47)) were shown to be independent risk factors for oesophageal varices. Prothrombin time was unhelpful. The values at these cut offs were not useful in predicting oesophageal varices in the other groups. CONCLUSION: We conclude that current guidelines recommended by the AASLD Single Topic symposium are invalid in our cohort of patients with PBC and PSC. Patients with a platelet count <200,000/mm3, an albumin level <40 g/l, and a bilirubin level >20 micromol/l should be screened for oesophageal varices.     

Long-term prognosis of patients with alcoholic liver cirrhosis: a 15-year follow-up study of 100 Norwegian patients admitted to one unit

BACKGROUND: Most follow-up studies in patients with alcoholic liver cirrhosis have been for a 5-year period or less. The aim of this study was to assess the long-term mortality and causes of death among patients with alcoholic liver cirrhosis and to identify predictors of mortality. METHODS: One hundred patients with alcoholic liver cirrhosis, consecutively admitted to one medical department, were included in the study from May 1984 until December 1988. All patients had a history of alcohol abuse of at least 100 g ethanol daily for several years. The study comprised 65 men and 35 women with a median age of 58 years (range 34-82). Percutaneous liver biopsies and/or autopsies were obtained on 89 patients. Sixty-seven had ascites at admission and 34% had bleeding oesophageal varices. All patients were followed prospectively until death or until October 2000. RESULTS: During the follow-up period 90% of the patients died, 68 of whom (76 %) had been autopsied. The cumulative actuarial mortality after 1, 3, 6 and 12 months was 18%, 28%, 36% and 49%, respectively and after 5, 10 and 15 years 71%, 84% and 90%, respectively. None of the patients underwent liver transplantation during the study. The causes of death were bleeding, liver failure or a combination of these two conditions in 52 of 90 patients (58%), while 9 (11%) died of hepatocellular carcinoma 0.5 to 73 months after inclusion in the study. Using the Cox regression analysis, age, alcohol abuse and alkaline phosphatase were independent and significant predictors of mortality, but Child-Pugh class was not. CONCLUSIONS: The mortality in a group of patients with advanced alcoholic cirrhosis was extremely high with 5 and 15 years' mortality in 71% and 90%, respectively. Independent predictors of a poor prognosis were high age, continuous alcohol consumption of more than 10 g ethanol per day and high levels of alkaline phosphatase.     

Rotavirus Causes Hepatic Transaminase Elevation

Rotavirus is one of the leading causes of acute gastroenteritis among children. While clinical complaints are generally intestinal including vomiting and diarrhea, there is evidence to suggest that disease outside the gastrointestinal tract occurs. This study examines the frequency of hepatic transaminase elevation in children with rotavirus gastroenteritis. Patients identified with rotavirus gastroenteritis by stool antigen testing between November 2005 and March 2006 had available serum analyzed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total bilirubin, direct bilirubin, and creatinine phoshosphokinase (CPK). Chart review was conducted to identify patients with possible liver injury unrelated to rotavirus. Among the 92 patients identified with rotavirus during the study period, 75 had serum specimens available for testing. Fifteen patients (20%) had elevated ALT and AST, including one patient with an increase in AST, ALT, alkaline phosphatase, and total and direct bilirubin. The mean ALT elevation was 56 IU/L (range, 44 to 114 IU/L), and the mean AST elevation was 80 IU/L (range, 57 to 126 IU/L). Fifty-three patients (71%) had an increase in AST alone, and three patients (4%) had an increase in AST and alkaline phosphatase. The mean AST values in these groups were 61 IU/L (range, 42 to 110 IU/L) and 79 IU/L (range, 59 to 96 IU/L), respectively. In conclusion, rotavirus commonly causes elevation of liver transaminases.     

Non-invasive predictors of the presence of large oesophageal varices in patients with cirrhosis

