慢性丙型肝炎患者肝纤维化程度与TLR2、TLR4 mRNA的关系

目的研究慢性丙型肝炎患者肝纤维化程度与Toll样受体2(TLR2)、Toll样受体4(TLR4)转录体(mRNA)的关系。方法对2019年1月到2019年12月因慢性丙型肝炎病毒(HCV)感染来舞钢市人民医院接受治疗的185例患者进行选择纳入试验,收录进慢性丙型肝炎(CHC)组,另选取同期在本院进行体检的185例健康人进行对照研究,收录进对照组,比较两组TLR2 mRNA、TLR4 mRNA水平;按照肝纤维化程度将CHC患者分成F1组(n=35)、F2组(n=63)、F3组(n=58)、F4组(n=29),比较四组TLR2 mRNA、TLR4 mRNA水平;利用Spearman系数分析肝纤维化程度分级F1、F2、F3、F4与TLR2 mRNA、TLR4 mRNA水平的相关性。结果CHC组TLR2 mRNA、TLR4 mRNA水平显著高于对照组,有显著差异(P<0.05)。比较CHC患者不同纤维化程度TLR2 mRNA、TLR4 mRNA水平F1组<F2组<F3组<F4组,有显著差异(P<0.05)。经相关性分析,CHC患者肝纤维化程度分级F1、F2、F3、F4与TLR2 mRNA、TLR4 mRNA表达呈正相关(P<0.05)。结论TLR2 mRNA、TLR4 mRNA水平会随CHC患者肝纤维化程度进展而不断升高。

老年慢性丙型肝炎患者的临床研究

目的:探讨老年慢性丙型肝炎的临床治疗特点。方法:对我院2004年1月～2010年12月住院的41例年龄大于60岁的慢性丙型肝炎患者的治疗情况进行回顾性分析。结果:老年慢性丙型肝炎患者的抗病毒治疗不良反应较多,SVR低于其他年龄阶段的人群。结论:老年慢性丙型肝炎患者的抗病毒治疗是一个较为复杂的问题,其治疗方案要注意个体化。

干扰素、辛伐他汀和利巴韦林联用对丙肝合并高脂血症患者血脂表达及炎性因子的影响

目的探讨聚乙二醇干扰素α-2a(polyethylene glycol interferon alpha 2a,PEG-IFNα-2a)、辛伐他汀和利巴韦林联合用药对慢性丙型肝炎(chronic hepatitis C,CHC)合并高脂血症患者的血脂表达及炎性因子的影响。方法选择本院2016年1月至2016年12月诊治的240例慢性丙型肝炎合并高脂血症患者作为研究对象,随机分为单药治疗治疗组(PEG-IFNα-2a组、辛伐他汀组和利巴韦林组各60例)和联合用药治疗组(60例)四组,分析比较治疗48周后患者的血脂水平及炎性因子表达。结果治疗前,四组患者的血脂水平和炎性因子表达差异无统计学意义(P>0.05)。治疗后,四组患者的总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDLC)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、基质金属蛋白酶-9(matix metalloproteinase-9,MMP-9)、C反应蛋白(C reactive protein,CRP)和丙二醛(methane dicarboxylic aldehyde,MDA)表达水平与治疗前相比均有显著下降,而高密度脂蛋白胆固醇(high-density lipoproteincholesterol,HDL-C)则显著上升,差异具有统计学意义(P<0.05)。且联合用药组的各项指标水平显著优于单药治疗组(P<0.05)。结论 PEG-IFNα-2a、辛伐他汀和利巴韦林均能有效降低CHC合并高脂血症患者的血脂水平和炎性因子表达,且三者联合治疗的疗效更佳,值得在临床进一步推广。

