Liver and inflammatory bowel disease.

Liver disease is exceptional in patients with inflammatory bowel disease. The most common manifestation, sclerosing cholangitis, characterized by inflammation and fibrosis of the intra- and\or extrahepatic bile ducts, is unusual in patients with inflammatory bowel disease. Conversely, inflammatory bowel disease (mainly chronic ulcerative colitis) is not infrequent in patients with sclerosing cholangitis. Gallstone disease, portal vein thrombosis, and hepatic abscesses are complications directly related to inflammatory bowel disease. Drugs prescribed for the treatment of inflammatory bowel disease can be the cause of rare but potentially serious hepatic manifestations which must be recognized and detected early. Recent studies have demonstrated the role of purine analogues in the development of nodular regenerative hyperplasia. Because of the poor prognosis, patients taking purine analogues should be monitored regularly to search for inaugural signs such as an elevation of serum alkaline phosphatase or low platelet counts (which may not necessarily reach thrombopenia). The risk of methotrexate-induced fibrosis is exceptional in inflammatory bowel disease. Patients should be monitored with non-invasive tests to recognize the development of fibrosis. Finally, because of the risk of viral reactivation, patients should be screened for hepatitis B virus surface antigen before introducing infliximab; chronic carriers should be given preventive treatment with nucleoside or nucleotide analogues.

[How to investigate and diagnose autochthonous hepatitis E?]. / Quand rechercher et comment diagnostiquer une hépatite E autochtone?

In developed countries, HEV infection was still recently considered as rare, and as an imported disease from endemic areas by travellers. Hepatitis E virus is now recognized mainly as an autochthonous disease in these countries. Although the source and the route of contamination remain uncertain, several cases of food-borne (zoonotic transmission) and blood-borne transmission have been recently reported. The mortality rates in industrialized countries seems to be higher than in endemic areas, since the infection occurs more frequently in elderly people with underlying chronic liver disease (mortality rate approaching 70% in this subgroup of patients). By contrast, whereas mortality rate rises by 20% during pregnancy in developing countries, no death in pregnant woman from developed countries secondary to an autochthonous case has been reported so far. Lastly, HEV infection may be a cause of chronic hepatitis in immunocompromised patients (mostly in solid organ-transplant recipients) which can evolve to cirrhosis.

Review article: the utility of reagent strips in the diagnosis of infected ascites in cirrhotic patients.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) can be diagnosed via leucocyte esterase reagent strips, although diagnostic performances vary. AIM: To perform critical review of literature on the use of reagent strips in SBP. METHODS: Nineteen studies were analysed (Medline search), comparing reagent strips in cirrhotic ascites vs. cytobacteriological methods. Diagnostic grades (G) were: GO = 0 leucocytes/mm3; G1 = 15; G2 = 70; G3 = 125; G4 = 500 for Multistix, GO = 0; G1 = 25; G2 = 75; G3 = 500 for Nephur, Combur, UriScan, and GO = 0; G1 = 25; G2 = 75; G3 = 250; G4 = 500 for Aution. RESULTS: Medians per study were: 75 patients (range: 31-1041), 136 ascites (47-2123), 17 SBP (5-117). For Multistix (12 studies), the sensitivities fell within the ranges 64.7-100% (G > or = 1), 45.7-83% (G > or = 2) and 45.3-89% (G > or = 3). For Nephur (n = 2), Combur (n = 6), UriScan (n = 1), sensitivities ranged 80.4-100% (G > or = 1), 63-100% (G > or = 2) and 67.7-97% (G > or = 3). For Aution (n = 3), sensitivities ranged 93-96% (G > or = 2) and 89% (G > or = 3). Nephur, Combur, UriScan displayed higher sensitivities than Multistix. However, in larger studies, sensitivities dramatically fell at 45.3% for Multistix (G > or = 3) if ascites polymorphonuclear count <1000/mm3 and 22.2% for bacterascites or 16.7-25% for asymptomatic patients. CONCLUSION: Use of reagent strips for the diagnosis of SBP cannot be recommended, in view of low sensitivity and a high risk of false negatives, especially in patients with SBP and low polymorphonuclear count.

[Is it possible to stop nucleos(t)ide analogue based therapy in chronic hepatitis B?]. / Peut-on arrêter un traitement par analogue nucléos(t)idique chez un malade atteint d'hépatite chronique B ?

