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Background & Aims: The impact of chronic liver disease on outcomes in patients with COVID-19 is uncertain. Hence, we aimed to explore this association., Methods: We explored the outcomes of all adult inpatients with COVID-19 in France, in 2020. We computed adjusted odds ratios to measure the associations between chronic liver disease, alcohol use disorders, mechanical ventilation and day-30 in-hospital mortality., Results: The sample comprised 259,110 patients (median [IQR] age 70 (54-83) years; 52% men), including 15,476 (6.0%) and 10,006 (3.9%) patients with chronic liver disease and alcohol use disorders, respectively. Death occurred in 38,203 (15%) patients, including 7,475 (28%) after mechanical ventilation, and 2,941 (19%) with chronic liver disease. The adjusted odds ratios for mechanical ventilation and day-30 mortality were 1.54 (95% CI 1.44-1.64, p <0.001) and 1.79 (1.71-1.87, p <0.001) for chronic liver disease; 0.55 (0.47-0.64, p <0.001) and 0.54 (0.48-0.61, p <0.001) for mild liver disease; 0.64 (0.53-0.76; p <0.001) and 0.71 (0.63-0.80, p <0.001) for compensated cirrhosis; 0.65 (0.52-0.81, p <0.001) and 2.21 (1.94-2.51, p <0.001) for decompensated cirrhosis; 0.34 (0.24-0.50; p <0.001) and 1.38 (1.17-1.62, p <0.001) for primary liver cancer; and 0.82 (0.76-0.89; p <0.001) and 1.11 (1.05-1.17; p <0.001) for alcohol use disorders. Chronic viral hepatitis; non-viral, non-alcoholic chronic hepatitis; organ, including liver, transplantation, and acquired immunodeficiency syndrome were not associated with COVID-19-related death., Conclusion: Chronic liver disease increased the risk of COVID-19-related death in France in 2020. Therapeutic effort limitation may have contributed to COVID-19-related death in French residents with a liver-related complication or an alcohol use disorder., Lay Summary: We studied the outcomes, including mechanical ventilation and day-30 mortality, of all adults with COVID-19 who were discharged from acute and post-acute care in France in 2020 (N = 259,110). Patients with mild liver disease; compensated cirrhosis; organ, including liver, transplantation; or acquired immunodepression syndrome were not at increased risk of COVID-19-related mortality. Patients with alcohol use disorders, decompensated cirrhosis, or primary liver cancer were at increased risk of COVID-19-related mortality but were less likely to receive mechanical ventilation. Our results suggest that therapeutic effort limitation may have contributed to the excess mortality in French residents with a liver-related complication or an alcohol use disorder., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

The FIB-4 index is a biomarker of advanced hepatic fibrosis in a context of fatty liver disease. The calculation of the FIB-4 index requires of age, serum ALT and AST transaminase levels and platelet count. A FIB-4 index<1.45 in a context of fatty liver disease excludes clinically significant hepatic fibrosis. Additional explorations are mandatory to excluded hepatic fibrosis for a a FIB-4 index>1.45 in a context of fatty liver disease. A complete hepatological workup is mandatory for a FIB-4 index>3.25 in a context of fatty liver disease., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Objectives: HIV/hepatitis C virus (HCV) co-infection leads to major complications, and noninvasive markers developed to stage liver fibrosis could be used as prognostic markers. We aimed to compare the performances of liver stiffness (LS), fibrosis-4 (FIB-4), and aspartate aminotransferase to platelet ratio index (APRI) to predict liver-related events in HIV/HCV co-infected patients., Patients and Methods: HIV/HCV co-infected patients from the ANRS CO13 HEPAVIH cohort were included if they had LS, FIB-4, and APRI measurements done in a window of 3 months. Primary outcome was the time between inclusion and occurrence of a liver-related event. Univariable and multivariable Fine and Gray models were performed. Predictive performances were compared by the area under the receiver operating characteristic (AUROC) differences after correction of optimistic by bootstrap samples. Best cutoffs to predict liver-related events were estimated by sensitivity and specificity maximization., Results: A total of 998 patients were included. Overall, 70.7% were men. Their median age was 46.8 years. According to LS value, 204 (20.4%) patients had cirrhosis. Overall, 39 patients experienced at least one liver-related event. In univariable analysis, LS AUROC curve was significantly superior to FIB-4 and APRI AUROC curves, being 87.9, 78.2, and 75.0%, respectively. After adjustment on age, CD4 levels, and insulin resistance, no differences were observed. The best cutoffs to identify patients at low or high risk of liver-related events were below 8.5, 1.00, and 0.35 and above 16.5, 4.00, and 1.75 for LS, FIB-4, and APRI, respectively., Conclusion: To predict HCV-related events, APRI had lower performance than LS and FIB-4. FIB-4 is as good as LS to predict HCV-related events, suggesting that it can be used for the management of HIV/HCV co-infected patients and replace LS.