药物联用对丙肝合并高脂血症患者NO及抗氧化酶活性的影响

目的:探讨聚乙二醇干扰素α-2a(PEG-IFNα七a)、辛伐他汀和利巴韦林联合用药对慢性丙型肝炎(CHC)合并高脂血症患者的血脂表达及炎性因子的影响。方法:240例CHC合并高脂血症患者随机分为4组,各60例,A组(PEG-IFNα-2a组)、B组(辛伐他汀组)、C组(利巴韦林组)和D组(联合用药组),比较治疗48周后患者的血脂水平及炎性因子表达。结果:治疗前,4组患者的一氧化氮(NO)水平和抗氧化酶活性差异无统计学意义(P>0.05)。治疗后,四组患者的NO、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平与治疗前相比均有显著上升(P<0.05)。而肿瘤坏死因子-α(tTNF-α)、基质金属蛋白酶-9(MMP-9)、C反应蛋白(CRP)和丙二醛(MDA)表达水平与治疗前相比均有显著下降,P<0.05。D组的各项指标水平显著优于ABC三组(P<0.05)。结论:PEG-IFNα-2a、辛伐他汀和利巴韦林均能有效提高CHC合并高脂血症患者的NO水平和抗氧化酶活性,三者联合治疗的疗效更佳。

Epidemiology of Hepatitis B and Associated Liver Diseases in China

Hepatitis B virus (HBV) infection has long been a critical public health challenge in China. National surveys revealed a prevalence of approximate 10% for chronic HBV infection in general population. HBV has been the leading cause of chronic hepatitis, cirrhosis, and liver cancers in Chinese population and a common pathogen of acute viral hepatitis. Meanwhile, the epidemic provided important opportunities to research the natural history, public health impact, and therapeutic and preventive interventions for HBV in China. In this review, we summarized the selected key epidemiological studies since 1970s regarding HBV infection and its associated liver diseases in China, and provided considerations for future research, prevention and treatment of HBV.

Pathophysiology of insulin resistance and steatosis in patients with chronic viral hepatitis

Chronic hepatitis due to any cause leads to cirrhosis and end-stage liver disease.A growing body of literature has also shown that fatty liver due to overweight or obesity is a leading cause of cirrhosis.Due to the obesity epidemic,fatty liver is now a significant problem in clinical practice.Steatosis has an impact on the acceleration of liver damage in patients with chronic hepatitis due to other causes.An association between hepatitis C virus (HCV) infection,steatosis and the onset of insulin resistance has been reported.Insulin resistance is one of the leading factors for severe fibrosis in chronic HCV infections.Moreover,hyperinsulinemia has a deleterious effect on the management of chronic HCV.Response to therapy is increased by decreasing insulin resistance by weight loss or the use of thiazolidenediones or metformin.The underlying mechanisms of this complex interaction are not fully understood.A direct cytopathic effect of HCV has been suggested.The genomic structure of HCV (suggesting that some viral sequences are involved in the intracellular accumulation of triglycerides),lipid metabolism,the molecular links between the HCV core protein and lipid droplets (the core protein of HCV and its transcriptional regulatory function which induce a triglyceride accumulation in hepatocytes) and increased neolipogenesis and inhibited fatty acid degradation in mitochondria have been investigated.

Serum concentration of sFas and sFasL in healthy HBsAg carriers,chronic viral hepatitis B and C patients

AIM:To estimate the amount of apoptosis among healthy HBsAg carriers,patients with chronic HBV infection treated wibh lamivudine and patients with chronic HCV infection treated with interferon alpha and ribavirin.Activity of apoptosis was evaluated by serum sFas/sFasL concentration measurement. Moreover dependence between apoptosis and HBV-DNA or HCV-RNA levels was studied. METHODS:Eighty-six persons were included into study:34 healthy HBsAg carders,33 patients with chronic HBV infecl^on and 19 patients with chronic HCV infection.Serum levels of sFas/sFasL were measured by ELISA assay.HBV-DNA and HCV-RNA were measured by RT-PCR assay.Levels of sFas/sFasL were determined before and 2 and 12 wk after therapy in patients with chronic hepatitis B and C infection. HBV-DNA or HCV-RNA was detected before treatment and 6 mo after treatment. RESULTS:Twenty-four (71%) healthy HBsAg carders showed HBV-DNA over 10~5/mL,which was comparable to the patients with chronic hepatitis B.independently from HBV-DNA levels, the concentration of sFas among healthy HBsAg carders was comparable to healthy persons.Among patients with chronic hepatitis B and C,the concentration of sFas was significantly higher in comparison to healthy HBsAg carriers and healthy persons.In chronic hepatitis B patients the concentration of sFas was decreased during lamivudine treatment.Among chronic hepatitis C patients the concentration of sFas was increased during IFN alpha and ribavirin treatment,sFasL was not detected in control group.Furbhermore sFasL occurred more frequently in chronic hepatitis C patients in comparison to chronic hepatitis B patients. CONCLUSION:There are no correlations between apoptosis and HBV-DNA levels.However ther is an association between apoptosis and activity of inflammation in patients with chronic HBV infection.Apoptosis can be increased in patients with chronic hepatitis C by effective treatment which may be a result of apoptosis stimulation by IFN-α.

