Is debrisoquine hydroxylation modified during acute viral hepatitis?

Drug metabolism in the liver may be decreased during liver diseases. However, the extent of impairment of specific isozymes of cytochrome P450 is largely unknown. We have studied the debrisoquine hydroxylation capacity of 17 patients with acute viral hepatitis and 106 unrelated healthy subjects. Debrisoquine metabolic ratio was increased in extensive metabolizers (EM) with acute viral hepatitis as compared with healthy EMs (median metabolic ratio: 1.20 vs 0.84, P < 0.05). However, there was no difference in phenotype prevalence between patients and controls. Our results suggest that acute viral hepatitis only has a marginal effect on the activity of CYP2D6 and that substrates of this enzyme may be given in normal therapeutic doses to this category of patients.

A twenty-year history of alveolar echinococcosis: analysis of a series of 117 patients from eastern France.

OBJECTIVES: Alveolar echinococcosis of the liver is a very rare and severe parasitic disease due to the growth of the larva of Echinococcus multilocularis. The aim of this paper was to describe a 20-year study of the epidemiological, clinical and therapeutic aspects of alveolar echinococcosis in eastern France. DESIGN: One hundred and seventeen consecutive cases, diagnosed and followed in our liver unit, were studied from 1972 to 1993. METHODS: Data from 85 patients followed since 1983 (period B) were compared to data from a first series of 32 patients (period A) collected from 1972 to 1982; 1983 was chosen as the cut-off year because of the numerous changes that occurred in the diagnosis, follow-up and treatment of the disease at this time, in particular the introduction of parasitostatic benzimidazoles. RESULTS: The results of patient follow-up were evaluated in December 1997. The cumulative prevalence was 2.5 per 100,000 persons in period A whereas it reached 6.6 per 100,000 in period B. The annual incidence in period B was 7.3 on average, compared with 2.7 in period A. Twenty-nine per cent of patients from period B were asymptomatic at the time of diagnosis compared with 10% in period A. This change was correlated with less advanced liver lesions, and was related to the extensive use of abdominal ultrasound, and from 1987, serological screening. Curative resections were performed in 24% of the cases in period B versus only 3% in period A. From 1986, liver transplantations were performed in eight patients from period A and 13 patients from period B. In period B, palliative surgery was frequently replaced by radiological non-operative procedures to treat abscesses and jaundice. From 1982, 73 patients received benzimidazoles for a period of time ranging from 4 to 138 months. Stabilization of the lesions was observed in two-thirds of the patients. Episodes of jaundice or digestive haemorrhage due to portal hypertension were 31.5 and 11 times less frequent respectively in patients from period B compared with period A. Actuarial survival at 5 years improved from 67% in period A to 88% in period B in patients of similar age. CONCLUSIONS: Radical changes in the diagnosis and the management of alveolar echinococcosis have occurred during the last decade. Together they have contributed to an improvement in the status of the patients affected by this very severe parasitic disease.

[Indications and results of liver transplantation for hepatocellular carcinoma. Retrospective study in 17 patients]. / Indications et résultats de la transplantation hépatique au cours du carcinome hépatocellulaire. Etude rétrospective de 17 malades.

Orthotopic liver transplantation has been considered as one of the therapeutic tools in certain patients with hepatocellular carcinoma. In our liver Unit in Besançon, 17 patients with hepatocellular carcinoma were treated by orthotopic liver transplantation between March 1986 and December 1991. This series included 14 men and 3 women. The mean age was 51 years (range: 36-62). In 11 cases, hepatocellular carcinoma was multifocal and larger than 5 cm, in 6 cases, the tumor was encapsulated, and was well differentiated in 11 cases. Lymph node invasion was observed in 2 cases and the portal vein was invaded in 5 cases. Before orthotopic liver transplantation, alpha foetoprotein was increased in 10 cases. Kaplan-Meier actuarial survival was 76%, 53%, 40%, at one, two and three years, respectively, and remained unchanged at four years. There were 9 recurrences of hepatocellular carcinoma. There were 8 deaths, 4 due to a tumor recurrence. A tumor larger than 5 cm was the only parameter statistically associated with recurrence in this study.

[Acute cytolytic hepatitis caused by coumarin. 2 cases]. / Hépatite aiguë cytolytique à la coumarine. Deux cas.

