Neurologic Disorders in Immunocompetent Patients with Autochthonous Acute Hepatitis E.

Neurologic disorders, mainly Guillain-Barré syndrome and Parsonage­Turner syndrome (PTS), have been described in patients with hepatitis E virus (HEV) infection in industrialized and developing countries. We report a wider range of neurologic disorders in nonimmunocompromised patients with acute HEV infection. Data from 15 French immunocompetent patients with acute HEV infection and neurologic disorders were retrospectively recorded from January 2006 through June 2013. The disorders could be divided into 4 main entities: mononeuritis multiplex, PTS, meningoradiculitis, and acute demyelinating neuropathy. HEV infection was treated with ribavirin in 3 patients (for PTS or mononeuritis multiplex). One patient was treated with corticosteroids (for mononeuropathy multiplex), and 5 others received intravenous immunoglobulin (for PTS, meningoradiculitis, Guillain-Barré syndrome, or Miller Fisher syndrome). We conclude that pleiotropic neurologic disorders are seen in HEV-infected immunocompetent patients. Patients with acute neurologic manifestations and aminotransferase abnormalities should be screened for HEV infection.

Changes of non-invasive markers and FibroScan values during HCV treatment.

The recent advent of non-invasive methods for assessment of fibrosis allows serial assessments in all patients with hepatitis C. The aim of this prospective study was to evaluate changes in liver fibrosis, as measured with non-invasive methods, in a large cohort of HCV-infected patients with and without treatment. From May 2003 through March 2006, all previously untreated HCV-infected patients were enrolled in this study. Liver fibrosis was staged with FibroScan and Fibrotest at inclusion, then every year in untreated patients, and at the end of treatment and 6 months later in treated patients. The study population consisted of 416 patients, of whom 112 started treatment after enrolment. In the treatment group, FibroScan and Fibrotest values were significantly higher before and after treatment than in untreated patients at baseline and after 1 year. However, there was no significant difference between treated and untreated patients at the end of follow-up. FibroScan and Fibrotest values fell in all treated patients, whatever their virological response. In multivariate analysis, treatment was the only factor independently associated with a fall in the FibroScan value. In conclusion, whatever the virological response, treatment for HCV infection is associated with an improvement of FibroScan and Fibrotest values. Further studies are needed to compare these non-invasive methods with liver biopsy. These non-invasive methods, and especially FibroScan, should be useful for assessing treatment efficacy in clinical trials of new drugs.

Liver fibrosis staging with contrast-enhanced ultrasonography: prospective multicenter study compared with METAVIR scoring.

We prospectively assessed contrast-enhanced sonography for evaluating the degree of liver fibrosis as diagnosed via biopsy in 99 patients. The transit time of microbubbles between the portal and hepatic veins was calculated from the difference between the arrival time of the microbubbles in each vein. Liver biopsy was obtained for each patient within 6 months of the contrast-enhanced sonography. Histological fibrosis was categorized into two classes: (1) no or moderate fibrosis (F0, F1, and F2 according to the METAVIR staging) or (2) severe fibrosis (F3 and F4). At a cutoff of 13 s for the transit time, the diagnosis of severe fibrosis was made with a specificity of 78.57%, a sensitivity of 78.95%, a positive predictive value of 78.33%, a negative predictive value of 83.33%, and a performance accuracy of 78.79%. Therefore, contrast-enhanced ultrasound can help with differentiation between moderate and severe fibrosis.

Structural enhancement and video endoscopy: results of a large prospective comparative study.