Nucleos(t)ide analogues are very efficient in the treatment of chronic hepatitis B. In the HBe antigen positive patients, the HBe seroconversion rates range from 12 to 22% after one year of treatment. When HBe seroconversion occure, it is possible to stop the treatment with analogue but only in non cirrhotic patients. If the treatment with analogue is continued for at least 6 months after confirmed HBeAg seroconversion, the HBe seroconversion is durable in 70-90% of patients. The follow up should be done during years. Stopping the treatment is more problematic in HBe antigen negative patients. A virological relapse occur in 44 to 80% of cases and a biochemical relapse occur in 30 to 70% of cases. Stopping the treatment with an analogue in this population should be considered only in a prospective study with careful monitoring and with a long term follow up.

[Hepatitis C: which strategy in case of treatment failure ?]. / Hépatite C : quelle stratégie en cas d'échec thérapeutique ?

After a treatment by peginterferon alpha and ribavirin, the percentages of non response and relapse are approximatively 33 and 18 % respectively. These treatment failures may be due either to viral resistance or to an insufficient treatment. The prevention of treatment failure is based on a good knowledge of the predictive factors of failure before and during the treatment. Among the patients who did not respond to interferon alpha and ribavirin, a new treatment with peginterferon alpha-2b and ribavirin makes it possible to obtain 45 % of sustained virological response (SVR) among the relapsers and 17 % of SVR among the non responders. Among the patients who did not respond to peginterferon alpha and ribavirin, a new treatment with peginterferon alpha-2b and ribavirin makes it possible to obtain 36 % of SVR among the relapsers and only 4 % of SVR among the non responders. New therapeutic strategies are necessary for the non responders. Until now no new therapeutic strategy allowed a significant benefit in term of SVR. Protease inhibitors are currently tested in non responders but there are some concerns about the risk of selection of multi-resistant strains.

Coeliac disease in chronic hepatitis C: a French multicentre prospective study.

BACKGROUND: A prevalence of 1.2% of coeliac disease (CD) in patients with chronic hepatitis C was recently reported, suggesting a possible epidemiological link between these two diseases. However, other studies have not found this relationship. AIM: To conduct a French multicentre prospective study to assess the prevalence of CD in hepatitis C virus (HCV)-infected patients. METHODS: Between June 2003 and November 2005, 624 consecutive HCV-positive out-patients were tested for antiendomysial IgA antibodies (AEA), antigliadin IgA and IgG antibodies (AGA). Patients with positive AEA or IgA AGA and positive IgG AGA in a context of a high suspicion of CD were asked to undergo gastroscopy with duodenal biopsies. RESULTS: Isolated IgA AEA, IgA AGA and IgG AGA were 0.16%, 5.7% and 4.4%, respectively. Gastroscopy was required for 39 patients, 31 were performed (eight refusals), but only 25 duodenal biopsies were performed as six patients had cirrhosis. CD was never detected. CONCLUSIONS: The prevalence of CD in HCV-positive patients was 0% (95% confidence interval: 0-0.59%), but there is a low prevalence of CD in the whole French population.

Epidemiology of chronic hepatitis B infection in France: risk factors for significant fibrosis--results of a nationwide survey.

BACKGROUND: Epidemiological data concerning hepatitis B are scarce in France. AIM: To describe epidemiological, clinical, virological and histological features of HBsAg-positive patients followed at non-academic hospitals in France. METHODS: Clinical, biological, virological and histological data of all HBsAg-positive consecutive patients observed from April 1, 2001 to May 31, 2002 in participating centres were recorded prospectively. Multivariate analyses of factors associated with significant fibrosis and cirrhosis were performed. RESULTS: Nearly 1166 HBsAg-positive patients were seen in the 58 centres: 671 males and 495 females from metropolitan France (32%) and from outside metropolitan France (68%); mean age 41 +/- 15 years. Twenty-nine percent of patients were probable HBsAg inactive carriers, while 50% had chronic hepatitis; 43% of these were HBeAg-positive and 57% HBeAg-negative. Liver biopsy had been performed in 558 (51%) patients; 205 (17.6%) patients had cirrhosis. By multivariate analysis, factors associated with significant fibrosis were: age >40 years (P < 0.05), HBeAg-negative status (P < 0.02) and histological activity (P < 0.0001). Factors associated with cirrhosis: age (P < 0.0001), platelet count <150 000/mm(3) (P < 0.0001) and viral co-infection (P < 0.03). CONCLUSION: HBV infection represents a significant workload for hepatogastroenterologists at non-academic hospitals in France.

