Ultrasound evaluation of perihepatic lymph nodes during antiviral therapy with the protease inhibitor telaprevir (VX-950) in patients with chronic hepatitis C infection

Previous studies have shown that the total perihepatic lymph node (PLN) volume is (1) associated with the extent of inflammatory activity in the liver and (2) changes according to the antiviral response in patients receiving interferon-based therapy for chronic hepatitis C (HCV) infection. The aim of this prospective pilot study was to examine whether the total PLN volume similarly changes in patients receiving antiviral monotherapy with the protease inhibitor telaprevir (VX-950). The present study was conducted in a subgroup of 19 patients with chronic hepatitis C genotype-1 infection treated with the protease inhibitor telaprevir (VX-950) or placebo in a phase Ib clinical trial. The total perihepatic lymph node volume was assessed using sonography before the initiation of antiviral therapy, at the end of 14 d of treatment, and at follow-up. Treatment with telaprevir resulted in a significant reduction of plasma HCV-RNA in all patients at the end of 14 d of treatment. In patients receiving telaprevir, the total PLN volume decreased significantly at the end of 14 d of treatment compared with pretreatment volume (1.26 mL to 0.76 mL, p=0.01). In contrast, no significant difference was seen in patients receiving placebo (1.00 mL to 1.06 mL, p=0.26). These results suggest that the perihepatic lymph node volume can be used as an indicator for viral and histologic response not only as previously reported in patients receiving interferon-based therapy, but also in patients receiving therapy with direct antivirals.     

Peripancreatic lymphoadenopathy and extrahepatic immunological manifestations in chronic hepatitis C

Abstract. The aim of the study was to determine the role of peripancreatic lymph node swelling in systemic immunological alterations during chronic hepatitis C (HC). The prospective study was carried out as a clinical study in a university hospital. Clinical, haematochemical and ultrasonographic findings in 182 patients were studied. Ultrasonography was performed by the same operator and the findings were evaluated blind without the operator knowing the clinical and haematochemical parameters. Hepatitis B virus (HBV) markers, anti-HCV antibodies. LKMl, cryoglobulinaemia, rheumatoid factor and anti-tissue antibodies were determined. Liver biopsy was carried out in 43 of the 182 patients. One or two pathological peripancreatic lymph nodes (PLNs) were present in 30 of the 182 patients and, of the 30, 28 were anti-HC positive. Only one patient in the non-PLN group was positive for anti-HCV, there being statistical significance ( P <0.0001) between the PLN and non-PLN groups. In HCV-positive patients, extrahepatic immunological manifestations were observed (cryoglobulinaemia; positivity to anti-smooth muscle, antinuclear and antimitochondrial antibodies; positivity to rheumatoid factor and LKMl). In five patients the presence of focal lymphocytic aggregates was detected by biopsy, whereas one patient presented typical ocular lesion of Mikulicz's syndrome. Our results may confirm the marked lymphotropism shown by the HC virus and indicate more complex immune system involvement, especially in view of the coexisting signs of immune system involvement related to the presence of intrahepatic cellular aggregates detected in our study. We believe that the peripancreatic adenopathy in chronic HCV hepatitis is an important diagnostic sign and may indicate an involvement of the C virus in the still unexplained extrahepatic immunological disorders.     

慢性丙型肝炎发生肝脂肪变与脂联素的关系

目的探讨慢性丙型肝炎(chronic hepatitis C,CHC)患者发生肝脂肪变与脂联素的关系。方法 80例CHC患者分为有肝脂肪变组8例与无肝脂肪变组72例,单纯非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)26例为对照组,比较各组血清脂联素等生化指标。结果 2组CHC患者糖代谢及脂代谢指标、丙型肝炎病毒核糖核酸水平、血清脂联素水平、肝脏炎症程度比较差异均无统计学意义(P>0.05),CHC组血清脂联素水平高于NAFLD组(P<0.01);脂联素与年龄、谷丙转氨酶、谷草转氨酶和丙型肝炎病毒核糖核酸水平呈正相关(P<0.05),与低密度脂蛋白胆固醇、载脂蛋白-B、三酰甘油和空腹血糖水平呈负相关(P<0.05)。结论 CHC患者发生肝脂肪变与血清脂联素无关;血清脂联素与年龄、肝脏炎症程度和丙型肝炎病毒核糖核酸水平呈正相关,与血糖、血脂水平呈负相关。     