Resting energy expenditure and glucose, protein and fat oxidation in severe chronic virus hepatitis B patients

AIM: To study and determine the resting energy ex- penditure (REE) and oxidation rates of glucose, fat and protein in severe chronic hepatitis B patients. METHODS: A total of 100 patients with liver diseases were categorized into three groups: 16 in the acute hepatitis group, 56 in the severe chronic hepatitis group, and 28 in the cirrhosis group. The REE and the oxidation rates of glucose, fat and protein were as- sessed by indirect heat measurement using the CCM-D nutritive metabolic investigation system. RESULTS: The REE of the severe chronic hepatitis group (20.7 ± 6.1 kcal/d per kg) was significantly lower than that of the acute hepatitis group (P = 0.014). The respiratory quotient (RQ) of the severe chronic hepatitis group (0.84 ± 0.06) was significantly lower than that of the acute hepatitis and cirrhosis groups (P = 0.001). The glucose oxidation rate of the severe hepatitis group (39.2%) was significantly lower than that of the acute hepatitis group and the cirrhosis group (P < 0.05), while the fat oxidation rate (39.8%) in the severe hepatitis group was markedly higher than that of the other two groups (P < 0.05). With improve- ment of liver function, the glucose oxidation rate in- creased from 41.7% to 60.1%, while the fat oxidation rate decreased from 26.3% to 7.6%. CONCLUSION: The glucose oxidation rate is signifi-cantly decreased, and a high proportion of energy is provided by fat in severe chronic hepatitis. These re- sults warrant a large clinical trail to assess the optimal nutritive support therapy for patients with severe liver disease.

HIV and HCV:from Co-infection to Epidemiology,Transmission,Pathogenesis,and Treatment

Human immunodeficiency virus (HIV) is the infectious agent causing acquired immu-nodeficiency syndrome (AIDS),a deadliest scourge of human society. Hepatitis C virus (HCV) is a major causative agent of chronic liver disease and infects an estimated 170 million people worldwide,resulting in a serious public health burden. Due to shared routes of transmission,co-infection with HIV and HCV has become common among individuals who had high risks of blood exposures. Among hemophiliacs the co-infection rate accounts for 85%; while among injection drug users (IDU) the rate can be as high as 90%. HIV can accelerate the progression of HCV-related liver disease,particularly when immunodeficiency has developed. Although the effect of HCV on HIV infection is controversial,most studies showed an increase in mortality due to liver disease. HCV may act as a direct cofactor to fasten the progression of AIDS and decrease the tolerance of highly active antiretroviral therapy (HARRT). Conversely,HAART-related hepatotoxicity may enhance the progression of liver fibrosis. Due to above complications,co-infection with HCV and HIV-1 has imposed a critical challenge in the management of these patients. In this review,we focus on the epidemiology and transmission of HIV and HCV,the impact of the two viruses on each other,and their treatment.

