Serum type I collagen and N-terminal peptide of type III procollagen in patients with alcoholic liver disease: relationship to liver histology.

This study compared, in patients with alcoholic liver disease, the serum concentration of N-terminal peptide of type III procollagen and of a novel serum marker, type I collagen, with liver histological data and assessed the role of these markers in the diagnosis and follow-up of liver changes. Ninety-six patients (mean age 51 years, 61 men and 35 women) were included. All had alcoholic liver disease diagnosed on usual clinical, biochemical, and histological criteria. Two histological scores, one for alcoholic hepatitis and one for fibrosis, were established. Serum N-terminal peptide of type III procollagen and type I collagen were assayed by liquid phase radioimmunoassay. Significant correlations between serum type I collagen and score of fibrosis (r = 0.34, p less than 0.001) and between serum N-terminal peptide of type III procollagen and score of alcoholic hepatitis (r = 0.60, p less than 0.0001) were noted. There was no significant correlation between serum aminotransferases and the score of alcoholic hepatitis. In 25 patients with alcoholic hepatitis reassessed between 3 and 6 months, serum N-terminal peptide of type III procollagen significantly decreased (p less than 0.05) as did the score of alcoholic hepatitis, but serum type I collagen and the score of fibrosis were not modified. These serum markers of collagen metabolism could be useful for the assessment and follow-up in patients with alcoholic liver disease.

Lymphocytic sialadenitis of Sjögren's syndrome associated with chronic hepatitis C virus liver disease.

Viral infection has often been suggested as a possible cause of Sjögren's syndrome or chronic lymphocytic sialadenitis, and Epstein-Barr virus has been found in the salivary glands of patients with this condition. After we had noted Sjögren's syndrome in several patients infected with hepatitis C virus (HCV), a virus also excreted in saliva, we set up a prospective study to investigate the association of chronic lymphocytic sialadenitis, with or without symptoms, to chronic HCV liver disease. The histological appearances of labial salivary glands in patients with proven HCV hepatitis or cirrhosis were compared with those in dead controls. Histological changes characteristic of Sjögren's syndrome were significantly more common in HCV-infected patients (16 of 28, 57%) compared with controls (1 of 20, 5%). Focal lymphocytic sialadenitis characteristic of Sjögren's syndrome (though only 10 patients had xerostomia and none complained of xerophthalmia) appears to be common in patients with chronic HCV liver disease; if this association is confirmed, identification of the underlying mechanism may improve our understanding of both disorders.

High-resolution CT of parenchymal lung disease: precise correlation with histologic findings.

To provide a precise correlation between high-resolution computed tomographic (CT) findings and histologic studies of various parenchymal lung diseases, 20 fixed and inflated lungs were studied as follows: (a) Every lung was cut at the corresponding CT level into 1.5-mm-thick sections, (b) selected slices were cut into small blocks to prepare histologic slides, (c) each slide was photographed, and (d) the image of the entire lung section was reconstituted with the enlarged photographs (assembled as in a jigsaw puzzle). Results obtained in cases of normal lungs, pulmonary edema, alveolitis, hypersensitivity pneumonitis, emphysema, Pneumocystis carinii pneumonia, silicosis-asbestosis, and idiopathic pulmonary fibrosis demonstrated the method to be accurate in correlating high-resolution CT findings and the corresponding histologic data.

Treatment of severe alcoholic hepatitis by infusion of insulin and glucagon: a multicenter sequential trial.

Severe alcoholic hepatitis is still a therapeutic challenge. It has been recently advocated that a 3-wk infusion with insulin and glucagon reduces its short-term mortality rate. A multicenter, randomized, single-blind, sequential trial was designed to compare this treatment with placebo. The triangular boundary was defined with alpha = 0.05, beta = 0.10 and estimated survival at 4 wk of 50% with placebo, 75% with treatment. Patients with biopsy-proven severe alcoholic hepatitis (presence of one or more of three criteria: encephalopathy, prothrombin activity less than or equal to 50%, bilirubinemia greater than or equal to 100 mumol/L) were randomized into two groups; one treatment group received an infusion (12 hr/day) of an association of insulin (30 IU) and glucagon (3 mg), and a control group received an infusion of glucose. Treatments were administered during a 3-wk period, and the mortality rate was noted at 4 wk. The decision to discontinue the trial was reached on the basis of results from the first 44 patients. Overall results were assessed in the 72 patients included at the time of this decision (treatment group: n = 37; control group: n = 35). Fifty-three patients had cirrhosis. No significant differences were noted between the two groups at inclusion on the basis of clinical, laboratory and histological criteria. The mortality rate was not significantly different in the two groups; 10 patients (27%) in the treatment group and 5 patients (14%) in the control group died. Causes of death were similar in the two groups and consisted primarily of gastrointestinal hemorrhage, hepatic failure and infectious events.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathogenesis of liver cirrhosis in alcoholic patients: histological evidence for hepatitis C virus responsibility.