慢性丙型肝炎患者发生代谢综合征的危险因素

目的探讨中国成年人慢性丙型肝炎（chronic hepatitis C,CHC）患者发生代谢综合征（metabolicsyndrome,MS）的危险因素。方法未经治疗的80例CHC患者,分为合并MS组9例与未合并MS组71例,比较2组HCV-RNA水平和基因分型、肝脏炎症程度及生化指标。结果 MS的发生率为11.25%（9/80）;2组胰岛素、胰高血糖素、胰岛素抵抗指数、瘦素、脂联素、HCV-RNA水平、肝脏炎症程度差异均无统计学意义（P〉0.05）;合并MS组总胆固醇、低密度脂蛋白胆固醇、载脂蛋白B、三酰甘油、体质量指数、空腹血糖均明显高于未合并MS组（P〈0.05）;多元回归分析显示体质量指数、三酰甘油是CHC患者发生MS的独立危险因素;基因1型MS发生率为8.5%,非基因1型MS发生率为11.1%,其差异无统计学意义（P〉0.05）。结论 CHC患者合并MS与体质量指数和三酰甘油密切相关,与丙型肝炎病毒本身、肝脏炎症程度及瘦素、脂联素水平无明显相关。     

Interferon-beta plus ribavirin therapy can be safely and effectively administered to elderly patients with chronic hepatitis C

AimThis study aims to evaluate the efficacy and safety of interferon-beta plus ribavirin therapy in older Japanese patients.Patients and methodsThis study enrolled 132 older patients (age, ≥65 years) with chronic hepatitis C who received 24–48 weeks of interferon-beta plus ribavirin (FR; n = 66) or pegylated interferon-alpha plus ribavirin (PR; n = 66) therapy.ResultsPatients with the ITPA genotype (CA/AA) in the PR group had significantly greater decreases in hemoglobin levels than those in the FR group at or after week 8. The proportions of patients with a dose reduction of interferon-beta and ribavirin in the FR group were significantly lower than those in the PR group. A significantly higher proportion of patients completed treatment in the FR group than in the PR group. The sustained virological response (intention-to-treat analysis) rate of naïve patients with genotype 1 was 29% (6 of 21) in the PR group and 29% (6 of 21) in the FR group. The sustained virological response (intention-to-treat) rate of those with genotype 2 was 67% (12 of 18) in the PR group and 72% (13 of 18) in the FR group.ConclusionInterferon-beta plus ribavirin therapy was safe in elderly patients, with lower proportions of patients with a dose reduction of interferon-beta or ribavirin and treatment discontinuation. In treatment-naïve patients, the sustained virological response rate was similar between interferon-beta plus ribavirin therapy and pegylated interferon-alpha plus ribavirin therapy, regardless of whether the patients had hepatitis C virus genotype 1 or 2.     

Predictors of liver-related complications in patients with chronic hepatitis C

Chronic hepatitis C is the leading cause of decompensated liver disease requiring liver transplantation and a major cause of hepatocellular carcinoma (HCC). In liver clinic series, about 20% of those chronically infected with hepatitis C virus (HCV) develop cirrhosis over 20 years. From epidemiological data, however, it is clear that certain subgroups of patients are more likely to develop liver-related complications than others. Both host and viral factors have been implicated in individual susceptibility to adverse outcomes. The impact of host factors, such as alcoholism, is now well defined, and viral factors, such as genotype and viral load, appear to be less influential than previously considered. Coinfections with HIV, hepatitis A virus (HAV) and hepatitis B virus (HBV) may influence the rate of fibrotic progression and the subsequent development of complications in patients with chronic hepatitis C. The stage of fibrosis on biopsy and biochemical markers, such as a low serum albumin, can help identify patients who are more likely to develop complications. The role of the immune system in modifying the course of HCV is only now being defined. This editorial explores the role of host and viral factors in the development of liver-related complications in HCV-infected individuals.     

