Prophylactic Proton Pump Inhibitors in Upper Gastrointestinal Bleeding: Impact and Underprescription in a French Multicentric Cohort.

BACKGROUND: Appropriate prescription of Proton pump inhibitors (PPIs) remains an important concern amid the rising overuse. A gap exists in the literature regarding the benefit of PPI prophylaxis and the consequences of underprescription in patients at risk for upper gastrointestinal bleeding (UGIB). AIMS: This study aims to describe the characteristics of hemorrhage in relation to PPI use in patients experiencing UGIB, with a focus on high-risk individuals requiring gastroprotection. METHODS: Data from a French multicentric cohort of patients experiencing UGIB were analyzed. Patients using PPI were compared to those without PPI considering bleeding etiologies and outcomes of peptic ulcer disease (PUD)-related hemorrhage. The rate of PPI use and its effect on bleeding characteristics in high-risk populations, defined based on international guidelines, were also assessed. RESULTS: Among 2497 included patients, 31.1% were on PPI at bleeding onset. PPI users exhibited a significantly lower rate of PUD-related bleeding in comparison with those without PPI (24.7 vs 40.8%, respectively, p < 0.0001). Similar difference was observed in high-risk populations, of whom, only 40.3% had gastroprotection with PPI before bleeding onset. PPI prophylaxis, however, did not influence the severity of bleeding in the general study population or in high-risk groups. Multivariate analysis identified age, comorbidities, and having more than two anti-thrombotic agents as predictors of severe bleeding. CONCLUSIONS: PPI users appear to have a lower rate of bleeding ulcers compared to non-users. However, underprescription in high-risk groups raises the need for standardized care to ensure appropriate PPI use.

Treatment with bulevirtide in HIV-infected patients with chronic hepatitis D: ANRS HD EP01 BuleDelta and compassionate cohort.

Background & Aims: In France, bulevirtide (BLV) became available in September 2019 through an early access program to treat patients with HDV. The aim of this analysis was to evaluate the efficacy and safety of BLV in patients with HIV and HDV coinfection. Methods: Patients received BLV 2 mg ± pegylated interferon-α (pegIFNα) according to the physician's decision. The primary endpoint (per-protocol analysis) was the virological response rate at Week 48, defined as the proportion of patients with undetectable serum HDV RNA or a HDV RNA decline >2 log10 IU/ml from baseline. Results: The characteristics of the 38 patients were as follows: 28 male, mean age 47.7 years, and mean baseline HDV RNA viral load 5.7 ± 1.2 log10 IU/ml. Median HIV viral load and mean CD4 count were 32 (30-65) copies/ml and 566 ± 307/mm3, respectively. Eight patients stopped treatment before Week 48. At Week 48, 10 of 19 patients (52.6%) in the 2 mg BLV group and five of seven patients (71.4%) in the 2 mg BLV + pegIFNɑ group had reached virological response (no HDV RNA available in four patients). At Week 48, seven of 19 patients in the 2 mg BLV group and three of six patients in the 2 mg BLV + pegIFNɑ group had a combined response (virological response and normal alanine aminotransferase level). Conclusions: Adults living with HIV coinfected with HDV can be treated by BLV with a virological response in more than 50% of patients. The combination of BLV and pegIFNɑ showed a strong virological response. Impact and implications: Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug-drug interaction is reported. Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug-drug interaction is reported. Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug-drug interaction is reported.

Hepatitis B Delta: assessment of the knowledge and practices of hepato-gastroenterologists practicing in non-academic settings in France.

