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Background & Aims: Liver adenomatosis (LA) is characterized by the presence of at least 10 hepatocellular adenomas (HCAs), but the natural history of this rare liver disorder remains unclear. Thus, we aimed to reappraise the natural history and the risk of complications in a cohort of patients with at least 10 HCAs., Methods: We analyzed the natural history of 40 patients with LA, excluding glycogen storage disorders, in a monocentric cohort. Pathological examination was performed, with immunostaining and molecular biology carried out on surgical specimens or liver biopsies., Results: Forty patients (36 female) were included with a median follow-up of 10.6 (1.9-26.1) years. Six (15%) patients had familial LA, all with germline HNF1A mutations. Median age at diagnosis was 39 (9-55) years. Thirty-three (94%) women had a history of oral contraception, and 29 (81%) women had a pregnancy before LA diagnosis. Overall, thirty-seven (93%) patients underwent surgery at diagnosis. Classification of HCAs showed 46% of patients with HNF1A-mutated HCA, 31% with inflammatory HCA, 3% with sonic hedgehog HCA, 8% with unclassified HCA. Only 15% of the patients demonstrated a "mixed LA" with different HCA subtypes. Hepatic complications were identified in 7 patients: 1 patient (3%) died from recurrent hepatocellular carcinoma after liver transplantation; 6 (15%) had hemorrhages, of which 5 occurred at diagnosis, with 1 fatal case during pregnancy, and 2 occurred in male patients with familial LA. Four patients (10%) had repeated liver resections. Finally, 4 (10%) patients developed extrahepatic malignancies during follow-up., Conclusions: The diversity in HCA subtypes, as well as the occurrence of bleeding and malignant transformation during long-term follow-up, underline the heterogeneous nature of LA, justifying close and specific management. In patients with germline HNF1A mutation, familial LA occurred equally frequently in males and females, with a higher rate of bleeding in male patients., Lay Summary: Liver adenomatosis is a rare disease characterized by the presence of 10 or more hepatocellular adenomas that may rarely be of genetic origin. Patients with liver adenomatosis have multiple adenomas of different subtypes, with a risk of bleeding and malignant transformation that justify a specific management and follow-up., (Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Data on extrahepatic cancers (EHCs) in compensated viral cirrhosis are limited. The objective of the prospective multicenter Agence Nationale de Recherche sur le SIDA et les Hépatites virales CO12 CirVir cohort was to assess the occurrence of all clinical events in patients with compensated viral cirrhosis, including all types of cancer. Patients with the following inclusion criteria were enrolled in 35 French centers: (1) biopsy-proven hepatitis B virus (HBV) or hepatitis C virus (HCV) cirrhosis, (2) Child-Pugh A, or (3) absence of previous liver complications including primary liver cancer (PLC). Patients were followed up prospectively every 6 months. The standardized mortality ratio (SMR) was calculated according to age and gender using 5-year periods. The impact of sustained viral response (SVR) in HCV patients and maintained viral suppression in HBV patients were assessed using time-dependent analysis. A total of 1,671 patients were enrolled between 2006 and 2012 (median age, 54.9 years; men, 67.3%; HCV, 1,323; HBV, 317; HCV-HBV, 31). Metabolic features and excessive alcohol and tobacco consumption were recorded in 15.2%, 36.4%, and 56.4% of cases, respectively. After a median follow-up of 59.7 months, 227 PLCs were diagnosed (5-year cumulative incidence [CumI] 13.4%) and 93 patients developed EHC (14 patients with lymphoid or related tissue cancer and 79 with solid tissue cancer; 5-year EHC CumI, 5.9%). Compared to the general French population, patients were younger at cancer diagnosis, with significantly higher risk of EHC in HCV patients (SMR, 1.31; 95 confidence interval [CI], 1.04-1.64; P = 0.017) and after SVR (SMR = 1.57; 95% CI, 1.08-2.22; P = 0.013). EHC was the fourth leading cause of death in the whole cohort and the first in patients with viral control/eradication., Conclusion: Compared to the general French population, HCV cirrhosis is associated with a higher risk of EHC and the first cause of death in patients with viral cirrhosis who achieve virological control/eradication. (Hepatology 2018)., (© 2018 by the American Association for the Study of Liver Diseases.)