INTRODUCTION: The structural-enhancement (SE) function electronically improves the video-endoscopic signal of Olympus processors (EXERA CV-160 or greater), enabling an increase in relief that may help in the detection of flat or ulcerated and raised lesions, especially those of small size. We assessed the diagnostic impact of this technique in the screening of lesions during basic video colonoscopy. METHODS: Maximum-level SE was programmed into processors on alternate weeks, and endoscopy dates were planned by an assistant unaware of the SE schedule, thus ensuring randomization. The endoscopists-senior practitioners with 3-29 years of digestive endoscopy practice-were informed of the experiment >3 weeks before it began and were not told about it again either before or during the study. This was to ensure that endoscopy examinations were performed without over-awareness of the technical conditions. GIF-100 to -160 Olympus endoscopes were used. RESULTS: During the study, 606 patients underwent upper digestive video-endoscopy, 305 with and 301 without the use of the SE function. Of 645 patients who underwent video colonoscopy, 593 were included in the study and 52 were excluded due to poor cleansing (8%); of those included, 330 were analyzed with and 263 without the SE function. We observed no differences in the detection of lesions (small or large) by either upper digestive endoscopy or video colonoscopy. CONCLUSION: This is the first study comparing video-endoscopy diagnosis with or without SE during upper digestive endoscopy and colonoscopy. The SE function available on Olympus video-endoscopy processors had no impact on the detection of lesions, not even on those of very small size.

Is physical activity possible and beneficial for patients with hepatitis C receiving pegylated interferon and ribavirin therapy?

The great majority of patients with chronic viral hepatitis C are treated with pegylated interferon-ribavirin therapy. The aim of this study was to demonstrate that these patients were able to have some form of physical exercise, and that this activity can lead to an improvement in their quality-of-life. Twelve volunteer patients with hepatitis C, who were either sedentary or had become sedentary and who had been treated by combination therapy for the past few weeks, were recruited at hepatology clinics in the Midi-Pyrénées region of France early in 2006. All patients attended a sports medicine consultation for an initial evaluation: maximal aerobic power and maximal oxygen consumption tests, maximum heart rate (MHR), search for contraindications for participation in the proposed program of physical exercise. The patients were given a heart rate monitor so they could measure their heart rate during physical exercise and check that they exercised under safe conditions and remained within the so-called "endurance" zone. The patients came to a sports facility daily for 5 days for the exercise program. The activities were divided into four sessions each day: an individual physical exercise selected by the patient, team physical exercise, recreational physical exercise, lectures on the different types of hepatitis and their treatment, on nutrition and on sports medicine assessments. Data on hepatitis, results of the cardiorespiratory examination and personal history and record of past physical activity were collected for each patient. Quality-of-life (SF36) was assessed at enrollment in the study and one month after the training sessions. At the initial sports medicine consultation, all patients reached their MHR and were found capable of participating in the proposed physical exercise program. One enrolled patient was excluded from the analysis because of the presence of sinusitis on arrival. Seven men and four women, mean age of 46 years completed the full course of the study protocol. All participated in the three types of proposed physical activity with no problem. The score of the general perception item of the SF36 questionnaire increased from 63 on day 0 to 71 at one month (p=0.07). In conclusion, patients with hepatitis C receiving pegylated interferon plus ribavirin may safely participate in a program of suitably supervised physical exercise. Taking part in physical exercise leads to clear changes in the way patients perceive their bodies and its capacities. Participating in sports activities could improve self-confidence and lead to far-reaching changes in the way patients perceive their disease and the constraints of treatment.

[Alcohol, steatohepatitis, insulin resistance and hepatitis C]. / Alcool, stéatohépatite métabolique, insulinorésistance et hépatite C.

Patients with chronic hepatitis C have frequently other morbidities, either because they are frequent in the general population (metabolic syndrome) and/or because the route of contamination (chronic alcohol consumption succeeding to drug abuse). These co-morbidities have a harmfull impact on fibrosis progression during the natural history of HCV infection and reduce the efficacy of antiviral treatments. Thus, it is crucial to diagnose early and treat these different diseases which may be combined. They are the metabolic syndrome and/or chronic alcohol consumption resulting in insuline resistance, infection by the human immune deficiency virus or by the hepatitis B virus as well as chronic tobacco use or excessive consumption of cannabis. An optimal is based on a multidisciplinary approach to reduce fibrosis progression and improve the efficiency of antiviral therapies. However, the hepatologist has to come back to a global care, which is mandatory at the individual level as well as for the public health.

