The candidate polymorphism rs12979860 of interleukin 28B(IL28B)gene was genotyped by means of polymerase chain reaction(PCR)amplification and direct PCR sequencing,and then the role of this single nucleotide polymorph...The candidate polymorphism rs12979860 of interleukin 28B(IL28B)gene was genotyped by means of polymerase chain reaction(PCR)amplification and direct PCR sequencing,and then the role of this single nucleotide polymorphism(SNP)in the response to the treatment of 172 Chinese patients with hepatitis C virus(HCV)chronic infection was analyzed.The results show that the frequencies of major homozygotes(CC)and heterozygotes(CT)of rs12979860 were 0.84 and 0.16,respectively,and the minor homozygotes(TT)wasn’t found in this cohort.A highly significant association was found between the CC genotype and sustained virological response(SVR)in HCV geno type 1 infected patients(P〈0.001)but not in HCV non-genotype 1 infected patients.In addition,a strong association was found between rs12979860 CC genotype and rapid virological response(RVR)in both HCV genotype 1 infected patients(P〈0.001)and non-genotype 1 infected patients(P〈0.001).Taken together,these results indicate that IL28B polymorphism plays a key role in response to hepatitis C therapy in Chinese patients.Combine assessment of clinical predictors and the IL28B polymorphism may be beneficial to the individualized treatment decision in Asian chronic hepatitis C(CHC)patients.展开更多
OBJECTIVE:To investigate the pharmacological effects and underlying mechanisms of Pinggan Yuyin Qingre formula(平肝育阴清热方,PGYYQR)in the treatment of meibomian gland dysfunction(MGD)through network pharmacology and...OBJECTIVE:To investigate the pharmacological effects and underlying mechanisms of Pinggan Yuyin Qingre formula(平肝育阴清热方,PGYYQR)in the treatment of meibomian gland dysfunction(MGD)through network pharmacology and in vivo validation.METHODS:A mouse model of MGD was induced using the stearoyl-coenzyme a desaturase 1 inhibitor,followed by PGYYQR treatment for 2 weeks.MGD sign scoring,hematoxylin and eosin(HE)staining,oil red o(ORO)staining,and serum inflammatory cytokine analysis were conducted to assess the effects of PGYYQR on meibomian gland(MG)function,histopathology,and associated inflammation.Network pharmacology was employed to identify the active compounds and potential targets of PGYYQR.Molecular mechanisms were further investigated using Western blotting,reverse transcription quantitative real-time polymerase chain reaction,and reactive oxygen species(ROS)assays.RESULTS:PGYYQR treatment significantly reduced the scores of MG orifice obstruction and meibum quality in MGD mice.HE and ORO staining further demonstrated that PGYYQR ameliorated glandular damage and lipid dysfunction.Enzyme-linked immunosorbent assay results revealed that PGYYQR markedly decreased the serum levels of key inflammatory cytokines,including interleukin(IL)-1β,IL-6,and tumor necrosis factor-α.Network pharmacology identified 162 active compounds and 598 target genes in PGYYQR.Among these,IL-6,IL-1β,matrix metalloproteinase-9,and C-X-C motif chemokine ligand 8 were recognized as core targets related to MGD and were mainly enriched in the IL-17/nuclear factor kappa B(NF-κB)signaling pathway.Further molecular analyses confirmed that PGYYQR significantly inhibited the IL-17/NF-κB axis by downregulating IL-17 expression and reducing phosphorylated NF-κB p65 levels at both the protein and m RNA levels in MG tissues.PGYYQR also effectively reduced ROS levels in the conjunctival tissues of MGD mice.CONCLUSION:PGYYQR effectively improves MG function and preserves local tissue morphology in MGD model mice,primarily by suppressing the inflammatory response through coordinated modulation of the IL-17/NF-κB signaling pathway and oxidative stress.展开更多
