Hepatitis B og C

by Parker Elijah Joshua, Cynthia Ogochukwu Nwauzor, Damian Chukwu Odimegwu, Uzochukwu Gospel Ukachukwu, Rita Onyekachukwu Asomadu, Timothy Prince Chidike Ezeorba Although aluminum-containing adjuvants are widely used in human vaccination due to their excellent safety profile, they exhibit low effectiveness with many recombinant antigens. This study investigated the adjuvanticity of snail mucin with recombinant Hepatitis B Vaccine (rHBsAg). Twenty-five (25) female mice distributed unbiasedly into 5 groups were used in the study and were administered different rHBsAg/Mucin formulation at 7 days intervals. Blood samples were collected a day following the administration for analysis. The results of liver function and body weight analysis were indications that snail mucin had no adverse effect on the mice. The treatment group (administer mucin and rHBsAg) showed significantly (p<0.05) higher mean titres of anti-HBsAg antibodies when compared with the negative controls and the positive control administered with two doses of rHBsAg after the boost doses (day 28). Furthermore, a comparable immune response to positive control administered with three doses rHBaAG was recorded. In silico prediction, studies of the protein-protein interaction of a homology modelled snail mucus protein and HBsAg gave an indication of enhanced HBV antigen-antibody interaction. Therefore, this study has shown that snail mucin possesses some adjuvant properties and enhances immune response towards rHBsAg vaccine. However, there is a need for further molecular dynamics studies to understand its mechanism of action.

Abstract Background Methadone therapy clinics have been recently introduced in Tanzania, aiming at reducing risk behaviors and infection rates of viral hepatitis and HIV among people who use drugs. The objective of this study was to estimate the prevalence, associated factors and knowledge level of these conditions among people who use drugs attending a methadone clinic in Tanzania. Methods We enrolled 253 People who using drugs receiving Methadone therapy. Clinical data was retrospectively collected from the medical records and face-to face interviews were conducted to determine the behavioral risk factors and respondents’ knowledge on viral hepatitis and HIV. Results An overall seroprevalence of viral hepatitis (either hepatitis B surface antigen or anti-hepatitis C virus) was 6.3%, while that of hepatitis B virus mono infection was 3.5% and anti-hepatitis C antibodies was 3.5%. Seroprevalence of HIV was 12.6%. Viral hepatitis was strongly predicted by advanced age (> 35 years) (p = 0.02) and staying at Kirumba area (p = 0.004), and HIV infection was predicted by increased age (> 37 years) (p = 0.04) and female sex (p < 0.001). Regarding the knowledge of viral hepatitis, majority of the respondents were unaware of the transmission methods and availability of hepatitis B virus vaccines and only 17% were classified as well informed (provided ≥4 correct answers out of 7 questions). Good knowledge was highly predicted by higher education level of the individual (p = 0.001). Conclusions Despite the efforts to curb viral hepatitis and HIV infections through Methadone clinics, infection rates among people who use drugs are still high and the general knowledge on preventive measures is inadequate.

Antimicrobial Agents and Chemotherapy, <a href="https://journals.asm.org/toc/aac/0/ja">Volume 0, Issue ja</a>, -Not available-.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are associated with high morbidity and mortality in the developing world due to the risk of developing cirrhosis, liver failure, hepatocellular carcinoma, and death (McMahon, 2009). According to the Global Hepatitis Report by the World Health Organization (WHO) in 2015, an estimated 257 million people worldwide were infected with HBV and 71 million people with HCV, causing about 1.34 million deaths annually (The Lancet GBD 2017, 2018).

