Is positivity for hepatitis C virus antibody predictive of lower risk of death in COVID-19 patients with cirrhosis?

Liver injury has been reported in coronavirus disease 2019 (COVID-19) cases but the impact of pre-existing liver damage and related etiology have not been completely elucidated. Our research interests include the potential reciprocal influence of COVID-19 and pre-existing liver damage related to hepatitis C virus (HCV) infection, in particular. To this end, we have evaluated three cohorts of patients admitted at three Italian hospitals during the coronavirus pandemic; these included 332 patients with COVID-19 and 1527 patients with HCV who were from established real-world antiviral treatment study cohorts (sofosbuvir/velpatasvir), with either liver disease (various severities; n = 1319) or cirrhosis (n = 208). Among the COVID-19 patients, 10 had cirrhosis (3%), including 7 of metabolic origin and 3 of viral origin. Mortality among the COVID-19 patients was 27.1%, with 70% of those with cirrhosis of metabolic etiology having died. Cirrhosis, older age, low white blood cell count and lymphocyte count being identified as risk predictors of death [odds ratio (OR) = 13.7, 95% confidence interval (CI): 2.59-83.01, P = 0.006; OR = 1.05, 95%CI: 1.03-1.08, P = 0.0001; OR = 1.09, 95%CI: 1.36-1.16, P = 0.001; OR = 0.61, 95%CI: 0.39-0.93, P = 0.023, respectively]. In the two cohorts of HCV patients, COVID-19 diagnosis was made in 0.07% of those with liver disease and 1% of those with cirrhosis. Thus, the prevalence of HCV antibodies among COVID-19-infected patients was comparable to that currently reported for the general population in Italy. Amongst the COVID-19 patients, pre-existing metabolic cirrhosis appears to be associated with higher mortality, while HCV antibodies may be suggestive of "protection" against COVID-19.

Correction: SVR12 rates higher than 99% after sofosbuvir/velpatasvir combination in HCV infected patients with F0-F1 fibrosis stage: A real world experience.

[This corrects the article DOI: 10.1371/journal.pone.0215783.].

SVR12 rates higher than 99% after sofosbuvir/velpatasvir combination in HCV infected patients with F0-F1 fibrosis stage: A real world experience.

BACKGROUND AND OBJECTIVES: The pangenotypic single tablet regimen of NS5B inhibitor sofobuvir (SOF) and NS5A inhibitor velpatasvir (VEL) is advised for 12 weeks in HCV-infected patients including those with compensated cirrhosis. Addition of ribavirin (RBV) may be considered in genotype 3 (GT3) with compensated and is recommended in decompensated cirrhosis. Real-life results with SOF/VEL are limited. To evaluate efficacy and safety in a large real-world-cohort including patients with different GTs and various fibrosis stages. DESIGN: In total, 1429 patients were treated with SOF/VEL 400/100 mg for 12 weeks in the Puglia registry between June 2017 and May 2018. 1319 (92.3%) reached week 12 post-treatment (SVR12) at the moment. Only 41 received RBV. Diagnosis of cirrhosis was based on transient elastography and/or APRI or FIB-4 scores. Sensitivity analysis in the population including all patients except non virological failure was conducted. Primary efficacy endpoint was the percentage of patients with SVR12. RESULTS: Patients' mean age was 63.8 years, 42.3% had GT1. The majority were naïve and 735 (55.5%) F0/F2. Of the remaining 587, 282 had cirrhosis. SVR12 was 98.5%, 98.0% in GT1, 99.4% in GT2, 97.1% in GT3, 100% in GT4. Overall, SVR12 by sensitivity analysis was 99.4%; 99.7% among F0-F1. Among 218 PWID, SVR12 was 94.5%. Discontinuation rates were 3.7% among PWID and 0.7% among non-PWID (p = 0.004). CONCLUSIONS: SOF/VEL treatment of chronic HCV infection reaches very high cure rates in a variety of patients; including those with F0/F1 and PWID.

Real life rates of sustained virological response (SVR) and predictors of relapse following DAA treatment in genotype 3 (GT3) patients with advanced fibrosis/cirrhosis.

