Predictors Of Spontaneous Clearance Research Articles

Polymorphisms in the Th17 cell-related RORC gene are associated with spontaneous clearance of HCV in Chinese women

BackgroundFemale gender and favorable IFNL3 genotypes are the primary independent predictors of spontaneous clearance of HCV infection. However, chronic hepatitis C infection occurs in numerous women carrying favorable IFNL3 genotypes, indicating that other host and/or virological factors contribute to the prognosis of infection.MethodsA cohort of 137 anti-HCV-positive female Han Chinese cases, including 64 chronic HCV carriers and 73 HCV spontaneous resolvers, was recruited in the study. 111 SNPs in 23 genes encoding HCV co-receptors, transcription factors, Toll-like receptors, co-stimulating molecules, and cytokines were selected for SNP analysis.ResultsAfter comparison of genotypes and allelotype frequencies of 111 SNPs in 23 genes in the primary cohort, the SNPs rs9826 (P = 0.024 for CC/TT/CT; P = 0.015 for C allele/T allele) and rs1521177 (P = 0.017 for GG/TT/GT; P = 0.006 for G allele/T allele) in the RORC gene were significantly associated with spontaneous HCV clearance. In the sub-cohort carrying favorable IFNL3 genotypes (rs12979860CC, rs8099917 TT, rs12980275 AA), rs1521177 (genotype: P = 0.040; allelotype: P = 0.021) remained significantly associated with spontaneous HCV clearance. Importantly, the most common RORC haplotype rs9826-T/rs1521177-T was presented at significantly different frequencies in resolvers and carriers in both the primary cohort (P = 0.0027) and the IFNL3 favorable sub-cohort (P = 0.0117).ConclusionsThis study indicates that genetic polymorphisms in human Th17-related RORC gene are associated with different natural prognosis of HCV infection. The RORC haplotype, rs9826-T/rs1521177-T, was favorable for spontaneous clearance of HCV infection.

Role of Functional IFNL4, IFNLR1, IFNA, IFNAR2 Polymorphisms in Hepatitis B virus-related liver disease in Han Chinese population.

Recent studies show that variants in some interferon genes together with interferon receptor genes are associated with the outcome of infectious diseases. We examined the association between the risk of hepatitis B virus (HBV)-related liver disease and the functional polymorphisms within IFNL4, IFNLR1, IFNA1, IFNA2, IFNA5 and IFNAR2 genes (14 loci in all) in a Han Chinese population. A total of 3128 people participated and were divided into 5 groups: healthy controls, natural clearance, chronic hepatitis B(CHB), liver cirrhosis and hepatocellular carcinoma (HCC). Significant associations were observed for 4 variants in IFNAR2, IFNLR1 with HBV infection, and IFNLR1-rs4649203 was associated with HBV recovery. Moreover, we demonstrated the clear relevance of 5 polymorphisms in IFNA1, IFNA2, IFNL4 with HCC. Three SNPs in IFNL4 gene may be important susceptible factors for the progression of HBV-related liver disease by trend chi-square test. The IFNL4 haplotype conformed by rs12971396_G, rs8113007_T and rs7248668A was more frequent in HCC than CHB and LC group. Three polymorphisms in the 5' region of the IFNL4 gene are associated with the progression of HBV-related liver disease. IFNA1- rs1831583 and IFNA2- rs649053 are associated with the development of HCC. IFNLR1- rs4649203, rs7525481 are predictors for HBV infection, and rs4649203 is a predictor of spontaneous clearance. IFNAR2 -rs1051393, rs12233338 may be predictive markers of HBV infection in the Chinese population.

Interferon lambda 4 (IFNL4) gene polymorphism is associated with spontaneous clearance of HCV in HIV-1 positive patients.