Objectives Community-based screening for hepatitis B virus (HBV) and hepatitis C virus (HCV) is essential for hepatitis elimination. This study attempted to increase screening accessibility and efficacy by using alternative tools. Design Population-based prospective cohort study. Setting Hepatitis elimination program at Yunlin County, Taiwan. Participants All 4552 individuals participated in 60 screening sessions of a community-based HBV and HCV screening project in five rural townships with approximately 95 000 inhabitants in central-western Taiwan. Interventions To increase accessibility, 60 outreach screening sessions were conducted in 41 disseminative sites. Quantitative HBV surface antigen (qHBsAg) and anti-HCV testing with reflex HCV core antigen (HCV Ag) tests were employed as alternative screening tools. Main outcome measures Calculate village-specific prevalence of HBsAg, anti-HCV and HCV Ag and establish patient allocation strategies according to levels of qHBsAg HCV Ag and alanine aminotransferase (ALT). Results Of 4552 participants, 553, 697 and 290 were positive for HBsAg, anti-HCV and HCV Ag, respectively; 75 of them had both HBsAg and anti-HCV positivity. The average (range) number of participants in each screening session was 98 (31–150). The prevalence rates (range) of HBsAg, anti-HCV and HCV Ag were 12.1% (4.3%–19.4%), 15.3% (2.6%–52.3%) and 6.4% (0%–30.2%), respectively. The HCV Ag positivity rate among anti-HCV-positive participants was 42% (0%–100%). Using cut-off values of >200 IU/mL for qHBsAg, >3 fmol/L for HCV Ag and >40 IU/mL for ALT as criteria for patient referral, we noted an 80.2% reduction in referral burden. Three villages had high anti-HCV prevalences of 52.3%, 53.8% and 63.4% with corresponding viraemic prevalences of 23.2%, 30.1% and 22% and thus constituted newly identified HCV-hyperendemic villages. Conclusion Outreach hepatitis screening increases accessibility for residents in rural communities. Screening HBV and HCV through qHBsAg and HCV Ag tests provides information concerning viral activities, which might be conducive to precise patient allocation in remote communities.

Abstract Background Despite the development of a safe and efficacious hepatitis B vaccine in 1982, the hepatitis B virus (HBV) remains a public health burden in sub-Saharan Africa. Due to shared risk factors for virus acquisition, men who have sex with men (MSM) and transgender women (TGW) living with HIV are at increased risk of HBV. We estimated the prevalence of HBV and associated factors for MSM and TGW living with or without HIV in Nigeria. Methods Since March 2013, TRUST/RV368 has recruited MSM and TGW in Abuja and Lagos, Nigeria using respondent driven sampling. Participants with HIV diagnosis, enrollment as of June 2015, and available plasma were selected for a cross-sectional study and retrospectively tested for hepatitis B surface antigen and HBV DNA. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with prevalent HBV infection. Results A total of 717 MSM and TGW had a median age of 25 years (interquartile range [IQR]: 21–27), 5% self-reported HBV vaccination, 61% were living with HIV, 10% had prevalent HBV infection and 6% were HIV-HBV co-infected. HIV mono-infected as compared to HIV-HBV co-infected had a higher median CD4 T cell count [425 (IQR: 284–541) vs. 345 (IQR: 164–363) cells/mm3, p = 0.03] and a lower median HIV RNA viral load [4.2 (IQR: 2.3–4.9) vs. 4.7 (IQR: 3.9–5.4) log10copies/mL, p < 0.01]. The only factor independently associated with HBV was self-report of condomless sex at last anal intercourse (OR: 2.2, 95% CI: 1.3, 3.6). HIV infection was not independently associated with HBV (OR: 1.0, 95% CI: 0.7–1.6). Conclusion HBV prevalence was moderately high but did not differ by HIV in this cohort of MSM and TGW. Recent condomless sex was associated with elevated HBV risk, reinforcing the need to increase communication and education on condom use among key populations in Nigeria. Evaluating use of concurrent HIV antiretroviral therapy with anti-HBV activity may confirm the attenuated HBV prevalence for those living with HIV.

Background Hepatitis B virus (HBV) infection is a major public health issue worldwide, with about 257 million people reported to be chronic carriers by the WHO fact sheet updated in 2018. HBV can be contracted via direct contact with infected body fluid and infection is almost always asymptomatic. Although healthcare workers (HCWs) are at high risk of HBV infection, little is known about the prevalence of the various HBV markers among HCWs in Cameroon. The present study was taken to evaluate the prevalence of different HBV serological markers among HCWs in the North-West Region of Cameroon. Methods This cross-sectional hospital-based study was carried out between April and September 2017 during which 395 HCWs were recruited. The serum of the HCWs were tested for the presence of HBV core antibody, hepatitis B surface antibody, hepatitis B e antibody and hepatitis B surface antigen using Monalisa ELISA kits produced by BIO-RAD laboratories. Data were analysed using SPSS V.20.0. Results Among the 395 participants, 270 (68.4%) of them were females, 187 (47.3%) had been exposed to HBV, 145 (36.7%) had resolved the infection, 42 (10.6%) were current HBV carriers, 10 (2.5%) were infective, 36 (9.1%) were vaccinated and 172 (43.5%) were still susceptible. Exposure to HBV, past infection and susceptibility were significantly associated with age while the rate of vaccination was significantly associated with the job of the HCW in the health facilities. Conclusion The prevalence of HBV exposure and infection among HCWs obtained in this study was high while the level of vaccination in this at-risk population was low. Adequate steps should be taken to sensitise this population on HBV and the vaccination procedure.

