exudates and Hepatitis-C--Chronic

In low-income and middle-income countries, affordable direct-acting antivirals are urgently needed to treat hepatitis C virus (HCV) infection. The combination of ravidasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, and sofosbuvir has shown efficacy and safety in patients with chronic HCV genotype 4 infection. STORM-C-1 trial aimed to assess the efficacy and safety of ravidasvir plus sofosbuvir in a diverse population of adults chronically infected with HCV.. STORM-C-1 is a two-stage, open-label, phase 2/3 single-arm clinical trial in six public academic and non-academic centres in Malaysia and four public academic and non-academic centres in Thailand. Patients with HCV with compensated cirrhosis (Metavir F4 and Child-Turcotte-Pugh class A) or without cirrhosis (Metavir F0-3) aged 18-69 years were eligible to participate, regardless of HCV genotype, HIV infection status, previous interferon-based HCV treatment, or source of HCV infection. Once daily ravidasvir (200 mg) and sofosbuvir (400 mg) were prescribed for 12 weeks for patients without cirrhosis and for 24 weeks for those with cirrhosis. The primary endpoint was sustained virological response at 12 weeks after treatment (SVR12; defined as HCV RNA <12 IU/mL in Thailand and HCV RNA <15 IU/mL in Malaysia at 12 weeks after the end of treatment). This trial is registered with ClinicalTrials.gov, number NCT02961426, and the National Medical Research Register of Malaysia, NMRR-16-747-29183.. Between Sept 14, 2016, and June 5, 2017, 301 patients were enrolled in stage one of STORM-C-1. 98 (33%) patients had genotype 1a infection, 27 (9%) had genotype 1b infection, two (1%) had genotype 2 infection, 158 (52%) had genotype 3 infection, and 16 (5%) had genotype 6 infection. 81 (27%) patients had compensated cirrhosis, 90 (30%) had HIV co-infection, and 99 (33%) had received previous interferon-based treatment. The most common treatment-emergent adverse events were pyrexia (35 [12%]), cough (26 [9%]), upper respiratory tract infection (23 [8%]), and headache (20 [7%]). There were no deaths or treatment discontinuations due to serious adverse events related to study drugs. Of the 300 patients included in the full analysis set, 291 (97%; 95% CI 94-99) had SVR12. Of note, SVR12 was reported in 78 (96%) of 81 patients with cirrhosis and 153 (97%) of 158 patients with genotype 3 infection, including 51 (96%) of 53 patients with cirrhosis. There was no difference in SVR12 rates by HIV co-infection or previous interferon treatment.. In this first stage, ravidasvir plus sofosbuvir was effective and well tolerated in this diverse adult population of patients with chronic HCV infection. Ravidasvir plus sofosbuvir has the potential to provide an additional affordable, simple, and efficacious public health tool for large-scale implementation to eliminate HCV as a cause of morbidity and mortality.. National Science and Technology Development Agency, Thailand; Department of Disease Control, Ministry of Public Health, Thailand; Ministry of Health, Malaysia; UK Aid; Médecins Sans Frontières (MSF); MSF Transformational Investment Capacity; FIND; Pharmaniaga; Starr International Foundation; Foundation for Art, Research, Partnership and Education; and the Swiss Agency for Development and Cooperation.

Topics: Adult; Aged; Antiviral Agents; Benzimidazoles; Coinfection; Drug Therapy, Combination; Female; Genotype; Hepacivirus; Hepatitis C, Chronic; HIV Infections; Humans; Liver Cirrhosis; Malaysia; Male; Middle Aged; RNA, Viral; Safety; Sofosbuvir; Sustained Virologic Response; Thailand; Treatment Outcome; Valine; Viral Nonstructural Proteins

This was an open-label, uncontrolled study with the aim of assessing the efficacy and safety of pegylated interferon alfa-2b plus ribavirin in the treatment of chronic hepatitis C. The study was conducted in Island Hospital, Penang beween January 2002 and December 2003. Thirty-three patients were enrolled in this study with ten defaulters. The overall sustained virological response (SVR) (Intention-To-Treat analysis) in naïve patients was 39.10%. However, when the study was adjusted to only include those who completed treatment and follow-up, overall SVR as 52.9%. Side-effects were tolerable in most patients with anaemia occurring in 22 patients (66.7%), leukopenia 23 patients (69.7%) and thrombocytopenia in 15 patients (45.5%). This study showed that pegylated interferon alfa-2b 1.5 mcg/kg/week plus ribavirin > 10.6 mg/kg/day is efficacious and safe to be used in the treatment of: chronic hepatitis C.