BACKGROUND/AIMS: The usual clinical practice is to screen all patients with established cirrhosis at the time of diagnosis by upper endoscopy for the presence of varices. Patients with large varices should be treated with non-selective beta blockers to reduce the incidence of first variceal bleeding. However, fewer than 50% of cirrhotic patients have varices at screening endoscopy and most have small sized varices, with a low risk of bleeding. The aim of the present study was to determine whether clinical or laboratory non-endoscopic parameters could predict the presence of large oesophageal varices. PATIENTS/METHODS: Seventeen variables considered relevant to the prevalence of oesophageal varices were tested in 184 patients with cirrhosis, who underwent screening endoscopy. Small varices were regarded as those which flatten with insufflation or slightly protrude into the lumen, while large varices are those which protrude into the lumen or touch each other. None of the patients was on beta blockers or other vasoactive drugs or had a history of variceal bleeding. RESULTS: Oesophageal varices were present in 92 patients (50%), and large varices in 33 patients (17.9%).Variables associated with the presence of large oesophageal varices on univariate analysis were the presence of ascites and splenomegaly either by clinical examination or by ultrasound (p < 0.01), the presence of spiders (p = 0.02), platelet count (p < 0.0001), and bilirubin (p = 0.01). Factors independently associated with the presence of large oesophageal varices on multivariate analysis were platelet count, size of spleen and presence of ascites by ultrasound. Using mean values as cut-off points, it is noteworthy that only five out of 39 patients (12.8%) with platelets > or = 18(x 10(9)/l), spleen length < or = 135 mm and no ascites had varices. Moreover, all these patients had small sized varices. On the other hand, 15 out of 18 patients (83.3%) with a platelet count < 118 x 10(9)/l, spleen length > 135 mm and ascites had varices. Moreover, five out of those 18 patients had large varices (28.3%). CONCLUSION: Thrombocytopenia, splenomegaly and ascites are independent predictors of large oesophageal varices in cirrhotic patients. We suggest that endoscopy could be avoided safely in cirrhotic patients with none of these predictive factors, as large varices are absent in this group of patients.     

Prevalence of esophagogastric varices in patients with non-alcoholic steatohepatitis.

Aim: In non-alcoholic steatohepatitis (NASH), fibrosis begins around the central veins, as also happens with alcoholic liver disease, so the symptoms of portal hypertension may be due to central vein occlusion. The aim of this study was to define the prevalence of esophagogastric varices and the clinical outcome after endoscopic treatment in NASH patients with severe fibrosis. Methods: The subjects were 72 patients with clinicopathologically confirmed NASH who had bridging fibrosis (F3) or cirrhosis (F4) determined by the examination of liver biopsy specimens, and who underwent upper gastrointestinal endoscopy. The prevalence and pattern of endoscopically detected varices at the time of liver biopsy were evaluated. The results of NASH patients (n = 11) with endoscopically treated esophageal varices were compared to those with alcoholic (n = 67) and hepatitis C virus-associated cirrhosis (n = 152). Results: Esophagogastric varices were detected in 34 out of the 72 (47.2%) patients; esophageal varices in 25 (34.7%) and gastric varices in nine (12.5%), while six of these patients had variceal bleeding. In NASH patients, the cumulative recurrence-free probability at 24 months after endoscopic treatment was 63.6%, the bleeding-free probability was 90.9%, and the 5-year survival was 100%. Only one out 11 patients died of liver failure at 70 months after treatment. Conclusion: About half of NASH patients with severe fibrosis had esophagogastric varices. The clinical status and course of the varices do not necessarily improve after endoscopic treatment. NASH patients with esophagogastric varices need to be followed up carefully, like patients with other chronic liver diseases.     

Cryoglobulins in primary biliary cirrhosis: prevalence and modulation by immunosuppressive therapy

Cryoglobulins were measured in 25 patients with PBC and, for comparison purposes, in 25 age- and sex-matched normal individuals as well as 25 patients with chronic active hepatitis (CAH). Cryoglobulins were present in all patients with PBC (median protein content 18 mg/l, range 8-233) and consisted predominantly of IgM, while none of the normal controls and only 20% of the patients with CAH had cryoglobulins. In PBC, a statistically significant correlation was found between cryoglobulin-IgM concentration and other immunological measurements, such as the serum IgM level (p = 0.003) and Clq binding (p less than 0.001). Cryoglobulin-IgM also correlated significantly with alkaline phosphatase (p = 0.002) and liver fibrosis (p = 0.013), but only in a larger group of patients with PBC. In a longitudinal study of patients with PBC, no changes in the cryoglobulin concentration were found following treatment with D-penicillamine alone or placebo, but the cryoglobulin-IgM level decreased significantly during low-dose combination therapy of D-penicillamine and prednisone (median 15,4 mg/l); this was accompanied by a statistically significant decrease in serum alkaline phosphatase. The relation between cryoglobulin-IgM, serum alkaline phosphatase and liver fibrosis is discussed with regard to the pathogenesis of PBC.     

