人丙型基因工程干扰素（rINF－γ）治疗异位性皮炎27例报告

我们采用ｒＩＮＦ－γ皮下注射治疗了２７例ＡＤ患者，经过３周及４～６周治疗后病情严重度积分较治疗前明显下降（Ｐ值均＜０．００１），而对照组１３例患者皮下注射白蛋白后病情严重度积分无明显下降（Ｐ均＞０．０５）；３周后治疗组总有效率（４８％）高于对照组（１５％），但无统计学意义，４～６周后治疗组总有效率（７５％）明显高于对照组（２２％）（Ｐ＜０．０５）。ｒＩＮＦ－γ的主要副作用为：发热、乏力、肌痛或／和关节痛。

小剂量α-干扰素联合胸腺肽a-1治疗失代偿期丙型肝炎肝硬化的疗效观察

目的:观察应用α-干扰素小剂量开始逐渐加量联合病毒唑、胸腺肽a-1方案治疗失代偿期丙型肝炎肝硬化的临床疗效。方法:16例失代偿期丙型肝炎肝硬化患者采用IFN-α及胸腺肽a-1治疗。初始剂量为100万U,每周3次,加病毒唑600 mg/日,胸腺肽a-1每周2次,每次1.6mg,治疗1个月后,将剂量增加至IFN300万U和病毒唑1000mg/日,治疗半年,观察疗效。结果:16例患者中有12例耐受尚好并完成IFN疗程,而4例无法耐受,IFN治疗提前终止。与治疗前比较,12例患者治疗后的ALT、AST、ALB、TBIL、PTA、HCV RNA、肝纤维化指标(HA、LN、PC-Ⅲ、C-Ⅳ)均有明显改善(P<0.01)。结论:IFNα小剂量开始逐渐加量联合病毒唑、胸腺肽a-1方案可治疗失代偿期丙型肝炎肝硬化患者。

不同干扰素治疗基因2a型慢性丙型肝炎临床分析

目的:探讨不同干扰素(聚乙二醇干扰素和普通干扰素a-1b)在慢性丙型肝炎基因(CHC)2a型患者中的疗效与复发情况。方法:收集2012年7月—2014年7月青海省第四人民医院基因分型2a型初治患者的70例,随机分为采用聚乙二醇干扰素组(A组)和普通干扰素a-1b组(B组)各35例,观察应答率和停药复发情况。结果:两组患者在经过48周的治疗后,聚乙二醇干扰素25例患者获得早期病毒学应答(EVR),30例患者获得持续病毒学应答(SVR),3例患者无应答(NR),5例患者复发。普通干扰素a-1b组21例患者获得早期病毒学应答(SVR),28例患者获得持续病毒学应答,6例患者无应答,8例患者复发。停药后复发率无明显差异。白细胞计数下降和血小板减少的发生率聚乙二醇干扰素高于普通干扰素a-1b,差异有统计学意义。结论:两组EVR、治疗结束时病毒学应答(ETVR)差异无统计学意义,普通干扰素联合利巴韦林取得较好的疗效,且不良反应减少,患者耐受性好,复发率低。

Effect of interferon in combination with ribavirin on the plus and minus strands of HCV RNA in patients with chronic hepatitis C

AIMS To probe the effect of interferon in combination with rib- avirin on the plus and minus strands of hepatitis C virus RNA (HCV RNA). METHODS Twenty-three cases diagnosed as chronic hepatitis C (CHC) according to positive HCV RNA/anti-HCV,fluctuating levels of aminotransferase activities (>1 year) and absence of other hepatitis virus marker,were studied. Among them,13 pa- tients received combined antiviral therapy (subcutaneous injection of 3MU of interferon-α three times per week for 3 months and intra- venous drip of 1 g of ribavirin per day during the first month of treatment with interferon) and 10 patients received single interfer- on therapy (the same as above-mentioned) as control. The plus and minus strands of HCV RNA in sera and peripheral blood mononuclear cells (PBMCs) of these patients were tested by means of nested reverse transcription-polymerase chain reaction (nested RT-PCR). RESULTS At the end of therapy,the abnormal ALT levels de- creased to normal range in 9 (69.23%) cases in the combined antiviral group. Of them,5 (55.56%)experienced post-therapy relapse and 4 (44.44%) were complete responders. In the inter- feron group,the ALT decreased to normal in 6 (60%) cases,of which,4 (66.67%) had post-therapy relapse and 2 (33.33%) were complete responders. The differences between the two groups were nonsignificant (P>0.05). At the end of therapy,the positive rate of the plus strand in sera decreased from 92.3% to 38.46% (P<0.05) and that of the minus strand in PBMCs,from 76.92% to 38.46% (P<0.05) in the combined antiviral group; and in the interferon group,the former decreased from 100% to 50% (P<0.05) and the latter,from 90% to 40% (P<0.05). Again,no significant differences were found between groups (P >0.05). The relapse occurred in patients whose plus strand HCV RNA in PBMCs remained positive before and after treatment. CONCLUSIONS Ribavirin could not enhance the antiviral effect of interferon. The absence of HCV RNA in serum does not mean complete clearance of HCV,and its value for evaluating the an- tiviral effect and prognosis is limited. Therefore,it is essential to measure the plus and minus strands of HCV RNA in sera and PBM- Cs simultaneously.