Approximately one-third of the individuals infected with human immunodeficiency virus type 1 (HIV-1) are co-infected with hepatitis C virus (HCV). Co-infected patients have an increased risk for developing end-stage liver diseases. Variants upstream of the IFNL3 gene have been associated with spontaneous and treatment-induced clearance of HCV infection. Recently, a novel polymorphism was discovered, denoted IFNL4 ΔG > TT (rs368234815), which seems to be a better predictor of spontaneous clearance than the IFNL4 rs12979860 polymorphism. We aimed to determine the prevalence of the IFNL4 ΔG > TT variants and to evaluate the association with spontaneous clearance of HCV infection in Brazilian HIV-1 patients. The IFNL4 ΔG > TT genotypes were analyzed by polymerase chain reaction followed by restriction digestion in 138 HIV-1 positive patients who had an anti-HCV positive result. Spontaneous clearance of HCV was observed in 34 individuals (24.6%). IFNL4 genotype distribution was significantly different between individuals who had spontaneous clearance and chronic HCV patients (p=0.002). The probability of spontaneous clearance of HCV infection for patients with the IFNL4 TT/TT genotype was 3.6 times higher than for patients carrying the IFNL4 ΔG allele (OR=3.63, 95% CI:1.51-8.89, p=0.001). The IFNL4 ΔG > TT polymorphism seems to be better than IFNL4 rs12979860 to predict spontaneous clearance of the HCV in Brazilian HIV-1 positive patients.

Interferon lambda 3 rs12979860 polymorphism in patients with haemophilia and HCV infection: a predictor of spontaneous viral clearance and sustained virological response

Chronic hepatitis C is the main cause of morbidity and mortality in adult haemophilic patients who received non-virally inactivated plasma-derived clotting factor concentrates. Overall, spontaneous viral clearance rate is 10-25% and the only approach that can halt disease progression is hepatitis C virus (HCV) eradication by means of antiviral therapy. In non-haemophilic patients a single nucleotide polymorphism located upstream the gene of interferon lambda 3 (IFNλ3) has been associated with both spontaneous viral clearance and sustained virological response after antiviral treatment. The aim of this study was to assess whether the rs12979860 polymorphism was a predictor of spontaneous viral clearance and of sustained virological response after antiviral therapy in a large cohort of haemophilic patients with HCV infection. The rs12979860 polymorphism, defined as CC genotype or T allele, was tested in a cohort of 342 haemophilic patients and evaluated as predictor of spontaneous clearance or response to antiviral therapy. By multivariate regression analysis the IFNλ3 CC genotype was an independent predictor of spontaneous viral clearance (odds ratio: 3.7, 95% confidence interval: 2.0-6.8). Sustained virological response rates were doubled in patients with the CC genotype than in those with the T allele (78% vs 44%; p<0.001), especially in patients with HCV type 1 (67% vs 32%; p<0.001) and higher sustained response rates were observed in patients with the CC genotype who did not achieve rapid virological response (61% vs 30% in T allele patients; p=0.006).

Factores predictivos para la expulsión de la litiasis ureteral

Medical treatment, extracorporeal shock wave lithotripsy (ESWL) and ureteroscopy are therapeutic options for ureteral stones. EWSL and endoscopic treatment of ureteral stones have a high success rate. However it has surgical as well as anaesthetic risks. For many patients, a medicinal treatment without invasive procedures is an option. Watchful waiting does not always result in stone clearance and may be associated with recurrent renal colic. The study of the prognostic factors for expulsion and the medical therapy will help us to select candidates for medical expulsive treatment. Objectives To evaluate the characteristics of the stones and the medication administered (alpha blockers, NSAIDs or a combination of both) as predictors of spontaneous passage of the stone. Material and methods A retrospective observational study of 260 patients with 278 ureteral stones was conducted. Primary endpoint was stone expulsion. Univariate and multivariate analysis were conducted testing the effect of stone location, size and composition, and medication (alpha-blockers, NSAIDs, or combination) on stone clearance. Results 34,2% of the stones studied were spontaneously eliminated. Stone location (pelvic ureter, OR= 1,823, p=0,013), size (<5 mm, OR=3,37, p<0,02), and medication (combination of alpha blockers and NSAIDs, OR= 8,70, p<0.001) were predictors of spontaneous clearance. Multivariate analysis confirmed size (p=0,006) and medication (p<0,001) as independent predictive factors. The use of the combination of NSAIDs and alpha-blockers versus observation multiplied times 8,21 (95% CI 3.37–20,01) the possibilities of spontaneous expulsion. Conclusions Size of stone and medication were confirmed as independent factors for spontaneous expulsion of ureteral stones.

