Autoantibodies in chronic hepatitis C: A clinical perspective

Non-organ-specific autoantibodies and thyroid autoantibodies have been frequently found in chronic carriers of hepatitis C virus(HCV). With respect to endomysial antibodies and tissue transglutaminase, it is controversial whether the prevalence of glutenrelated seromarkers is higher in patients with HCV. In such cases, in addition to acknowledging any currently existing autoimmune disease, recognizing the risk of the patient developing an autoimmune disease during interferon(IFN)-based treatment must be a principle concern. From a clinical point-of-view, the presence of autoantibodies arouses suspicion that an autoimmunedisease may be present or may be precipitated by IFNbased HCV treatment. In this paper, we review the prevalence of autoantibodies in individuals with hepatitis C, the clinical significance of these autoantibodies, and the approach recommended for such situations.     

Immunosuppressive Activity of Mouse Amniotic Fluid

Conventional Swiss mice were treated from birth through young adulthood with intraperitoneal injections of homologous mouse amniotic fluid. A significant suppression of the primary splenic plaque-forming cells (PFC) antibody response to sheep red blood cells was demonstrated in these animals. A pronounced suppressive effect by amniotic fluid was noted on the γA and γG PFC, with variable degrees of immunosuppression observed on the γM response.     

IFN-α治疗慢性乙型肝炎中出现HBeAg血清学转换的预测因素分析

目的 观察慢性乙型病毒性肝炎(chronic hepatitis B,CHB)患者治疗后不同时期外周血谷丙转氨酶(alanine aminotransferase,ALT)、乙肝病毒脱氧核糖核酸(hepatitis B virus deoxyribonucleic acid,HBV DNA)、乙肝表面抗原(hepatitis B surface antigen,HBsAg)、乙肝e抗原(hepatitis B e antigen,HBeAg)滴度的变化,并探讨其预测HBeAg血清学转换的价值.方法 对72例选择干扰素(interferon,IFN)治疗的HBeAg阳性CHB患者随访48周,在治疗0、12、24、48周收集患者的血清,定量检测HBsAg、HBeAg、HBV DNA、ALT水平.结果 基线ALT、HBeAg水平与治疗应答相关.治疗12、24周时HBsAg＜4.33、4.07(lg IU/ml),下降率＞65％、47％,治疗12、24周时HBeAg＜2.38、0.87(lg S/CO),下降率＞71％、95％预测治疗48时出现HBeAg血清学转换的敏感性、特异性高(均有P＜0.05).结论 IFN治疗HBeAg阳性CHB患者时,动态监测HBsAg、HBeAg的水平变化能作为预测是否出现HBeAg血清学转换的良好指标.     

花生衣煎剂预防α干扰素治疗慢性丙型肝炎患者骨髓抑制临床疗效

观察花生衣煎剂对慢性丙型肝炎患者在使用IFN-α治疗过程中所致的骨髓抑制的防治作用。方法给予36例慢性丙型肝炎患者聚乙二醇干扰素联合利巴韦林治疗,同时给予花生衣煎剂口服;18例患者只接受干扰素和利巴韦林治疗,观察治疗48 w和随访24 w的疗效。结果治疗组和对照组患者在治疗48 w和随访24 w时,病毒学应答率分别为94.4%和88.8%及88.9%和83.3%（P〉0.05）;两组患者外周血白细胞和血小板计数分别为[（5.4±1.0）×10^9/L和（249.2±37.5）×10^9/L,及（2.5±1.0）×10^9/L和（81.1±25.0）×10^9/L,P〈0.01]。结论在给予IFN-α治疗慢性丙型肝炎患者过程中,加用花生衣煎剂可减轻干扰素所致的骨髓抑制。     

Treatment of pig serum-induced rat liver fibrosis with Boschniakia rossica, oxymatrine and interferon-α

AIM: To investigate the effect of Boschniakia rossica (BR), oxymatrine (OM) and interferon-alpha (IFN-α) 1b on the therapy of rat liver fibrosis and its mechanism. METHODS: By establishing a rat model of pig serum-induced liver fibrosis, liver/weight index and serum alanine transaminase (ALT) were observed to investigate the therapeutic effect of BR,OM and IFN-α. Radioimmunoassay was utilized to measure procollagen type Ⅲ (PCⅢ) and collagen type Ⅳ (CIV). RT-PCR was used to assay the expression of liver transforming growth factor- beta 1 (TGF-β1) mRNA. Immunohistochemistry of alpha-smooth muscle actin (α-SMA) and pathologic changes of liver tissues were also under investigation. RESULTS: Serum PCⅢ and CIV in BR, OM and IFN-α groups were significantly declined compared with those in model group, and their RT-PCR revealed that TGF-β1 mRNA expression was also reduced more than that in model group. Immunohistochemistry demonstrated that α-SMA also declined more than that in model group. Serum ALT in IFN-α, control and model groups was within normal level. Serum ALT in BR group had no significant difference from those of IFN-α, control and model groups. Serum ALT in OM group was significantly higher than those in BR, IFN-α, model, and control groups. CONCLUSION: BR, OM and IFN-α can prevent pig serum-induced liver rat fibrosis by inhibiting the activation of hepatic stellate cells and synthesizing collagen. OM has hepatotoxicity to rat liver fibrosis induced by pig serum.     