Effect of in vitro interferon-beta administration on hepatitis C virus in peripheral blood mononuclear cells as a predictive marker of clinical response to interferon treatment for chronic hepatitis C

AIM:To test whether in vitro incubation of peripheral blood mononuclear cells (PBMC) with interferon (IFN) could efficiently decrease hepatitis C virus-RNA (HCV-RNA) amount and to analyze whether this effect was associated with clinical response to IFN.METHODS:Twenty-seven patients with histologically proven chronic hepatitis C were given intravenous administration of 6 million units (MU) IFN-β daily for 6 weeks followed by three times weekly for 20 weeks. PBMC collected before IFN therapy were incubated with IFN-β and HCV-RNA in PMBC was semi-quantitatively determined.RESULTS: Twenty-five patients completed IFN therapy.Eight patients (32%) had sustained loss of serum HCV-RNA with normal serum ALT levels after IFN therapy (complete responders).HCV-RNA in PBMC was detected in all patients,whereas it was not detected in PBMC from healthy subjects.In vitro administration of IFN-β decreased the amount of HCV-RNA in PMBC in 18 patients (72%). Eight of these patients obtained complete response. On the other hand,none of the patients whose HCV-RNA in PBMC did not decrease by IFN-β was complete responders. Multiple logistic regression analysis revealed that the decrease of HCV-RNA amount in PBMC by IFN-β was the only independent predictor for complete response (P<0.05).CONCLUSION:The effect of in vitro IFN-β on HCV in PBMC reflects clinical response and would be taken into account as a predictive marker of IFN therapy for chronic hepatitis C.

Co-infection of SENV-D among chronic hepatitis C patients treated with combination therapy with high-dose interferon-alfa and ribavirin

AIM： The clinical significance of co-infection of SENV-D among patients with chronic hepatitis C （CHC） and response of both viruses to combination therapy with high-dose interferon-alfa （IFN） plus ribavirin remain uncertain and are being investigated.METHODS： Total 164 （97 males and 67 females, the mean age 48.1＋11.4 years, range： 20-73 years, 128 histologically proved） naive CHC patients were enrolled in this study. SENV-D DNA was tested by PCR method.Detection of serum HCV RNA was performed using a standardized automated qualitative RT-PCR assay （COBAS AMPLICOR HCV Test, version 2.0）. HCV genotypes la,lb, 2a, 2b, and 3a were determined by using genotypespecific primers. Pretreatment HCV RNA levels were determined by using the branched DNA assay （Quantiplex HCV RNA 3.0）. There are 156 patients receiving combination therapy with IFN 6 MU plus ribavirin for 24 wk and the response to therapy is determined.RESULTS： Sixty-one （37.2%） patients were positive for SENV-D DNA and had higher mean age than those who were negative （50.7＋ 10.6 years vs 46.6＋ 11.6 years,P = 0.026）. The rate of sustained viral response （SVR） for HCV and SENV-D were 67.3% （105/156） and 56.3% （27/48）, respectively. By univariate analysis, the higher rate of SVR was significantly related to HCV genotype non-1b （P〈0.001）, younger ages （P = 0.014）, lower pretreatment levels of HCV RNA （P = 0.019） and higher histological activity index （HAI） score for intralobular regeneration and focal necrosis （P= 0.037）. By multivariate analyses, HCV genotype non-lb, younger age and lower pretreatment HCV RNA levels were significantly associated with HCV SVR （odds ratio （OR）/95% confidence interval （CI）： 12.098/0.02-0.19, 0.936/0.890-0.998, and 3.131/1.080-9.077, respectively）. The SVR of SENV-D was higher among patients clearing SENV-D than those who had viremia at the end of therapy （P = 0.04）.CONCLUSION： Coexistent SENV-D infection, apparently associated with higher ages, is found in more than onethird Taiwan Residents CHC patients. Both HCV and SENV-D are highly susceptible to combination therapy with high-dose IFN and ribavirin and SENV-D co-infection does not affect the HCV response. HCV genotype, pretreatment HCV RNA levels and age are predictive factors for HCV SVR.