by Hung-Yin Liu, Yi-Hung Lin, Pei-Ju Lin, Pei-Chien Tsai, Shu-Fen Liu, Ying-Chou Huang, Jia-Jiun Tsai, Ching-I Huang, Ming-Lun Yeh, Po-Cheng Liang, Zu-Yau Lin, Chia-Yen Dai, Jee-Fu Huang, Wan-Long Chuang, Chung-Feng Huang, Ming-Lung Yu Background/Aims Hepatitis C Virus (HCV) infection is diagnosed by the presence of antibody to HCV and/or HCV RNA. This study aimed to evaluate the accuracy of anti-HCV titer (S/CO ratio) in predicting HCV viremia in patients with or without hepatitis B virus (HBV) dual infection. Methods Anti-HCV seropositive patients who were treatment-naïve consecutively enrolled. Anti-HCV antibodies were detected using a commercially chemiluminescent microparticle immunoassay. HCV RNA was detected by real-time PCR method. Results A total of 1321 including1196 mono-infected and 125 HBV dually infected patients were analyzed. The best cut-off value of anti-HCV titer in predicting HCV viremia was 9.95 (AUROC 0.99, p<0.0001). Of the entire cohort, the anti-HCV cut-off value of 10 provided the best accuracy, 96.8%, with the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 96.3%, 98.9%, 99.7% and 87.3% respectively. The best cut-off value of anti-HCV titer in predicting HCV viremia was 9.95 (AUROC 0.99, p<0.0001) and 9.36 (AUROC 1.00, p<0.0001) in patients with HCV mono-infection and HBV dual-infection respectively. Among the HBV dually infected patients, the accuracy of anti-HCV titer in predicting HCV viremia reached up to 100% with the cut-off value of 9. All the patients were HCV-viremic if their anti-HCV titer was greater than 9 (PPV 100%). On the other hand, all the patients were HCV non-viremic if their anti-HCV titer was less than 9 (NPV 100%). Conclusions Anti-HCV titer strongly predicted HCV viremia. This excellent performance could be generalized to either HCV mono-infected or HBV dually infected patients.

by Laura Cordeiro Gomes, Marina Cordeiro Gomes Sanson, Philip Brainin, Maria da Conceição Vieira de Melo, Rodrigo Medeiros de Souza, Janaína Mazaro, Karine Oliveira Lima, Júnia Silva Resende, Isabelle Victória Martins Vieira, Edinilson da Silva Mesquita, Luan Oliveira Matos, Isabelle Caroline Silva Dutra, Giuseppe Palmisano, Carsten Wrenger, Claudio Romero Farias Marinho, Rita do Socorro Uchôa da Silva Background Despite completion of the vaccine schedule for hepatitis B virus (HBV), children may display levels of HBV surface antibodies (anti-HBs) that are considered inadequate for sufficient protection (…

Hepatitis B virus infection is an important public health problem. We analyzed the cost-effectiveness of the first-line therapies including nucleotide analogues (NAs), namely tenofovir alafenamide fumarate (TAF), tenofovir disoproxil fumarate (TDF) and entecavir, and Peg-IFN for patients with chronic hepatitis B (CHB) in China.

Abstract Background Current clinical guidelines recommend treating chronic hepatitis B virus (HBV) infection in a minority of cases, but there are relatively scarce data on evolution or progression of liver inflammation and fibrosis in cases of chronic HBV (CHB) that do not meet treatment criteria. We aimed to assess the impact of TDF on liver disease, and the risk of renal impairment in treated CHB patients in comparison to untreated patients. Methods We studied a longitudinal ethnically diverse CHB cohort in the UK attending out-patient clinics between 2005 and 2018. We examined TDF treatment (vs. untreated) as the main exposure, with HBV DNA viral load (VL), ALT, elastography scores and eGFR as the main outcomes, using paired tests and mixed effects model for longitudinal measurements. Additionally, decline of eGFR during follow-up was quantified within individuals by thresholds based on clinical guidelines. Baseline was defined as treatment initiation for TDF group and the beginning of clinical follow-up for untreated group respectively. Results We included 206 adults (60 on TDF, 146 untreated), with a median ± IQR follow-up duration of 3.3 ± 2.8 years. The TDF group was significantly older (median age 39 vs. 35 years, p = 0.004) and more likely to be male (63% vs. 47%, p = 0.04) compared to the untreated group. Baseline difference between TDF and untreated groups reflected treatment eligibility criteria. As expected, VL and ALT declined significantly over time in TDF-treated patients. Elastography scores normalised during treatment in the TDF group reflecting regression of inflammation and/or fibrosis. However, 6/81 (7.4%) of untreated patients had a progression of fibrosis stage from F0-F1 to F2 or F3. There was no evidence of difference in rates or incidence of renal impairment during follow-up in the TDF vs. untreated group. Conclusions Risk of liver inflammation and fibrosis may be raised in untreated patients compared to those receiving TDF, and TDF may benefit a larger percentage of the CHB population.