Long‐term prognosis of patients with alcoholic liver cirrhosis: a 15‐year follow‐up study of 100 Norwegian patients admitted to one unit

Background: Most follow‐up studies in patients with alcoholic liver cirrhosis have been for a 5‐year period or less. The aim of this study was to assess the long‐term mortality and causes of death among patients with alcoholic liver cirrhosis and to identify predictors of mortality. Methods: One hundred patients with alcoholic liver cirrhosis, consecutively admitted to one medical department, were included in the study from May 1984 until December 1988. All patients had a history of alcohol abuse of at least 100?g ethanol daily for several years. The study comprised 65 men and 35 women with a median age of 58 years (range 34–82). Percutaneous liver biopsies and/or autopsies were obtained on 89 patients. Sixty‐seven had ascites at admission and 34% had bleeding oesophageal varices. All patients were followed prospectively until death or until October 2000. Results: During the follow‐up period 90% of the patients died, 68 of whom (76 %) had been autopsied. The cumulative actuarial mortality after 1, 3, 6 and 12 months was 18%, 28%, 36% and 49%, respectively and after 5, 10 and 15 years 71%, 84% and 90%, respectively. None of the patients underwent liver transplantation during the study. The causes of death were bleeding, liver failure or a combination of these two conditions in 52 of 90 patients (58%), while 9 (11%) died of hepatocellular carcinoma 0.5 to 73 months after inclusion in the study. Using the Cox regression analysis, age, alcohol abuse and alkaline phosphatase were independent and significant predictors of mortality, but Child‐Pugh class was not. Conclusions: The mortality in a group of patients with advanced alcoholic cirrhosis was extremely high with 5 and 15 years' mortality in 71% and 90%, respectively. Independent predictors of a poor prognosis were high age, continuous alcohol consumption of more than 10?g ethanol per day and high levels of alkaline phosphatase.     

Cholesterol and bile acid metabolism in moderately advanced, stable cirrhosis of the liver.

We have selected for this study a well-defined group of patients with moderately advanced but compensated alcoholic cirrhosis. They were well-nourished and had no ascites, varices, azotemia, or encephalopathy. Liver biopsy showed little or no necrosis and inflammation despite wide-spread fibrosis. Serum bilirubin, transaminase, alkaline phosphatase, albumin and globulins were essentially normal. Biochemical evidence for liver disease was restricted to modest elevation of BSP retention, gamma GTP, serum bile acid concentrations, and urinary bile acid excretion. Except for changes in the interrelationships among the three biliary lipids, they were generally spared the abnormalities of sterol metabolism described in other patients with more advanced, more active liver disease. Thus, striking abnormalities in the metabolism of cholesterol and bile acids probably require severe reductions in functioning hepatocellular mass, major portal-systemic shunting, high disease activity, or all three to become manifest.     

Alpha-fetoprotein and carcinoembryonic antigen in patients with primary liver carcinoma, metastatic liver disease, and alcoholic liver disease

Alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), alkaline phosphatase (ALP) and gamma-glutamyltranspeptidase (GT) were determined in three groups of patients: 21 with primary liver carcinoma (PLC), 106 with metastatic liver disease, and 110 with various degrees of alcoholic liver diseases. AFP was elevated in 12 out of 14 with hepatocellular carcinoma but in none of 7 with cholangiocarcinoma. CEA was elevated in 8 of 14 with hepatocellular carcinoma and in 5 of 7 with cholangiocarcinoma. In metastatic liver disease, 83% had elevated CEA greater than or equal to 5.0 micrograms/l, 50% having CEA levels greater than 20 micrograms/l. AFP was moderately elevated in 26% of the patients, the values being less than 100 micrograms/l in all but one. In patients with alcoholic liver disease, 31% had elevated CEA levels greater than or equal to 5.0 micrograms/l; one of these had an extremely high value of 245 micrograms/l. AFP was moderately elevated to less than 100 micrograms/l in only 9%. CEA is a sensitive indicator of metastases: a value above 20 micrograms/l is almost always associated with malignancy. However, the presence of alcoholic liver diseases must be considered in evaluating patients with increased CEA levels. AFP and CEA seemed to be of value in differentiation between primary and secondary liver carcinoma. ALP and GT are also relatively sensitive indicators of malignant liver disease, but they are more unspecific than AFP and CEA.     