动态观察血清HBV-DNA水平预测干扰素治疗慢性乙型肝炎疗效的意义

目的　研究干扰素 α 2a治疗慢性乙型病毒性肝炎 (慢性乙肝 )期间 ,患者血清中HBV-DNA定量的动态变化与疗效的关系。方法　 5.8例慢性乙肝患者皮下注射干扰素 α-2a3MIU 次 ,每周 3次 ,疗程 6个月。观察患者血清中HBV DNA定量和丙氨酸转氨酶 (ALT)的动态变化。结果　完全有效组治疗 1个月后 ,患者血清中HBV DNA定量显著降低 [(3 99± 0.91)log1.0 ],明显低于部分有效组[(5.6 3± 1.31)log1 0 ]和无效组 [(6.6 9± 1.4 2 )log1 0 ],(P <0.0 5 )。疗效不同的 3组患者经过 1个月的治疗 ,血清中HBV DNA定量分别下降 (2.5 0± 0.4 4 )log1 0 、(1 6 2± 1.12 )log1 0 和 (1 0 5± 1.35 )log1 0 。通过多因素分析 ,用干扰素 α-2a治疗 1个月后患者血清中HBV DNA阴转 ,提示干扰素 α-2a的疗效好 ;治疗前ALT高水平和无家族史也与其疗效好相关。结论　患者治疗 1个月后血清中HBV DNA定量是预测干扰素 α 2a疗效的重要因素     

Establishment and characterization of a novel CD34-positive human myeloid leukemia cell line: MHH225 growing in serum-free culture

A new human multilineage myeloid leukemia cell line, MHH225, has been established in our laboratory from the bone marrow of a 60-year-old patient suffering from acute megakaryoblastic leukemia (M7); it provides a unique model for studying the effect of biologic and chemical agents on the lineage specificity of a multipotent myeloid leukemia clone containing a mixed population of megakaryoblast, erythroblast, and myeloblast cells in a serum-free culture. Morphologically, all 225 cells are large blast cells with basophilic cytoplasm containing no granules, large round nucleus containing 2–3 prominent nucleoli, and fine chromatin structure and a large nuclear/cytoplasm ratio. The MHH225 cells are CD34⁺HLA-DR⁺CD33⁺CD13⁺ with 57.6%, 28.3%, and 7.8% of them being CD41⁺, glycophorin A⁺, and CD15⁺, respectively, and all lymphoid-specific antigens are negative. The karyotype analysis of MHH225 cells revealed a deletion of the short arm of chromosome 7: del(7)(p13)-, a whole-arm translocation between the long arms of chromosomes 9 and 21: t(9;21)(q10;q10), and a chromosome 11 with an elongated long arm due to duplication of chromosome 11 material as well as to translocation of part of chromosome 9 onto 11q+. Also, chromosome 21 was deleted in some metaphases or showed a ring formation in other metaphases. Utrastructurally, MHH25 cells display a strong platelet peroxidase activity in the nuclear envelope and the endoplasmic reticulum. The MHH25 cells have been grown exponentially without growth factors or conditioned media or serum only in RPMI1640 culture medium. None of the myelopoietic growth factors, i.e., interleukin-3, GM-CSF, G-CSF, erythropoietin, or interleukin-6, has any effect on the proliferation and differentiation of MHH25 cells. The two, hematopoietic inhibitory cytokines, interferon-alpha and tumor necrosis factor-alpha, have only minimal growth inhibitory effect. Stem cell factor showed only weak growth-stimulatory effect on MHH225 cells but significantly inhibited chemotherapy-induced apoptosis in these cells. The new cell line MHH225 should constitute a useful model for studying stem cell antigen (CD34)-positive human multilineage myeloid leukemia cells carrying a deletion in the short arm of chromosome 7 and an aberration in chromosome 11 and provide a unique tool for investigating human hematopoietic stem cell biology and its cytokine regulation in serum-free cultures. To our knowledge, the MHH225 cell line is the first human CD34-positive leukemia cell line growing in serum-free cultures to be established.     

