[Primary biliary cirrhosis and pregnancy]. / Cirrhose biliaire primitive et grossesse.

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease, asymptomatic during a protracted time, characterized by changes in the small-sized bile ducts near portal spaces. The etiology of PBC is undefined, but immunologic and environmental disturbances may contribute to the disease. Infertility is often associated with PBC and cirrhosis, but pregnancy may well occur in women with PBC and without cirrhosis or in some others with compensated cirrhosis. A pluridisciplinary approach including gastroenterologists and obstetricians is recommended. The patient must be closely monitored throughout her pregnancy with maternal and routine antenatal care. Medical treatment requires ursodeoxycholic acid (UDCA). In non-cirrhotic UDCA-treated women with PBC, pregnancy often follows a normal course with vaginal delivery. In cirrhotic patients, UDCA must be continued during pregnancy, esophageal and gastric varices must be evaluated before pregnancy, and endoscopic ligature is recommended for treating large varices. Additionally, beta-blocker therapy may be associated, especially when variceal rupture occurred previously. Elective cesarean section is recommended in patients with large esophageal or gastric varices because of the potentially increased risk of variceal bleeding during maternal expulsive efforts in case of vaginal delivery.

[Liver and preeclampsia]. / Foie et prééclampsie.

HELLP syndrome complicates PE in 5 to 20 % of cases. The clinical manifestations (i.e. epigastric pain, elevated liver enzymes, thrombocytopenia and hemolysis) are secondary to the fibrin deposit within the peri-portal sinusoids. The clinical presentation of HELLP syndrome can be misleading. It is therefore necessary to suspect this complication whenever a PE patient develops gastro-intestinal pain. The interruption of pregnancy is the only effective treatment against HELLP syndrome. If it can be safely performed passed the 34(th) week of amenorrhea, a protective attitude should be adopted prior to reaching this date. This consists of the administration of corticosteroid therapy for fetal pulmonary maturation, intensive clinical, biological and sonographic monitoring of the mother's parameters. The administration of corticosteroids or performing a plasmapharesis is not recommended for the treatment of established HELLP syndrome because neither improves the maternal or neonatal outcome. The differential diagnosis may also include acute fatty liver of pregnancy. An early liver impairment, polyuria-polydipsia syndrome and a rise in INR support this diagnosis.

[Amniocentesis and viral risk (hepatitis B, C virus and HIV)]. / Amniocentèse et risque viral (hépatites virales B, C et VIH).

Very few studies have properly addressed to the risk of fetal hepatitis B (HBV), hepatitis C (HCV) or human immunodeficiency virus (HIV) infection through amniocentesis. For HBV, this risk is low. However, knowledge of the maternal hepatitis B e antigen status is valuable in the counselling of risks associated with amniocentesis. For HCV, the risk is not well known but cannot be excluded. For HIV, it seems rational to propose a viral test before amniocentesis for patients with contamination's risk and to postpone the sampling in cases with positive results in order to obtain an undetectable HIV-1 RNA viral load. For these reasons, it can be useful to analyse for each virus the benefit of amniocentesis and the risk of mother-to-infant transmission, and to inform the patient.

Conversion from cyclosporine to FK506 in adult liver transplant recipients: a combined North American and European experience.

BACKGROUND: Although cyclosporine (CsA) made clinical liver transplantation possible, side effects and development of rejection have limited its use. In some patients, conversion to tacrolimus has been necessary to abrogate side effects and to preserve allograft function. METHODS: The results of conversion from CsA to tacrolimus were studied retrospectively in 94 liver allograft recipients from a North American and a European transplant center (Duke University Medical Center, Durham, NC, and Hopital Beaujon, Clichy, France). RESULTS: Forty-seven of 94 patients (50%) were converted for steroid-resistant acute rejection. Conversion was successful in 91% of these patients, whereas 9% of patients developed chronic rejection. A further nine patients were converted for chronic allograft rejection with positive results in eight of nine grafts. Mean serum bilirubin in these nine patients was 8.7 mg/dl before conversion and 2.1 mg/dl 6 months after conversion (P=0.02). Nine patients were converted due to inability to wean steroid. Of these, six patients remains steroid free 1 year after conversion. Twenty-three patients (24%) were converted for nephrotoxicity with a reduction in serum creatinine from 167+/-36 mmol/L to 119+/-28 mmol/L 1 year after conversion (P=0.006). Eight of 11 patients converted for neurotoxicity improved after conversion. Conversion to tacrolimus had no effect on seizure frequency or memory loss. CONCLUSIONS: These results suggest that conversion to tacrolimus from CsA is an appropriate paradigm for graft rescue and treatment of a variety of side effects after liver transplant. However, some situations such as memory loss and hypertension may require other strategies.

