[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.

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.

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.

[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.

Interaction of ribavirin with azathioprine metabolism potentially induces myelosuppression.

BACKGROUND: The interaction of ribavirin, an inosine monophosphate dehydrogenase inhibitor, with azathioprine metabolism, potentially leading to myelotoxicity, remains unexplored. AIM: To underline the interaction of ribavirin, an inosine monophosphate dehydrogenase inhibitor, with azathioprine metabolism, potentially leading to myelotoxicity. METHODS: The medical records of eight patients who developed severe pancytopenia following concomitant use of azathioprine and ribavirin were retrospectively reviewed. RESULTS: Bone marrow suppression reached nadir after a mean interval of 4.6 +/- 1.6 weeks following HCV therapy initiation in seven patients. At the time of pancytopenia, the mean platelet count was 69.75 +/- 82.8 x 10(-3)/mm(3), mean haemoglobin level 7.75 +/- 1.3 g/dL and mean neutrophil count 0.45 +/- 0.26 x 10(-3)/mm(3). All patients had normal thiopurine methyltransferase genotype. In two patients, a prospective monitoring of azathioprine metabolites was available. Myelotoxicity was accompanied by elevated total methylated metabolite levels (16,500 and 15,000 pmol/8 x 10(8) erythrocytes) with a concomitant decrease in 6-tioguanine nucleotide levels; 1 month after azathioprine, pegylated interferon alfa and ribavirin were discontinued and full blood count returned to normal in both patients. No haematological toxicity occurred after the reintroduction of peginterferon plus ribarivin or azathioprine alone in eight patients. CONCLUSION: Collectively, the benefit/risk ratio favours avoidance of inosine monophosphate dehydrogenase inhibitors in purine analogue-treated patients with normal thiopurine methyltransferase activity, a situation frequently encountered in clinical practice.

[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.

A national survey of acute hepatitis E in France.

BACKGROUND: Few data are available on the incidence, risk factors and contamination pathways involved in acute indigenous hepatitis E in developed countries. AIMS: To draw up an overall picture of hepatitis E cases, to confirm whether or not the majority of the cases were indigenous and to attempt to identify the risk factors and contamination pathways involved in hepatitis E. METHODS: This study was performed in the framework of a national network (ANGH) including 96 participating centres. The 19 centres with at least one case of acute HEV reported a total number of 53 cases. RESULTS: A decreasing South-to-North geographic gradient was observed. A nonspecific clinical profile was observed in many cases. Acute hepatitis E was of indigenous origin in 90% of the patients. The most relevant and/or frequent possible risk factors among the 47 indigenous metropolitan cases were water consumption from a personal water supply, uncooked shellfish consumption and the recent acquisition of a pet pig. CONCLUSIONS: This national survey confirmed that acute indigenous hepatitis E is an emerging disease in developed countries such as France, and suggests that various risk factors are responsible for acute indigenous hepatitis E contamination in non-endemic countries.

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.

Myelofibrosis in a patient with pachydermoperiostosis.

Pachydermoperiostosis (idiopathic or primary hypertrophic osteoarthropathy) is a rare condition of unknown origin involving the skin and the skeleton, with an autosomal dominant transmission. We report a case of anaemia in a patient with pachydermoperiostosis indicating myelofibrosis, and review the literature and the pathogenetic mechanisms.

Idiopathic non-cirrhotic intrahepatic portal hypertension in the West: a re-evaluation in 28 patients.

BACKGROUND: Non-cirrhotic portal hypertension of unknown cause is a poorly understood condition attributed to obstructive portal venopathy. AIM: To reassess the manifestations, course, and causes, with special attention to thrombosis. METHODS: Analysis of a cohort of 28 patients. RESULTS: Gastrointestinal bleeding occurred in 11 patients. Liver failure developed at the time of concurrent disease in eight patients, including all four patients who died. Portal vein thrombosis developed in 13 patients. A prothrombotic disorder was found in 12 of 23 fully investigated patients. Hepatoportal sclerosis was observed in 11 patients (with associated perisinusoidal fibrosis and/or nodular regenerative hyperplasia in six); periportal fibrosis, perisinusoidal fibrosis, nodular regenerative hyperplasia, or a combination thereof were observed in other patients. A morphometric evaluation showed an increased number of portal vessels in patients with hepatoportal sclerosis. There was no relation between pathological results and haemodynamic findings or prothrombotic disorders. CONCLUSIONS: Outcome was related to associated conditions. Overlap in pathological, haemodynamic, and causal features suggests a single entity, with prothrombotic disorders as major causal factors, and injury to sinusoids as well as to portal venules as the primary mechanism. Activated coagulation could mediate vascular injury in the absence of thrombosis. Anticoagulation should be considered.