BACKGROUND: Treatment of GT3 remains challenging compared to other genotypes. AIMS: To explore real life SVR rates and to identify predictors of virological failure across the most recently used Direct acting antiviral (DAA) regimens in a large cohort of Italian patients with cirrhosis or advanced fibrosis (F3 or F4). METHODS: Between May 2015 and June 2017, the combinations of sofosbuvir (SOF) plus daclatasvir (DCV) ± RBV and SOF plus velpatasvir (VEL) ± RBV become available in our Country. Patients were treated following Italian guidelines within a protocol implemented by 11 centers working together on genetics. RESULTS: Of 336 patients, 38.1% were Peg/IFN-experienced. SOF/DCV was used in 65.1%, SOF/VEL in the remaining. Overall SVR12 was 90.2% ranging from 87.2% after SOF/DCV to 95.7% after SOF/VEL (p = 0.012). No additional benefits of RBV use were observed for both regimens. 155 patients (46.1%) had cirrhosis. SVR12 was 87.1% (135/155) for cirrhotic patients and 92.8% (169/182) for non-cirrhotic (p = 0.09). NS5A-RASs were present at baseline in 6.4% of patients, PNPLA3GG and IL28BCC genotypes in 7.3% and 33.0%, respectively. No association between favorable genetics and SVR12 was observed. Predictors of relapse were: history of Peg/IFN/RBV failure (OR = 6.34, 95% CI 2.04-19.66, P = .001), baseline NS5A-RASs (OR = 8.7, 95% CI 1.58-47.92, P = 0.013) and treatment regimen (OR = 5.57 95% CI 1.64-18.95.96, P = 0.006). CONCLUSIONS: Our real-world results validate the efficacy of current GT3 IFN-free regimens suggesting that, among patients with severe disease, Peg/IFN/RBV experience and NS5A associated RASs are predictors of relapse. Their relevance can be expected to decline with the use of SOF/VEL. (250).

Hepatitis C and immigration: a multicentre study.

This retrospective multicentre study aims to evaluate the clinical and epidemiological features of HCV infection in a cohort of immigrants in Italy. Tests were carried out on 194 HCV positive subjects, who represented 5.7% of the participants at baseline screening: the virological (viral load, genotype) and biochemical appearance of their infection was determined, and the disease was staged by histological examination in the patients who had indicated their willingness. Standard therapy (peg-interferon + ribavirin) was implemented in patients who agreed to undergo treatment. The majority of immigrants were of East-European origin (48.4%), females were globally slightly predominant and the average age was 41.4 years. Of the 194 patients, 119 (63.1%) proved to be viraemic: genotype 1 was the most frequent, followed by genotype 4, the latter mainly in African patients. The histological staging of liver disease conducted in 25 patients showed mild hepatitis in 13 subjects, moderate/severe hepatitis in eight subjects and cirrhosis in four. Although 45 out of 119 patients (37.8%) with determinable HCV RNA agreed to undergo treatment, 11 of them independently stopped taking medication before the course of therapy was completed, without any significant side effects. At the sixth month of follow-up, the overall sustained virological response (SVR) was shown by 22/45 patients (48.8%). In our study, migrant populations had higher rates of HCV-related chronic hepatitis than the indigenous population; in some cases the infections were contracted in the country of origin, but in others the infection took place in Italy. The most commonly represented genotype, besides 1, was 4, especially among Africans. The therapeutic management of immigrants proved to be very difficult, mostly but not exclusively because of social factors.

Interleukin-28B genetic variants in untreated Italian HCV-infected patients: a multicentre study.

BACKGROUND & AIMS: Different prevalence of favourable IL28BCC genotype have been reported in studies performed in different countries around the world. Data on distribution of IL28B genotypes in healthy Italian subjects are lacking. METHODS: Studies on prospectively collected untreated chronic HCV-infected Italian patients led to conflicting results. To investigate the prevalence of IL28B genotypes in untreated HCV-infected patients and in subjects able to clear HCV, and to compare them to the prevalence registered in healthy Italian controls. To evaluate IL28B prevalence across different HCV genotypes. RESULTS: IL28BCC was observed in 30.9% of chronic HCV patients, in 71.0% of subjects able to clear HCV infection and in 41.6% of the Italian controls. The frequency of IL28BCC was higher in HCV genotype 2 and 3 than in 1 (38.3 vs. 28.2) (P = 0.02). Levels of ALT higher in IL28BCC than in non-CC were observed regardless of HCV genotypes (P = 0.0014). CONCLUSIONS: IL28BCC frequencies progressively decline from subjects with spontaneous HCV clearance to normal non-infected subjects and to chronically infected. This study suggests that patients with IL28BCC, if genotype 1, are able to clear HCV more often than if genotype 2 and 3 infected, and that CC genotype is associated with higher grade of necro-inflammation.

