Interaction of IFNL3 with insulin resistance,steatosis and lipid metabolism in chronic hepatitis C virus infection

Metabolic changes are inextricably linked to chronic hepatitis C(CHC).Recently polymorphisms in the IFNL3(IL28B)region have been shown to be strongly associated with spontaneous and treatment induced recovery from hepatitis C virus(HCV)infection.Further,circumstantial evidence suggests a link between IFNL3single nucleotide polymorphisms and lipid metabolism,steatosis and insulin resistance in CHC.The emerging picture suggests that the responder genotypes of IFNL3polymorphisms are associated with a higher serum lipid profile,and less frequent steatosis and insulin resistance.This review analyzes the current data regarding this interaction and its meaning for HCV pathogenesis and disease progression.

Insulin resistance,adipokine profile and hepatic expression of SOCS-3 gene in chronic hepatitis C

AIM:to analyze adipokine concentrations,insulin resistance and hepatic expression of suppressor of cytokine signaling 3(SOCS-3)in patients with chronic hepatitis C genotype 1 with normal body weight,glucose and lipid profile.METHODS:The study group consisted of 31 patients with chronic hepatitis C and 9 healthy subjects.Total levels of adiponectin,leptin,resistin,visfatin,omentin,osteopontin and insulin were measured using an ELISA kit.The hepatic expression of SOCS-3 was determined by the use of the reverse transcription polymerase chain reaction method.RESULTS:Homeostasis model assessment for insulin resistance(HOMA-IR)values were significantly higher in hepatitis C virus(HCV)infected patients without metabolic disorders compared to healthy controls(2.24 vs 0.59,P=0.0003).Hepatic steatosis was observed in 32.2%of patients with HCV infection and was found in patients with increased HOMA-IR index(2.81 vs1.99,P=0.05)and reduced adiponectin level(5.96vs 8.37,P=0.04).Inflammatory activity(G≥2)was related to increased osteopontin concentration(34.04vs 23.35,P=0.03).Advanced liver fibrosis(S≥2)was associated with increased levels of omentin and osteopontin(436.94 vs 360.09,P=0.03 and 32.84 vs20.29,P=0.03)and reduced resistin concentration(1.40 vs 1.74,P=0.047).No correlations were reported between adipokine profile,HOMA-IR values and hepatic expression of the SOCS-3 gene.CONCLUSION:We speculated that no relationship between adipokines and HOMA-IR values may indicate that HCV can induce insulin resistance itself.Some adipokines appear to be biochemical markers of steatosis,inflammation and fibrosis in patients with chronic HCV infection.

Prevalence of IFNL3 rs4803217 single nucleotide polymorphism and clinical course of chronic hepatitis C

AIM To evaluate the association of IFNL3(IL28B) SNP rs4803217 with severity of disease and treatment outcome in chronic hepatitis C(CHC).METHODS The study enrolled 196 CHC Polish patients(82 women and 114 men in age 20-64) infected with hepatitis C virus(HCV) genotype 1. They were treatment na?ve and qualified to pegylated interferon alpha(PEG-IFN-α) and ribavirin(RBV) therapy. The analyzed baseline parameters included: degree of inflammation, stage of fibrosis, viral load as well as alanine aminotransferase(ALT), asparagine aminotransferase(AST) and total bilirubin(TBIL). The analysis of response to therapy included: sustained virological response(SVR), defined as undetectable serum HCV RNA level six month after completion of 48-wk therapy, and relapse, defined as achieving undetectable viral load at the end of treatment but not SVR. HCV genotyping and HCV RNA quantification were performed using commercially available tests. DNA was isolated from peripheral blood mononuclear cells or from buccal cell swabs. In addition to rs4803217, also single nucleotide polymorphisms(SNPs)(rs12979860, rs8099917 and rs12980275) of known significance in predicting of HCV clearance were analyzed. SNPs were determined by high resolution melt analysis and confirmed by sequencing of amplicons. RESULTS Frequency of rs4803217 genotypes in studied group was as follows: 27.55%; 54.59% and 17.86% for CC, CA and AA, respectively. The rs4803217 SNP, similar to other analyzed SNPs, was not associated with severity of CHC(grade of inflammation, stage of fibrosis, baseline viral load as well as biochemical parameters: ALT, AST, TBIL). It was demonstrated that the rs4803217 C allele is associated with SVR(C vs A: P < 0.0001; dose of C allele: P = 0.0002) and nonrelapse(C vs A: P = 0.001; dose of C allele: P = 0.002). Moreover, it was found that patients with CC genotype have significantly higher response rates as compared with CA/AA patients(P < 0.0001), whereas patients carrying A allele are significantly predisposed to relapse after treatment(P = 0.0007). Moreover, the association of rs4803217 with SVR was comparable to that of rs12979860 and stronger as observed for rs12980275 and rs8099917. Association of rs4803217 with relapse, was the strongest as compared with the other SNPs. The analysis of combined rs4803217 and rs8099917 genotypes demonstrated that additional genotyping of rs8099917 had no significant impact on the prediction of SVR. Multivariate analysis revealed that among analyzed SNPs only rs4803217 is an independent predictor of SVR(P = 0.016) and relapse(P = 0.024). CONCLUSION The rs4803217 SNP is a strong, independent and superior predictor of SVR and relapse in HCV genotype 1 infected CHC patients treated with PEG-IFN-α and RBV.

