Non-invasive tests for fibrosis and liver stiffness predict 5-year survival of patients chronically infected with hepatitis B virus.

BACKGROUND: Liver stiffness and non-invasive tests predict overall survival in chronic hepatitis C. However, in patients chronically infected with hepatitis B virus (HBV), only the association between liver stiffness and the risk of hepatocellular carcinoma has been published. AIM: To evaluate the 5-year prognostic value of liver stiffness, non-invasive tests of liver fibrosis, and liver biopsy, to predict overall survival in chronic hepatitis B. METHODS: In a consecutive cohort, we prospectively assessed fibrosis, with liver stiffness, FibroTest, APRI, FIB-4 and liver biopsy (if indicated). We examined death and liver transplantation during a 5-year follow-up, and factors associated with overall survival. RESULTS: A total of 600 patients (men 64%, mean age 42 years, inactive carriers 36%) with chronic hepatitis B were included. At 5 years, 25 patients were dead (13 liver-related deaths) and four patients had liver transplantation. Overall survival was 94.1% and survival without liver-related death 96.3%. No liver-related death was observed in inactive carriers. Survival was significantly decreased in patients diagnosed with severe fibrosis, whatever the non-invasive method used (P < 0.0001), or liver biopsy (P = 0.02). Patients' prognosis decreased as liver stiffness and FibroTest increased. In multivariate analysis, FibroTest and liver stiffness had the highest hazard ratio with survival. The association persisted after adjustment on age, necro-inflammatory histological activity presumed by ActiTest and treatment. CONCLUSIONS: Liver stiffness measurement or FibroTest can predict survival in chronic HBV infection. Thus, these tools may help physicians to early assess prognosis and discuss specific treatments, such as liver transplantation.

Transient elastography and biomarkers for liver fibrosis assessment and follow-up of inactive hepatitis B carriers.

BACKGROUND: Non invasive methods for fibrosis evaluation remain to be validated longitudinally in hepatitis B. AIM: To evaluate longitudinally transient elastography (TE) and biomarkers for liver fibrosis assessment and follow-up of hepatitis B virus (HBV) inactive carriers. METHODS: Three hundred and twenty-nine consecutive HBeAg-negative HBV patients (201 inactive carriers) who underwent TE, Fibrotest and aspartate to platelet ratio index (APRI) the same day were studied. RESULTS: TE (median 4.8 vs. 6.8 kPa, P < 0.0001), Fibrotest (0.16 vs. 0.35, P < 0.0001) and APRI values (0.28 vs. 0.43, P < 0.0001) were significantly lower in inactive carriers than in the remaining patients whereas they did not differ among inactive carriers according to HBV DNA levels. In 82 inactive carriers with repeated examinations, although differences were observed among individual patients, TE values did not differ significantly over time (median intra-patient changes at end of follow-up relative to baseline: -0.2 kPa, P = 0.12). Conversely, significant fluctuations were observed for Fibrotest (+0.03, P = 0.012) and APRI (-0.01, P < 0.05). Eleven inactive carriers (5.5%) had initial elevated TE values (>7.2 kPa) confirmed during follow-up in two with significant fibrosis (F2 and F3) on liver biopsy. CONCLUSION: Non-invasive tools, particularly TE, could be useful, in addition to HBV DNA and transaminase levels, for follow-up of HBV inactive carriers as well as better selection of patients who require a liver biopsy.

Changes of non-invasive markers and FibroScan values during HCV treatment.