Abstract Background & Aims There is limited evidence on the efficacy and safety of nucleos(t) ide analogues (NAs) in the treatment of HBV-ACLF. Our objective was to evaluate the outcomes among TAF, TDF and ETV, three first-line antivirals against chronic hepatitis B, in patients with HBV-ACLF. Methods Patients with HBV-related ACLF were recruited and received daily TAF (25 mg/d), TDF (300 mg/d) and ETV (0.5 mg/d). They were prospectively followed-up. The primary endpoint was overall survival at week 12 and week 48, the secondary endpoints were virological response and biochemical response. Results Forty gender and age matched eligible subjects were recruited and divided into three groups: TAF group, TDF group and ETV group. By week 48, 8 (80%) patients in TAF group, 6 (60%) patients in TDF group and 17 (85%) patients in ETV group survived without liver transplantation (P = 0.251). After 4 weeks of NAs treatment, all three groups showed paralleling reduction of HBV DNA levels. All three groups presented similar biochemical responses at week 4, patients treated with TAF showed a priority in total bilirubin reduction, albumin and cholesterol maintenance. Additionally, although there was no significant difference in changes of serum urea, serum creatinine, serum cystatin C and estimated GFR among the three groups by treatment week 4, TDF showed unfavorable renal safety even in short -term treatment. The treatment using NAs was well-tolerated and there was no serious drug-related adverse event reported. Conclusions TAF, TDF and ETV are of similar efficacy and safety in short-term and long-term treatment of HBV-ACLF. Trial registration This study is ongoing and is registered with ClinicalTrials.gov, NCT03640728 (05/02/2019).

Journal of Medical Virology, EarlyView.

HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) are commonly encountered blood-borne infectious microorganisms. Infection with these viruses typically requires long-lasting drug therapy. Coinfections, especially with tuberculosis, pose a challenge to the creation of a regimen with adequate efficacy and minimal drug–drug interactions and adverse effects. We present the case of a young man with a history of intravenous drug misuse who was diagnosed with disseminated tuberculosis and with a triple infection with HBV, HCV, and HIV.

The safety and efficacy of TAV shows its usefulness for the prevention of HBV infection in adults, including those with stable and controlled chronic conditions.

Clinical & Experimental Immunology, Accepted Article.

by Zelalem Alamrew Anteneh, Estifanose Wondaye, Endalkachew Worku Mengesha Background Hepatitis B virus (HBV) kills millions of people globally; it is worse in pregnant women. HBV and Human Immune Virus (HIV) co-infection is associated with increased liver diseases such as cirrhosis and hepatocellular carcinoma. This study aimed at identifying the determinants of HBV infection among HIV-positive pregnant women. Methods A multicentre unmatched case-control study was conducted among 109 cases (HBV/HIV co-infected) and 327 controls (HIV positive) pregnant women in seven hospitals of the Eastern Amhara region. Interview and chart review data collection techniques were employed by trained personnel. A binary logistic regression model was used to identify independent predictors of hepatitis B virus infection. Variables with a p-value of…

Journal of Medical Virology, Accepted Article.