Background: The objective was to examine the role of a sustained virological response (SVR) on major adverse cardiovascular events (MACEs) in patients with compensated hepatitis C virus (HCV) cirrhosis., Methods: Patients with the following criteria were enrolled in 35 French centers: (1) biopsy-proven HCV cirrhosis; (2) Child-Pugh A; (3) positive viremia; and (4) no prior liver complication, and then prospectively followed. All patients received HCV treatment after inclusion. MACEs included stroke, myocardial infarction, ischemic heart disease, heart failure, peripheral arterial disease, cardiac arrest, and cardiovascular death. SVR, defined as negative viremia 12 weeks posttreatment, was considered as a time-dependent covariate, and its effect on MACE occurrence was assessed. The median follow up was 57.5 months, ending in December 2015., Results: Sixty-two of 878 (7.1%) patients presented a total of 79 MACEs. The main predictive baseline factors of MACEs were Asian ethnic origin, history of MACEs, arterial hypertension, diabetes mellitus, current smoking, low serum albumin level, high total bilirubin level, and low platelet count. In multivariate analysis, SVR was associated with a decreased risk of MACEs (hazard ratio=0.35, 95% CI 0.09-0.97, P=.044), whereas Asian ethnic origin, arterial hypertension, smoking, and low serum albumin level remained predictive of MACE occurrence. The 5-year survival rate was 60.1% versus 87.5% in patients who did versus those who did not present a MACE (P<.001)., Conclusions: In patients with compensated HCV-related cirrhosis, Asian ethnic origin, arterial hypertension, smoking, and low serum albumin are independent predictive factors of cardiovascular events, whereas an SVR is associated with a decreased rate of cardiovascular events., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Unlabelled: Various critical events, liver related or not, occur in patients with compensated cirrhosis, but their respective burden remains to be prospectively assessed. The aim of this prospective cohort study involving 35 French centers was to capture the whole spectrum of complications occurring in compensated viral cirrhosis (VC) using competing risks analyses. Inclusion criteria were: histologically proven cirrhosis resulting from hepatitis C virus (HCV) or hepatitis B virus (HBV); Child-Pugh A; and no previous hepatic complications. The cohort was considered as a multistate disease model, cumulative incidences (CumIs) of events were estimated in a competing risks framework. A total of 1,654 patients were enrolled from 2006 to 2012 (HCV, 1,308; HBV, 315; HCV-HBV, 31). During a median follow-up of 34 months, at least one liver nodule was detected in 271 patients, confirmed as hepatocellular carcinoma (HCC) in 128 (4-year cumI: 10.5%) and cholangiocarcinoma in 3. HCC incidence was higher in HCV (4-year cumI: 11.4% vs. 7.4%; P = 0.05). HCC fulfilled Milan criteria in 79.3%, leading to curative treatment in 70.4%. Liver decompensation occurred more frequently in HCV patients (4-year cumI: 10.8% vs. 3.6%; P = 0.0004). Virological eradication/control was achieved in 34.1% of HCV and 88.6% of HBV patients and was associated with a marked decrease in HCC, decompensation, and bacterial infection incidences. Survival was shorter in HCV patients (4-year cumI: 91.6% vs. 97.2%; P = 0.0002). Death (n = 102; missing data: 6) was attributed to liver disease in 48 (47%; liver cancer: n = 18; miscellaneous, n = 30) and extrahepatic causes in 48 (47%; bacterial infection: n = 13; extrahepatic cancers: n = 10; cardiovascular events: n = 5; miscellaneous, n = 20)., Conclusion: After 3 years of follow-up, extrahepatic events still explained half of deaths in patients with compensated VC. A strong decrease in complications was linked to virological eradication/control., (© 2015 by the American Association for the Study of Liver Diseases.)

