Evaluation of liver disease progression in the German hepatitis C virus (1b)-contaminated anti-D cohort at 35 years after infection.

UNLABELLED: The natural course of HCV infection remains controversial. The German HCV (1b)-contaminated anti-D cohort provides an ideal population to investigate the natural course of HCV infection in a large, homogenous cohort of young women from the date of HCV inoculation. Our previous follow-up studies at 20 and 25 years after infection suggested slow fibrosis progression rates in this unique cohort. The aim of our prospective, community-based, multicenter study was to reevaluate the liver disease progression in 718 patients of the original anti-D cohort at 35 years after infection. Patients with self-limited HCV infection (n = 189) were compared to those who failed to eliminate the virus spontaneously (n = 529), comprising patients who were treatment naïve (n = 197) or achieved a sustained virological response (SVR; n = 149), respectively, failed to clear the virus (non-SVR; n = 183) after antiviral therapy. In the overall cohort, 9.3% of patients showed clinical signs of liver cirrhosis at 35 years after infection. Liver disease progression largely depended on HCV infection status. The highest proportion of patients with clinical signs of end-stage liver disease was observed in the non-SVR group (15.3%), whereas decreased cirrhosis rates were detected in the SVR group (6%) and in patients with self-limited HCV infection (1.1%; P = 6.2 × 10(-6)). Overall survival was significantly enhanced after SVR, compared to treatment-naïve patients or non-SVR (P = 0.027). CONCLUSION: The present study provides further evidence for a mild, but significant, disease progression at 35 years after infection in the German HCV (1b)-contaminated anti-D cohort. Patients with self-limited HCV infection or SVR after antiviral treatment were protected from progressive liver disease and showed the best clinical long-term outcome.

The predictive value of IL28B gene polymorphism for spontaneous clearance in a single source outbreak cohort is limited in patients carrying the CCR5Δ32 mutation.

BACKGROUND & AIMS: The CCR5Δ32 mutation has been suspected to adversely affect outcomes of HCV infection, although reports have remained controversial. Here, we investigated the relative genetic contributions of the CCR5Δ32 deletion and the IL28B rs12979860 polymorphisms to spontaneous clearance of hepatitis C in a single-source outbreak. METHODS: We retrieved 396 Caucasian women (119 women with spontaneous HCV clearance) who had been infected with HCV genotype 1-contaminated anti-D immunoglobulin in 1978, and determined their IL28B and CCR5 alleles. RESULTS: IL28B CC, CT, and TT genotypes were found in 35.4%, 50%, and 14.6% of patients and corresponded to spontaneous clearance rates of 50%, 21.2%, and 12.1% (Chi(2)=38.7, p=5.0×10(-10)), respectively. CCR5 WT/WT, WT/Δ32, and Δ32/Δ32 genotypes were observed in 76%, 22.7%, and 1.3% of patients and corresponded to clearance rates of 33.2%, 21.2%, and 0% (Chi(2)=6.9, p=0.009), respectively. In a stepwise forward-conditional multivariate regression model both CCR5 (OR 2.1, p=0.01 for WT/WT) and IL28B genetic variants (OR 4.3, p=4.6×10(-10) for the C/C genotype) were identified as independent predictors of spontaneous HCV clearance. Importantly, favorable response rates were associated with the IL28B CC genotype only in CCR5 wild-type homozygous women, while HCV clearance in CCR5Δ32 carriers remained poor even in patients with the rs12979860 CC genotype. CONCLUSIONS: Both IL28B rs1297860 and CCR5Δ32 allelic variants are independent genetic determinants of spontaneous HCV clearance. The variable relative distribution between IL28B rs1297860 and CCR5Δ32 allelic variants in different populations may have masked the role of the CCR5Δ32 mutation in some studies.

A polymorphism near IL28B is associated with spontaneous clearance of acute hepatitis C virus and jaundice.

BACKGROUND & AIMS: A single nucleotide polymorphism (SNP) upstream of the IL28B gene has been associated with response of patients with chronic hepatitis C to therapy with pegylated interferon and ribavirin and also with spontaneous clearance of acute hepatitis C in a heterogeneous population. We analyzed the association between IL28B and the clinical presentation of acute hepatitis C virus (HCV) infection in a homogeneous population. METHODS: We analyzed the SNP rs12979860 in 190 women from the German anti-D cohort (infected with HCV genotype 1b via contaminated rhesus prophylaxis) and its association with spontaneous clearance. Clinical data were available in 136 women with acute infection who were also evaluated for IL28B genotype. Based on results of a TaqMan polymerase chain reaction assay, the rs12979860 SNP genotypes studied were C/C, C/T, or T/T. RESULTS: Spontaneous clearance was more common in patients with the C/C genotype (43/67; 64%) compared with C/T (22/90; 24%) or T/T (2/33; 6%) (P < .001). Jaundice during acute infection was more common among patients with C/C genotype (32.7%) than non-C/C patients (with C/T or T/T) (16.1%; P = .032). In C/C patients, jaundice during acute infection was not associated with an increased chance of spontaneous clearance (56.3%) compared with those without jaundice (60.6%). In contrast, in non-C/C patients, jaundice was associated with a higher likelihood of spontaneous clearance (42.9%) compared with those without jaundice (13.7%). CONCLUSIONS: The SNP rs12979860 upstream of IL28B is associated with spontaneous clearance of HCV. Women with the C/T or T/T genotype who did not develop jaundice had a lower chance of spontaneous clearance of HCV infection.