The role of hepatitis C virus (HCV) heterogeneity in the severity of chronic hepatitis C infection remains unclear. Our aim was to study the hypervariable region 1 (HVR1) heterogeneity in patients with chronic hepatitis C infected with genotype 1b or 3 and with normal or abnormal alaninc aminotransferase (ALT). HVR1 quasispecies were assessed by single strand conformational polymorphism (SSCP) in 67 patients with chronic hepatitis C, including 3 5 with persistently normal ALT and 32 with abnormal ALT. Sixty-two patients underwent a liver biopsy. Among the 67 patients, 40 were infected with genotype 1b and 27 with genotype 3. In univariate analysis, low heterogeneity (5 3 bands at SSCP) was significantly associated with normal ALT (P<0.001). milder histological lesions (activity, P=0.02; fibrosis, P=0.04), and at the limit of significance for genotype 1b (P=0.07). In multivariate analysis, low heterogeneity was significantly and independently associated with normal ALT (P=0.09) and genotype 1b (P=0.03). In patients with chronic hepatitis C, a low viral heterogeneity is significantly and independently associated with normal ALT and genotype 1b. These results are consistent with the view that patients with normal ALT have a different immune response against HCV resulting in a low HCV heterogeneity.

We report the case of a 66-year-old man with chronic hepatitis C and a slowly growing left chest wall mass. Two years after the patient first noticed the mass, it was resected. A diagnosis of hepatocellular carcinoma (HCC) was established. The liver was studied by ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and angiography, but no mass was found. Blind liver biopsy showed mild chronic hepatitis without cirrhosis or HCC. Three years after the discovery of the chest wall HCC, no liver mass had appeared at CT and MRI. We conclude that solitary extrahepatic HCC (i) may arise in ectopic liver tissue; (ii) should not be considered as a metastasis of an occult HCC; and (iii) can be amenable to cure through resection.

A possible hepatotoxicity of cigarette smoke has been recently suggested by epidemiological and experimental studies. Our aim was to study the possible relationships between smoking and liver fibrosis and activity in patients with chronic hepatitis C. A cross-sectional study was performed in a group of 310 patients with chronic hepatitis C consecutively hospitalized for their first liver biopsy. The relationships between age, gender, alcohol consumption, route of contamination, tobacco consumption, and Knodell fibrosis and activity scores were examined in univariate, age-adjusted, and multivariate analyses. One hundred and seventy-six patients (57%) were current smokers. Smokers were younger (P <.001), more often of male gender (P =.001), more often alcohol consumers (P =.001), and more often had a history of intravenous drug use (P =.0001) than never smokers. Smoking was related to increased fibrosis and activity scores in age-adjusted (P =.009 and P =.005, respectively) and multivariate analyses (P =.03 and P =.04, respectively). Smoking increases the severity of hepatic lesions in patients with chronic hepatitis C.

BACKGROUND & AIMS:The outcome of portal vein thrombosis in relation to associated prothrombotic states has not been evaluated. We assessed current outcome and predictors of bleeding and thrombotic events in a cohort of 136 adults with nonmalignant, noncirrhotic portal vein thrombosis, of whom 84 received anticoagulant therapy.METHODS:Multivariate Cox model analysis for event-free survival and analysis taking into account multiple events were used.RESULTS:Median follow-up was 46 months. The incidence rate of gastrointestinal bleeding was 12.5 (95% confidence interval [CI], 10-15) per 100 patient-years. Large varices were an independent predictor for bleeding. Anticoagulant therapy did not increase the risk or the severity of bleeding. The incidence rate of thrombotic events was 5.5 (95% CI, 3.8-7.2) per 100 patient-years. Underlying prothrombotic state and absence of anticoagulant therapy were independent predictors for thrombosis. In patients with underlying prothrombotic state, the incidence rates of splanchnic venous infarction were 0.82 and 5.2 per 100 patient-years in periods with and without anticoagulant therapy, respectively (P = 0.01). Two nonanticoagulated patients died of bleeding and thrombosis, respectively.CONCLUSIONS:In patients with portal vein thrombosis, the risk of thrombosis is currently as clinically significant as the risk of bleeding. The benefit-risk ratio favors anticoagulant therapy.

