Serial quantitative determination of hepatitis C virus RNA levels after liver transplantation. A useful test for diagnosis of hepatitis C virus reinfection.

After liver transplantation for hepatitis C virus (HCV)-related cirrhosis, recurrent viral infection is almost constant, resulting in acute graft dysfunction in 30-75% of cases. Acute graft dysfunction in the post-transplant period may also be the result of various causes (such as rejection, CMV infection, sepsis, or technical problems). Therefore, the role of HCV reinfection is often difficult to document. The aim of this study was to assess the diagnostic value of serial HCV RNA quantitation in this setting. Fourteen patients transplanted with follow-up greater than 6 months were studied. HCV RNA was quantitated before and serially after transplantation, using branched DNA technology. In cases of acute graft dysfunction, usual investigations and additional HCV RNA quantitation were conducted. There were 15 episodes of acute graft dysfunction in 12 patients. Six episodes had a hepatitic biochemical pattern, and 5 of them were associated with a concomitant HCV RNA peak. Nine episodes had a mixed, hepatitic, and cholestatic biochemical pattern, and 5 of them were associated with a concomitant peak of HCV RNA. Overall, 10 of 15 (66%) episodes of acute graft dysfunction were associated with HCV RNA peak, which strongly suggests that HCV was the etiologic factor. In 9 of these 10 episodes, no other cause of dysfunction was found, and one had associated CMV disease. In 5 cases, no peak of HCV RNA was observed and the causes of dysfunction were CMV (in 2 cases) and rejection, granulomatosis, and unknown (in 1 case each). Serial quantitations of HCV RNA levels after liver transplantation for cirrhosis C provide a useful tool in the diagnosis of HCV reinfection of the graft.

Increased incidence of oropharyngeal squamous cell carcinomas after liver transplantation for alcoholic cirrhosis.

BACKGROUND: THE aim of this study was to describe the features of posttransplantation tumors observed in a series of liver transplant recipients with special reference to patients receiving a transplant for alcoholic cirrhosis. METHODS: Among 171 consecutive liver transplant recipients, 90 patients who had received a first liver allograft for cirrhosis were studied. After liver transplantation, detection of de novo malignancies was prospectively undertaken and the characteristics of the patients in whom tumors occurred were compared with those in whom tumors did not develop. RESULTS: With a follow-up of 45.2+/-21.2 months, 11 tumors were observed in 90 patients (overall incidence of 12.2%). The incidence of tumors was higher in patients receiving a transplant for alcoholic cirrhosis than in patients receiving a transplant for nonalcoholic cirrhosis (26.7% vs. 5.0%, P<0.01). Squamous cell carcinoma (SCC) of the oropharynx or esophagus and posttransplant lymphoproliferative disorders were mainly observed. SCC (uvula in two cases, tongue in one case, esophagus in one case, pharynx in one case) occurred exclusively in patients transplanted for alcoholic cirrhosis (16.7% vs. 0%, P=0.001). The incidence of posttransplant lymphoproliferative disorders was similar in alcoholics and nonalcoholics (6.7% vs. 5%, NS). Survival was not influenced by the occurrence of SCC. CONCLUSION: The incidence of oropharyngeal SCC could be high in patients receiving a transplant for alcoholic cirrhosis. This could be due to an additional effect of posttransplantation immunosuppression in patients exposed to alcohol and tobacco before transplant. Careful posttransplantation screening of oropharyngeal SCC is warranted after liver transplantation for alcoholic cirrhosis.

Inhibitor against coagulation factor V after liver transplantation.

A new case of anti-factor V inhibitor is described in a 46-year-old man, who received a liver transplantation for hepatocellular carcinoma, without exposure to bovine thrombin or fibrin glue during the operative course. The inhibition occurred on the 14th postoperative day, while the patient was being treated with oxacillin, azathioprine, and a new immunosuppressive drug, FK506. The inhibition was of short duration (3 days), and no bleeding complication occurred despite a very low plasmatic level of factor V activity and antigen (<5%). Plasma samples drawn after cessation of FK506 disclosed a dose-dependent inhibitory activity when alcoholic solutions of FK506 were exogeneously added; this suggests a possible role of the FK506 drug in the occurrence of this anti-factor V inhibitor.