Topics: Adult; Aged; Antiviral Agents; Drug Therapy, Combination; Female; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Malaysia; Male; Middle Aged; Polyethylene Glycols; Recombinant Proteins; Ribavirin

A scaled-up treatment cascade with direct-acting antiviral (DAA) therapy is necessary to achieve global WHO targets for hepatitis C virus (HCV) elimination in Malaysia. Recently, limited access to sofosbuvir/daclatasvir (SOF/DAC) is available through compulsory licensing, with access to sofosbuvir/velpatasvir (SOF/VEL) expected through voluntary licensing due to recent agreements. SOF/VEL has superior clinical outcomes but has higher drug acquisition costs compared to SOF/DAC. A stratified treatment cascade might be the most cost-efficient approach for Malaysia whereby all HCV patients are treated with SOF/DAC except for patients with cirrhosis who are treated with SOF/VEL.. This study aimed to conduct a 5-year budget impact analysis of the proposed stratified treatment cascade for HCV treatment in Malaysia. A disease progression model that was developed based on model-predicted HCV epidemiology data was used for the analysis, where all HCV patients in scenario A were treated with SOF/DAC for all disease stages while in scenario B, SOF/DAC was used only for non-cirrhotic patients and SOF/VEL was used for the cirrhotic patients. Healthcare costs associated with DAA therapy and disease stage monitoring were included to estimate the downstream cost implications.. The stratified treatment cascade with 109 in Scenario B was found to be cost-saving compared to Scenario A. The cumulative savings for the stratified treatment cascade was USD 1.4 million over 5 years.. A stratified treatment cascade with SOF/VEL was expected to be cost-saving and can result in a budget impact reduction in overall healthcare expenditure in Malaysia.

Topics: Antiviral Agents; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Humans; Malaysia; Sofosbuvir

While the availability of generic direct-acting antivirals (DAAs) opens the door for large-scale treatment, the care for people living with hepatitis C virus (HCV) in Malaysia is shifting toward a tripartite partnership between the public health system, correctional settings and civil society organizations (CSOs). This study aimed to explore the barriers to scaling up HCV treatment in Malaysia from the perspective of key stakeholders.. Eighteen focus-group discussions (FGDs) were conducted with 180 individuals, who actively engaged in coordinating, executing or supporting the implementation of the national strategic plan for HCV. An analytical framework was adapted to guide the data collection and thematic analysis. It covered four key aspects of HCV treatment: geographical accessibility, availability, affordability and acceptability.. Movement restrictions in times of coronavirus disease 2019 (COVID-19) outbreaks and being marginalized translated into barriers to treatment access in people living with HCV. Barriers to treatment initiation in health and correctional settings included limited staffing and capacity; disruption in material supply; silos mentality and unintegrated systems; logistical challenges for laboratory tests; and insufficient knowledge of care providers. Although no-cost health services were in place, concerns over transportation costs and productivity loss also continued to suppress the treatment uptake. Limited disease awareness, along with the disease-related stigma, further lowered the treatment acceptability.. This study disclosed a series of supply- and demand-side barriers to expanding the treatment coverage among people living with HCV in Malaysia. The findings call for strengthening inter-organizational collaborations to overcome the barriers.

Topics: Antiviral Agents; COVID-19; Health Services; Hepatitis C; Hepatitis C, Chronic; Humans; Malaysia; SARS-CoV-2

Hepatitis C virus (HCV) infects more than 71 million people worldwide and chronic HCV infection increases the risk of liver cirrhosis and failure. Haemodialysis (HD) is one of the renal replacement therapies with risk of HCV transmission. Anti-HCV antibodies are the serological screening test for HCV infection that does not detect active phase of infection. Majority HCV infected HD patients in Malaysia do not have further HCV RNA performed due to high cost and thus HCV treatment is less frequently offered. HCV Core Antigen (HCV Ag) can potentially be used to diagnose active HCV infection in HD population in comparison to HCV RNA, at lower cost.. We conducted a cross-sectional study to assess the correlation between HCV Ag and HCV RNA and to identify the prevalence of active HCV infection among HCV seropositive HD patients from dialysis centres across West Malaysia from July 2019 to May 2020. Pre-dialysis blood was taken and tested for both HCV Ag and HCV RNA tests. HCV Ag was tested with Abbott ARCHITECT HCV Ag test.. We recruited 112 seropositive HD patients from 17 centres with mean age of 54.04 ± 11.62 years, HD vintage of 14.1 ± 9.7 years, and male constitute 59.8% (67) of the study population. HCV Ag correlates well with HCV RNA (Spearman test coefficient 0.833, p < 0.001). The sensitivity was 90.7%, specificity 100%, positive predictive value (PPV) 100%, negative predictive value (NPV) 76.5%, and accuracy 92.9%. For HCV RNA level > 3000 IU/mL, HCV Ag had a higher sensitivity of 95.1% and greater correlation (Spearman test coefficient 0.897, p < 0.001). The prevalence of active HCV infection was 76.8% among HCV seropositive HD patients.. Although HCV Ag is less sensitive, it shows an excellent correlation with HCV RNA and has 100% PPV. HCV Ag can be considered as an alternative diagnostic tool for chronic active HCV infection among HD cohort, who can then be considered for HCV treatment. For seropositive HD patient with negative HCV Ag, we recommend to follow-up with HCV RNA test.