Serum markers for necroinflammatory activity in patients with chronic viral hepatitis and normal or mildly elevated aminotransferase levels

Background: Reports on the usefulness of serum markers for predicting liver necroinflammation are limited. The aim of this study was to determine the serum markers that predict significant inflammation in patients with chronic hepatitis B (CHB) and C (CHC) and normal or mildly elevated serum aminotransferase levels. Methods: Two hundred twenty‐seven patients with CHB or CHC with normal or mildly elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (≤60 IU/L) were enrolled in this study. Significant inflammation was defined as inflammatory grade ≥3 activities using the Batt–Ludwig scoring system. The correlation between liver histology and serum markers of liver inflammation was analysed. Results: Forty‐eight (21.1%) and eight patients (3.5%) had grade 3 and 4 inflammation respectively. Univariate analysis revealed that age, platelet coun, and AST, ALT, γ‐glutamyl transpeptidase, alkaline phosphatase, hyaluronic acid, haptoglobin, apolipoprotein A1 and procollagen III N‐terminal peptide levels were significantly different between the patients with and without significant inflammation. There were no significant differences in the cytokeratin‐18 fragment levels between the two groups. On the basis of multivariate analysis, the AST and apolipoprotein A1 levels and stage of fibrosis were highly predictive of significant inflammation. Using AST and apolipoprotein cut‐off values ≥44 IU/L and ≤100 ng/ml, respectively, the presence of significant inflammation was predicted with high specificity (96.5%) and with a negative predictive value of 76.3%. Conclusion: The AST and apolipoprotein A1 levels were shown to be independent predictors of significant inflammatory activities in patients with CHB and CHC and normal or mildly elevated aminotransferase levels.     

Liver stiffness measurement selects patients with cirrhosis at risk of bearing large oesophageal varices

BACKGROUND/AIMS: Periodic endoscopic screening for oesophageal varices is recommended in patients with cirrhosis, but might be limited to a subgroup of patients if a simple non-invasive test was available to select those at risk of bleeding. METHODS: We studied in 165 patients with cirrhosis the relation between the presence of oesophageal varices assessed by endoscopy, and liver stiffness measurement by Fibroscan, a non-invasive parameter related to liver fibrosis. The results were compared to those of other parameters reflecting portal hypertension, splenic size, platelet count, and platelet count/spleen size ratio. RESULTS: Liver stiffness measurement was correlated to the grade of oesophageal varices (r = 0.6, p < 0.0001). AUROC values of liver stiffness measurement were 0.84 (95% CI: 0.78-0.90) for the presence of oesophageal varices and 0.83 (0.76-0.89) for varices grade > or = II. Liver stiffness measurement value < 19 kPa was highly predictive of the absence of oesophageal varices grade > or = II (Se: 84%, PPV: 47%, NPV: 93%). CONCLUSIONS: Liver stiffness measurement allows to predict the presence of large oesophageal varices in patients with cirrhosis, and may help to select patients for endoscopic screening.     

Incidence and fate of antral varices.

OBJECTIVE: To study the incidence of antral varices (AV) and their fate in patients with portal hypertension so as to formulate a management policy. DESIGN: Prospective cohort study. SETTING: Single surgical unit specializing in portal hypertension management in a tertiary level centre. PARTICIPANTS: Three hundred and seventy-one patients [cirrhosis 170, non-cirrhotic portal fibrosis (NCPF) 53, extrahepatic portal venous obstruction (EHPVO) 148] with history of bleeding from oesophageal varices were inducted in the chronic sclerotherapy programme. INTERVENTIONS: Protocol-based endoscopic sclerotherapy and management of bleeding for oesophageal varices. OUTCOME MEASURES: Development or disappearance of AV, bleeding from AV. RESULTS: No patient had AV on index endoscopy. Thirteen (3.5%) patients developed AV, in cirrhosis 2.9%, EHPVO 4.1%, NCPF 3.8% (P = 0.86). AV developed after a mean of 15 months. Oesophageal varices took a longer number of sessions to obliterate in patients with AV (11.1 vs 5.98 sessions, P<0.0001). Only one patient bled, having coexistent oesophageal varices and gastropathy. AV disappeared spontaneously in seven patients, recurring in only one. Of seven persisting AV, none have bled over a mean follow-up of 30 months (SD 23.2). CONCLUSIONS: AV are seen in a small proportion of patients, and are distributed equally amongst the aetiologies of portal hypertension. They rarely bleed and may be ignored during sclerotherapy of oesophageal varices.     