It is widely accepted that human immunodeficiency virus (HIV) infection is a risk factor for increased severity of hepatitis C virus (HCV) liver disease. However, owing to better efficacy and safety of combination antiretroviral therapy (cART), and increased access to HCV therapy, whether this condition remains true is still unknown. Overall, 1,253 HCV mono-infected patients and 175 HIV/HCV co-infected patients with cirrhosis, included in two prospective French national cohorts (ANRS CO12 CirVir and CO13 HEPAVIH), were studied. Cirrhosis was compensated (Child-Pugh A), without past history of complication, and assessed on liver biopsy. Incidences of liver decompensation (LD), hepatocellular carcinoma (HCC), and death according to HIV status were calculated by a Fine-Gray model adjusted for age. Propensity score matching was also performed to minimize confounding by baseline characteristics. At baseline, HIV/HCV patients were younger (47.5 vs. 56.0 years; P < 0.001), more frequently males (77.1% vs. 62.3%; P < 0.001), and had at baseline and at end of follow-up similar rates of HCV eradication than HCV mono-infected patients. A total of 80.4% of HIV/HCV patients had an undetectable HIV viral load. After adjustment for age, 5-year cumulative incidences of HCC and decompensation were similar in HIV/HCV and HCV patients (8.5% vs. 13.2%, P = 0.12 and 12.8% vs. 15.6%, P = 0.40, respectively). Overall mortality adjusted for age was higher in HIV/HCV co-infected patients (subhazard ratio [SHR] = 1.88; 95% confidence interval [CI], 1.15-3.06; P = 0.011). Factors associated with LD and HCC were age, absence of sustained virological response, and severity of cirrhosis, but not HIV status. Using a propensity score matching 95 patients of each group according to baseline features, similar results were observed. Conclusion: In HCV-infected patients with cirrhosis, HIV co-infection was no longer associated with higher risks of HCC and hepatic decompensation. Increased mortality, however, persisted, attributed to extrahepatic conditions., (© 2018 by the American Association for the Study of Liver Diseases.)

Background: Coffee intake has been shown to modulate both the effect of ethanol on serum GGT activities in some alcohol consumers and the risk of alcoholic cirrhosis in some patients with chronic diseases. This study aimed to analyze the impact of coffee intake and alcohol consumption on advanced liver fibrosis (ALF) in HIV-HCV co-infected patients., Methods: ANRS CO13-HEPAVIH is a French, nationwide, multicenter cohort of HIV-HCV-co-infected patients. Sociodemographic, behavioral, and clinical data including alcohol and coffee consumption were prospectively collected using annual self-administered questionnaires during five years of follow-up. Mixed logistic regression models were performed, relating coffee intake and alcohol consumption to ALF., Results: 1019 patients were included. At the last available visit, 5.8% reported high-risk alcohol consumption, 27.4% reported high coffee intake and 14.5% had ALF. Compared with patients with low coffee intake and high-risk alcohol consumption, patients with low coffee intake and low-risk alcohol consumption had a lower risk of ALF (aOR (95% CI) 0.24 (0.12–0.50)). In addition, patients with high coffee intake had a lower risk of ALF than the reference group (0.14 (0.03–0.64) in high-risk alcohol drinkers and 0.11 (0.05–0.25) in low-risk alcohol drinkers)., Conclusions: High coffee intake was associated with a low risk of liver fibrosis even in HIV-HCV co-infected patients with high-risk alcohol consumption., Competing Interests: The authors declare no conflict of interest. The funding sources were not involved in the study design, data analysis, or in the writing and submission of the manuscript.

