The relationship between liver stiffness measurement and outcome in patients with chronic hepatitis C and cirrhosis: a retrospective longitudinal hospital study.

BACKGROUND: There is a relationship between liver stiffness measurement (LSM) and outcome of HCV patients. AIM: To evaluate the performance of LSM to predict outcome of HCV patients at risk of liver-related complication. METHODS: We established a retrospective longitudinal cohort of 341 HCV patients with unequivocal cirrhosis. All underwent LSM and were followed from September 2006 to July 2015. Outcome measure was a composite end-point of end-stage liver disease (ESLD) and/or hepatocellular carcinoma (HCC). Cox models and areas under receiver operating characteristic (AUROC) curves were used to evaluate independent risk factors of outcome. RESULTS: Overall, LSM was below the 12.5 kPa threshold in 129 (37.8%) patients, including three-fourth and one-third of patients with or without a sustained virological response respectively. Liver disease progressed in 136 (39.9%) patients after a median observational period of 23.5 months. Older age, male gender, alcohol use disorders, metabolic syndrome and LSM were independent risk factors of liver disease progression. Age, alcohol use disorders and LSM were independently associated with ESLD. Age, gender and metabolic syndrome, but not LSM, were associated with HCC. The AUROC curves for disease progression, ESLD and HCC were 0.67, 0.70 and 0.58 respectively. Patients with a liver stiffness >12.5 kPa were at the highest risk of liver disease progression; below 12.5 kPa, liver stiffness was not discriminant. CONCLUSION: Liver stiffness measurement is not a surrogate of disease progression of HCV patients with cirrhosis. HCV patients with cirrhosis should undergo the recommended follow-up, regardless of liver stiffness measurement.

T-cell responses to hepatitis B splice-generated protein of hepatitis B virus and inflammatory cytokines/chemokines in chronic hepatitis B patients. ANRS study: HB EP 02 HBSP-FIBRO.

A new hepatitis B virus (HBV) protein, hepatitis B splice-generated protein (HBSP), has been detected in liver biopsy specimens from patients with chronic active hepatitis. The aim of this study was to characterize the phenotype and functions of peripheral HBSP-specific T cells and to determine whether these T-cell responses may be implicated in liver damage or viral control. Two groups of patients were studied: HBV-infected patients with chronic active hepatitis and HBV-infected patients who were inactive carriers of hepatitis B surface antigen. HBSP-specific T-cell responses were analysed ex vivo and after in vitro stimulation of peripheral blood mononuclear cells. Soluble cytokines and chemokines were analysed in sera and in cell culture supernatants. Few HBSP- or capsid-specific T-cell responses were detected in patients with chronic active hepatitis whereas frequency of HBV-specific T cells was significantly higher in inactive carrier patients. HBSP activated CD8+ and CD4+ T cells that recognized multiple epitopes and secreted inflammatory cytokines. The IL-12 level was significantly lower in sera from asymptomatic carrier patients compared to patients with chronic active hepatitis. IL-12 and IP-10 levels in the sera were significantly and independently correlated with both alanine amino transferase and HBV DNA levels. Our results show that the HBSP protein activates cellular immune responses in HBV-infected patients but has probably no prominent role in liver damage. The pattern of cytokines and chemokines in sera was linked to HBV viral load and was consistent with the level of inflammation during chronic hepatitis.

The accuracy of the FIB-4 index for the diagnosis of mild fibrosis in chronic hepatitis B.

BACKGROUND: The Fib-4 index is a simple and inexpensive biomarker to delineate liver fibrosis in chronic hepatitis C. AIM: To assess the accuracy of the FIB-4 index in chronic hepatitis B. METHODS: We compared the FIB-4 index with 138 synchronous liver biopsies and with 372 synchronous FibroTest performed either in France or in an endemic area (Mayotte, an overseas collectivity of France). RESULTS: The FIB-4 index allowed the correct identification of patients with nil-to-moderate fibrosis with an area under the receiving operating characteristic curve of 0.81 (P < 0.001), increasing as a function of the length of the liver biopsy (up to 0.94 for liver biopsies >or=20 mm). A cut-off value

[Chronic hepatitis B: unusual situations: dialysis, renal transplantation and pre-emptive therapy in immune compromised patients]. / Hépatite chronique B : situations rares : dialyse, transplantation rénale et traitements pré-emptifs en situation d'immunosuppression.