Treatment of genotype 2 and 3 chronic hepatitis C virus-infected patients

AIM: Before pegylated interferon alpha (IFN) was introduced for the therapy of chronic hepatitis C virus(HCV)-induced hepatitis, conventional thrice weekly IFN therapy was supplemented by ribavirin. Also, at that time,higher and more frequent doses of IFN were expected to be more effective than the standard regimen of 3 MU thrice weekly. As ribavirin significantly increases side effects and negatively influences the quality of life particularly in young patients, we started a prospective non-randomized study with a daily IFN-2a monotherapy as an initial treatment for chronic hepatitis C.METHODS: Forty-six consecutive chronic HCV-infected patients received 3 MU IFN-2a per day as an initial treatment. Patients with genotype 2 or 3 (n = 12) were treated for 24 wk, and patients with genotypes other than 2 or 3 (n = 34) for 48 wk. Treatment outcome was followed up for 48 wk after the end of treatment (EOT).Virological response was defined as the absence of detectable serum HCV-RNA. Patients without virological response at 12 wk after the start of treatment received RESULTS: During treatment, three genotype 3 patients were excluded from the study due to incompliance. The remaining patients (n = 9) infected with genotype 2 or 3showed an initial virological response rate of 100%. Six patients (66.7%) were still found to be virus-free at the end of follow-up period. In these patients, initial virological response was evident already after 2 wk of treatment. In contrast, initial virological response occurred first after 4 wk of treatment in the three patients who relapsed(33.3%). In comparison, patients infected with genotypes other than 2 or 3 (n = 34) showed an initial virological response rate of only 23.5% (n = 8), and even in combination with ribavirin a sustained virological response(SVR) rate of only 11.8% (n = 4) could be achieved.CONCLUSION: In chronic HCV-infected patients with genotype 2 or 3, a SVR can be expected after 24 wk of daily dose IFN-2a treatment without ribavirin, if initial virological response develops early. This finding is worth to be confirmed in a prospective randomized study with pegylated IFN.

Daclatasvir plus asunaprevir in treatment-na?ve patients with hepatitis C virus genotype 1b infection

AIM To assess daclatasvir plus asunaprevir(d UAL) in treatment-na?ve patients from China's Mainland, Russia and South Korea with hepatitis C virus(HCV) genotype 1 b infection. METHODS Patients were randomly assigned(3:1) to receive 24 wk of treatment with d UAL(daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily) beginning on day 1 of the treatment period(immediate treatment arm) or following 12 wk of matching placebo(placebodeferred treatment arm). The primary endpoint was a comparison of sustained virologic response at posttreatment week 12(SVR12) compared with the historical SVR rate for peg-interferon plus ribavirin(70%) among patients in the immediate treatment arm. The first 12 wk of the study were blinded. Safety was assessed in d UAL-treated patients compared with placebo patients during the first 12 wk(doubleblind phase), and during 24 wk of d UAL in both arms combined.RESULTS In total, 207 patients were randomly assigned to immediate(n = 155) or placebo-deferred(n = 52) treatment. Most patients were Asian(86%), female(59%) and aged < 65 years(90%). Among them, 13% had cirrhosis, 32% had IL28 B non-CC genotypes and 53% had baseline HCV RNA levels of ≥ 6 million IU/m L. Among patients in the immediate treatment arm, SVR12 was achieved by 92%(95% confidence interval: 87.2-96.0), which was significantly higher than the historical comparator rate(70%). SVR12 was largely unaffected by cirrhosis(89%), age ≥ 65 years(92%), male sex(90%), baseline HCV RNA ≥ 6 million(89%) or IL28 B non-CC genotypes(96%), although SVR12 was higher among patients without(96%) than among those with(53%) baseline NS5 A resistanceassociated polymorphisms(at L31 or Y93 H). during the double-blind phase, aminotransferase elevations were more common among placebo recipients than among patients receiving d UAL. during 24 wk of d UAL therapy(combined arms), the most common adverse events(≥ 10%) were elevated alanine aminotransferase and upper respiratory tract infection; emergent grade 3-4 laboratory abnormalities were infrequently observed, and all grade 3-4 aminotransferase abnormalities(alanine aminotransferase, n = 9; aspartate transaminase, n = 6) reversed within 8-11 d. Two patients discontinued d UAL treatment; one due to aminotransferase elevations, nausea, and jaundice and the other due to a fatal adverse event unrelated to treatment. There were no treatment-related deaths.CONCLUSION d UAL was well-tolerated during this phase 3 study, and SVR12 with d UAL treatment(92%) exceeded thehistorical SVR rate for peg-interferon plus ribavirin of 70%.