BACKGROUND: Data on the management of Hepatitis B-Delta (HB-D) by hepatogastroenterologists (HGs) practicing in nonacademic hospitals or private practices are unknown in France. OBJECTIVE: We aimed to evaluate the knowledge and practices of HGs practicing in nonacademic settings regarding HB-D. METHODS: A Google form document was sent to those HGs from May to September 2021. RESULTS: A total of 130 HGs (mean age, 45 years) have participated in this survey. Among HBsAg-positive patients, Delta infection was sought in only 89% of cases. Liver fibrosis was assessed using FibroScan in 77% of the cases and by liver biopsy in 81% of the cases. A treatment was proposed for patients with >F2 liver fibrosis in 49% of the cases regardless of transaminase levels and for all the patients by 39% of HGs. Responding HGs proposed a treatment using pegylated interferon in 50% of cases, bulevirtide in 45% of cases and a combination of pegylated interferon and bulevirtide in 40.5% of cases. Among the criteria to evaluate the treatment efficacy, a decrease or a normalization of transaminases was retained by 89% of responding HGs, a reduction of liver fibrosis score for 70% of them, an undetectable delta RNA and HBsAg for 55% of them and a 2 log 10 decline in delta viremia for 62% of the cases. CONCLUSION: Hepatitis Delta screening was not systematically performed in HBsAg-positive patients despite the probable awareness and knowledge of the few responders who were able to prescribe treatments of hepatitis delta.

Prognostic factors associated with upper gastrointestinal bleeding based on the French multicenter SANGHRIA trial.

Background and study aims Prognostic and risk factors for upper gastrointestinal bleeding (UGIB) might have changed overtime because of the increased use of direct oral anticoagulants and improved gastroenterological care. This study was undertaken to assess the outcomes of UGIB in light of these new determinants by establishing a new national, multicenter cohort 10 years after the first. Methods Consecutive outpatients and inpatients with UGIB symptoms consulting at 46 French general hospitals were prospectively included between November 2017 and October 2018. They were followed for at least for 6 weeks to assess 6-week rebleeding and mortality rates and factors associated with each event. Results Among the 2498 enrolled patients (mean age 68.5 [16.3] years, 67.1 % men), 74.5 % were outpatients and 21 % had cirrhosis. Median Charlson score was 2 (IQR 1-4) and Rockall score was 5 (IQR 3-6). Within 24 hours, 83.4 % of the patients underwent endoscopy. The main causes of bleeding were peptic ulcers (44.9 %) and portal hypertension (18.9 %). The early in-hospital rebleeding rate was 10.5 %. The 6-week mortality rate was 12.5 %. Predictors significantly associated with 6-week mortality were initial transfusion (OR 1.54; 95 %CI 1.04-2.28), Charlson score > 4 (OR 1.80; 95 %CI 1.31-2.48), Rockall score > 5 (OR 1.98; 95 %CI 1.39-2.80), being an inpatient (OR 2.45; 95 %CI 1.76-3.41) and rebleeding (OR 2.6; 95 %CI 1.85-3.64). Anticoagulant therapy was not associated with dreaded outcomes. Conclusions The 6-week mortality rate remained high after UGIB, especially for inpatients. Predictors of mortality underlined the weight of comorbidities on outcomes.

Management of primary biliary cholangitis: results from a large real-life observational study in France and Belgium.

BACKGROUND AND AIMS: To assess the characteristics, care, treatment response, and outcomes of primary biliary cholangitis (PBC) patients recently followed-up by hepato-gastroenterologists in various French and Belgian healthcare settings. METHODS: This retrospective cohort study included patients with PBC who recently visited 79 hepato-gastroenterologists in France and Belgium. Data were collected at the time of diagnosis and at last visit and were compared according to biochemical response (BR) to ursodeoxycholic acid (UDCA) (BR), using Paris I-II criteria, and clinical outcomes. RESULTS: A total of 436 patients (mean age at diagnosis 57 years, 88% females, median follow-up 5.2 years) were included. Liver biopsy, transient elastography, or none of these two procedures were performed at baseline in 216 (50%), 194 (45%), and 107 (25%) patients, respectively. Late-stage disease (histological stage III or IV, or transient elastography ≥9.6 kPa, or bilirubin >17 µM and albumin <35 g/L, or platelets <150.000/µl, or unequivocal signs of portal hypertension or cirrhosis) was reported in 37% of patients. UDCA was taken by 95% of patients (27% had suboptimal dosage). Inadequate BR was observed in 37% of patients. Clinicians overestimated disease control. Liver-related complications occurred in 9% of patients. Bilirubin and albumin independently predicted inadequate BR; advanced disease stage and inadequate BR independently predicted complications. CONCLUSIONS: Recently followed-up French and Belgian patients with PBC had homogeneous management. Late stage at diagnosis and inadequate BR were reported in around 40% of patients. Disease control was frequently overestimated by clinicians. Disease stage and BR were the main prognostic factors.