Acute inflammatory demyelinating polyneuropathy associated with pegylated interferon α 2a therapy for chronic hepatitis C virus infection

The combination of pegylated interferon (Peg-IFN) and ribavirin is the standard of care for chronic hepatitis C virus (HCV) infection treatment. In general, common side effects related to this combination therapy are mild and are very well tolerated. However, peripheral neuropathy including demyelinating polyneuropathy related to Peg-IFN is extremely rare. We present the first case of an acute inflammatory demyelinating polyneuropathy (AIDP) associated with Peg-IFN-α 2a (Pegasys) after 16 wk of a combination therapy with Pegasys and ribavirin in a 65-year-old woman with chronic HCV infection. She developed tingling, numbness, and weakness of her upper and lower extremities and was hospitalized for acute neurological deficits. Her clinical course, neurological findings, an electromyogram (EMG), nerve conductions studies (NCS), muscle biopsy, and a sural nerve biopsy were all consistent with AIDP likely related to Pegasys use. The patient recovered completely with the use of intravenous immunoglobulin (IVIG) including physical therapy and neurological rehabilitation. It is very important that gastroenterologists and/or hepatologists recognize this rare neurological complication related to Peg-IFN treatment very early, since it requires a prompt discontinuation of therapy including an immediate referral to a neurologist for the confirmation of diagnosis, management, and the prevention of long-term neurological deficits.

Gastric autoimmune disorders in patients with chronic hepatitis C before,during and after interferon-alpha therapy

AIM:To explore the prevalence of autoimmune gastritis in chronic hepatitis C virus (HCV) patients and the influence of α-interferon (IFN) treatment on autoimmune gastritis. METHODS:We performed a prospective study on 189 patients with positive anti-HCV and viral RNA enrolled in a 12-month IFN protocol.We evaluated:a) the baseline prevalence of autoimmune gastritis,b) the impact of IFN treatment on development of biochemical signs of autoimmune gastritis (at 3,6 and 12 months),c) the evolution after IFN withdrawal (12 months) in terms of anti-gastric-parietal-cell antibodies (APCA),gastrin,anti-thyroid,and anti-non-organ- specific antibodies. RESULTS:APCA positivity and 3-fold gastrin levels were detected in 3 (1.6%) and 9 (5%) patients,respectively,at baseline,in 25 (13%) and 31 (16%) patients at the end of treatment (both P<0.001,vs baseline),and in 7 (4%) and 14 (7%) patients 12 months after withdrawal (P=0.002 and P=0.01 respectively,vs baseline;P=not significant vs end of treatment).The development of autoimmune gastritis was strictly associated with the presence of autoimmune thyroiditis (P=0.0001),no relationship was found with other markers of autoimmunity. CONCLUSION:In HCV patients,IFN frequently precipitates latent autoimmune gastritis,particularly in females.Following our 12-month protocol,the phenomenon generally regressed.Since APCA positivity and high gastrin levels are associated with the presence of antithyroid antibodies, development of autoimmune thyroiditis during IFN treatment may provide a surrogate preliminary indicator of possible autoimmune gastritis to limit the need for invasive examinations.