Impact of hepatitis C virus genotype 3 on liver disease progression in a Chinese national cohort

Background:Hepatitis C virus(HCV)genotype 3,particularly subtype 3b,is increasing in prevalence and distribution in China.This study evaluated the prevalence,regional distribution,clinical characteristics,host factors,treatment outcomes,and disease progression of patients with HCV genotype 3 in China.Methods:A 5-year follow-up was preceded by a cross-sectional study.Treatment choices were at the discretion of treating physicians.Estimated infection time to overall-disease-progression(defined by≥1 of:newly diagnosed cirrhosis;cirrhosis at baseline,Child-Turcotte-Pugh score increased 2 points or more;progression from compensated cirrhosis to decompensated cirrhosis;hepatocellular carcinoma;liver transplantation;or death)was calculated using the Kaplan-Meier method.Cox regression analyses were conducted to evaluate the risk factors for disease progression.Results:The cross-sectional study enrolled 997 patients,including 91 with HCV genotype 3 infection.Among them,subtype 3b(57.1%)was more dominant than subtype 3a(38.5%).Five hundred and twelve patients were included into the follow-up phase.Among patients analyzed for estimated infection time to overall-disease-progression,52/304(17.1%)patients with HCV genotype 1 and 4/41(9.8%)with HCV genotype 3(4/26 with genotype 3b,0/13 with genotype 3a,and 0/2 with undefined subtype of genotype 3)experienced overall-disease-progression.Patients with HCV genotype 3 were younger than those with genotype 1(mean age:39.5±8.7 vs.46.9±13.6 years)and demonstrated more rapid disease progression(mean estimated infection time to overall-disease-progression 27.1 vs.35.6 years).Conclusions:HCV genotype 3,specifically subtype 3b,is associated with more rapid progression of liver disease.Further analysis to compare HCV subtype 3a and 3b is needed in high prevalence regions.

慢性丙肝患者HCV-RNA载量与血清25-OH-D_(3)、铁代谢表达相关性的分析

目的:探讨慢性丙型肝炎患者核糖核酸(HCV-RNA)载量与末梢血血清25羟维生素D3(25-OH-D_(3))、铁代谢表达的相关性,以期为临床提供有效的诊治依据。方法:选取2019年11月-2020年11月我院接受的83例慢性丙型肝炎患者作为研究对象,根据HCV-RNA水平将病例分为高载量组(n=48,1×10^(6)~1×10^(8)copy/mL)与低载量组(n=35,1×10^(3)~1×10^(6)copy/mL),采用酶联免疫吸附检测各组血清25-OH-D3,自动生化分析法检测铁代谢相关指标,对上述结果进行统计学分析。结果:高载量组中阳性45例,阳性率为93.75%,低载量组中阳性12例,阳性率为34.29%;高载量组25-OH-D_(3)水平明显低于低载量组(P<0.05);高载量组血清铁(SI)、血清铁蛋白(SF)明显高于低载量组,总铁结合力(TIBC)明显低于低载量组(P<0.05);经Pearson相关性分析显示慢性丙型肝炎患者HCV-RNA与25-OH-D3水平、TIBC呈显著的负相关(P<0.05),与SI、SF呈显著的正相关(P<0.05)。结论:慢性丙型肝炎患者HCV-RNA载量与血清25-OH-D_(3)、铁代谢指标均具有明显相关性,均可作为其长期治疗的重要观察指标,而且也提示25-OH-D_(3)可能是慢性丙型肝炎的保护因素,能通过补充25-OH-D_(3)改善患者临床症状。