AIM:To investigate the association between interleukin-28B(IL28B) genotype and response to treatment and hepatic fibrosis in patients with hepatitis C virus(HCV) genotype 4.METHODS:Two hundred and one HCV-genotype 4 p...AIM:To investigate the association between interleukin-28B(IL28B) genotype and response to treatment and hepatic fibrosis in patients with hepatitis C virus(HCV) genotype 4.METHODS:Two hundred and one HCV-genotype 4 patients were included.All patients were treated with Peginterferon alph2a/Ribavirin for 48 wk.End of treatment response(ETR) was defined as loss of detectable serum HCV RNA at the end of treatment.Sustained viral response(SVR) was defined as loss of detectable serum HCV RNA at the end of 24 wk follow up.Genotyping of IL28B rs12979860 was performed using the TaqMan assay.We used logistic regression to estimate the adjusted odds ratio(aOR) and 95%CI.RESULTS:The study included 201 HCV-genotype 4 patients.The majority of patients were men(89.6%),with a median age of 47 years,inter-quartile range(40-51).Approximately 62.5% of patients had ETR,and 49.6% had SVR.Individuals who achieved SVR were more likely to be younger(χ 2 = 4.91,P = 0.027),and less likely to have fibrosis(χ 2 = 15.54,P < 0.0001),or inflammation(χ 2 = 7.58,P = 0.006).The genotype distribution of rs12979860 was 36.2%,49.0% and 14.8% for genotypes CC,CT,and TT,respectively.In these participants,rs12979860 genotype distribution did not differ by gender(P = 0.466),pretreatment viral load(P = 0.600),inflammation(P = 0.435),or fibrosis(P = 0.291).The frequencies of IL28B rs12979860 genotypes were TT(14.8%),CT(49.0%),and CC(36.2%).Compared to rs12979860 genotype TT,aORs(95%CI) for ETR and SVR were:CC genotype,[17.55(5.34-57.69) and 5.92(2.09-16.76),respectively];CT genotype,[5.15(1.80-14.78) and 2.48(0.94-6.52),respectively].In the current study,the patients who did not achieve ETR or SVR had a lower prevalence of rs12979860 CC(17.4% and 23.3%,respectively) than individuals who had ETR or SVR(47.9% and 47.2%,respectively).Individuals with rs12979860 CC genotype had approximately 6 times the odds of SVR compared to individuals with TT genotype(aOR = 5.92;95%CI:2.09-16.76).Similarly,patients with CT genotype had SVR more often than patients with TT genotype(aOR = 2.48;95%CI:0.94-6.52).Carrying at least one copy of the C allele(genotypes CT and CC) had almost 8 times the probability of ETR compared to those with genotype rs12979860 TT(aOR = 7.87;95%CI:2.84-21.82),and approximately 3 times the odds of SVR compared to those with genotype rs12979860 TT(aOR = 3.46;95%CI:1.37-8.74).In addition,data were consistent with a significant gene-dose relationship(aOR = 4.05/allele;95%CI:2.27-7.22).The association between rs12979860 genotype and SVR was similar among those who achieved and those who did not achieve SVR.CONCLUSION:In HCV-genotype 4 patients,rs12979860 is a sensitive predictor of viral clearance,independent of viral load,age,gender or fibrosis,with no similar relation to severity of fibrosis.展开更多
BACKGROUND Excessive endoplasmic reticulum(ER)stress in intestinal epithelial cells can lead to damage to the intestinal mucosal barrier,activate the signal transducer and activator of transcription 3(STAT3)/nuclear f...BACKGROUND Excessive endoplasmic reticulum(ER)stress in intestinal epithelial cells can lead to damage to the intestinal mucosal barrier,activate the signal transducer and activator of transcription 3(STAT3)/nuclear factor kappa B(NF-κB)signaling pathway,and exacerbate the inflammatory response,thus participating in the pathogenesis of ulcerative colitis(UC).Mesalazine is a commonly used drug in the clinical treatment of UC.However,further studies are needed to determine whether mesalazine