Randomized controlled trial of consensus interferon with or without zinc for chronic hepatitis C patients with genotype 2

AIM:The beneficial effect of zinc supplementation onthe efficacy of interferon as a treatment for chronichepatitis C had been demonstrated in hepatitis virusgenotype 1b of high viral load.This study focusedon patients with genotype 2,which is more sensitiveto interferon than genotype 1b,and used consensusinterferon(CIFN)with or without zinc.METHODS:We randomized 83 patients with chronichepatitis C to CIFN at 18 MIU six times/wk for 4 wk,followed by CIFN at 18 MIU six times/wk for another 20wk,in combination with polaprezinc 300 mg(regimen A,n=41)or as monotherapy(regimen B,n=42).Thirty-one patients in regimen A and 33 patients in regimenB completed the clinical trial;the remaining patientswithdrew because of side effects or a transfer to anotherhospital.RESULTS:Sustained biochemical response,defined asa normal aminotransferase level at the end of the 6-mopost-treatment observation,was 68% and 69%,andsustained virological response,defined as undetectableHCV-RNA at the end of the 6-mo post-treatmentobservation,was 54% and 67% for regimens A and B,respectively.CONCLUSION:CIFN treatment combined with zinc didnot enhance the effect of CIFN as shown by biochemical,virological criteria.No side effects related to polaprezincwere noted.     

Treatment rates in patients with chronic hepatitis C after liver biopsy

Hepatitis C virus (HCV) infection is a major health problem in the United States. Only about 30% of patients infected with HCV are being treated despite the development of increasingly effective therapies. The aims of this study were to determine the rate of treatment for patients with HCV after undergoing liver biopsy, to assess any change in their treatment rates over recent years and to delineate the reasons for nontreatment. We retrospectively reviewed the charts of all HCV patients who had liver biopsies at Beth Israel Medical Center, New York between 1998 and 2002. The data gathered included patient demographics, stage of liver fibrosis, insurance information, treatment history and reasons for nontreatment. There were 433 liver biopsies done for chronic hepatitis C between 1998 and 2002. Of those, 267 (61%) were men. The mean age was 47 years (range, 18-72). Only 159 (37%) patients were treated after liver biopsy. Overall there were no significant differences in the treatment rates from 1999 to 2002. The common reasons for nontreatment included minimal/mild disease (stage 0-1 fibrosis, 38%), lost to follow-up or noncompliance (31%) and patient refusal (22%). Older patients more frequently had co-morbid conditions (P = 0.009). Younger age and female gender correlated with minimal disease on biopsy (P = 0.004 and 0.01, respectively). Men were lost to follow-up more frequently than women (37%vs 22%, P = 0.01). Multivariate analysis showed that age and gender were both independent predictors of minimal disease. Patients having Medicaid with or without Medicare were significantly more likely to be treated than patients with private or commercial insurance or patients with Medicare alone. A minority of HCV infected patients were treated even after having undergone liver biopsy. The proportion of HCV patients being treated after liver biopsy has been relatively stable despite advances in therapeutic success. Liver histology frequently identified patients with mild disease in whom antiviral therapy was deemed not urgent.     

Sustained virological response of patients with hepatitis C virus genotype 2 depends on pegylated interferon compliance

Aim: Patients infected with hepatitis C virus (HCV) genotype 2 are more sensitive to interferon (IFN) therapy than those infected with genotype 1, but 10–20% of patients do not achieve a sustained viral response (SVR) to combination therapy with pegylated (PEG) IFN and ribavirin (RBV). This study examines the prognostic factors associated with SVR in patients infected with HCV genotype 2 treated with PEG IFN and RBV. Methods: We treated 149 patients with chronic hepatitis C caused by HCV genotype 2. The patients received s.c. PEG IFN‐α‐2b (1.5 µg/kg) and a weekly weight‐adjusted dose of RBV (600, 800 and 1000 mg per <60, 60–80 and >80 kg, respectively) for 24 weeks and then prognostic factors associated with the SVR were examined. Results: Among the 149 patients, 138 completed the combination therapy and a sustained viral response was achieved in 71.8% of them. Univariate analysis showed that age, as well as mean RBV and PEG IFN doses were factors affecting the SVR (P = 0.012, =0.021, =0.014). Multivariate analysis identified age and mean PEG IFN dose (P = 0.021, =0.018, respectively) as factors involved in the SVR, but not mean RBV dose. Conclusion: The SVR of patients infected with HCV genotype 2 depended on the dosage of PEG IFN, but not of RBV. Selecting sufficient doses of PEG IFN for combination with RBV is critical for treating such patients.     

