[Non-A, non-B hepatitis: clinical aspects and course].
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Biomedical subjects
Publications and source records attributed to J F Cadranel.
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Hypoxaemia is observed in almost 30 per cent of patients with cirrhosis of the liver, irrespective of the cause of cirrhosis. Two main physiopathological mechanisms can be described: hypoxaemia may be secondary to intrapulmonary vascular abnormalities or due to a regional disequilibrium of the ventilation/perfusion ratio. In the first case, the severity of hypoxaemia often requires complex and invasive investigations, while in the second case, by far the most frequent, hypoxaemia is moderate, usually asymptomatic and in practice only needs a few investigations.
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A patient with long lasting non-parathyroid hormone mediated hypercalcaemia occurring within the context of hepatitis B virus chronic hepatitis is reported. Hepatocellular carcinoma and bone malignancy were carefully excluded. The biological pattern associated hypercalcaemia with normal phosphataemia, low nephrogenic cAMP level and high level of tubular reabsorption of phosphate. The usual causes of hypercalcaemia were ruled out. Hypercalcaemia may represent a rare biological feature of some advanced liver disease. The underlying mechanisms remain to be elucidated.
The effect of therapeutic doses of cyclosporine A (CyA) on bile flow and bile salt output was studied in the rat. Thirty male Sprague-Dawley rats (250 to 380 g) were injected intraperitoneally with CyA (n = 15) or vehicle (n = 15) at the dose of 10 mg.kg-1 for 3 weeks. The effect of CyA on basal and taurocholate-induced bile flow, on basal bile salt output and bile salt output under taurocholate infusion, and the effect of chronic administration of CyA on bile salt-independent bile flow was evaluated. Administration of CyA was associated with a decrease in basal bile flow (5.6 +/- 0.7 vs 6.7 +/- 0.7 microliters.min-1.100 g-1; p less than 0.001) and bile flow under taurocholate infusion (8.0 +/- 0.8 vs 10.9 +/- 1.1 microliters.min-1.100 g-1; p less than 0.001). Basal bile salt output (133.9 +/- 48.2 vs 173.8 +/- 53.6 nmol.min-1.100 g-1; p less than 0.003) and bile salt output under the infusion of taurocholate were significantly lower in cyclosporine-treated rats than in controls (443.3 +/- 48.2 vs 617.2 +/- 172.7 nmol.min-1.100 g-1; p less than 0.001). There was no significant difference in bile salt-independent bile flow between the 2 groups. There was no modification of seric alanine aminotransferase activity or hepatic histology. This study confirms that chronic administration of CyA at therapeutic doses can induce cholestasis. Cholestasis is related mainly to a decrease in bile salt secretion and bile salt-dependent flow.
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The long-term follow-up of 80 heart transplant patients (70 men, 10 women) from January 1982 to July 1985 who had received cyclosporine (CsA) showed a high incidence of mild to severe liver dysfunction. Fifty patients (62.5%) had long-lasting postoperative biological disturbances (alanine amino transferase greater than 2N and/or alkaline phosphatase greater than 1.5N for 3 months or more). Most patients were asymptomatic; eight were icteric, and one had arthralgia. The most common biological feature consisted of isolated elevation of ALAT (27 cases). Assessment of causes led to a definite etiology in 42 patients: 7 cardiac failure, 13 HBsAg-positive liver disease (26%) (chronic persistent hepatitis 8, chronic active hepatitis 2, subacute necrosis 2). Fourteen patients (28%) sustained non-A, non-B (NANB) hepatitis (chronic persistent hepatitis 5, chronic active hepatitis 1, cirrhosis 1), and 7 (14%) sustained a drug-related hepatitis. Liver biopsy and complete virus screening was contributive to the diagnosis in nearly all patients. Additionally, prolonged impairment of liver function tests occurred in 62% of heart transplant recipients, mostly during the first 6 postoperative months. Hepatitis B virus (HBV) and NANB hepatitis accounted for 26% and 28% of the cases of liver dysfunction, respectively; drug-induced hepatitis may have been involved in 14% of the cases. Complete hepatitis virus screening should be performed before heart transplant and in any case of abnormal liver function posttransplantation. HBV vaccination prior to heart transplant is recommended in HBsAg- and HBcAb-negative candidates for heart replacement. Long-term follow-up of these patients is mandatory to assess the severity of these liver dysfunctions.
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Hepatocellular pseudotumor (HCP) occurs in cirrhotic liver and can resemble hepatocellular carcinoma. Liver ultrasonography shows a space-occupying lesion. The aim of this study was to describe the clinical, radiological and histologic features of HCP based on seven patients (3 women, 4 men), mean age 48 years (24 to 62), with histologically proven cirrhosis (alcoholic, 4 cases; autoimmune, 1 case; postnecrotic, 1 case, idiopathic, 1 case). Serum alphafetoprotein was below 16 ng/ml in 5 patients and remained over 120 ng/ml in the remaining 2. Desgammacarboxyprothrombin, performed in 3 cases, was below the upper limit of normal range. Real time ultrasonography of the liver showed a homogeneous parenchyma in 1 case and median size (20-48 mm) space-occupying nodular lesions in 6 cases. Sonography patterns of hepatocellular pseudotumor were as follows: anechoic lesions in 5 cases and mixed pattern (sonodense and hypoechogenic) in 1 case. Angiographic findings exhibited different patterns: hypervascular or hypovascular nodules, multinodular uptake after lipiodol bolus injection. Computed tomography showed iso- or hypodense space-occupying lesions. Lipiodol injection, performed in 3 cases, showed nodular lipiodol uptake. Fine needle biopsy always showed normal hepatocytes. At laparotomy, performed in 3 cases, an hyperplastic nodule was found in 1 case only. All patients were alive at 12 to 36 months. These findings are consistent with the fact that hepatocellular pseudotumor is a true entity. Differential diagnosis is difficult. Iodine oil nodular fixation on CT scan may be non specific for hepatocellular pseudotumor. Histologic data is mandatory before beginning a non surgical therapeutic regimen for suspected hepatocellular carcinoma.
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Esophageal perforations are rare and usually occur after instrumentation. We relate here a case unsuspected spontaneous esophageal perforation. Computed chest tomography firstly showed signs of mediastinal abscess. Secondary barium meal confirmed the diagnosis.
Delta coinfection or superinfection in a patient with chronic hepatitis B is characterized by a very transient delta antigenemia and an early seroconversion of IgM to IgG anti-delta. The persistent expression of delta antigen in the liver can be associated with acute, severe, or chronic hepatitis. In our two patients, delta antigenemia persisted respectively 10 weeks and 14 months with aggravation of liver histopathologic lesions without seroconversion. Such a serologic profile during delta infection does not seem to have been reported previously. These two cases concerned two patients with an important immunosuppression, one by a major immunosuppressive therapy and HIV superinfection, the other by an acquired immunodeficiency syndrome. The cytotoxic effect of delta virus in such circumstances is discussed.
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