Individualized treatment of genotype 1 naïve patients: an Italian multicenter field practice experience.

BACKGROUND: Triple therapy including Telaprevir or Boceprevir still represents in many European countries the standard of care for patients with Hepatitis C Virus genotype 1 infection. The number of patients who received this treatment resulted generally lower than expected. We investigated, among naïve patients, number and characteristics of treatment candidates who were started on triple or dual therapy in comparison to those who were deferred. PATIENTS AND METHODS: 621 naïve treatment candidates were prospectively evaluated at each center. Factors associated with decision to defer or treat with dual or triple therapy were investigated by univariate and multivariate analyses. Rates of Sustained Virological Response and safety profile were analysed. RESULTS: Of candidates to treatment, 33% did not received it. It was mostly due to high risk of Interferon-induced decompensation. Of 397 patients who were started on treatment, 266 (67%) received triple, 131 dual. Among patient receiving treatment, unfavorable IL28B, severe liver damage and higher albumin were independently associated with the physician decision to administer triple therapy. Sustained Virological Response after dual therapy was 66.4%, after triple 73.7% (p = 0.14). 142 patients received Telaprevir. The choice of Telaprevir-based therapy was associated with higher Body Mass Index and advanced liver disease. Sustained Virological Response rates were 71.1% after Telaprevir and 76.6% after Boceprevir. CONCLUSIONS: Individualizing treatment with available regimens allows to maximize Sustained Virological Response and to reduce the number of patients who remain untreated. High proportion of patients with severe liver damage urgently need Interferon free treatment.

Feasibility of pegylated interferon and ribavirin in hepatitis C-related cirrhosis with neutropenia or thrombocytopenia.

AIM: To investigate the feasibility of pegylated interferon plus ribavirin treatment in cirrhotic patients who presented with, or developed while on-treatment, platelet counts ≤ 80,000/µL and/or neutrophil counts ≤ 1,500/µL. METHODS: A retrospective analysis of prospectively gathered data on 123 cirrhotic patients treated with pegylated interferon and ribavirin. Adverse effects and haematological changes were monitored: bleeding and infectious events were registered and related to platelet and absolute neutrophil counts. RESULTS: Among the 58 patients (47.2%) with nadir platelets ≤ 50,000/µL during therapy, 6 (10.3%) experienced a bleeding episode; of the remaining 65 patients with platelets constantly >50,000/µL, 3 (4.6%) bled. Of the 11 bleedings, 3 manifested during an infection, while patients had platelets >50,000/µL. Nadir neutrophils ≤ 750/µL occurred in 45 patients (38.2%) during treatment, and 14 of them (29.8%) had an infectious event. Infections were also documented in 18 of the 76 patients (23.7%) with neutrophils constantly >750/µL. CONCLUSIONS: The study reveals the feasibility of treating cirrhotic patients with cytopenia with pegylated interferon and ribavirin, as bleeding or infectious events under therapy were unrelated to platelet and neutrophil counts. Withdrawal of therapy or variations in the pre-assigned dosages of either pegylated interferon or ribavirin owing to abnormally low haematological parameters seems to no longer be tenable.

Limited use of interleukin 28B in the setting of response-guided treatment with detailed on-treatment virological monitoring.

UNLABELLED: A single-nucleotide polymorphism upstream of the interleukin-28B (IL28B) gene is associated with pegylated interferon-alfa-induced viral clearance in hepatitis C virus (HCV) genotype 1 patients. Using a well-characterized cohort of patients randomized to standard versus response-guided therapy, we studied whether the favorable CC type allows shortening of treatment duration. Association with viral kinetics, sustained viral response (SVR), and predictors of response were also analyzed. In the original study, 696 patients were randomized to either standard or variable therapy of 24, 48, or 72 weeks according to first undetectable HCV RNA. Association between IL28B determined by genotyping rs12979860 and end of treatment response and SVR by treatment arm was tested; baseline predictors of response were analyzed using multiple logistic regression. A total of 454 patients were evaluated. The frequency of IL28B type was CC = 29%, CT = 53%, TT = 18%. CC type was strongly associated with rapid virological response (RVR) as well as higher rates of week 8 and week 12 response. CC type was associated with SVR in both arms. In patients with RVR, SVR was high and IL28B type was not associated with SVR. In RVR patients, there was no significant difference in SVR or relapse rates after 24 or 48 weeks by IL28B type. Among non-RVR patients, CC type was associated with SVR at a higher rate than CT/TT, both in standard and variable analysis. However, when week 8 and week 12 responders were considered separately, IL28B type was no longer predictive of SVR. Few CC patients remained viremic beyond week 8 to allow the analysis of relationships between IL28B type and extended treatment. CONCLUSION: In HCV-1 patients, the favorable CC type strongly predicted higher rates of on-treatment virological milestones and SVR. However, achievement of on-treatment virological milestones was the critical factor in determining outcome. IL28B type appeared to have limited potential for response-guided treatment strategies.