Serum procollagen III peptide in alcoholic and other chronic liver diseases

Increased levels of serum procollagen III peptide (P-III-P) have been found in patients with alcoholic hepatitis and cirrhosis. Serum P-III-P was increased (greater than 15 micrograms/l) in 38 of 44 (86%) patients with alcoholic liver cirrhosis, in 6 of 20 (30%) with fatty liver, in 1 of 13 (8%) with non-alcoholic fatty liver, and in 3 of 14 (21%) with other chronic liver diseases. Median serum P-III-P was almost three times higher in alcoholic liver cirrhosis than in alcoholic fatty liver (p less than 0.001). Serum P-III-P was increased in three of six patients with alcoholic fatty liver and periportal fibrosis. In the total material (n = 91), a statistically significant negative correlation between serum P-III-P and albumin (r = -0.71, p less than 0.001) and Normotest (r = -0.63, p less than 0.001), respectively, and a positive correlation between serum P-III-P and bilirubin (r = 0.65, p less than 0.001) were found. The serum level of P-III-P had no prognostic value concerning the mortality in patients with alcoholic cirrhosis.     

Prognostic value of serum hyaluronan in patients with compensated HCV cirrhosis

BACKGROUND/AIM: Serum hyaluronan (HA) levels increase according to the degree of liver fibrosis in patients with chronic viral hepatitis C. Patients with liver disease and markedly high serum HA levels have cirrhosis with typical signs of hepatic sinusoidal capillarization, a factor of aggravation of cirrhosis The aim of this study was to evaluate the prognostic value of serum HA for severe complications in asymptomatic patients with HCV cirrhosis. METHODS: Six hundred and sixty-eight patients with anti-HCV antibodies and increased serum alanine aminotransferase were referred to our hospital for evaluation, including liver biopsy. At entry, serum HA levels were measured in 91 patients (64 men, 27 women, 56 +/-11 years old) out of 103 who had asymptomatic, biopsy-proven cirrhosis According to the criteria of Child-Pugh, 82 were classified A and 9 B. The follow-up period was 6 to 82 months (median: 38 months), and 51 of these patients received alpha-interferon therapy during the first year. Severe complications were defined as death or liver transplantation, ascites, bleeding from esophageal varices, encephalopathy, or hepatocellular carcinoma. RESULTS: Serum HA levels at entry were higher in the cirrhotic patients in whom severe complications occurred during the follow-up period (520+/-426 microg/l vs 197+/-146 microg/l, p<0.0001). The patients with serum hyaluronan levels >350 microg/l displayed higher probabilities of occurrence of severe complications (p<0.0001). Other factors associated with the occurrence of complications or death were: serum bilirubin >18mol/l (p = 0.03), platelet count <112x10(9)/l (p= 0.02), prothrombin time <63% (p<0.0001), serum albumin <36 g/l (p=0.002), alkaline phosphatase >81 IU/l (p=0.01), and no interferon treatment (p= 0.0003). Multivariate analysis identified five independent factors predictive of severe clinical complications, namely: hyaluronan (p=0.006), prothrombin time (p=0.04), bilirubin (p=0.04), albumin (p=0.04), and no therapy (p=0.03). CONCLUSION: Serum HA level is predictive for occurrence of severe complications in HCV cirrhosis, and can be used as a prognostic marker, in addition to the parameters of the Child-Pugh score, particularly in patients with compensated cirrhosis.     

Serum levels of YKL-40 and PIIINP as prognostic markers in patients with alcoholic liver disease

BACKGROUND/AIMS: YKL-40 (growth factor) and PIIINP (N-terminal propeptide of Type III procollagen) are potential markers of liver fibrosis. The aim was to evaluate the prognostic value of serum YKL-40 and PIIINP levels in patients with alcoholic liver disease. METHODS: Three hundred and seventy patients with alcoholic liver disease were studied in a trial of malotilate with a median follow-up period of 470 days; 75 patients died; 336 patients had a liver biopsy on entry. Serum levels of YKL-40 and PIIINP were determined by radioimmunoassay (RIA). RESULTS: Serum YKL-40 and PIIINP were elevated in the patients compared to controls. Patients with steatosis or no fibrosis had the lowest serum levels of YKL-40 and PIIINP, whereas patients with alcoholic hepatitis and/or cirrhosis had the highest levels. Serum YKL-40 was associated with the presence of fibrosis, and serum PIIINP was also associated with the different grades of fibrosis. Patients with elevated serum YKL-40 or PIIINP had shorter survival than patients with normal serum levels of YKL-40 (P<0.0001) or PIIINP (P=0.044). High degree of fibrosis predicted shorter survival (P=0.004). CONCLUSIONS: Serum levels of YKL-40 and PIIINP are elevated in alcoholic patients, related to the presence of liver fibrosis and may provide prognostic information.     