regulates the ER stress of intestinal epithelial cells,downregulates the STAT3/NF-κB pathway to play a role in the treatment of UC.AIM To study the therapeutic effects of mesalazine on spontaneous colitis in interleukin-10(IL-10)-/-mice.METHODS The 24-week-old IL-10-/-mice with spontaneous colitis were divided into the model group and the 5-amino salicylic acid group.Littermates of wild-type mice of the same age group served as the control.There were eight mice in each group,four males and four females.The severity of symptoms of spontaneous colitis in IL-10-/-mice was assessed using disease activity index scores.On day 15,the mice were sacrificed.The colon length was measured,and the histopathological changes and ultrastructure of colonic epithelial cells were detected.The protein expressions of STAT3,p-STAT3,NF-κB,IκB,p-IκB,and glucoseregulated protein 78 were identified using Western blotting.The STAT3 and NF-κB mRNA expressions were identified using real-time polymerase chain reaction.The glucose-regulated protein 78 and C/EBP homologous protein expressions in colon sections were detected using immunofluorescence.RESULTS Mesalazine reduced the symptoms of spontaneous colitis in IL-10 knockout mice and the histopathological damage of colonic tissues,and alleviated the ER stress in epithelial cells of colitis mice.Western blotting and quantitative real-time polymerase chain reaction results showed that the STAT3/NF-κB pathway in the colon tissue of model mice was activated,suggesting that this pathway was involved in the pathogenesis of UC and might become a potential therapeutic target.Mesalazine could down-regulate the protein expressions of p-STAT3,NF-κB and p-IκB,and down-regulate the mRNA expression of STAT3 and NF-κB.CONCLUSION Mesalazine may play a protective role in UC by reducing ER stress by regulating the STAT3/NF-κB signaling pathway.展开更多
AIM: To clarify the association of interleukin-28B (IL28B) single nucleotide polymorphisms (SNPs) with hepatitis C virus (HCV) viremia changes for assessment of interferon (IFN) response.
In a recent genome-wide association study, single nucleotide polymorphisms (SNPs) located near the interleukin-28B gene (IL28B), which encodes type Ⅲ interferon (IFN) λ3, were shown to be strongly associated with a ...In a recent genome-wide association study, single nucleotide polymorphisms (SNPs) located near the interleukin-28B gene (IL28B), which encodes type Ⅲ interferon (IFN) λ3, were shown to be strongly associated with a viral response to pegylated IFNα (PEG-IFNα) and ribavirin (RBV) combination therapy and spontaneous viral clearance in patients chroni-cally and acutely infected with hepatitis C virus (HCV), respectively. The global distribution of allele frequencies shows a remarkable pattern, in which a favorable allele is nearly fixed in East Asia, has an intermediate frequency in Europe, and is least frequent in Africa. Although the under-lying mechanisms responsible for viral responses associated with IL28B SNPs have not been completely elucidated, IFN-stimulated gene expression in patients with unfavorable IL28B genotypes tends to be high at baseline and is insufficiently induced by exogenous IFN administration, resulting in poor treatment outcomes. Clinically, triple therapy with PEG-IFNα/RBV together with direct-acting anti-viral agents (DAAs) is currently used to treat chronic hepatitis C as a first-line therapy. Although the predictive power of IL28B status may be attenuated, the IL28B genotype will remain relevant to the outcomes of DAA therapy when used in combination with PEG-IFNα as a backbone. Even with the introduction of IFN-free therapies with a new class of highly effective DAAs, IL28B SNPs are still useful predictors of treatment outcomes and can be used to individualize treat-ment strategies to maximize cost-effectiveness and identify patients at risk of being refractory to treatment. This review summarizes the current understanding of the clinical sig-nificance and role of IL28B in HCV infection and response to therapy.展开更多