Coumarin is a drug which is extensively used to treat lymphedema. We report two cases of acute hepatitis probably due to coumarin. Two women, 40 year and 45 year-old, were treated with 90 mg/d of coumarin for 5 months. Clinical features included jaundice, pruritus, and diarrhea. A marked increase in serum aminotransferases was observed (ALT: 30 and 100 times the upper limit of normal, respectively). Coumarin withdrawal was rapidly followed by a favorable outcome in both cases. Rechallenge in one case induced a relapse of symptoms and liver test abnormalities. Coumarin can induce acute cytolytic hepatitis.

[Prevalence of and changes in hepatitis C virus antibodies in 64 patients with liver transplant]. / Prévalence et évolution des anticorps dirigés contre le virus de l'hépatite C chez soixante-quatre transplantés hépatiques.

The aim of this retrospective study was to assess the prevalence of hepatitis C virus antibodies and their follow-up in a series of 64 orthotopic liver transplantation patients. Indications for transplantation were cirrhosis in 28 cases, primary biliary cirrhosis in 6 cases, liver cancer in 11 cases, fulminant hepatitis in 2 cases, and alveolar echinococcosis in 17 cases. The prevalence of serum antibodies to hepatitis C virus was assessed by an ELISA test (Ortho-Diagnostic-Systems). Sera were tested before liver transplantation and every two months after. Twenty-nine patients seronegative before transplantation remained negative. Four patients seropositive before liver transplantation remained seropositive. Twenty-eight patients seropositive before transplantation, became seronegative after, and 3 patients seronegative before transplantation became seropositive after. The prevalence of seroconversion was 9.3 percent. The prevalence of seropositive patients after transplantation was 11 percent. The high number of seropositive patients before transplantation (50 percent) could be explained by false positive results. Seropositivity before transplantation appeared to be related to hypergammaglobulinemia (p less than 0.001). This hypothesis was confirmed a posteriori by a concomitant disappearance of both seropositivity and hypergammaglobulinemia after transplantation in 62 percent of patients.

[Complications in 52 liver transplantations excluding graft rejection]. / Complications de la transplantation hépatique à l'exclusion du rejet. A propos de 52 transplantations.

We analyzed the postoperative complications excluding graft rejection in 52 consecutive orthotopic liver transplantations performed from March 1986 to November 1988 in 48 patients. Thirteen patients died: one intraoperatively, seven during the first 2 months, and five between 5 and 28 months. Complications were predominant during the first 3 months; infection was the most common complication. The main cause was viral agents. Cytomegalovirus was responsible for infection in 62 percent of cases, but was symptomatic in only 37 percent of patients and always had a favorable outcome. Six cases of disseminated candidiasis were observed with fatal outcome in 3 cases. Ten patients had septicemia due to Gram positive germs with a favorable course in all cases. Two patients required retransplantation on the 2nd postoperative day because of primary graft failure. Three patients had hepatic infarction which was fatal in one case. Technical complications were represented by intra-abdominal bleeding in 3 cases, perihepatic hematoma in 10 cases and stenosis of the biliary anastomosis in 8 cases; in one patient, partial portal vein thrombosis occurred; no hepatic arterial thrombosis occurred during the first postoperative days but this complication was diagnosed later in 3 instances by arteriography. Five out of 7 patients transplanted for malignant liver disease experienced recurrence which cause death in 4 cases. In 3 out of the 5 patients transplanted for postviral B cirrhosis, chronic active hepatitis occurred 6 months after transplantation and one of these patients had to be retransplanted at 13 months for recurrence of cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

[Granuloma annulare of the photoexposed areas in two liver transplant recipients]. / Granulome annulaire des zones photo-exposées chez deux malades ayant eu une greffe hépatique.