Effects of Age on Treatment of Chronic Hepatitis C with Direct Acting Antivirals.

INTRODUCTION AND AIM: Data on the efficacy and tolerance of interferon-free treatment in chronic hepatitis C (CHC) in elderly patients are limited in phase II-III trials. MATERIAL AND METHODS: A prospective cohort of adult patients with CHC treated in French general hospitals. RESULTS: Data from 1,123 patients, distributed into four age groups, were analyzed. Of these, 278 were > 64 years old (fourth quartile) and 133 were > 73 years old (tenth decile). Elderly patients weighed less, were more frequently treatment-experienced women infected with genotype 1b or 2, while they less frequently had genotype 3 or HIV coinfection, but had more frequent comorbidities and drug consumption. Half of the patients had cirrhosis, whatever their ages. The main treatment regimens were sofosbuvir/ledipasvir (37.8%), sofosbuvir/daclatasvir (31.8%), sofosbuvir/simeprevir (16.9%), sofosbuvir/ribavirin (7.8%); ribavirin was given to 24% of patients. The overall sustained virological response (SVR) rate was 91.0 % (95% CI: 89.292.5%) with no difference according to age. Logistic regression of the independent predictors of SVR were albumin, hepatocellular carcinoma and treatment regimen, but not age. The rate of severe adverse events (66 in 59/1062 [5.6%] patients) tended to be greater in patients older than 64 years of age (21/261,8.1%), but the only independent predictors of SAE by logistic regression were cirrhosis and baseline hemoglobin. Patient-reported overall tolerance was excellent in all age groups, and patient-reported fatigue decreased during and after treatment, independent of age. CONCLUSIONS: The high efficacy and tolerance of interferon-free regimens is confirmed in elderly patients in real-life conditions.

Hepatitis C treatment with all-oral direct-acting antivirals: Effectiveness and tolerance in a multicenter, prospective, observational study from French general hospitals (APROVVIE, ANGH).

BACKGROUND AND AIMS: According to clinical trials, the treatment of patients with chronic hepatitis C (CHC) with second-generation direct acting antiviral agents (DAAs) is highly efficient and well tolerated. The goal of this study was to investigate the effectiveness and safety of various combinations of these drugs during their first 2 years of use in the real-world practice of French general hospitals. METHODS: Data from patients treated with all-oral DAAs in 24 French non-academic hospital centers from March 1, 2014 to January 1, 2016, were prospectively recorded. The sustained virological response 12-24 weeks after treatment (SVR 12-24) was estimated and severe adverse events (SAE) were evaluated and their predictive factors were determined using logistic regression. RESULTS: Data from 1123 patients were analyzed. The population was 69% genotype (G) 1, 13% G3, 11.5% G4, 5% G2, 49% with cirrhosis and 55% treatment-experienced. The treatment regimens were sofosbuvir/ledipasvir (38%), sofosbuvir/daclatasvir (32%), sofosbuvir/simeprevir (17%), ombitasvir+paritaprevir+ritonavir (5%) (with dasabuvir 3.5%), and sofosbuvir/ribavirin (8%). Ribavirin was given to 24% of patients. The SVR 12-24 was 91.0% (95% CI: 89.2-92.5%). Sofosbuvir-ribavirin was less effective than other regimens. The independent predictors of SVR 12-24 by logistic regression were body weight, albumin, previous hepatocellular carcinoma and treatment regimen (sofosbuvir/ribavirin vs. others). Sixty-four severe adverse events (SAE) were observed in 59 [5.6%] patients, and were independently predicted by cirrhosis and baseline hemoglobin. Serum creatinine increased during treatment (mean 8.5%, [P<10-5]), satisfying criteria for acute kidney injury in 62 patients (7.3%). Patient-reported overall tolerance was excellent, and patient-reported fatigue decreased during and after treatment. CONCLUSIONS: Second generation DAAs combinations are as effective and well tolerated in a « real-world ¼ population as in clinical trials. Further studies are needed on renal tolerance.