Hepatitis C virus genotypes and hepatic fibrosis regulate 24-h decline of serum hepatitis C virus RNA during interferon therapy in patients with chronic hepatitis C

BACKGROUND AND AIMS: Recently, hepatitis C virus (HCV) dynamics during interferon (IFN) therapy have been studied in detail. We examined factors that regulate the viral kinetics and the relationship between the viral kinetics and clinical effect of IFN therapy. METHODS: Eighty-eight patients with chronic hepatitis C entered this study. All patients had been treated with 3 MU of IFN-beta twice a day for the first 2-4 weeks, then IFN-alpha for the next 20-22 weeks (three injections per week). The levels of serum HCV RNA were determined by Amplicor HCV Monitor version 1.0, before and 24 h after the first injection of IFN; then the decline of HCV was calculated. Liver inflammation and fibrosis were scored as 0 (none), 1 (mild), 2 (moderate) or 3 (severe) using biopsy specimens. RESULTS: The decline of serum HCV RNA was 1.42 +/- 0.65 log copies/mL in genotype 1b and 1.83 +/- 0.72 in genotype 2a or 2b (P < 0.01). By a logistic regression model, genotype (1b, 2a or 2b) and hepatic fibrosis (0 or 1, 2 or 3) associated with 24-h decline of serum HCV RNA, independently. As the predictor of IFN therapy, the decline of serum HCV RNA and serum HCV RNA levels before IFN therapy were the independent significant factors (P < 0.001). CONCLUSIONS: The decline of serum HCV RNA during the first 24 h of IFN therapy was regulated by genotypes and hepatic fibrosis. The decline of serum HCV RNA and initial HCV load were independent factors that can be the predictor of the subsequent sustained viral response to IFN therapy.     

Efficacy and safety of a novel pegylated interferon alpha-2a in Egyptian patients with genotype 4 chronic hepatitis C

BACKGROUND:

Hepatitis C virus (HCV) genotype 4 is a common infection in Egypt and is the leading cause of liver disease.

OBJECTIVE:

To study the efficacy and safety of a novel 20 kD pegylated interferon alpha-2a derived from Hansenula polymorpha in combination with ribavirin for the treatment of Egyptian patients with genotype 4 chronic hepatitis C (CHC).

METHODS:

One hundred seven patients with genotype 4 CHC were involved in the present study. Liver biopsy was performed in all patients. All patients received a fixed weekly dose of 160 μg of a novel pegylated interferon in combination with ribavirin in standard and adjusted doses. Serum HCV RNA levels were assessed by a real-time sensitive polymerase chain reaction assay at four, 12, 48 and 72 weeks after the start of therapy. Patients demonstrating an early virological response (EVR) completed a 48-week course of treatment.

RESULTS:

The overall sustained virological response (SVR) was 60.7%. The SVR in patients with a rapid virological response was significantly higher (91.7%) than in patients with complete EVR (67.74%) (P=0.033) and partial EVR (56.14%) (P=0.003). SVR was also significantly higher in patients with a low degree of liver fibrosis according to Metavir score (F1 and F2) (67.57%) compared with those with a high degree of liver fibrosis (F3 and F4) (45.45%) (P=0.017). The baseline viral load had no impact on SVR in the present series nor were any serious adverse events reported.

CONCLUSION:

The novel pegylated interferon alpha-2a assessed in the present study was effective for the treatment of patients with genotype 4 CHC, and was safe and well tolerated.     