慢性丙型肝炎患者抗核抗体谱的表达及临床意义

目的分析慢性丙型肝炎患者抗核抗体谱(LIA-ANAs)的表达,探讨慢性丙型肝炎患者出现自身抗体的临床意义。方法采用回顾性研究,选取2018年3—7月海军军医大学附属长海医院感染科门诊和住院收治的慢性丙型肝炎患者81例作为慢性丙型肝炎组,同时选取81例体检健康者作为健康对照组,检测2组LIA-ANAs、丙型肝炎病毒(HCV)-RNA载量及肝功能结果并进行统计学分析。结果81例慢性丙型肝炎患者共37例检出LIA-ANAs,阳性率为45.67%,阳性率显著高于健康对照组的4.93%(4/81),差异有统计学意义(χ^2=33.300,P<0.001)。30例(37.04%)患者检出1种特异性自身抗体,占LIA-ANAs阳性者的81.08%;6例(7.40%)检出2种特异性自身抗体,占LIA-ANAs阳性者的16.21%;1例(1.23%)检出3种特异性自身抗体,占LIA-ANAs阳性者的2.70%。81例慢性丙型肝炎患者中,ANA滴度≥1∶100共6例;24例HCV-RNA≥1×103 copies/mL。LIA-ANAs阳性和阴性组间HCV-RNA载量水平差异有统计学意义(χ^2=4.645,P<0.05),2组丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)的中位数差异有统计学意义,LIA-ANAs阳性组ALT和AST水平均高于阴性组(U=595.000、597.500,P=0.0382、0.0403)。81例慢性丙型肝炎患者LIA-ANAs阳性和阴性组间年龄(t=0.720,P=0.479)、性别(χ^2=0.400,P=0.520)差异无统计学意义。结论慢性丙型肝炎患者容易产生自身抗体,自身抗体的产生与性别、年龄无关,但与肝功能(ALT、AST)、HCV-RNA载量有关。对慢性丙型肝炎患者血清进行LIA-ANAs的检测,将有助于临床诊治的需求。     

不同注射部位对干扰素治疗慢性丙型肝炎的效果比较

目的:探讨腹部皮下注射法与传统的三角肌皮下注射法在干扰素治疗慢性丙型肝炎的疗效及副作用。方法:将64例符合《病毒性肝炎防治方案》中拟定的标准的丙型肝炎病毒慢性感染患者随机分为实验组36例和对照组28例,均给予皮下注射聚乙二醇干扰素α-2a 135μg/次,1次/周,同时口服利巴韦林1 000 mg/d,共治疗48周。实验组采用腹部皮下注射法,对照组给予三角肌皮下注射法。结果:实验组注射部位疼痛程度、皮肤局部红肿、硬结情况优于对照组(P<0.01,P<0.05)。结论:腹部皮下注射法既能达到治疗目的,又可减少疼痛程度、皮下硬结的发生,值得临床推广。     

福建省慢性丙型肝炎患者丙型肝炎病毒基因分型的分析

目的观察福建省慢性丙型肝炎患者基因型分布特点以及与患者性别、年龄、丙型肝炎病毒（HCV） RNA 之间的关系。方法应用反转录聚合酶链反应（RT-PCR）和 SANGER 测序法对155例慢性丙型肝炎患者的HCV 进行基因分型。结果在155例标本中,HCV 基因1型占55．48％,基因2型占18．71％,基因3型13．51％,基因6型12．26％,未见基因4、5型;男女慢性 HCV 感染均以1型为主要基因型,在其他基因型中,男性3型、6型多于2型,女性则以2型为主,差异有统计学意义（P ＜0．05）;基因2型平均年龄为（49岁）,3型平均年龄为（35岁）,差异有统计学意义（P＜0．05）。结论福建地区 HCV 基因型以1b 型为主,其次是2a 型,未见基因4、5型;基因2型的感染者平均年龄较基因3型大。     

