Mycophenolate mofetil treatment in patients with autoimmune hepatitis failing standard therapy with prednisolone and azathioprine.

BACKGROUND: Data on rescue treatment of autoimmune hepatitis in patients that fail standard treatment are sparse. AIMS: To report our long-term experience with mycophenolate mofetil. METHODS: Retrospective study in 22 patients with autoimmune hepatitis who failed azathioprine and prednisolone due to adverse events (n = 14, 64%), lack of remission (n = 5, 23%) or a combination (n = 3, 13%). RESULTS: Mycophenolate mofetil was started at a dose of 20 mg/kg/day and increased to a maximum of 3 g/day. Follow-up was 0-6 months in 7 patients; more than 12 months in 15 (68%) and more than 24 months in 10. Normal aminotransferase levels were obtained (n = 3) or maintained (n = 7) in 10 patients (45%) after three to 30 weeks. 12 patients (55%) were withdrawn during the first 6 months, due to adverse events. Three patients were switched to cyclosporine and one underwent liver transplantation. Successful treatment with mycophenolate mofetil continued in 10 patients (45%) for a median of 71 months (range 20-124). Of these, one stopped prednisolone, five have a prednisolone dose <5 mg daily and four patients 5-10 mg. CONCLUSION: Approximately one of two patients with autoimmune hepatitis that fail standard treatment benefit from long-term maintenance with mycophenolate mofetil, especially those with previous intolerance to thiopurines, where mycophenolate mofetil is effective in two thirds.

Increased hope following successful treatment for hepatitis C infection.

AIMS: To evaluate hope in hepatitis C patients 9 years after curative treatment with pegylated interferon and ribavirin. BACKGROUND: Successful treatment of hepatitis C leads to improved quality of life in responders compared with non-responders. The long-term effect of successful treatment on hope in these patients is not known. DESIGN: Cross-sectional follow-up study of patients who displayed a sustained virological response to previous hepatitis C treatment. METHODS: Patients infected with hepatitis C genotype 2 or 3 from a randomized controlled study during 2004-2006 were included. A representative subgroup of those who achieved a sustained virological response was re-evaluated in 2012-2014. The patients were examined, had a blood test and completed a questionnaire (Herth Hope Index and demographic and clinical characteristics). The hope level was compared between patients and an age-matched sample from the general population (N = 1,481). The data were analysed using multiple regression. RESULTS: A total of 104 Norwegian and Swedish hepatitis C patients were included in this follow-up study; their mean age was 48 years, and 61% were men. Patients treated for hepatitis C scored higher than the general population on the total Herth Hope Index and for 11 of the 12 individual items. Age, gender, educational level, employment status and civil status were associated with a higher Herth Hope Index in those who had received hepatitis C treatment. CONCLUSION: Patients achieving a sustained viral response had a higher hope level than the general population 9 years after successful treatment of hepatitis C virus infection.

Histological improvement of liver fibrosis in well-treated patients with autoimmune hepatitis: A cohort study.

Autoimmune hepatitis (AIH) is a chronic autoimmune liver disease that if left untreated may lead to the development of cirrhosis. Previous studies on AIH patients have suggested that fibrosis and even cirrhosis can be reversed by medical treatment. The aim of this study was to evaluate the efficacy of medical treatment for protection of developing fibrosis and cirrhosis.A total of 258 liver biopsies from 101 patients (72 women, 29 men) were analyzed by a single pathologist and classified according to the Ishak grading (inflammation) and staging (fibrosis) system. Liver histology was stratified according to the temporal changes of fibrosis stage (increased, decreased, or stable), and groups were compared.Complete or partial response to medical treatment was 94.9%. Reduction of fibrosis stage from the first to the last biopsy was seen in 63 patients (62.4%). We found an association between a reduction in the fibrosis stage and continuous glucocorticoid medication, as well as lowered scores of inflammation at last biopsy. Twenty-one patients had cirrhosis (Ishak stage 6) at least in one of the previous biopsies, but only 5 patients at the last biopsy.Histological improvement is common in AIH patients that respond to medical treatment, and a reduction or stabilization of fibrosis stage occurs in about 2/3 of such patients.