The interferon inducing pathways and the hepatitis C virus

The innate immune response is triggered by a variety of pathogens, including viruses, and requires rapid induction of typeⅠ?interferons (IFN), such as IFNβ and IFNα. IFN induction occurs when specific pathogen motifs bind to specific cellular receptors. In non-professional immune, virally-infected cells, IFN induction is essentially initiated after the binding of dsRNA structures to TLR3 receptors or to intracytosolic RNA helicases, such as RIG-Ⅰ/MDA5. This leads to the recruitment of specific adaptors, such as TRIF for TLR3 and the mitochondrial-associated IPS-1/VISA/MAVS/CARDIF adapter protein for the RNA helicases, and the ultimate recruitment of kinases, such as MAPKs, the canonical IKK complex and the TBK1/IKKε kinases, which activate the transcription factors ATF-2/ c-jun, NF-κB and IRF3, respectively. The coordinated action of these transcription factors leads to induction of IFN and of pro-inflammatory cytokines and to the establishment of the innate immune response. HCV can cleave both the adapters TRIF and IPS-1/VISA/MAVS/ CARDIF through the action of its NS3/4A protease. This provokes abrogation of the induction of the IFN and cytokine pathways and favours viral propagation and presumably HCV chronic infection.

Expression of interferon-alpha/beta receptor protein in liver of patients with hepatitis C virus-related chronic liver disease

ABM: To study the expression of interferon-alpha/beta (IFN-α/β) receptor protein in liver of patients with hepatitis C virus (HCV)-related chronic liver disease and its clinical significance. METHODS: A total of 181 patients with HCV-related chronic liver disease included 56 with HCV-related liver cirrhosis (LC) and 125 with chronic hepatitis C (CHC). CHC patients were treated with five megaunits of interferon-α1b six times weekly for the first 2 weeks and then every other day for 22 wk. The patients were divided into interferon (IFN) treatment-responsive and non-responsive groups, but 36 patients lost follow-up shortly after receiving the treatment. The expression of IFN-α/β receptor (IFN-α/βR) protein in liver of all patients was determined with immunofluorescence. RESULTS: In liver of patients with HCV-related chronic liver disease, the expression of IFN-α/βR protein in liver cell membrane was stronger than that in cytoplasm and more obvious in the surroundings of portal vein than in the surroundings of central vein. Moreover, it was poorly distributed in hepatic lobules. The weak positive, positive and strong positive expression of IFN-α/βR were 40% (50/125), 28% (35/125), 32% (40/125), respectively in CHC group, and 91.1% (51/56), 5.35% (3/56), and 3.56% (2/56), respectively in LC group. The positive and strong positive rates were higher in CHC group than in LC group (P<0.01). In IFN treatment responsive group, 27.8% (10/36) showed weak positive expression; 72.2% (26/36) showed positive or strong positive expression. In the non-responsive group, 71.7% (38/53) showed weak positive expression; 28.3% (15/53) showed positive or strong positive expression. The expression of IFN-α/βR protein in liver was more obvious in IFN treatment responsive group than in non-responsive group. CONCLUSION: Expression of IFN-α/βR protein in liver of patients with HCV-related chronic liver disease is likely involved in the response to IFN treatment.

Efficacy and safety of pegylated-interferon α-2a in hemodialysis patients with chronic hepatitis C

AIM： To evaluate the efficacy and safety of pegylated- interferon alpha-2a in hemodialysis patients with chronic hepatitis C. METHODS： Thirty-six hemodialysis patients with chronic hepatitis C were enrolled in a controlled and prospective study. All patients were treatment naive, positive tested for anti-HCV antibodies, and positive tested for serum HCV-RNA. Twenty-two patients received 135 μg peglyated-interferon α-2a weekly for 48 wk （group A）. The remaining patients were left untreated, eleven refused therapy, and three were not candidates for kidney transplantation and were allocated to the control group （group B）. At the end of the treatment biochemical and virological response was evaluated, and 24 wk after completetion of therapy sustained virological response （SVR） was assessed. Side effects were monitored. RESULTS： Of 22 hemodialysis patients, 12 were male and 10 female, with a mean age of 35.2 ± 12.1 years. Virological end-of-treatment response was observed in 14 patients （82.4%） in group A and in one patient （7.1%） in group B （P = 0.001）. Sustained virological response was observed in 11 patients （64.7%） in group A and in one patient in group B （7.1%）. Biochemical response parameters normalized in 10/14 patients （71.4%） at the end of the treatment. ALT levels in group B were initially high in six patients and normalized in one of them （25%） at the end of the 48 wk. In five patients （22.7%） therapy had to be stopped at mo 4 due to complications of weakness, anemia, and bleeding. CONCLUSION： SVR could be achieved in 64.7% of patients on hemodialysis with chronic hepatitis C by a treatment with peglyated-interferon α-2a. Group A had a significantly better efficacy compared to the control group B, but the side effects need to be concerned.