Background-The role of factor V Leiden as a cause of Budd-Chiari syndrome has only recently been described.Aims-To assess the specific features of factor V Leiden related Budd-Chiari syndrome.Patients-Sixty three consecutive patients with hepatic vein or terminal inferior vena cava thrombosis.Methods-Standardised chart review.Results-Factor V Leiden was found in 20 patients (31% (95% CI 20-43)). In the subgroup of patients with, compared with the subgroup without, factor V Leiden, a combination of prothrombotic states was more common (70% (95% CI 50-90) nu 14% (95% CI 3-24)); inferior vena cava thrombosis was more frequent (40% (95% CI 19-61) nu 7% (95% CI 0-14)); and distribution of initial alanine aminotransferase values was bimodal (almost normal nr extremely increased) versus unimodal (p=0.003). Factor V Leiden accounted for four of five cases of massive ischaemic necrosis (transaminases >50-fold the upper limit of normal values) (p=0.014), and also for all three cases developing during pregnancy. Patients with and without factor V Leiden did not differ with regard to mortality, portosytemic shunting, or Listing for liver transplantation. Hepatocellular carcinoma developed in two patients; both had factor V Leiden and indolent obstruction of the inferior vena cava.Conclusions-In patients with Budd-Chiari syndrome, factor V Leiden (a) is common; (b) precipitates thrombosis mostly when combined with another risk factor; (c) is associated with one of two contrasting clinical pictures: indolent thrombosis-particularly of the inferior vena cava-or massive ischaemic necrosis; and (d) is a major cofactor of Budd-Chiari syndrome developing during pregnancy.

AIM To evaluate the natural course of focal nodular hyperplasia according to hormonal status. METHODS Forty-four patients were included in this retrospective study. Tumor size was assessed with ultrasound examination. We studied the influence of hormone status on the course of the disease. RESULTS All patients were women, the median age at diagnosis was 35 years and the median follow-up was 45 months. Ten patients were symptomatic at diagnosis, while none were symptomatic at the end of follow-up. The median size of the lesions was 56 mm. No complications occurred. The size of the tumor remained stable in 19 patients, increased in 12 and decreased in 13. Twenty-one of 37 patients stopped taking oral contraceptives at diagnosis: the lesion remained stable in 11 patients, increased in 3 and decreased in 7. Two patients didn't stop taking oral contraceptives: the lesion increased in one, decreased in the other. Six patients became pregnant and 6 patients went into menopause during follow-up: the lesion remained stable in 3 and 4 patients respectively. CONCLUSION Focal nodular hyperplasia is a benign lesion. Tumor size remained stable in most cases. It seems that the hormonal status has little or no influence on the course of the disease.

Magnetic resonance cholangiopancreatography (MRCP) has received much attention as a non-invasive alternative to endoscopic retrograde cholangiopancreatography, primarily for investigation of choledocholithiasis, but also for evaluation of less common biliary anomalies. We present a case of haemobilia causing acute pancreatitis after percutaneous liver biopsy in which the diagnosis could be made clearly by MRCP, thus avoiding endoscopic retrograde cholangiopancreatography and sphincterotomy.

OBJECTIVE: Hemophagocytic syndrome has been defined as the combination of a proliferation of cytologically benign, actively phagocytic macrophages in bone marrow, spleen, or lymph nodes in association with fever, cytopenia, splenomegaly, and hypertriglyceridemia. Hepatic dysfunction is often present but the nature of the hepatic lesions and related manifestations have not been fully characterized. The aim of this study was to ascertain the features of hepatic involvement in hemophagocytic syndrome. METHODS: Thirty patients with hemophagocytic syndrome were retrospectively studied. Inclusion criteria included:1) bone marrow with hemophagocytic histiocytosis, 2) clinical or biological signs of hepatic involvement, and 3) available liver specimen. RESULTS: The association of fever, jaundice, and hepatomegaly or splenomegaly was present in 50% of the patients. Median value for serum alanine transaminase activity was five times the upper limit of normal values (range, 0.3–125), for serum alkaline phosphatase activity 2.7 upper limit of normal values (range, 0.2–47.7), for total bilirubin 136 μmol/L (range, 4–681 μmol/L), and for factor V 70% (range, 19–145%). Sinusoidal dilatation with hemophagocytic histiocytosis were found in the biopsy specimen in all patients. An underlying condition potentially responsible for altered immune function (lymphoma, leukemia, liver transplantation) was identified in 29 patients. Liver biopsy was diagnostic for the underlying condition in 15 patients (including eight cases with nonspecific bone marrow biopsy findings). High serum bilirubin, elevated serum alkaline phosphatase activity, low factor V level, and lack of treatment for the underlying disease were associated with a poor prognosis. CONCLUSIONS: Hemophagocytic syndrome should be suspected in immunodeficient patients with fever, jaundice, and hepatosplenomegaly. Hepatic lesions are characterized by nonspecific sinusoidal dilatation with hemophagocytic histiocytosis and in 50% of the patients by alterations specific to the underlying condition. Liver biopsy is a useful diagnostic procedure in patients with this clinical presentation.

