美国FDA批准丙肝治疗新药波普瑞韦

美国FDA于2011年5月批准美国默克公司的慢性丙型肝炎治疗新药波普瑞韦（Boceprevir,商品名Victrelis）上市。波普瑞韦获准与长效干扰素聚乙二醇干扰素a和利巴韦林联用治疗CHC基因I型慢性丙肝感染,适用于患有代偿性肝脏疾病（包括肝硬化）的18岁及以上的成年患者,这些患者以前未经治疗或之前用干扰素和利巴韦林治疗失败。     

抗病毒治疗对Ib型慢性丙肝患者PBMCIL-10、IL-12水平变化影响的研究

目的 对Ⅰ b 型慢性丙肝患者进行抗病毒治疗,研究对其PBMC IL-10、IL-12 水平变化的影响.方法 选取某院2010 年6 月～ 2012 年6月期间收治的Ⅰ b 型慢性丙肝患者100 例,所有患者血清HCV-RNA 检查均为阳性,使用利巴韦林联合聚乙二醇干扰素α-2a 抗病毒治疗48 周,检查患者的PBMC IL-12、IL-10 水平及谷草转氨酶水平（AST）、谷丙转氨酶（ALT）.结果 经过利巴韦林联合聚乙二醇干扰素α-2a 抗病毒治疗后,检查患者的PBMC IL-12、IL-10 及ALT、AST 水平与治疗前相比差异有统计学意义（P 〈 0.05）.结论 对于Ⅰ b 型慢性丙肝患者,给予利巴韦林联合聚乙二醇干扰素α-2a 抗病毒治疗效果显著,值得临床应用及推广.     

抗病毒治疗对Ⅰb型慢性丙肝患者PBMC IL-10、IL-12水平变化影响的研究

目的：对Ⅰb型慢性丙肝患者进行抗病毒治疗,研究对其PBMC IL-10、IL-12水平变化的影响。方法选取某院2010年6月～2012年6月期间收治的Ⅰb型慢性丙肝患者100例,所有患者血清HCV-RNA检查均为阳性,使用利巴韦林联合聚乙二醇干扰素α-2a抗病毒治疗48周,检查患者的PBMC IL-12、IL-10水平及谷草转氨酶水平（AST）、谷丙转氨酶（ALT）。结果经过利巴韦林联合聚乙二醇干扰素α-2a抗病毒治疗后,检查患者的PBMC IL-12、IL-10及ALT、AST水平与治疗前相比差异有统计学意义（P＜0.05）。结论对于Ⅰb型慢性丙肝患者,给予利巴韦林联合聚乙二醇干扰素α-2a抗病毒治疗效果显著,值得临床应用及推广。     

聚乙二醇干扰素α-2a联合利巴韦林治疗代偿期丙肝后肝硬化的临床体会

目的分析研究聚乙二醇干扰素α-2a联合利巴韦林治疗代偿期丙型肝炎(丙肝)后肝硬化的临床效果。方法随机数字抽样选取我院收治的33例慢性丙肝后肝硬化患者为肝硬化组,以及同期接受治疗的33例慢性丙型肝炎患者为肝炎组,均给予患者采用聚乙二醇干扰素α-2a联合利巴韦林治疗,比较两组患者病毒学应答率以及不良反应情况。结果两组RVR、EVR、ETVR比较无明显差异,SVR比较差异显著,肝硬化组的骨髓抑制以及贫血发生率明显高于肝炎组,P<0.05比较差异有统计学意义。结论代偿期丙肝后肝硬化患者,采用聚乙二醇干扰素α-2a联合利巴韦林治疗,其早期应答效果良好,治疗效果显著。     

欧盟批准聚乙二醇干扰素α-2b与利巴韦林联用治疗丙型肝炎病毒感染

欧委会于2007-11—15批准聚乙二醇干扰素α-2b（PegIntron或Rebetol，由Schering—Plough Corp生产）注射液与利巴韦林（ribavirin）片剂联用，治疗对干扰素-α＋利巴韦林联合治疗未获得持续应答的成年慢性丙型肝炎病毒（HCV）感染患者。     