Antiviral therapy in hepatitis C virus cirrhotic patients in compensated and decompensated condition

The main goals of treating cirrhotic patients with antiviral therapy are to attain sustained viral clearance(SVR),halt disease progression,and prevent re-infection of the liver graft.However,while the medical need is great,the use of interferon and ribavirin might expose these patients to severe treated-related side effects as a large proportion of them have pre-existing hematological cytopenias.We have reviewed potential benefits and risks associated with antiviral drugs in patients with liver cirrhosis,due to hepatitis C virus(HCV) infection.In cases presenting with bridging fibrosis or cirrhosis,current regimens of antiviral therapy have attained a 44%-48% rate of SVR.In cirrhotic patients with portal hypertension,the SVR rate was 22% overall,12.5% in patients with genotype 1,and 66.7% in those with genotypes 2 and 3 following therapy with low doses of either Peg-IFN alpha-2b and of ribavirin.In patients with decompensated cirrhosis,full dosages of Peg-IFN alpha-2b and of ribavirin produced a SVR rate of 35% overall,16% in patients with genotype 1 and 4,and 59% in those with genotype 2 and 3.Use of hematological cytokines will either ensure full course of treatment to be accomplished with and prevent development of treatment-associated side effects.Major benefits after HCV eradication were partial recovery of liver metabolic activity,prevention of hepatitis C recurrence after transplantation,and removal of some patients from the waiting list for liver transplant.Several observations highlighted that therapy is inadvisable for individuals with poor hepatic reserve(Child-Pugh-Turcotte score ≥ 10).Although SVR rates are low indecompensated cirrhotics due to hepatitis C,these patients have the most to gain as successful antiviral therapy is potentially lifesaving.

Interferon alpha plus ribavirin combination treatment of Japanese chronic hepatitis C patients with HCV genotype 2:A project of the Kyushu University Liver Disease Study Group

AIM： To determine the efficacy of an interferon alpha and ribavirin combination treatment for Japanese patients infected with hepatitis C virus （HCV） of genotype 2, a multi-center study was retrospectively analyzed. METHODS： In total, 173 patients with HCV genotype 2 started to receive interferon-alpha subcutaneously thrice a week and 600-800 mg of ribavirin daily for 24 wk. RESULTS： The overall sustained virological response （SVR）, defined as undetectable HCV RNA in serum, 24 wk after the end of treatment, was remarkably high by 84.4%, （146/173） by an intention-to-treat analysis. A significant difference in SVR was found between patients with and without the discontinuation of ribavirin （46.9% vs 92.9 %）, but no difference was found between those with and without a dose reduction of ribavirin. A significant difference in SVR was also found between patients with less than 16 wk and patients with 16 or more weeks of ribavirin treatment （34.8 % vs 92.0 %）. CONCLUSION： The 24-wk interferon and ribavirin treatment is highly effective for Japanese patients with HCV genotype 2. The significant predictor of SVR is continuation of the ribavirin treatment for up to 16

Intraocular complications of IFN-α and ribavirin therapy in patients with chronic viral hepatitis C

We report a panel of severe inflammatory and vascular intraocular disorders occurring during interferon-alpha （IFN-α） treatment in eight hepatitis C virus （HCV）- infected patients. These events include three cases of Vogt-Koyanagi-Harada like （VKH） disease （an association of panuveitis, retinal detachment, ear and meningeal detachment and skin and hair changes）, two cases of central retinal vein occlusion, one case of central retinal artery occlusion, one case of severe hypertensive retinopathy and one case of bilateral ischemic optic neuropathy with severe visual impairment. Rare as they are, such severe ophthalmological complications require a close follow-up of HCV-infected patients under IFN-α breabnent with ophthalmological monitoring if any ocular manifestation occurs.