The recent advent of non-invasive methods for assessment of fibrosis allows serial assessments in all patients with hepatitis C. The aim of this prospective study was to evaluate changes in liver fibrosis, as measured with non-invasive methods, in a large cohort of HCV-infected patients with and without treatment. From May 2003 through March 2006, all previously untreated HCV-infected patients were enrolled in this study. Liver fibrosis was staged with FibroScan and Fibrotest at inclusion, then every year in untreated patients, and at the end of treatment and 6 months later in treated patients. The study population consisted of 416 patients, of whom 112 started treatment after enrolment. In the treatment group, FibroScan and Fibrotest values were significantly higher before and after treatment than in untreated patients at baseline and after 1 year. However, there was no significant difference between treated and untreated patients at the end of follow-up. FibroScan and Fibrotest values fell in all treated patients, whatever their virological response. In multivariate analysis, treatment was the only factor independently associated with a fall in the FibroScan value. In conclusion, whatever the virological response, treatment for HCV infection is associated with an improvement of FibroScan and Fibrotest values. Further studies are needed to compare these non-invasive methods with liver biopsy. These non-invasive methods, and especially FibroScan, should be useful for assessing treatment efficacy in clinical trials of new drugs.

Liver fibrosis on account of chronic hepatitis C is more severe in HIV-positive than HIV-negative patients despite antiretroviral therapy.

The recent availability of non-invasive tools to measure liver fibrosis has allowed examination of its extent and determination of predictors in all patients with chronic hepatitis C virus (HCV) infection. On the other hand, most information on hepatic fibrosis in HCV/human immunodeficiency virus (HIV)-coinfected patients has been derived from liver biopsies taken before highly active antiretroviral therapy (HAART) was widely available. All consecutive HCV patients with elevated aminotransferases seen during the last 3 years were evaluated and liver fibrosis measured using transient elastography (FibroScan) and biochemical indexes. Patients were split according to their HIV serostatus. A total of 656 (69.6%) HCV-monoinfected and 287 (30.4%) HIV/HCV-coinfected patients were assessed. Mean CD4 count of coinfected patients was 493 cells/muL and 88% were under HAART (mean time, 4.2 +/- 2.4 years). Advanced liver fibrosis or cirrhosis was recognized in 39% of the coinfected and 18% of the monoinfected patients (P < 0.005). A good correlation was found between FibroScan) and biochemical indexes [AST to platelet ratio index (r = 0.405, P < 0.0001), FIB-4 (r = 0.393, P < 0.0001) and Forns (r = 0.407, P < 0.0001)], regardless of the HIV status. In the multivariate analysis, age >45 years, body mass index (BMI) >25 kg/m(2), and HIV infection were independently associated with advanced liver fibrosis or cirrhosis. HIV/HCV-coinfected patients have more advanced liver fibrosis than HCV-monoinfected patients despite the immunologic benefit of HAART.

Peginterferon alpha-2b plus ribavirin for treatment of chronic hepatitis C with severe fibrosis: a multicentre randomized controlled trial comparing two doses of peginterferon alpha-2b.

We compared sustained virological response (SVR) in chronic hepatitis C patients with severe fibrosis treated with pegylated interferon (Peg-IFN) alpha-2b 1.5 microg/kg/week or 0.75 microg/kg/week in combination with ribavirin 800 mg/day for 48 weeks. This was a multicentre randomized controlled study. SVR was observed in 44.5% (45/101) of patients treated with the standard dose of Peg-IFN and 37.2% (38/102) of patients treated with the low dose (NS). In patients with genotypes 1, 4 and 5, SVR was observed in 25.0% of patients who received the standard dose and 16.9% of patients who received the low dose of Peg-IFN (P = NS). In patients with genotypes 1, 4 and 5 and low viraemia, SVR was obtained in 27.3% of patients treated with the standard dose and 25.8% of patients treated with the low dose (P = NS). In the high-viraemia subgroup, SVR was obtained in 24.0% and 9.1% of patients, respectively. In patients with genotypes 2 and 3, SVR was similar in both groups (73.2%vs 73.0%). Thus, (1) patients with genotypes 2 and 3 and severe fibrosis can be treated with low dose of Peg-IFN and ribavirin, (2) this study suggests that patients with genotypes 1, 4 and 5 and high viraemia could receive a standard dose of Peg-IFN associated with ribavirin for 48 weeks, (3) side effects limit the efficacy of the treatment with standard dose of Peg-IFN in patients with genotypes 1, 4 and 5 and low viraemia, (4) more studies are needed for patients with genotype 2 or 3 to define the optimal duration (24 or 48 weeks) in patients with severe fibrosis.