安络化纤丸对干扰素联合利巴韦林治疗慢性丙型肝炎疗效的影响

目的评价安络化纤丸对干扰素/利巴韦林治疗慢性丙型肝炎疗效的影响。方法将43例慢性丙型肝炎患者随机分为治疗组25例和对照组18例,治疗组给予安络化纤丸、重组人IFNα-2b和利巴韦林联合治疗,对照组给予重组人IFNα-2b和利巴韦林治疗。动态观察HCV RNA定量、丙氨酸氨基转移酶（ALT）、肝纤维化血清学指标、血常规、血糖、甲状腺功能等指标及不良反应。结果治疗组血清ALT及肝纤维化指标水平恢复均优于对照组（P〈0.05）,不良反应发生率低于对照组（P〈0.05）。结论安络化纤丸在护肝降酶,抗肝纤维化方面对干扰素/利巴韦林治疗慢性丙型肝炎患者具有良好的影响。     

2011年上半年美国FDA批准新药（续）

（续上期） 5.2波塞瑞韦胶囊 由Merck公司开发,2011年5月13日获得FDA批准,用于联合聚乙二醇化α-干扰素（peginterferon alfa）和利巴韦林（ribavirin）方案治疗≥18岁成人无既往治疗史或已经既往α-干扰素（interferon alfa）和利巴韦林方案治疗失败的呈代偿性肝病、包括已伴肝硬化的基因型为1的慢性丙型肝炎（CHC）患者。     

干扰素a-2b联合利巴韦林治疗慢性丙型肝炎过程中IL-10的动态观察

目的　采用干扰素 a- 2 b(IFNa- 2 b)联合利巴韦林 (Ribavirin病毒唑 )治疗慢性丙型肝炎 ,以预测慢性丙肝患者对本治疗方法的治疗反应。方法　用 EL ISA分别检测 4 0例慢性丙型肝炎患者在治疗前、治疗 6个月、1 8个月时 PBMC在血凝素 IL- 1 0的水平。结果　 1 6例干扰素应答患者 IL- 1 0的水平在治疗 6个月、1 8个月后较治疗前显著降低。2 4例无应答患者在治疗 6个月、1 8个月以及追加治疗 3个月后与治疗前相比 IL - 1 0的水平无显著变化。结论　用 IFNa- 2 b联合利巴韦林治疗后 ,高水平 IL- 1 0持续不降低 ,提示慢性丙肝患者对 IFNa- 2 b和利巴韦林无应答     

低剂量干扰素与利巴韦林治疗丙肝代偿期肝硬化的效果探究

目的分析低剂量干扰素与利巴韦林治疗丙肝代偿期肝硬化的效果。方法抽取入住我院的38例丙肝代偿期肝硬化患者(2010年11月至2014年9月)作为本次实验的研究对象,对其实施随机分组。对照组19例患者采取利巴韦林治疗,实验组19例患者采取低剂量干扰素与利巴韦林治疗,比较两组丙肝代偿期肝硬化患者的临床疗效(持续病毒学应答率、HCV-RNA阴转率及ALT复常率)及不良反应发生率。结果对照组患者的不良反应发生率(15.79%)和实验组患者(21.05%)无明显区别,但实验组和对照组丙肝代偿期肝硬化患者的持续病毒学应答率、HCV-RNA阴转率及ALT复常率存在明显差异,P<0.05。结论对丙肝代偿期肝硬化患者采取低剂量干扰素与利巴韦林进行治疗,效果明显,可有效抑制病毒复制,降低患者的病死率。     