Mutations in carboxy-terminal part of E2 including PKR/eIF2αphosphorylation homology domain and interferon sensitivity determining region of nonstructural 5A of hepatitis C virus 1b:Their correlation with response to interferon monotherapy and viral load

AIM： To study the amino acid substitutions in the carboxy （C）-terminal part of E2 protein and in the interferon （IFN） sensitivity determining region （ISDR） and their correlation with response to IFN and viral load in 85 hepatitis C virus （HCV）-lb-infected patients treated with IFN. METHODS： The C-terminal part of E2 （codons 617-711） including PKR/eIF2α phosphorylation homology domain （PePHD） and ISDR was sequenced in 85 HCV-1b-infected patients treated by IFN monotherapy. RESULTS： The amino acid substitutions in PePHD detected only in 4 of 85 patients were not correlated either with response to iFN or with viral load. The presence of substitutions in a N-terminal variable region （codons 617-641） in the C-terminal part of E2 was significantly correlated with both small viral load （33.9% vs 13.8%, P = 0.0394） and sustained response to iFN （25.0% vs 6.9 %, P = 0.0429）. Four or more substitutions in ISDR were significantly correlated with both small viral load （78.6% vs 16.2%, P 〈 0.0001） and sustained response to iFN （85.7% vs 2.9%, P 〈 0.0001）. In multivariate analysis, ISDR in nonstructural （NS） 5A （OR = 0.39, P 〈 0.0001） and N-terminal variable region （OR = 0.51, P = 0.039） was selected as the independentpredictors for small viral load, and ISDR （OR = 39.0, P 〈 0.0001） was selected as the only independent predictor for sustained response. CONCLUSION： The N-terminal variable region in the C-terminal part of E2 correlates with both response to IFN monotherapy and viral load and is one of the factors independently associated with a small viral load.

Clearance of hepatitis C virus after living-donor liver transplantation in spite of residual viremia on end date of interferon therapy before transplantation

Interferon （IFN） therapy is the only treatment strategy for hepatitis C virus （HCV） infection after liver transplantation （LT）, but prophylactic and treatable IFN therapy after LT has been shown to be insufficient due to the adverse effects of IFN and rivabirin. In this paper, we describe the disappearance of HCV after LT without IFN therapy in the presence of residual viremia on the day of LT. We herein report our findings since this is considered an important case for the anti-HCV strategy of post LT. A 60-year old woman with LC and HCC was referred to Nagasaki University Hospital in August 2004. After she underwent LT on February 18, 2005, we injected peg- IFN-α-2a the 11th time at 18 wk and HCV-RNA was still positive in the serum at LT. The serum HCV-RNA was negative one month after operation and subsequently dissolved 15 mo after operation without IFN therapy. As a result, we speculate that if HCV-RNA is positive while HCV core antigen is negative before LT, then it may lead to dearance of HCV after LT. Therefore long acting peg-IFN- α-2a is thus considered a potentially effective agent for the treatment of HCV-related cirrhosis before LT.

Is pegylated interferon superior to interferon,with ribavarin,in chronic hepatitis C genotypes 2/3?

Over the past decade, significant improvements have been made in the treatment of chronic hepatitis C （CHC）, especially with the introduction of combined therapy using both interferon and ribavarin. The optimal dose and duration of treatment is still a matter of debate and, importantly, the efficacy of this combined treatment varies with the viral genotype responsible for infection. In general, patients infected with viral genotypes 2 or 3 more readily achieve a sustained viral response than those infected with viral genotype 1. The introduction of a pegylated version of interferon in the past decade has produced better clinical outcomes in patients infected with viral genotype 1. However, the published literature shows no improvement in clinical outcomes in patients infected with viral genotypes 2 or 3 when they are treated with pegylated interferon as opposed to nonpegylated interferon, both given in combination with ribavarin. This is significant because the cost of a 24-wk treatment with pegylated interferon in lessdeveloped countries is between six and 30 times greater than that of treatment with interferon. Thus, clinicians need to carefully consider the cost-versusbenefit of using pegylated interferon to treat CHC, particularly when there is no evidence for clinically measurable benefits in patients with genotypes 2 and 3 infections.