Introduction: The use of human albumin for the management of cirrhosis has increased. Recommendations have been published for therapeutic paracentesis (TP), spontaneous bacterial peritonitis (SBP), and type 1 hepatorenal syndrome (HRS). The goal of this survey was to assess the prescription practices of French hepatogastroenterologists., Methods: All hepatogastroenterologists were contacted. The questionnaire evaluated (1) the use of albumin in validated indications and (2) the prescription of albumin for nonvalidated clinical situations., Results: Responses were analyzed from 451 (50.1%) practitioners. The mean age was 40 years (range, 24 to 67 y). Physicians practiced in a university hospital (47.7%) or a general hospital (45.8%). There were 56.7% senior practitioners. Overall 99.6% of the practitioners compensated for TP. Albumin was used by 87.8% of the physicians, with a fixed dose being used by 84.6%. For SBP, 94% of the physicians used albumin concomitantly with antibiotics. The recommended protocol was followed by 56.2% of the practitioners: more often by senior university hospital practitioners than by senior general hospital practitioners (P=0.015). About 66.5% used albumin infusion for the diagnosis of HRS: used more often by senior university hospital practitioners (P=0.0006). Albumin was used concomitantly with vasopressor treatment by 84%; the dose and the duration varied considerably. About 23.5% used albumin for severe bacterial infection, 47.9% for severe hyponatremia, 43.9% for severe hypoalbuminemia, and 65.9% for hydrothorax., Conclusions: In this large French survey, albumin is only prescribed in accordance with recommendations for TP. The schedule for SBP is followed by only 56% of the practitioners. The use of albumin for HRS is not adapted to recommendations, which are not well known, suggesting that they should be more diffused.

Background: Human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients with cirrhosis have long been considered to be difficult to treat, and real-life efficacy and tolerance data with all-oral direct-acting antiviral (DAA) combinations in these patients are scarce., Methods: Cirrhotic HIV/HCV-coinfected patients enrolled in the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) CO13 HEPAVIH cohort initiating an all-oral DAA regimen were consecutively included. A negative HCV RNA result at 12 weeks of follow-up or thereafter was assumed as a sustained virologic response (SVR12). Adjusted exact logistic regression was used to study factors associated with treatment outcome., Results: We included 189 patients who initiated an all-oral DAA regimen with the following characteristics: median age 53.2 years; 74.6% male; Centers for Disease Control and Prevention classification A/B/C: 37%/31%/32%; Child-Pugh class A/B/C: 91%/8%/1%; 87% with HIV RNA <50 copies/mL; 99% on antiretrovirals; median CD4 count: 489 cells/µL; HCV treatment naive 29%; HCV genotype 1/2/3/4: 58%/4%/17%/21%. Sofosbuvir (SOF) + daclatasvir ± ribavirin (RBV) was used in 123 patients, SOF + RBV in 30, SOF + simeprevir in 11, and SOF + ledipasvir in 23. An SVR12 was reported in 93.1% of the patients (95% confidence interval, 88.5%-96.3%). In adjusted analyses, no difference was found between 12 or 24 weeks of treatment, in patients receiving RBV or not, and in treatment-naive vs experienced patients. Premature stop of DAA was reported for 8 patients. One patient died during treatment (unknown cause), and 12 other patients developed liver-related events., Conclusions: In this prospective real-life cohort, all-oral DAA regimens were well tolerated and associated with a high virologic efficacy in cirrhotic HIV/HCV-coinfected patients. This should not alleviate the surveillance for liver-related events in these patients., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Objectives: To measure azygos, portal and aortic flow by two-dimensional cine phase-contrast magnetic resonance imaging (2D-cine PC MRI), and to compare the MRI values to hepatic venous pressure gradient (HVPG) measurements, in patients with cirrhosis., Methods: Sixty-nine patients with cirrhosis were prospectively included. All patients underwent HVPG measurements, upper gastrointestinal endoscopy and 2D-cine PC MRI measurements of azygos, portal and aortic blood flow. Univariate and multivariate regression analyses were used to evaluate the correlation between the blood flow and HVPG. The performance of 2D-cine PC MRI to diagnose severe portal hypertension (HVPG ≥ 16 mmHg) was determined by receiver operating characteristic curve (ROC) analysis, and area under the curves (AUC) were compared., Results: Azygos and aortic flow values were associated with HVPG in univariate linear regression model. Azygos flow (p < 10(-3)), aortic flow (p = 0.001), age (p = 0.001) and presence of varices (p < 10(-3)) were independently associated with HVPG. Azygos flow (AUC = 0.96 (95 % CI [0.91-1.00]) had significantly higher AUC than aortic (AUC = 0.64 (95 % CI [0.51-0.77]) or portal blood flow (AUC = 0.40 (95 % CI [0.25-0.54])., Conclusions: 2D-cine PC MRI is a promising technique to evaluate significant portal hypertension in patients with cirrhosis., Key Points: • Noninvasive HVPG assessment can be performed with MRI azygos flow. • Azygos MRI flow is an easy-to-measure marker to detect significant portal hypertension. • MRI flow is more specific that varice grade to detect portal hypertension.