Treatment of chronic hepatitis C in Europe

The lifetime cumulative risk of developing cirrhosis and hepatocellular carcinoma is the rationale for treating patients with chronic hepatitis C with antivirals. The standard treatment is combination therapy with interferon-alfa and ribavirin. In patients with high transaminases and histologic signs of chronic hepatitis, 6- to 12-month therapy with 3 mega units (MU) interferon-alfa thrice weekly, combined with ribavirin, yielded up to 30% sustained responders, and this was increased to 50% with pegylated interferon combined with ribavirin. Favorable predictors of response to the former treatment were genotype 2 or 3, less than 2 million copies of hepatitis C virus (HCV), no portal fibrosis at biopsy, age less than 40 years, and female sex. The same was true for the latter treatment; however, with body weight less than 82?kg replacing female sex. A 98% cure of community-acquired acute hepatitis C was achieved with early treatment with daily doses of 5?MU interferon, compared with a calculated 30% HCV-RNA clearance in untreated patients. More cost-effective strategies for ceasing treatment, based upon early clearance of HCV, are under investigation, with cutoff equal to or more than a 2?log decrease in serum HCV-RNA at week 12. This approach has 100% negative predictive value and 80% positive predictive value. Treatment can also be optimized by combination retreatment of relapsers and nonresponders to monotherapy, which yielded sustained responses of 50% and 25%, respectively. There are difficult-to-treat patients who have high viremia, genotype 1 and 4, or coinfection with HIV or HBV, or carry an organ graft, and those who did not respond to combination therapy. Extended treatment of the latter patients with pegylated interferon might slow down the progression of fibrosis.     

Pegylated interferon plus ribavirin for genotype Ib chronic hepatitis C in Japan

AIM：To evaluate the efficacy of pegylated interferon α-2b（peg-IFNα-2b） plus ribavirin（RBV） therapy in Japanese patients with chronic hepatitis C（CHC） genotype Ib and a high viral load.METHODS：One hundred and twenty CHC patients（58.3% male） who received peg-IFNα-2b plus RBV therapy for 48 wk were enrolled.Sustained virological response（SVR） and clinical parameters were evaluated.RESULTS：One hundred（83.3%） of 120 patients completed 48 wk of treatment.53 patients（44.3%） achieved SVR.Early virological response（EVR） and end of treatment response（ETR） rates were 50% and 73.3%,respectively.The clinical parameters（SVR vs non-SVR） associated with SVR,ALT（108.4 IU/L vs 74.5 IU/L,P = 0.063）,EVR（76.4% vs 16.4%,P 〈 0.0001）,adherence to peg-IFN（≥ 80% of planned dose） at week 12（48.1% vs 13.6%,P = 0.00036）,adherence to peg-IFN at week 48（54.7% vs 16.2%,P 〈 0.0001） and adherence to RBV at week 48（56.1% vs 32.1%,P = 0.0102） were determined using univariate analysis,and EVR and adherence to peg-IFN at week 48 were determined using multivariate analysis.In the older patient group（〉 56 years）,SVR in females was significantly lower than that in males（17% vs 50%,P = 0.0262）.EVR and adherence to Peg-IFN were demonstrated to be the main factors associated with SVR.CONCLUSION：Peg-IFNα-2b plus RBV combination therapy demonstrated good tolerability in Japanese patients with CHC and resulted in a SVR rate of 44.3%.Treatment of elderly female patients is still challenging and maintenance of adherence to peg-IFNα-2b is important in improving the SVR rate.     

Poor response to interferon treatment for chronic hepatitis C in human immunodeficiency virus-infected haemophiliacs.

We performed a pilot study to evaluate the factors associated with response to interferon (IFN) therapy for chronic hepatitis C (CHC) with human immunodeficiency virus (HIV) coinfected haemophiliacs. Seven haemophiliacs, coinfected with HIV and hepatitis C virus (HCV), received 9 mega-units (MU) of natural IFN-alpha daily during the first 2 weeks and then three times a week for 22 weeks, all injected subcutaneously. Six patients were receiving zidovudine (AZT) 600 mg day-1 and didanosine (ddI) 200 mg day(-1) during IFN therapy. This treatment was safe and well tolerated. Four patients had no detectable serum HCV-RNA at the end of therapy, but long-term, none of the seven patients achieved a sustained response, i.e. undetectable serum HCV-RNA with persistently normal serum alanine aminotransferase (ALT) 6 months after therapy. IFN did not affect CD4-positive cell counts. Most of our patients had high HCV-RNA loads and/or low CD4 counts, both unfavourable markers for IFN therapy. In conclusion, IFN therapy did not eradicate HCV from haemophiliacs coinfected with HIV.     

