[Prevalence and prognostic value of serum anti-p53 antibodies in hepatocellular carcinoma. A study of 159 patients]. / Prévalence et valeur pronostique des anticorps sériques anti-p53 au cours du carcinome hépatocellulaire. Etude chez 159 malades.

OBJECTIVES: Genetic alterations in the p53 protein may induce serum anti-p53 antibodies. The aim of this study was to assess the prevalence of serum anti-p53 antibodies in a large series of Western patients with hepatocellular carcinoma and the prognostic value of these antibodies on survival. METHODS: Serum anti-p53 antibodies were assayed in 159 patients with hepatocellular carcinoma, at diagnosis, using an immunoenzymatic method. The initial patient characteristics were compared according to anti-p53 status. The prognostic value of these antibodies on survival was determined by univariate and multivariate analysis. RESULTS: One hundred fifty nine patients with hepatocellular carcinoma were included in the study (129 men, mean age: 68 years). The main associated causes of chronic liver disease were alcohol (n=86), virus C (n=34), and virus B (n=18); 151 patients had cirrhosis. Median follow-up was 306 days. Among the 159 patients, 19 (12%) had serum anti-p53 antibodies. Detection of serum anti-p53 antibodies was significantly correlated with the presence of a multinodular or infiltrative tumor (P<0.03). Survival was not influenced by the presence of anti-p53 antibodies. Serum albumin, ALAT, and alfa-fetoprotein levels were independent prognostic variables. CONCLUSION: In our study, anti-p53 antibodies were rarely found in the serum of patients with hepatocellular carcinoma. Although they were correlated with multinodular or infiltrative tumors, they had no prognostic influence on survival. Thus, assaying serum anti-p53 antibodies does not seem to have any clinical value in those patients.

[Minimally invasive surgery for diverticula of the thoracic esophagus. Results in 11 patients]. / Traitement par vidéo-chirurgie des diverticules de l'oeophage thoracique.

OBJECTIVES: Surgical treatment of diverticula of the esophagus is associated with substantial mortality and morbidity. Few data have been published concerning results of minimally invasive surgery. The aim of the study was to retrospectively assess the results of minimally invasive surgery (either thoracoscopy or laparoscopy) in a first series of patients with diverticula of the thoracic esophagus. METHODS: Eleven consecutive patients with symptomatic thoracic diverticula of the esophagus were operated on between December 1992 and March 1999. Five were operated on by right thoracoscopy, 4 by laparoscopy and 2 by thoracoscopy and laparoscopy. The procedure performed varied according to the location and the macroscopic aspect of the diverticulum, as well as of the associated disorders (gastroesophageal reflux, hiatal hernia and/or motor disorders). RESULTS: Postoperative mortality was nil. Three patients developed an esophageal fistula; one with an esophago-bronchial fistula required another operation. Postoperative pain was treated with morphine (median duration 4 days) or IV paracetamol (5 days). Long term results were excellent in 1 patient, good in 6, fair in 2 and poor in 2. These 2 latter patients were operated on another time. One of them was operated on 3 years later for aperistalsis of the esophagus and the other one was operated 4.5 years later for paraesophageal hernia; late results of these operations were fair. CONCLUSION: These results suggest that minimally invasive surgery does not confer significant benefit compared with open surgery in the treatment of diverticula thoracic esophagus.

[Looking for large-cell dysplasia in liver needle biopsies how and why?]. / Comment et pourquoi rechercher la dysplasie hépatocytaire à grandes cellules sur ponction-biopsie hépatique?

