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.

KLF6 transcription factor protects hepatocellular carcinoma-derived cells from apoptosis.

Hepatocellular carcinoma (HCC) is a major public health concern because of the absence of early diagnosis and effective treatments. Efficient diagnosis modalities and therapies to treat HCC are needed. Kruppel-like factor (KLF) family members, such as KLF6, are involved in cell proliferation and differentiation. KLF6 is inactivated in solid tumors, which may contribute to pathogenesis. However, KLF6 status in HCC is controversial. Thus, we undertook the characterization of KLF6 expression and function in HCC and HCC-derived cell lines. We found that HCC, HepG2 and HuH7 cells expressed KLF6 messenger ribonucleic acid and protein. Next, using RNA interference, we demonstrated that inhibiting KLF6 expression in vitro strongly impaired cell proliferation-induced G1-phase arrest, inhibited cyclin-dependent kinase 4 and cyclin D1 expression, and subsequent retinoblastoma phosphorylation. Finally, KLF6 silencing caused p53 upregulation and inhibited Bcl-xL expression, to induce cell death by apoptosis. Taken together, these data demonstrated that KLF6 is essential for HCC-derived cells to evade apoptosis.

Study of the association between major histocompatibility complex class II genes and the response to interferon alpha in patients with chronic hepatitis C infection.

OBJECTIVE: The aim of the study was to determine the influence of HLA class II genes on the response to interferon-alpha (IFN-alpha) in patients with chronic hepatitis C. METHODS: The distribution of HLA DRB1 and DQB1 alleles was assessed in 170 caucasoïd patients treated with IFN-alpha for chronic hepatitis C. 50 patients had a long term sustained response to treatment whereas 120 patients were nonresponders. RESULTS: Female sex, non-1 HCV genotype particularly genotype 2 and pretreatment low serum HCV RNA level were associated with long-term sustained response to IFN-alpha. A trend towards a higher prevalence of DRB1*07 allele in non responders than in patients with sustained response (45% vs. 28%, odds ratio 2.1; P < 0.05) on the one hand and of DQB1*06 allele in HCV genotype 1 patients with sustained response than in HCV genotype 1 nonresponders (75% vs 27.3%, odds ration 7.9; P < 0.02) on the other hand, were observed. However, none of these two differences remained significant after Bonferroni's correction. CONCLUSION: Accordingly, we conclude that the response to IFN-alpha therapy is more tightly related to virus factors than to host's HLA class II genes.

Evaluation of alpha-fetoprotein assay in ascitic fluid for the diagnosis of hepatocellular carcinoma.

Ascites and hepatocellular carcinoma are frequently associated. We evaluated the usefulness of alpha-fetoprotein assay in ascitic fluid versus the serum assay, for the diagnosis of hepatocellular carcinoma, in 125 patients with peritoneal effusions (31 patients with hepatocellular carcinoma, 14 with extra-hepatic malignancies and 80 with a benign effusion). Albumin and total protein were also assayed and cytological analysis of the ascitic fluid performed. Alpha-fetoprotein appeared to be lower in ascitic fluid than in serum. For a diagnostic specificity of 95%, the thresholds were 18.9 microg/l in serum and 4 microg/l in ascitic fluid and the diagnostic sensitivity of alpha-fetoprotein was identical in serum and ascitic fluid (67.7%). Various ratios between alpha-fetoprotein and albumin or total protein did not enhance the diagnostic performance. Thus alpha-fetoprotein concentration in ascitic fluid reflected the serum concentration and proved to be of similar value for the diagnosis of hepatocellular carcinoma, providing that the appropriate thresholds are considered.

[Emergency colonoscopy in lower intestinal occlusion]. / La coloscopie en urgence au cours des occlusions intestinales basses.