Background:Interleukin-28B (IL-28B) polymorphism is an important predictor for hepatitis C virus (HCV) treatment response.Whether IL-28b genotypes also influence other nontreatment related clinical parameters is uncle...Background:Interleukin-28B (IL-28B) polymorphism is an important predictor for hepatitis C virus (HCV) treatment response.Whether IL-28b genotypes also influence other nontreatment related clinical parameters is unclear.Methods:Patients with HCV-related chronic liver diseases who attended our department during 2012-2014 were retrospectively analyzed.The single nucleotide polymorphisms (SNPs) of rs12979860 (IL-28B) were correlated with various clinical parameters.We also compared these parameters in patients with and without overt diabetes to identify possible associations.Results:A total of 115 patients were included (median age 48,range 15-76 years;70% males).Overall,43/115(37%) patients had chronic hepatitis,while the remaining 72/115 (63%) had cirrhosis.The most common IL-28B genotype was CC,which was found in 53% of patients (61/115),while the remaining 47% were nonCC [CT 42% (48/115) and T-r 5% (6/115)].Clinical and laboratory parameters like Hb,white blood cell (WBC),platelets,bilirubin,transaminases,and albumin were similar in the CC and nonCC genotypes.Overt diabetes mellitus was present in 22% (25/115) of patients.Patients with nonCC genotype had significantly higher prevalence of overt diabetes mellitus than patients with CC genotype (31% [17/54] versus 13% [8/61];p < 0.05).When parameters were compared in patients with and without overt diabetes mellitus,only IL-28B and age were significantly associated with overt diabetes mellitus (p < 0.05).Conclusion:In HCV patients,overt diabetes mellitus was more commonly associated with the nonCC genotype of IL-28B than the CC genotype.Carriers of the T-allele of SNP rs12979860 were more likely to have insulin resistance than CC homozygotes,and this finding may explain the higher prevalence of diabetes in non-CC genotypes.Thus,an IL-28B test may be useful in patients of HCV in order to determine their likelihood of developing diabetes mellitus.展开更多
基金Supported by the State Key Disciplines of Clinical Projects and the National Natural Science Foundation of China(No.30970415)
文摘The candidate polymorphism rs12979860 of interleukin 28B(IL28B)gene was genotyped by means of polymerase chain reaction(PCR)amplification and direct PCR sequencing,and then the role of this single nucleotide polymorphism(SNP)in the response to the treatment of 172 Chinese patients with hepatitis C virus(HCV)chronic infection was analyzed.The results show that the frequencies of major homozygotes(CC)and heterozygotes(CT)of rs12979860 were 0.84 and 0.16,respectively,and the minor homozygotes(TT)wasn’t found in this cohort.A highly significant association was found between the CC genotype and sustained virological response(SVR)in HCV geno type 1 infected patients(P〈0.001)but not in HCV non-genotype 1 infected patients.In addition,a strong association was found between rs12979860 CC genotype and rapid virological response(RVR)in both HCV genotype 1 infected patients(P〈0.001)and non-genotype 1 infected patients(P〈0.001).Taken together,these results indicate that IL28B polymorphism plays a key role in response to hepatitis C therapy in Chinese patients.Combine assessment of clinical predictors and the IL28B polymorphism may be beneficial to the individualized treatment decision in Asian chronic hepatitis C(CHC)patients.