Impact on adherence and sustained virological response of psychiatric side effects during peginterferon and ribavirin therapy for chronic hepatitis C.

BACKGROUND: The psychiatric side effects of interferon, often responsible for dose reduction or treatment discontinuation, represent a major limitation in the treatment of chronic hepatitis C (CHC). AIM: To prospectively assess the impact on adherence and sustained virological response (SVR) of the occurrence of psychiatric side effects during peginterferon and ribavirin therapy for CHC. METHODS: Ninety-eight consecutive treatment-naïve CHC patients receiving a standard course of peginterferon plus ribavirin were systematically screened for psychiatric side effects, using DSM-IV, at baseline and both during and after treatment. RESULTS: Psychiatric side effects occurred in 38 patients (39%), mostly within the first 12 weeks (87%), and always consisted of mood disorders. Overall, 68% of patients achieved an SVR (71% of patients with mood disorders and 68% of those without; P = N.S.). Peginterferon and ribavirin dose reductions did not differ between patients with mood disorders and those without (46% vs. 37%, respectively; P = N.S. and 13% vs. 22%, respectively; P = N.S.). Anti-viral therapy had to be discontinued in four patients (nonresponse: two, hyperthyroidism: one, psychiatric event: one). CONCLUSION: Early detection and appropriate management of psychiatric side effects during peginterferon and ribavirin therapy for CHC allow optimizing adherence and virological efficacy.

Lifestyle changes and beliefs regarding disease severity in patients with chronic hepatitis C.

The aim of this prospective study was to investigate beliefs regarding disease severity and lifestyle changes following hepatitis C diagnosis in patients with chronic hepatitis C (CHC). One hundred and eighty-five consecutive CHC patients were interviewed by means of self-questionnaires exploring several aspects of their disease. Most patients (93%) identified cirrhosis and liver cancer as the two main complications of CHC. More than half of patients (59%) thought that CHC was always associated with a fatal outcome whereas 3% thought that they would stay healthy. HCV viral load was the most commonly reported factor associated with disease severity. Sex life changes were reported by 107 patients (58%) whereas dietary intake changes were reported by 88 patients (48%). In multivariate analysis, changes in sex life were associated with male gender [odds ratio (OR): 2.57, 95% CI: 1.30-5.08, P < 0.007], perceived disease severity (OR: 1.02, 95% CI: 1.00-1.03, P < 0.03) and anxiety (OR: 1.05, 95% CI: 1.01-1.08, P < 0.003), whereas changes in dietary intake were associated with age (OR: 1.04, 95% CI: 1.02-1.08, P < 0.003) and anxiety (OR: 1.04, 95% CI: 1.01-1.08, P < 0.006). Our results show the considerable impact of CHC diagnosis on patients' lifestyle. They emphasize the need for improving CHC patient counselling in order to avoid unnecessary sex life and dietary intake changes.

[Hepatitis C-autoimmune hepatitis overlap syndrome: five new cases]. / Association hépatite auto-immune et hépatite virale C: cinq nouvelles observations.