From March 1980 to June 1983, 23 patients presenting with clinical and or radiological manifestations of colonic obstruction and with uncertainty as to medical/surgical possibilities of management, underwent emergency colonoscopy in the intensive care unit of our Digestive Disease Department. The investigations were conducted without preparation (enema) or premedication, using an ordinary colonoscope. The endoscopic examination led to correct diagnosis in 21 patients out of 23 (91.3 p. 100). The main causes of occlusion were: colonic or rectal cancer (11 cases), Ogilvie's syndrome (6 cases), volvulus of the sigmoid colon (3 cases). Endoscopy contributed to treatment in eight patients with good results in six. It was unsatisfactory in two cases of volvulus of the sigmoid colon which recurred. In two instances complications occurred which were attributable to the method: one pneumoperitoneum without frank perforation and a transtumoral perforation in a case of sigmoid cancer, discovered at laparotomy. No septic complication or mortality resulted from endoscopy. Colonoscopy under normal conditions should not be advocated systematically, but can be used as a method of investigation and possibly of therapy in selected cases of colonic obstruction admitted into intensive care units.

[Posterior fundoplication of 270 degrees. pH results after one and 5 years]. / Fundoplicature postérieure de 270 degrees. Résultats ph-métriques à 1 an et 5 ans.

This prospective study compared pre- and postoperative pH monitoring one and five years after a 270 degrees posterior fundoplication. Thirty-six consecutive patients with gastroesophageal reflux were included over a period of 3 years. All patients had preoperative esophagoscopy and 3 hour post-prandial pH monitoring. Thirty-three patients had esophagitis. At one year follow-up, pH monitoring was performed in 31 patients and esophagoscopy in 29. At five years, 23 patients accepted a new pH control. Appraisal of efficacy was assessed by Kaye's acid reflux score (normal < or = 90) and the percentage of time (t) below pH 5 (normal < or = 10%). Among the 23 patients who were submitted 3 times to pH monitoring, Kaye's acid reflux score evolved from 149 (+/- 68) before fundoplication to 1.1 (+/- 2) and 16 (+/- 29) after one and five years respectively. The value of t decreased from 20% (+/- 16) to 0.4% (+/- 0.8) after one year and to 2.5% (+/- 3) after five years. The 270 degrees posterior valve corrects pH recordings at one year. Its efficacy remained steady after 5 years, although there was a slight increase in acid reflux scores. The mean value of these scores was always within normal limits.

[Outcome of patients after obliteration of esophageal varices by endoscopic sclerosis. Results of a prospective study]. / Devenir des malades après éradication des varices oesophagiennes par sclérose endoscopique. Résultats d'une étude prospective.

The purpose of this prospective was study to investigate the course of patients after obliteration of bleeding esophageal varices by endoscopic sclerotherapy and to outline prognostic factors. Sixty-seven patients (45 men, 22 women, mean age: 53.3 +/- 14 years) were followed for a mean of 14 +/- 8 months median = 15 months-range: 1-33 months) from the time of obliteration. Etiology of portal hypertension was portal vein thrombosis in 3 patients and cirrhosis in 64, 44 of whom (65 p. 100) were due to alcoholism (Child-Pugh's class: A: 8 p. 100, B: 42 p. 100, C: 50 p. 100). Recurrence of varices was observed in 23 patients within 1.4 to 25 months (median: 6.6 months). The recurrence rate increased in a linear fashion with time. Reobliteration was achieved in one to three sessions of sclerotherapy. More than one bleeding episodes was observed more often, before sclerotherapy (p less than 0.05) and esophageal stenosis was seen less often during treatment (p less than 0.05) than in patients without recurrence. Variceal bleeding occurred in 14 patients (21 p. 100) within 0.1 to 23 months (median = 5.6), 6 of whom (43 p. 100) died. In the subgroup of alcoholic cirrhosis, absence of withdrawal was associated with a higher risk of rebleeding (p = 0.04). Fifteen patients (22 p. 100) died within 1 to 26 months (median = 12.3). They had a higher mean age (p less than 0.01) and a lower blood fibrinogen (p less than 0.05) than survivors.(ABSTRACT TRUNCATED AT 250 WORDS)

[Obstructive intramural hematoma of the esophagus. A rare complication of endoscopic sclerotherapy of esophageal varices]. / Hématome intramural obstructif de l'oesophage. Une complication rare de la sclérose endoscopique des varices oesophagiennes.

