Intestinal microbiota contributes to individual susceptibility to alcoholic liver disease.

OBJECTIVE: There is substantial inter-individual diversity in the susceptibility of alcoholics to liver injury. Alterations of intestinal microbiota (IM) have been reported in alcoholic liver disease (ALD), but the extent to which they are merely a consequence or a cause is unknown. We aimed to demonstrate that a specific dysbiosis contributes to the development of alcoholic hepatitis (AH). DESIGN: We humanised germ-free and conventional mice using human IM transplant from alcoholic patients with or without AH. The consequences on alcohol-fed recipient mice were studied. RESULTS: A specific dysbiosis was associated with ALD severity in patients. Mice harbouring the IM from a patient with severe AH (sAH) developed more severe liver inflammation with an increased number of liver T lymphocyte subsets and Natural Killer T (NKT) lymphocytes, higher liver necrosis, greater intestinal permeability and higher translocation of bacteria than mice harbouring the IM from an alcoholic patient without AH (noAH). Similarly, CD45+ lymphocyte subsets were increased in visceral adipose tissue, and CD4(+)T and NKT lymphocytes in mesenteric lymph nodes. The IM associated with sAH and noAH could be distinguished by differences in bacterial abundance and composition. Key deleterious species were associated with sAH while the Faecalibacterium genus was associated with noAH. Ursodeoxycholic acid was more abundant in faeces from noAH mice. Additionally, in conventional mice humanised with the IM from an sAH patient, a second subsequent transfer of IM from an noAH patient improved alcohol-induced liver lesions. CONCLUSIONS: Individual susceptibility to ALD is substantially driven by IM. It may, therefore, be possible to prevent and manage ALD by IM manipulation.

[Nonalcoholic fatty liver disease in a severely obese adolescent. An arguable liver biopsy]. / Stéatohépatite non alcoolique chez une adolescente obèse: une biopsie hépatique discutable.

The growing epidemic of juvenile obesity has prompted pediatricians to investigate obesity-related conditions in obese teenagers. We report a clinical case of severe hepatic fibrosis in an adolescent with severe and recent obesity. Because of elevated serum aminotransferase levels, abnormal hepatic ultrasonography and insulin resistance (impaired glucose tolerance), we suspected nonalcoholic steatohepatitis (NASH). Disease activity and fibrosis were confirmed on liver biopsy. Considering the risk of progression toward cirrhosis and its complications, and the pathological liver lesions, we started long-term medical monitoring and drug therapy to control weight loss. At present, although biopsy is the only validated way to establish the diagnosis of NASH, there is no consensus on its indication when NASH is suspected. Noninvasive strategies are attractive but require validation in children.

Chromosomal breakpoints characterization of two supernumerary ring chromosomes 20.

The occurrence of an additional ring chromosome 20 is a rare chromosome abnormality, and no common phenotype has been yet described. We report on two new patients presenting with a supernumerary ring chromosome 20 both prenatally diagnosed. The first presented with intrauterine growth retardation and some craniofacial dysmorphism, and the second case had a normal phenotype except for obesity. Conventional cytogenetic studies showed for each patient a small supernumerary marker chromosome (SMC). Using fluorescence in situ hybridization, these SMCs corresponded to ring chromosomes 20 including a part of short and long arms of chromosome 20. Detailed molecular cytogenetic characterization showed different breakpoints (20p11.23 and 20q11.23 for Patient 1 and 20p11.21 and 20q11.21 for Patient 2) and sizes of the two ring chromosomes 20 (13.6 Mb for case 1 and 4.8 Mb for case 2). Review of the 13 case reports of an extra r(20) ascertained postnatally (8 cases) and prenatally (5 cases) showed varying degrees of phenotypic abnormalities. We document a detailed molecular cytogenetic chromosomal breakpoints characterization of two cases of supernumerary ring chromosomes 20. These results emphasize the need to characterize precisely chromosomal breakpoints of supernumerary ring chromosomes 20 in order to establish genotype-phenotype correlation. This report may be helpful for prediction of natural history and outcome, particularly in prenatal diagnosis.

[Disseminated tuberculosis with severe multi- organ failure in a patient with AIDS]. / Tuberculose disséminée avec défaillance multiviscérale foudroyante au cours d'un sida.

INTRODUCTION: Tuberculosis is the most common infectious complication in HIV infected patients. The incidence of tuberculosis and the proportion of disseminated disease increase with more severe immuno-suppression. Septic shock and multiple organ failure are uncommon but are of markedly bad prognostic significance. CASE REPORT: A forty-four year old HIV seropositive man was admitted to the intensive care unit (ICU) with acute respiratory distress. The patient had been febrile for the previous two weeks. His thoracic radiograph showed a discrete interstitial infiltrate and at bronchoscopy small whitish granulations were observed in the main bronchi. All bacteriological investigations remained negative at the time of ICU admission. The patient died sixteen hours later due to multiple organ failure. Mycobacteria were identified after patient's death on the smear from BAL, from blood cultures, and in a postmortem liver biopsy. CONCLUSIONS: Septic shock is an infrequent complication of disseminated tuberculosis. Mortality is very high. Treatment should be started early in cases with a high diagnostic suspicion.