Epidemiology and causes of death in a Swedish cohort of patients with autoimmune hepatitis.

BACKGROUND: Epidemiological studies of autoimmune hepatitis (AIH) show varying figures on prevalence and incidence, and data on the long-term prognosis are scarce. Objective To investigate the epidemiology, long-term prognosis and causes of death in a Swedish AIH cohort. MATERIAL AND METHODS: Data collected from 634 AIH patients were matched to the Cause of Death Registry, and survival analyses were made. Prevalence and incidence were calculated for university hospitals with full coverage of cases and compared to the County of Västerbotten in Northern Sweden. RESULTS: AIH point prevalence was 17.3/100,000 inhabitants in 2009, and the yearly incidence 1990-2009 was 1.2/100,000 inhabitants and year. The time between diagnosis and end of follow-up, liver transplantation or death was in median 11.3 years (range 0-51.5 years). Men were diagnosed earlier (p < .001) and died younger than women (p = .002). No gender differences were found concerning transplant-free, overall survival and liver-related death. Cirrhosis at diagnosis was linked to an inferior survival (p < .001). Liver-related death was the most common cause of death (32.7%). The relative survival started to diverge from the general population 4 years after diagnosis but a distinct decline was not observed until after more than 10 years. CONCLUSIONS: Long-term survival was reduced in patients with AIH. No gender difference regarding prognosis was seen but men died younger, probably as a result of earlier onset of disease. Cirrhosis at diagnosis was a risk factor for poor prognosis and the overall risk of liver-related death was increased.

The Usefulness of Defining Rapid Virological Response by a Very Sensitive Assay (TMA) during Treatment of HCV Genotype 2/3 Infection.

The aim of this study was to determine in patients with HCV genotype 2 or 3 the performance at week 4 of two assays with different sensitivities for HCV RNA detection, for the prediction of SVR and stratification for treatment duration (14 and 24 weeks). Recruitment was from two trials comparing 14 and 24 weeks treatment to patients with rapid virological response (RVR) (n = 550). RVR was originally defined as HCV RNA <50 IU/ml at week 4. Patients with an available frozen plasma sample drawn at week 4 and with follow-up data week 24 post-treatment were included (n = 429). HCV-RNA was prospectively measured with COBAS Amplicor V2, Roche (CA) (lower detection limit 50 IU/ml) and retrospectively assessed with VERSANT HCV-RNA Qualitative Assay, Siemens (TMA) (lower limit detection 10 IU/ml). Genotype 3 was present in 80% and genotype 2 in 20%. A SVR was achieved in 82%. At week 4 HCV-RNA was undetectable in 74.8% and 63% of serum samples tested with CA and TMA, respectively. CA undetectable/TMA positive was observed in 61/341 (18%) of the samples. In genotype 3 patients a relapse was seen in 9% of the patients with both CA and TMA undetectable and in 25% of the patients who were CA undetectable/TMA positive (p = 0.006). In patients allocated to 14 weeks treatment a relapse was observed in 11% of TMA undetectable patients and 26% of TMA positive (p = 0.031). In genotype 2 patients treated for 14 weeks relapse was observed in 6% of the patients with both CA and TMA undetectable week 4. Assays with high sensitivity for HCV RNA identifies patients at week 4 with high risk of virological relapse. We recommend that patients with genotype 3 and detectable HCV RNA at levels below 50 IU/ml do not receive truncated therapy with pegIFN and ribavirin.

Peg-IFN and ribavirin treatment for recurrence of genotype 2 and 3 hepatitis C after liver transplantation.