Obstructive intramural hematoma of the esophagus is an unusual complication of endoscopic sclerotherapy. We report three patients with liver cirrhosis who experienced such a complication. In our series, the frequency was 1.6 percent. A few hours after sclerotherapy, all three patients complained of low retrosternal pain, dysphagia and hypersialorrhea. Endoscopy was performed in two patients and showed a typical bluish submucosal mass occupying the esophageal lumen. Outcome was favorable in all patients within one week of conservative treatment. We hypothesized that hematoma could be ascribed to variceal puncture. The extension of the hematoma with dissection of the esophageal wall which had been fragilized by previous sclerotherapy sessions could have been facilitated by impaired coagulation.

[Embolization of esophageal varices by the transjugular route in severe digestive hemorrhage in cirrhotic patients. Prospective study of 83 patients]. / Embolisation des varices oesophagiennes par voie transjugulaire dans les hémorragies digestives graves du cirrhotique. Etude prospective de 83 patients.

A prospective study was undertaken to assess the results of embolization of esophageal varices by the transjugular approach, in 83 patients with advanced cirrhosis (65 p. 100 Child's class C) admitted with severe bleeding (mean of 10 units of blood per patient). Embolization was successfully completed in 65 patients (78 p. 100) and complete obliteration was achieved in 50 (60 p. 100). Twenty-nine procedures were performed on actively bleeding patients. Cessation of bleeding was observed in 22 (76 p. 100). Excluding the 5 patients in whom embolization could not be achieved, the success rate was 92 p. 100. Embolization was attempted as an elective procedure in 54 patients who were not actively bleeding. Recurrent hemorrhage occurred in 18 patients (33 p. 100) during the first month of follow-up. Finally, 38 patients rebled and 57 died. No accident could be ascribed to the procedure. It is concluded that: (a) the transjugular approach proved to be safe in actively bleeding patients with severe cirrhosis; (b) variceal obliteration effectively controlled active bleeding. The efficacy of this procedure was limited in time. The use of embolization is further hindered by a consistent failure rate and by the development of new therapeutic modalities, such as sclerotherapy.

[Treatment of hemorrhages by rupture of cardio-tuberous varices with transjugular intrahepatic portasystemic shunt]. / Traitement des hémorragies par rupture de varices cardio-tubérositaires par anastomose porto-systémique intra-hépatique par voie trans-jugulaire.

Twelve consecutive patients admitted for bleeding from ruptured gastric varices were treated with transjugular intrahepatic portosystemic shunts and followed for a mean of 6 +/- 3 months (range: 8-293 days). The shunt was performed successfully in all 12 patients. The shunt occluded in 3 patients (respectively 19, 101 and 103 days after insertion) of whom one remained asymptomatic and two experienced rebleeding. Four patients presented with acute encephalopathy, spontaneously in two and after rebleeding in two. Three patients died, two after rebleeding and one of septic shock secondary to pneumonia. Overall, 9 patients survived a mean of 211 +/- 92 days with no rebleeding, 8 of whom have not yet experienced any complications. These results suggest that transjugular intrahepatic portosystemic shunts could be useful in treating hemorrhages from ruptured gastric varices and in preventing their recurrence.

[Immunochemical diagnosis of hepatic localizations in malignant lymphoid hematologic diseases. Study of 80 cases]. / Diagnostic immunohistochimique des localisations hépatiques des hémopathies lymphoïdes malignes. Etude de 80 cas.