Predicting interferon therapy efficacy from hepatitis C virus genotype and RNA titer

We classified 53 Japanese patients with chronic hepatitis C who were treated with natural interferon- into genotypes and also tested the amounts of hepatitis C virus (HCV) RNA. The rate of the long-term complete response group, whose alanine aminotransferase levels remained within the normal range during the six months after therapy, was significantly higher (P<0.01) in the type-III patients (4/5, 80.0%) than in type-II patients (4/43, 9.3%). For these long-term complete responders, the amounts of HCV RNA was less than 10⁷ copies/ml serum in type-II patients, whereas two type-III patients with relatively high amounts of HCV RNA responded completely. These results confirm that the genotype of HCV is an important factor for predicting the response to interferon therapy. The amounts of HCV RNA can also predict its efficacy in type-II patients.This work was supported by a Grant-in-Aid from the Ministry of Education, Science and Culture, Japan, and the Research Group of Intractable Hepatitis sponsored by the Ministry of Health and Welfare of Japan.     

Interferon treatment of cirrhotic patients with chronic hepatitis C

SUMMARY. Hepatitis C virus (HCV) infection is one of the more important infectious diseases yet to be conquered. An estimated 3.5 million people in the USA have chronic HCV. Each year, 8000 to 10000 of these chronically infected patients die of a liver-related complication of their infection. The introduction of effective blood screening assays has resulted in a remarkable decrease in the incidence of post-transfusion HCV infection. Nonetheless it is essential to have a treatment programme for chronic HCV disease that prevents the development and the progression of compensated cirrhosis to either decompensated cirrhosis or hepatocellular carcinoma, as many individuals present to the health care system with chronic active hepatitis or cirrhosis. A completely safe and effective treatment strategy for chronic HCV, with or without cirrhosis, remains to be developed. Of the various treatment alternatives currently available, only interferon (IFN) has been evaluated extensively. IFN therapy has been shown to induce remissions of the hepatic inflammatory process and also to eliminate the viral infection in some treated cases. As a result, the selection of patients for treatment and the dose and the duration of therapy with IFN are still controversial issues. It is widely held that cirrhotic individuals do not respond to IFN therapy and that treatment of decompensated cirrhotic individuals with HCV infection is dangerous. Here we review data regarding the available experience with IFN treatment of HCV-positive individuals with cirrhosis and compare the response rates of cirrhotics to those reported for individuals with chronic active HCV.     

IL28B polymorphisms predict response to therapy among chronic hepatitis C patients with HCV genotype 4

Summary. Genetic polymorphisms near IL28B are associated with spontaneous and treatment‐induced clearance of hepatitis C virus (HCV). Our objective was to assess the predictive value of IL28B polymorphisms in the treatment of chronic hepatitis C of patients with HCV genotypes 4, for which data are currently limited. We analysed the association of IL28B polymorphisms with the virological response to treatment among 182 naïve chronic hepatitis C patients with HCV genotype 4, all from Syria. Associations of alleles with the response patterns were evaluated by univariate analysis and multivariate logistic regression, accounting for all relevant covariates. Sustained virological response (SVR) was achieved in 26% of rs8099917 TG/GG carriers compared with 60% of TT carriers (P < 0.0001) and 35% of rs12979860 CT/TT carriers compared with 62% of CC carriers (P = 0.0011). By multivariate analysis, the association between rs8099917 and SVR remained significant (OR = 0.19, 95% CI 0.07–0.50, for TG/GG vs TT, P = 0.0007), with the only significant covariate being advanced fibrosis (OR = 0.13, 95% CI 0.04–0.37, P = 0.0002). In conclusion, IL28B polymorphisms are the strongest predictors of response to therapy among chronic hepatitis C patients with HCV genotype 4.     