BSM公布新型聚乙二醇干扰素临床试验结果

在第46届欧洲肝病研究学会年会上,百时美施贵宝（BSM）公布了新型聚乙二醇干扰素λ的Ⅱb期EMERGE临床试验结果,数据表明：与目前标准的聚乙二醇干扰素＆alPHa;联合利巴韦林治疗方案相比,使用聚乙二醇干扰素λ联合利巴韦林治疗慢性丙肝初治患者可获得更高的快速病毒学应答率,且安全性和耐受性表现良好,流感样症状、血细胞减少等不良反应发生率较低,这将有利于改善患者的治疗依从性,从而提高治疗效果。     

IL28B polymorphisms, IP-10 and viral load predict virological response to therapy in chronic hepatitis C

Aliment Pharmacol Ther 2011; 33: 1162–1172

Summary

Background Hepatitis C virus (HCV) is a major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma and the identification of the predictors of response to antiviral therapy is an important clinical issue. Aim To determine the independent contribution of factors including IL28B polymorphisms, IFN‐gamma inducible protein‐10 (IP‐10) levels and the homeostasis model assessment of insulin resistance (HOMA‐IR) score in predicting response to therapy in chronic hepatitis C (CHC). Methods Multivariate analysis of factors predicting rapid (RVR) and sustained (SVR) virological response in 280 consecutive, treatment‐naive CHC patients treated with peginterferon alpha and ribavirin in a prospective multicentre study. Results Independent predictors of RVR were HCV RNA <400 000 IU/mL (OR 11.37; 95% CI 3.03–42.6), rs12980275 AA (OR 7.09; 1.97–25.56) and IP‐10 (OR 0.04; 0.003–0.56) in HCV genotype 1 patients and lower baseline γ‐glutamyl‐transferase levels (OR = 0.02; 0.0009–0.31) in HCV genotype 3 patients. Independent predictors of SVR were rs12980275 AA (OR 9.68; 3.44–27.18), age <40 years (OR = 4.79; 1.50–15.34) and HCV RNA <400 000 IU/mL (OR 2.74; 1.03–7.27) in HCV genotype 1 patients and rs12980275 AA (OR = 6.26; 1.98–19.74) and age <40 years (OR 5.37; 1.54–18.75) in the 88 HCV genotype 1 patients without a RVR. RVR was by itself predictive of SVR in HCV genotype 1 patients (OR 33.0; 4.06–268.32) and the only independent predictor of SVR in HCV genotype 2 (OR 9.0, 1.72–46.99) or genotype 3 patients (OR 7.8, 1.43–42.67). Conclusions In HCV genotype 1 patients, IL28B polymorphisms, HCV RNA load and IP‐10 independently predict RVR. The combination of IL28B polymorphisms, HCV RNA level and age may yield more accurate pre‐treatment prediction of SVR. HOMA‐IR score is not associated with viral response.     

The prevalence and clinical characteristics of coinfection of SENV-H among Taiwanese chronic hepatitis C patients with combination therapy of high-dose interferon-alfa and ribavirin

The clinical significance of coinfection of SENV-H among patients with chronic hepatitis C (CHC) and the response to combination therapy with high-dose interferon-alpha (IFN) plus ribavirin in Taiwan are uncertain. A total of 151 (120 histologically proved) na?ve CHC patients who received 6 MU IFN thrice a week plus ribavirin for 24 weeks therapy were enrolled in this study. SENV-H DNA was tested by PCR method. Of 151 patients, 29 (19.2%) were positive for SENV-H DNA. The positive SENV-H DNA was significantly associated with HCV genotype 1b than non-1b infection (69.0% versus 43.4%; P = 0.011). No other clinical, histopathological and virological factor was related to positive SENV-H DNA. After combination therapy, the rate of sustained viral response (SVR) of HCV and SENV-H were 66.9 and 78.3%, respectively. By multivariate analyses, the significant factors associated with HCV SVR after combination therapy were HCV genotype non-1b, pretreatment HCV RNA levels less than 200,000 IU/mL, and younger age. We conclude that coexistent SENV-H infection, apparently associated with HCV genotype 1b, is found among 19.2% of Taiwanese CHC patients. Both HCV and SENV-H are highly susceptible to combination therapy with high dose IFN and ribavirin and SENV-H coinfection does not affect the HCV response.     