Retrospective investigation of patients exposed to possible transmission of hepatitis C virus by a capillary blood glucose meter.

A 75-year-old female with no known risk factors for hepatitis C virus (HCV) infection was hospitalized and a diagnosis of HCV seroconversion was established (HCV immunoblot and a positive quantitative viral load). An epidemiological investigation revealed that, during a previous hospitalization resulting in a diagnosis of diabetes, she had shared a Glucotrend capillary blood glucose meter (CBGM; Roche Diagnostics, France) with a known HCV-positive diabetic patient. Poor hygiene practices were observed when using this device. Since the Glucotrend CBGM had been purchased, the suspected source patient had been hospitalized eight times and another 19 diabetic patients with known anti-HCV antibodies also regularly attended the same hospital. Consequently, 35 diabetic patients who had been hospitalized at the same time as the suspected source patient and 1305 patients who had used the Glucotrend CBGM were invited to undergo serum anti-hepatitis B virus, anti-HCV and anti-human immunodeficiency virus testing. Among the 35 diabetic patients, none of the 24 subjects tested were positive. Among the 1305 other patients, 995 were tested and 19 (2%) were anti-HCV positive. Although this prevalence is higher than that reported in the general French population, this excess risk cannot be attributed to use of the CBGM. Furthermore, molecular analysis showed that the two HCV strains isolated did not belong to the same phylogenetic cluster. However, as a result of this incident, measures were taken to minimize the transmission of bloodborne viruses in the hospital concerned. Other French hospitals were informed by a national alert message from the French Agency for the Safety of Health Products.

Chronic liver dysfunction in heart transplant recipients, with special reference to viral B, C, and non-A, non-B, non-C hepatitis. A retrospective study in 80 patients with follow-up of 60 months.

In order to assess the prevalence, causes, and severity of chronic liver dysfunction (LD) in heart transplant patients, 80 transplanted patients followed for 60 months (median; range, 1.5-98 months) were reviewed. Sustained liver dysfunction was found in 50 patients, occurring during the first year after heart transplantation in 42 (84%) of them. Most patients were asymptomatic (80%). Causes for the liver dysfunction included non-A, non-B hepatitis in 16 cases (32%), viral B hepatitis in 13 (26%), delta hepatitis in one (2%), drug-induced hepatitis in six (12%), and cardiac failure in seven (14%). Anti-HCV antibodies were found in 56.2% of patients with non-A, non-B hepatitis and in 22% of patients with HBV hepatitis. It was found neither in patients with drug-induced hepatitis cardiac failure nor in patients with normal liver tests. This study outlines a high prevalence of LD (62.5%) in heart transplant patients, the high frequency of viral-related chronic LD (usually of moderate severity), and high incidence of HCV and HBV hepatitis.

Flumazenil vs. placebo in hepatic encephalopathy in patients with cirrhosis: a meta-analysis.

BACKGROUND: Randomized controlled trials testing flumazenil in hepatic encephalopathy have shown conflicting results. AIM: To compare flumazenil and placebo in hepatic encephalopathy in patients with cirrhosis. METHODS: An overview of randomized controlled trials comparing flumazenil and placebo in hepatic encephalopathy in patients with cirrhosis was performed. For each end-point, heterogeneity and treatment efficacy were assessed by Peto and Der Simonian methods. As most trials were crossover in nature, a sensitivity analysis was performed including the two treatment periods. RESULTS: Six double-blind randomized controlled trials, including 641 patients (326 treated with flumazenil and 315 with placebo), were identified. The treatment duration ranged from 5 min to 3 days. Heterogeneity tests between control groups were not significant. The mean percentages of patients with clinical improvement (five trials) were 27% in treated groups and 3% in placebo groups. This difference was significant by both methods (Peto: odds ratio=6.15; 95% confidence interval, 4.0-9.5; P < 0.001; Der Simonian: mean rate difference, 29%; 95% confidence interval, 17-41; P < 0.001). The mean percentages of patients with electroencephalographic improvement were 19% in treated groups and 2% in placebo groups. This difference was significant only with the Peto method (odds ratio=5.8; 95% confidence interval, 3.4-9.7; P < 0.001). The sensitivity analysis showed similar results. CONCLUSIONS: This meta-analysis shows that flumazenil induces clinical and electroencephalographic improvement of hepatic encephalopathy in patients with cirrhosis.