Individualized treatment with combination of Peg-interferon alpha 2b and ribavirin in patients infected with HCV genotype 3.

BACKGROUND & AIMS: The benefit of individualizing treatment for patients with genotype 3 HCV infection on the basis of viral clearance at week 4 (wk4-R) has not been firmly established. METHODS: Four hundred and fourteen patients received Peg-interferon alpha-2b plus 1000-1200 mg of ribavirin daily according with body weight > or <75 kg. Patients were randomized to standard 24 weeks (Std24) or to a 12 or 36 weeks variable treatment duration (Var12/36). In the variable treatment arm, patients with or without wk4-R were allocated to either 12 or 36 weeks duration. RESULTS: At treatment week 4, HCV RNA was undetectable in 262 patients (63.3%), 136 in the Std24, and 126 in the Var12/36 group (p=0.41). In patients with wk4-R, end-of-treatment (EOT) responses were 80.4% (CI 85.4-95.3) and 97.6% (CI 94.9-99.9) in the two arms, respectively (p=0.019). In patients without wk4-R, corresponding rates were 61.9% (50.6-73.2) and 75.3% (CI 65.9-84.6) (p=0.08). SVR was attained in 302 patients, 71.4% (CI 65.3-77.6) in the St24 group and 74.3% (CI 58.4-80.3) in the variable 12/36 arm. Among patients with wk4-R, SVR was 81.6% (CI 75.1-88.1) and 82.5% (75.9-89.1), respectively. In patients without wk4-R, SVR amounted to 52.1% (CI 40.4-63.7) and 61.7 (CI 51.1-72.3) in the two arms (p=0.25). CONCLUSIONS: HCV genotype 3 patients with week4-R may be treated safely with 12 weeks of therapy, provided that sufficiently high doses of ribavirin are administered. For patients still viremic at treatment week 4, SVR rates were numerically higher after 36 weeks of treatment than after the currently recommended 24 weeks.

An IL28B polymorphism determines treatment response of hepatitis C virus genotype 2 or 3 patients who do not achieve a rapid virologic response.

BACKGROUND & AIMS: Polymorphisms in the region of the interleukin (IL)-28B gene on chromosome 19 have been associated with peginterferon-alfa-induced clearance of genotype 1 hepatitis C virus (HCV); there are no data for patients with genotype 2 or 3 HCV. We evaluated the effects of IL-28B polymorphisms on response to treatment with peginterferon and ribavirin in a well-characterized cohort of genotype 2/3 patients. METHODS: DNA was analyzed from 268 patients (Caucasian: genotype 2, 213; genotype 3, 55). Patients were randomly assigned to groups that received standard duration (24 wk; n = 68) or variable durations of therapy. Patients who received variable durations (VD) and had a rapid virologic response (RVR) were treated for 12 weeks (VD12; n = 122); those without an RVR were treated for 24 weeks (VD24; n = 78). IL-28B genotypes (rs12979860) were analyzed for association with treatment response. RESULTS: The frequencies of the IL-28B genotypes were as follows: CC, 37%; CT, 48%; and TT, 15%; 82% of patients with the CC genotype achieved a sustained virologic response (SVR), compared with 75% with the CT and 58% with the TT genotypes (P = .0046). Differences between IL-28B genotypes were greatest among patients who failed to attain RVR (VD24 SVR rates: CC, 87%; CT, 67%; and TT, 29%; P = .0002). Among patients with RVRs (61%), the IL-28B genotype was not associated with SVR (>70% for all IL-28B genotypes). In a multivariable logistic regression model, IL-28B genotype predicted SVR (odds ratio, 1.76; 95% confidence interval, 1.16-2.7). CONCLUSIONS: An IL-28B polymorphism was associated with an SVR in patients infected with genotype 2/3 HCV who did not achieve a RVR. Analysis of IL-28B genotype might be used to guide treatment for these patients.