Preliminary results of individual therapy of chronic hepatitis C by Ukrain and interferon-alpha

The effects of Ukrain and recombinant human interferon-alpha 2b (IFN) on the state of the thiol-disulfide ratio (SH/SS) of the blood (Russian Federation patent no. 2150700) were studied in vitro using the amperometric titration method. The blood of 73 chronic hepatitis C (CHC) hepatitis C virus (HCV)-RNA-positive patients was examined. Ukrain was tested in doses of 0.05-2.0 micrograms/ml and IFN in 20-1000 U/ml of blood. After in vitro examination, 59 patients were treated: 28 with Ukrain and 31 with IFN. The first group of 16 patients (including eight with HCV genotype 1b) was treated with individually selected optimal doses of Ukrain (0.5-2.5 mg every second day). The second group of 12 patients was treated with doses of 2.5 mg Ukrain independent of in vitro test results. The third group of 31 patients was treated with individually selected optimal doses of IFN (0.5-2 MU 3 times a week). It was found that 79.4% of CHC patients were sensitive to Ukrain in vitro and 65.1% were sensitive to IFN. CHC patients with genotype 1b were sensitive to IFN only in 16.7% of cases while the figure for Ukrain was 92.3%. CHC patients with other HCV genotypes (3, 1a, 2) were sensitive to Ukrain in 86.7% of cases and to IFN in 70.6%. After 1 month of individual therapy with Ukrain, 87.5% of CHC patients, including six of eight cases with HCV genotype 1b, became PCR-HCV negative. In the group receiving the standard dose of Ukrain, virological response was only 33.3%. After 1 month, 74.2% of CHC patients treated with individual doses of IFN became PCR-HCV negative and after 3 months 90.3% were PCR-HCV negative. The prognostic significance of the method for screening preparations for the treatment of CHC patients was 89.8%. Treatment with Ukrain was without serious negative effects and the number of side effects of IFN in individual therapy was significantly reduced. Ukrain can be used in the treatment of CHC patients, alone or in combination with IFN preparations; in the cases with HCV genotype 1b Ukrain seems more promising than IFN. Individual therapy with Ukrain and IFN increased the efficacy of treatment 2.5-fold in comparison with standard monotherapy with the same preparations, significantly decreased the number of side effects and dramatically improved cost-effectiveness.     

Tumor necrosis factor alpha promoter polymorphisms at position -308 in Taiwanese chronic hepatitis C patients treated with interferon-alpha

A G-to-A polymorphic sequence at position -308 in the tumor necrosis factor alpha promoter (TNF308.2) might be associated with disease susceptibilities. To investigate the association between -308 TNF-alpha variants and pathogenesis of hepatitis C virus (HCV) infection and response to interferon-alpha (IFN-alpha) treatment for chronic hepatitis C (CHC), -308 TNF-alpha genotypes were determined in 100 unrelated Taiwanese CHC patients treated with IFN-alpha and in 100 unrelated healthy subjects. The distribution of -308 TNF-alpha genotypes did not differ between CHC patients and controls. Age, sex, HCV genotype, and the necroinflammatory activity of liver histopathology did not differ among CHC patients with different -308 TNF-alpha genotypes. Although pretreatment HCV RNA serum levels, aminotransferase and the rate of severe fibrosis decreased with the copy number of TNF308.2, the difference did not reach significance. We failed to demonstrate any association between -308 TNF-alpha promoter polymorphisms and response to IFN therapy, which was inversely correlated to liver cirrhosis, pretreatment serum HCV RNA levels and genotype 1b by using multivariate analysis. In conclusion, our findings suggest that -308 TNF-alpha promoter polymorphisms do not play a direct role in the susceptibility and pathogenesis of HCV infection, and in the response to interferon-alpha therapy for CHC.     