Alcoholic liver disease presenting with marked elevation of serum alkaline phosphatase

Twenty patients with longstanding alcoholism and biopsy-proven alcoholic liver disease presented with marked elevation of serum alkaline phosphatase (in excess of four times the upper limit of normal). None had a past or present history to suggest pancreatitis or biliary tract disease, nor had any of these patients recently taken medication which could be implicated in cholestatic joundice. Thirteen (65%) of this group either had radiologic or post mortem confirmation of nonobstructed biliary sytems. The histologic findings in this group of patients were compared with those of a group of patients with alcoholic liver disease and normal or only mild elevation of serum alkaline phosphatase. Significantly more hepatocellular necrosis (P<0.05), alcoholic hyaline (P<0.02), and cholestasis (P<0.002) were noted in the severely hyperphosphatasemic group. Minimal degrees of steatosis were found in both groups. These data indicate that intrahepatic cholestasis occurs in patients with alcoholic liver disease, and this may often be secondary to alcoholic hepatitis. Overemphasis has previously been given to alcoholic fatty liver as a cause of this syndrome.     

Non-invasive monitoring of oxidant stress in alcoholic liver disease

OBJECTIVE: In alcoholic liver disease (ALD), progression from initial steatosis, through hepatitis to cirrhosis is well described, resulting in 20,000 deaths in the UK annually. However, pathological mechanisms are not well understood and drug trials have led to conflicting results. It has been established that alcohol consumption increases hepatic free radical production and oxidant stress has been implicated in the disease process. MATERIAL AND METHODS: Markers of lipid peroxidation, antioxidant status, hepatic fibrogenesis, inflammation and liver function were measured in blood and urine from 24 patients with established alcoholic cirrhosis and in 49 age- and sex-matched controls. RESULTS: In the ALD group, lipid peroxidation markers 8-isoprostane and malondialdehyde were significantly increased (p<0.001), as was the ratio of oxidized to reduced glutathione (p=0.027). The antioxidants selenium, glutathione (whole blood and plasma) and vitamins A, C and E were all significantly decreased (p<0.001); median plasma glutathione levels were only 19% of control levels. Type III procollagen peptide (PIIINP), a serum marker of hepatic fibrogenesis, and C-reactive protein (CRP) were both increased (p<0.001). Urinary 8-isoprostane correlated positively with PIIINP, CRP and markers of cholestasis (alkaline phosphatase and bilirubin) and negatively with glutathione (whole blood), vitamins A and E and albumin. CONCLUSIONS: Oxidant stress, as reflected in blood and urine by a wide range of pro- and antioxidant markers, is a significant feature of alcoholic cirrhosis, providing a mechanism by which alcohol intake may be linked to hepatic inflammation and fibrosis. Non-invasive markers could prove valuable in monitoring response to treatment during clinical trials.     

晚期血吸虫病与血管内皮素及血清肝纤维化指标的相关性分析

目的了解晚期血吸虫病患者内皮素(ET)、透明质酸(HA)、三型前胶原(PCⅢ)、四型胶原(IV.C)、层粘蛋白(LN)与肝纤维化形成、晚期血吸虫病患者肝功能损伤程度的相关性及门脉高压的关系。方法用放射免疫分析法测定了60例晚期血吸虫病患者和150例慢性血吸虫病患者血清ET、HA、PCIII、IV.C、LN含量,并与肝功能分级进行比较分析。结果晚期血吸虫病患者ET血清浓度明显增高,与慢血组比较差异有统计学意义(P<0.01)。晚期血吸虫病患者ET、HA、PCⅢ、IV.C、LN水平随着chuild-pugh分级及肝纤维化程度增高而增高;晚期血吸虫病伴食道静脉曲张与无食道静脉曲张患者血清ET、HA、PCⅢ、IV.C、LN含量差异有统计学意义(P<0.01)。结论ET、HA、PCⅢ、IV.C、LN可能在晚期血吸虫病肝纤维化形成和门脉高压的形成中起重要作用,并与肝功能损害程度有关。