Reverse seroconversion of hepatitis B after allogeneic bone marrow transplantation: a retrospective study of 37 patients with pretransplant anti-HBs and anti-HBc.

BACKGROUND: Reverse seroconversion to hepatitis B virus (HBV), i.e., HBV reactivation in patients with pretransplant antibodies to hepatitis B surface antigen (anti-HBs) and to hepatitis B core antigen (anti-HBc), is rarely re-ported after allogeneic bone marrow transplantation. METHODS: To determine this risk, we studied clinical outcome and serological changes in 37 patients with pretransplant anti-HBs and anti-HBc. RESULTS: In 33 cases, no change in HBV markers was observed in the posttransplant period. In four cases, anti-HBs and anti-HBc were lost, and hepatitis B surface antigen, hepatitis B e antigen, and HBV DNA emerged together with acute hepatitis, after cessation of immunosuppression. The actuarial risk of reactivation in the 37 patients was 20.5% (median follow-up 20 months). No reactivation occurred in patients with anti-HBs-positive donors. CONCLUSION: Although few cases of postallogeneic bone marrow transplantation reverse seroconversion to HBV have been reported, this study demonstrates that the actuarial risk is relatively high and suggests that donor vaccination might be proposed prophylactically or that HBs-specific immunoglobulin infusions might be warranted.

[Sclerosing cholangitis after chemotherapy by continuous hepatic intra-arterial infusion of fluorodeoxyuridine]. / Cholangite sclérosante après chimiothérapie par perfusion intra-artérielle hépatique continue de fluorodésoxyuridine (FUDR).

A case of sclerosing cholangitis after a two-month treatment by hepatic artery infusion of FUDR is reported. The patient presented with jaundice and a marked increase in serum alkaline phosphatase activity which persisted after withdrawal of FUDR infusion. Endoscopic retrograde cholangiogram revealed a stricture of the middle part of the common bile duct, which was treated by endoprosthesis insertion. From this report, as well as those previously published, it is concluded that sclerosing cholangitis may complicate continuous hepatic artery infusion with FUDR. This lesion could be secondary to an FUDR-induced arteritis in the branches of hepatic artery which supply bile ducts.

[Association of hepatocellular adenoma and focal nodular hyperplasia of the liver in a woman on oral contraceptives]. / Association d'un adénome hépatocellulaire et d'une hyperplasie nodulaire focale du foie chez une femme sous contraceptifs oraux.

PIP: The case of a 37-year old woman with no previous pathology who developed liver adenoma and focal nodular hyperplasia after taking various oral contraceptive (OC) combined preparations over 15 years is described. The woman was hospitalized after discovery of a mass in the right hypochondrium. Other clinical findings were normal. During laparotomy 2 hepatic tumors were found: a mass 10 cm in diameter in the right lobe found at histological examination to be a focal nodular hyperplasia, and a mass 1 cm in diameter discovered fortuitously in the left lobe and which demonstrated the histological characteristics of a hepatic adenoma. The role of OCs in the development of hepatic adenomas is supported by epidemiological evidence, but the relationship between pills and focal nodular hyperplasia is much less clear. Although they occur in men and children, their development and the appearance of occasionally serious hemorrhagic complications appear to be encouraged by OCs. The complications are probably due to the vascular modifications observed in the tumor during OC use. The association of the 2 types of tumor in 1 patient has apparently been reported only once previously. Various hypotheses may be advanced to explain the occurrence.^ieng

[Ultrasonographic and x-ray computed tomographic aspects of Mirizzi's syndrome]. / Aspects échotomographiques et tomodensitométriques du syndrome de Mirizzi.

The Mirizzi syndrome is due to common hepatic duct obstruction secondary to the impaction of a large gallstone in the neck of the gallbladder or the cystic duct. The sonographic and computed tomography features in 3 cases of Mirizzi syndrome are described and compared with percutaneous transhepatic cholangiography or endoscopic retrograde cholangiography findings. The Mirizzi syndrome was diagnosed preoperatively on sonography in 2 out of 3 cases and on plain computed tomography scans in all 3 cases. However pre or intraoperative visualization of the biliary tract is mandatory in suspected Mirizzi syndrome to detect the presence or absence of cholecystobiliary fistula, in order to adapt the operative strategy.