The diagnostic value of immunohistochemistry using monoclonal antibodies was assessed in 100 liver biopsy specimens. The majority of these cases were hepatic localizations of lymphoid malignancies. Ten normal and reactive inflammatory liver biopsies were used as controls. Some monoclonal antibodies directed against leukocyte antigens revealed unexpected reactivities with normal liver structures: biliary tract (anti-CD10, anti-B MB2) and hepatocytes (anti-B LN1). In 12/17 cases of hepatic involvement by large cell malignancy, immunohistochemistry allowed the diagnosis of non Hodgkin's lymphoma (NHL); the remaining 5 cases were metastatic undifferentiated carcinoma. It was difficult to differentiate small cell liver NHL from reactive inflammatory infiltration. New anti-B (MB1, MB2, 4KB5, LN1 and LN2) and anti-T (MT1 and UCHL1) monoclonal antibodies suitable for use on paraffin sections were of value to phenotype NHL when only fixed material was available. But, information was too limited to distinguish malignant from reactive infiltrates. Immunohistochemistry on frozen sections was often necessary to diagnose inflammatory infiltrates and to phenotype NHL. Most NHL were of B cell origin (11/13 cases) and showed monotypic surface immunoglobulins as well as B cell-associated antigens (CD22+). The expression of the T CD5 antigen by B-cell NHL may have some diagnostic value. When monotypic surface immunoglobulins could not be demonstrated (due to background staining) the expression of this antigen by B lymphocytes was considered to be highly indicative of their neoplastic nature. Hairy cell leukemia exhibited a pathognomonic phenotype on frozen sections (CD11c+, CD22+, CD25+). T NHL were rare (2 cases) and difficult to diagnose due to the lack of clonal markers. The diagnosis of Hodgkin's disease in liver (15/20 cases) was facilitated by using paraffin sections of both monoclonal antibodies anti-CD15 (Leu M1) and anti-CD30 (Ber-H2) which detect fixation-resistant antigens expressed by Sternberg cells.

[Evaluation of the effects of molsidomine and propranolol-molsidomine combination on portal hemodynamics by pulsed Doppler ultrasound]. / Etude par échographie Doppler pulsé des effets de la molsidomine et de l'association propranolol-molsidomine sur l'hémodynamique portale.

Molsidomine, a long acting vasodilator with antianginal properties, has been shown to decrease porto-hepatic pressure gradient in patients with cirrhosis. The present study aimed at assessing the effects of molsidomine, propranolol and of the association of these two drugs on portal vein blood flow as measured using Doppler and B-mode sonography. In 10 patients without liver disease (group 1), portal flow time average mean velocity (TAV) and portal vein blood flow (PVBF) were measured under basal conditions, 1 hour then 2 hours after ingestion of 4 mg of molsidomine. The same measurements were performed in 15 patients with cirrhosis (group 2) under basal conditions, 1 then 2 hours after double-blind administration of either molsidomine (10 patients) or placebo (5 patients). Fifteen further patients with cirrhosis (group 3) were studied after the double blind administration of 80 mg of propranolol and two hours later of 4 mg of molsidomine (10 patients) or placebo (5 patients); TAV and PVBF were measured under basal conditions, two hours after propranolol ingestion or placebo, then one and two hours after molsidomine or placebo ingestion. TAV and PVBF remained unchanged in patients treated with placebo. Molsidomine reduced TAV by 23.8 +/- 19.5% in group 1 (P < 0.01) and by 25.6 +/- 21.4% in group 2 (P < 0.01). In group 3, a 10% decrease was observed after propranolol (NS). When molsidomine was added, TAV was further decreased (-17.6 +/- 13.3% vs baseline, P < 0.01). PVBF remained unchanged in the three groups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Enterovenous fistula. An unusual complication of Crohn disease]. / La fistule entéro-veineuse. Une complication exceptionnelle de la maladie de Crohn.

We report a case of enterovenous fistula in a young 22-year-old patient with Crohn's disease associated with jaundice. Ultrasound and computed tomography showed stationary gaz and barium in the liver. Pathological examination showed a fistula between the lumen of the inflamed segment of the ileum and the superior mesenteric venous system. This unusual finding in Crohn's disease may be a severe complication.

[Familial autoimmune pathology comprising 2 cases of primary biliary cirrhosis]. / Pathologie auto-immune familiale comportant deux cas de cirrhose biliaire primitive.