Outcome of a Hepatitis C Outbreak Among Patients in a Pain Management Clinic

The aims of this study are to evaluate the natural history and response to therapy of patients following a hepatitis C outbreak in a pain management clinic. A retrospective cohort study was conducted on patients who acquired hepatitis C virus (HCV) at a pain management clinic. Medical records were retrospectively reviewed for 77% of patients with hepatitis C included in the outbreak to obtain data regarding laboratory results, treatment, and outcomes. Chi-square, Fisher's exact, and Student's t-test were used to determine variables that were significantly associated with spontaneous clearance or sustained virologic response to therapy. Fifty Caucasian patients (31 women, 19 men; mean age 52 years) were included. Eleven of 50 (22%) patients cleared HCV spontaneously (clearers). The mean age of clearers was 47 years as compared with 57 years for nonclearers (P = 0.04). Liver biopsies were obtained by treating gastroenterologists in 31 patients with mean grade and stage of 2.1 and 1.7, respectively. Gastroenterologists treated 31 of 39 patients with pegylated interferon and ribavirin after a median of 354 (range 140-1,099) days post exposure. Sustained viral response (SVR) was observed in 65% (20/31) on an intention-to-treat basis. In patients who completed therapy, 91% (20/22) achieved SVR. Age, sex, weight, pretreatment alanine aminotransferase (ALT), and histologic parameters were not associated with SVR. In this large cohort of US immunocompetent patients with recent HCV infection, 22% resolved spontaneously. Younger age was the only predictor of spontaneous clearance. In patients with early chronic HCV, 65% achieved SVR.

Prognostic factors of spontaneous expulsion in ureteral lithiasis

Medical treatment, extracorporeal shock wave lithotripsy (ESWL) and ureteroscopy are therapeutic options for ureteral stones. EWSL and endoscopic treatment of ureteral stones have a high success rate. However it has surgical as well as anaesthetic risks. For many patients, a medicinal treatment without invasive procedures is an option. Watchful waiting does not always result in stone clearance and may be associated with recurrent renal colic. The study of the prognostic factors for expulsion and the medical therapy will help us to select candidates for medical expulsive treatment. ObjectivesTo evaluate the characteristics of the stones and the medication administered (alpha blockers, NSAIDs or a combination of both) as predictors of spontaneous passage of the stone. Material and methodsA retrospective observational study of 260 patients with 278 ureteral stones was conducted. Primary endpoint was stone expulsion. Univariate and multivariate analysis were conducted testing the effect of stone location, size and composition, and medication (alpha-blockers, NSAIDs, or combination) on stone clearance. Results34.2% of the stones studied were spontaneously eliminated. Stone location (pelvic ureter, OR=1.823, p=0.013), size (<5mm, OR=3.37, p<0.02), and medication (combination of alpha blockers and NSAIDs, OR=8.70, p<0.001) were predictors of spontaneous clearance. Multivariate analysis confirmed size (p=0.006) and medication (p<0.001) as independent predictive factors. The use of the combination of NSAIDs and alpha-blockers versus observation multiplied times 8.21 (95% CI 3.37–20.01) the possibilities of spontaneous expulsion. ConclusionsSize of stone and medication were confirmed as independent factors for spontaneous expulsion of ureteral stones.