According to a recent hypothesis, venous thrombosis results from the concurrence of several factors. This hypothesis was assessed in patients with portal or hepatic venous thrombosis by simultaneously investigating most of the currently identified prothrombotic disorders, local precipitating factors, and other risk factors such as oral contraceptive use. Patients with a tumorous obstruction and patients with cirrhosis with portal vein thrombosis were excluded. The prothrombotic disorders that were investigated included classical and occult myeloproliferative disorders; antiphospholipid syndrome; protein C; protein S and antithrombin deficiency; factor V Leiden; factor II; and methylene-tetrahydrofolate-reductase gene mutations. We found 1 or several prothrombotic disorders and a local precipitating factor in 26 and 10 of the 36 patients with portal vein thrombosis, respectively; and in 28 and none of the 32 patients with hepatic vein thrombosis, respectively. We found a combination of prothrombotic disorders in 5 and 9 patients with portal and hepatic vein thrombosis, respectively, whereas such a combination is expected in less than 1% of asymptomatic subjects. Of the 10 patients with a local precipitating factor, 8 had a prothrombotic disorder. Of the 13 patients who use oral contraceptives, 10 had a prothrombotic disorder. We conclude that portal or hepatic venous thrombosis should be regarded as an index for 1 or several prothrombotic disorders, whether or not local precipitating factors or oral contraceptive use are found. Concurrence of prothrombotic disorders is more common than expected. Extensive investigation of prothrombotic disorders and anticoagulation should be considered in patients with portal or hepatic venous thrombosis.

Generalized pustular psoriasis can result in systemic complications. We report the case of a woman with relapsing generalized pustular psoriasis and recurring episodes of cholestatic jaundice. Liver biopsy performed during an attack showed a neutrophilic infiltrate surrounding and invading portal triad bile ducts. Ultrasonographic exams and retrograde cholangiography ruled out biliary tract disease. This observation suggests that recurring cholestatic jaundice in pustular psoriasis is related to a neutrophilic cholangitis.

Cystic dilatations of the biliary tree are defined by cysts which communicate with the biliary channels. Caroli's disease is characterized by macroscopic dilatations of segmental bile ducts (who drain the segments of the liver). It is not familial. Kidneys are usually normal. The main symptom is cholangitis. Complications are intrahepatic stones and cholangiocarcinoma. Treatment of cholangitis is antibiotics. In resistant cases, partial hepatectomy (if cysts are localized in one part of the liver) or hepatic transplantation (if cysts are diffuse) should be considered. Congenital hepatic fibrosis is characterized by microscopic dilatations of interlobular bile ducts and portal fibrosis. It is an autosomal recessive disease associated with renal abnormalities. The major clinical manifestation is digestive haemorrhage due to portal hypertension. Caroli's syndrome is the association of Caroli's disease and congenital hepatic fibrosis. Choledocal cyst is characterized by a cystic dilatation of the common bile duct or hepatic duct. The main manifestations are jaundice and cholangitis. Cholangiocarcinoma may occur. Treatment is surgical resection.

Hepatic and bile duct involvement are common in sickle cell disease. This article reports the case of a young woman with cholangiopathy, homozygous sickle cell disease, and protracted anemia. We suggest that sickle cell disease was directly responsible for ischemic cholangiopathy through anoxia.

It has been shown that certain patients with cirrhosis have asymptomatic cardiac abnormalities that have not yet been explained. Thus, cardiac troponin I, a specific marker of myocardial injury, has been measured in patients with cirrhosis without previous cardiac disease. Thirty‐two consecutive patients (age 49 ± 11) with cirrhosis and normal ECG were selected, 22 of which were alcoholic. Hemodynamic investigations were performed. Left ventricular function and mass were evaluated by echocardiography. Serum creatine kinase MB mass, myoglobin, and cardiac troponin I concentrations were measured. Cardiac troponin I concentrations were elevated in 10 patients (32%) (range 0.06‐0.25 μg/L) whereas creatine kinase MB mass and myoglobin were normal in all patients. Abnormal troponin I values were not related to the severity of cirrhosis, to the degree of portal hypertension, or to other hemodynamic values. In contrast, elevated serum cardiac troponin I concentrations were related to a decreased stroke‐volume index (P < .05) and a decreased left ventricular mass (P < .05). These results show a high prevalence of slightly elevated serum cardiac troponin I in patients with cirrhosis, especially in those with alcoholic cirrhosis. Elevated troponin I is associated with subclinical left ventricular myocardial damage. These findings may be linked to a lack of left ventricular adaptation in certain patients with cirrhosis and alcoholic cardiomyopathy.