Ectopic hepatocellular carcinoma arising in the left chest wall: a long-term follow-up.

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.

Haemobilia causing acute pancreatitis after percutaneous liver biopsy: diagnosis by magnetic resonance cholangiopancreatography.

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.

Wilson's disease with severe hepatic insufficiency: beneficial effects of early administration of D-penicillamine.

BACKGROUND: Wilson's disease, heralded by severe hepatic insufficiency, is a rare disorder for which emergency liver transplantation is considered to be the only effective therapy. AIMS: To report the features of Wilson's disease with severe hepatic insufficiency in a series of 17 patients and, during the second period of the study, to assess the efficacy of a policy consisting of early administration of D-penicillamine. PATIENTS: Seventeen consecutive patients with Wilson's disease were studied. During the first period of the study (up to 1979), none of the patients received D-penicillamine. During the second period (after 1979), all patients without encephalopathy at admission received D-penicillamine. RESULTS: The four patients observed during the first period who did not have encephalopathy at admission and did not receive D-penicillamine progressed to encephalopathy and died. Among the 13 consecutive patients observed during the second period, two patients with encephalopathy at admission did not receive D-penicillamine and were transplanted. The 11 remaining patients all received D-penicillamine. Ten of these patients survived without the need for transplantation and returned to compensated liver disease without liver insufficiency. In one patient, liver insufficiency progressed and transplantation had to be performed. CONCLUSIONS: In most patients with Wilson's disease heralded by severe hepatic insufficiency and without encephalopathy at admission, early administration of D-penicillamine was associated with survival without transplantation. These results suggest the importance of early diagnosis of this form of Wilson's disease before the onset of encephalopathy, and favour early administration of D-penicillamine which could avoid the need for transplantation in most cases.

Hepatitis after intravenous buprenorphine misuse in heroin addicts.

BACKGROUND: Sublingual buprenorphine is used as a substitution drug in heroin addicts. Although buprenorphine inhibits mitochondrial function at high concentrations in experimental animals, these effects should not occur after therapeutic sublingual doses, which give very low plasma concentrations. CASE REPORTS: We report four cases of former heroin addicts infected with hepatitis C virus and placed on substitution therapy with buprenorphine. These patients exhibited a marked increase in serum alanine amino transferase (30-, 37-, 13- and 50-times the upper limit of normal, respectively) after injecting buprenorphine intravenously and three of them also became jaundiced. Interruption of buprenorphine injections was associated with prompt recovery, even though two of these patients continued buprenorphine by the sublingual route. A fifth patient carrying the hepatitis C and human immunodeficiency viruses, developed jaundice and asterixis with panlobular liver necrosis and microvesicular steatosis after using sublingual buprenorphine and small doses of paracetamol and aspirin. CONCLUSIONS: Although buprenorphine hepatitis is most uncommon even after intravenous misuse, addicts placed on buprenorphine substitution should be repeatedly warned not to use it intravenously. Higher drug concentrations could trigger hepatitis in a few intravenous users, possibly those whose mitochondrial function is already impaired by viral infections and other factors.

[Acute intracranial hypertension and anicteric cholestasis revealing Whipple's disease without digestive involvement]. / Hypertension intra-crânienne aiguë et cholestase anictérique révélant une maladie de Whipple sans atteinte digestive.

Whipple's disease is a rare infectious disease with potential central nervous system manifestations and a poor prognosis. We report the case of a young woman who presented with acute intracranial hypertension associated with cholestasis which revealed Whipple's disease without digestive involvement. The diagnosis was supported by the presence of PAS-diastase positive hepatic granulomas. A long course of antibiotics resulted in complete remission of the disease without relapse. An acute neurologic syndrome associated with cholestasis should suggest Whipple's disease.

