Peginterferon still has a place in the treatment of hepatitis C caused by genotype 3 virus

Despite recent advances in therapy for chronic hepatitis C (CHC), the disease caused by genotype 3 virus (GEN3) is still considered a treatment challenge in certain patient subgroups. The aim of this retrospective study was to evaluate the effectiveness and safety of the peginterferon (Peg-IFN) and ribavirin (RBV) combination treatment for GEN3/CHC patients, and to evaluate sustained virological response (SVR) indicators and early treatment interruption due to serious adverse events (SAE). This was a retrospective observational study of GEN3/CHC patients, co-infected or not by HIV and treated with Peg-IFN/RBV in nine Brazilian healthcare centers. The study sample included 184 GEN3/CHC patients70 (38%) were co-infected with HIV. The overall SVR rate was 57.1% (95% CI 50-64). Among co-infected and mono-infected patients, the SVR rate was 51.4% (36/70) and 60.5% (69/114), respectively (p=0.241). Thirty-four (18.5%) patients experienced SAE and interrupted treatment. SVR was negatively associated with the use of Peg-IFN alpha 2b (PR 0.7595% CI 0.58-0.99p=0.045) and to early treatment interruption due to SAE (PR 0.3695% CI 0.20-0.68p=0.001). Early treatment interruption due to SAE was associated with age (PR 1.0695% CI 1.02-1.10p<0.001) and occurrence of liver cirrhosis (PR 2.0695% CI 1.11-3.83p=0.022). In conclusion, Peg-IFN/RBV might represent an adequate treatment option, mainly in young patients without advanced liver disease or when the use of direct-action drugs is limited to specific patient groups.Univ Sul Santa Catarina, Fac Med, Dept Ciencias Biol & Saude & Ciencias Sociais Apl, Disciplina Doencas Infecciosas, Av Pedra Branca 25, BR-88137270 Palhoca, SC, BrazilUniv Fed Sao Paulo, Disciplina Infectol, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med, Div Gastroenterol & Hepatol, Sao Paulo, SP, BrazilUniv Fed Estado Rio de Janeiro, Dept Clin Med, Disciplina Gastroenterol, Rio De Janeiro, RJ, BrazilUniv Fed Espirito Santo, Serv Infectol, Vitoria, ES, SpainUniv Sao Paulo, Fac Med Ribeirao Preto, Div Gastroenterol, Ribeirao Preto, SP, BrazilInst Infectol Emilio Ribas, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med, Dept Doencas Infecciosas & Parasitarias, Sao Paulo, SP, BrazilSecretaria Estadual Saude, Unidade Mista Saude, Unimista 508 509, Brasilia, DF, BrazilUniv Sao Paulo, Inst Med Trop Sao Paulo, Lab Virol, LIM 52, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Disciplina Infectol, Sao Paulo, SP, BrazilWeb of Scienc

Effectiveness and safety of first-generation protease inhibitors in real-world patients with hepatitis C virus genotype 1 infection in Brazil: a multicenter study

OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p 465 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts.Univ Sao Paulo, Fac Med, Dept Molestias Infecciosas & Parasitarias, Sao Paulo, SP, BrazilUniv Fed Rio de Janeiro, Rio De Janeiro, RJ, BrazilCtr Referencia & Treinamento DST Aids, Sao Paulo, SP, BrazilCDH, Rio De Janeiro, RJ, BrazilHosp Fed Servidores Estado Rio de Janeiro HFSE, Setor Gastrohepatol, Rio De Janeiro, RJ, BrazilUniv Sao Paulo, Fac Med, Dept Gastroenterol & Hepatol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Disciplina Gastroenterol, EPM, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, EPM, Disciplina Infectol, Sao Paulo, SP, BrazilUniv Sao Paulo, FMRP, Dept Clin Med, Div Gastroenterol, Sao Paulo, SP, Brazil| Univ Fed do Maranhao UFMA, HUPD, Ctr Pesquisa Clin, Sao Luis, MA, BrazilUniv Fed Estado Rio de Janeiro UNIRIO, Disciplina Clin Med & Gastroenterol, Rio De Janeiro, RJ, BrazilUniv Fed Rio do Grande Sul UFRGS, Dept Med Interna, Porto Alegre, RS, BrazilUniv Fed Espirito Santo, Ambulatorio HIV AIDS Hepatites Virais, Vitoria, ES, BrazilSMS, Ctr Orientacao & Aconselhamento, Foz Do Iguacu, PR, BrazilUniv Estado Rio de Janeiro UERJ, Serv Gastroenterol, Rio De Janeiro, RJ, BrazilIMT, Lab Virol LIM 52, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Disciplina Gastroenterol, EPM, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, EPM, Disciplina Infectol, Sao Paulo, SP, BrazilWeb of Scienc