BACKGROUND: Relapse of hepatitis C virus (HCV) infection after liver transplantation (LT) is universal. Tolerance for treatment with pegylated-interferon (peg-IFN) and ribavirin (RBV) is suboptimal and withdrawals due to adverse events frequent. We sought to improve tolerance for treatment to improve outcome. METHODS: We used concentration-guided RBV dosing to achieve an intended 10 µmol/L concentration with darbepoetin support in combination with peg-IFN alfa-2a, 180 µg for genotype 1 and 135 µg for genotype 2/3 to improve tolerance. RESULTS: A total of 51/54 patients (94%) completed a full treatment course. In the per-protocol analysis 43% of patients (22/51) achieved sustained virological response (SVR), 82% with HCV genotype 2/3 and 22% with genotype 1, p = 0.0001. Patients with IL28B CC achieved SVR in 73% (8/11) and patients with non-CC in 33% (14/43), p = 0.016. Patients with mild fibrosis (fibrosis stage 1-2) achieved SVR in 56% (15/27), and patients with advanced fibrosis (fibrosis stage 3-4) in only 26% (7/27), p = 0.0267. CONCLUSIONS: Concentration-guided RBV dosing with darbepoetin support substantially improves tolerance and offers high adherence to a full peg-IFN and RBV treatment course in patients with post-transplant HCV relapse. With this approach genotype 2 and 3 infections can be treated cost-effectively post-transplant. Genotype 1, IL28B non-CC genotype, and advanced fibrosis predicted a low SVR rate.

Hepatocellular and extrahepatic cancer in patients with autoimmune hepatitis--a long-term follow-up study in 634 Swedish patients.

OBJECTIVES: Cirrhosis is a well-known risk factor for hepatocellular cancer, but the true risk in autoimmune hepatitis (AIH) is scarcely studied. Other cancers may arise after prolonged use of immune-modulating drugs. The aim of this study was to investigate the cancer risk in a large cohort of AIH patients. MATERIAL AND METHODS: Six hundred and thirty-four Swedish patients in a well-defined cohort were matched to the Cause of Death Registry and the Cancer Registry. Standard incidence ratios were calculated by relating the incidences in the cohort to an age-matched material from the Swedish background population. RESULTS: A higher overall incidence of malignancies than the background population was found, counting from the date of diagnosis (standard incidence ratio (SIR) 2.08, 95% CI 1.68-2.55). The highest risk was found for hepatocellular carcinoma (HCC). We found 10 cases (4.0%) in 248 patients with cirrhosis, which gives an incidence rate of 0.3%. Standard incidence ratio for developing hepatobiliary cancer was 54.55 (95% CI 19.92-99.99). HCC only occurred in cirrhotic patients. There was also an increased risk for non-melanoma skin cancer (SIR 9.87, 95% CI 6.26-14.81). CONCLUSION: A slightly enhanced risk for malignancies in general compared to the background population was found. The risk of hepatobiliary cancer was increased, but the annual risk over the observational period was well under the postulated 1.5% when surveillance in cirrhotic patients is considered to be cost-effective.

A risk for hepatocellular carcinoma persists long-term after sustained virologic response in patients with hepatitis C-associated liver cirrhosis.