Treatment of chronic viral hepatitis with nitazoxanide and second generation thiazolides

Nitazoxanide,the first thiazolide,was originally developed for the treatment of Cryptosporidium parvum.More recently,antiviral activity of nitazoxanide against hepatitis B virus(HBV)and hepatitis C virus was recognized in in vitro systems.These basic studies led to phaseⅡclinical trials that demonstrated the safety and efficacy of nitazoxanide in combination with peginterferon,with or without ribavirin,in the treatment of chronic hepatitis C genotype 4.The sustained virologic response rate was 79%and 80%in two studies,which was higher than the response rate of 50%with the standard of care with peginterferon plus ribavirin.In very preliminary studies of patients with chronic hepatitis B,nitazoxanide suppressed serum HBV DNA and led to loss of hepatitis B e antigen in the majority of patients and hepatitis B surface antigen in approximately a quarter of patients.Randomized controlled studies of naive and nonresponder patients with chronic hepatitis C genotype 1 are underway,new second generation and controlled release thiazolides are being developed,and future studies of patients with chronic hepatitis B are planned.

Spectrum of anemia associated with chronic liver disease

Anemia of diverse etiology is a common complication of chronic liver diseases. The causes of anemia include acute or chronic gastrointestinal hemorrhage, and hypersplenism secondary to portal hypertension. Severe hepatocellular disease predisposes to hemorrhage because of impaired blood coagulation caused by deficiency of blood coagulation factors synthesized by hepatocytes, and/or thrombocytopenia. Aplastic anemia, which is characterized by pancytopenia and hypocellular bone marrow, may follow the development of hepatitis. Its presentation includes progressive anemia and hemorrhagic manifestations. Hematological complications of combination therapy for chronic viral hepatitis include clinically signif icant anemia, secondary to treatment with ribavirin and/or interferon. Ribavirininduced hemolysis can be reversed by reducing the dose of the drug or discontinuing it altogether. Interferons may contribute to anemia by inducing bone marrow suppression. Alcohol ingestion is implicated in the pathogenesis of chronic liver disease and may contribute to associated anemia. In patients with chronic liver disease, anemia may be exacerbated by defi ciency of folic acid and/or vitamin B12 that can occur secondary to inadequate dietary intake or malabsorption.

Hyperferritinemia is a risk factor for steatosis in chronic liver disease

AIM: To investigate the relationship between ferritin and steatosis in patients with chronically abnormal liver function tests (LFTs) and high ferritin level. METHODS: One hundred and twenty-four consecutive patients with hyperferritinemia (male > 300 ng/mL, female > 200 ng/mL) were evaluated; clinical, biochemical and serological data, iron status parameters, HFE gene mutations and homeostasis model assessment score were obtained. Steatosis was graded by ultrasound as absent or present. Histology was available in 53 patients only. RESULTS: Mean level of ferritin was 881 ± 77 ng/mL in men and 549 ± 82 ng/mL in women. The diagnosis was chronic hepatitis C in 53 (42.7%), non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in 57 (45.9%), and cryptogenic liver damage in 14 (11.3%). None was diagnosed as hereditary hemochromatosis (HH). Hepatic siderosis on liver biopsy was present in 17 of 54 (32%) patients; grade 1 in eight and grade 2 in nine. Overall, 92 patients (74.2%) had steatosis. By logistic regression, ferritin and γ-glutamyltransferase were independent predictors of steatosis. Ferritin levels were signifi cantly related to low platelet count, steatosis and hepatitis C virus infection. CONCLUSION: In a non-obese cohort of non-alcoholic patients with chronically abnormal LFTs without HH, high serum ferritin level is a risk factor for steatosis.

Effect of cytokine gene polymorphism on histological activity index, viral load and response to treatment in patients with chronic hepatitis C genotype 3