Background: Hyperemesis gravidarum is the most severe form of nausea and vomiting of pregnancy. This condition has been rarely studied in France., Objectives: To study the clinical and biological features of a French cohort of women with hyperemesis gravidarum., Methods: Retrospective data was searched in medical records for all the women admitted for hyperemesis gravidarum in the gynecologic units of the university center of Tours between January 2001 and December 2010. Data were available for 109 women., Results: The prevalence of hyperemesis gravidarum was 3.9 per 1000 deliveries in our center. Half the women were not of French origin. The mean duration of the first hospitalization was 4.6±2.6 days (range: 1-17). Hyperemesis gravidarum was recurrent in 1/3 of the women. Routine liver function tests were found abnormal at admission or during hospitalization in 39.6% of cases with an increased ALT (>35IU/L) in 28.7% of patients. Women with elevated ALAT had more often a body mass index>25kg/m(2) (odds ratio [OR], 3.98; 95% confidence interval [CI], 1.29-12.59; P=0.01), a weight loss ≥6kg (OR, 4.52; CI, 1.53-13.77; P=0.002), and a hospital stay≥6 days (OR, 3.43; CI, 1.19-9.97; P=0.009). There was no difference in pregnancy outcomes between women with normal or increased ALT. Prothrombin time was decreased (<70%) in 25.6% of cases secondary to a vitamin K deficiency., Conclusion: This study shows that hyperemesis gravidarum in our center is frequently associated with a non-French origin, and that abnormal liver function tests and decreases of prothrombin time are common in this condition. Our results suggest that increased ALT is a factor of severity in hyperemesis gravidarum., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Objective: Intrahepatic cholestasis of pregnancy (ICP) is the most commonly encountered pregnancy-specific liver disease. This condition, with no proven maternal morbidity, has been associated with an increased risk of prematurity and intrauterine fetal death. There is, to date, no scientific obstetrical guideline for clinical practice in France. The objective of our study was to precise, in this situation, how French obstetricians manage patients suffering from ICP., Methods: We carried out, during 2010, a national descriptive practice survey of ICP management in France in association with the "Collège national des gynécologues-obstétriciens français". An inquiry form with 27 multiple-choice questions was sent to all obstetricians and gynecologist officiating in a maternity hospital recorded by the French Ministry of Health. The participants answered questions regarding diagnosis, perinatal management and treatment of ICP. Only the first answer received from each maternity hospital was analyzed., Results: Of the 575 maternity hospitals, 275 (41.6%) responded after one mail recovery. Among them, almost half used a standardized management protocol for ICP. In most of the cases, perinatal management was performed by obstetricians alone (73%), and in only 20% of the cases in collaboration with the specialist in hepatology. Induction of labor at 37-38 weeks was the most common policy for the majority of respondents (92.4%)., Conclusion: This is the first French national survey for ICP management. This study demonstrated that ICP is, in most of the cases, managed by the obstetrician alone, and that fetal risks warrants an active management with induction of labor in late pregnancy., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

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.

Background: Knowing the facts and displaying the proper attitudes and behaviors are critical in preventing the spread of infectious diseases. Hepatitis C is a common infection, but the public's understanding of it has not been studied., Methods: A convenience sample of 431 French adults, ages 18 to 81 years, completed a questionnaire designed to assess knowledge of hepatitis C and acquired immune deficiency syndrome. A group of nine medical experts also answered the hepatitis C questions., Results: The lay participants had many uncertainties about hepatitis C, and their beliefs frequently differed from medical understanding about hepatitis C. Their responses were correlated more closely with their own responses to the AIDS questions than with the experts' understanding of hepatitis C., Conclusions: Information regarding hepatitis C should emphasize the distinctions between hepatitis C and AIDS as well as between hepatitis C and hepatitis B and between seropositivity and infection. People should also be informed that blood donation is safe, that using injected drugs is the main risk factor for hepatitis C, that alcohol aggravates hepatitis C, that hepatitis C can cause cancer, that an effective treatment for hepatitis C exists, and that they are not put at risk by mere causal contact with people ill with hepatitis C., (Copyright 2002 Elsevier Science (USA).)