Parenteral and community-acquired routes of contamination sanguins of hepatitis B virus (HBV) explain its frequency (9 to 20%) in dialysis patients and kidney recipients. In dialysis, HBV infection has few impact on morbidity and mortality; by contrast, in kidney recipients HBV: 1. reduces the allograft survival; 2. the patients survival in association with a frequent and rapid evolution to cirrhosis and hepatocellular carcinoma or rare cholestatic fibrosis. Finally, cirrhosis contra-indicates renal transplantation alone given its poor short-term prognosis and a combined liver-kidney transplantation has to be discussed. Thus, it is necessary to evaluate the liver severity of the liver disease. The treatement of HBV in allograft recipients and dialysis is based on nucleos(t)idic analogues like in the general population with the same advantages and questions. The variations of the immune status either in an HBV-infected patients at the induction or at the reduction of chemotherapies (solid tumors or hemopathies) or allograft transplantation may result in two, potentially severe, events in miror: a reactivation or a spontaneous discontinuation of viral replication (seronconversion). These risks evidence that any HBs Ag carrier exposed to immune suppression has to be diagnosed, evaluated for viral replication and underlying liver disease and has to be treated by a so-called pre-emptive treatment based on analogues.

[Occult hepatitis B virus infection]. / L'hépatite B occulte.

Occult hepatitis B virus (HBV) infection is a peculiar form of chronic viral infection identified since the early 80's and can be defined as the presence of HBV DNA in the serum and/or in the liver tissue of patients negative for the HBV surface antigen (HBsAg) using usual serological tests. The data about the prevalence of occult HBV infection are contrasting and the reported prevalences in various categories of individuals are highly diverse. The molecular basis of the occult HBV infection is the covalently closed-circular DNA (cccDNA) that persists in the cell nuclei and that serves as a template for gene transcription. The physiopathology of occult HBV infection is still unclear. However, the available data suggest that the host's immune response, the co-infections with other infectious agents and epigenetic factors may play important roles in indicing the occult status. The clinical relevance of occultHBVinfection remains debated but it may impact in four clinical contexts: 1) the transmission of the infection by blood transfusion or organ transplantation; 2) the acute reactivation when an immunosuppressive status occurs mainly in patients with isolated anti-HBc (chemotherapy, transplantations, immunodepression, new immunosuppressive therapy as anti-CD20 or anti TNF); 3) the potent but non proved progression of liver fibrosis in HCV infected patients or in patients with cryptogenetic liver disease; and, 4. the risk factor for hepatocellular carcinoma development.

[The role of contrast-enhanced ultrasonography for the detection of hepatocellular carcinoma]. / La place de l'échographie de contraste dans la détection du carcinome hépatocellulaire.

The incidence of the hepatocellular carcinoma (HCC) is increasing in Occident, as well as in France. Primary prevention is the only solution for early detection. The combination of ultrasound (US) and alphaFP each 4 to 6 Months dosage has many limitations. The sensitivity of US examination is rather poor (less than 70% for lesions below 2 cm in diameter) and serum alphaFP values remain normal in almost 50% of HCC. US contrast agents (USCAs) with perfluorocarbon gases increase the backscattered signals during all phases of the liver transit, including arterial, portal and delayed phases. Hepatocellular lesions exhibit a specific kinetics with strong enhancement during arterial phase, and rapid wash-out during portal and delayed phases. USCAs increase the detection of HCCs and allow characterization of additional focal lesions found in cirrhotic livers (regenerative and dysplastic nodules, haemangiomas.). Indeed, regenerative nodules contrast uptake is synchronous to the surrounding parenchyma, and usually disappear during portal and delayed phases. However, US in cirrhosis remains a difficult examination, with limitations due to limited access to sub-diaphragmatic localization, attenuation of the ultrasound beam and shortness of the arterial phase.

Hepatitis C and human immune deficiency coinfection at the era of highly active antiretroviral therapy.

Interactions between human immunodeficiency virus (HIV) and hepatitis C virus (HCV) have been widely studied before the introduction of highly active antiretroviral therapies (HAART). We reviewed the potential impact of HAART on hepatitis C as well as the interactions between HIV and HCV therapies. Physicians should be aware of the potential risk of: (i) symptomatic liver disease in HCV-HIV-coinfected patients at the era of triple antiretroviral therapy; (ii) potential liver deterioration paralleling immune restoration; (iii) lack of impact of triple antiretroviral therapy on HCV load; and (iv) potential drug-related hepatitis which may modify the natural history of HCV-related liver disease. Liver biopsies should be performed regularly in these patients in order to identify patients with severe liver disease who require early initiation of anti-HCV therapy under close monitoring of their immune status. Treatment is, to date, based on the combination of ribavirin and interferon with an expected sustained response rate around 25%. An important unresolved issue is to better delineate the temporal place of anti-HCV and anti-HIV antiviral therapies. At least in coinfected patients with significant liver disease, namely necro-inflammatory activity and/or fibrosis >or= 2, we believe that anti-HCV therapy is the priority since it lessens the risk of drug-induced hepatitis and of hepatitis due to immune restoration.