Hepatitis C virus (HCV) has been proposed to be a cofactor in the pathogenesis of cirrhosis in patients with chronic alcoholism. The demonstration of a different liver histological pattern in anti-HCV positive patients might provide additional evidence. We studied 164 patients with chronic alcoholism, and histologically proven cirrhosis. For all of them, serum samples were collected at the time of a liver biopsy and stored at -80 degrees C. Testing for anti-HCV antibodies was done using the Ortho Diagnostic Systems Anti-HCV ELISA test. Only reproducible results were considered positive. A semi-quantitative assessment of seven histological parameters was made independently on liver biopsy samples. In the study group, 29 patients (18%) had anti-HCV antibodies. When compared with anti-HCV negative patients, both groups had similar ALT and AST seric activities. Anti-HCV positive patients had a greater score of mononuclear cells infiltrate (0.71 +/- 0.57 vs 0.41 +/- 0.52; p less than 0.05) and a lesser score of alcoholic hepatitis (0.19 +/- 0.57 vs 0.74 +/- 0.74; p less than 0.005). The scores for steatosis, perisinusoidal and perinodular fibrosis, and hepatocellular necrosis were similar in the two groups. In anti-HCV positive patients, with a clearly positive recombinant immunobinding assay (RIBA, Chiron-Ortho Diagnostic Systems), a greater score for hepatic necrosis and a lesser one for fibrosis were demonstrated. Among the seven patients with active cirrhosis, six were anti-HCV positive. Therefore, HCV is likely to play a role in the pathogenesis of liver damage in a few patients with alcoholic cirrhosis, especially, those with active cirrhosis.

[Intra-epithelial cancer of the anal canal. Pathogenic study apropos of 5 cases]. / Le cancer intra-épithélial du canal anal. Etude pathogénique à propos de 5 observations.

Anal carcinomas are rare and their precancerous conditions are not well known. Two populations at risk are described, elderly women and, recently, homosexual males. Early detection of dysplastic lesions or intraepithelial carcinoma in the anal mucosa could lead to preservation on the anal sphincter and consequently to improvement of quality of survival. The present study included 3 women and 2 men. The pathological examination of the surgical specimens in these 5 cases (hemorrhoidal procidence, rectal prolapsus, fibrous polyps, fissure) showed, in all cases, an intraepithelial carcinoma developed in the squamous epithelium of the anal canal. In one of the 5 cases, the anal lesion was concomitant with an intraepithelial carcinoma of the uterine cervix. Complete local resection of the lesions were performed in all cases, associated with complementary radiotherapy in one patient. On follow-up, we observed one recurrence after 8 months in one out of 5 patients. All patients are alive. Histogically, the specimens showed an intraepithelial carcinoma in all 5 cases, with a microinvasive carcinoma in one case. The transitional mucosa of the anal canal showed dysplatic modification in all cases. Immunohistochemical study of the 5 cases did not discern the papilloma virus antigene. In the one case where it was performed, molecular hybridization showed a type 33 papillomavirus. The risk factors of anal carcinomas seems to be changing, in particularly the incidence is increasing in the homosexual patients. In this particular population, as in the uterine cervix, the human papilloma virus is probably one of the main etiological factors. The management of these lesions is not well-defined.(ABSTRACT TRUNCATED AT 250 WORDS)

Sonography and computed tomography of macroscopic tuberculosis of the liver.

Four patients with macronodular tuberculosis of the liver were examined with ultrasonography. The findings included 1 case with multiple hypoechoic areas and 3 cases with a solitary lesion, one hypoechoic mass without calcifications, and two partially calcified masses. Some ultrasound features are suggestive: a mass with irregular calcifications, ascites, spleen enlargement with defects, enlarged nodes, and complete resolution of the lesions in a few months with effective antituberculous therapy. The first case was also examinated with computed tomography.

Treatment of alcoholic hepatitis with colchicine. Results of a randomized double blind trial.