Topics: Adult; Aged; Cross-Sectional Studies; Female; Hepacivirus; Hepatitis C Antibodies; Hepatitis C Antigens; Hepatitis C, Chronic; Humans; Kidney Failure, Chronic; Malaysia; Male; Middle Aged; Renal Dialysis; RNA, Viral; Sensitivity and Specificity; Serologic Tests

Mixed-genotypes hepatitis C virus (HCV) infections are normally ignored in chronic hemodialysis patients. The aim of this study is to investigate the prevalence of mixed-genotypes infections among hemodialysis patients in Pahang province, Malaysia. Reverse-transcription and polymerase chain reaction methods were performed using two different sets of primers, targeting the 5' untranslated region and nonstructural 5B region. Target region base sequences were obtained by direct sequencing. Discrepancy in outcomes from phylogenetic analysis of both regions suggests double infections. Of 40 subjects in eight hemodialysis centres, evidence of mixed-genotypes infections was found in 5 subjects (12.5%) from three different centres. Four patients were infected with mixed genotypes 3 and 1 and one with genotypes 3 and 4. Cases of mixed HCV genotypes infection were considered high among hemodialysis patients in Pahang. However, further investigation is needed to confirm whether they are true mixed infections or perhaps infection with recombinant virus and also to assess the clinicopathologic characteristics of the infection.

Topics: Base Sequence; Female; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Malaysia; Male; Middle Aged; Molecular Sequence Data; Prevalence; Renal Dialysis; Reverse Transcriptase Polymerase Chain Reaction

To determine the etiology of liver cirrhosis and risk factors for hepatocellular carcinoma (HCC) in a multiracial Asian population.. Consecutive patients with liver cirrhosis presenting to outpatient clinics and inpatient service at the University of Malaya Medical Centre from 1 April 2006 to 31 May 2009 were included.. A total of 460 patients were included in the study: 317 male patients (68.9%) and 143 female patients (31.1%), with a mean age of 58.8years (range: 15-87years). The major causes of cirrhosis were: chronic hepatitis B, n=212, 46.1%; chronic hepatitis C, n=85, 18.5%; cryptogenic, n=71, 15.4%; alcohol, n=58, 12.6% and autoimmune, n=9, 2.0%. Alcohol was the main etiology in Indians (51.1%) compared to Malay (0%) and Chinese (4.4%) (both P<0.001). Hepatitis B was the predominant etiology in Malay (47.9%) and Chinese (58.8%) compared to Indians (5.6%) (both P<0.001). Hepatitis C cirrhosis was highest in Malays (25.0%). 136 patients (29.6%) had concurrent HCC. Male sex (P<0.001), age>60years (P=0.014), hepatitis B (P<0.001), hepatitis C (P=0.006) and cryptogenic cause (P=0.002) were found to be independent risk factors for HCC.. The etiology of cirrhosis has a peculiar pattern based on racial differences in alcohol intake and in the prevalence of hepatitis B.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alcohol Drinking; Asian People; Carcinoma, Hepatocellular; Chi-Square Distribution; China; Cross-Sectional Studies; Female; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; India; Liver Cirrhosis; Liver Neoplasms; Malaysia; Male; Middle Aged; Odds Ratio; Prevalence; Risk Assessment; Risk Factors; Young Adult

An analysis of 105 consecutive patients with chronic hepatitis C at the gastroenterology outpatient's clinic in Hospital Kuala Lumpur was performed. The clinical, laboratory and virological data was prospectively recorded in the case notes and comprised of data on patient characteristics, risk factors, clinical features, laboratory features, virology screen and management. Chronic Hepatitis C cases accounted for 2.1% of the total number of cases seen at this clinic during the entire period. There were 78 (74%) males and 27 (26%) females. The ethnic breakdown consisted of Chinese (44.2%), Malays (39.4%), Indians (15.4%) and others (1%). There was higher male preponderance in all the ethnic groups. The main mode of transmission was blood transfusion comprising 51 patients (48.8%). A total of 35.2% of cases underwent treatment, of which a proportion had interferon monotherapy for 6 or 12 months and a subsequent group of naïve patients and non-responders underwent combination therapy with interferon and ribavarin.

Topics: Adolescent; Female; Hepatitis C, Chronic; Humans; Malaysia; Male; Middle Aged; Outpatient Clinics, Hospital