[Value of a powerful initial immunosuppression after liver transplantation. Prospective study of 60 cases]. / Intérêt d'une forte immunosuppression initiale après transplantation hépatique. Etude prospective de 60 cas.

With usual immunosuppression, the incidence of acute rejection after liver transplantation is higher than 60% in most series. The aim of this prospective study was to assess the value of a powerful initial immunosuppression on acute rejection, mortality and morbidity. REGIMEN. Group 1: patients with normal postoperative renal function (serum creatinaemia < 150 mumol/L) received cyclosporine from day 1 to day 15 by continuous i.v. infusion to reach a whole blood level of 400 to 500 ng/mL; after day 15, cyclosporine was reduced. Group 2: in cases of postoperative renal failure (serum creatinine > or = 150 mumol/L), anti-thymocyte globulins were used for 10 days; cyclosporine was introduced after recovery of renal failure at usual doses. In addition, all patients received steroids and azathioprine according to usual regimens. RESULTS. From January 1989 to June 1992, 60 cases were studied in 59 patients: 45 (75%) entered group 1 and 15 (25%) entered group 2. In group 1, there were 11 acute rejection episodes (24%) and one postoperative death at three months (2.3%). In group 2, two early deaths (within 5 days) were excluded from the study of rejection. Among the 13 remaining cases, there were three episodes of acute rejection (23%) and one hospital death at three months. Overall, there were 14 episodes of acute rejection (24%), 12 of which were steroid-responsive (86%), no chronic rejection, a usual rate of infections (57%), one retransplantation (1.7%) and a hospital mortality of 6.8% (4 of 59 cases). One year survival was 78%, with 5 of 7 late deaths due to recurrent cancer. CONCLUSIONS. Our results suggest that, after liver transplantation, a) high initial cyclosporine dose in patients with normal postoperative renal function is associated with reduced incidence and severity of acute rejection without increased mortality and morbidity, b) antithymocyte globulins are an efficient alternative to cyclosporine in patients with postoperative acute renal failure and saves OKT3 for the treatment of steroid-resistant rejection.

[Chronic active hepatitis and cirrhosis induced by wild germander. 3 cases]. / Hépatite chronique active et cirrhose induites par la germandrée petit-chêne. Trois cas.

We report 3 cases of chronic liver injury that were observed after prolonged treatment with wild germander, a herbal medicine recently prohibited by French Ministry of Health, following several reports suggesting its hepatotoxicity. Chronic active hepatitis was found in 2 cases, and active cirrhosis in 1 case. The onset of hepatitis occurred after 6 to 7 months of treatment. Serum anti-nuclear and anti-smooth muscle antibodies were present in 2 patients. In 2 cases, wild-germander involvement was recognized several months after appearance of liver injury. Following treatment discontinuation, outcome was favorable in the 3 patients. These observations suggest that diagnosis of acute or chronic liver injury of unknown origin should always include the search for herbal medicine treatment.

[Hepatic cholesterol ester storage disease. Two new cases diagnosed in adults]. / Surcharge hépatique en esters de cholestérol. Deux nouveaux cas diagnostiqués chez l'adulte.

Cholesterol ester storage disease is a rare disorder characterized by an hereditary deficiency of lysosomal acid lipase that induces an accumulation of cholesterol ester in most tissues of the body, particularly in liver. The diagnosis is usually made during childhood. The aim of this article is to report two new cases diagnosed in adult age. Two patients, 25 and 20 years old, respectively, presented with hepatomegaly, a slight to moderate increase in serum transaminases, and esophageal varices. In both cases, diagnosis was based on the presence of hypercholesterolemia, fatty infiltration of the liver with lipid droplets in hepatic parenchymal cells, foamy macrophages, hepatic storage of cholesterol esters, and low activity of lysosomal acid lipase. Histological abnormalities were associated with portal and periportal fibrosis in one patient and a micronodular cirrhosis in the other; these lesions were probably the cause of portal hypertension. Fibrosis of varied degrees has been previously reported in cholesterol ester storage disease. Its mechanism remains unclear.