基金Supported by National Famous and Senior Chinese Medicine Expert Heritage Studio Construction Project:Zhi Nan Heritage Studio(No.75[2022])Beijing Municipal Key Traditional Chinese Medicine Specialty Development Project during the 14th Five-Year Plan Period(No.BJZKBC0029)。
文摘OBJECTIVE:To investigate the pharmacological effects and underlying mechanisms of Pinggan Yuyin Qingre formula(平肝育阴清热方,PGYYQR)in the treatment of meibomian gland dysfunction(MGD)through network pharmacology and in vivo validation.METHODS:A mouse model of MGD was induced using the stearoyl-coenzyme a desaturase 1 inhibitor,followed by PGYYQR treatment for 2 weeks.MGD sign scoring,hematoxylin and eosin(HE)staining,oil red o(ORO)staining,and serum inflammatory cytokine analysis were conducted to assess the effects of PGYYQR on meibomian gland(MG)function,histopathology,and associated inflammation.Network pharmacology was employed to identify the active compounds and potential targets of PGYYQR.Molecular mechanisms were further investigated using Western blotting,reverse transcription quantitative real-time polymerase chain reaction,and reactive oxygen species(ROS)assays.RESULTS:PGYYQR treatment significantly reduced the scores of MG orifice obstruction and meibum quality in MGD mice.HE and ORO staining further demonstrated that PGYYQR ameliorated glandular damage and lipid dysfunction.Enzyme-linked immunosorbent assay results revealed that PGYYQR markedly decreased the serum levels of key inflammatory cytokines,including interleukin(IL)-1β,IL-6,and tumor necrosis factor-α.Network pharmacology identified 162 active compounds and 598 target genes in PGYYQR.Among these,IL-6,IL-1β,matrix metalloproteinase-9,and C-X-C motif chemokine ligand 8 were recognized as core targets related to MGD and were mainly enriched in the IL-17/nuclear factor kappa B(NF-κB)signaling pathway.Further molecular analyses confirmed that PGYYQR significantly inhibited the IL-17/NF-κB axis by downregulating IL-17 expression and reducing phosphorylated NF-κB p65 levels at both the protein and m RNA levels in MG tissues.PGYYQR also effectively reduced ROS levels in the conjunctival tissues of MGD mice.CONCLUSION:PGYYQR effectively improves MG function and preserves local tissue morphology in MGD model mice,primarily by suppressing the inflammatory response through coordinated modulation of the IL-17/NF-κB signaling pathway and oxidative stress.
基金Supported by Hamad Hospital-HMC and Qatar UniversityHealth Sciences-Biomedical Labssponsored by HMC
文摘AIM:To investigate the association between interleukin-28B(IL28B) genotype and response to treatment and hepatic fibrosis in patients with hepatitis C virus(HCV) genotype 4.METHODS:Two hundred and one HCV-genotype 4 patients were included.All patients were treated with Peginterferon alph2a/Ribavirin for 48 wk.End of treatment response(ETR) was defined as loss of detectable serum HCV RNA at the end of treatment.Sustained viral response(SVR) was defined as loss of detectable serum HCV RNA at the end of 24 wk follow up.Genotyping of IL28B rs12979860 was performed using the TaqMan assay.We used logistic regression to estimate the adjusted odds ratio(aOR) and 95%CI.RESULTS:The study included 201 HCV-genotype 4 patients.The majority of patients were men(89.6%),with a median age of 47 years,inter-quartile range(40-51).Approximately 62.5% of patients had ETR,and 49.6% had SVR.Individuals who achieved SVR were more likely to be younger(χ 2 = 4.91,P = 0.027),and less likely to have fibrosis(χ 2 = 15.54,P < 0.0001),or inflammation(χ 2 = 7.58,P = 0.006).The genotype distribution of rs12979860 was 36.2%,49.0% and 14.8% for genotypes CC,CT,and TT,respectively.In these participants,rs12979860 genotype distribution did not differ by gender(P = 0.466),pretreatment viral load(P = 0.600),inflammation(P = 0.435),or fibrosis(P = 0.291).The frequencies of IL28B rs12979860 genotypes were TT(14.8%),CT(49.0%),and CC(36.2%).Compared to rs12979860 genotype TT,aORs(95%CI) for ETR and SVR were:CC genotype,[17.55(5.34-57.69) and 5.92(2.09-16.76),respectively];CT genotype,[5.15(1.80-14.78) and 