Background: In patients with cirrhosis, decreased rotational thromboelastometry (ROTEM) parameters suggest hypocoagulability secondary to liver dysfunction. However, observed normal or increased thrombin generation suggests preserved haemostasis and/or a procoagulant state. The correlated levels of both coagulation factors and inhibitors also support preserved haemostasis., Objective: The objective of this study is to investigate the correlation between three specific approaches of haemostasis (ROTEM, thrombin generation and coagulation factors/inhibitors) on the same plasma sample from patients with cirrhosis., Design: A prospective, observational study., Setting: Single university hospital., Participants: Forty patients with cirrhosis., Intervention: Measurement of the following factors: model for end-stage liver disease (MELD) scores; ROTEM maximum clot firmness (ROTEM-MCF) in EXTEM, INTEM, FIBTEM assays; fibrinogen; factors V and VIII; von Willebrand factor; protein C; protein S; antithrombin; and the thrombin generation test (TGT) enabling the calculation of endogenous thrombin potential without and with thrombomodulin, and the ratio of endogenous thrombin potential with-to-without thrombomodulin (regarded as an index of hypercoagulability)., Results: ROTEM-MCF values were distributed within the normal and hypocoagulation ranges; were correlated to variations in factor V, fibrinogen, protein C and S and antithrombin; and were inversely correlated to MELD scores (ρ > 0.5; P < 0.05). Levels of von Willebrand factor were above normal and were not correlated with any other factor levels. After addition of thrombomodulin, endogenous thrombin potential values were distributed within or above normal values. Factor V variation was correlated to the ratio of endogenous thrombin potential with-to-without thrombomodulin., Conclusion: ROTEM indicated hypocoagulability correlated to liver dysfunction. In contrast, the TGT indicated a preserved or even increased coagulation profile (which was supported by the correlation between coagulant factors and inhibitors) and a potential for hypercoagulability inversely correlated to the degree of liver dysfunction. ROTEM may not be appropriate for haemostasis assessment in patients with liver cirrhosis and could lead to the unnecessary transfusion of fresh frozen plasma., Trial Registration: S.C. 3024 - ID RCB: 2012-A01728-35.

