scholarly journals Genetic Association of Hepatitis C-Related Mixed Cryoglobulinemia: A 10-Year Prospective Study of Asians Treated with Antivirals

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 464
Author(s):  
Ming-Ling Chang ◽  
Su-Wei Chang ◽  
Shiang-Chi Chen ◽  
Rong-Nan Chien ◽  
Chia-Lin Hsu ◽  
...  

Genetic profiles of hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC) in Asians remain elusive. A 10-year prospective cohort study was conducted with 1043 consecutive HCV Ab-positive Taiwanese surveyed with 13 single nucleotide polymorphisms (SNPs). Of 1043, 589 (56.5%) had baseline MC, 934 (89.5%) had positive HCV RNA, 796 completed anti-HCV therapy, and 715 had sustained virological responses (SVRs). SNP associations were surveyed withgenotypic, allelic, trend, permutation and multivariate analyses. At baseline, higher male sex and MC rates were noted in HCV RNA-positive than RNA-negative patients; higher female sex and positive HCV RNA rates but lower HCV RNA levels were noted in patients with than those without MC. Baseline associations were: HLA II-rs9461776 A allele, IFNL3-rs12979860 T allele, SERPINE1-rs6976053 C allele and MC with HCV RNA positivity; IFNL3-rs12979860 C allele, ARNTL-rs6486122 T allele and HCV RNA positivity with baseline MC. In SVR patients, RETN-rs1423096 C allele and SERPINE1-rs6976053 T allele were associated with 24-week and 10-year post-therapy MC, respectively. Conclusions: HCV RNA, IFNL3-rs12979860 and ARNTL-rs6486122 were associated with baseline MC; RETN-rs1423096 and SERPINE1-rs6976053 were associated with short- and long-term post-therapy MC in SVR patients, respectively. Links with HCV RNA and immune-associated SNPs suggest MC an immune reaction to expel HCV.

Author(s):  
S. I. Semenov ◽  
A. I. Fedorov ◽  
V. L. Osakovsky ◽  
S. S. Maksimova ◽  
F. A. Platonov

Aim. Study clinical outcomes in patients with, chronic hepatitis C depending on genotype of hepatitis C virus (HCV) and IL28B gene polymorphism. Materials and methods. 592 individuals were examined, 75 of those had HCV RNAgenotypes determined by PCR. Genotyping of single nucleotide polymorphisms (SNP) - rs 12979860 (C/T) and rs8099917 (T/G) in IL28B gene was carried out by real-time PCR. Results. HCV RNA was detected in 72 examined residents of Yakutia. HCV lb genotype was determined in 74.2% of cases, 3a - in 11.4%, la and 2 - 5.7% each. Frequency of polymorph variant rsl2979860 CC was 72.2%, CT - 27.8%, rs8099917 TT - 61.1%, TG - 23.2%. Conclusion. Combination of HCV lb with polymorphic variants of IL28B gene rs.l.2979860 CC and rs8099917 CT showed a less aggressive course of the disease. On the other hand, HCV infection of individuals with genotype 3a and polymorphism rsl2979860 CC or rs809917 TT of IL28B gene showed a more severe clinical presentation. The presence of polymorph variants rs8099917 T/G and rs 12979860 C/T showed more severe clinical outcomes of HCV infection (viral load up to 19035212 copies, cirrhosis with ascite, hepatocarcinoma).


Blood ◽  
2010 ◽  
Vol 116 (3) ◽  
pp. 343-353 ◽  
Author(s):  
Franco Dammacco ◽  
Felicia Anna Tucci ◽  
Gianfranco Lauletta ◽  
Pietro Gatti ◽  
Valli De Re ◽  
...  

AbstractThis study illustrates the use and efficacy of a combination of pegylated interferon-α (Peg-IFN-α) and ribavirin (RBV), with or without rituximab (RTX), in hepatitis C virus (HCV)–related mixed cryoglobulinemia (MC). Twenty-two patients with HCV-related MC received Peg-IFN-α (2a: 180 μg or 2b: 1.5 μg/kg) weekly plus RBV (1000 or 1200 mg) daily for 48 weeks, and RTX (375 mg/m2) once a week for 1 month followed by two 5-monthly infusions (termed PIRR). Fifteen additional patients received Peg-IFN-α/RBV with the same modalities as the PIRR schedule. Complete response was achieved in 54.5% (12/22) and in 33.3% (5/15) of patients who received PIRR and Peg-IFN-α/RBV, respectively (P < .05). Clearance of HCV RNA and conversion of B-cell populations from oligoclonal to polyclonal in liver, bone marrow, and peripheral blood was maintained for up to 3 years in 10 of 12 (83.3%) and in 2 of 5 (40%) patients receiving PIRR and Peg-IFN-α/RBV, respectively (P < .01). Cryoproteins in 22.7% (5/22) of patients with PIRR and in 33.3% (5/15) with Peg-IFN-α/RBV persisted despite sustained HCV RNA clearance. No response occurred in remaining 5 patients of both groups. PIRR therapy is well tolerated and more effective than Peg-IFN-α/RBV combination in HCV-related MC. Its effect may last for more than 3 years.


1993 ◽  
Vol 8 (1) ◽  
pp. 1-6 ◽  
Author(s):  
H. YATSUHASHI ◽  
O. INOUE ◽  
K. INOKUCHI ◽  
M. KOGA ◽  
S. NAGATAKI ◽  
...  

