Enhanced liver fibrosis score is stable after withdrawal in patients with heavy alcohol consumption: A pilot study.

BACKGROUND: Enhanced liver fibrosis (ELF) score is an accurate, noninvasive test for assessing the severity of liver fibrosis in chronic liver disease, including alcohol-related liver disease. However, whether the ELF score changes during alcohol withdrawal is unknown. This pilot study assessed changes in the ELF score during withdrawal in patients with a history of excessive alcohol intake. METHODS: In this prospective study, ELF was performed on day 0 (D0, at the beginning of hospitalization), at day 7 (D7, on discharge from hospital), and at follow-up visits on days 30 (D30) and 90 (D90). Transient elastography (TE) was also assessed on days 4 (D4) and D30. RESULTS: The study included 35 patients (71% male) with a mean alcohol intake of 139 g/day. On D30 and D90, 8 and 13 patients had resumed alcohol consumption (mean intake of 90 and 80 g/day, respectively). In patients who remained abstinent, the mean ELF score was 8.93 on D0, 9.14 on D30 (p = 0.32), and 9.27 on D90 (p = 0.14). In patients who resumed alcohol, mean ELF score was 9.7 on D0, 10.05 on D30 (p = 0.09), and 9.71 on D90 (p = 0.12). ELF score was comparable over the first months after withdrawal, although there was a slight increase in the first week (mean ELF score increased from 9.24 on D0 to 9.74 on D7, p < 0.001). Mean TE value was 7.9 kPa on D4 and 8.1 kPa on D30 (p = 0.84) in patients who resumed alcohol consumption, and 8.3 and 7.5 kPa (p = 0.03) on D4 and D30, respectively, in abstinent patients. CONCLUSION: The ELF score is stable during the first months after withdrawal and thus appears to be a useful tool to assess liver fibrosis or cirrhosis in this setting. Nevertheless, because in the first week there is a transient increase in ELF score, caution in interpretation is warranted.

An observational, prospective, multicenter study on the utilization and effectiveness of elbasvir-grazoprevir treatment association for chronic hepatitis C in France (ZEPHYR study).

Background and Aim: The efficacy and safety profiles of elbasvir-grazoprevir (EBR/GZR) has been established in more than 10 clinical trials. However, the characteristics of patients treated in routine clinical practice may differ. The present study was therefore designed to assess the real-life effectiveness of EBR/GZR therapy in the general population and among subgroups with a high hepatitis C virus (HCV) prevalence in France. Methods: The Zephyr study was designed as a French, multicentre, prospective, observational study on EBR/GZR use and effectiveness in current practice in chronic hepatitis C patients. These results are based on data regarding the adult patients who received at least one dose of EBR/GZR between December 2017 and June 2019 in 67 French hospitals and clinics. Results: Overall, 478 patients were included. The Full Analysis Set corresponded to the 467 patients who met all the inclusion criteria and none of the exclusion criteria. Gender was balanced and the mean age was 55.7 ± 13.3 years. The patients were mainly treatment-naive (89.5%) and infected with Genotype 1b (70.4%). Among the 75 patients with HCV Gt1a genotype, 56% had HCV RNA ≥ 800,000 IU/ml. F3-F4 fibrosis stage involved 24.2% of our population. Our subgroups were distributed among 110 migrants (23.6%), 58 (15.3%) using opioid agonist treatment, including people who inject drugs, 30 (6.8%) with chronic kidney disease Stages 3-5, 9 (1.9%) with an inherited blood disorder, and 4 (0.9%) coinfected with HIV. The remaining 269 (58.7%) were included in the general population subgroup. Overall, sustained virologic response 12 weeks after the end of treatment reached 98.0% and remained consistent among genotype, HCV RNA values, fibrosis stage, and the subgroup of interest. The rate of Alcohol Use Disorders Identification Test-Consumption​​​ and Life Habit questionnaire completion was high at each visit, with data suggesting alcohol consumption decrease and an improvement in quality of life. Conclusions: Using real-world evidence data on a French population representative of HCV patients, we confirmed the results obtained during EBR/GZR development program.

Evolution of Hepatitis C Virus Treatment During the Era of Sofosbuvir-Based Therapies: A Real-World Experience in France.