慢性乙型肝炎干扰素治疗后长期随访复发与再治疗后复发研究

目的观察和分析慢性乙型病毒性肝炎（CHB）经重组α干扰素（rIFN-α）治疗取得联合应答后,在长期随访过程中的复发情况,及再次rIFN-α治疗后的复发情况。方法523例经肝穿刺活检证实的CHB患者,给予rIFN-α1b治疗,每次500万u,每周3次,疗程6～37个月（中位数10个月）,治疗中每1～3个月检测肝功能、HBVDNA、乙肝炎e抗原（HBeAg）。治疗后随访至少12个月,随访时每3～6个月检查肝功能、HBVDNA、HBeAg,随访中的复发病例,予以第2次rIFN-α治疗。结果523例患者HBeAg（＋）403例,HBeAg（-）120例。初次rIFN—α治疗结束后,HBeAg（＋）组近期应答225例（55．8％）,HBeAg（-）组77例（64．2％）,差异无统计学意义（Χ^2=2．633,P=0．105）。302例近期应答者,经随访（39±22）个月,复发119例（39．4％）,其中HBeAg（＋）组76／225例（33．8％）、HBeAg（-）组43／77例（55．8％）,差异有统计学意义（Χ^2=19．335,P=0.000）。按随访每12个月为一时间段,分1～12个月、13～24个月、25～36个月、37～48个月、49～60个月和≥61个月6个时间段,各时间段复发的发生率差异有统计学意义（Χ^2=73．518,df=5,P=0．000）,累计复发率差异亦有统计学意义（Χ^2=32．167,df=5,P=0．000）。各时间段复发发生的HBeAg阳性比差异无统计学意义,Χ^2=2．518,df=4,P=0．641,累计复发的HBeAg阳性比差异亦无统计学意义,）（Χ^2=0．370,df=5,P=0．996。57例复发者[HBeAg（＋）组25例,（-）组32例]接受第2次rIFN-α治疗,治疗结束时全部取得联合应答,但HBeAg（＋）组13例,（-）组7例第2次复发,差异有统计学意义（Χ^2=5．592,P=0．018）。结论CHB患者经初次rIFN-α治疗后,HBeAg阴性组与HBeAg阳性组的近期应答率相同,而HBeAg阴性组的复发率高于HBeAg阳性组。复发者第2次rIFN-α治疗结束时可全部取得联合应答,而第2次复发HBeAg阴性组低于HBeAg阳性组。     

干扰素雾化吸入治疗毛细支气管炎临床疗效观察

目的观察干扰素α1b（赛若金）雾化吸入治疗毛细支气管炎的临床疗效。方法86例临床诊断为毛细支气管炎患儿单号入观察组42例,双号入对照组44例,观察组给予雾化吸入干扰素α1b20μg,每天2次;对照组给予雾化吸入利巴韦林50mg,每天2次;疗程均7d。观察两组患儿喘憋缓解及肺部哕音消失时间、发热消退时间、住院病程长短及有效率。结果一观察组喘憋缓解时间（t=1．756,P〈0．05）、肺部哕音消失时间（t=2．413,P〈0．01）、住院时间（t=2．547,P〈0．01）均少于对照组;观察组总有效率为88．0％（37／42）,高于对照组的47．7％（21／44）（χ2=15．59,P〈0．01）;两组治疗中均未发现明显不良反应。结论干扰素α1b雾化吸入治疗毛细支气管炎疗效显著,值得临床推广应用。     

Association of IL28B Polymorphisms With the Response to Peginterferon Plus Ribavirin Combined Therapy in Polish Patients Infected With HCV Genotype 1 and 4

Background

Three single nucleotide polymorphisms (SNPs) near interleukin-28B (IL-28B) gene were shown to be highly associated with treatment response (SVR) in patients with chronic hepatitis C virus (HCV) infection. There is limited data about the role of single and combined IL-28B polymorphisms in HCV-infected Polish population.

Objectives

This study''s aim was to determine predictability of three IL-28B gene polymorphisms and other known prognostic factors on the treatment response in HCV genotype 1 and 4 infected Polish patients. The effect of IL-28B polymorphisms on therapy was also compared with other known prognostic factors.

Patients and Methods

We genotyped IL-28B polymorphisms (rs12979860, rs12980275 and rs8099917) by polymerase chain reaction-based restriction fragment length polymorphism assay in a group of 293 patients from which a selected cohort of 174 treatment-naiev patients underwent treatment.

Results

We showed that rs12979860 CC [odds ratio (OR) = 4.6, P < 0.001], rs12980275 AA (OR = 2.9, P = 0.002) and rs8099917 TT (OR = 2.2, P = 0.016) genotypes were associated with successful treatment compared to the rs12979860 CT-TT, rs12980275 AG-GG and rs8099917 TG-GG, respectively. Patients bearing of IL-28B profile including the three favourable genotypes do not have much chance of a recovery (OR = 3.4, P = 0.002). Except for IL-28B polymorphisms, there was no association of SVR with any other pretreatment clinical data in analyzed group. The correlation of SNPs with other host and viral factors revealed association of favorable genotypes of IL-28B markers with high levels of alanine aminotransferase and baseline HCV viral load.

Conclusions

IL-28B polymorphisms were the strongest pretreatment predictors of response to pegylated interferon and ribavirin in Polish patients chronically infected with HCV genotype 1 and 4. This study confirm the strongest impact of IL-28B rs12979860 on SVR, nevertheless rs12980275 AA seems to be more important than rs8099917 TT in predicting positive treatment response.