Caspase-3在慢性病毒性乙、丙型肝炎及非酒精性肝炎中的表达及意义

目的:检测慢性乙型肝炎、慢性丙型肝炎和非酒精性脂肪性肝炎中Caspase-3的表达,探讨其临床及病理学意义.方法:应用免疫组织化学方法检测Caspase-3在70例慢性乙型肝炎,50例慢性丙型肝炎,50例非酒精性脂肪性肝炎和15例正常肝组织的表达.结果:(1)Caspase-3在慢性乙型肝炎、慢性丙型肝炎、非酒精性脂肪性肝炎中的表达(57.1%、72.0%、82.0%),高于其在正常肝组织中表达(18.8%),差异有统计学意义(P<0.05);并与肝细胞凋亡密切相关(r=0.356,P<0.001);(2)Caspase-3在慢性乙型肝炎、慢性丙型肝炎和非酒精性脂肪性肝炎随病理损伤程度加重其阳性表达率增高,有统计学意义(P<0.05).结论:Caspase-3与慢性乙型肝炎、丙型肝炎和非酒精性脂肪性肝炎的肝细胞凋亡密切相关,并参与肝炎的发病过程.

血清AFP水平和组织GPC3、VEGF蛋白表达在丙肝相关肝癌中的意义

目的探讨在慢性丙型肝炎病毒(hepatitis C virus,HCV)感染患者中检测血清甲胎蛋白(alpha fetoprotein,AFP)水平和组织中磷脂酰肌醇蛋白聚糖-3(glypican-3,GPC3)、血管内皮生长因子(vascular endothelial growth factor,VEGF)蛋白表达在丙肝相关肝癌(HCV-related hepatocellular carcinoma,HCV-HCC)中的临床应用价值。方法采用电化学发光分析技术和免疫组化染色技术检测30例慢性丙型肝炎(chromc hepatitis C,CHC)、35例丙肝相关肝硬化(HCV-related liver cirrhosis,HCV-Cirr)、30例HCV-HCC患者和30例对照组血清AFP水平和组织中GPC3、VEGF蛋白的表达,分析评价在慢性HCV感染患者肝脏病变的不同阶段中血清AFP水平变化和组织中GPC3、VEGF蛋白的表达情况。结果血清AFP水平在HCV-HCC组和HCV-Cirr组均显著高于CHC组和对照组(P <0. 05),但HCV-HCC组与HCV-Cirr组之间血清AFP水平差异无统计学意义(P> 0. 05)。GPC3、VEGF蛋白在对照组无阳性表达,在HCV-HCC组的阳性表达率分别为86. 7%(26/30)、76. 7%(23/30),显著高于HCV-Cirr组的31. 4%(11/35)和40. 0%(14/35)(χ~2=20. 10、P <0. 001;χ~2=8. 86、P <0. 05)和CHC组的10. 0%(3/30)、16. 7%(5/30)(χ~2=35. 31、P <0. 001,χ~2=21. 69、P <0. 001),且HCV-Cirr组显著高于CHC组(χ~2=4. 39、P <0. 05,χ~2=4. 25、P <0. 05)。GPC3蛋白在中、低分化肝癌组中的阳性率显著高于高分化组(P <0. 05);而VEGF在高分化组与中、低分化组之间差异无统计学意义(P=0. 120)。HCV-HCC组中10例血清AFP阴性者组织中GPC3、VEGF蛋白阳性表达分别为6例和5例,且两者联合检测的阳性率为70. 0%(7/10); HCV-HCC组中GPC3与VEGF蛋白表达呈正相关(r=0. 479、P=0. 03)。结论 GPC3和VEGF蛋白在HCV-HCC组织中高表达与HCV-HCC的发生、发展有关。在HCV-Cirr患者的持续监测中联合检测血清AFP和组织中GCP3、VEGF蛋白有助于提高临床对HCV-HCC的鉴别水平。