The objective of the study was to compare the clinical sensitivity and specificity of versions 1.0 and 2.0 of the branched DNA (bDNA)-based hepatitis C virus (HCV) RNA quantification assay, and also to compare the values yielded by the two versions according to the HCV genotype. Serum samples from 268 patients tested routinely by a non-quantitative HCV RNA PCR assay (group A) were tested with version 2.0 of the bDNA assay. Samples from 342 HCV PCR-positive patients with chronic hepatitis C eligible for interferon treatment (group B) were tested with both version 1.0 and version 2.0 of the bDNA assay. Version 2.0 had a clinical sensitivity of 92% (95% confidence interval (CI): 87–97%) in group A and 89% (86–92%) in group B. In group B, the gain in sensitivity with bDNA 2.0 was 16% relative to bDNA 1.0 (P<0.001). The log values of the two assays correlated with samples positive by both assays (r=0.83, P<0.0001), but the distribution of values was larger in samples containing HCV genotypes 2 and 3. The mean ratio of assay 2.0/assay 1.0 values was 1.69±1.44 (range: 0.33–13.43). The mean ratio was close to 1 with samples containing genotype 1 or 4, but ranged from 0.33 to more than 5. The mean ratio was close to 3 with samples containing genotype 2 or 3, and ranged from 0.5 to more than 13. HCV RNA levels were significantly lower in samples containing genotype 4 than in those containing other genotypes. Sera from 200 anti-HCV-negative, HCV RNA PCR-negative blood donors (group C), and from 164 anti-HCV-negative patients with symptoms of chronic liver disease (group D) were used to assess the clinical specificity of bDNA 2.0. In addition, samples with an HCV RNA titer between 0.2 (assay cutoff) and 0.5 MEq/ml from a group of 546 patients tested routinely for HCV RNA load by bDNA 2.0 (group E) were retested by bDNA 2.0 and by qualitative PCR. The specificity of bDNA 2.0 was 100% (98–100%) in group C and 99% (97–100%) in group D. Among the 41 samples from group E, 38 were positive by bDNA2.0 retesting (36 were PCR-positive) and three were negative by bDNA2.0 retesting (all were PCR-positive). It is concluded that version 2.0 of the bDNA assay is markedly more sensitive than version 1.0 and has a good specificity. In contrast with version 1.0, version 2.0 is not influenced by the HCV genotype. The relationship between values obtained with assays 1.0 and 2.0 on clinical specimens is not linear, indicating that HCV RNA titers cannot reliably be calculated from the results of version 1.0.

Objectives: To utilize cytokine levels to predict sustained response (SR) to alpha interferon (IFN α) therapy in chronic hepatitis C patients, and to determine the relationship between serum tumor necrosis factor α (TNF α), interleukin (IL) IL 6, IL 8, IL 12, transforming growth factor beta (TGF β 1) and the degree of liver damage as reflected by traditional markers.Design and methods: Serum cytokine levels were assessed using ELISA in 18 patients included in a controlled clinical trial of IFN α.Results: Of the 18 patients, 27% were sustained responders (SR), 27% were response and relapse responders (RR), and 46% were non-responders (NR). Multivariate analysis showed that a low serum TNF α level and high serum IL 8 levels were independent factors associated with SR to IFN α therapy. Serum TNF α level highly correlated with viral load and genotype predictive values (p < 0.001). Therapy lowered the IL 6 and IL 12 profile. TGF β 1 levels in serum are positively correlated with fibrinogenesis.Conclusions: IFN α therapy modulates immune response to hepatits C virus, contributing to sustained response.

