Metabolic syndrome in patients with chronic hepatitis C virus genotype 1 infection who do not have obesity or type 2 diabetes

OBJECTIVE:

The individual components of metabolic syndrome may be independent predictors of mortality in patients with liver disease. We aimed to evaluate the prevalence of metabolic syndrome and its related components in hepatitis C virus–infected patients who are not obese and do not have type 2 diabetes.

METHODS:

This cross-sectional study included 125 patients infected with hepatitis C virus genotype 1. Metabolic syndrome was defined according to the International Diabetes Federation. Anthropometric data were measured according to standardized procedures. Bioimpedance analysis was performed on all patients.

RESULTS:

Metabolic syndrome was diagnosed in 21.6% of patients. Of the subjects with metabolic syndrome, 59.3% had hypertension, 77.8% had insulin resistance, 85.2% were overweight, 48.1% had a high waist circumference, 85.2% had an increased body fat percentage, and 92.3% had an elevated waist:hip ratio. In the bivariate analysis, female sex (OR 2.58; 95% CI: 1.09–6.25), elevated gamma-glutamyl transferase (γGT) (OR 2.63; 95% CI: 1.04–7.29), elevated fasting glucose (OR 8.05; 95% CI: 3.17-21.32), low HDL cholesterol (OR 2.80; 95% CI: 1.07–7.16), hypertriglyceridemia (OR 7.91; 95% CI: 2.88–22.71), elevated waist circumference (OR 10.33; 95% CI: 3.72–30.67), overweight (OR 11.33; 95% CI: 3.97–41.07), and increased body fat percentage (OR 8.34; 95% CI: 2.94–30.08) were independent determinants of metabolic syndrome. Using the final multivariate regression model, similar results were observed for abdominal fat (OR 9.98; 95% CI: 2.63–44.41) and total body fat percentage (OR 8.73; 95% CI: 2.33–42.34). However, metabolic syndrome risk was also high for those with blood glucose ≥5.55 mmol/L or HDL cholesterol <0.9 mmol/L (OR 16.69; 95% CI: 4.64–76.35; OR 7.23; 95% CI: 1.86–32.63, respectively).

CONCLUSION:

Metabolic syndrome is highly prevalent among hepatitis C virus–infected patients without type 2 diabetes or obesity. Metabolic syndrome was significantly associated with hypertension, insulin resistance, increased abdominal fat, and overweight.     

慢性丙型肝炎患者HCV血清学分型研究

目的探讨HCV基因分型与血清学分型的关系。方法对来自14家医院的104例已知HCV基因型的慢性丙型肝炎患者血清，经ELISA方法，用Murex HCV Serotyping 1-6 Assay血清分型试剂进行HCV的血清学分型。结果104例血清中的86（82，69％）例可分出血清型，检出血清型病毒株91株，病毒株检出率为78．4％。血清型与基因型的总符合率为62，1％，血清型1型、2型和3型的符合率分别为69，4％、51，2％和70．0％，以2b基因型的符合率和漏检率最低（54．5％）。结论HCV血清型特异性受病毒基因型的影响，与基因型存在一定的差异。     

Human platelet antigen genotype is associated with progression of fibrosis in chronic hepatitis C

Although progression of fibrosis in the chronic hepatitis C depends on environmental, viral, and host factors, genetic polymorphisms have been associated recently with this progression, including the expression of integrins, adhesion proteins. Some integrins expressed on the platelet membrane show polymorphic antigenic determinants called human platelet antigens (HPA), where the major ones are HPA‐1, ‐3, ‐5. The association between HCV infection and HPA‐5b has been demonstrated. Similarly, the HPA profile could determine if HPA is related to progression of fibrosis. The goal of this study was to evaluate the association between the frequencies of HPA‐1, ‐3, and ‐5 and degree of fibrosis in HCV‐infected patients. Genomic DNA from 143 HCV‐infected patients was used as the source for HPA genotyping by PCR‐SSP or PCR‐RFLP. Progression of fibrosis was evaluated using the METAVIR scoring system, and the patients were grouped according to degree of fibrosis into G1 (n = 81, with F1, portal fibrosis without septa or F2, few septa) and G2 (n = 62, with F3, numerous septa, or F4, cirrhosis). Statistical analysis was performed using the proportional odds model. The genotypic frequency of HPA‐1a/1b was significantly higher in the patients in G2. To evaluate the influence of the time of infection to the development of fibrosis and its effect on the genetic factor HPA‐1, 96 patients from 143 studied were evaluated considering the time of HCV infection, and these results suggest that the HPA‐1a/1b genotype promotes the development of fibrosis in HCV infection with time. J. Med. Virol. 84:56–60, 2011. © 2011 Wiley Periodicals, Inc.     