IFN-α治疗对慢性丙型肝炎患者CD8^+T细胞亚群Tim-3表达水平的影响

为探讨应用IFN-α治疗和未治疗的慢性丙型肝炎患者外周血CD8+T细胞亚群细胞频数及各亚群上Tim-3表达的变化。采用流式细胞术检测IFN-α治疗和未治疗的慢丙肝患者外周血中CD8+T细胞及各亚群频数及膜表面Tim-3表达水平的方法;q T-PCR检测血清中HCV-RNA水平;Spearman相关性分析CD8+T细胞频数、Tim-3表达与HCV-RNA之间的相关性。结果显示,慢丙肝患者外周血CD8+T细胞频数较健康对照组、IFN-α治疗组显著降低(P<0.01)。初始T细胞明显增加(P<0.01)。TCM、TEM细胞分布频率降低(P<0.01)。经IFN-α治疗后,CD8+T细胞百分率上升(P<0.05),初始T细胞数量下降(P<0.01),TCM、TEM细胞频数均升高(P<0.01)。三组人群TEMRA细胞频数无统计学差异。与健康对照组、IFN-α治疗组相比,慢丙肝患者CD8+T细胞及各亚群Tim-3表达水平均有上调(P<0.05)。经抗病毒治疗后,CD8+T细胞、Naive细胞、TEM细胞、TEMRA细胞亚群Tim-3表达明显降低(P<0.05),TCM细胞亚群中Tim-3表达也有降低,但无统计学差异。Spearman相关性分析发现:慢丙肝患者外周血CD8+T细胞百分率与病毒载量呈反比(r=-0.3775,P<0.01),而Tim-3表达水平与病毒载量正相关(r=0.6230,P<0.0001)。由此可知,HCV感染慢性化时可出现CD8+T细胞亚群分布异常及各亚群Tim-3过表达。IFN-α通过调节各CD8+T细胞亚群分化状态,及下调各群细胞表面Tim-3的表达,促进HCV免疫清除。

索磷布韦/维帕他韦联合或不联合利巴韦林治疗基因3型慢性丙型肝炎肝硬化患者的疗效和安全性

目的探讨索磷布韦/维帕他韦±利巴韦林(sofosbuvir/velpatasvir±ribavirin,SOF/VEL±RBV)治疗基因3型丙型肝炎肝硬化患者的疗效和安全性。方法回顾性纳入2018年6月至2023年2月就诊于昆明市第三人民医院诊断为基因3型(GT3)肝硬化患者,使用SOF/VEL+RBV治疗12周,如有RBV禁忌或者RBV不耐受,则采用SOF/VEL治疗12或24周。分析患者在治疗前、治疗4周、12周及停药后12周的病毒学指标、肝肾功能指标和不良反应等。结果最终纳入319例GT3肝硬化患者,其中SOF/VEL+RBV组308例,SOF/VEL组11例。停药12周后,SOF/VEL+RBV组持续病毒学应答(SVR12)率达98.37%(303/308),与基线相比,APRI评分和FIB-4指数水平均下降(P<0.05),总胆红素、天冬氨酸转氨酶、丙氨酸转氨酶水平均下降,差异均有统计学意义(均P<0.05)。SOF/VEL组SVR12率为72.73%(8/11)。SOF/VEL+RBV组的不良反应为轻度溶血性贫血(15.26%)、乏力(8.12%)和皮疹(8.77%),SOF/VEL组为1例乏力(9.09%)。结论索磷布韦/维帕他韦联合利巴韦林方案在基因3型丙肝感染的代偿期肝硬化和失代偿期肝硬化患者中都能获得较高SVR12率(98.37%),生化学指标和肝纤维化程度均较治疗前有所改善且安全性好。

接受索磷布韦/维帕他韦治疗的慢性丙型肝炎患者免疫检查点TIM-3、PD-1表达情况及临床意义

目的观察接受索磷布韦维帕他韦治疗的慢性丙型肝炎(CHC)患者免疫检查点T细胞免疫球蛋白黏蛋白3(TIM-3)、程序性细胞死亡受体-1(PD-1)的表达及临床价值。方法选择2020年8月—2022年8月南京医科大学附属淮安第一医院收治的120例CHC患者作为CHC组,另选取同期于本院体检的118例研究对象,将其作为健康对照组,CHC组给予CHC组患者索磷布韦/维帕他韦治疗,连续治疗3个月。比较两组血生化指标、单核亚群细胞以及各亚群TIM-3、PD-1水平进行检测。结果未进行治疗时,CHC患者血清ALT、AST水平分别为[(74.0±35.8)U/L、(55.1±26.0)U/L]相较于健康对照组[(14.9±6.3)U/L、(19.2±7.0)U/L]显著升高;在治疗3个月末,CHC患者PD-1 CD4、PD-1 CD8、TIM-3 CD8、TIM-3 CD4水平分别为[(0.6±0.1)%、(1.7±0.6)%、(2.5±1.0)%、(6.5±1.0)%]比对照组[(0.4±0.1)%、(1.5±0.7)%、(1.7±0.8)%、(6.0±2.4)%]高(均P<0.05)。结论索磷布韦/维帕他韦治疗CHC,有助于患者肝功能的改善,而CHC患者存在外周血部分淋巴细胞比例紊乱,负性免疫检查点分子的高表达可对细胞免疫进行调控,对于单药治疗未见症状改善的患者,可在应用索磷布韦治疗的基础上加用维帕他韦治疗。