Liver large cell dysplasia (LCD) is identifiable only at the microscopic level as foci of large hepatocytes with pleomorphic hyperchromatic nuclei and prominent nucleoli. LCD is mainly observed in cirrhotic livers, on surgical specimens, within macroregenerative nodules or low grade dysplastic nodules but also on liver needle biopsies. For needle biopsies, the prevalence of LCD ranges between 15% and 20%. in case of associated hepatocellular carcinoma, the prevalence is around 40%. LCD is more frequent in hepatitis B virus-induced liver cirrhosis than in cirrhosis related to other causes. Two prospective studies showed that LCD is a predictive factor for the occurrence of hepatocellular carcinoma in cirrhotic patients. Nevertheless LCD is probably not a precancerous lesion; dysplastic hepatocytes are biologically senescent polyploid cells unable to carry out normal cell division. Diagnosis of LCD on liver needle biopsy is indicative for the presence of large and numerous foci of LCD within the whole parenchya and allows consequently to select cirrhosis associated with advanced liver cell secescence, i.e. cirrhosis in which multistep genetic alterations of liver cell carcinogenesis could have happened with the greatest probability. Therefore pathologists have to identify and indicate the presence of LCD in the reports of liver needle biopsies

Latent autoimmune thyroiditis in untreated patients with HCV chronic hepatitis: a case-control study.

In order to establish a relationship between Hepatitis C virus (HCV) chronic infection and autoimmune thyroiditis, 97 untreated patients with biopsy-proven HCV chronic hepatitis and 97 controls were studied. An ultrasound examination of the thyroid and an assay of serum thyroid-stimulating hormone (TSH), thyroid hormones and anti-thyroid antibodies were performed in all cases. The overall prevalence of thyroid abnormalities was higher in patients than in controls (17 vs. 4%, P<0.01) and the prevalence of anti-thyroid antibodies was significantly different between the two groups (P<0. 02). HCV patients with (n=13) compared to HCV patients without anti-thyroid antibodies (n=84) were older, predominantly female, and more frequently had increased serum TSH levels or a hypoechogenic pattern of the thyroid gland, while Knodell's score and prevalence of cirrhosis were similar. Latent autoimmune thyroiditis is more frequent in untreated HCV patients than in controls. This finding raises questions about the mechanism of autoimmunity induced by HCV and provides an explanation for the high rate of overt autoimmune thyroiditis during interferon treatment in these patients.

Clinical and biological relevance of hepatocyte apoptosis in alcoholic hepatitis.

BACKGROUND/AIMS: Although human and experimental studies have shown that apoptosis plays a role in hepatocyte death in alcoholic liver disease, its clinical and biological significance has not been investigated in alcoholic hepatitis (AH). The aim of this study was to quantify hepatocyte apoptosis in AH and to attempt to relate it to the clinical and biological severity of the disease. METHODS: The hepatocyte apoptotic index was determined using a double in situ transferase-mediated dUTP nick end (TUNEL) and CD15 (neutrophils) labelling on 35 liver biopsies from patients with AH lesions of different severities. The specificity of TUNEL labelling for apoptosis was monitored both by morphology and fractin (a caspase actin cleavage site) immunostaining. RESULTS: The hepatocyte apoptotic index ranged from 0.3 to 28% and was related to the severity of alcoholic hepatitis as measured by the Maddrey score (P < 0.05; Mann-Whitney test) while ballooning (which reflects hepatocytes potentially undergoing necrosis) and neutrophil indexes were not. CONCLUSIONS: This suggests that hepatocyte apoptosis could be a therapeutic target to treat or to prevent alcoholic hepatitis in cirrhotic patients. Co-localization of apoptotic hepatocytes with neutrophils and the strong quantitative correlation would suggest an apoptosis dependent transmigration of neutrophils.

Worsening of hepatic dysfunction as a consequence of repeated hydroxyethylstarch infusions.