Genotype 4 hepatitis C virus-a review of a diverse genotype

PurposeHepatitis C virus (HCV) infection remains a major health problem and one of the leading causes of chronic liver disease worldwide. The purpose of this paper was to summarize knowledge about the epidemiology of HCV genotype (GT) 4 infection, similarities and differences with other genotypes, specific problems associated with this genotype, and treatment regimens used to treat GT4-infected patients.MethodsWe performed an accurate search for literature using the PubMed database to select high-quality reviews and original articles concerning this topic.ResultsGT4 with a global prevalence of 8% takes third place, closing the global HCV podium in terms of frequency. However, there are regions where GT4 infections are dominant, such as sub-Saharan and North Africa, and the Middle East. The disease course and complications are generally similar to those of chronic hepatitis C caused by other genotypes, although the faster progression of fibrosis was demonstrated in patients with coexisting schistosomiasis. In the era of interferon-based therapy, GT4-infected patients were described as difficult to treat due to suboptimal response. A breakthrough in the treatment of HCV-infected patients, including those with GT4 infection, was the introduction of direct-acting antiviral drugs.ConclusionsThe availability of safe and effective therapy has created a real opportunity for HCV eradication in line with the goal set by the World Health Organization. An example of a country where this is happening is Egypt, where GT4 accounts for more than 90% of HCV infections. There, broad access to therapy has been effectively supported by population-based screening.     

Elevation of plasma soluble human leukocyte antigen-G in patients with chronic hepatitis C virus infection

The subversion of immune responses that hepatitis C virus (HCV) uses to escape immune surveillance and to establish persistent infection has been poorly understood. The immune-suppressive molecule human leukocyte antigen-G (HLA-G) has been supposed to play important roles in viral infection. In the current study, HCV genotype was analyzed in 67 chronic HCV-infected (CHC) patients. Plasma soluble sHLA-G (including sHLA-G1 and HLA-G5), interleukin-10 (IL-10), and interferon-γ (IFN-γ) levels were determined in these CHC patients and in healthy subjects by enzyme-linked immunosorbent assay, and the sHLA-G isoforms present in plasma were determined by Western blot. Data showed that HCV 1b was the predominant genotype, with a prevalence of 64.2%. sHLA-G was dramatically increased in CHC patients (median: 85.54 U/ml, range: 19.40-204.07) over that in normal controls (median: 9.13 U/ml, range: 5.07-69.56) (p < 0.001). Western blotting revealed that plasma sHLA-G was derived from sHLA-G1 and HLA-G5. IL-10 and IFN-γ levels were also significant higher in CHC patients than in normal controls (median: 16.3 pg/ml vs 1.8 pg/ml, p < 0.001, and 1025.3 pg/ml vs 858.3 pg/ml, p = 0.03, respectively). No significant association was observed for the HCV genotype and viral RNA load with the levels of sHLA-G, IL-10, and IFN-γ in CHC patients. These results indicate that elevation of sHLA-G expression in HCV patients was independent of viral genotype and viral RNA load. Given its immunotolerant property, an increase in sHLA-G may play a role in the persistency of HCV infection.     

Ledipasvir and sofosbuvir: Interferon free therapy for hepatitis C virus genotype 1 infection

Hepatitis C virus (HCV) has infected more than 200 million people around the globe. From 2001-2011, interferon plus ribavirin remained the standard of care for patients with HCV infection. The therapy had a limited response with a number of side effects. Recently, results for phase III trials of ledipasvir and sofosbuvir combination therapy have been announced. In treatment naïve patients, 12 wk of therapy with ledipasvir and sofosbuvir showed a sustained virological response (SVR) rate of 99%. In treatment experienced patients, 12-24 wk of therapy with ledipasvir and sofosbuvir in the absence or presence of ribavirin showed an SVR rate of 94%-99%. In cirrhotic patients the rate of SVR was 86% and 99% for 12 and 24 wk of therapy, respectively. The ledipasvir and sofosbuvir therapy showed very good results in different subgroups of patients regardless of patient’s race, alanine aminotransferase levels, sex and host genetic factors. The combination therapy was well tolerated with no emergence of resistant mutants. The most common adverse effects were nausea, headache and fatigue. With the availability of interferon free therapy with minimal adverse effects, it will be easy to decrease the future morbidity and mortality caused by HCV infection.     