PNPLA3 I148M polymorphism and progressive liver disease

The 148 Isoleucine to Methionine protein variant(I148M)of patatin-like phospholipase domain-containing 3(PNPLA3),a protein is expressed in the liver and is involved in lipid metabolism,has recently been identified as a major determinant of liver fat content.Several studies confirmed that the I148M variant predisposes towards the full spectrum of liver damage associated with fatty liver:from simple steatosis to steatohepatitis and progressive fibrosis.Furthermore,the I148M variant represents a major determinant of progression of alcohol related steatohepatitis to cirrhosis,and to influence fibrogenesis and related clinical outcomes in chronic hepatitis C virus hepatitis,and possibly chronic hepatitis B virus hepatitis,hereditary hemochromatosis and primary sclerosing cholangitis.All in all,studies suggest that the I148M polymorphism may represent a general modifier of fibrogenesis in liver diseases.Remarkably,the effect of the I148M variant on fibrosis was independent of that on hepatic steatosis and inflammation,suggesting that it may affect both the quantity and quality of hepatic lipids and the biology of non-parenchymal liver cells besides hepatocytes,directly promoting fibrogenesis.Therefore,PNPLA3 is a key player in liver disease progression.Assessment of the I148M polymorphism will possibly inform clinical practice in the future,whereas the determination of the effect of the 148M variant will reveal mechanisms involved in hepatic fibrogenesis.

Tim-3和PD-1在慢性丙型肝炎患者不同单核细胞亚群的表达水平分析

目的分析慢性丙型肝炎(CHC)患者外周血单核细胞亚群分布,同时观察负性调节分子T细胞免疫球蛋白及黏蛋白域蛋白3(Tim-3)和程序性细胞死亡蛋白1(PD-1)在各亚群表达的变化及意义。方法利用流式细胞术检测CHC患者外周血单核细胞亚群比例和各亚群Tim-3、PD-1表达,并与临床指标如丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)采用Spearman方法进行相关性分析。结果与健康对照组比较,CHC患者外周血CD14^+CD16^+单核细胞比例增高,以CD14CD16^+单核细胞比例增高显著。Tim-3在CD14CD16-单核细胞和CD14^+CD16单核细胞上表达水平升高;PD-1在CD14CD16-单核细胞和CD14CD16^+单核细胞上表达水平升高。CHC患者单核细胞亚群以及各亚群Tim-3、PD-1和临床指标ALT及AST无明显相关性。结论 Tim-3和PD-1在不同单核细胞亚群表达水平不同。

慢性丙型肝炎患者血浆IRF-3水平的变化及临床意义

目的探讨慢性丙型肝炎(CHC)患者干扰素调节因子(IRF)-3水平的变化及其与丙型肝炎病毒(HCV)RNA载量、肝脏损伤程度及干扰素抗病毒疗效的关系。方法检测57例CHC患者抗病毒治疗前及26名体检健康者(正常对照组)血浆IRF-3、β-干扰素(IFN-β)水平,同时检测丙氨酸氨基转移酶(ALT)活性、Ⅳ型胶原(CⅣ)水平及HCV RNA载量。根据ALT、CⅣ和HCV RNA载量分别分组;根据抗病毒疗效分为应答组和无应答组。采用Spearman秩相关分析评估各项目之间的相关性。结果CHC组血浆IRF-3、IFN-β水平明显低于正常对照组(P<0.01)。ALT升高组与ALT正常组之间、CⅣ升高组与CⅣ正常组之间、HCV RNA高载量组与HCV RNA低载量组之间血浆IRF-3水平差异均有统计学意义(P<0.05)。Spearman秩相关分析结果显示,CHC患者IRF-3与IFN-β呈正相关(r=0.930,P<0.01),与HCV RNA载量、ALT、CⅣ均呈负相关(r值分别为-0.321、-0.290、-0.345,P<0.05)。应答组血浆IRF-3水平低于无应答组(P<0.05),血浆IFN-β水平2个组之间差异无统计学意义(P>0.05)。结论CHC患者血浆IRF-3水平与HCV RNA载量、肝细胞损伤程度及纤维化程度有关,对干扰素疗效的判断也有一定的价值。

