Recovery from Hepatitis C virus (HCV) infection is considered infrequent (<20%) in western populations but reaches 50% in West Africa where genotype 2 infection is predominant. To investigate the role of cellular immune responses and host genetics in this phenomenon, samples from 104 Ghanaian blood donors reactive with anti-HCV assays were collected between 2000 and 2005. HCV antibody was confirmed by Western blot using genotype 2 recombinant core, E2 and NS3 proteins. Viral load and genotype were determined. Samples were stratified into 37 chronic, 35 recovered infections and 32 false positive. Eighty-one percentage of subjects with chronic infection (RNA positive) carried genotype 2 HCV. Cellular immune response was investigated in 35 frozen peripheral blood mononuclear cell (PBMC) samples suitable for interferon-gamma ELISPOT assay. Twelve out of 24 confirmed recovered, 1 out of 5 chronically infected and none of the 6 false-positive controls reacted to recombinant proteins. HLA-A, -B and -DR types were determined by DNA methodology. HLA-B*57 was significantly more frequent in the group which had recovered from HCV infection compared with chronically infected subjects (P = 0.0053, OR = 8.02). In conclusion, it is hypothesized that the dominance of genotype 2 HCV strains may be an important factor explaining the high rate of recovery from HCV infections in Ghana via an efficient contribution of HLA-B*57 which is relatively frequent in the population.

To date, all studies regarding hepatitis C virus (HCV) F protein have been based on expression in vitro/in vivo of recombinant protein or monoclonal antibodies derived from genotype 1a or 1b sequences, but not from other genotypes. The objective of this study was to prepare a putative genotype 2 recombinant F protein and evaluate its reactivity in plasma from individuals with chronic HCV infection or who had recovered from infection. One genotype 2 strain was selected for F protein (F-2) and core expression in bacterial culture. An ELISA was developed and applied to samples from patients with chronic infection or recovered infection of various genotypes. The anti-F-2 response in 117 samples showed a significantly higher reactivity in chronic than in recovered HCV-infected blood donors (P<0.001), but no difference was found among genotypes. However, the correlation between anti-F and anti-core was more significant in genotypes 1 and 2 than in genotype 3. Anti-F-2 titres were also significantly higher in chronic than in recovered individuals (P<0.0001). Antibody titres to recombinant genotype 2 core protein or to genotype 1 multiple proteins used in commercial anti-HCV assays paralleled the anti-F-2 end-point antibody titre. This study thus demonstrated the antigenicity of genotype 2 HCV F protein, although the exact location of the natural frameshift position remains unknown. The difference in anti-F-2 response between chronic and recovered infection, the cross-reactivity irrespective of genotype and the correlation of antibody response with structural and non-structural antigens suggest that the immune response to F protein is an integral part of the natural HCV infection.

Background Corticosteroid injection for knee osteoarthritis is limited by its modest duration of treatment effect. The liposome formulation of dexamethasone sodium phosphate (TLC599) was developed for the sustained relief of osteoarthritis pain. This clinical study was conducted to evaluate the efficacy and safety of TLC599 at two dose levels in patients with knee osteoarthritis. Methods A randomized, double-blinded, placebo-controlled study was conducted in 75 patients with osteoarthritis of the knee from 13 study centers. Patients were randomized and administered a single intra-articular injection of TLC599 or placebo and assessed for efficacy and safety for 24 weeks. Patient-reported outcomes included the Western Ontario and McMaster Universities Arthritis (WOMAC) Index for pain and function and visual analog scale for pain. Results TLC599 at 12 mg demonstrated significantly greater reduction in WOMAC pain through 12 weeks (least squares (LS) mean difference = − 0.37, p = 0.0027) and through 24 weeks (LS mean difference = − 0.35, p = 0.0037) when compared to placebo. TLC599 12 mg also exhibited significantly greater improvement in function when compared to placebo at 24 weeks (LS mean difference = − 0.26, p = 0.0457). TLC599 18 mg did not significantly improve pain or function in comparison with placebo. The use of acetaminophen during the study was less in both TLC599 groups in comparison with placebo. No major or unexpected safety issues were reported. Conclusions In participants with symptomatic knee osteoarthritis, TLC599 is a well-tolerated treatment that reduces pain and improves function for up to 24 weeks, a longer duration than that reported for existing IA treatments. Trial registration ClinicalTrials.gov, NCT03005873. Registered on 29 December 2016

Background  Recovery from Hepatitis C virus (HCV) infection is considered infrequent (<20%) in western populations but reaches 50% in West Africa where genotype 2 infection is predominant (Candotti J Virol 2003; 77: 7914). Aim  To investigate cellular immune responses as alternative diagnostic of HCV infection and the possible involvement of viral or host genetic factors in recovery. Methods  Samples from 104 Ghanaian blood donors screened with anti‐HCV rapid tests and enzyme immunoassay were collected between 2000 and 2005. HCV antibody screening was confirmed using genotype 2 recombinant core, E2 and NS3 proteins by Western blot. HCV viral load and genotype were determined. Cellular response to recombinant HCV genotype 2 proteins was tested by IFN gamma ELISpot on frozen cells. HLA genotype was determined by sequence specific oligonucleotide probes. Results  A total of 104 donors were stratified in 37 chronic, 35 recovered infections and 32 false positive. 81% of subjects with chronic infections with RNA detected carried genotype 2 HCV RNA. Cellular immune response was investigated in 35 frozen peripheral blood mononuclear cell (PBMC) samples suitable for interferon‐gamma ELISpot assay. 12 confirmed recovered, one chronically infected and no false positive controls reacted to at least one recombinant protein. The magnitude of response was considerably higher in recovered cases. HLA‐B*57 was significantly more frequent in the group which had recovered from HCV infection compared with chronically infected subjects (P < 0.01, OR = 8.02). This allele is significantly more frequent in West Africa than in Europe or North America. Discussion and conclusions  Cases classified as recovered by serological means were confirmed by the presence of T‐cells stimulated by viral proteins. Genotype 2 HCV tends to have lower viral load and better response to anti‐viral treatment suggesting that the local genotype might be more susceptible to immune control. However, genetic factors of the host might also influence the clinical outcome. It could be hypothesised that HLA‐B*5703 is the HLA molecule most efficient at presenting peptides from genotype 2 HCV in this population.