Background & Aims: The efficacy and safety of triple therapy combining boceprevir (BOC) or telaprevir (TVR) with pegylated interferon-alfa and ribavirin (PegIFN/RBV) has rarely been investigated in human immunodeficiency virus/hepatitis C virus (HIV/HCV) genotype 1-coinfected patients with cirrhosis., Methods: We conducted a European (France, Italy, Germany, Netherlands) multicentre study of triple therapy in cirrhotic HIV/HCV GT1-coinfected patients., Results: Fifty-nine patients (47 TVR, 12 BOC) were studied. Median CD4 cell count was 457 (293-578)/mm(3), and HIV viral load was <50 copies/ml in 93% of patients. The HCV genotype was GT1a (78%) or GT1b (13%). Previous PegIFN/RBV therapy had resulted in non-response (73%) or relapse (12%), and 15% of patients were treatment-naïve. The sustained virological response rate at week 12 (SVR12) was 53% overall (57% with TVR, 36% with BOC). A baseline HCV-RNA level <800 000 IU/ml tended to be associated with SVR12 (65 vs 42%, P = 0.11). In multivariate analysis, a virological response at week 4 after BOC or TVR initiation was significantly associated with SVR12 (P = 0.040). Early discontinuation of triple therapy was frequent (n = 26, 44%), because of non-response/breakthrough (65%) or adverse events (AEs) (35%). Three patients died. Severe anaemia (<9 g/dl) occurred in 14 patients (25%), leading to RBV dose reduction (22%), erythropoietin use (56%) or blood transfusion (14%). In multivariate analysis, lack of RBV dose reduction was significantly associated with severe AEs (P = 0.006)., Conclusions: More than half of HIV/HCV GT1-coinfected patients with cirrhosis achieved a SVR12. To avoid unnecessary adverse effects, therapy should be discontinued if no response is obtained at week 4., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: Quantitative shear wave elastography was shown to be an effective tool for the non-invasive diagnosis and staging of chronic liver diseases. The liver shear modulus, estimated from the propagation velocity of shear waves, is correlated to the degree of fibrosis and can therefore be used for the non-invasive staging of fibrosis., Methods: We performed a clinical prospective study in a total of 120 patients with various chronic liver diseases to compare the accuracy of supersonic shear imaging (SSI), a technique based on acoustic radiation and ultrafast ultrasound imaging, to 1D transient elastography (FibroScan) for the staging and grading of fibrosis as assessed by liver biopsy. Since shear wave propagation spectroscopy can also provide additional mechanical information on soft tissues, such as viscosity, we also investigated those new mechanical parameters as possible predictors of fibrosis, steatosis, and disease activity., Results: SSI was successfully performed in 98.3% of patients and it was shown to be as accurate as FibroScan for the staging of fibrosis both for the whole population (N=120) and for the subgroup with viral hepatitis (n=70) (AUC=0.85 [0.77-0.96] and 0.89 [0.81-0.97] for significant fibrosis, AUC=0.90 [0.83-0.97] and 0.87 [0.75-0.98] for cirrhosis, with respect to SSI [n=68/70] and FibroScan [n=66/68]). Viscosity could also be used to stage the degree of fibrosis (AUC=0.76 [0.64-0.87] for significant fibrosis and AUC=0.87 [0.74-0.99] for cirrhosis), for the subgroup of patients with viral hepatitis (n=67/70) but was a poor predictor of disease activity and steatosis levels., Conclusions: Supersonic shear imaging is a robust technique for the staging of liver fibrosis. Liver viscosity was found to be correlated with fibrosis but not to steatosis or disease activity., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Alcoholic liver disease (ALD) causes more than 5000 deaths per year in France. Most of those deaths could be prevented by an early diagnosis, which would give the patients the opportunity to modify their alcohol consumption while liver lesions are still reversible. Hepatic histology is the main parameter that predicts morbidity and mortality in patients with ALD. Non-invasive methods such as biomarker tests (e.g. FibroTest(®) or FibroMetre A(®)) or hepatic elastography (FibroScan(®)) may allow diagnosing alcohol-induced liver lesion without systematic biopsy. Despite promising preliminary results, those methods are not validated yet in ALD. A validation of non-invasive methods for ALD could allow a large screening of the severe forms of this pathology., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Background and Aims: Hepatic stellate cells, the major producers of extracellular matrix in the liver, and hepatocytes bear CXCR4 and CCR5, the two main co-receptors for entry of the human immunodeficiency virus (HIV). In vitro studies suggest that HIV-envelope proteins can modulate the replication of hepatitis C virus (HCV) and fibrogenesis. We investigated the influence of HIV tropism on liver fibrosis and the concentration of HCV RNA in HIV-HCV co-infected patients., Methods: We used a phenotypic assay to assess HIV tropism in 172 HCV-HIV co-infected patients: one group (75 patients) had mild fibrosis (score ≤F2) and the other (97 patients) had severe fibrosis (score >F2). We also assessed the relationship between HIV tropism and HCV RNA concentration in all these patients. We also followed 34 of these patients for 3 years to determine the evolution of HIV tropism and liver fibrosis, estimated by liver stiffness., Results: Initially, most patients (91.8%) received a potent antiretroviral therapy. CXCR4-using viruses were found in 29% of patients. The only factor associated with a CXCR4-using virus infection in multivariate analysis was the nadir of CD4 cells: <200/mm(3) (OR: 3.94, 95%CI: 1.39-11.14). The median HCV RNA concentrations in patients infected with R5 viruses, those with dual-mixed viruses and those with X4 viruses, were all similar. The prevalence of CXCR4-using viruses in patients with mild fibrosis (≤F2) (31%) and those with severe fibrosis (F3-F4) (28%, p = 0.6) was similar. Longitudinal analyses showed that the presence of CXCR4-using viruses did not increase the likelihood of fibrosis progression, evaluated by measuring liver stiffness., Conclusions: The presence of CXCR4-using viruses in patients receiving a potent antiretroviral therapy does not influence HCV RNA concentration or liver fibrosis.