索磷布韦/维帕他韦联合或不联合利巴韦林治疗基因3型慢性丙型肝炎病毒感染者的疗效及安全性:一项真实世界研究

目的评估索磷布韦/维帕他韦(sofosbuvir/velpatasvir,SOF/VEL)联合或不联合利巴韦林(ribavirin,RBV)治疗基因3型慢性丙型肝炎病毒(hepatitis c virus,HCV)感染者的有效性及安全性。方法以2018年12月至2020年1月至成都市公共卫生临床医疗中心就诊的84例基因3型慢性HCV感染者为研究对象,其中慢性丙型肝炎56例,代偿期肝硬化17例,失代偿期肝硬化11例。根据患者病情予以SOF/VEL联合或不联合RBV抗病毒治疗12~24周,检测患者基线、治疗4周、治疗结束时以及治疗结束后12周肝功能[丙氨酸氨基转移酶(alanine transaminase,ALT)、天门冬氨酸氨基转移酶(aspartate transaminase,AST)、总胆红素(total bilirubin,TBil)、白蛋白(albumin,ALB)]、肾功能[尿素、肌酐(creatinine,Cr)]和血常规[白细胞(white blood cell,WBC)、血红蛋白(hemoglobin,HGB)和血小板(platelet,PLT)]等指标,检测基线和治疗结束后12周的肝硬度值。同时详细记录患者在治疗期间的不良事件。主要结局指标为治疗结束后12周的持续病毒学应答(sustained virological response,SVR)和治疗中不良事件的发生情况。结果共80例患者(95.2%)达到SVR12,其中慢性丙型肝炎、代偿期肝硬化及失代偿期肝硬化患者的SVR12分别为100%(56/56)、94.1%(16/17)和72.7%(8/11),差异有统计学意义(P=0.003)。慢性丙型肝炎组、代偿期肝硬化及失代偿期肝硬化患者治疗结束后12周肝硬度值均较基线显著降低[(6.7±0.7)kPa vs(7.4±1.1)kPa,(17.8±3.1)kPa vs(25.9±3.4)kPa,(23.0±4.5)kPa vs(31.0±4.9)kPa;P均<0.001]。3组患者治疗后ALT和AST均较基线显著降低(P均<0.05),尿素、Cr、WBC和PLT差异无统计学意义(P均>0.05)。代偿期肝硬化和失代偿期肝硬化患者治疗后ALB较基线显著升高,HGB较基线显著降低(P均<0.05)。84例患者总体不良事件发生率为13.1%(11/84),其中慢性丙型肝炎、代偿期肝硬化和失代偿期肝硬化患者不良事件发生率分别为8.9%(5/56)、11.8%(2/17)和36.4%(4/11),差异无统计学意义(P=0.055),常见的不良事件包括疲劳、头痛和贫血等,无严重不良事件发生,无因不良事件导致的治疗中止。结论应用SOF/VEL联合或不联合RBV方案治疗基因3型慢性HCV感染者具有较高的SVR12,不良事件发生率较低,疗效显著,安全性良好。

基于索磷布韦的药物治疗3型慢性丙型肝炎患者疗效和安全性观察:一项单中心真实世界回顾性分析

目的探讨真实世界中索磷布韦/维帕他韦(SOF/VEL)联合或不联合利巴韦林(RBV)方案治疗云南地区3型慢性丙型肝炎(CHC)患者的疗效及安全性。方法选择2018年1月至2022年3月期间219例3型CHC患者,以SOF/VEL联合或不联合RBV方案治疗12周或24周,停药后随访12周。收集患者的一般人口学资料、HCV RNA定量、肝功能、肝硬度测定值等指标。结果219例3型CHC患者中,停药12周时异常生化指标和肝硬度值较基线明显降低,持续病毒应答率为95.4%(209/219),共有60例报告轻度不良反应,主要为贫血、乏力和头痛,未见严重不良反应。结论SOF/VEL联合或不联合RBV方案治疗无肝硬化或合并代偿期肝硬化的3型丙型肝炎患者可获得较高应答率,但治疗合并慢性肝衰竭的3型丙肝患者应答率较低。患者使用该方案后不良反应较轻,安全性可接受。

中国慢性丙型肝炎基因3型患者的现状、治疗和展望

慢性丙型肝炎是全球慢性肝病的重要病因之一,其中基因3型的慢性丙型肝炎与肝脏疾病的进展关系密切,其治疗仍然具有挑战性。随着时间推移,我国的慢性丙型肝炎基因3型患者比例已呈上升趋势,加大了治疗难度。为此,需要结合国内外研究,探索出更适合我国慢性丙型肝炎基因3型患者的治疗方案。