BACKGROUND: Treatment of hepatitis C virus (HCV) has been dramatically improved with the introduction of direct-acting antiviral agents (DAAs). Universal access to pangenotypic DAAs was provided in France from 2017, expanding the type of patients treated. Real-world studies are important to confirm effectiveness and safety in clinical practice, particularly in vulnerable populations. AIMS: To assess real-world effectiveness and safety of sofosbuvir-based therapy in adults with chronic HCV infection before and after universal access to DAAs in France. METHODS: This multicenter, non-interventional, prospective study assessed the effectiveness, safety, patient-reported outcomes and adherence with sofosbuvir-based regimens from October 2015 to July 2016 (Period 1: sofosbuvir-based therapy excluding sofosbuvir/velpatasvir) and from October 2017 to July 2018 (Period 2: pangenotypic sofosbuvir/velpatasvir-based therapy). RESULTS: Baseline data were documented for 1029 patients. Overall, 797 (77%) had sustained virologic response data available ≥ 9 weeks after treatment completion. Per protocol response was high (97%) irrespective of age, alcohol consumption, recreational drug use, or HIV/HCV coinfection. Adverse events occurred in approximately 25% of patients with the majority experiencing Grade 1 or 2 events. Sofosbuvir-based regimens improved health-related quality of life from baseline to end of treatment in patients with data at all timepoints. Overall, 99% of patients reported total or almost total adherence to therapy. CONCLUSIONS: Sofosbuvir-based therapy, including pangenotypic sofosbuvir/velpatasvir, is effective for the treatment of HCV in real-world clinical practice. This is an important step towards HCV elimination.

Effectiveness and Safety of Tenofovir Disoproxil Fumarate in Chronic Hepatitis B: A 3-Year, Prospective, Real-World Study in France.

BACKGROUND AND AIMS: Tenofovir disoproxil fumarate (TDF) demonstrated potent and sustainable antiviral efficacy and a good safety profile in patients with chronic hepatitis B (CHB) in controlled clinical trials. Real-world data are important to confirm effectiveness and safety data in patient populations encountered in routine clinical practice. METHODS: This non-interventional, prospective, 36-month study included treatment-naïve and treatment-experienced patients with CHB initiating their first TDF regimen (monotherapy or combination therapy) in routine clinical practice in France. Clinical, virologic, biochemical, compliance, and safety data were collected. RESULTS: Data from 440 consecutive patients from 58 centers were analyzed. The majority of the cohort was male (71 %), hepatitis B "e" antigen-negative (HBeAg-) (74 %), and treatment-experienced (56 %); 11 % were aged ≥65 years; and comorbidities were reported in 39 %. After 12 months, 92 % of the overall cohort achieved virologic response (HBV DNA <69 IU/mL) which was maintained to 36 months (96 %); virologic response was achieved by >90 % of patients irrespective of HBeAg status, age, or prior treatment history. At 36 months, 77 % of patients had normal alanine aminotransferase levels. Fourteen patients lost hepatis B surface (HBs) antigen, and seven seroconverted to anti-HBs. TDF was well tolerated over the 36-month study, including in 14 women who became pregnant during the study. Median estimated glomerular filtration rate did not change markedly from baseline irrespective of prior treatment history. CONCLUSIONS: TDF demonstrated potent virologic and biochemical responses across a broad range of patients reflective of routine clinical practice. The safety profile was consistent with results from pivotal trials.

Effect of detoxification on liver stiffness assessed by Fibroscan® in alcoholic patients.

AIMS: The aims of this study were to determine whether alcohol consumption or cessation influences transient elastography (TE) measurements and whether TE is a useful tool to monitor alcoholic patients. PATIENTS: Twenty-three consecutive heavy drinkers (20 men and 3 women; mean age 47.2 years) admitted for a 7-day hospitalization for alcohol detoxification were included. On admission (D0), a detailed medical history was taken and the following laboratory tests were performed [aspartate aminotransferase (ASAT), gamma glutamyltransferase (γGT), and carbohydrate-deficient transferrin (CDT) levels, and Fibroscan(®)]. All examinations were repeated on D8, D30, and D60. Variation in the median Fibroscan value of >20% was considered significant. RESULTS: After 1 week of detoxification, the % variation in TE was -21.67 ± -27.6%. The median variation in TE between D8 and D60 was -20% in the abstinent group and 32% in the relapse group (p = 0.007). An increase in proportion of patients with a significant decrease in TE was observed with an increased duration of abstinence: 41.7% at D8 and 66.7% at D60. TE values were significantly correlated with ASAT, γGT, and CDT at D0 and D8, and with ASAT and γGT at D60. CONCLUSIONS: TE in alcoholics is influenced by major variations in the biochemical activity of the disease. The kinetics of variation of TE suggest that this method may be useful to assess alcohol abuse and control.

