METHODS: Retrospective data pertaining to 713 patients from January 2009 to December 2013 were retrieved from hospital and disease notification records for analysis. The risk factors for hepatitis C virus (HCV) infection were grouped into IVDU and non-IVDU risk factors for analysis using multiple logistic regression.

RESULTS: Of the hepatitis C patients included in this study, the most common age group was 31 to 40 years (30.2%), and male patients (91.2%) made up the overwhelming majority. Ethnic Malays constituted approximately 80.4% of the patients, and IVDU was the main risk factor (77.8%) for HCV infection. Multiple logistic regression showed that male patients were 59 times more likely to have IVDU as a risk factor for HCV infection. Single patients were 2.5 times more likely to have IVDU as a risk factor. Patients aged ≥71 years were much less likely than patients aged ≤30 years to have IVDU as a risk factor for HCV infection.

METHODS: We established a multi-country cross-sectional dataset of first available quantitative HCV RNA linked to demographic and clinical data. We excluded individuals on HCV treatment. We analyzed the distribution of HCV RNA and determined critical thresholds for detection of HCV viraemia. We then performed logistic regression to evaluate factors associated with LLV, and derived relative sensitivities for significant covariates.

RESULTS: The dataset included 66,640 individuals with HCV viraemia from Georgia (44.4%), Canada (40.9%), India (8.1%), Cambodia (2.6%), Egypt (1.6%), Pakistan (1.3%), Cameroon (0.4%), Indonesia (0.2%), Thailand (0.2%), Vietnam (0.1%), Malaysia (0.05%), and Mozambique (0.02%). The 97% LOD was 1,318 IU/mL (95% CI 1298.4, 1322.3). Factors associated with LLV were younger age 18-30 vs. 51-64 years (OR 2.56 95% CI 2.19, 2.99), female vs. male sex (OR 1.32, 95% CI 1.18, 1.49), and advanced fibrosis stage F4 vs. F0-1 (OR 1.44, 95%CI 1.21, 1.69). Only the younger age group had a decreased relative sensitivity below 95% at 93.3%.

CONCLUSIONS: In this global dataset, a test with an LOD of 1,318 IU/mL would identify 97% of viraemic HCV infections among almost all populations. This LOD will help guide manufacturers in the development of affordable POC diagnostics to expand HCV testing and linkage to care in LMICs.

METHODS: 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.

FINDINGS: 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.

INTERPRETATION: 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.

METHODS: Five databases were searched from 1990-2016 for studies that took place in countries with a GDP per capita of $7,000 to $13,000 USD. The data extraction was performed based on information regarding prevalence, sample size, age of participants, duration of intravenous drug use (IDU), recruitment location, dates of data collection, study design, sampling scheme, type of tests used in identifying antibody reactivity to HCV, and the use of confirmatory tests. The synthesis was performed with a random effects model. The Cochrane statistical Q-test was used to evaluate the statistical heterogeneity of the results.

RESULTS: The 33 studies included in the analysis correspond to a sample of seven countries and 23,342 observations. The point prevalence value estimates and confidence intervals of the random effects model were 0.729 and 0.644-0.800, respectively for all seven countries, and were greatest for China (0.633; 0.522-0.732) as compared to Brazil (0.396; 0.249-0.564). Prevalence for Montenegro (0.416; 0.237-0.621) and Malaysia (0.475; 0.177-0.792) appear to be intermediate. Mexico (0.960) and Mauritania (0.973) had only one study with the largest prevalence. A clear association was not observed between age or duration of IDU and prevalence of HCV, but the data from some groups may indicate a possible relationship. The measures of heterogeneity (Q and I2) suggest a high level of heterogeneity in studies conducted at the country level and by groups of countries.

CASE PRESENTATION: A 52-year-old Malay gentleman, with hepatitis C virus and HIV infection was admitted to the intensive care unit for severe lactic acidosis, with concurrent Escherichia coli bacteremia with multiorgan dysfunction. The patient was started on highly active antiretroviral therapy, which included tenofovir, 5 weeks before presentation. Antimicrobial therapy, continuous veno-venous hemofiltration, and other supportive treatments were instituted. However, the patient eventually succumbed to his illness.