BACKGROUND: The long-term effect of sustained virologic response (SVR) to antiviral therapy on the risk of developing hepatocellular carcinoma (HCC), liver complications, liver-related death, and overall death in hepatitis C virus (HCV)-infected patients with liver cirrhosis is not fully known. METHODS: These risks were evaluated during long-term follow-up in 351 patients with HCV-related cirrhosis. One hundred ten patients with SVR, 193 with non-SVR, and 48 who were untreated were included in a multicenter cohort that was initiated in 2001 and prospectively followed up for a mean of 5.3 (SD, 2.8) years. Complementary follow-up data from national registries were used to minimize the loss of patients during follow-up. RESULTS: Six patients with SVR developed HCC at 0.04, 0.64, 2.4, 7.4, 7.4, and 7.6 years, respectively, after achieving SVR. The incidences of HCC, any liver complication, liver-related death, and overall death per 100 person-years were significantly lower in SVR time with 1.0, 0.9, 0.7, and 1.9, compared to 2.3, 3.2, 3.0, and 4.1 in non-SVR and 4.0, 4.9, 4.5, and 5.1 in untreated time. The long-term consequences did not decline significantly after >3 years versus during the first 3 years of follow-up. CONCLUSIONS: The risk for HCC, liver decompensation, and death in patients with liver cirrhosis related to HCV was markedly reduced after SVR, but a long-term risk of developing HCC remains for up to 8 years. Cirrhotic patients with HCV who achieve SVR should therefore maintain long-term surveillance for HCC. Future studies aimed to better identify those with remaining long-term risk for HCC are needed.

Genetic variants at the ITPA locus protect against ribavirin-induced hemolytic anemia and dose reduction in an HCV G2/G3 cohort.

OBJECTIVES: Two functional genetic variants in the inosine triphosphatase (ITPA) gene have been shown to be strongly associated with protection from ribavirin (RBV)-induced hemolysis. We aimed at evaluating this finding in a chronic hepatitis C genotype 2/3 cohort with a predominance of genotype 3 patients where available data are scarce. A second objective was to determine whether a protective association translated into the need for RBV reduction and hence a possible impact on treatment response. METHODS: Overall, 457 patients were recruited from two trials of genotype 2/3 patients treated with pegylated interferon α-2b and weight-based RBV. rs1127354 and rs7270101 were genotyped and a composite ITPAase deficiency variable was graded according to the two single nucleotide polymorphisms. The primary endpoints were hemoglobin (Hb) decline from baseline and Hb decline of more than 3 g/dl at week 4. RESULTS: Both single nucleotide polymorphisms and the composite ITPAase deficiency variable were strongly and independently associated with protection from a decline in Hb at week 4 in multivariate linear regression models (Prs1127354=7.0×10, Prs7270101=0.0036, PITPase deficiency variable =6.3×10). Patients with any degree of reduced ITPAase activity were less likely to have their RBV dose reduced (odds ratio 0.39, 95% confidence interval 0.16-0.96, P=0.040), although this did not translate into increased rapid viral response or sustained viral response (Prvr=0.93, Psvr=0.22). CONCLUSION: We have confirmed a strong association between functional ITPA variants and RBV-induced hemolysis and showed protection from RBV dose reduction, although this did not translate into increased rapid viral response or sustained viral response.

Infliximab or cyclosporine as rescue therapy in hospitalized patients with steroid-refractory ulcerative colitis: a retrospective observational study.

BACKGROUND: Cyclosporine (CsA) or infliximab (IFX) are used as rescue therapies in steroid-refractory, severe attacks of ulcerative colitis (UC). There are no data comparing the efficacy of these two alternatives. METHODS: Outcome of rescue therapy was retrospectively studied in two cohorts of patients hospitalized due to steroid-refractory moderate to severe UC: 1) a Swedish-Danish cohort (n = 49) treated with a single infusion of IFX; 2) an Austrian cohort (n = 43) treated with intravenous CsA. After successful rescue therapy, maintenance immunomodulator treatment was given to 27/33 (82%) of IFX patients and to 31/40 (78%) of CsA patients. Endpoints were colectomy-free survival at 3 and 12 months. Kaplan-Meier and Cox regression models were used to evaluate the association between treatment groups and colectomy. RESULTS: At 15 days, colectomy-free survival in the IFX cohort was 36/49 (73%) versus 41/43 (95%) in the CsA cohort (P = 0.005), at 3 months 33/49 (67%) versus 40/43 (93%) (P = 0.002), and at 12 months 28/49 (57%) versus 33/43 (77%) (P = 0.034). After adjusting for potential confounding factors, Cox regression analysis yielded adjusted hazard ratios for risk of colectomy in IFX-treated patients of 11.2 (95% confidence interval [CI] 2.4-53.1, P = 0.002) at 3 months and of 3.0 (95% CI 1.1-8.2, P = 0.030) at 12 months in comparison with CsA-treated patients. There were no opportunistic infections or mortality. CONCLUSIONS: Colectomy frequencies were significantly lower after rescue therapy with CsA than with a single infusion of IFX both at 3 and 12 months' follow-up. The superiority of CsA was seen principally during the first 15 days.