The expansion of endoscopic submucosal dissection in France: A prospective nationwide survey.

INTRODUCTION: Early reports of endoscopic submucosal dissection (ESD) in Europe suggested high complication rates and disappointing outcomes compared to publications from Japan. Since 2008, we have been conducting a nationwide survey to monitor the outcomes and complications of ESD over time. MATERIAL AND METHODS: All consecutive ESD cases from 14 centers in France were prospectively included in the database. Demographic, procedural, outcome and follow-up data were recorded. The results obtained over three years were compared to previously published data covering the 2008-2010 period. RESULTS: Between November 2010 and June 2013, 319 ESD cases performed in 314 patients (62% male, mean (±SD) age 65.4 ± 12) were analyzed and compared to 188 ESD cases in 188 patients (61% male, mean (±SD) age 64.6 ± 13) performed between January 2008 and October 2010. The mean (±SD) lesion size was 39 ± 12 mm in 2010-2013 vs 32.1 ± 21 for 2008-2010 (p = 0.004). En bloc resection improved from 77.1% to 91.7% (p < 0.0001) while R0 en bloc resection remained stable from 72.9% to 71.9% (p = 0.8) over time. Complication rate dropped from 29.2% between 2008 and 2010 to 14.1% between 2010 and 2013 (p < 0.0001), with bleeding decreasing from 11.2% to 4.7% (p = 0.01) and perforations from 18.1% to 8.1% (p = 0.002) over time. No procedure-related mortality was recorded. CONCLUSIONS: In this multicenter study, ESD achieved high rates of en bloc resection with a significant trend toward better outcomes over time. Improvements in lesion delineation and characterization are still needed to increase R0 resection rates.

Middle-term mortality and re-bleeding after initial diverticular bleeding: A nationwide study of 365 mostly elderly French patients.

BACKGROUND AND AIMS: The aim of this study was to determine the mortality and re-bleeding rates, and the risk factors involved, in a cohort of patients with previous diverticular bleeding (DB). METHODS: In 2007, data on 2462 patients with lower gastrointestinal (GI) bleeding were collected prospectively at several French hospitals. We studied the follow-up of patients with DB retrospectively. The following data were collected: age, mortality rates and re-bleeding rates, drug intake, surgery and comorbidities. RESULTS: Data on 365 patients, including 181 women (mean age 83.6 ± 9.8 years) were available. The median follow-up time was 3.9 years (IQR 25-75: 1.7-5.4). Of these, 148 patients died (40.5%). Among the 70 patients (19.2%) who had at least one re-bleeding episode, nine died and three underwent surgical procedures. Anticoagulation and antiplatelet therapy was discontinued in 70 cases (19.2%). The independent risk factors contributing to mortality were age > 80 years (HR = 3.18 (2.1-4.9); p < 0.001) and a Charlson comorbidity score > 2 (1.91 (1.31-2.79); p = 0.003). Discontinuation of therapy was not significantly associated with a risk of death due to cardiovascular events. No risk factors responsible for re-bleeding were identified, such as antiplatelet and anticoagulant therapy in particular. CONCLUSIONS: In this cohort, the rates of mortality and DB re-bleeding after a median follow-up time of 3.9 years were 19.2% and 40.5%, respectively. The majority of the deaths recorded were not due to re-bleeding.

Factors associated with adenoma detection rate and diagnosis of polyps and colorectal cancer during colonoscopy in France: results of a prospective, nationwide survey.