Virological response in patients with hepatitis C virus genotype 1b and a high viral load: impact of peginterferon-alpha-2a plus ribavirin dose reductions and host-related factors

BACKGROUND and objective: In Japan the prevalence of the hepatitis C virus (HCV) antibody is highest in the elderly population. Therefore, it is important for elderly patients to undergo interferon (IFN) therapy. In patients with HCV genotype 1b and a high viral load, the sustained virological response (SVR) rate is lower in older compared with younger patients receiving combination antiviral therapy. In addition, inadequate adherence to combination therapy is often seen in elderly patients, and is associated with reduced response rates. The aim of this retrospective analysis was to evaluate the effects of host-related factors (i.e. sex, age, baseline HCV RNA level, bodyweight and fibrosis stage) and peginterferon (PEG IFN)-alpha-2a plus ribavirin dose reductions on SVR rates. METHODS: A total of 192 treatment-naive patients with a HCV genotype 1b infection and a high viral load were included in the analysis. Patients had been enrolled into a phase III trial of 48 weeks of treatment with PEG IFN-alpha-2a plus ribavirin or PEG IFN-alpha-2a plus placebo. All patients were evaluated for effect of drug exposure on SVR. In addition, the impact of host-related factors or dose reductions on SVR was assessed. RESULTS: Approximately 30% of patients were considered elderly (> or =60 years of age). The overall SVR rate was significantly higher in patients treated with combination therapy versus monotherapy (59.4% vs 24.0%, p < 0.001). Attainment of an SVR following combination therapy was not influenced by any factor evaluated in the analysis, although elderly males were associated with decreased SVR rates. Younger age (odds ratio [OR] 1.081; 95% CI 1.125, 1.034; p = 0.0009), lower baseline HCV RNA levels (OR 1.003; 95% CI 1.006, 1.001; p = 0.006) and a severe fibrosis stage (F3/4) [OR 6.194; 95% CI 1.037, 37.000; p = 0.0455] significantly increased the likelihood of achieving an SVR with monotherapy. In the combination therapy group, patients maintaining a full dosage schedule of PEG IFN-alpha-2a and ribavirin and those requiring dose reductions of either study drug had similar SVR rates (64.5% vs 61.9%). However, the SVR rate was reduced to 33.3% among patients who discontinued combination therapy. Three out of the 31 patients who received the full dosage schedule were elderly patients. In addition, of the 15 patients who discontinued combination therapy, three were <50 years of age and six were > or =60 years of age. The SVR rate was reduced in patients with cumulative PEG IFN-alpha-2a and ribavirin doses of <60%; the majority of these patients were elderly. CONCLUSION: The attainment of an SVR following PEG IFN-alpha-2a plus ribavirin combination therapy was not influenced by any of the host-related factors evaluated in this analysis, although elderly males were associated with a decreased SVR rate. Younger age, male sex and lower baseline HCV RNA levels significantly increased the likelihood of achieving an SVR with monotherapy. In addition, dose reductions appeared to have a negative impact on SVR in elderly patients. Therefore, it is important to minimize PEG IFN-alpha-2a and ribavirin dose reductions by effectively managing treatment-related adverse events in elderly patients.     

Combined antiviral options for the treatment of chronic hepatitis C

In the absence of antiviral treatment, chronic hepatitis C virus (HCV) infection is a liver disease characterized by the development of necroinflammatory changes and progressive liver fibrosis, leading to cirrhosis, end-stage liver disease and hepatocellular carcinoma (HCC). The approval of ribavirin in combination therapy regimens with interferon (IFN) dramatically improved therapy. Another advance was the introduction of pegylated IFNs, which allow a once-weekly subcutaneous administration and show more favorable pharmacokinetics and greater efficacy. Two forms are available: pegylated IFN alpha-2b (12 kDa) (1.5 microg/kg) and pegylated IFN alpha-2a (40 kDa) (fixed dosage of 180 microg). Ribavirin is administered orally, at doses > or =10.6 mg/kg, resulting in higher sustained virological responses (SVR) than IFN monotherapy. The highest SVR rates are attained with pegylated IFNs in combination with ribavirin. Factors associated with treatment outcome include HCV genotype, viral load, body weight, age, cirrhosis or bridging fibrosis, coinfection with HIV or hepatitis B virus, and treatment adherence and tolerance. Currently, the main therapeutic challenges ahead are: (a) the dosage optimization of pegylated IFNs and ribavirin according to the patients' characteristics; and (b) to evaluate the efficacy and safety of this combination therapy for difficult-to-treat patients, such as nonresponders, cirrhotics, transplant recipients, renal disease patients or those coinfected with HIV.     