AIM： To investigate the association between cytokine gene polymorphism and disease status in chronic hepatitis C genotype 3 by liver biopsy, ALl, HCV RNA levels and response to treatment. METHODS： Patients with chronic hepatitis C genotype 3 were analyzed for single nucleotide polymorphisms of interleukin （IL）-10, IL-1 beta, interferon-gamma （IFN-y）, tumor necrosis factor-alpha （TNF-y） and transforming growth factor-beta （TGF-β） by polymerase chain reaction using sequence-specific oligonucleotide primers. Liver biopsies were assessed by modified histological activity index （HAI） scoring system using a scale of 0-18 for grading the necro-inflammatory activity and 0-6 for staging the fibrosis. HCV RNA levels were determined by bDNA assay. The patients were treated with interferon alpha and ribavirin for 6 mo. Sustained virological response was assessed 6 mo after the completion of the treatment. RESULTS： Out of the 40 patients analyzed, 26 were males. Mean age was 40.5±12.5 years （range 18- 65 years）. The frequencies of different dimorphic polymorphisms based on single nucleotide substitution were as follows： IL-10-1082 G/A 85%, A/A 12.5%, G/ G 2.5%; IL-10-819 A/C 87.5%, C/C 10%, A/A 2.5%; IL-10-592 C/A 72.5%, C/C 27.5%; IL-1 C 90%, U 10%; IFN-874 T/A 50%, T/T 27.5%, A/A 22.5%; TNF-308 A/G 95%, G/G 5%; TGF-10 T/C 52.5%, C/C 35%, T/T 12.5%. The mean grades of necroinflammatory activity of different genotypes of IL-10 at promoter site -1082 were A/A = 3.6, A/G = 5.0, and G/G = 10.0 and the difference was significant （P = 0.029）. The difference in the stage of disease at a scale of 0-6 was A/A 0.8, A/G 2.3, and G/G 4.0 （P = 0.079）. The difference in the HAI seemed to be related to the presence of allele -1082G.For IL-10 -819 genotypes, mean scores of fibrosis were A/A = 6.0, A/C = 2.2, and C/C = 1.0 （P = 0.020） though the inflammatory activity was not much different. No significant differences in HAI were noted among polymorphisms of other cytokines. Moreover, ALT and HCV RNA levels were not significantly different among different cytokine polymorphisms. There was a significant correlation of HAI and HCV RNA levels with the duration of disease. TGFI3 -10 genotype CC patients had a better end of treatment response than those with other genotypes （P = 0：020）. Sustained virological response to the treatment was not influenced by the cytokine polymorphism. No effect of other factors like viral load, degree of fibrosis, gender, steatosis, was observed on sustained virological response in this population infected with genotype 3. CONCLUSION： There is no significant correlation between cytokine polymorphisms and HAI except for the polymorphisms of anti-inflammatory cytokine IL-10, which may influence hepatic inflammatory activity and fibrosis in patients with chronic hepatitis C genotype 3. Sustained virological response in this genotype does not seem to be influenced by cytokine gene polymorphisms.

HBeAg negative serological status and low viral replication levels characterize chronic hepatitis B virus-infected women at reproductive age in Greece: A one-year prospective single center study

AIM： To evaluate the seroprevalence of hepatitis B surface antigen （HBsAg） in 13 581 women at reproductive age and the hepatitis B e antigen （HBeAg）/anti-HBe status as well as serum hepatitis B virus （HBV）-DNA levels in a subgroup of HBsAg（＋） pregnant women at labor in Greece. METHODS： Serological markers were detected using enzyme immunoassays. Serum HBV-DNA was determined by a sensitive quantitative PCR assay. Statistical analysis of data was based on parametric methodology. RESULTS： Overall, 1.156% of women were HBsAg（＋） and the majority of them （71.3%） were Albanian. The prevalence of HBsAg was 5.1% in Albanian women, 4.2% in Asian women and 1.14% in women from Eastern European countries. The prevalence of HBsAg in African （0.36%） and Greek women （0.29%） was very low. Only 4.45% of HBsAg （＋） women were also HBeAg（＋） whereas the vast majority of them were HBeAg（-）/anti-HBe（＋）. Undetectable levels of viremia （〈200 copies/mL） were observed in 32.26% of pregnant women at labor and 29.03% exhibited extremely low levels of viral replication （〈400 copies/mL）. Only two pregnant women exhibited extremely high serum HBV- DNA levels （〉10 000 000 copies/mL）, whereas 32.26% exhibited HBV-DNA levels between 1 500 and 40 000 copies/mL. CONCLUSION： The overall prevalence of HBsAg is relatively low among women at reproductive age in Greece but is higher enough among specific populations. The HBeAg（-）/anti-HBe（＋） serological status and the extremely low or even undetectable viral replicative status in the majority/of HBsAg（＋） women of our study population, suggestthat only a small proportion of HBsAg（＋） women in Greece exhibit a high risk for vertical transmission of the infection.