PURPOSE: The hepatitis C-Autoimmune hepatitis overlap syndrome is an uncommon condition whose management can be difficult in both diagnosis and treatment. PATIENTS AND METHODS: Five cases of hepatitis C and autoimmune hepatitis overlap syndrome, brought by a retrospective study, are reported. Hepatitis C was proven by a positive HCV viral load and the autoimmune hepatitis was proven by characteristic immunological and/or histological features. RESULTS: All patients were female, the mean age at diagnosis was 54.2 years (+/-6.6), only one patient had a history of autoimmune disease (autoimmune thyroiditis). Four patients had significant autoantibodies levels (over 1/320) and 4 had a high serum gammaglobulin level (over 1.5 times the upper normal limit). Liver biopsy showed characteristic features of autoimmune hepatitis in all cases and characteristic features of chronic HCV infection in 3 cases. Corticosteroid and/or immunosuppressive treatment was given as a first line therapy in 4 cases while an antiviral treatment has been tried in 4 cases with a good viral response in 2 of them. Corticosteroid and/or immunosuppressive treatment enhanced HCV viral load in all cases, however a histological improvement was observed in every case in which a control biopsy has been performed (3 cases). CONCLUSION: This study highlights the deciding contribution of the initial histological findings in the diagnosis of such a HCV/autoimmune hepatitis overlap syndrome; it also demonstrates that histological outcome is not necessarily compromised by corticosteroid and/or immunosuppressive treatment.

[Hepatitis B and C virological tests: interpretation and practical results in women]. / Sérologie des hépatites B et C: interprétation et conséquences pratiques chez la femme.

Chronic Hepatitis C or B infection can lead to liver cirrhosis and hepatocellular carcinoma. In women, these viral infections can be responsible for transmission to the spouse and to the child during delivery. Concerning the hepatitis C virus, the factors most strongly associated with infection are injection-drug use and blood transfusion before 1991. The risk of mother-to-infant transmission of hepatitis C virus is uncommon (5 per cent): except for the viral eradication before pregnancy, there is no preventive measure to propose. Pregnancy is not contra-indicated. Hepatitis C virus transmission by sexual contact in steady monogamous partnerships is low (< 1 per cent). In most developed parts of the world where the prevalence of chronic hepatitis B infection is low, most infections occur among high-risk adult populations including injection drug users and multiple heterosexual partners. On the contrary, in high prevalence areas, infection occurs during either the perinatal period or early in childhood. The risk of maternal-infant contamination is high, from 20 to 90 per cent according to the viral load. Vaccination prevents risk of infection and is strongly advised to persons at high risk of infection. Universal vaccination of infants is highly recommended.

Clinical criteria for the diagnosis of bullous pemphigoid: a reevaluation according to immunoblot analysis of patient sera.

BACKGROUND: We previously proposed a set of 4 clinical criteria for the diagnosis of bullous pemphigoid (BP) that consisted of age greater than 70 years, absence of atrophic scars, absence of mucosal involvement and absence of predominant bullous lesions on the neck and head. These results have been challenged because direct immunoelectron microscopy (IEM), which was used as the standard diagnostic criterion in our initial study, does not identify the different antigens of the basement membrane zone. OBJECTIVE: To reassess the validity of these clinical criteria for the diagnosis of BP using immunoblot analysis of patient sera as the main diagnostic criterion, in order to precisely identify the antigens recognized by patient sera. METHODS: One hundred and eighty-nine sera from patients with various subepidermal autoimmune blistering diseases (AIBDs) were tested by immunoblotting using dermal and epidermal extracts. IEM was used as a complementary diagnostic procedure in a few patients whose serum recognized BPAG2 exclusively or was negative in immunoblotting. RESULTS: 142 patients (75%) had at least 3 of the 4 clinical diagnostic criteria. Sera from patients who lacked the set of BP clinical criteria were more frequently immunoblot negative (34%) than sera from patients who had the criteria (18%; p = 0.025). BPAG1 was more frequently recognized by sera from patients with the set of BP clinical criteria (78%) than by sera from patients without the criteria (45%; p = 5.10(-4)). In contrast, BPAG2 was recognized by a great number of sera from patients who lacked the criteria of BP (71%), which was in accordance with the presence of numerous patients with cicatricial pemphigoid in this group. Among patients with various subepidermal AIBDs, the diagnosis of BP could be made with a sensitivity of 86%, a specificity of 90% and an excellent prognostic positive value over 95%, if 3 of these clinical criteria were present. CONCLUSION: These results confirm the interest of this set of clinical criteria for the rapid diagnosis of BP.