Regional variability in the prevalence of hepatitis B (HBV) and C (HCV) is reported in sub-Saharan Africa, although data for people with HIV are sparse. We determined the prevalence of HBV/HCV in 2,473 people of African ancestry with HIV in the UK. Overall, 6.2% were co-infected with HBV and 1.3% with HCV. Central (aOR 2.40 [95%CI 1.23-4.67] and West (2.10 [1.29-3.41]) African ancestry was associated with HBV and Central (6.98 [2.00-24.43]) African ancestry with HCV. Correspondence to Frank A. Post, MMed, FCP(SA), PhD, FRCP, King's College Hospital NHS Foundation Trust, Weston Education Centre (rm 2.53), Cutcombe Road, London SE5 9RJ, United Kingdom. Tel: +44 207 848 5779; fax: +44 207 848 5769; e-mail: frank.post@kcl.ac.uk Received 1 December, 2020 Revised 12 April, 2021 Accepted 19 April, 2021 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2021 Wolters Kluwer Health, Inc.

by Joana Vieira Barbosa, Roland Sahli, Vincent Aubert, Aziz Chaouch, Darius Moradpour, Montserrat Fraga Background Hepatitis B virus (HBV) is a major global health challenge with approximately 250-350 million chronically infected individuals. An improved understanding of the demographic features and outcomes of chronic HBV infection and hepatitis D virus (HDV) infection in low-endemic areas may improve prevention, early identification and management both at individual and community levels. Here, we retrospectively analyzed the demographic and clinical characteristics, treatment rates and outcomes of adult patients with chronic HBV infection with or without HDV coinfection examined at Lausanne University Hospital, Switzerland over a 10-year period. Methods We analyzed the medical records of all adult patients with chronic HBV and HDV infection examined in our center between 2007 and 2016. Liver-related outcome was defined as the occurrence of cirrhosis, hepatocellular carcinoma, liver transplantation or liver-related death. Analyses were performed using logistic regression and results were reported as odds ratio (OR) and 95% confidence interval (CI). Results Of 672 consecutive patients, 421 (62.6%) were male, median age was 36 years (interquartile range, 28-46 years), and 233 (34.7%) were of African origin. The prevalence of HDV coinfection was 7.1% and the proportion of anti-HDV-positive patients with detectable HDV RNA was 70.0%. In multivariate analysis, HDV coinfection was the strongest predictor for liver-related outcome (OR 6.06, 95% CI 2.93-12.54, p<0.001), followed by HBeAg positivity (OR 2.47, 95% CI 1.30-4.69, p = 0.006), age (OR per 10-year increase 2.03, 95% CI 1.63-2.52, p<0.001) and sex (OR for female 0.39, 95% CI 0.22-0.71, p = 0.002). The predictive accuracy of the multivariate model was high (receiver operator characteristic area under the curve 0.81). Conclusion This retrospective study underscores the importance of migration in the epidemiology of chronic hepatitis B in low-endemic areas. HDV coinfection, HBeAg positivity and age predicted liver-related outcomes while female sex had a protective effect.

A major hurdle in the long-term treatment of chronic hepatitis B (CHB) patients is to maintain viral suppression in the absence of drug resistance. To date, no evidence of resistance to tenofovir disoproxil fumarate (TDF) has been observed. A cumulative evaluation of CHB patients who qualified for resistance surveillance over 8 years of TDF treatment was conducted. Patients in studies GS-US-174-0102 (HBeAg-) and GS-US-174-0103 (HBeAg+) were randomized 2:1 to receive TDF or adefovir dipivoxil (ADV) for 48 weeks followed by open-label TDF through year 8. Population sequencing of HBV pol/RT was attempted for all TDF-treated patients at baseline and, annually if viremic, at discontinuation, or with addition of emtricitabine. Overall, 88/641 (13.7%) patients qualified for sequence analysis at one or more time points. The percentage of patients qualifying for sequence analysis declined over time, from 9 to 11% in years 1-2 to <4% over years 3-8. Forty-one episodes of virologic breakthrough (VB) occurred throughout the study, with most (n=29, 70%) associated with nonadherence to study medication. Fifty-nine per cent of VB patients with an opportunity to resuppress HBV achieved HBV DNA resuppression. A minority of patients who qualified for sequencing had polymorphic (41/165, 24.8%) or conserved (17/165, 10.3%) site changes in pol/RT, with six patients developing lamivudine and/or ADV resistance-associated mutations. No accumulation of conserved site changes was detected. The long-term treatment of CHB with TDF monotherapy maintains effective suppression of HBV DNA through 8 years, with no evidence of TDF resistance or accumulation of conserved site changes.

In phase 2 trials, treatment with the combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir resulted in high rates of sustained virologic response in patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3.

A simple treatment regimen that is effective in a broad range of patients who are chronically infected with the hepatitis C virus (HCV) remains an unmet medical need.