[The liver and methotrexate]. / Foie et méthotrexate.

Methotrexate is proposed for the treatment of inflammatory disorders such as rheumatoid arthritis, psoriasis and Crohn's disease. The liver toxicity of methotrexate has been investigated and prolonged treatment can induce liver fibrosis. Moreover, alcohol consumption, diabetes and obesity are associated with liver fibrosis in patients treated with this drug. Therefore, liver fibrosis associated with methotrexate could be due to associated factors instead of methotrexate itself. Recommendations to monitor and diagnose methotrexate induced liver damage vary depending on the disease. Frequent evaluation of liver fibrosis with liver biopsy is recommended during therapy, especially in patients treated for psoriasis. Noninvasive methods, such as the FibroScan, could be useful for the assessment of liver fibrosis associated with methotrexate and hence, need further evaluation.

Diagnosis of liver fibrosis using FibroScan and other noninvasive methods in patients with hemochromatosis: a prospective study.

BACKGROUND: The role of hepatic iron overload in the development of hepatic fibrosis in patients with hemochromatosis is well-established. Transient elastography (FibroScan) is a new noninvasive, rapid, reproducible bedside method, allowing assessment of liver fibrosis by measuring liver rigidity. OBJECTIVES: The aim of this prospective study was to evaluate liver fibrosis with FibroScan and other noninvasive biochemical methods in patients with hemochromatosis (C282Y homozygosity) compared with control patients. PATIENTS AND METHODS: From January 2004 through October 2006, all consecutive patients with hemochromatosis were evaluated for liver fibrosis using noninvasive methods (FibroScan and biochemical markers). These patients were compared with patients who had chronic cytolysis and no fibrosis on liver biopsy. RESULTS: One hundred and three consecutive patients (57 cases and 46 controls) were fully investigated. Median FibroScan values were similar in both groups, 5.20 kPa versus 4.9 kPa, respectively. No differences were observed between cases and controls for all biochemical markers. A strong correlation was observed between FibroScan and many biochemical markers, although ferritin levels did not correlate with FibroScan values. The prevalence of patients with FibroScan values greater than 7.1 kPa (cut-off level for significant fibrosis) was 22.8% in patients with hemochromatosis and 0% in the controls (P<0.0001). CONCLUSION: FibroScan and biochemical markers could be reliable noninvasive methods for detecting liver fibrosis in patients with hemochromatosis. Such patients have high FibroScan values more often than do control patients. Further longitudinal and prospective studies are necessary to confirm these preliminary data.

A French prospective observational study of the treatment of chronic hepatitis C in drug abusers.

The objective of this prospective, multicenter, observational study was to evaluate healthcare for hepatitis C virus (HCV)-infected drug abusers in France and to determine predictors of successful therapeutic intervention. A total of 170 drug users were recruited from 40 French centers. Three centers recruited 66 participants (38.8%), and one to eight patients each were enrolled from 37 other centers (n=104). A sustained viral response (SVR) was seen in 65 (38.2%) patients. SVR rates were significantly higher in compliant than in non-compliant patients (43.5% versus 23.9%; P=0.019), in patients from high- rather than low-recruiting centers (54.5% versus 27.9%; P<0.001) and in patients receiving Buprenorphine rather than methadone (48.1% versus 21.8%; P=0.001). In patients, who completed both the treatment and follow-up (n=94), SVR rate was 57.4%. Buprenorphine substitution therapy and genotypes 2 or 3 HCV infection were associated with significantly higher rates of SVR (P<0.01, for both comparisons). In conclusion, successful care of hepatitis requires an active treatment policy of every center toward drug addicts. Additional studies are needed to explore the difference in SVR with methadone versus Buprenorphine therapy.