Viral and host causes of fatty liver in chronic hepatitis B

AIM: To investigate the viral and host causes of fatty liver in chronic hepatitis B patients and the role of fat deposits in liver damage.METHODS: A total of 164 patients (113 males and 51 females, average age 35±11.3 years, and range 10-62 years) with previously untreated chronic hepatitis B were included in the study. The patients were divided into two groups depending on the result of liver biopsy: group without steatosis (100 patients with ＜5% hepatosteatosis) and group with steatosis (64 patients with ＞5% hepatosteatosis). The groups were compared in terms of gender, body mass index (BMI), liver enzymes (ALT, AST, ALP, GGT), cholesterol, triglyceride, HBeAg, viral load, and histological findings. In the group with steatosis, the patients were subdivided depending on the degree of steatosis into mild group (45 patients with 5-24% steatosis), and severe group (19 patients with ＞25% steatosis). RESULTS: In the group of chronic hepatitis B with steatosis, the mean age, BMI, cholesterol, and triglyceride levels were significantly higher than those in the group without steatosis (P＜0.05). Steatosis was found in 53 (46.9%) of male patients and 11 (22%) of female patients (P＜0.05). No significant difference was found in the positivity of ALT, AST, ALP, GGT, HBeAg, viral load, histological activity index (HAI) and stage between the two groups (P＞0.05). In the group with severe steatosis, the BMI was significantly higher than that in the group with mild steatosis (P＜0.05). No significant difference was found in the other parameters between the groups (P＞0.05). CONCLUSION: Steatosis in chronic hepatitis B appears to be a result of metabolic factors of the host rather than the effect of viruses. Steatosis is unrelated to the HAI and degree of fibrosis, which are considered as the histological indicators of liver damage.

Improvement of quantitative testing of liver function in patients with chronic hepatitis C after installment of antiviral therapy

MM： To investigate if and to what extent antiviral therapy influenced a broad panel of quantitative testing of liver function （QTLF）. METHODS： Fifty patients with chronic hepatitis C were either treated with interferon （n = 8）, interferon/ribavirin （n = 19） or peg-interferon/ribavirin （n = 23）. Quantitative testing of liver function, including aminopyrine breath test （ABT）, galactose elimination capacity （GEC）, sorbitol clearance （SCI） and indocyanine green clearance （ICG） was performed before and 3 mo after initiation of antiviral therapy. RESULTS： After 3 mo of antiviral treatment, 36 patients showed normal transaminases and were negative for HCVRNA, 14 patients did not respond to therapy. ABT and GEC as parameters of microsomal and cytosolic liver function were reduced in all patients before therapy initiation and returned to normal values in the 36 therapy responders after 3 too. Parameters of liver perfusion （SCl and ICG） were not affected by antiviral therapy. In the 14 non-responders, no changes in QTLF values were observed during the treatment period. CONCLUSION： ICG and SCI remained unaffected in patients with chronic hepatitis C, while ABT and GEC were significantly compromised. ABT and GEC normalized in responders to antiviral therapy. Early determination of ABT and GEC may differentiate responders from non-responders to antiviral treatment in hepatitis C.

Spontaneous resolution of systemic sarcoidosis in a patient with chronic hepatitis C without interferon therapy

A 39-year-old male patient complaining of bilateral hand joint arthralgia was evaluated and found to have chronic hepatitis C and systemic sarcoidosis involving lung, skin, liver, and spleen. Hepatic and cutaneous sarcoidoses were confirmed by the presence of numerous noncaseating granulomas on histological examination. Pulmonary and splenic involvements were diagnosed by imaging studies. Fifteen months later, the sarcoidotic lesions in lung, liver, and spleen were resolved by radiological studies and a liver biopsy showed no granuloma but moderate to severe inflammatory activity, systemic sarcoidosis is a rare comorbidity of chronic hepatitis C which may spontaneously resolve.