Effect of sustained virological response on long-term clinical outcome in 113 patients with compensated hepatitis C-related cirrhosis treated by interferon alpha and ribavirin

AIM： To assess the long-term clinical benefit of sustained virological response （SVR） in patients with hepatitis C virus （HCV） cirrhosis treated by antiviral therapy using mostly ribavirin plus interferon either standard or pegylated.METHODS： One hundred and thirteen patients with uncomplicated HCV biopsy-proven cirrhosis, treated by at least one course of antiviral treatment ≥ 3 mo and followed ≥ 30 mo were included. The occurrence of clinical events [hepatocellular carcinoma （HCC）, decompensation and death] was compared in SVR and non SVR patients.RESULTS： Seventy eight patients received bitherapy and 63 had repeat treatments. SVR was achieved in 37 patients （33%）. During a mean follow-up of 7.7 years, clinical events occurred more frequently in non SVR than in SVR patients, with a significant difference for HCC （24/76 vs 1/37, P = 0.01）. No SVR patient died while 20/76 non-SVR did （P = 0.002）, mainly in relation to HCC （45%）.CONCLUSION： In patients with HCV-related cirrhosis, $VR is associated with a significant decrease in the incidence of HCC and mortality during a follow-up period of 7.7 years. This result is a strong argument to perform and repeat antiviral treatments in patients with compensated cirrhosis.

L-carnitine supplementation improves hematological pattern in patients affected by HCV treated with Peg interferon-α 2b plus ribavirin

AIM：To evaluate the efficacy of L-carnitine on alleviating anemia,thrombocytopenia and leukopenia,and minimizing dose reductions in patients with chronic hepatitis C virus（HCV）in treatment with Interferonα（IFN-α）plus ribavirin.METHODS：Sixty-nine patients with chronic hepatitis C were enrolled in the study and divided into two groups.group A（n=35）received Peg-IFN-α2b plus ribavirin plus L-carnitine,and group B（n=34）received Peg-IFN-αand ribavirin for 12 mo.All patients underwent laboratory investigations including：red cell count,he-moglobin,white cell count,platelets,bilirubin,alanineaminotransferase（ALT）,aspartate aminotransferase（AST）,and viremia.RESULTS：After 12 mo in group A compared to group B we observed significant differences in AST 108.8 vs 76.8（IU/L;P0.001）,ALT 137.vs 112.3（IU/L;P 0.001）,viremia 4.04 vs 2.36（106 copies/mL;P 0.001）,Hb 1 vs 3.5（g/dL;P0.05）,red blood cells 0.3 vs 1.1（1012/L;P0.001）,white blood cells 1.5 vs 3（10/L;P0.001）and platelets 86 vs 85（×10/L;P0.001）.The end treatment responders were 18 vs 12（60%vs 44%）and the non responders were 12 vs 15（40%vs 50%）[odds ratio（OR）1.65,5%CI =0.65-5.37,P0.05.In group A compared to group B there was a significant improvement of sustained vi-rological response in 15 vs 7 patients（50%vs25%）,while the relapsers were 3 vs 5（10%vs 18%）（OR 3.57,5%CI=0.65-1.3,P0.001）.CONCLUSION：L-carnitine supplementations modulate erythropoiesis,leucopoiesis and thrombocytopoiesis,and may be useful in patients treated for HCV.L-carni-tine treatment offers the possibility of achieving a sus-tained virological response while preventing overtreat-ment.

Ketoprofen,peginterferon 2a and ribavirin for genotype 1 chronic hepatitis C:A phaseⅡ study

AIM:To evaluate the safety of adding ketoprofen to pegylated-interferon(PEG-IFN)with or without ribavirin and the effect on viral kinetics,STAT1 activity and expression of 2'-5'-oligoadenylate synthetase (2'-5'OAS)in genotype 1 chronic hepatitis C in a phaseⅡstudy. METHODS:Forty-five patients were studied:fifteen were randomized to PEG-IFN plus ribavirin(PR),16 to PEGIFN plus ketoprofen and 14 to PR and ketoprofen.Themolecular study of IFN-dependent signal transduction was conducted in 9 patients from each group. RESULTS:The combination of ketoprofen and PEG- IFN with or without ribavirin was safe and well tolerated.An early activation of STAT1 was observed in ke-toprofen-treated patients,but this activation was less sustained over time.Conversely,ketoprofen plus PEG- IFN and ribavirin induced an early and sustained increase of 2'-5'OAS transcription starting 24 h after the first dose until the 36th wk.These data are consistent with the clinical results,showing a better sustained virological response and a lower relapse rate in patients receiving ketoprofen plus PEG-IFN and ribavirin. CONCLUSION:The addition of ketoprofen to the standard therapy of chronic hepatitis C should be explored in larger randomized clinical studies.