Association of human platelet antigens polymorphisms with the levels of serum fibrosis marks in chronic hepatitis C patients

BackgroundHost genetic polymorphisms influence the fibrosis progression of chronic hepatitis C (CHC) patients. Previous studies have shown the association of human platelet antigens (HPAs) polymorphisms with CHC. However, little is known regarding the association of HPAs polymorphisms with the fibrosis progression of CHC. The aim of this study was to determine the association of HPA -2, -3, -5 and -15 polymorphisms with the levels of serum fibrosis marks in CHC patients.MethodsThe HPA -2, -3, -5 and -15 were genotyped by 5ˊ-nuclease assay in 211 CHC patients, while the serum concentration of hyaluronic acid (HA), collagen IV (CIV), amino-terminal pro-peptide of type III procollagen (PIIINP), and laminin (LN) from the same samples were measured by time resolved fluorescence immunoassay.ResultsThe level of serum LN was significantly lower in CHC patients with HPA-15aa genotype compared to those with HPA-15ab/bb (P = 0.032) but did not differ among HPA-2, -3 and -5 genotypes. There were no difference in HA, CIV and PIIINP levels among HPA-2, -3,-5 and -15 genotypes.ConclusionsThis study demonstrates that HPA-15 aa polymorphism is associated lower serum LN in CHC, which suggests that HPA -15 aa may be involved in the fibrosis progression of CHC.     

Zinc supplementation therapy improves the outcome of patients with chronic hepatitis C

We administered zinc supplementation therapy over three years to patients with chronic hepatitis C and reported and that the aspartate aminotransferase (AST) and alanine aminotaransferase (ALT) levels decreased, and platelet counts increased, significantly in the group with increased serum zinc concentrations. We are continuing this treatment to clarify the long-term consequences and report here the changes in serum zinc concentrations over seven years and compare the cumulative incidence of hepatocellular carcinoma (HCC). We administered polaprezinc to 32 patients, randomly selected for zinc therapy (treatment group), while another 30 formed the control group. We measured the serum zinc and albumin concentrations and conducted a prospective study to determine long-term outcomes. The changes and rates of change of serum zinc concentrations after seven years were 76.7 ± 18.2 µg/dl and +0.302 ± 0.30% in the treatment group and 56.7 ± 12.4 µg/dl and +0.033 ± 0.21% in the control group and had increased significantly (p = 0.0002, p = 0.0036). Progression of liver disease seemed to vary, depending on serum albumin concentrations. In the group with baseline serum albumin concentrations of 4.0 g/dl or more, the change and rate of change of serum zinc concentrations increased significantly, and the cumulative incidence of HCC tended to decrease, in the treated group. According to multivariate analysis, the factors that contribute to a reduction in the incidence of HCC are zinc therapy (risk ratio: 0.113, 95% CI: 0.015–0.870, p = 0.0362), and platelet counts (0.766, 0.594–0.989, 0.0409). Zinc supplementation therapy seems to improve liver pathology and reduce the incidence of HCC.     