Portal hypertension due to intrahepatic obstruction in non-Hodgkin's lymphoma.

Portal hypertension is rare in the setting of non-Hodgkin's lymphoma. We report here the case of a 73-year-old man presenting with diffuse high-grade B-cell lymphoma affecting predominantly the liver with large space occupying lesions. Histological examination of liver specimens showed abnormal large lymphoid cells whereas adjacent non-tumoural liver was normal. Portal hypertension was documented by upper gastrointestinal endoscopy that showed grade II oesophageal varices and measurement of portal pressures via transjugular approach showing increased hepatic venous pressure gradient (24 mmHg). We assume that portal hypertension was mainly related to these space occupying lesions.

Flumazenil therapy for hepatic encephalopathy in cirrhotic patients: a double-blind pragmatic randomized, placebo study.

OBJECTIVE: To evaluate the effects of flumazenil on hepatic encephalopathy in patients with cirrhosis. DESIGN: Double-blind randomized study. SETTING: Liver intensive care unit over a 2-year period. PATIENTS: Fourteen patients with cirrhosis (median age 54 years, range 41-73 years), comprising 10 men and four women enrolled during 18 episodes of hepatic encephalopathy. METHODS: Placebo or flumazenil (1 mg at 0.1 mg/min infusion rate) was infused in coded vials. The patients' hepatic encephalopathy was graded clinically and by electroencephalography (EEG). RESULTS: In eight episodes of hepatic encephalopathy the placebo was infused first and no improvement occurred (0%). During 12 episodes of hepatic encephalopathy, flumazenil was administered and the EEG recording improved within 7 min (range 4-47 min; 12 out of 18 cases; 66 versus 0% for flumazenil versus placebo, respectively; P < 0.01); a modest clinical improvement in hepatic encephalopathy was observed within 83 min (range 30-340 min). The amount of flumazenil infused averaged 0.7 mg (range 0.4-1 mg). CONCLUSIONS: The infusion of 0.4-1 mg flumazenil results in a modest but rapid improvement in the EEG grading of hepatic encephalopathy and to a moderate but delayed improvement in the clinical grade of hepatic encephalopathy.

Cyamamezine-induced acute hepatitis after unique massive intake: a case report.

Hepatotoxicity of cyamamezine, a phenothiazine structurally related to chlorpromazine, has been rarely documented. We report here a case of acute symptomatic hepatitis following a unique massive intake of cyamamezine in a suicide attempt and discuss the mechanisms of such injury.

Marked increase in serum CA 19-9 level in patients with alcoholic cirrhosis: report of four cases.

We report four cases of marked increase in serum carbohydrate antigen (CA 19-9) levels in patients with severe alcoholic cirrhosis without any evidence of gastric or pancreatic carcinoma. Brief reports were obtained from two hepatology units of four cirrhotic patients, three of them with alcoholic hepatitis. In the four cases, improvement of liver function and disappearance of jaundice were associated with a decrease to normal serum CA 19-9 levels. These observations show that a marked increase in serum CA 19-9 level in patients with severe hepatic dysfunction is not diagnostic of pancreatic or gastric carcinoma.

Blindness following gastrointestinal haemorrhage.

Loss of vision is a rare but well known complication of distant and recurrent haemorrhage. It shares a poor prognosis, with only 10-14% of cases likely to make a complete recovery. Visual symptoms, due to ischaemic anterior optic neuropathy, vary from blurred vision to complete loss of vision in one or both eyes. The pathogenesis of such ischaemia remains unclear. Gastrointestinal bleeding seems to be the leading cause of loss of vision secondary to haemorrhage. However, complete and permanent blindness following gastrointestinal bleeding has rarely been reported. We report the case of a 51 -year-old woman who complained of complete blindness following blood loss, secondary to peptic ulcer, and discuss the pathogenesis of such a complication.

Cyclosporin A-mediated cholestasis in patients with chronic hepatitis after heart transplantation.