Impact on adherence and sustained virological response of psychiatric side effects during peginterferon and ribavirin therapy for chronic hepatitis C.

BACKGROUND: The psychiatric side effects of interferon, often responsible for dose reduction or treatment discontinuation, represent a major limitation in the treatment of chronic hepatitis C (CHC). AIM: To prospectively assess the impact on adherence and sustained virological response (SVR) of the occurrence of psychiatric side effects during peginterferon and ribavirin therapy for CHC. METHODS: Ninety-eight consecutive treatment-naïve CHC patients receiving a standard course of peginterferon plus ribavirin were systematically screened for psychiatric side effects, using DSM-IV, at baseline and both during and after treatment. RESULTS: Psychiatric side effects occurred in 38 patients (39%), mostly within the first 12 weeks (87%), and always consisted of mood disorders. Overall, 68% of patients achieved an SVR (71% of patients with mood disorders and 68% of those without; P = N.S.). Peginterferon and ribavirin dose reductions did not differ between patients with mood disorders and those without (46% vs. 37%, respectively; P = N.S. and 13% vs. 22%, respectively; P = N.S.). Anti-viral therapy had to be discontinued in four patients (nonresponse: two, hyperthyroidism: one, psychiatric event: one). CONCLUSION: Early detection and appropriate management of psychiatric side effects during peginterferon and ribavirin therapy for CHC allow optimizing adherence and virological efficacy.

Diagnosis of liver fibrosis by transient elastography (FibroScan) and non-invasive methods in Crohn's disease patients treated with methotrexate.

BACKGROUND: Methotrexate is an effective treatment in Crohn's disease, which may induce liver fibrosis with high cumulative doses. Transient elastography (FibroScan, Echosens, Paris, France) is a new non-invasive rapid, allowing assessment of liver fibrosis by measurement of liver stiffness. AIM: A prospective study to evaluate liver fibrosis with FibroScan and non-invasive biochemical methods in Crohn's disease patients treated with methotrexate. METHODS: Consecutive Crohn's disease patients had evaluation of liver fibrosis with non-invasive methods. Two subgroups of patients were compared: cumulative dose of methotrexate of more than 1500 mg (group 1) and naive for methotrexate (group 2). Liver biopsy was performed in patients with persistent liver enzyme abnormalities or FibroScan value >8.7 kPa. RESULTS: Fifty-four consecutive Crohn's disease patients were fully investigated (45 females, mean age 41 +/- 14 years). Median FibroScan values were similar in group 1 (n = 21) and in group 2 (n = 33), 5.5 and 4.5 kPa, respectively. FibroScan values were not correlated with the cumulative dose of methotrexate. CONCLUSION: In Crohn's disease patients treated with a high dose of methotrexate, significant liver fibrosis is rare and not accurately detected with liver enzymes abnormalities. FibroScan could be recommended and liver biopsy could be performed only with patients with high values and/or with chronic liver enzymes abnormalities.

Severe hepatic cytolysis: incidence and risk factors in patients treated by antiretroviral combinations. Aquitaine Cohort, France, 1996-1998. Groupe dEpidémiologie Clinique de Sida en Aquitaine (GECSA).