From 1981 to 1990 nine patients suffering from amebic liver abscess were under observation at the Tours hospital. Hepatic amebiasis is scarce in France. Most of the subjects have stayed in endemic areas. Most of the time patients are male adults suffering from fever and abdominal pains. In most cases the liver ultrasonography shows a single cut of the right lobe with variable and non specific aspects. Once the diagnosis has been given a metronidazole treatment must be prescribed. The diagnosis will be confirmed by serology reactions. Clinical supervision is essential. The clinical effectiveness of the treatment is spectacular. Comparatively it will take about six months until serology reactions and liver ultrasonography get back to normal. Management of hepatic amebiasis need exceptionally echo-guided percutaneous puncture or surgery.

Study Objective: To evaluate (1) the prevalence of protein-energy malnutrition in elderly patients; (2) the changes in nutritional status during the hospital stay; and (3) (main objective) the relationship between simple nutritional parameters and short-term in-hospital mortality., Design: Prospective time series at admission and on the 15th day of hospitalization., Setting: Medical care unit in a teaching hospital., Participants: Consecutive sample of 324 hospitalized patients greater than or equal to 70 years (86.4% of eligible patients). Norms of measurements were obtained from a referred sample of healthy control subjects (26 males and 36 females)., Main Outcome Measures: Mid-arm circumference, triceps skinfold thickness, serum albumin, prealbumin, and retinol-binding protein levels were measured in patients at admission and on the 15th day., Results: (1) Prevalence of PEM was 30% in male and 41% in female patients. (2) Both mid-arm circumference and serum albumin level decreased over the first 15 days of hospital stay (53 patients, paired t test, P less than 0.05). Triceps skinfold thickness did not change. (3) A step-wise discriminant-function analysis determined the utility of the parameters at admission as predictors of in-hospital mortality before the 15th day. Mid-arm circumference, triceps skinfold thickness, albumin, and prealbumin levels, as well as age, are predictors of in-hospital mortality, with 73% sensitivity, 69% specificity, and 70% of correctly classified patients of both sexes., Conclusions: Parameters used are predictors for short-term in-hospital mortality of elderly patients hospitalized in an acute medical unit. The lean body mass is preferentially mobilized for energy during hospitalization.

A 6 years retrospective study (1981-1986) of 153 consecutive cases of HBsAg positive acute hepatitis was carried out to assess the prevalence of delta virus infections in the Indre-et-Loire a district of the Loire Valley in France. Diagnostic value of the various serum markers of delta infection, i. e. HDAg, anti-HD and anti-HD IgM, were evaluated using immunoenzyme assays. During the survey, 22 cases of delta hepatitis were diagnosed (12 co-infections, 10 superinfections). They all involved young adults, 21 of them were drug-addicts, and one young woman was the consort of a drug-addict. In Indre-et-Loire, delta virus infection was responsible for half of acute HBsAg positive hepatitis among drug-users in the last 3 years of our study. Clinical and biological features of acute delta hepatitis were compared to those of the other HBsAg positive hepatitis: two cases of fulminant hepatitis occurred among the 12 co-infections; 4 of 6 superinfection that could be followed up to 6 months developed biopsy-proven chronic active hepatitis. Delta Ag was found constantly during the first week of the disease, its disappearance was always followed by a seroconversion to anti-HD after four weeks. Anti-delta IgM was an inconstant and late marker: it was detected within the first 4 weeks in only one case (a co-infection); it persisted only in superinfections. Our study shows that delta Ag is an efficient serum marker for the early diagnosis of acute delta hepatitis.