Noninvasive procedures to evaluate liver involvement in HIV-1 vertically infected children.

OBJECTIVES: : Progressive liver injury is a concern in HIV-infected children exposed to long-term antiretroviral drugs and to the cytopathic effect of HIV. Yet liver biopsy is usually considered too invasive to be repeated in these patients. The aims of this study are to evaluate the feasibility of noninvasive hepatic investigations in HIV-1-infected children, assess the prevalence of signs of liver affection, and analyse the influence of the HIV disease severity and the exposure to antiretroviral therapy. MATERIALS AND METHODS: : A cross-sectional study conducted in 26 HIV-1 vertically infected children ages 8 to 18 years old. Liver function was assessed with standard serum biochemical markers, FibroTest, ActiTest, SteatoTest, Forns index, aspartate aminotransferase to platelet ratio index, ultrasound, and Fibroscan. RESULTS: : Nineteen (>60%) children had signs of liver affection on at least 1 of the test results: 13 (50%) had elevated liver enzymes, 15 (63%), 8 (33%), 5 (21%), and 5 (21%) had abnormal FibroTest, ActiTest, Forns index, and aspartate aminotransferase to platelet ratio index results, respectively. Four children (17%) had mild liver steatosis on ultrasound. Fibroscan measures were significantly higher in patients than in age-matched healthy children. Patients with elevated Fibroscan measures also had significantly higher FibroTest results. Age, HIV stage N in the Centers for Disease Control and Prevention classification and exposure duration to nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor drugs were the main risk factors for hepatotoxicity. CONCLUSIONS: : More than half of our population of HIV-infected children had biological and/or radiological signs of liver affection. Regular follow-up of liver function is necessary in these patients, which is now possible with noninvasive procedures.

Factors predictive of alcohol abstention after resident detoxication among alcoholics followed in an hospital outpatient center.

OBJECTIVES: A cohort of patient hospitalized for alcohol detoxification between January 2004 and January 2005 were followed prospectively to search for factors predictive factors of sustained abstinence. PATIENTS AND METHODS: One hundred and fifteen patients (79 males, 36 females, median age 45.9+/-10.7 years), were hospitalized for alcohol detoxification. Demographic, social, and medical data including daily alcohol intake and co-addictions were noted at inclusion and six months later. Patients who did not attend their six-month visit were contacted by phone. RESULTS: Among the 115 included patients, six month follow-up data could be collected for 73. Abstinence rate was 54.8%. Factors predictive of unsuccessful cessation were homelessness (P=0.004), duration of alcohol consumption (P=0.004), smoking (P=0.02), drug substitution (P=0.04) and multiple addictions (P=0.04). At multivariate analysis, multiple addictions was the only independent factor predictive of unsuccessful detoxification. Naltrexone or acamprosate treatments were not associated with a better rate of alcohol detoxification. CONCLUSION: Patient follow-up is problematic due to the large number of dropouts among alcoholics. Early screening in search for factors predictive of unsuccessful detoxification (long duration of alcohol consumption, multiple addiction) would be helpful in elaborating appropriate pluridisciplinary management.

Hepatitis C awareness among adolescents in the Alpes-Maritimes area of France.

OBJECTIVES: Certain practices with a potential risk of hepatitis C virus (HCV) transmission begin early, during adolescence. In 2004, primary prevention interventions targeting adolescents aged 13-17 years attending school in the Alpes-Maritimes region of France were conducted by the "Réseau Hépatite C Ville Hôpital Côte d'Azur". The aim of this study was to assess the adolescents' knowledge about HCV and to evaluate the impact of such interventions. METHODS: A random sample of secondary state schools in the Alpes-Maritimes was invited to participate in the study. Before and after presenting a slide show about HCV in the selected classrooms, the investigators asked the students to complete an anonymous self-administered questionnaire designed to assess their knowledge about HCV infection. RESULTS: The intervention concerned a study population of 2,946 students, mean age 14.4 +/- 2.5 years. Before the interventions, 21% had good knowledge of HCV infection and 24% had good know-ledge of disease contagion. These percentages increased significantly after the interventions to 95% and 84% respectively. Knowledge improvement was more significant among high school students and among students whose parents had an employment. CONCLUSIONS: Adolescents are poorly informed about HCV infection. The present intervention enabled significant improvement in their knowledge about the infection and disease contagion, independently of gender, age and geographical area.