BACKGROUND/AIMS: Due to its apparent safety and low cost, hydroxyethylstarch (HES) is increasingly used as a volume expander. The aim of this retrospective study was to highlight the risk of hepatic dysfunction after iterative HES infusions. METHODS: Between April 1996 and April 1998, nine patients were referred for worsening of their clinical condition after repeated HES infusions. Six patients had previous chronic liver disease, cirrhosis in four cases. All patients underwent a liver biopsy. RESULTS: All post-HES liver biopsies showed diffuse microvacuolization of Kupffer cells, which was associated with focal hepatocyte vacuolization in seven cases. The vacuoles contained periodic acid Schiff positive material at their margins and were lysosomal by electron microscopy. The clinical symptoms of hepatic disease, although difficult to interpret in cirrhotic patients, worsened after HES infusions. Portal hypertension was noted in three non-cirrhotic patients. Serum alkaline phosphatase and gammaglutamyl transferase activities were increased when compared with previous values. Eight patients died, six of them within 1-4 weeks of hepatic failure or septic shock. In the only living patient, symptoms improved after HES withdrawal. CONCLUSIONS: Repeated administration of HES could favour severe portal hypertension, liver failure and sepsis, particularly in the setting of chronic liver disease. The basis of these adverse effects is the lysosomal storage of HES in Kupffer cells and hepatocytes.

Hepatitis C virus related cirrhosis: time to occurrence of hepatocellular carcinoma and death.

BACKGROUND: In patients with hepatitis C virus (HCV) infection and cirrhosis, long term outcome and the incidence of hepatocellular carcinoma (HCC) are still debated. DESIGN: From January 1987 to January 1997, 416 patients (240 male, median age 57 years) with uncomplicated Child-Pugh A HCV related cirrhosis were followed in two Paris area centres from diagnosis of cirrhosis until death or reference date (1 June 1998). The analysis used a three state disability model generalising the Cox model. RESULTS: Of the 416 patients, 60 developed HCC with a five year rate of 13.4% (95% confidence interval (CI) 9.0-17.8%) and 83 died (including 34 with HCC), with a five year death rate of 15.3% (95% CI 12.6-18.0%). By multivariable analysis, time to HCC relied on age (hazard ratio (HR) 1.05 per year; p=0.0005), male sex (HR 2.13; p=0.01), oesophageal varices (HR 2.36; p= 0.008), decreased platelet count (HR 0.99; p=0. 03), and bilirubin level (HR 1.01; p=0.003), while death after HCC was mainly related to tobacco consumption (HR 1.04; p=0.0006). In contrast, death free of HCC was dependent on age (HR 1.04; p=0.01), oesophageal varices (HR 2.75; p=0.001), low platelet count (HR 0.99; p=0.006), and albumin level (HR 0.90; p=0.0001). CONCLUSION: The incidence of HCC and mortality should be higher in these patients than previously stated, and prognostic factors of HCC and death are closely related age and symptoms of portal hypertension.

Liver iron is predictive of death in alcoholic cirrhosis: a multivariate study of 229 consecutive patients with alcoholic and/or hepatitis C virus cirrhosis: a prospective follow up study.

BACKGROUND/AIMS: A study was undertaken of liver biopsy samples from 229 consecutive patients with alcoholic or hepatitis C virus related cirrhosis who were prospectively followed until January 1996 to evaluate the influence of liver iron content on survival and the occurrence of hepatocellular carcinoma. METHODS: Hepatic iron content was measured with a validated semiquantitative score, and its predictive value for survival and the occurrence of hepatocellular carcinoma was assessed. RESULTS: 130 patients had detectable iron at enrollment. During follow up (57 (28) months), 95 patients died and 39 patients developed hepatocellular carcinoma. No significant relation was found between hepatic iron and the occurrence of hepatocellular carcinoma. Conversely, the presence of iron was predictive of death in alcoholic patients (p = 0.007) by the log rank test but not in patients with hepatitis C virus related (p = 0.71) or mixed (p = 0.98) cirrhosis. The predictive value of hepatic iron content in patients with alcoholic cirrhosis was confirmed by the Cox model using either a binary coding (p = 0.009; relative risk = 2.27; 95% confidence interval 1.2 to 4.19) or the continuous values (p = 0.002). CONCLUSIONS: These results suggest that hepatic iron enhances liver lesions caused by alcohol but not those caused by hepatitis C virus.