Development of Novel Therapeutics for Chronic Hepatitis B

Chronic infection of hepatitis B virus (HBV) presents one of the serious public health challenges worldwide. Current treatment of chronic hepatitis B (CHB) is limited, and is composed of interferon and nucleoside/nucleotide reverse transcriptase inhibitors (NRTI). Interferon is poorly tolerated and is only responsive in a small fraction of CHB patients and NRTIs often face the problem of emergence of drug resistance during long-term treatment. The current treatment of CHB can be improved in several ways including genotyping mutations associated with drug resistance before treatment to guide the choice of NRTIs and suitable combinations among NRTIs and interferon. It is important to continue research in the identification of novel therapeutic targets in the life cycle of HBV or in the host immune system to stimulate the development of new antiviral agents and immunotherapies. Several antiviral agents targeting HBV entry, cccDNA, capsid formation, viral morphogenesis and virion secretion, as well as two therapeutic vaccines are currently being evaluated in preclinical studies or in clinical trials to assess their anti-HBV efficacy.

YMDD mutations in patients with chronic hepatitis B untreated with antiviral medicines

AIM: To polymerase P region (YMDD) mutations of hepatitis B virus gene (HBV DNA) in patients with chronic hepatitis B (CHB) untreated with antiviral medicines and to explore its correlation with pre-c-zone mutations, HBV genotypes and HBV DNA level, and to observe its curative effect.METHODS: A total of 104 cases (38 cases in group of familial aggregation and 66 cases in group of non-familial aggregation) were randomly chosen from 226 patients with CHB who did not receive the treatment of lamivudine (LAM)and any other antivirus drugs within the last one year.Their serum YMDD mutations were detected by microcosmic nucleic acid and cross-nucleic acid quantitative determination,HBV genotypes by PCR-microcosmic nucleic acid crossELISA, HBV DNA quantitative determination and fluorescence ration PCR analysis, hepatitis B virus markers (HBVM) by ELISA. LAM was taken by 10 patients with YMDD mutations and its curative effect was observed.RESULTS: Twenty-eight cases (26.9%) had YMDD mutations, of them 11 cases (28.9%) were in familial aggregation group (38 cases) and 17 cases (25.8%) in nonfamilial aggregation group (66 cases) with no significant difference between the two groups. Twenty-seven point one percent (16/59) cases were positive for HBeAg YMDD mutations, and 26.7% (12/45) cases were negative for HBeAg and positive for anti-HBe. There was also no significant difference between the two groups. Different YMDD incidence rate existed in different HBV genotypes.HBV DNA level did not have a positive correlation with the incidence of YMDD mutations. LAM was effective for all patients with mutations.CONCLUSION: Wild mutant strains in HBV and their incidence rate have no significant difference between familial aggregation and non-familial aggregation. It may have no significant relationship between YMDD mutations and pre-c-zone mutations. HBV DNA level may not have a positive correlation with YMDD mutations. LAM is clinically effective for CHB patients with YMDD mutations.

Prevalence of autoantibodies and the risk of autoimmune thyroid disease in children with chronic hepatitis C virus infection treated with interferon-α

AIM： To evaluate the prevalence of autoantibodies in chronic hepatitis C virus （HCV）-infected children focusing on thyroid autoimmunity.METHODS： We investigated the prevalence of autoantibodies in 123 chronic HCV-infected children before, during and after monotherapy with interferon-alpha （IFN-α） or combined treatment with interferon-α or peginterferon-α and ribavirin. Besides antibodies against smooth muscle （SMA）, nuclei （ANA）, and liver/kidney microsomes （1KM）, the incidence of antithyroid peroxidase antibodies as well as thyroid function parameters （TSH, FT3 and FT4） were determined.RESULTS： We found that 8% of children had autoantibodies before treatment. During treatment, 18% of children were found positive for at least one autoantibody; 15.5% of children developed pathologic thyroid values during IFN-α treatment compared to only one child before therapy. Six children had to be substituted while developing laboratory signs of hypothyroidism.CONCLUSION： Our data indicate a strong correlation between interferon-α treatment and autoimmune phenomena, notably the emergence of thyroid antibodies. The fact that some children required hormone replacement underlines the need of close monitoring in particularly those who respond to therapy and have to be treated for more than 6 mo.