A pilot study of recombinant interferon beta‐1a for the treatment of chronic hepatitis C

Abstract: Aims: Interferon alpha monotherapy induces a sustained response in less than 20% of patients treated for chronic hepatitis C. Interferon beta represents a potential therapeutic alternative for the treatment of chronic hepatitis C. The aim of this pilot study was to evaluate the efficacy and tolerance of recombinant interferon beta‐1a administered subcutaneously. Methods: Twenty‐one drug‐naive patients with chronic hepatitis C were treated with recombinant interferon beta‐1a administered, subcutaneously, for 24 weeks using two different regimens: 9 MU, three times per week (n=11) and 12 MU, three times per week (n=10). Results: At the end of the treatment period, nine (43%) patients had a biochemical and virological response (i.e. normal ALT and absence of hepatitis C virus RNA by PCR). Four of these patients were in the 9 MU group and five in the 12 MU group. A biochemical and virological sustained response occurred in four (19%) patients, all in the 9 MU dose group. The 4 patients with a sustained response maintained their response during a follow‐up period of 33 to 58 months. Side effects were mild and 19 (90%) patients completed the treatment period. Conclusions: The results of this pilot study indicate that interferon beta‐1a administered subcutaneously is an effective therapy for some patients with chronic hepatitis C, and suggest that interferon beta‐1a deserves further evaluations in larger trials especially in combination with ribavirin.     

Interferon-related thyroid autoimmunity and long-term clinical outcome of chronic hepatitis C

BACKGROUND: A high incidence of thyroid autoantibodies and/or disorders was observed in subjects with hepatitis C virus-related chronic hepatitis during interferon-alpha therapy. AIM: To evaluate whether thyroid autoimmunity and dysfunction, induced by interferon-alpha therapy, could be viewed as predictors for treatment response and as valid prognostic markers of liver disease progression. PATIENTS: A total of 136 subjects (96 males/40 females; median age 48 years; range 23-64) affected by biopsy-proven chronic hepatitis C (33.1% with compensated liver cirrhosis). METHODS: All subjects were treated with interferon-alpha therapy at 6 MU 3 times weekly for 12 months and then followed up for an average period of 60 months (range 12-108). Routine laboratory tests, virological assessment, liver ultrasound, thyroid function tests (serum free-triiodothyronine, free-thyroxine, serum thyrotropin), and autoimmunity were performed for all subjects. RESULTS: Percentage of thyroid autoimmunity and thyroid dysfunction in long-term responders was not significantly different compared to that in non-responders (47.0% and 11.8% vs 35.3% and 5.9%, respectively; non significant). The multivariate model demonstrated that the absence of cirrhosis was the only factor significantly related to successful response to therapy (odds ratio: 14.9; 95% confidence interval: 1.9-115.0 for chronic hepatitis C vs presence of cirrhosis). Moreover, the occurrence of thyroid autoimmunity during interferon therapy was similar both in patients with or without worsening of liver disease (33.3% and 39.8%, respectively; p = not significant). No subject with on-going liver disease developed thyroid dysfunction during treatment, as opposed to the 10/118 (8.4%) with a better course of liver disease; however, this difference was not statistically significant. The multivariate model showed that age was the only covariate significantly associated with unfavourable outcome of liver disease (odds ratio: 18.6; 95% confidence interval: 2.3-151.9, for those over 48 years vs younger patients). CONCLUSIONS: There is no evidence that the immune mechanism involved in the pathogenesis of thyroid autoimmune phenomena is the same as that regulating the therapeutic clearance of HCV or modulating the unfavourable course of HCV-related chronic hepatitis. However, our study confirmed that liver disease seems to progress more slowly in younger subjects.     