Decrease in serum ALT and increase in serum HCV RNA during pregnancy in women with chronic hepatitis C.

BACKGROUND/AIMS: The natural history of chronic hepatitis C infection during pregnancy has not been clearly established, and thus our aim was to assess serum alanine aminotransferase levels and serum HCV RNA levels during pregnancy. METHODS: Twenty-six pregnant women with chronic hepatitis C were studied. Serum alanine aminotransferase was assessed within the 3 months before, monthly during and within the 3 months after pregnancy. In 12 women, serum HCV RNA levels were quantified by the branched DNA assay. Twenty-six age-matched non-pregnant women with chronic hepatitis C were followed up for 1 year, and used as a comparison group. RESULTS: During pregnancy, serum alanine aminotransferase levels decreased in the second and third trimesters. The third trimester levels were significantly lower than serum alanine aminotransferase levels before pregnancy (p=0.0001). Seventy-seven percent of the pregnant women with increased pre-pregnancy levels had normalization of serum alanine aminotransferase levels. In the second or third trimesters, serum HCV RNA levels increased. The third trimester serum HCV RNA levels were significantly higher than levels before pregnancy (p=0.01). No significant change in serum alanine aminotransferase or HCV RNA levels was observed in the control group. CONCLUSION: In pregnant women with chronic hepatitis C, serum alanine aminotransferase levels decrease, and serum HCV RNA levels increase during the second and third trimesters.

Elevated circulating cardiac troponin I in patients with cirrhosis.

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 microg/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.

Studies of portal hemodynamics and hepatic oxygen consumption during acute liver allograft rejection.

Hemodynamics and oxygen variables, plasma cytokines, and histological features of a liver tissue sample obtained by transvenous biopsy were evaluated during 65 episodes of acute rejection. The hepatic venous pressure gradient was significantly higher in patients with acute rejection than in those without (5.1+/-0.3 vs. 3.1+/-0.2 mmHg, P<0.01). The increase in pressure gradient was related to the severity of rejection lesions. Hepatic blood flow was significantly lower in patients with than in those without acute graft rejection (1.28+/-0.11 vs. 1.75+/-0.13 L/min, P<0.05). Plasma interleukin-6 levels were significantly increased in patients with acute rejection and positively correlated with pressure gradient values. In patients with acute rejection, a significant decrease in hepatic venous oxygen content (-16%) was associated with a significant increase in hepatic oxygen consumption (+24%), whereas hepatic oxygen transport did not change significantly. In treated patients with a favorable response, the pressure gradient decreased significantly by 46%, but it remained elevated in patients who later developed chronic graft rejection. In conclusion, this study confirms that acute graft rejection may induce an increase in portal pressure, which is related to the severity of rejection lesions. It also shows that acute rejection decreases hepatic blood flow and increases hepatic oxygen consumption. In addition, it suggests that the hepatic venous pressure gradient might be useful to determine the outcome of rejection.

Apoptosis after ischemia-reperfusion in human liver allografts.

Little is known about the possible contribution of apoptosis to ischemia-reperfusion injury in human liver transplantation. Therefore, we studied postreperfusion surgical biopsy specimens of 16 human liver allografts using the TUNEL assay for in situ demonstration of apoptotic cells. In all patients, a variable proportion of hepatocytes and sinusoidal endothelial cells presented labeled nuclei. The mean +/- standard deviation percentages of positive hepatocytes were 18.7% +/- 12.2% in the whole section, 30.4% +/- 18.7% in the subcapsular region, 14.5% +/- 13.5% in the centrilobular zones, and 10.3% +/- 9.5% in the periportal zones. The percentage of positive hepatocytes were not correlated with the duration of cold ischemia but was higher in grafts harvested from donors with elevated preoperative aspartate aminotransferase (AST) levels. The percentage of positive hepatocytes was correlated with postoperative serum levels of AST (P = .015) and inversely correlated with postoperative serum levels of factor V (P = .019). Apoptotic biliary epithelial cells were detected in only 3 cases. In conclusion, apoptosis is a frequent event in postreperfusion biopsy specimens of liver allografts and probably contributes to preservation injury of hepatocytes.