2.48(0.94-6.52),respectively].In the current study,the patients who did not achieve ETR or SVR had a lower prevalence of rs12979860 CC(17.4% and 23.3%,respectively) than individuals who had ETR or SVR(47.9% and 47.2%,respectively).Individuals with rs12979860 CC genotype had approximately 6 times the odds of SVR compared to individuals with TT genotype(aOR = 5.92;95%CI:2.09-16.76).Similarly,patients with CT genotype had SVR more often than patients with TT genotype(aOR = 2.48;95%CI:0.94-6.52).Carrying at least one copy of the C allele(genotypes CT and CC) had almost 8 times the probability of ETR compared to those with genotype rs12979860 TT(aOR = 7.87;95%CI:2.84-21.82),and approximately 3 times the odds of SVR compared to those with genotype rs12979860 TT(aOR = 3.46;95%CI:1.37-8.74).In addition,data were consistent with a significant gene-dose relationship(aOR = 4.05/allele;95%CI:2.27-7.22).The association between rs12979860 genotype and SVR was similar among those who achieved and those who did not achieve SVR.CONCLUSION:In HCV-genotype 4 patients,rs12979860 is a sensitive predictor of viral clearance,independent of viral load,age,gender or fibrosis,with no similar relation to severity of fibrosis.
基金Supported by Xi’an Science and Technology Plan Project,No.23YXYJ0162Shaanxi Province Traditional Chinese Medicine Research and Innovation Talent Plan Project,No.TZKN-CXRC-16+2 种基金Project of Shaanxi Administration of Traditional Chinese Medicine,No.SZYKJCYC-2025-JC-010Shaanxi Province Key Research and Development Plan Project-Social Development Field,No.S2025-YF-YBSF-0391the Science and Technology Innovation Cultivation Program of Longhua Hospital affiliated to Shanghai University of Chinese Medicine,No.YD202220。
文摘BACKGROUND Excessive endoplasmic reticulum(ER)stress in intestinal epithelial cells can lead to damage to the intestinal mucosal barrier,activate the signal transducer and activator of transcription 3(STAT3)/nuclear factor kappa B(NF-κB)signaling pathway,and exacerbate the inflammatory response,thus participating in the pathogenesis of ulcerative colitis(UC).Mesalazine is a commonly used drug in the clinical treatment of UC.However,further studies are needed to determine whether mesalazine regulates the ER stress of intestinal epithelial cells,downregulates the STAT3/NF-κB pathway to play a role in the treatment of UC.AIM To study the therapeutic effects of mesalazine on spontaneous colitis in interleukin-10(IL-10)-/-mice.METHODS The 24-week-old IL-10-/-mice with spontaneous colitis were divided into the model group and the 5-amino salicylic acid group.Littermates of wild-type mice of the same age group served as the control.There were eight mice in each group,four males and four females.The severity of symptoms of spontaneous colitis in IL-10-/-mice was assessed using disease activity index scores.On day 15,the mice were sacrificed.The colon length was measured,and the histopathological changes and ultrastructure of colonic epithelial cells were detected.The protein expressions of STAT3,p-STAT3,NF-κB,IκB,p-IκB,and glucoseregulated protein 78 were identified using Western blotting.The STAT3 and NF-κB mRNA expressions were identified using real-time polymerase chain reaction.The glucose-regulated protein 78 and C/EBP homologous protein expressions in colon sections were detected using immunofluorescence.RESULTS Mesalazine reduced the symptoms of spontaneous colitis in IL-10 knockout mice and the histopathological damage of colonic tissues,and alleviated the ER stress in epithelial cells of colitis mice.Western blotting and quantitative real-time polymerase chain reaction results showed that the STAT3/NF-κB pathway in the colon tissue of model mice was activated,suggesting that this pathway was involved in the pathogenesis of UC and might become a potential therapeutic target.Mesalazine could down-regulate the protein expressions of p-STAT3,NF-κB and p-IκB,and down-regulate the mRNA expression of STAT3 and NF-κB.CONCLUSION Mesalazine may play a protective role in UC by reducing ER stress by regulating the STAT3/NF-κB signaling pathway.