Efficacy and safety of entecavir for chronic HBV in HIV/HBV coinfected patients receiving lamivudine as part of antiretroviral therapy

Background: Prolonged use of lamivudine in patients coinfected with HIV and hepatitis B virus (HBV) leads to an increasing risk of lamivudine resistance in both diseases. We investigated the addition of entecavir, a potent inhibitor of HBV polymerase, to lamivudine-containing highly active antiretroviral therapy (HAART) in patients who experienced rebound in HBV viremia while maintaining Suppression of plasma HIV RNA less than 400 copies/ml. Methods: Sixty-eight patients were randomized to entecavir 1 mg (n = 51) or placebo (n = 17) once daily for 24 weeks; 65 patients continued the study with entecavir for an additional 24 weeks. Lamivudine-containing HAART was continued throughout. Results: At week 24, the mean HBV DNA in entecavir-treated patients was 5.52 log(10) - copies/ml versus 9.27 log(10) copies/ml for placebo, and at week 48, it was 4.79log(10) copies/ml versus 5.63log(10) copies/ml, respectively. The mean HBV DNA change from baseline for entecavir was -3.65 log(10) copies/ml (versus + 0.11 for placebo, P < 0.0001) and alanine aminotransferase normalization in 34%. of patients (versus 8% for placebo, P=0.08)At 48 weeks, mean change in HBV DNA reached -4.20log(10) copies/ml inpatients who received entecavir for the entire 48 weeks. The frequency of adverse events with entecavir and placebo was comparable. Through 48 weeks, no clinically relevant changes in HIV viremia or CD4 cell Counts were identified. Conclusion: In this study, entecavir was associated with rapid, clinically significant reductions in HBV DNA, with maintenance of HIV viremia suppression, in HIV/HBV coinfected patients with HBV viremia while on lamivudine treatment. (C) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

A potential clinical based score in hepatitis C virus cirrhotic patients to exclude small hepatocellular carcinoma

Aim: Hepatitis C virus (HCV) cirrhosis is an important cause of hepatocellular carcinoma (HCC). This study aimed to identify factors of HCC presence among HCV cirrhotic patients with and without small diameter HCC (≤ 3 cm).Methods: A case control transversal study between 1998 and 2003 including 93 patients: 31 with small diameter HCC and 62 without HCC. Groups were matched by age and gender. Multiple logistic regression analysis using Akaike Information Criteria to estimate the probability of HCC was performed. A model score was generated and bootstrap analysis was performed for internal validation.Results: Three significant laboratorial variables for HCC presence were found: alanine aminotransferase &gt; 37 U/L [odds ratio (OR): 7.43 (1.61-34.19), P = 0.01], alpha-fetoprotein &gt; 20 ng/mL [OR: 16.2 (4.17-63.01), P &lt; 0.001] and platelet count &lt; 100,000/mm3 [OR: 3.62 (1.43-9.14), P = 0.007]. A model score with an area under curve of 0.79 (95% CI: 0.7-0.89) was built based on these variables. The negative predictive value of those classified as at low risk of HCC was 99.1%.Conclusion: An easy and practical model score was generated. It may be an auxiliary tool for identification of HCV patients with low probability of small diameter HCC at initial evaluation composed of three serum examinations used in routine outpatient clinical practice

Executive Summary of the KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease

Infection with the hepatitis C virus (HCV) has adverse liver, kidney, and cardiovascular consequences in patients with chronic kidney disease (CKD), including those on dialysis therapy or with a kidney transplant. Since the publication of the Kidney Disease: Improving Global Outcomes (KDIGO) HCV Guideline in 2018, advances in HCV management, particularly in the field of antiviral therapy and treatment of HCV-associated glomerular diseases, coupled with increased usage of HCV-positive kidney grafts, have prompted a reexamination of the 2018 guideline. As a result, the Work Group performed a comprehensive review and revised the 2018 guidance. This Executive Summary highlights key aspects of the updated guideline recommendations for 3 chapters: Chapter 2: Treatment of HCV infection in patients with CKD; Chapter 4: Management of HCV-infected patients before and after kidney transplantation; and Chapter 5: Diagnosis and management of kidney diseases associated with HCV infection.Funding Agencies|KDIGO</p

Effectiveness and safety of first-generation protease inhibitors in real-world patients with hepatitis C virus genotype 1 infection in Brazil : a multicenter study

OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-totreat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, po0.001) and a higher incidence of serious adverse events (50.7% vs. 34.8%, po0.001). Multivariate analysis revealed that sustained viral response was associated with the absence of cirrhosis, viral recurrence after previous treatment, pretreatment platelet count greater than 100,000/mm3, and achievement of a rapid viral response. Female gender, age465 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts

Fibrates for the Treatment of Primary Biliary Cholangitis Unresponsive to Ursodeoxycholic Acid: An Exploratory Study