Is sclerosing angiomatoid nodular transformation (SANT) of the splenic red pulp identical to inflammatory pseudotumour? Report of 16 cases.

AIMS: To report 16 cases of sclerosing angiomatoid nodular transformation (SANT) of the splenic red pulp. METHODS AND RESULTS: Patients were selected in two phases. An initial group of seven patients was diagnosed with SANT based on the presence of angiomatoid nodules. Sheets of inflammatory fibrosis were found in three patients, resembling inflammatory pseudotumour (IPT); nine further cases of IPT were reviewed. Angiomatoid nodules were detected, leading to the diagnosis of SANT in all cases. The splenic mass (10-150 mm in diameter) was polycyclic, composed of multiple small nodules of loose connective tissue comprising myofibroblasts and a dense network of capillaries as well as some remnants of sinuses. Collagenous fibrosis surrounded them. Bands or large sheets of fibrosis, infiltrated by various inflammatory cells, particularly polytypic plasmacytes, resembling IPT, were present in 10 cases. CONCLUSIONS: SANT of the red pulp is a distinct benign pseudotumorous lesion of the spleen characterized by the presence of angiomatoid nodules. We observed such angiomatoid nodules in all our cases of splenic IPT, which were not follicular dendritic cell or myofibroblastic tumours. We therefore recommend careful examination for angiomatoid nodules in all suspected cases of splenic IPT.

[Juvenile dermatomyositis: diagnosis and treatment]. / La dermatomyosite de l'enfant: diagnostic et prise en charge.

Juvenile dermatomyositis is a rare inflammatory myopathy with characteristic skin manifestations and muscular weakness. Muscle biopsy is important for establishing the diagnosis. Four patients with juvenile dermatomyositis were studied retrospectively. Steroids remain the first line treatment. Corticosteroids resistance is the primary indication for the use of intravenous immunoglobulins or immunosuppressive drugs. Further studies are necessarily aimed at finding biological markers to select and guide new therapeutical approaches for those patients.

Stability of the m.8993T->G mtDNA mutation load during human embryofetal development has implications for the feasibility of prenatal diagnosis in NARP syndrome.

BACKGROUND: Mitochondrial DNA (mtDNA) mutations cause a wide range of serious genetic diseases with maternal inheritance. Because of the high transmission risk and the absence of therapy in these disorders, at-risk couples often ask for prenatal diagnosis (PND). However, because heteroplasmy load (coexistence of mutant and wild-type mtDNA) may vary among tissues and with time, the possibility that a single fetal sample may not reflect the whole neonate impedes prenatal diagnosis of mtDNA diseases. METHODS: We performed 13 prenatal diagnoses for the NARP (neurogenic weakness, ataxia, retinitis pigmentosa) m.8993T-->G mtDNA mutation (p.Leu156Arg) in the ATP synthase subunit 6 gene. Analyses were performed on chorionic villous (CVS) and/or amniocyte samples carried out at various stages of pregnancy, using a method enabling quantification of low DNA amounts. RESULTS: Maternal mutant loads ranged from 0 to 75% in blood and had no predictive value for the fetus status, except for women with no detectable mutant DNA, whose fetuses were consistently mutation-free. In 8/13 PND, mutant load was <30%. These children are healthy at 2-7 years of age. In 5/13 PND, mutant load ranged from 65 to 100%, and parents preferred to terminate the pregnancies (15-22 weeks of gestation). Single-cell analysis of 20 trophoblastic cells and 21 amniocytes isolated from two affected fetuses found an average mutant load close to the overall CVS and amniocyte mutant load, despite striking intercellular variation. The m.8993T-->G mutant loads, assessed in 7, 17, 11, and 5 different tissues from 4 terminations, respectively, were identical in all tissues from a given individual (mean (SD) 78 (1.2)%, 91 (0.7)%, 74 (2)%, and 63 (1.6)% for the 4 fetuses, respectively). CONCLUSIONS: Our results indicate that the placental/amniotic mutant loads do reflect the NARP mutant mtDNA load in the whole fetus, even when the sample amount is small, and suggest that heteroplasmy level remains stable during pregnancy, at least after 10 weeks of gestation. Although these data establish the feasibility of PND for this mutation, assessing more precisely the correlation between mutant load and disease severity should further help in interpreting PND results.

Fibrosis progression occurs in a subgroup of heavy drinkers with typical histological features.