抗病毒药物治疗时间和剂量对慢性丙型肝炎患者治疗效果影响的研究

目的研究抗病毒药物治疗时间及剂量对慢性丙型肝炎患者治疗效果的影响。方法选择2010年6月至2014年4月接受治疗的慢性丙型肝炎患者90例。所有患者均采用聚乙二醇干扰素联合利巴韦林治疗,血红蛋白均降至100 g/L。将其按随机数表法随机分为两组,严格组(n=45)和放宽组(n=45),严格组当血红蛋白≤100 g/L时减量,血红蛋白≤80 g/L时停药;放宽组当血红蛋白≤80 g/L时减量,血红蛋白≤60/L时停药。观察两组患者的持续病毒学应答(SVR)、复发率、总胆红素(TBil)、天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、γ-谷氨酰氨基转移酶(γ-GT)等指标和不良反应。结果两组患者在治疗结束停药后随访观察6个月,放宽组患者的SVR明显高于严格组,复发率低于严格组,TBil、AST、ALT和γ-GT与严格组患者相比均有所下降,差异均有统计学意义(P0.05)。两组患者在治疗过程中均出现多种不良反应,但两组患者的不良反应种类及发生率比较差异无统计学意义(P0.05)。结论对于采用聚乙二醇干扰素联合利巴韦林治疗的慢性丙型肝炎患者,放宽利巴韦林剂量调整可以提高患者的SVR,降低患者的复发率,患者的肝脏指标有所改善,并未增加患者的不良反应,值得在临床推广应用。     

白介素-18在慢性丙型肝炎患者中的表达及意义研究

目的：了解慢性丙型肝炎（CHC）患者血清白介素-18（IL-18）与丙型肝炎病毒抗体（HCV-Ab）、病毒载量、丙氨酸氨基转移酶（ALT）的关系,探讨IL-18在CHC患者中的表达情况与临床意义。方法收集2012年12月至2013年4月广西医科大学第一附属医院门诊及病区就诊的47例CHC患者为CHC患者组,检测IL-18、病毒载量、HCV-Ab、ALT ,分析丙型肝炎病毒阳性、阴性,HCV-Ab阳性、阴性以及不同ALT 浓度患者IL-18的表达情况。另纳入同期高校体检学生20例为健康对照组,分析CHC患者与健康体检者IL-18的表达情况。结果 CHC患者组与健康对照组相比,IL-18浓度显著升高,差异有统计学意义（P＜0．01）。IL-18在 HCV-RNA阳性与阴性、HCV-Ab阳性与阴性间表达差异均无统计学意义（P＞0．05）;血清ALT水平与IL-18水平相关性分析,结果无明显相关性（r＝0．291,P＞0．05）。结论 IL-18与HCV慢性感染有关,但与HCV复制及其所致的肝损伤无明显相关性。     

Anticardiolipin antibodies and vascular access thrombosis in Taiwanese haemodialysis patients with chronic hepatitis C: a retrospective study

Hepatitis C virus causes various extrahepatic immunologic abnormalities. Vascular access thrombosis (VAT) is a major cause of morbidity in chronic haemodialysis (HD) patients. Immunoglobulin-G anticardiolipin antibody (IgG-ACA) is strongly associated with venous and arterial thrombosis in patients with normal renal function. Previous investigations have reported the association of raised IgG-ACA titre recurrent with VAT in HD patient, and also few equivalent studies were reported the same in Taiwan. This study attempted to determine whether raised IgG-ACA titres are associated with increased risk of recurrent VAT in HD patients with chronic hepatitis C. This study enrolled 98 chronic hepatitis C patients undergoing HD. IgG-ACA titre and hepatitis C marker were measured for all subjects. Raised IgG-ACA titres were present in 29.6% (29/98) of patients. In both groups (raised and normal IgG-ACA), the type of shunt did not differ (p = 0.416). There was strong association between raised IgG-ACA titre and recurrent VAT (p = 0.0004). In predicting for more or one episodes of VAT using multiple logistic regression, synthetic graft (p < 0.0001), raised IgG-ACA titre (p = 0.039), presence of hepatitis B (p = 0.004) and haemodialysis duration (p = 0.039) were significant factors. The prevalence of raised IgG-ACA titres was 39.6% among chronic hepatitis C with HD patients. There was strong association between raised IgG-ACA titre and recurrent VAT, and this finding may be the consequence of pathogenetic role of raised IgG-ACA titres on the development of VAT status in HD patients with chronic hepatitis C.     