OBJECTIVE: To study hepatic cytolysis in patients treated by highly active antiretroviral therapy (HAART) with protease inhibitor or with two nucleoside reverse transcriptase inhibitors (NRTIs). METHODS: We selected patients of the Aquitaine Cohort who initiated HAART or two NRTIs before 1 January 1998, had alanine amino-transferase (ALT) < or = 200 IU/I at baseline and at least one follow-up measure. Cox model was used to study the association between occurrence of severe hepatic cytolysis (ALT>200 IU/l) and age, gender, HIV transmission group, baseline CD4 and CD8 cell count, history of hepatic cytolysis, antiretroviral drug, baseline liver enzymes (WHO classification level 0: < or = 50 IU/l, level 1: 51 to 100, level 2: 101 to 200), hepatitis B and C co-infection. RESULTS: Sixty-four of 748 (8.5%) patients treated with HAART and 71 of 1249 (5.7%) treated with two NRTIs developed cytolysis. The probability of occurrence was 7.9% after 1 year [95% confidence interval (CI), 5.9-10.4] for patients treated with HAART and 4.8% (95% CI, 3.6-6.4) for patients treated with two NRTIs (log-rank test, P = 0.01). The median time to occurrence was 164 days for HAART-treated patients and 252 days for those treated with two NRTIs. In multivariate analysis, the history of cytolysis [hazard ratio (HR) = 2.3; 95% CI, 1.2-4.4], baseline value of ALT (HR = 2.4; 95% CI, 1.2-4.8 and HR = 3.3; 95% CI, 1.4-7.4 for levels 1 and 2, respectively), hepatitis B (HR = 3.0; 95% CI, 1.4-6.2) and C co-infections (HR = 3.2; 95% CI, 1.7-6.2) remained significantly associated with the occurrence of severe hepatic cytolysis among HAART-treated patients. History of cytolysis, hepatitis B and C were associated with cytolysis in patients treated with two NRTIs (HR = 14.8, 2.6 and 2.7, respectively). CONCLUSION: Hepatic cytolysis is more frequent among patients treated with HAART than with two NRTIs. Hepatitis B and C are the major risk factors after initiation of HAART or treatment with NRTIs. Co-infections with hepatitis B virus or hepatitis C virus may modify the management of HIV-infected patients treated by HAART.

Segmented 5 versus nonsegmented flow quantitation: comparison of portal vein flow measurements.

RATIONALE AND OBJECTIVES: Times of acquisition, mean velocities, mean flows, and their respective standard deviations provided by segmented and nonsegmented flow quantifications (FQ) were compared in the main portal veins of ten healthy adults. METHODS: The segmented FQ performed five phase-encoding lines per segment. The authors successively applied the two electrocardiogram-triggered techniques in the same slice perpendicular to the portal flow direction. Their measurements were compared in particular by means of the statistical analysis proposed by Bland and Altman. RESULTS: The segmented 5 FQ reduced the acquisition time by two compared with the nonsegmented FQ. The mean velocity and mean flow values of the two techniques were not significantly different. The standard deviations were similar. CONCLUSIONS: The segmented 5 FQ showed its major advantage in the portal vein: the acquisition time was reduced without any loss of accuracy or any uncertainty enhancement.

Chromosomal analysis of colonic adenomatous polyps.

Chromosomal analysis of 25 colonic adenomatous polyps was performed by a direct method similar to that used in prenatal diagnosis of chromosomal aberration on chorionic villi. Fourteen lesions showed an abnormal karyotype. Two changes were recurrent: trisomy 7 (observed in eight cases) and trisomy 13 (observed in seven cases). No monosomy of the short arm of chromosome 17 was observed even at the level of two polyps with in situ carcinoma lesions.

Chromosome analysis of adenomatous polyps of the colon: possible existence of two differently evolving cytogenetic groups.

A chromosomal study of 42 colonic adenomatous polyps was performed using a technique of direct chromosome analysis derived from the prenatal procedure for diagnosing chromosomal alterations from chorionic villi sampling. Abnormal karyotypes were found in 22 cases. Trisomy 7, the most frequently found alteration, was found in 13 cases, followed by trisomy 13 (nine cases). Monosomy 18 was observed in two cases; in one of these, that of a polyp which had degenerated into an intra-mucosal adenocarcinoma, it was associated with 17p monosomy. Interestingly, these two types of alterations (trisomy 7 versus 18 and 17p monosomy) were not found together in the same lesion. This suggests that there could be two distinct chromosomal behaviors which might be related to the two cytogenetic groups described for colorectal adenocarcinoma. However, the respective frequencies of such cytogenetic groups varied inversely between adenomas and adenocarcinomas, thus suggesting that they evolve differently.