BACKGROUND: Studies using consecutive liver biopsies constitute an attractive approach to gaining insight into the pathogenesis of alcoholic liver disease. AIM: To analyse histological factors at baseline, which are predictive of fibrosis progression and recurrence of alcoholic hepatitis. RESULTS: A total of 193 drinkers underwent consecutive biopsies at an interval of 4 years. At baseline, 20 had normal livers, 135 steatosis, five fibrosis and 33 alcoholic hepatitis. The fibrosis score increased from 1.07 +/- 0.07 to 1.7 +/- 0.94 (P < 0.001). In multivariate analysis, only steatosis (P = 0.04), alcoholic hepatitis (P = 0.0004) and stage of fibrosis (P < 0.0001) were independent predictive factors of the fibrosis score at the second biopsy. Cirrhosis developed more frequently in patients with steatosis (11%) and alcoholic hepatitis (39%) than in others (0%, P < 0.0001). Alcoholic hepatitis recurred more frequently in patients with alcoholic hepatitis at baseline: 58% vs. 15%, P < 0.0001. In multivariate analysis, alcoholic hepatitis at the first biopsy was the only predictive factor of its recurrence (P < 0.0001). CONCLUSIONS: In a large cohort of drinkers with consecutive biopsies, steatosis, fibrosis stage and alcoholic hepatitis at baseline were independent predictive factors of fibrosis progression. In terms of mechanisms, we propose a novel concept of multiple hits of alcoholic hepatitis occurring in the same patient.

Evaluation of smoking cessation success in adults.

BACKGROUND: Smoking is a preventable cause of increased morbidity and mortality. Therefore, interventions have been used to assist smokers in overcoming their addiction. The aim of the study was to describe factors associated with smoking cessation, in patients applied to our smoking cessation (SC) unit in 1999, in a prospective study. METHODS: Patients were followed-up during two years. Detailed medical history, Fagerstrom test, Hospital Anxiety and Depression (HAD) scale questionnaire, Motivation scale and replacement therapy were systematically recorded. RESULTS: Three hundred patients (58% men, 42% women) applied to the SC unit from January to December 1999. The mean age was 42 yrs old. They smoked in average 24 cig/d. Mean duration of smoking was 20 years. Fagerstrom score was 5.86 (min 0; max: 10). Patients seemed to be more anxious (score 9.6) than depressed (5.09), according to the HAD score. 79% of them received both psychosocial intervention, pharmacotherapy and nicotine replacement therapy. 66% of patients were followed-up (n=198). Two years later, the smoking cessation rate was 12% (n=36). Motivation, Fagerstrom and HAD scores were not associated with the quitting rate. Quitting rate was higher (25.9%) in patients who attempted to quit smoking for the first time than in others (19%). By contrast, the quitting rate was significantly associated with age (P=0.03). CONCLUSION: Success to quit smoking was positively associated with age, and negatively with alcohol dependence.

Hyperthyroidism in two patients with Crohn disease and Takayasu arteritis.

Thyroid abnormalities and Takayasu arteritis (TA) have been reported separately in patients with Crohn disease (CD). We report two patients with hyperthyroidism, CD and Takayasu arteritis and discuss hypothetical mechanisms. Case 1. A thyrotoxic goiter was diagnosed in 1987 in a 34-year-old woman treated since 1969 for severe CD and TA. Iodine urinary excretion was 405 microg/mL (20-500). Anti-thyrotropin receptor (TRAK) and anti-thyroid antibodies were not detectable. The ultrasonography showed a nodule in the right lobe of the thyroid and two nodules in the left lobe. A 123I thyroid scan showed a multinodular goiter with no hot nodule. She was treated successfully with propylthiouracile until 1991, when a new episode of thyrotoxicosis led to a subtotal thyroidectomy. Case 2. Hyperthyroidism was diagnosed in February 2000 in a 49-year-old woman treated for CD and TA, both diagnosed in 1980. TRAK and anti-thyroid peroxydase antibodies were not detectable. The ultrasonography disclosed a normal thyroid volume with an inhomogeneous parenchymal structure and nodular images in both lobes. A 123I thyroid scan showed one hot nodule in the lower part of each lobe. A subtotal thyroidectomy was performed. The association of these three diseases may not be fortuitous, possibly explained by genetic predisposing factors and disease-related iodine deficiency both involving Nuclear Factor kappaB pathway.

[Pseudotumoral enterocolic phlebitis of the cecum and rutoside. A case report]. / Phlébite entérocolique pseudotumorale du caecum et rutoside. Une nouvelle observation.

INTRODUCTION: Enterocolic phlebitis is an entity characterized by ischemic injury of the gastrointestinal tract caused by thrombophlebitis of the mesenteric veins without arterial involvement or systemic disease. EXEGESIS: We report a case of enterocolic phlebitis in a 57-year-old female treated by rutoside, revealed by intestinal obstruction related to a pseudotumoral lesion of the caecum. CONCLUSION: This case adds to the four cases of enterocolic phlebitis under rutoside already reported in the literature, suggesting a possible involvement of this drug in this rare disease.

Acute liver failure as initial manifestation of low-grade non-Hodgkin's lymphoma transformation into large-cell lymphoma.

Acute liver failure as an initial manifestation of primary non-Hodgkin's lymphoma is a rare phenomenon with a grim prognosis. We report for the first time on a patient with a history of follicular lymphoma in complete remission, presenting fulminant liver failure due to massive liver infiltration by transformed lymphoma cells and portal vein thrombosis, as an initial manifestation of transformation into large-cell lymphoma.