Polymorphisms in the interferon-gamma gene at position +874 in patients with chronic hepatitis C treated with high-dose interferon-alpha and ribavirin

To investigate the influence of the T-to-A polymorphic sequence at position +874 in the interferon (IFN)-gamma gene (+874 IFN-gamma) on the response to combination therapy with high-dose interferon and ribavirin, the single nucleotide polymorphisms were determined by using a polymerase chain reaction sequence-specific primers approach in 150 histologically proved chronic hepatitis C (CHC) patients. The distribution of genotypes for +874 IFN-gamma were T/T: 6 (4.0%), T/A: 31 (20.7%) and A/A: 113 (75.3%) and 24.7% (37/150) of patients were inherited T allele. After undergoing combination therapy with high-dose IFN-alpha and ribavirin, 70.7% (106/150) of patients achieved sustained viral response (SVR). Based on multivariate regression analyses, the independent factors predicting HCV SVR after combination therapy were HCV genotype non-1b (P<0.001) and low pretreatment HCV RNA levels (P=0.041) (odds ratios/95% C.I.: 10.150/4.023-25.609 and 0.581/0.345-0.979, respectively). No association between genotypes, A or T alleles of +874 IFN-gamma and response to combination therapy with high-dose IFN-alpha and ribavirin. In conclusion, we found that with high SVR rates after combination therapy with high-dose IFN-alpha and ribavirin, HCV genotypes and pretreatment serum HCV RNA levels, but not inheritance of the IFN-gamma polymorphism at the position +847, were predictors for SVR.     

Meta-analysis: re-treatment of genotype I hepatitis C nonresponders and relapsers after failing interferon and ribavirin combination therapy

Aliment Pharmacol Ther 2010; 32: 969–983

Summary

Background The efficacy of re‐treating genotype I hepatitis C virus (HCV) patients who failed combination therapy with interferon/pegylated interferon (PEG‐IFN) and ribavirin remains unclear. Aims To quantify sustained virological response (SVR) rates with different re‐treatment regimens through meta‐analysis of randomized controlled trials (RCTs). Methods Randomized controlled trials of genotype I HCV treatment failure patients that compared currently available re‐treatment regimens were selected. Two investigators independently extracted data on patient population, methods and results. The pooled relative risk of SVR for treatment regimens was computed using a random effects model. Results Eighteen RCTs were included. In nonresponders to standard interferon/ribavirin, re‐treatment with high‐dose PEG‐IFN combination therapy improved SVR compared with standard PEG‐IFN combination therapy (RR = 1.49; 95% CI: 1.09–2.04), but SVR rates did not exceed 18% in most studies. In relapsers to standard interferon/ribavirin, re‐treatment with high‐dose PEG‐IFN or prolonged CIFN improved SVR (RR = 1.57; 95% CI: 1.16–2.14) and achieved SVR rates of 43–69%. Conclusions In genotype I HCV treatment failure patients who received combination therapy, re‐treatment with high‐dose PEG‐IFN combination therapy is superior to re‐treatment with standard combination therapy, although SVR rates are variable for nonresponders (≤18%) and relapsers (43–69%). Re‐treatment may be appropriate for select patients, especially relapsers and individuals with bridging fibrosis or compensated cirrhosis.     