Chronic hepatitis C virus (HCV) infection is associated with several extrahepatic manifestations. Patients with HCV may develop mixed cryoglobulinemia and its sequelae, ranging from cutaneous and visceral vasculitis to glomerulonephritis and B-cell non-Hodgkin lymphoma. HCV-infected patients have increased rates of insulin resistance, diabetes, and atherosclerosis, which may lead to increased cardiovascular morbidity and mortality. Neurological manifestations of HCV infection include fatigue and cognitive impairment. The mechanisms causing the extrahepatic effects of HCV infection are likely multifactorial and may include endocrine effects, HCV replication in extrahepatic cells, or a heightened immune reaction with systemic effects. Successful eradication of HCV with interferon alfa and ribavirin was shown to improve some of these extrahepatic effects; sustained virological response is associated with resolution of complications of cryoglobulinemia, reduced levels of insulin resistance, reduced incidence of diabetes and stroke, and improved fatigue and cognitive functioning. The availability of new interferon-free, well-tolerated anti-HCV treatment regimens is broadening the spectrum of patients available for therapy, including those in whom interferon was contraindicated, and will likely result in greater improvements in the extrahepatic manifestations of HCV. If these regimens are shown to confer significant benefit in the metabolic, cardiovascular, or neuropsychiatric conditions associated with HCV infection, extrahepatic manifestations of HCV may become a major indication for treatment even in the absence of liver disease.

Worldwide, although predominantly in low-income countries in the Middle East and Africa, up to 13% of hepatitis C virus (HCV) infections are caused by HCV genotype 4. For patients with HCV genotype 1, the combination of ledipasvir and sofosbuvir has been shown to cure high proportions of patients with excellent tolerability, but this regimen has not been assessed for the treatment of HCV genotype 4. We assessed the efficacy, safety, and tolerability of 12 weeks of combination therapy with ledipasvir and sofosbuvir for patients with chronic HCV genotype 4 infections.

Novel interferon- and ribavirin-free regimens are needed to treat hepatitis C virus (HCV) infection.

The Phase-2 C-SALVAGE study evaluated an investigational interferon-free combination of grazoprevir (a NS3/4A protease inhibitor) and elbasvir (a NS5A inhibitor) with ribavirin for patients with chronic HCV genotype-1 infection who had failed licensed DAA-containing therapy.

Hepatitis C virus (HCV) genotype 4 accounts for about 13% of global HCV infections. Because interferon-containing treatments for genotype 4 infection have low efficacy and poor tolerability, an unmet need exists for effective all-oral regimens. We examined the efficacy and safety of an all-oral interferon-free regimen of ombitasvir, an NS5A inhibitor, and paritaprevir (ABT-450), an NS3/4A protease inhibitor dosed with ritonavir (ombitasvir plus paritaprevir plus ritonavir), given with or without ribavirin.

Patients with cirrhosis resulting from chronic hepatitis C virus (HCV) infection are at risk of life-threatening complications, but consistently achieve lower sustained virological response (SVR) than patients without cirrhosis, especially if treatment has previously failed. We assessed the efficacy and safety of the NS5A inhibitor ledipasvir and the nucleotide polymerase inhibitor sofosbuvir, with and without ribavirin.

Interferon-free regimens are needed to treat hepatitis C virus (HCV) infections. We investigated the efficacy of combined simeprevir and sofosbuvir.

Effective treatment for hepatitis C virus (HCV) genotype 1 infection in patients who have not had a sustained virologic response to prior interferon-based therapy represents an unmet medical need.

In this phase 3 trial we evaluated the efficacy and safety of the interferon-free combination of ABT-450 with ritonavir (ABT-450/r), ombitasvir (also known as ABT-267), dasabuvir (also known as ABT-333), and ribavirin for the retreatment of HCV in patients who were previously treated with peginterferon-ribavirin.