Outcome of liver transplantation in Wilson's disease: A demonstrative case.

A Wilson's disease (WD) patient developed a progressive liver cirrhosis and a disabling 'rubral' tremor, despite decoppering therapy, and subsequently underwent orthotopic liver transplantation (OLT). This case illustrates the outcome of OLT in WD, by demonstrating: (a) correction of the metabolic syndrome without further deposition of copper in the transplanted liver, (b) improvement of the neurological condition, (c) concomitant mobilization of copper deposits, as suggested by the fading of the Kayser-Fleischer corneal rings, (d) fading of brain MRI signal abnormalities on T2 weighted images. This case illustrates that OLT can be considered in WD, but only with caution because of the significant morbidity of the procedure.

[Congenital hepatic fibrosis disclosed late by hepatic encephalopathy]. / Fibrose hépatique congénitale tardivement révélée par une encéphalopathie hépatique.

A case of hepatic encephalopathy revealing congenital hepatic fibrosis in a 47-year-old woman is reported. The characteristic features of this observation were: a) the long clinical latency of a congenital disease usually discovered in childhood or in adolescence; b) the existence of hepatocellular insufficiency which appeared without any other reason than an ordinary infection; c) the absence of digestive bleeding or portacaval shunt, factors always found in the rare, previously described cases of encephalopathy in congenital hepatic fibrosis.

[Pharmacokinetics of cimetidine in ascitic cirrhotics]. / Pharmacocinétique de la cimétidine chez le cirrhotique ascitique.

Eleven patients with ascitic cirrhosis and eleven patients without liver disease received 200 mg of cimetidine orally and intravenously. Plasma concentrations of cimetidine were analysed by high pressure liquid chromatography. No differences were observed in cimetidine half-life (2.53 +/- 0.63 and 2.33 +/- 0.40 h) between the two groups. Cimetidine clearance was diminished by about 30 p 100 in cirrhotic patients (0.426 +/- 0.138 vs. 0.649 +/- 0.163 l/h/kg). The apparent volume of distribution was also significantly diminished (1.50 +/- 0.44 vs. 2.14 +/- 0.55 l/kg) in patients with cirrhosis and ascites.

[Geographical distribution and pathogenesis of chronic calcifying pancreatitis in tropical zones. Results of a multicenter survey in French-speaking Black Africa]. / Distribution géographique et pathogénie des pancréatites chroniques calcifiantes en zones tropicales. Résultats d'une enquête multicentrique en Afrique Noire francophone.

Chronic calcifying pancreatitis (CCP) is rare in countries with low alcohol consumption except in some tropical countries where malnutrition is widespread (southwest India) and in which CCP occurs in young non-alcoholics. In Black Africa sporadic cases of CCP have been reported in English-speaking countries (Uganda, Nigeria). The purpose of this study was to: a) assess the geographical distribution of CCP in French-speaking Africa; b) estimate the relative proportion of alcoholic CCP (ACCP) and juvenile tropical pancreatitis (JCCP). A total of 92 cases were included in this study, conducted in 16 French-speaking African countries (including Madagascar). There were no cases in countries with partly desert to climates and Moslem populations. Of these 92 cases, 86 corresponded to ACCP due to over consumption of various types of alcoholic beverages depending on the region. All were males with a mean age at diagnosis of 40.7 yrs. The remaining 6 cases were JCCP which were observed in areas of malnutrition with low intakes of animal protein and lipids. In this group the male/female ratio was 1/1 and the mean age at discovery was 15 yrs. Manioc toxicity did not appear to play any role. The "mixed" form, i.e. associating current alcohol consumption with childhood malnutrition, which has been described in young moderate drinkers in Burundi, was a possibility in 4 of the 86 cases of ACCP.