IL28B genetic variation and treatment response in patients with hepatitis C virus genotype 3 infection.

UNLABELLED: Polymorphisms near the IL28B gene, which code for interferon (IFN)-λ3, predict response to pegylated interferon-α (PEG-IFN) and ribavirin treatment in hepatitis C virus (HCV) genotype 1 infected patients. Follow-up studies of the effect of IL28B gene in HCV non-genotype 1 infected patients have almost always used predominantly HCV genotype 2-infected or mixed genotype 2/3-infected cohorts with results partly conflicting with HCV genotype 1. We performed a retrospective analysis of 281 patients infected with HCV genotype 3 for association of response to therapy with IL28B polymorphisms. We found that the HCV genotype 1 responder genotypes at rs12979860 and rs8099917 did not associate with sustained virological response to PEG-IFN/ribavirin therapy. However, the responder genotypes of both SNPs showed association with rapid viral response measured at 4 weeks (rs12979860, P = 3 × 10(-5) ; rs8099917, P = 3 × 10(-4) ). In multivariate analysis, age (<40 years), baseline viral load (<4 × 10(5) IU/mL) and the responder genotypes of SNPs rs12979860 or rs8099917 remained significant independent predictors of rapid viral response to therapy. Furthermore, we show that IL28B polymorphisms are associated with relapse in patients who achieve rapid viral response to PEG-IFN/ribavirin therapy. The responder genotypes also showed association with markers of stage and activity of liver disease, namely high aspartate aminotransferase platelet ratio index (APRI, rs12979860, P = 0.018; rs8099917, not significant) and high alanine aminotransferase (ALT, rs12979860, P = 0.002; rs8099917, P = 0.001), in addition to a high baseline viral load (rs12979860, P = 1.4 × 10(-5) ; rs8099917, P = 7.3 × 10(-6) ). CONCLUSION: Polymorphisms near the IL28B gene show association with rapid viral response but not sustained viral response to PEG-IFN/ribavirin therapy in HCV genotype 3-infected patients.

In patients with HCV genotype 2 or 3 infection and RVR 14 weeks treatment is noninferior to 24 weeks. Pooled analysis of two Scandinavian trials.

AIM: To compare 14 and 24 weeks treatment to patients with HCV genotype 2 or 3 infection and rapid virological response (RVR). MATERIALS AND METHODS: Patients included in two Scandinavian trials, one nonrandomized pilot trial (n=122) and one randomized controlled trial (RCT) (n=428) were entered into a pooled database. In both trials treatment naïve patients with genotype 2 or 3 were treated with pegylated interferon alpha 2b (1.5 microg/kg, subcutaneous) weekly and ribavirin (800-1400 mg, orally) daily. Primary endpoint was sustained virological response (SVR). RVR was defined as HCV RNA less than 50 IU/ml after 4 weeks of treatment. In the pilot trial all patients with RVR were treated for 14 weeks and in the RCT patients with RVR were randomised to either 14 or 24 weeks treatment. Patients treated per protocol were included in the primary analysis. The noninferiority margin was set to be 10% between the two groups with a one-sided 5% significance level. RESULTS: In patients with RVR and genotype 2 or 3 SVR was obtained in 181 of 199 (91.0%) and 93 of 98 (94.9%) after 14 and 24 weeks treatment, respectively. The observed difference in SVR rates was 3.9% (90% confidence interval: +1 to -8.8). The relapse rate was highest among those older than 40 years and those with genotype 3 and high viral load, but prolongation of treatment from 14 to 24 weeks did not reduce the relapse rate substantially in any of these groups. CONCLUSION: In patients with HCV genotype 2 or 3 infection and RVR 14 weeks treatment is noninferior to 24 weeks.