Two cases of primary biliary cirrhosis (PBC) were observed in two brothers. Clinical, biochemical, immunological and genetic investigations (in particular by HLA typing) were systematically undertaken in nine subjects of this family (including the two above mentioned cases) in two generations. One case of granulomatous hepatitis associated with auto-immune thyroiditis was discovered in a sister. Immunological abnormalities were observed in six out of nine members of the family: anti-nuclear (four cases), anti-mitochondrial (two cases), anti-thyroid (two cases), auto-antibodies and rheumatoid factors (two cases). Six subjects (including the three with hepatic disease) had the same HLA haplotype (with in particular HLA DR4, which has been previously associated with sporadic PBC). However, the role of this haplotype in the transmission of PBC in a family could not be demonstrated. Biochemical and immunological survey might be of importance in the kindred of patients with PBC, thereby contributing to the screening of asymptomatic hepatic disease.

[Position of dietary factors in large bowel cancers (author's transl)]. / Place des facteurs nutritionnels dans la carcinogenèse colique.

Epidemiological studies suggest that environmental factors, especially dietary ones, are more relevant in the causation of large bowel cancer than host factors. High meat and high-fat, low-fiber and low-vegetable diets appear to be the most plausible etiological candidates. Metabolic epidemiology and experimental studies point out that changes in the composition of the intestinal bacteria and of the neutral sterol and bile acid excretion are likely to yield colon tumor promoters. Implications of the available data are discussed in terms of colon cancer prevention.

[Granulomatous hepatitis. Apropos of 112 cases in adults]. / Hépatite granulomateuse. A propos de 112 cas chez l'adulte.

In this series, the commonest aetiology was tuberculosis (24 cases), Hodgkin's disease (21 cases), sarcoidosis (14 cases) and Q fever (14 cases). Some morphological features such as number and size of granulomas seemed useful for aetiological diagnosis. A granuloma with a central fat vacuole surrounded by fibrinoid material was in favour of Q fever. A dense mononuclear sinusoidal infiltration was associated with granulomas in MNI or CMV infections. 19 cases were cryptogenetic.

[A human pancreatic glucagonoma, ultrastructural, immunocytochemical and radioimmunological investigations (author's transl)]. / Etude ultrastructurale, immunocytochimique et radioimmunologique d'un glucagonome pancréatique humain.

The authors report a case of glucagonoma in a 52 years old man presenting a migratory necrolytic erythema. By conjugated means of arteriography and splenoportography with plasma glucagon assays the tumour was localized in the tail of the pancreas. Surgical excision was easy but hepatic metastases revealed the malignant nature of the tumor. This glucagonoma has been investigated by several approaches including electron microscopy, immunocytochemistry and radioimmunological techniques. The tumor contained scattered glucagon and pancreatic polypeptide immunoreactive cells; insuline, glucagon, somatostatin, pancreatic polypeptide, gastrin and VIP antisera gave negative results. Ultrastructurally, these cells showed atypical secretory granules different from A granules of the normal glucagon cell. Radio immunological determinations carried out after gel permeation chromatography of plasma revealed high molecular weight (4 000, 9 000, 14 000) immunoreactive glucagon peptides. They have been thought to be proglucagon forms which did not react with specific antiglucagon sera used in cytological studies. Reported data are consistent with the classification of this tumor in the category of glucagonoma with the "glucagonoma syndrome".

[Intrahepatic porto-systemic shunt in the treatment of hemorrhage in portal hypertension]. / Le shunt intra-hépatique porto-systémique dans le traitement des hémorragies de l'hypertension portale.

UNLABELLED: PREVENT RECURRENT BLEEDING: Digestive hemorrhage due to portal hypertension is the cause of one-third of the mortality in cirrhosis. Transjugular intrahepatic portosystemic shunt (TIPS) creates a calibrated anastomosis between the portal vein and hepatic vein. The technique is now well established and a trained team can install a shunt in approximately 2 hours with a risk of failure of less than 10%. RESULTS: TIPS can be effective for the treatment and prevention of variceal bleeding subsequent to portal hypertension. Preliminary results have not however provided the precise indications for this technique in the therapeutic armamentanium. COMPLICATIONS: Hepatic encephalopathy and obstruction are the main complications. Encephalopathy can occur as an acute episode; frequency appears to fall off after endothelialization of the prosthesis. The degree of shunt obstruction can reach 40% at one year and remains the major problem with this technique. Its pathogenesis is unknown and there is no prevention. Regular surveillance is required to detect this complication and take the necessary steps.