2016 ◽  
Vol 10 (1) ◽  
pp. 37-41
Author(s):  
Fatima Abood Chaloob

Infection with hepatitis C virus (HCV) imposes a global challenge with over 180 million cases worldwide. Only few patients spontaneously had their virus neutralized, while most patients develop chronic HCV infection. This implies a key role of genetic factors in viral clearance or persistence. The current study aimed at clarifying the effect of certain single nucleotide polymorphisms (SNPs) on individual's susceptibility to HCV infection.  A total of 60 patients with confirmed HCV infection and 35 apparently healthy individuals were enrolled in this study. Blood sample was obtained from each participant, from which DNA was extracted. The JAK1gene was amplified with conventional PCR technique using three sets of primers targeting three SNPs in this gene: rs2780895, rs4244165 and rs17127024. Restriction fragment length polymorphism (RFLP) was used for genotyping of PCR products. Each of rs2780895 and rs17127024 had two genotypes in both patients and controls, however, only the heterozygous genotype of the SNP rs2780895 (CT) significantly associated with the susceptibility to HCV. The SNP rs4244165 appeared in only with homozygous wild genotype (GG) in both patients and controls. It can be concluded that allele T of the SNP rs2780895 could be considered as a risk factor for infection with HCV


2020 ◽  
Author(s):  
Faisal Aziz ◽  
Berthold Reichardt ◽  
Caren Sourij ◽  
Hans-Peter Dimai ◽  
Daniela Reichart ◽  
...  

Abstract Background: Previous data show a high incidence of major lower extremity amputations (LEA) in Austria. Moreover, recent data on the epidemiology of major LEA are sparse in the Country. This study estimated the incidence and mortality rates of major LEA and assessed risk factors of post major LEA mortality in individuals with diabetes.Methods: A retrospective cohort analysis of 507,180 individuals with diabetes enrolled in the Austrian Health Insurance between 2014 and 2017 was performed. Crude and age-standardized rates of major LEA (hip, femur, knee, lower leg) were estimated by extracting their procedure codes from the database. Short- (30-day, 90-day) and long-term (1-year, 5-year) all-cause cumulative mortality after major LEA was estimated from the date of amputation till the date of death. Poisson regression was performed to compare rates by characteristics and assess the annual trend. The Cox-regression was performed to identify significant risk factors of all-cause mortality after major LEA.Results: A total of 2,165 individuals with diabetes underwent major LEA between 2014 and 2017. The mean age was amputees was 73.0 ±11.3 years, 62.7% were males, and 87.3% had a peripheral vascular disease (PVD). The overall age-standardized rate was 6.44 per 100,000 population. The rate increased with age (p<0.001) and was higher (p<0.001) in males (9.38) than females (5.66). The rate was 5.71 in 2014, 6.86 in 2015, 6.71 in 2016, and 6.66 in 2017, with an insignificant annual change of 3% (p=0.825). The cumulative 30-day mortality was 13.5%, 90-day was 22.0%, 1-year was 34.4%, and 5-year was 66.7%. Age, male sex, above-knee amputation, Charlson index, and heart failure were significantly associated with both short- and long-term mortality. Cancer, dementia, heart failure, PVD, and renal disease were only associated with long-term mortality.Conclusions: The rate of major LEA remained stable between 2014 and 2017 in Austria. Short and long-term mortality rates were considerably high after major LEA. Old age, male sex, above-knee amputations, heart failure, and Charlson Index were significant predictors of both short- and long-term mortality, whereas, comorbidities such as cancer, dementia, PVD, and renal disease were significant predictors of long-term mortality only.


2010 ◽  
Vol 28 (30) ◽  
pp. 4587-4593 ◽  
Author(s):  
Lee Mei-Hsuan ◽  
Hwai-I Yang ◽  
Sheng-Nan Lu ◽  
Chin-Lan Jen ◽  
Shiou-Hwei Yeh ◽  
...  

Purpose Hepatitis C virus (HCV) contributes to one third of hepatocellular carcinoma cases worldwide. Long-term predictors for HCV-related hepatocellular carcinoma are essential for early intervention. Serum HCV RNA and ALT levels and HCV genotype were assessed for their predictability of hepatocellular carcinoma risk. Methods A prospective cohort of 925 participants positive for antibodies against HCV and age 30 to 65 years was recruited and followed from 1991 to 2006. Serum HCV RNA and ALT levels and HCV genotypes at enrollment and during follow-up were examined. Newly developed hepatocellular carcinoma was identified by health examination and computerized linkage with national cancer registration and death certification profiles. Multivariate adjusted hazard ratios with 95% CIs were estimated using Cox regression models. Results Fifty-five participants newly developed hepatocellular carcinoma during 8,476 person-years of follow-up, giving an incidence rate of 648.9 per 100,000 person-years. The cumulative hepatocellular carcinoma risk increased from 1.1% for HCV RNA seronegative status to 6.4% for low HCV RNA levels and to 14.7% for high HCV RNA levels (P < .001). The cumulative risk also increased with elevated serum ALT levels from 1.7% for persistently ≤ 15 U/L to 4.2% for ever more than 15 U/L but never more than 45 U/L and to 13.8% for ALT ever ≥ 45 U/L (P < .001). Having HCV genotype 1 was associated with a higher cumulative hepatocellular carcinoma risk (12.6%) than not having HCV genotype 1 (4.5%; P < .001). Conclusion Elevated serum levels of HCV RNA and ALT and HCV genotype 1 infection are independent risk predictors of hepatocellular carcinoma. These findings have strong implications for the management of chronic HCV.


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