Four-week pegylated interferon α-2a monotherapy for chronic hepatitis C with genotype 2 and low viral load: A pilot, randomized study

AIM: To assess the efficacy and advantages of 4-wk pegylated interferon α-2a (peg-IFN-α2a) monotherapy for chronic hepatitis C patients with strong predictors of sustained virologic response (SVR).METHODS: Patients (n = 33) with genotype 2 and low viral load (< 100 KIU/mL), who became HCV RNA negative after 1 wk of IFN treatment, were randomly allocated to receive a 4- or 12-wk treatment course at a ratio of 2:1, respectively, with a subsequent 24-wk follow-up period. Peg-IFN-α2a was administered subcutaneously at a dose of 180 μg or 90 μg once weekly. SVR was defined as absence of serum HCV RNA at the end of the follow-up period. RESULTS: All patients completed the treatment schedule, and more than half were symptom-free during the treatment. In the 4-wk treatment group, 20 of 22 (91%) patients achieved SVR. Two patients relapsed, but achieved SVR following re-treatment with peg-IFN-α2a alone. In the 12-wk treatment group, 11 of 11 (100%) patients attained SVR.CONCLUSION: Our results show that a 4-wk course of peg-IFN-α2a monotherapy can achieve a high SVR rate in "IFN-sensitive" patients, without negatively affecting outcome.     

Four-week pegylated interferon a-2a monotherapy for chronic hepatitis C with genotype 2 and low viral load：A pilot,randomized study

AIM：To assess the efficacy and advantages of 4-wk pegylated interferon a-2a（peg-IFN-a2a） monotherapy for chronic hepatitis C patients with strong predictors of sustained virologic response（SVR）.METHODS：Patients（n = 33） with genotype 2 and low viral load（〈 100 KIU/mL）,who became HCV RNA negative after 1 wk of IFN treatment,were randomly allocated to receive a 4-or 12-wk treatment course at a ratio of 2：1,respectively,with a subsequent 24-wk follow-up period.Peg-IFN-a2a was administered subcutaneously at a dose of 180 μg or 90 μg once weekly.SVR was defined as absence of serum HCV RNA at the end of the follow-up period.RESULTS：All patients completed the treatment schedule,and more than half were symptom-free during the treatment.In the 4-wk treatment group,20 of 22（91%） patients achieved SVR.Two patients relapsed,but achieved SVR following re-treatment with peg-IFN-a2a alone.In the 12-wk treatment group,11 of 11（100%） patients attained SVR.CONCLUSION：Our results show that a 4-wk course of peg-IFN-a2a monotherapy can achieve a high SVR rate in ＂IFN-sensitive＂ patients,without negatively affecting outcome.     

Clinical impact of genotype 1 TT virus infection in patients with chronic hepatitis C and response of TT virus to alpha-interferon

BACKGROUND: The relationship between genotype 1 TT virus (TTV) infection and the status of chronic hepatitis C was studied. METHODS: A total of 52 patients with chronic hepatitis C who were treated with interferon (IFN)-alpha were enrolled in the present study. Of those, 12 were infected with genotype 1 TTV and 40 were uninfected. RESULTS: Clinical backgrounds, including mean age, sex, blood transfusion history, serum alanine aminotransferase (ALT) level, and the results of liver biopsy did not differ between patients with and without genotype 1 TTV infection. The distribution of hepatitis C virus (HCV) genotypes did not differ between the two groups of patients, but TTV-infected patients tended to have a lower serum HCV-RNA level than uninfected patients (median (range) 26.0 (< 1-460) vs 135 (1.2-740) kilo copies/mL, respectively; P = 0.065). Patients with a sustained response of HCV to IFN-alpha were significantly more common in TTV-infected than -uninfected patients (58 vs 23%, respectively; P = 0.018). Multivariate logistic regression analysis revealed that patients with a sustained response of HCV correlated significantly with the serum HCV-RNA level (P = 0.006), but not with the presence or absence of genotype 1 TTV infection (P = 0.161). Serum TTV-DNA decreased with IFN-alpha therapy in all 12 patients and remained negative in six patients even after treatment. There was no correlation between patients with a sustained response of HCV and the same of TTV. Serum ALT levels correlated with changes in the status of HCV viremia, but not with changes in the status of TTV viremia. CONCLUSIONS: An opposing relationship between HCV and TTV proliferation was suggested, but coinfection with genotype 1 TTV did not affect the status of chronic hepatitis C.     

Distribution of different hepatitis C virus genotypes in patients with hepatitis C virus infection

AIM:To investigate the presence of mixed infection and discrepancy between hepatitis C virus(HCV) genotypes in plasma,peripheral blood mononuclear cells(PBMCs),and liver biopsy specimens.METHODS:From September 2008 up to April 2009,133 patients with chronic hepatitis C referred to Firouzgar Hospital for initiation of an antiviral therapy were recruited in the study.Five milliliters of peripheral blood was collected from each patient and liver biopsy was performed in those who gave consent or had indications...     