丙型肝炎病毒感染者病毒载量与血脂代谢指标的相关性分析

目的探讨丙型肝炎病毒感染者血脂代谢状况及与外周血病毒载量的相关性。方法 75例丙型肝炎病毒感染者分为HCV RNA高复制组、低复制组及阴性组。利用荧光定量PCR方法检测外周血HCV RNA水平,应用全自动生化分析仪检测患者TG、CHO、Apo A1、Apo B、HDL-C、LDL-C等血脂代谢指标。结果甘油三酯(TG)、脂蛋白Apo B和低密度脂蛋白胆固醇(LDL-C)在HCV RNA阴性组和高复制组有显著差异,上述3个指标均与HCV RNA呈正相关。结论慢性丙型肝炎病毒感染伴随着TG、Apo B、LDL-C水平的上升,且与病毒载量呈正相关关系,并提示通过有效的抗病毒治疗可能有助于血脂代谢紊乱的纠正。     

2'-,5'-Oligoadenylate synthetase response ratio predicting virological response to PEG-interferon-alpha2b plus ribavirin therapy in patients with chronic hepatitis C

OBJECTIVE: Although all the mechanisms of elimination of hepatitis C virus (HCV) by Interferon (IFN) have not been fully elucidated, the 2'-5'-oligoadenylate (2-5A) system is one of the mechanisms of the antiviral effect of IFN. Consequently, the measurement of 2'-5'-oligoadenylate synthetase (2-5AS) activity could be useful for the evaluation of IFN treatment. This retrospective study was aimed at assessing whether 2-5AS activity functions as a clinical marker of virological response to PEG-interferon-alpha2b (PEG-IFN) plus ribavirin therapy of chronic hepatitis C. METHODS: The 32 patients included in this study had high viral loads of serum HCV-RNA of genotype 1b with chronic hepatitis C. All the patients received a regimen of PEG-IFN plus ribavirin for 48 weeks, and were then divided into two groups: one group (effective group) with undetectable serum HCV-RNA levels at 24 weeks (n = 22) of therapy, the other group (ineffective group) with persistent presence of HCV-RNA in serum at 24 weeks (n = 10). The 2-5AS activity in serum was measured 2, 8 and 12 weeks before initial administration. RESULTS: The 2-5AS response ratio (measured value/measured value of baseline 2-5AS) at 2, 8 and 12 weeks after the administration in the effective group was significantly higher than that in the ineffective group. CONCLUSIONS: These results suggest that the ratio of 2-5AS is closely related to the antiviral effect, and that the measurement of 2-5AS response ratio may be a useful clinical parameter of virological response to PEG-IFN plus ribavirin therapy of chronic hepatitis C.     

Efficacy and safety of interferon-free regimens in patients affected by chronic hepatitis C and psychiatric disorders

The presence of psychiatric disorders (PD) in patients affected by chronic hepatitis C (CHC) was a major contraindication for the treatment with interferon (IFN)-based regimens. The novel IFN-free approach using the direct-acting antiviral agents (DAAs) is an interesting and promising chance for these subjects. In this retrospective analysis we focused the attention on the virological response and safety of CHC patients affected by PD and treated with IFN-free regimens.136 subjects were enrolled in this study. Treatment naïve were 78 (57.3), experienced 58 (42.6%). Major depression was present in 25 patients (18.4%), anxiety disorders in 37 (27.2%), bipolar disorders in 23 (16.9%), schizophrenia in 17 (12.5%), behavioral disturbance in 21 (15.4%), psychosis in 13 (9.5%). Psychoactive medication taken by patients were: benzodiazepines (n = 29, 21.3%), antidepressants (n = 24, 17.6%), neuroleptics (n = 29, 21.3%), mood stabilizers (n = 19, 14%), combinations of different drugs (n = 17, 12.5%). Sustained virological response at 12 weeks of follow-up (SVR12) was observed in 128 patients (94.1%), drop-out were 3 (2.2%). No adverse events or significant drug-related side-effects were reported.The treatment with novel IFN-free therapies against CHC were higher effective and well tolerated also in patients with PD taking psychoactive medications.