Characterisation and utility of thiopurine methyltransferase and thiopurine metabolite measurements in autoimmune hepatitis.

BACKGROUND & AIMS: Corticosteroids alone or in conjunction with azathioprine (AZA) is the standard treatment in autoimmune hepatitis (AiH). Individual variations in thiopurine (TP) metabolism may affect both drug efficacy and toxicity. Our aim was to investigate the utility of thiopurine methyltransferase (TPMT) as well as thioguanine nucleotide (TGN) and methylthioinosine monophosphate (meTIMP) metabolite measurements with regard to clinical outcome. METHODS: Two hundred thirty-eight patients with AiH were included in this cross-sectional study. TPMT status was assessed in all patients, while TGN and meTIMP were measured in patients with ongoing TP medication. Clinical outcome was evaluated by liver tests and the ability to withdraw steroids. RESULTS: TPMT genotyping (n=229) revealed 207 (90.4%) wild-type and 22 heterozygous patients. One hundred forty-three patients had ongoing TP therapy with AZA (n=134) or mercaptopurine (MP; n=9); response was judged as complete response (CR) in 113 patients and partial response (PR) in 30 patients. Both TP dose (1.64 vs 1.19 mg/kg; p=0.012) and TPMT activity (14.3 vs 13.5; p=0.05) were higher in PR, resulting in similar TGN levels (PR: 121 pmol/8 x 10(8) red blood cells [RBC]; CR: 113 pmol/8 x 10(8) RBC; p=0.33) but higher meTIMP levels in PR (1350 vs 400 pmol/8 x 10(8) RBC; p=0.004). Patients able to withdraw steroids or who were using 5 mg prednisolone daily were treated with lower TP doses than patients on higher steroid doses (1.15 vs 1.18 vs 1.82 mg/kg; p<0.001). CONCLUSIONS: TP metabolite measurements are of clinical value in AiH patients who do not respond to standard TP treatment and for the identification of a shifted metabolism, which may demand an alternative treatment strategy.

Health-related quality of life in patients with different stages of liver disease induced by hepatitis C.

OBJECTIVE: Patients with hepatitis C have been shown to have impaired health-related quality of life (HRQoL). The aim of this study was to determine HRQoL in patients in different stages of hepatitis C virus (HCV) and to compare HRQoL in HCV cirrhosis with non-HCV-induced cirrhosis. MATERIAL AND METHODS: Out of 489 consecutive patients who fulfilled the inclusion criteria, 472 (96%) agreed to participate in the study: 158 patients with mild/moderate fibrosis with chronic hepatitis C (CHC group), 76 patients with HCV compensated cirrhosis (CC), 53 patients with HCV decompensated (DC) cirrhosis, 52 non-cirrhotic patients with sustained viral response (SVR), and a control group consisting of 32 patients with non-HCV CC and 101 with non-HCV DC who completed the Short Form-36 (SF-36) and EQ-5D questionnaire. RESULTS: The CHC group had significantly lower SF-36 scores than healthy controls, with the exception of scores for the dimensions physical function and bodily pain. HCV patients with DC had lower scores in all SF-36 dimensions in comparison with those of the CHC group, as well as in physical and mental component summaries (p<0.001). In comparison with the CHC group, the HCV CC group had lower scores on the SF-36 general health dimension (p<0.05) and lower SF-36 physical component summary (PCS) scores (p<0.05). No major differences were seen in patients with HCV- and non-HCV-induced cirrhosis. CONCLUSIONS: Impairment in HRQoL in patients with HCV was associated with the severity of liver disease, patients with decompensated cirrhosis exhibiting the highest impairment in HRQoL. The etiology of liver disease does not seem to be important in determining HRQoL in cirrhosis.