Insulin resistance is independently associated with significant hepatic fibrosis in Asian chronic hepatitis C genotype 2 or 3 patients

Background and Aim: The role of insulin resistance (IR) and hepatic steatosis in fibrogenesis in chronic hepatitis C infection (CHC) has yielded conflicting data and few studies have been performed in Asian‐region populations. We retrospectively investigated the relationship between host metabolic variables, including IR and hepatic steatosis, to hepatic fibrosis in Asian‐region CHC genotype 2/3 patients. Methods: A total of 303 treatment‐naïve Asian‐region patients with CHC genotype 2/3 were enrolled in a multicenter phase 3 study of albinterferon alfa‐2b plus ribavirin for 24 weeks. IR was defined as Homeostasis Model for Assessment of IR (HOMA‐IR) > 2. Baseline liver biopsy was evaluated by a single expert histopathologist. Post hoc subgroup logistic regression modeling selected for independent variables associated with significant fibrosis (METAVIR stage F2‐F4). Results: Insulin resistance was available in 263 non‐diabetic Asian‐region patients (hepatitis C virus‐2 [HCV‐2] = 171, HCV‐3 = 92), and 433 non‐Asian region patients (407 “Caucasian”); METAVIR fibrosis prevalence F0‐F1 (minimal fibrosis) = 201 (77%) and F2‐F4 (significant fibrosis) = 59 (23%), and steatosis prevalence of grade 0 = 169 (65%), grade 1 = 64 (25%), grade 2/3 = 27 (10%). Median HOMA‐IR was 1.8 (interquartile range: 1.2–2.7); 100 (38%) patients had HOMA‐IR > 2. Factors independently associated with significant fibrosis included HOMA‐IR (odds ratio [OR] = 8.42), necro‐inflammatory grade (OR = 3.17), age (OR = 1.07) and serum total cholesterol levels (OR = 0.008). This was similar to non‐Asian region patients, but steatosis was not associated with significant fibrosis in either cohort. Conclusions: In this subgroup study of Asian‐region HCV genotype 2 or 3 patients, insulin resistance, along with age, cholesterol levels and necro‐inflammation, but not steatosis may be associated with significant hepatic fibrosis.     

HCV基因型对慢性丙型肝炎干扰素疗效的影响

目的 探讨HCV基因型对慢性丙型肝炎的干扰素（IFN）治疗效果的影响。方法 采用随机、开放和对照的多中心临床试验设计。208例受试者按1：1随机分到聚乙二醇干扰素α—2a(Peg-IFN）组和IFN-α-2a组。在治疗之前，用Simmonds基因分型法酶切分型，在治疗24周结束和完成24周的随访后检测患者的ALT和HCV RNA，以HCV RNA的阴转率作为主要评价指标，经ITT人群的统计学分析。结果 202例患者确定了HCV基因型，基因1型158例（78.2%），非基因1型44例（21.8%），治疗结束病毒应答率（ETVR）和持续病毒应答率（SVR）基因1型患者分别为53.8%和25.3%，非基因1型患者分别为61.4%和43.2%，SVR两组患者差异有显著性，x^2=5.313,P=0.021。Peg IFN组基因1型和非1型患者的ETVR分别为76.8%和81.0%，SVR分别为35.4%和66.7%，SVR两组患者差异有显著性，x^2=6.735,P=0.01。病毒复发率基因1型和非基因1型患者分别为55.6%和23.5%，差异有显著性，x^2=5.496,P=0.02.IFN-α-2a组，ETVR和SVR基因1型患者分别为29.0%和14.5%，非基因1型患者分别43.5%和21.7%，差异无显著性。病毒复发率基因1型患者为72.7%，非基因1型患者为50.0%，差异无显著性。结论 IFN对基因1型丙型肝炎患者的疗效低于非基因1型，HCV基因型主要影响IFN对慢性丙型肝炎的持续应答，也与药物和IFN的疗程相关。