Portal hypertension, the most important complication with cirrhosis of the liver, is a serious disease. Sorafenib, a tyrosine kinase inhibitor is validated in advanced hepatocellular carcinoma. Because angiogenesis is a pathological hallmark of portal hypertension, the goal of our study was to determine the effect of sorafenib on portal venous flow and portosystemic collateral circulation in patients receiving sorafenib therapy for advanced hepatocellular carcinoma. Porto-collateral circulations were evaluated using a magnetic resonance technique prior sorafenib therapy, and at day 30. All patients under sorafenib therapy had a decrease in portal venous flow of at least 36%. In contrast, no specific change was observed in the azygos vein or the abdominal aorta. No portal venous flow modification was observed in the control group. Sorafenib is the first anti-angiogenic therapy to demonstrate a beneficial and reversible decrease of portal venous flow among cirrhotic patients.

Background: The efficacy of a maintenance therapy in non-responder patients with chronic hepatitis C has been essentially evaluated by histological semiquantitative scores., Aim: The aim was to evaluate the efficiency of 2 years of treatment with peginterferon alpha-2a vs alpha-tocopherol in these patients by histology, morphometry and blood markers of fibrosis., Method: Hundred and five HCV patients with a Metavir fibrosis score > or = 2 were randomized to receive peginterferon alpha-2a 180 microg/week (PEG) (n=55) or alpha-tocopherol (TOCO) 1000 mg/day (n=50) for 96 weeks. The primary endpoint was improvement or stabilization of the Metavir fibrosis score by biopsy performed at week 96. Secondary endpoints included a quantitative assessment of fibrosis by morphometry and changes in blood markers of fibrosis., Results: There was no difference at baseline between PEG and TOCO according to the metavir (83.3 vs 86.8%, P=0.751) stage. The median fibrosis rate, measured with morphometry was 2.72 and 2.86% at day 0, and 3.66 and 2.82% at week 96, in the PEG and TOCO groups (P=0.90) respectively. However, the percentage of patients with metavir activity grade improvement was significantly higher in the PEG group vs the TOCO group (52.8 vs 23.7%, P=0.016). Non-invasive markers analysis did not show any significant change in both groups., Conclusion: Long-term therapy with peginterferon alpha-2a did not reduce liver fibrosis degree assessed by morphometry and blood tests as compared with alpha-tocopherol. Blood tests could be useful to assess liver fibrosis changes in clinical trials.

Patients with cirrhosis are immunocompromised and have an increased risk of infection, with a worse outcome. Some of those infections may be prevented by vaccination. Immunization can reduce the morbidity and mortality associated with cirrhosis. Immunizations against hepatitis A and B viruses, influenza and pneumococcus are recommended by the French Haute Autorité de Santé since 2007. Vaccination against hepatitis A is recommended in non-immunized cirrhotic patients. Vaccination against hepatitis B is recommended in every cirrhotic patient with no serological markers, and post-vaccinal antibodies titer should be checked. Annual influenza immunization can be done in cirrhotic patients, and pneumococcal polysaccharide vaccine should be repeated after 3-5 years. Few data regarding vaccination coverage are available, but studies suggest that immunization rates are too low in this population.

Since highly active antiretroviral therapies became available, the future of HIV-infected patients has been transformed. However, 20 to 25% of HIV patients are co-infected with hepatitis B or C viruses, and the course of these diseases has worsened, since these patients have an enhanced sensitivity to the hepatic toxicity of antiretrovirals. The relation between high antiretroviral concentrations and toxicity has been clearly demonstrated with certain protease inhibitors and non-nucleoside reverse transcriptase inhibitors (NNRTI) that have a predominantly hepatic metabolism (CYP4503A4). The nucleoside reverse transcriptase inhibitors (NRTI) are not predominantly metabolized by the liver, but may nevertheless be toxic for the liver through mitochondrial involvement. The hepatic toxicity observed in a patient treated with early or delayed antiretrovirals may be due to a cytolytic, cholestatic or mixed, direct or indirect, mechanism. Before initiating antiretroviral treatments, hepatic fibrosis must be explored (punch biopsy, biological fibrosis test, and Child-Pugh's score). It is recommended that the most hepatotoxic drugs be avoided, notably didanosine, didanosine+stavudine, nevirapine, and full-dose ritonavir. Although it is possible to initiate an antiretroviral at the standard dose in patients with cirrhosis (the therapeutic margin with antiretrovirals is wide), early assays are essential, particularly with PI and NNRTI, to adjust the dose and avoid adverse events. In any event rigorous monitoring is a must.