Aim: Up to 40% of patients with primary biliary cholangitis (PBC) will have a suboptimal biochemical response to ursodeoxycholic acid (UDCA), which can be improved by the addition of fibrates. This exploratory study aims to evaluate the long-term real-life biochemical response of different fibrates, including ciprofibrate, in subjects with UDCA-unresponsive PBC.Methods: The Brazilian Cholestasis Study Group multicenter database was reviewed to assess the response rates to UDCA plus fibrates in patients with UDCA-unresponsive PBC 1 and 2 years after treatment initiation by different validated criteria.Results: In total, 27 patients (100% women, mean age 48.9 +/- 9.2 years) with PBC were included. Overall response rates to fibrates by each validated criterion varied from 39 to 60% and 39-76% at 12 and 24 months after treatment combination, respectively. Combination therapy resulted in a significant decrease in ALT and ALP only after 2 years, while GGT significantly improved in the first year of treatment. Treatment response rates at 1 and 2 years appear to be comparable between ciprofibrate and bezafibrate using all available criteria.Conclusion: Our findings endorse the efficacy of fibrate add-on treatment in PBC patients with suboptimal response to UDCA. Ciprofibrate appears to be at least as effective as bezafibrate and should be assessed in large clinical trials as a possibly new, cheaper, and promising option for treatment of UDCA-unresponsive PBC patients

Response to Ursodeoxycholic Acid May Be Assessed Earlier to Allow Second-Line Therapy in Patients with Unresponsive Primary Biliary Cholangitis

Background Response to ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) has been traditionally assessed 1 to 2 years after treatment initiation. With the development of new drugs, some patients may benefit from an earlier introduction of second-line therapies. Aims This study aims to identify whether well-validated response criteria could correctly identify individuals likely to benefit from add-on second-line therapy at 6 months. Methods Analysis of a multicenter retrospective cohort which included only patients with clear-cut PBC. Results 206 patients with PBC (96.6% women; mean age 54 +/- 12 years) were included. Kappa concordance was substantial for Toronto (0.67), Rotterdam (0.65), Paris 1 (0.63) and 2 (0.63) criteria at 6 and 12 months, whereas Barcelona (0.47) and POISE trial (0.59) criteria exhibited moderate agreement. Non-response rates to UDCA was not statistically different when assessed either at 6 or 12 months using Toronto, Rotterdam or Paris 2 criteria. Those differences were even smaller or absent in those subjects with advanced PBC. Mean baseline alkaline phosphatase was 2.73 +/- 1.95 times the upper limit of normal (x ULN) among responders versus 5.05 +/- 3.08 x ULN in non-responders (p < 0.001). Conclusions After 6 months of treatment with UDCA, the absence of response by different criteria could properly identify patients who could benefit from early addition of second-line therapies, especially in patients with advanced disease or high baseline liver enzymes levels

Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study

BACKGROUND: The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate viral hepatitis by 2030. Although no virological cure exists for hepatitis B virus (HBV) infection, existing therapies to control viral replication and prophylaxis to minimise mother-to-child transmission make elimination of HBV feasible. We aimed to estimate the national, regional, and global prevalence of HBsAg in the general population and in the population aged 5 years in 2016, as well as coverage of prophylaxis, diagnosis, and treatment. METHODS: In this modelling study, we used a Delphi process that included a literature review in PubMed and Embase, followed by interviews with experts, to quantify the historical epidemiology of HBV infection. We then used a dynamic HBV transmission and progression model to estimate the country-level and regional-level prevalence of HBsAg in 2016 and the effect of prophylaxis and treatment on disease burden. FINDINGS: We developed models for 120 countries, 78 of which were populated with data approved by experts. Using these models, we estimated that the global prevalence of HBsAg in 2016 was 3·9% (95% uncertainty interval [UI] 3·4-4·6), corresponding to 291 992 000 (251 513 000-341 114 000) infections. Of these infections, around 29 million (10%) were diagnosed, and only 4·8 million (5%) of 94 million individuals eligible for treatment actually received antiviral therapy. Around 1·8 (1·6-2·2) million infections were in children aged 5 years, with a prevalence of 1·4% (1·2-1·6). We estimated that 87% of infants had received the three-dose HBV vaccination in the first year of life, 46% had received timely birth-dose vaccination, and 13% had received hepatitis B immunoglobulin along with the full vaccination regimen. Less than 1% of mothers with a high viral load had received antiviral therapy to reduce mother-to-child transmission. INTERPRETATION: Our estimate of HBV prevalence in 2016 differs from previous studies, potentially because we took into account the effect of infant prophylaxis and early childhood vaccination, as well as changing prevalence over time. Although some regions are well on their way to meeting prophylaxis and prevalence targets, all regions must substantially scale-up access to diagnosis and treatment to meet the global targets. FUNDING: John C Martin Foundation.status: publishe