A randomized double-blind trial of colchicine vs placebo was conducted in 67 patients with histologically proven alcoholic hepatitis, 33 of whom had cirrhosis. Patients with hepatic encephalopathy, ascites, protracted prothrombin time, severe thrombocytopenia, hepatocellular carcinoma, evident lack of discipline or refusal to participate in the trial were not included. Thirty-three patients received colchicine (1 mg/day) and 34 received placebo for 6 months. Blood parameters including N-terminal peptide of type III procollagen were assessed in the serum, and a percutaneous liver biopsy was performed at the start of the trial and after 3 and 6 months. Alcoholic hepatitis and fibrosis scores were established for each biopsy specimen. Twenty-eight percent of patients were lost to follow-up at 3 months, and fifty-two percent at 6 months. One patient died of liver failure. Fifty-eight percent of patients were abstaining from alcohol at 3 months and fifty percent at 6 months. No significant effect of treatment was noted. Nevertheless, improvement in alcoholic hepatitis core at 3 months was more important in the colchicine group than in the placebo group. No side-effects were noted except transient diarrhea. Our results suggest that colchicine has no important effect on the course of alcoholic hepatitis. A trial including of at least 260 patients might be necessary for the observed alcoholic hepatitis score difference at 3 months, favoring colchicine, to be statistically significant.

[Treatment of alcoholic hepatitis with silymarin. A double-blind comparative study in 116 patients]. / Traitement de l'hépatite alcoolique par la silymarine. Une étude comparative en double insu chez 116 malades.

A randomized double-blind trial of silymarin versus placebo was carried out in 116 patients with histologically proven alcoholic hepatitis, 58 of them with cirrhosis. Patients were not included in case of hepatic encephalopathy, contraindication to percutaneous liver biopsy, hepatocellular carcinoma, evident lack of discipline or refusal to enter the trial. Fifty-seven patients received silymarin orally 420 mg/day and 59 received placebo during 3 months. Biologic parameters were assessed in the serum, and a percutaneous liver biopsy was obtained at the start of the trial and 3 months later. Histologic scores of alcoholic hepatitis and fibrosis were established on each biopsy specimen by two independent pathologists. The 2 groups were comparable at inclusion; 26 p. 100 of patients were lost to follow-up at 3 months, abstinence was obtained in 46 p. 100 of patients at the end of the trial. These percentages were similar in the two groups. Four patients died of hepatic failure during the trial, 3 in the placebo group. Significant improvement in the score of alcoholic hepatitis and serum amino transferase activity, was noted in both groups during the trial, irrespective of treatment with silymarin or placebo. No side-effects were noted. Our results suggest that silymarin 420 mg/d is not clinically relevant in the treatment of moderate alcoholic hepatitis.

Distinction between hepatocellular carcinoma, cholangiocarcinoma, and metastatic carcinoma based on immunohistochemical staining for carcinoembryonic antigen and for cytokeratin 19 on paraffin sections.

An antiserum to carcinoembryonic antigen (CEA) and a monoclonal antibody to cytokeratin 19 (CK 19) were studied for their suitability as diagnostic reagents for the differential diagnosis of primary and secondary malignant epithelial tumours of the liver, on paraffin sections. With the antiserum to CEA, positive bile canalicular structures were found in 60 per cent of the hepatocellular carcinomas. All the cholangiocarcinomas and 66.6 per cent of the metastatic carcinomas were positive for CEA, without displaying a canalicular staining pattern. All the hepatocellular carcinomas were negative for CK 19. All the cholangiocellular carcinomas and the metastatic carcinomas were positive for CK 19. This staining profile may prove helpful in difficult diagnostic cases.

[Ultrasound-guided cytopuncture and hepatic microbiopsy in focal lesions of the liver. Apropos of 160 cases]. / Apport de la cytoponction et de la microbiopsie hépatique (CMH) guidée par échographie dans les lésions focales du foie. A propos de 160 cas.

A retrospective study was carried out in 160 patients explored by ultrasound guided cytopuncture and hepatic microbiopsy for focal lesions of liver over a 5 1/2 year period. Results are analyzed as a function of clinical and ultrasound findings, the frequency of unexpected histology (20 cases) being emphasized and justifying the wide use of hepatic microbiopsy.

[Hepatic lipid overload in 2 cases of cholestasis associated with parenteral feeding]. / Etude de la surcharge lipidique hépatique au cours de deux cas de cholestase associée à la nutrition parentérale.

The authors report 2 cases of patients with ileal stenosis who developed progressive jaundice while receiving total parenteral nutrition including lipids (Intralipid). In both cases the histologic and histochemical study of the liver demonstrated lipid overload in Kupffer cells and to a lesser extent hepatocytes. Biochemical study established that linoleic acid, a component of Intralipid, associated with a digalactosyl-diglyceride from vegetal origin were the main components of the hepatic overload. The authors hypothesize that two associated mechanisms were responsible for jaundice in their patients: Kupffer cell dysfunction due, at least in part, to lipid overload and intestinal bacterial overgrowth leading to endotoxinemia.