非基因3型慢性丙型肝炎合并非酒精性脂肪性肝病的流行病学调查

目的对非基因3型慢性丙型肝炎患者发生非酒精性脂肪性肝病进行流行病学调查。方法回顾性分析2013年1月至2018年10月在湖州市中心医院诊治的196例非基因3型慢性丙型肝炎患者的临床资料,将89例合并非酒精性脂肪性肝病(排除因长期饮酒导致的脂肪肝)患者设为试验组,将107例未发生脂肪肝患者设置为对照组。对所有入组患者的一般特征、血清生化指标、丙型肝炎病毒载量等指标进行统计学分析,调查慢性丙型肝炎患者合并非酒精性脂肪性肝病的流行病学特征。结果 89例非基因3型慢性丙型肝炎合并非酒精性脂肪性肝病的患者中男女性别差异无统计学意义(P>0.05);>40~50岁年龄段患者合并非酒精性脂肪性肝病的发生率(43.8%)显著高于其他年龄段患者(20~40岁10.1%,>50~60岁29.2%,>60岁16.9%),差异有统计学意义(P<0.05);拥有脂肪肝家族史、肥胖、糖尿病与其发病密切相关,差异有统计学意义(P<0.05)。治疗结束后试验组体质量指数(BMI)[(23.49±2.06)kg/m^2vs(19.97±1.82)kg/m^2]、丙氨酸氨基转移酶[(76.57±21.58)U/L vs(40.52±15.93)U/L]、总胆固醇[(6.71±0.80)mmol/L vs(3.15±0.67)mmol/L]、甘油三酯[(3.17±0.68)mmol/L vs(1.02±0.37)mmol/L]均高于对照组,差异有统计学意义(P均<0.05)。结论非基因3型慢性丙型肝炎合并非酒精性脂肪性肝病与拥有脂肪肝家族史、肥胖、糖尿病密切相关,原因可能与这部分人群遗传基因易感或合并代谢综合征有关。40~50岁年龄段患者发病率显著高于其他年龄段人群,可能与这一年龄阶段人群机体代谢水平较青年人群下降以及生活方式不当(过量进食或饮酒、运动量少)有关。

血清五聚蛋白3水平对慢性丙型肝炎肝纤维化的诊断价值

目的:探究慢性丙型肝炎(CHC)患者血清五聚蛋白3(PTX3)的表达水平,并分析PTX3对肝纤维化分期诊断的临床意义。方法:选取2016年9月至2019年10月济宁医学院附属医院消化内科收治的178例CHC患者为CHC组,男92例,女86例,年龄(42.28±13.70)岁,年龄范围为24~67岁。另选取同时期体检的30例健康者作为健康组,男19例,女11例,年龄(43.05±12.88)岁,年龄范围为22~66岁。应用酶联免疫吸附法(ELISA)检测血清白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、透明质酸、层黏连蛋白(LN)、Ⅲ型前胶原肽(PⅢP)、Ⅳ型胶原蛋白(CⅣ)及PTX3的水平。结果:CHC组血清IL-2水平[(97.27±26.39)pg/ml]显著低于健康组[(146.4±31.02)pg/ml],IL-6[(72.65±10.26)pg/ml]、TNF-α水平[(32.58±6.75)pg/ml]均显著高于健康组[(36.61±11.05)pg/ml、(11.13±2.34)pg/ml],差异有统计学意义(P<0.05);CHC患者的血清透明质酸[(255.22±69.98)μg/L]、LN[(173.36±33.02)μg/L]、PⅢP[(163.23±40.89)μg/L]、CⅣ[(227.20±72.77)μg/L]、PTX3水平[(4.47±1.20)μg/L]均显著高于健康组[(74.97±15.73)μg/L、(78.36±12.82)μg/L、(71.95±6.10)μg/L、(44.86±2.64)μg/L、(0.37±0.11)μg/L],差异有统计学意义(P<0.05);经Pearson相关性分析,血`清PTX3水平与IL-2呈显著负相关,而与IL-6、TNF-α、透明质酸、LN、PⅢP、CⅣ等均呈显著正相关(P<0.05);CHC组不同肝纤维化程度患者血清PTX3水平上差异显著(P<0.05),且CHC患者病理学结果显示,F1期为39例、F2期为61例、F3期为33例、F4期为45例。4组CHC患者在PTX3水平上比较,F4期>F3期>F2期>F1期,差异有统计学意义(P<0.05);诊断价值采用ROC曲线结果显示F1期的诊断以PTX3取2.070μg/L诊断效果最佳,AUC为0.628,特异度为0.921,灵敏度为0.402;F2期的诊断以PTX3取2.430μg/L诊断效果最佳,AUC为0.661,特异度为0.770,灵敏度为0.615;F3期的诊断以PTX3取3.245μg/L诊断效果最佳,AUC为0.789,特异度为0.727,灵敏度为0.872;F4期的诊断以PTX3取4.530μg/L诊断效果最佳,AUC为0.842,特异度为0.844,灵敏度为0.923。结论:血清PTX3水平在CHC患者中显著升高,且与CHC患者肝纤维化程度密切相关,可作为辅助诊断CHC肝纤维化程度的新指标。