Les progres rapides de la biologie moleculaire ont permis d'elucider le mecanisme de plusieurs cholestases hereditaires. La cholestase recurrente benigne est une affection a transmission recessive qui debute le plus souvent avant 20 ans. Elle se caracterise par des episodes de prurit et d'ictere durant de quelques semaines a plusieurs mois et cessant spontanement. La gammaGT est generalement normale ou peu elevee. Il n'y a pas d'evolution vers une cirrhose. Le gene mute, FIC1, code pour une proteine qui a une grande homologie avec des ATPases de type P, dont la fonction est de transporter certains phospholipides du feuillet externe vers le feuillet interne de la membrane plasmique. La cholestase intrahepatique familiale progressive, de phenotype 1, decrite chez des enfants de la communaute Amish aux Etats-Unis, se caracterise par une steatorrhee, un ictere avec des exacerbations intermittentes, un prurit feroce, une hepatosplenomegalie et un retard de croissance. La gammaGT est normale. L'evolution se fait vers la cirrhose biliaire avec hypertension portale et insuffisance hepatocellulaire. Le gene mute est le meme que celui de la cholestase recurrente benigne, FIC1. Les mutations semblent compromettre la fonction de la proteine plus severement que dans le cas de la cholestase recurrente benigne. La cholestase intrahepatique familiale progressive, de phenotype 2, identifiee chez des enfants n'appartenant pas a la communaute Amish, ressemble a la precedente, avec en particulier une gammaGT normale, mais son evolution est encore plus severe. La proteine mutee est le transporteur canaliculaire des acides biliaires SPGP (sister P-glycoprotein) ou BSEP (bile salt export pump). La cholestase intrahepatique familiale progressive, de phenotype 3, est caracterisee par un prurit moins intense, une augmentation marquee de la gammaGT et une cirrhose biliaire avec une intense proliferation de neoductules biliaires a l'examen histologique. La proteine mutee, MDR3, permet le transport des phospholipides vers le feuillet externe de la membrane canaliculaire, etape indispensable a leur excretion biliaire. Les memes lesions sont observees chez la souris apres inactivation du gene mdr2, l'equivalent murin de MDR3. Ces lesions sont la consequence de la toxicite des micelles d'acides biliaires depourvues de phospholipides, micelles qui ont un fort pouvoir detergent.

The aim of this study was to assess the influence of human immunodeficiency virus (HIV) infection on chronic hepatitis B. In a series of 132 (65 anti-HIV positive) homosexual non-drug addicted men with chronic hepatitis B, the liver function was assessed with biochemical tests; the degree of hepatitis B virus (HBV) replication was assessed with serum HBV DNA level and with immunoperoxidase staining of hepatitis B core (HBc) antigen on liver specimens; and the severity of liver lesions was assessed with an histology activity index. Anti-HIV-positive and anti-HIV-negative patients were not different for serum aspartate transaminase activity, bilirubin, prothrombin, and histology activity index. Anti-HIV-positive patients had lower serum alanine transaminase activity levels (P =.0001), lower serum albumin levels (P =.0009), and higher serum HBV DNA levels (P =.01). There was a higher prevalence of cirrhosis in anti-HIV-positive patients (P =.04). In homosexual men with chronic hepatitis B, HIV infection is associated with a higher level of HBV replication and a higher risk for cirrhosis without increased liver necrotico-inflammatory process.

The aim of this study was to assess the factors, including surgical portosystemic shunts, which affect survival in adults with Budd-Chiari syndrome. Multivariate retrospective analysis was performed using characteristics recorded at the time of diagnosis in 120 patients admitted from 1970 to 1992, of whom 82 were treated with surgical portosystemic shunts and 38 received only medical therapy. The 1-, 5-, and 10-year survival rates were 77 ± 4%, 64 ± 5%, and 57 ± 6%, respectively. Survival was significantly better in the subgroup of patients diagnosed after versus before 1985. In both subgroups, and in patients with, as well as in patients without surgical shunts, 4 factors were found to be inversely and independently related to survival: age, response of ascites to diuretics, Pugh score, and serum creatinine. In patients diagnosed since 1985, an index combining these 4 factors allowed to differentiate patients with a good outcome (5-year survival 95%) from those with a poor outcome (5-year survival 62%; P < .05). There was no statistically significant and independent influence of surgical portosystemic shunts on survival. In conclusion, age, severity of liver failure, and presence of refractory ascites are the main prognostic factors in Budd-Chiari syndrome. Increased survival in recent years is consistent with improved management of hypercoagulable states as well as improved general care. It is uncertain whether surgical portosystemic shunting favorably modifies survival. Therefore, we recommend that surgical shunting should be restricted to management of refractory ascites or variceal bleeding in patients with otherwise good prognostic factors.