慢性丙型肝炎患者HCV基因型调查

目的 研究丙型肝炎病毒（ＨＣＶ）基因型的流行病学特点。方法 采用ＩＮＮＯ－ＬＩＰＡ反向线形探针杂交法，对来自我国南方（上海，武汉，徐州）、北方（北京、天津）和东北（大连、沈阳）７市的１０７例慢性丙型肝炎患者进行了ＨＣＶ基因型调查。结果（１）地域性，ＨＣＶ１ｂ是主要的基因型，其检出率达８３．１７％，其中东北２市（７２．２２％）低于北方２市（８７．６５％，Ｐ〈０．０１）；２型的检出率较低，仅占６．８６     

双环醇片对乙型肝炎病毒B、C基因型感染的疗效比较

目的比较双环醇片对乙型肝炎病毒B、C基因型感染的疗效。方法选择乙型肝炎病毒B基因型感染者26例、C基因型感染者44例，同时给予双环醇片口服，50mg／次，每日3次，疗程24周。观察受试者的临床症状、体征变化，并于治疗前、治疗期间（第12周）及治疗结束时（第24周），分别检测血常规、肝功能、乙肝三系和血清HBVDNA水平。结果双环醇片能明显改善B、C基因型乙型肝炎病毒感染者的临床症状和肝功能，并有一定的抑制病毒作用，两组患者治疗24周时的血清HBVDNA阴转率分别为19．2％和15．9％，差异无统计学意义。结论双环醇片不仅能保护慢性乙型肝炎患者的肝功能，同时能抑制乙型肝炎病毒复制，对B、C基因型乙型肝炎病毒感染者的疗效相近。     

New treatments for chronic hepatitis C

Treatments for chronic hepatitis C has evolved significantly in the past 15 years. The standard of care (SOC) is peginterferon alfa-2a/-2b with ribavirin for 48 weeks or 24 weeks in patients infected with HCV genotype 1 or 2/3, respectively. The treatment duration can be individualized based on the baseline viral load and the speed of the virologic response during treatment. However, current therapies are associated with side effects, complications, and poor patient tolerability. Therefore, there is an urgent need to identify better strategies for treating this disease. An improved sustained virologic response (SVR) can be achieved with new HCV-specific inhibitors against NS3/4A and NS5B polymerases. Recent trials have found SVR rates in patients with HCV genotype 1 infection of 61~68% and 67~75% for combining the SOC with the protease inhibitors telaprevir and boceprevir, respectively. Several new HCV-specific inhibitors such as protease inhibitors and nucleoside and non-nucleoside polymerase inhibitors as well as non-HCV-specific compounds with anti-HCV activity are currently in clinical evaluation. In this review we discuss these new treatments for chronic hepatitis C.     

慢性丙型肝炎患者氧化损伤的研究

目的 探讨慢性丙型肝炎(CHC)患者体内氧化损伤的情况.方法 52例CHC患者,按丙氨酸转氨酶(ALT)水平分为A组(ALT上升组)和B组(ALT正常组).正常对照组为20例健康志愿者.利用酶联免疫吸附法(ELISA)测定研究对象血清黄嘌呤氧化酶(XOD),丙二醛(MDA),氧化型谷胱甘肽(GSSG),谷胱甘肽(GSH),谷胱甘肽过氧化物酶(GSH-Px),谷胱甘肽巯基转移酶(GST),谷胱甘肽还原酶(GR)及维生素C(Vc)水平,并作出统计分析.结果 CHC患者血清XOD,MDA,GST和GR水平较正常对照组显著升高,而GSH,GSH-Px和Vc水平则明显降低.同时,A组患者血清XOD,MDA,GSSG,GST及GR水平较B组患者显著上调,而GSH,GSH-Px和Vc水平则显著下调.在CHC患者中,血清XOD,MDA,GSSG,GST水平与ALT水平呈正相关,血清GSH,GSH-Px,Vc与ALT水平呈负相关;血清XOD,MDA,GSSG,GR,GST水平与AST水平呈正相关,血清GSH-Px水平与AST水平呈负相关;血清GR水平与GGT水平呈正相关,血清GSH水平与GGT水平呈负相关;血清MDA,GR水平与AKP水平呈正相关.在CHC组中,仅血清XOD水平与血清HCV RNA水平间存在正相关关系.结论 CHC患者体内存在一定程度的氧化损伤,随血清ALT水平的升高,机体氧化损伤程度进一步加重.     