No data are available about the prediction of long-term survival using repeated noninvasive tests of liver fibrosis in chronic hepatitis C (CHC). We aimed to assess the prognostic value of 3-year liver stiffness measurement (LSM), aspartate aminotransferase to platelet ratio index (APRI), and fibrosis 4 (FIB-4) evolution in CHC. CHC patients with two LSM (1,000-1,500 days interval) were prospectively included. Blood fibrosis tests APRI and FIB-4 were calculated the day of baseline (bLSM) and follow-up (fLSM) LSM. Evolution of fibrosis tests was expressed as delta: (follow-up-baseline results)/duration. Date and cause of death were recorded during follow-up that started the day of fLSM. In all, 1,025 patients were included. Median follow-up after fLSM was 38.0 months (interquartile range [IQR]: 27.7-46.1) during which 35 patients died (14 liver-related death) and seven had liver transplantation. Prognostic accuracy (Harrell C-index) of multivariate models including baseline and delta results was not significantly different between LSM and FIB-4 (P ≥ 0.24), whereas FIB-4 provided more accurate prognostic models than APRI (P = 0.03). By multivariate analysis including LSM variables, overall survival was independently predicted by bLSM, delta (dLSM), and sustained virological response (SVR). Prognosis was excellent in patients having bLSM <7 kPa, SVR, or no increase (<1 kPa/year) in 7-14 kPa bLSM. Prognosis was significantly impaired in patients with an increase (≥ 1 kPa/year) in 7-14 kPa bLSM, or decrease (≤ 0 kPa/year) in ≥ 14 kPa bLSM (P = 0.949 between these two groups). Patients with an increase (>0 kPa/year) in ≥ 14 kPa bLSM had the worst prognosis. Baseline and delta FIB-4 also identified patient subgroups with significantly different prognosis.

All-oral combination therapy is desirable for patients with chronic hepatitis C virus (HCV) infection. We evaluated daclatasvir (an HCV NS5A replication complex inhibitor) plus sofosbuvir (a nucleotide analogue HCV NS5B polymerase inhibitor) in patients infected with HCV genotype 1, 2, or 3.

Early treatment of acute hepatitis C virus (HCV) infection with interferon alfa monotherapy is very effective, with cure rates of greater than 85%. However, spontaneous clearance of HCV occurs in 10-50% of cases. We aimed to assess an alternative treatment strategy of delayed antiviral therapy in patients who do not eliminate the virus spontaneously compared with immediate treatment.

Earlier studies have suggested neurocognitive impairment in patients with chronic hepatitis C virus (HCV) infection even before liver cirrhosis has developed. Since these deficits might be reversible after successful antiviral therapy, we analyzed the long-term course of neurocognitive parameters in HCV patients with and without successful virus elimination by an interferon-based antiviral treatment. In a multicenter study including 168 HCV patients receiving antiviral therapy (peginterferon alpha-2b and ribavirin) we performed a long-term follow-up of neurocognitive performance before and after treatment. Neurocognitive function was psychometrically assessed using the computer-aided TAP (Test Battery of Attentional Performance). When tested at least 12 months after termination of antiviral treatment, patients with sustained virologic response (SVR) had improved significantly as compared to their pretreatment performance in three of five TAP subtasks (vigilance, P < 0.001; shared attention: optical task, P < 0.001; working memory, P < 0.001). Patients who failed to eradicate the virus, however, showed no significant long-term changes in neurocognitive performance in all five subtasks assessed (0.194 < P < 0.804). In the posttreatment evaluation, neurocognitive function was significantly better in responders to the antiviral therapy as compared to nonresponders.

A national survey for chronic hepatitis C has not been performed in Denmark and the prevalence is unknown. Our aim was to estimate the prevalence of chronic hepatitis C from public registers and the proportion of these patients who received specialized healthcare.

Since 2000 outbreaks of acute hepatitis C virus (HCV) among HIV-positive men who have sex with men (MSM) who denied injecting drug use have been reported from Europe, the United States, Canada and Australia. Given the burden of liver disease, in particular HCV, on the morbidity and mortality in HIV patients in the era of combination antiretroviral therapy, the rapid and significant rise in the incidence of HCV in the HIV-infected MSM population in high-income countries is alarming. This relates to a significant change in the epidemiology of HCV that has occurred, with HCV emerging as a sexually transmitted infection within this population. Work to date suggests that this permucosal HCV transmission results from high-risk sexual and noninjecting drug use behaviours, reopening the discussion on the importance of sexual transmission. Given this occurs almost exclusively in HIV-infected MSM, HIV probably has a critical role mediated either through behavioural and/or biological factors. Finally, the management of acute HCV in HIV infection is complicated by concomitant HIV infection and combination antiretroviral therapy. This review will synthesize the most recent epidemiological, immunological and management issues that have emerged as a result of the epidemic of acute HCV among HIV-infected MSM.

Tenofovir disoproxil fumarate (DF) is a nucleotide analogue and a potent inhibitor of human immunodeficiency virus type 1 reverse transcriptase and hepatitis B virus (HBV) polymerase.