[Chronic active hepatitis associated with anti-native DNA antibodies: incidence of drug etiology]. / Hépatites chroniques actives associées à des anticorps anti-ADN natif: fréquence de l'étiologie médicamenteuse.

Of 75 patients with HBsAg negative chronic active hepatitis (CAH), 28 had antinuclear antibodies in their serum. We have tested these patients' sera for serum antibodies against double stranded (native) DNA (anti-ds-DNA), by immunofluorescence with Crithidia luciliae as substrate. They were found in 14 patients (50 p. 100). Thirteen of the patients with anti-ds-DNA and 11 of those without were female; the mean ages were 64 +/- 16 and 56 +/- 19 years, respectively. The clinical and biological signs seemed to be more severe in patients with anti-ds-DNA than in those without. Liver histological activity and frequency of cirrhosis (about 50 p. 100) were similar in patients with or without anti-ds-DNA. Ten of the 14 patients with anti-ds-DNA had been given hepatotoxic drugs whereas only 2 patients lacking these antibodies had taken a hepatotoxic drug (p less than 0.01). In subjects with anti-ds-DNA, clometacin was the most common hepatotoxic drug, taken alone in 5 patients or together with other hepatotoxic drugs in 3 subjects. Only 4 of the patients with anti-ds-DNA displayed symptoms of systemic lupus erythematosus and two of these subjects took a hepatotoxic drug. In our experience, serum anti-ds-DNA were frequently found in patients with CAH and antinuclear antibodies; in this group CAH was often associated with hepatotoxic drugs, especially clometacin. Thus, the presence of anti-ds-DNA in sera of patients with HBsAg negative CAH may be an indication of drug-induced liver damage.

[What vasoactive agent should be chosen in rupture of esophageal varices in cirrhosis?]. / Quelle substance vaso-active choisir dans la rupture de varices oesophagiennes de la cirrhose?

Variceal esophageal bleeding is a frequent and severe complication of portal hypertension. Balloon compression was the standard therapy for many years. Currently, endoscopic hemostasis with sclerosis or ligation appears to be more effective but requires an experienced operator who is not always present at emergency situations. Parenteral administration of vasoactive agents is one therapeutic option offering new perspectives for the future. Data in the literature suggest that terlipressin or somatostatin would be the preferential choice because of the adverse effects of vasopressin. Data is insufficient concerning sandostatin. Currently, the trend is to administer vasoactive agents as soon as possible, prior to hospitalization and, perhaps, in association with endoscopic hemostasis. Treatment should be maintained for several days although the cost/benefit ratio remains a question of debate.

[Double liver-kidney transplantation in the presence of a positive T cross-match]. / Double transplantation hépatique et rénale en présence d'un cross-match T positif.

Kidney transplantation, when performed across a positive T lymphocyte cross-match, is always followed by the occurrence of a hyperacute rejection. On the other hand, successful hepatic allografts have been reported under these same conditions. Furthermore, clinically and experimentally hepatic allograft has been reported to induce tolerance of other organs from the same donor. Thus, combined liver-kidney transplantation constitutes an ideal application of these immunological events. We report here the case of a sequential liver-kidney transplantation in which liver transplantation performed prior to kidney transplantation with an organ from the same donor induced kidney tolerance despite an initial positive T lymphocyte cross-match.

[Liver transplantation associated with combined adjuvant treatment in hepatocellular carcinoma. Feasibility and preliminary results]. / Transplantation hépatique associée à un traitement adjuvant combiné dans le carcinome hépatocellulaire. Faisabilité et résultats préliminaires.

Combined adjuvant therapy was prospectively assessed in 7 patients receiving orthotopic liver transplantation for hepatocellular carcinoma complicating cirrhosis. The protocol included hepatic arterial chemotherapy while waiting for transplant, immediate preoperative liver irradiation, and early postoperative chemotherapy. There were no postoperative deaths, and morbidity included mainly hematologic toxicity of chemotherapy. Two patients died of tumor recurrence 6 and 14 months after transplant. The remaining 5 patients are alive and free of disease with a follow-up of 7 to 26 months. These results show the feasibility of aggressive adjuvant therapy in patients transplanted for hepatocellular carcinoma and suggest a possible effect of such a protocol on the prevention of tumor recurrence.