Viral chronic hepatitis often occurs in heart transplant recipients receiving cyclosporin. This essential immunosuppressive drug may induce cholestasis. We investigated the effect of treatment with cyclosporin on serum conjugated bile acids in patients with chronic hepatitis developing after heart transplantation. Fifty-nine patients were studied: 17 with chronic hepatitis, 15 heart transplant patients with normal alanine aminotransferase activity, and 27 heart transplant patients with chronic hepatitis, the last two groups receiving cyclosporin. Hepatic biochemical tests and total bile acid concentration were determined on fasting blood samples. The individual glyco- and tauroconjugated bile acids were quantified by high-performance liquid chromatography and direct spectrometry. In patients taking cyclosporin the bilirubin concentration and the alkaline phosphatase activity were increased only when hepatitis was present, in association with a slight increase in cholic acid level (5.13 microM vs. 0.68 microM; P < 0.01). Conjugated lithocholate concentration was dramatically higher when hepatitis and immunosuppression with cyclosporin were associated (1.17 microM vs. 0.03 and 0.04 microM; P < 0.01). Chenodeoxycholate was the main circulating bile acid only in the heart transplant patients treated with cyclosporin but without hepatitis. These results suggest that the mechanisms which explain the cyclosporin-associated modifications of the bile acid pool are different according to the presence or absence of hepatitis. The occurrence of hepatitis in patients on cyclosporin led to an increase in serum lithocholate and primary bile acid concentrations. Further studies are required to assess the effect of ursodeoxycholic acid for this cholestasis.

Hepatitis C virus infection risk factors in patients admitted in hospital emergency departments in Picardy. Value of oriented screening based on recommendations of the 'Direction Générale de la Santé'.

OBJECTIVE AND DESIGN: Oriented hepatitis C virus (HCV) screening on the basis of transfusion, previous or current parenteral drug addiction, invasive procedures, and in family members of patients with hepatitis C, was recommended in France by the 'Direction Générale de la Santé' (DGS). The aim of this study was to estimate the frequency of these risk factors in patients admitted in hospital emergency departments in Picardy. METHODS: Between 1 June and 31 July 1996, physicians of the emergency units of seven hospitals in Picardy were asked to question admitted patients about risk factors mentioned in the DGS recommendations, and to suggest a screening test when at least one of these risk factors was present. RESULTS: Among 1648 patients, 68.7% had at least one of these risk factors. Screening was accepted by 723 patients, 58.7% of those with at least one risk factor, and more than 70% of those with history of transfusion and/or drug addiction. It was immediately performed in 451, and 2.4% had anti-HCV antibodies. The prevalence of anti-HCV antibodies was 1.5% in patients without history of transfusion or drug addiction and 7.9% in those with at least one of these two risk factors. CONCLUSION: Oriented screening based on transfusion or drug addiction history seems to have better efficiency than the screening policy recommended by the DGS. Poor reliability of answers about medical history was observed probably because of stress related to emergency circumstances. A screening test proposed to patients with these major risk factors by their usual physician would be probably more efficient.

Spontaneous dialytic ultrafiltration with intraperitoneal reinfusion of the concentrate versus large paracentesis in cirrhotic patients with intractable ascites: a randomized study.

Dialytic ultrafiltration of ascites through a hemofilter associated with peritoneal reinfusion (DUF) of the concentrate has been proposed for the treatment of refractory ascites. In five cirrhotic patients, 18 ascites evacuation procedures were randomized either to DUF (n = 8) or to large paracenteses (LP) (n = 10). The effects of these two methods on hemodynamic and renal function were assessed. After DUF, the protein concentration in ascites increased transiently from 28 +/- 7 g/l to 64.8 +/- 8 g/l (p less than 0.04); urinary output increased from day 1 to day 4 (1000 +/- 100) VS 1430 +/- 140 ml/24h; p less than 0.02). After LP, ascitic protein concentration and urinary output were unchanged. No side effects were observed with the two methods. The mean amount of albumin infused was 20 +/- 15 g after DUF and 15 +/- 5 after LP (ns).

Spontaneous dialytic ultrafiltration with intraperitoneal reinfusion of the concentrate in 15 cirrhotic patients with intractable ascites.

The clinical efficacy and tolerance of dialytic ultrafiltration of ascites through a hemofilter (DUF) with peritoneal reinfusion of the concentrate was evaluated in 15 cirrhotic patients with intractable ascites. All together, 51 DUF procedures were carried out. An average of 8.6 was ultrafiltered during 12 h with no significant change in blood pressure, hemoglobin, coagulation parameters or plasma creatinine. A significant increase in ascitic protein concentration was observed immediately after the procedure and a slight but significant increase in 24 h urinary output. A controlled evaluation of DUF compared to large paracenteses seems to be justified by these preliminary results.