The diagnosis and treatment of hepatocellular carcinoma (HCC) have witnessed major changes over the past decade. Until the early 1990s, HCC was a relatively rare malignancy, typically diagnosed at an advanced stage in a symptomatic patient, and there were no known effective palliative or therapeutic options. However, the rising incidence of HCC in several regions around the world coupled with emerging evidence for efficacy of screening in high-risk patients, liver transplantation as a curative option in select patients, ability to make definitive diagnosis using high-resolution imaging of the liver, less dependency on obtaining tissue diagnosis, and proven efficacy of transarterial chemoembolization and sorafenib as palliative therapy have improved the outlook for HCC patients. In this article, we present a summary of the most recent information on screening, diagnosis, staging, and different treatment modalities of HCC, as well as our recommended management approach.

Entecavir, a drug approved by the Food and Drug Administration for the treatment of chronic hepatitis B virus (HBV) infection, is not believed to inhibit replication of human immunodeficiency virus type 1 (HIV-1) at clinically relevant doses. We observed that entecavir led to a consistent 1-log(10) decrease in HIV-1 RNA in three persons with HIV-1 and HBV coinfection, and we obtained supportive in vitro evidence that entecavir is a potent partial inhibitor of HIV-1 replication. Detailed analysis showed that in one of these patients, entecavir monotherapy led to an accumulation of HIV-1 variants with the lamivudine-resistant mutation, M184V. In vitro experiments showed that M184V confers resistance to entecavir. Until more is known about HIV-1-resistance patterns and their selection by entecavir, caution is needed with the use of entecavir in persons with HIV-1 and HBV coinfection who are not receiving fully suppressive antiretroviral regimens.

Entecavir is a potent and selective guanosine analogue with significant activity against hepatitis B virus (HBV).

The natural history of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected patients has never been studied according to the concept of liver fibrosis progression. The aim of this work was to assess the fibrosis progression rate in HIV-HCV coinfected patients and in patients infected by HCV only. A cohort of 122 HIV-HCV coinfected patients was compared with a control group of 122 HIV-negative HCV-infected patients. Groups were matched according to age, sex, daily alcohol consumption, age at HCV infection, and duration and route of HCV infection. The fibrosis progression rate was defined as the ratio between fibrosis stage (METAVIR scoring system) and the HCV duration. The prevalence of extensive liver fibrosis (METAVIR fibrosis scores 2, 3, and 4) and moderate or severe activity were higher in HIV-infected patients (60% and 54%, respectively) than in control patients (47% and 30%, respectively; P <.05 and P <.001, respectively). The median fibrosis progression rate in coinfected patients and in control patients was 0.153 (95% confidence interval [CI], 0.117-0.181) and 0.106 (95% CI, 0.084-0.125) fibrosis units per year, respectively (P <.0001). HIV seropositivity (P <.0001), alcohol consumption (>50 g/d, P =.0002), age at HCV infection (<25 years old, P <.0001), and severe immunosuppression (CD4 count 50 g/d), CD4 count ( PMID: 10498659

Our aim was to assess the natural history of liver fibrosis progression in hepatitis C and the factors associated with this progression.

Few data are available concerning the long-term prognosis of chronic liver disease associated with hepatitis C virus infection. This study examined the morbidity and survival of patients with compensated cirrhosis type C.

We measured antibody (anti-HCV) to hepatitis C virus, which causes non-A, non-B hepatitis, by radioimmunoassay in prospectively followed transfusion recipients and their donors. Of 15 patients with chronic non-A, non-B hepatitis documented by liver biopsy, all seroconverted for the antibody; of 5 with acute resolving non-A, non-B hepatitis, 3 (60 percent) seroconverted. The development of anti-HCV was delayed (mean delay, 21.9 weeks after transfusion, or 15 weeks after the onset of clinical hepatitis) and took approximately one year in one patient. Antibody has persisted in 14 of the 15 patients with chronic disease (mean follow-up, greater than or equal to 6.9 years; maximum, greater than or equal to 12), but has disappeared in the 3 with acute resolving disease after a mean of 4.1 years. Anti-HCV was detected in samples of donor serum given to 14 (88 percent) of the 16 anti-HCV-positive patients for whom all donor samples were available. Only 33 percent of the anti-HCV-positive donors tested had an elevated serum concentration of alanine aminotransferase; 54 percent were positive for antibody to the hepatitis B core antigen (anti-HBc). We conclude that hepatitis C virus is the predominant agent of transfusion-associated non-A, non-B hepatitis and that screening of donors for anti-HCV could prevent the majority of cases of the disease. "Surrogate" assays for anti-HBc and alanine aminotransferase would have detected approximately half the anti-HCV-positive donors involved in the transmission of hepatitis that we identified.