Determinants of relapse after a short (12 weeks) course of antiviral therapy and re-treatment efficacy of a prolonged course in patients with chronic hepatitis C virus genotype 2 or 3 infection.

UNLABELLED: In hepatitis C virus (HCV) genotypes 2 and 3 patients, the high rate of relapse after 12 to 16 weeks of antiviral therapy is the main concern for shortening treatment duration. This study was undertaken to delineate predictors of relapse after short treatment in patients with undetectable HCV RNA at treatment week 4 (RVR), and to report in RVR patients with relapse the sustained virological response (SVR) after a second 24-week course of therapy. RVR patients received pegylated interferon (Peg-IFN) alfa-2b (1.5 microg/kg) and ribavirin (1000-1200 mg/day) for 12 weeks; those who relapsed were re-treated with the same drug doses but for the extended standard duration of 24 weeks. Logistic regression analysis was applied to delineate predictors of relapse by using age, sex, route of transmission, body mass index (BMI), serum alanine aminotransferase (ALT), HCV genotypes, serum HCV RNA levels, and platelet counts as covariates. Of 718 patients with genotypes 2 and 3 who were started on therapy, 496 (69.1%) had undetectable HCV RNA at week 4. Of them, 409 patients (82.5%, CI 79.1-85.8) attained SVR, and 67 (14.1%, CI 10.4-16.5) relapsed. At regression analysis, only platelet count less than 140,000 mm(3) [odds ratio, 2.51; confidence interval (CI), 1.49-4.20] and BMI 30 or higher (odds ratio, 1.7; CI, 1.03-2.70) were independently associated with relapse. Forty-three of 67 patients with relapse agreed to be re-treated, and an SVR was achieved in 30 (70.0%) of them. CONCLUSION: We recommend 12 weeks course of therapy for patients with undetectable HCV RNA at treatment week 4, providing they present with no advanced fibrosis and low BMI.

Individualized treatment duration for hepatitis C genotype 1 patients: A randomized controlled trial.

UNLABELLED: It was hypothesized that in hepatitis C virus (HCV) genotype 1 patients, variable treatment duration individualized by first undetectable HCV RNA is as effective as standard 48-week treatment. Patients (n = 696) received peginterferon alfa-2a, 180 mg/week, or peginterferon alfa-2b, 1.5 mg/kg/week, plus ribavirin, 1000-1200 mg/day, for 48 weeks (standard, n = 237) or for 24, 48, or 72 weeks if HCV-RNA-negative at weeks 4, 8, or 12, respectively (variable, n = 459). Sustained virologic response (SVR) was achieved in 45.1% [95% confidence interval (CI) 38.8-51.4] of the patients in the standard group and in 48.8% (CI 44.2-53.3) of the patients in the variable group (P = 0.37). The percentages of patients who first achieved undetectable HCV RNA at weeks 4, 8, or 12 were 26.7%, 27.8%, and 11.3%, respectively. In the standard treatment group, 87.1%, 70.3%, and 38.1% of patients who first achieved undetectable HCV RNA at 4, 8, or 12 weeks attained SVRs, respectively. In the variable group, corresponding SVR rates were 77.2%, 71.9%, and 63.5%. Low viremia levels and young age were independent predictors of response at week 4 [rapid virologic response (RVR)]. RVR patients with baseline viremia >or=400,000 IU/mL achieved higher SVR rates when treated for 48 weeks rather than 24 weeks (86.8% versus 73.1%, P = 0.14). The only predictive factor of SVR in RVR patients was advanced fibrosis. CONCLUSION: Variable treatment duration ensures SVR rates similar to those of standard treatment duration, sparing unnecessary side effects and costs.

A case of vacuolar myopathy during the course of chronic hepatitis C.

Several cases of inflammatory myopathy have been reported during the chronic course of hepatitis C (HC) in recent years. It has been suggested that this muscular inflammatory involvement in HC is related to an immune-mediated mechanism caused by the hepatitis C virus (HCV), as HCV RNA has been detected in the muscle of patients with concomitant inflammatory myopathy and chronic HC. Herein, we report on a patient with a history of chronic HC, who developed a slowly progressive proximal muscle weakness; muscle biospy revealed a vacuolar myopathy. Histological, immunohistochemical and biochemical study did not disclose any known cause of vacuolar myopathy. To our knowledge, this is the first report of a vacuolar myopathy during the course of HC. We suggest that it may be opportune to include HC among the possible aetiologies of vacuolar myopathy, should other reports confirm this association.

Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3.

BACKGROUND: We hypothesized that in patients with hepatitis C virus (HCV) genotype 2 or 3 in whom HCV RNA is not detectable after 4 weeks of therapy, 12 weeks of treatment is as effective as 24 weeks. METHODS: A total of 283 patients were randomly assigned to a standard 24-week regimen of peginterferon alfa-2b at a dose of 1.0 mug per kilogram weekly plus ribavirin at a dose of 1000 mg or 1200 mg daily, on the basis of body weight. Of these, 70 patients were assigned to the 24-week regimen (standard-duration group) and 213 patients to a variable regimen (variable-duration group) of 12 or 24 weeks, depending on whether tests for HCV RNA were negative or positive at week 4. The primary end point was HCV that was not detectable by polymerase-chain-reaction (PCR) assay 24 weeks after the completion of therapy. RESULTS: In the standard-duration group, 45 (64 percent) patients had HCV that was not detectable by PCR assay at week 4, as compared with 133 (62 percent) in the variable-duration group (difference [the rate in the standard-duration group minus that in the variable-duration group], 2 percent; 95 percent confidence interval, -11 to 15 percent). Fifty-three patients (76 percent) in the standard-duration group and 164 patients (77 percent) in the variable-duration group had a sustained virologic response (difference, -1 percent; 95 percent confidence interval, -13 to 10 percent). Fewer patients in the variable-duration group receiving the 12-week regimen had adverse events and withdrew than in the group receiving the 24-week regimen (P=0.045). The rate of relapse (defined as HCV not detectable at the end of treatment but detectable at the end of follow-up) was 3.6 percent in the standard-duration group and 8.9 percent in the variable-duration group (P=0.16). Overall, the rate of sustained virologic response was 80 percent among patients with HCV genotype 2 and 66 percent among those with genotype 3 (P<0.001). CONCLUSIONS: A shorter course of therapy over 12 weeks with peginterferon alfa-2b and ribavirin is as effective as a 24-week course for patients with HCV genotype 2 or 3 who have a response to treatment at 4 weeks.

High doses of interferon in combination with ribavirin are more effective than the standard regimen in patients with HCV genotype 1 chronic hepatitis.

BACKGROUND/AIMS: The aim of the present, open-labelled, controlled study was to determine whether 5 MU of interferon (IFN) alpha 2b combined with a standard dose of ribavirin might increase the rate of viral clearance in all patients with chronic HCV hepatitis or at least in those with an unfavourable genotype. METHODS: A total of 298 previously untreated patients with chronic hepatitis C were randomized to 5 or 3 MU of interferon alpha 2b 3 times per week with 1000-1200 mg of ribavirin daily (148 and 150 patients, respectively). Patients were treated for 12 months and observed for 6 months posttreatment. RESULTS: In patients infected with HCV genotype 1, the sustained virologic response was 37.8% (95% CI 27.3-48.1) with IFN 5 MU and 19.2% (95% CI 10.1-28.2) with IFN 3 MU (P=0.008). Out of 45 sustained responders with genotype 1, 31 (69%) had received 5 MU and 14 (31.1%) the standard 3 MU dose of IFN in combination with ribavirin (P=0.01). Of the 86 responders infected with genotype non-1, 39 (45.3%) were from the 5 MU IFN group and 47 (54.6%) were from the 3 MU IFN group; these figures were not significant. At the multivariate analysis of baseline features for all patients, the variables with an independent effect for a sustained response were genotype non-1 (odds ratio (OR) 3.98, 95% CI 2.36-6.40), and the histological grading (score 0-2) (OR 2.48, 95% CI 1.12-5.51) and staging (score 0-1) (OR 1.73, 95% CI 1.02-2.95). For patients with genotype 1 only the high regimen of IFN entered the model (OR 2.39, 95% CI 1.13-5.05), whereas for patients with genotype non-1 an age of <40 years (OR 2.64, 95% CI 1.23-5.70) and staging (score 0-1) (OR 2.38, 95% CI 1.07-5.28) were independent predictors of a sustained response. CONCLUSIONS: Our study suggests that when treating naive patients with genotype 1, there is a significant increase in the rate of sustained virologic clearance by increasing the dose of IFN given in combination with ribavirin.