Management of patients with chronic hepatitis C infection

Abstract Chronic infection with hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality throughout the world. Although reliable figures regarding the global prevalence of HCV infection are wanting, it is likely that HCV prevalence will continue to increase. Injection drug use is the most important source of HCV transmission in the developed world, while unsafe therapeutic injection is an important source of transmission in developing nations. The majority of exposed individuals become chronically infected, of whom 50% develop chronic liver injury. Cirrhosis and hepatocellular carcinoma can arise in those chronically infected over a mean of 20–30 years. Despite this high prevalence and morbidity, recommendations regarding who to screen by antibody testing remain disparate. Quantitative measurement of HCV RNA and HCV genotyping is useful in predicting response to antiviral therapy. Noninvasive methods of detecting liver injury, such as serologic batteries, have not been as informative or predictable as liver biopsy. The current pharmacologic standard of care for chronic HCV infection is the combination of subcutaneous peginterferon and oral ribavirin, which yields sustained virologic response in 54%–56%. Higher rates of SVR are seen in those patients who are infected with HCV genotypes 2 and 3. As intravenous drug use remains the most important source of HCV transmission in the US and Europe, education within this group is an important preventive tool.     

Th1／Th2在慢性乙型、丙型肝炎中的作用

病毒性肝炎的发病及转归与细胞免疫机制有很密切的关系。辅助性T细胞（Th）是体内一类重要的调节细胞,根据其产生细胞因子的不同分为Th1和Th2亚型,分别参与调节细胞免疫和体液免疫。Th1和Th2细胞在病毒性肝炎中发挥重要作用,Th1／Th2失衡引起病毒性肝炎慢性化。采用单种细胞因子纠正Th1／Th2失衡方法在慢性乙型、丙型肝炎临床治疗中的研究进展,为治疗慢性病毒性肝炎提供了新思路。     

1年以上血透患者HCV感染状况的调查

目的 研究1年以上的长期血液透析患者丙型肝炎（HCV）感染状况。方法 用ELISA法和RT－PCR法检测137例长期血透患者血清中的抗－HCV和HCVRNA,并且同时检测谷丙转氨酶（ALT）和谷草转氨酶（AST）,计算其变动率。结果 透析时间超过1年以上的137例患者中仅抗－HCV阳性8例,仅HCV－RNA阳性13例,抗－HCV与HCVRNA同时阳性者24例,感染率34．3％。且透析时间小于2年的,HCV感染率为15％,透析时间大于2年以上的其感染率增至37．6％。结论 血透患者中HCV的感染应引起重视,透析的年限越长,被HCV感染的机率就越大。酶学指证的变动率不能作为长期透析患者HCV感染的敏感指标。     

中国南北两城市乙型肝炎病毒基因型与血清型的构成差异

目的对我国南北两城市530份乙型肝炎(乙肝)病毒(HBV)进行血清型和基因型分型,以了解HBV基因型和血清型分布的特点和差异。方法 对黑龙江省哈尔滨市和广东省廉江市530份乙肝病毒表面抗原(HBsAg)阳性血清进行HBV DNA基因扩增,并对扩增产物直接测序,分析HBV血清亚型和基因型。结果 哈尔滨和廉江市HBV血清型以adrq为最多,分别为87.2％和73.5％,其次为adw2,分别为12.0％和25.7％,其分布差异有非常显著意义(P<0.001);两市HBV基因型均以C型为主,分别为87.8％,73.2％,其次为B型,分别为12.2％和26.1％,其分布差异有非常显著意义(P<0.001),在廉江市仅有1例D型,1例B、C混合型。结论我国南北两城市HBV血清亚型和基因型的构成较为单纯,均只有两个类型,其比例构成差异有非常显著意义。     

A Duffy antigen receptor for chemokines (DARC) polymorphism that determines pro-fibrotic chemokine serum concentrations is not directly associated with severity of hepatitis C infection

Genetic host factors influence the progression of hepatitis C infection (HCV). Chemokines play important roles in HCV-induced liver fibrosis. Recently, a single nucleotide polymorphism in the Duffy antigen receptor for chemokines (DARC) was identified which strongly determines the serum concentrations of pivotal pro-fibrotic chemokines, including CCL2. We here tested the hypothesis that this genetic variant (rs12075 A/G) is a risk factor for liver fibrosis in HCV infection. Overall, 880 patients with HCV from three cohorts and 108 controls were genotyped for rs12075. Although serum CCL2 levels were associated with early liver fibrosis, rs12075 itself was not associated with HCV infection or the severity of liver disease in any of the cohorts. The lack of association was evident in qualitative and quantitative analysis despite sufficient statistical power. We conclude that gene variations that strongly determine serum concentrations of chemokines are not necessarily risk markers of the disease traits in which these molecules play pathophysiological roles.