Prospective study of nosocomial transmission of hepatitis C in a Swedish gastroenterology unit .

A prospective study of incident hepatitis C in 515 gastroenterology patients was conducted by follow-up sampling at 3-6 months after admission to the gastroenterology unit to test for antibodies to hepatitis C virus and for hepatitis C virus RNA. Universal precautions were implemented, and the use of multidose vials had been banned in this unit. Despite 5,964 exposure-days for several risk factors associated with nosocomial hepatitis C virus transmission, no incident case of hepatitis C occurred.

Prevalence of hepatitis C in Swedish diabetics is low and comparable to that in health care workers.

OBJECTIVES: An association between hepatitis C virus (HCV) infection and diabetes has been reported, in particular from countries with a high prevalence of HCV. To assess if this association could be found in a region with low prevalence of HCV (0.33%), we determined the prevalence of anti-HCV in a large cohort of patients with diabetes. METHODS: The prevalence of anti-HCV was determined with an enzyme-linked immunosorbent assay in 874 patients with diabetes representing 72.5% of a total research cohort of 1205 patients who were invited to participate. The results were confirmed with immunoblot. Samples from confirmed patients were tested for HCV RNA and genotyped. RESULTS: In 499 patients with type 1 diabetes and 375 patients with type 2 diabetes six patients were anti-HCV positive (four with type 1 diabetes and two with type 2 diabetes corresponding to a prevalence of 0.80 and 0.53%, respectively, in accordance with the prevalence among health care workers in Sweden; 0.68%). Liver biopsies in three of the patients showed only mild inflammation without fibrosis and in two of the other three the albumin and/or PT-INR level was normal contradicting any substantial impairment of the liver function. CONCLUSIONS: The low anti-HCV prevalence that we found contradicts an etiologic role of HCV in the development of diabetes in Sweden. The risk of being infected with HCV when attending the health care system seems to be rather small in a low-prevalence area.

Pegylated interferon alfa and ribavirin for 14 versus 24 weeks in patients with hepatitis C virus genotype 2 or 3 and rapid virological response.

UNLABELLED: A recent nonrandomized pilot trial showed that hepatitis C virus (HCV) patients with genotype 2/3 and rapid virological response (RVR) had a 90% sustained virological response (SVR) rate after 14 weeks of treatment. We aimed to assess this concept in a randomized controlled trial. In the trial, 428 treatment-naïve HCV RNA-positive patients with genotype 2 or 3 were enrolled. Patients with RVR were randomized to 14 (group A) or 24 (group B) weeks of treatment. Patients were treated with pegylated interferon alpha-2b (1.5 microg/kg) subcutaneously weekly and ribavirin (800-1400 mg) orally daily. The noninferiority margin was set to be 10% between the two groups with a one-sided 2.5% significance level. RVR was obtained in 302 of 428 (71%), and 298 of these were randomized to group A (n = 148) or group B (n = 150). In the intention-to-treat analysis, SVR rates were 120 of 148 (81.1%) in group A and 136 of 150 (90.7%) in group B (difference, 9.6%; 95% confidence interval, 1.7-17.7). Among patients with an HCV RNA test 24 weeks after the end of treatment, 120 of 139 (86.3%) patients in group A achieved SVR compared with 136 of 146 (93.2%) in group B (difference, 6.9%; 95% confidence interval, -0.1 to +13.9). CONCLUSION: We cannot formally claim that 14 weeks of treatment is noninferior to 24 weeks of treatment. However, the SVR rate after 14 weeks of treatment is high, and although longer treatment may give slightly better SVR, we believe economical savings and fewer side effects make it rational to treat patients with genotype 2 or 3 and RVR for only 14 weeks.