INTRODUCTION: Colonoscopy can prevent deaths due to colorectal cancer (CRC) through early diagnosis or resection of colonic adenomas. We conducted a prospective, nationwide study on colonoscopy practice in France. METHODS: An online questionnaire was administered to 2,600 French gastroenterologists. Data from all consecutive colonoscopies performed during one week were collected. A statistical extrapolation of the results to a whole year was performed, and factors potentially associated with the adenoma detection rate (ADR) or the diagnosis of polyps or cancer were assessed. RESULTS: A total of 342 gastroenterologists, representative of the overall population of French gastroenterologists, provided data on 3,266 colonoscopies, corresponding to 1,200,529 (95% CI: 1,125,936-1,275,122) procedures for the year 2011. The indication for colonoscopy was CRC screening and digestive symptoms in 49.6% and 38.9% of cases, respectively. Polypectomy was performed in 35.5% of cases. The ADR and prevalence of CRC were 17.7% and 2.9%, respectively. The main factors associated with a high ADR were male gender (p=0.0001), age over 50 (p=0.0001), personal or family history of CRC or colorectal polyps (p<0.0001 and p<0.0001, respectively), and positive fecal occult blood test (p=0.0005). The prevalence of CRC was three times higher in patients with their first colonoscopy (4.2% vs. 1.4%; p<0.0001). CONCLUSIONS: For the first time in France, we report nationwide prospective data on colonoscopy practice, including histological results. We found an average ADR of 17.7%, and observed reduced CRC incidence in patients with previous colonoscopy.

Epidemiology and adherence to guidelines on the management of bleeding peptic ulcer: a prospective multicenter observational study in 1140 patients.

BACKGROUND AND OBJECTIVE: Mortality of upper gastrointestinal bleeding seems declining. Whether practice guidelines for the management of peptic ulcer bleeding are followed is unknown. We aimed to update epidemiology of peptic ulcer bleeding and to assess the adherence to guidelines in the French community. METHODS: Between March, 2005 and February, 2006, a prospective multicenter study was conducted including all patients with communautary upper gastrointestinal bleeding. Data from patients with peptic ulcer bleeding were extracted and analyzed. RESULTS: Out of 3203 analyzable patients included, 1140 (35.6%) had a peptic ulcer bleeding and 965 of them a duodenal and/or gastric ulcer. Seven hundred and thirty-five were male (64.5%) and mean age was 66.4 years (±18.8). Overall, 699 patients (61.3%) were taking medication inducing upper gastrointestinal bleeding. Two-hundred and sixty-eight (23.5%) patients had endoscopic therapy, 190 (70.9%) of whom had epinephrine injection alone. Among the 349 patients with high risk stigmata on endoscopy (Forrest IA, IB, IIA), 209 (59.9%) underwent endoscopic therapy. One thousand one hundred and seven patients (97.1%) were given proton-pump inhibitors. One hundred and thirty-four patients (11.8%) experienced haemorrhagic recurrence. Forty-eight patients (4.2%) underwent surgery and 61 (5.4%) died. CONCLUSIONS: Consistently with previous studies, mortality of upper gastrointestinal bleeding seems declining. Further progress lies above all in prevention but also probably in better adherence to therapeutic guidelines and management of comorbidities.

Education by a nurse increases response of patients with chronic hepatitis C to therapy with peginterferon-α2a and ribavirin.

BACKGROUND & AIMS: Education of patients with chronic hepatitis C has been proposed to increase response to therapy with peginterferon and ribavirin. We performed a prospective study to determine the effects of systematic consultation by a nurse on patient adherence and the efficacy of therapy. METHODS: We analyzed data from 244 patients who received either systematic consultation after each medical visit from a nurse who used a standard evaluation grid and provided information about the disease and treatment (group A [GrA], n = 123) or the conventional clinical follow-up procedure (group B [GrB], n = 121). Treatment lasted 24 to 48 weeks. RESULTS: Characteristics of each group were similar at baseline, including prior treatment (42.6% in GrA and 36.0% in GrB). Overall, GrA had significantly better adherence to treatment than GrB (74.0% vs 62.8%), especially among patients who received 48 weeks of treatment (69.7% vs 53.2%; P < .03). Significantly more patients in GrA had a sustained virologic response, compared with GrB overall (38.2% vs 24.8%; P < .02), as well as treatment-naive patients (47.1% vs 30.3%; P < .05), and those with genotypes 1, 4, or 5 infections (31.6% vs 13.3%; P < .007). There were no differences between GrA and GrB in response of patients with genotypes 2 or 3 infections or advanced fibrosis. Prognostic factors for a sustained virologic response (based on bivariate and multivariate analyses) were virologic response at week 12 (odds ratio [OR], 1.9; P < .0001), genotypes 2 or 3 (OR, 2.9; P < .0001), therapeutic education (OR, 2.5; P < .02), and lack of previous treatment (OR, 2.3; P < .005). CONCLUSIONS: Therapeutic education by a specialized nurse increases the response of patients with hepatitis C to therapy, particularly in difficult-to-treat patients.