BACKGROUND: We report two cases of generalized granuloma annulare occurring in photoexposed areas in two liver transplant recipients. CASE REPORTS: Case 1 was a 65-year-old man who had undergone liver transplantation in 1992. He was given immunosuppressive and antihypertensive therapy. Within 18 months of transplantation, he developed a confluent rash with maculae on sun-exposed areas (neck opening, nape, arms) and sparing the undershirt area. Clinical examination was normal. Skin biopsy revealed a palissade infiltrate located in the middle and upper derma, suggestive of granuloma annulare, with elastophagocytosis patterns (orcein stain and ultrastructure study). Photoexposure granuloma was diagnosed. Case 2 was a 59-year-old man who had undergone liver tranplantation in 1994. He was given immunosuppressive and antihypertensive therapy and developed within 4 months a dark rash on the neck opening and nape, sparing photoprotected areas. Histopathology revealed granuloma annulare. Elastophagocytosis was disclosed by orcein stain and the ultrastructure study. DISCUSSION: This clinical presentation of granuloma annulare in two liver transplant recipients is unusual. We discuss the clinical and histopathological patterns observed in our two cases and the relationships between granuloma annulare and immunosuppression.

[Indications and contraindications for liver transplantation]. / Indikácie a kontraindikácie transplantácie pecene.

Liver transplantation (LT) is a therapeutic method in many, otherwise infaust diseases of the liver. During the recent decade the experimental therapeutic procedure has become a routine therapeutical method. The stage of clinical experiment was ultimated by the Washington Conference held on the consensus in LT indications (1983). Large centries (USA, England, Germany) yield 80-100 liver transplantations per year. The recent years have recorded a change in some principal opinions on LT. It is possible to state that liver transplantation is being abstained from cases with more extensive primary neoplamatic affliction of the liver. Conservative therapy in primary biliary cirrhosis of the liver by means of ursodeoxycholic acid has shifted the LT indication into the later stages of the disease. The opinions on the meaning of LT in alcoholic cirrhosis remain still unsettled. LT remains unambiquously indicated in life-endangering fulminant and subfulminant liver failures. Among the viral diseases, attention is paid to liver cirrhosis caused by infection by the hepatitis C virus. Cirrhosis due to hepatitis B has a better prognosis, owing to the complex antiviral therapy. Liver transplantation represents, beside the main indications, the therapy of first selection, e.g. also in Wilson's disease, alpha-1-antitrypsin deficiency, alveolar echinococcosis etc. (Tab. 1, Fig. 2, Ref. 54.)

Nursing, occupational therapy, and physical therapy preparation in rheumatology in the United States and Canada.

Directors of undergraduate programs in nursing, physical therapy, and occupational therapy in the United States and Canada were surveyed to determine the amount and perceived adequacy of the current degree of classroom and clinical exposure to the rheumatic diseases. One hundred ninety-one (73%) of the 262 mailed questionnaires were returned. Results indicate that regardless of the actual degree of rheumatologic classroom exposure, directors in all three disciplines view current amounts as adequate. A larger proportion views levels of clinical exposure as inadequate. In general, the Canadian programs had a greater emphasis on rheumatology than their United States counterparts.

[Bilateral purulent pleurisy and spontaneous rupture of the esophagus (Boerhaave's syndrome). Apropos of a case]. / Pleurésie purulente bilatérale et rupture spontanée de l'oesophage (syndrome de Boerhaave). A propos d'un cas.

The authors report a case of bilateral purulent pleurisy consecutive to spontaneous rupture of the oesophagus (Boerhaave's syndrome). In such cases Mackler's triad, when complete, confirms the diagnosis. Standard radiography of the chest remains essential as it shows, at an early stage, the presence of mediastinal emphysema.

Evaluation of an education program on the management of rheumatic diseases for physical therapists.

An educational program on the management of rheumatic diseases was developed for physical therapists. It was community based and designed to measure changes in patient care and physician behavior in the utilization of physical therapy services. Substantial changes in the utilization of physical therapy services were documented in 3 intervention communities, but not in control communities. In patients undergoing total hip arthroplasty, there was a 1.8 day reduction in the hospitalization, significant increases in the use of preoperative physical therapy and a shift in the use of walking aids. These data suggest that physical therapists can play an important role in physician and patient education, and this may result in lower costs and improved outcomes.

Orthotopic liver transplantation for incurable alveolar echinococcosis of the liver: report of 17 cases.