HCVRNA载量在慢性丙肝、肝硬化、肝癌患者中的变化及基因分型

目的了解丙型肝炎病毒RNA（HCVRNA）载量在慢性丙型肝炎、丙型肝炎肝硬化、丙肝相关的肝癌（HCV—HCC）患者中的变化及基因分型对疾病进展的影响。方法回顾性分析2010年2月至2013年8月门诊及住院的1386例HCVRNA阳性且未进行抗病毒治疗的丙型肝炎患者的临床病例资料,把患者按诊断分为丙型肝炎组、丙肝肝硬化组、丙肝相关的肝癌组,采用qRT—PCR检测患者血清的HCVRNA载量与基因分型,多组比较采用方差分析或卡方检验,两组间比较采用t检验。结果丙型肝炎组、丙肝肝硬化组及丙肝相关的肝癌组患者HCVRNA载量分别为（6．47±1．03）lgIU／mL,（6．18±1．09）lgIU／mL和（6．07±1．13）lgIU／mL,三组患者HCVRNA载量不同,丙型肝炎组HCVRNA明显高于其他二种,且差别有统计学意义（F=12．80,P〈0．05）,但丙肝肝硬化组与HCV—HCC组患者HCVRNA载量差别无统计学意义（t=0．65,P〉0．05）。1386例患者中816例进行了HCV基因型检测,1型基因型529例（64．83％）,2型基因型287例（35．17％）,丙型肝炎组患者1型基因型者为400例,2型基因型者为226例,1b型基因型为主（63．10％）,丙肝肝硬化组1型基因型117例,2型基因型为57例,1b型基因型为主（65．52％）,HCV—HCC组1型基因型为12例,2型基因型为4例,1b型基因型为主（68．75％）,三组患者基因型比例无明显差别（x^2=1．02,P=0．31）。结论HCVRNA载量在慢性丙型肝炎发展为肝硬化、肝癌的过程中减低,河南地区丙肝患者以1型基因型为主,且1型、2型基因型对疾病的进展没有影响。     

Patterns of hepatocellular carcinoma development in hepatitis B virus and hepatitis C virus related cirrhosis.

To compare incidence, risk factors and morphologic pattern of hepatocellular carcinoma (HCC) development in hepatitis B virus (HBV) and hepatitis C virus (HCV) related cirrhosis, 401 patients were followed prospectively by periodic ultrasound examination for 14-189 months (mean: 84.8+/-36.7). During follow-up, 77 (19.2%) patients developed HCC, with 5 and 10 year cumulative incidence of 10 and 27.5%, respectively. The risk of HCC was significantly higher in HBV and HCV co-infected patients (P=0.014) compared to those with single HBsAg or anti-HCV (antibodies to hepatitis C virus) positivity. In anti-HCV positive cases the annual risk of HCC increased from 2% in the first 5 year period to 4% in the third 5 year period, while it decreased from 2 to 0% in the same time periods in the HBsAg positive group. By Cox's regression, age above 59 years (P=0.001), male sex (P=0.09), longer duration (P=0.04) and more advanced stage (P=0.01) of cirrhosis, lower platelets count (P=0.001) and higher ALT levels were significant risk factors for HCC in anti-HCV positive patients, while only high alpha-fetoprotein (AFP) levels during follow-up (P=0.04) was a significant risk factor for HCC in HBsAg positive cases. The pattern of HCC was nodular in 63 (81.8%) patients and infiltrating in 14 (18.2%), and the former type was associated with older age (P=0.0001), longer duration (P=0.002) and more advanced stage (P=0.0001) of cirrhosis but not with the viral etiology of disease. In contrast, development of infiltrating HCC was unrelated to age and disease duration and stage, and was associated with male sex (P=0.01), HBV infection (P=0.06) and HBV and HCV co-infection (P=0.0001). Our results indicate different incidence profile, risk factors and patterns of morphogenesis of HCC development in HBV and HCV associated cirrhosis, suggesting different mechanisms of carcinogenesis.