基金Supported by Department of Medical Science,University of Turin
文摘AIM: To clarify the association of interleukin-28B (IL28B) single nucleotide polymorphisms (SNPs) with hepatitis C virus (HCV) viremia changes for assessment of interferon (IFN) response.
文摘In a recent genome-wide association study, single nucleotide polymorphisms (SNPs) located near the interleukin-28B gene (IL28B), which encodes type Ⅲ interferon (IFN) λ3, were shown to be strongly associated with a viral response to pegylated IFNα (PEG-IFNα) and ribavirin (RBV) combination therapy and spontaneous viral clearance in patients chroni-cally and acutely infected with hepatitis C virus (HCV), respectively. The global distribution of allele frequencies shows a remarkable pattern, in which a favorable allele is nearly fixed in East Asia, has an intermediate frequency in Europe, and is least frequent in Africa. Although the under-lying mechanisms responsible for viral responses associated with IL28B SNPs have not been completely elucidated, IFN-stimulated gene expression in patients with unfavorable IL28B genotypes tends to be high at baseline and is insufficiently induced by exogenous IFN administration, resulting in poor treatment outcomes. Clinically, triple therapy with PEG-IFNα/RBV together with direct-acting anti-viral agents (DAAs) is currently used to treat chronic hepatitis C as a first-line therapy. Although the predictive power of IL28B status may be attenuated, the IL28B genotype will remain relevant to the outcomes of DAA therapy when used in combination with PEG-IFNα as a backbone. Even with the introduction of IFN-free therapies with a new class of highly effective DAAs, IL28B SNPs are still useful predictors of treatment outcomes and can be used to individualize treat-ment strategies to maximize cost-effectiveness and identify patients at risk of being refractory to treatment. This review summarizes the current understanding of the clinical sig-nificance and role of IL28B in HCV infection and response to therapy.
文摘Background:Interleukin-28B (IL-28B) polymorphism is an important predictor for hepatitis C virus (HCV) treatment response.Whether IL-28b genotypes also influence other nontreatment related clinical parameters is unclear.Methods:Patients with HCV-related chronic liver diseases who attended our department during 2012-2014 were retrospectively analyzed.The single nucleotide polymorphisms (SNPs) of rs12979860 (IL-28B) were correlated with various clinical parameters.We also compared these parameters in patients with and without overt diabetes to identify possible associations.Results:A total of 115 patients were included (median age 48,range 15-76 years;70% males).Overall,43/115(37%) patients had chronic hepatitis,while the remaining 72/115 (63%) had cirrhosis.The most common IL-28B genotype was CC,which was found in 53% of patients (61/115),while the remaining 47% were nonCC [CT 42% (48/115) and T-r 5% (6/115)].Clinical and laboratory parameters like Hb,white blood cell (WBC),platelets,bilirubin,transaminases,and albumin were similar in the CC and nonCC genotypes.Overt diabetes mellitus was present in 22% (25/115) of patients.Patients with nonCC genotype had significantly higher prevalence of overt diabetes mellitus than patients with CC genotype (31% [17/54] versus 13% [8/61];p < 0.05).When parameters were compared in patients with and without overt diabetes mellitus,only IL-28B and age were significantly associated with overt diabetes mellitus (p < 0.05).Conclusion:In HCV patients,overt diabetes mellitus was more commonly associated with the nonCC genotype of IL-28B than the CC genotype.Carriers of the T-allele of SNP rs12979860 were more likely to have insulin resistance than CC homozygotes,and this finding may explain the higher prevalence of diabetes in non-CC genotypes.Thus,an IL-28B test may be useful in patients of HCV in order to determine their likelihood of developing diabetes mellitus.