Between 1986 and 1989, orthotopic liver transplantations were performed in our unit for 17 patients with incurable alveolar echinococcosis. Ten patients had hilar involvement (group I), and seven patients had posterior localization (five of them had chronic Budd-Chiari syndrome) (group II). The delay between diagnosis and the orthotopic liver transplantation was more than 48 mo in group Ia (six patients), less than 24 mo in group Ib (four patients) and less than 48 mo in group II. Previous operations were more common in group Ia than in group Ib and II. Five patients have died-four in group I and one in group II. The actuarial survival rate at 15 mo was 75%. Early reoperations were frequent (69%), mainly caused by rebleeding. Bacterial and fungal infections occurred only in group Ia (four cases) and group II (three cases). In eight patients (palliative group), residual foci of infected nonhepatic tissue occurred after surgery. The titer of specific antibodies decreased during the first 3 mo in all the patients but one. In patients with radical liver transplantation, the complete disappearance of specific antibodies occurred within 2 yr in four cases. In the remaining five patients, specific antibodies remained detectable, but no evidence of recurrence has been obtained up to now. In the palliative group, a peak of specific IgM occurred at 3 mo; an increase of specific IgG was observed later. The growth of residual parasitic foci was relatively slow, and all these patients remained asymptomatic with a mean follow-up of 19 mo. We conclude that orthotopic liver transplantation is feasible in incurable alveolar echinococcosis and could be proposed without delay to patients with parasitic Budd-Chiari syndrome or complicated secondary biliary cirrhosis. In the other cases, the best time to perform an orthotopic liver transplantation is more difficult to determine. Nevertheless, in the perspective of an orthotopic liver transplantation, the management of these patients has to change, and repetitive laparotomies for palliative surgical procedures have to be replaced by interventional radiology.

Stability of debrisoquine (CYP2D6) phenotype in liver transplant patients.

Liver metabolism may be modified after liver transplantation according to the phenotype of the donor and may be influenced by posttransplantation complications. The CYP2D6 phenotype was assessed in 13 patients (group I) before and after liver transplantation using debrisoquine. CYP2D6 activity was also assessed in vitro on microsomes from the liver of the recipients and the donors, using dextromethorphan. Twelve patients were extensive metabolizers both before and after transplantation. One apparently poor metabolizer was transplanted with the liver of another poor metabolizer. The intrinsic clearance of dextromethorphan (CL(int)) measured on recipient liver microsomes was significantly lower than that on donor liver microsomes (p < 0.05). In extensive metabolizers, the debrisoquine metabolic ratio was correlated with CL(int) before (r = 0.78, p < 0.05) and after (r = 0.89, p < 0.0005) transplantation. Debrisoquine phenotype was measured repeatedly in nine additional patients (group II) up to 3 years after liver transplantation. Their phenotype was stable during the follow-up observation, although the variations observed may be clinically relevant. Therefore, no change in CYP2D6 phenotype (extensive/poor metabolizer) was observed because of the liver transplantation, and the debrisoquine log metabolic ratio was largely unaffected by the liver complications observed during the posttransplantation follow-up observation.

Anti-inflammatory drugs and variceal bleeding: a case-control study.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) can have severe gastrointestinal effects and cause peptic ulcers to bleed. Acute bleeding from oesophageal varices is a major complication of cirrhosis of the liver. AIMS: To investigate the role, using a case-control study, of NSAIDs in first bleeding episodes associated with oesophageal or cardial varices in cirrhotic patients. PATIENTS/METHODS: A structured interview was conducted of 125 cirrhotic patients with bleeding mainly related to oesophageal varices and 75 cirrhotic controls with oesophageal varices who had never bled. RESULTS: Cirrhotic patients who were admitted for bleeding related to portal hypertension were more likely to have used NSAIDs during the week before the index day (31 of 125 (25%)) than the cirrhotic controls (eight of 75 (11%); odds ratio = 2.8, p = 0.016). Use of aspirin alone or combined with other NSAIDs was also more prevalent in the cases (21 of 125 (17%)) than in the controls (three of 75 (4%); odds ratio = 4.9, p = 0.007). Logistic regression analysis showed that NSAID use (p = 0.022, odds ratio = 2. 9, 95% confidence interval = 1.8 to 4.7) and variceal size (p<0.001, odds ratio = 4.0, 95% confidence interval = 1.4 to 11.5) were the only variables independently associated with the risk of bleeding. CONCLUSIONS: Aspirin, used alone or combined with other NSAIDs, was associated with a first variceal bleeding episode in patients with cirrhosis. Given the life threatening nature of this complication, the possible benefit of this treatment should be weighed against the risk shown here. No firm conclusions could be drawn on non-aspirin NSAIDs used alone.