Patient information for liver biopsy: impact of a video movie.

AIMS: The information given to patients before a medical procedure is usually delivered verbally and in the form of a written document. Viewing a video movie about the procedure might be helpful in improving the quality of patient information and thus contributed to reduce patient anxiety. The aim of this prospective study on the methods used to deliver information to patients scheduled for liver biopsy was to determine, in comparison with standard information delivery, the impact on anxiety and understanding of additional information provided by a video movie. METHODS: Patients included in this study were scheduled for liver biopsy. Three days before the procedure, a physician informed the patients about liver biopsy and gave them a written information document. After this standard information delivery, the patients were randomly assigned to two groups, to view or not a video movie illustrating liver biopsy and recalling the information provided in the information document. Anxiety was measured after the information visit and just before the biopsy procedure using Spielberger's self-administered STAI-Y questionnaire. Patient understanding of and satisfaction with the information received were evaluated respectively before and after the procedure. RESULTS: Among the 67 patients retained for analysis, 33 viewed the information video and 34 did not. The level of anxiety measured at the information visit and before liver biopsy was similar in the two groups (38.8 and 37.4 with video versus 38.9 and 40.1 without video). The patients had an excellent understanding of the information received (12.3/14 with video; 12.7/14 without video) and were well satisfied with the information received. CONCLUSION: The patients understood and were well satisfied with the information received about liver biopsy. Complementary information in the form of a video movie had no effect on patient anxiety.

High dose daily interferon-alpha induction and secondary adjunction of ribavirin in treatment-naive patients with chronic hepatitis C. A multicentric, randomised, controlled trial.

OBJECTIVES: To evaluate in naive patients with chronic hepatitis C 1- the efficacy and safety of one month interferon alpha (IFN-alpha) induction regimen; 2- the potential virological benefit of a secondary adjunction of ribavirin among HCV RNA negative patients after 20 weeks of IFN therapy, with or without an initial 4-week IFN induction. MATERIAL AND METHODS: 151 naive HCV-RNA positive patients presenting with biopsy- proven chronic hepatitis C and elevated ALT were randomised in a 2: 1 ratio in two arms: IFN-alpha 3 MU thrice a week (tiw) for 24 weeks (non-induced patients); IFN-alpha 6 MU daily for two weeks, then 3 MU daily for two weeks then 3 MU tiw for 20 weeks (induced patients). At week 24, HCV-RNA negative patients were randomised to receive in addition or not ribavirin 1-1.2 g daily for 24 additional weeks. Induction efficacy was assessed on the early viral response (EVR) defined as undetectable HCV RNA at week 4 then week 20. Ribavirin efficacy was assessed on the proportion of maintained complete response until the end of follow-up, 24 weeks after discontinuation of treatment. Data were analysed on an intent-to-treat basis. RESULTS: Efficacy of IFN-alpha induction: 104 patients were randomised to the non-induction group, 47 to the induction group. Gender, age, genotype distribution and HCV viral load at baseline did not differ significantly between the two groups. There was one treatment discontinuation because of adverse events in induced patients versus four in non-induced patients (P > 0.05). The 4 week EVR was significantly greater in induced patients in patients with HCV genotype 1, 4 or 5 (47% vs 12%, P=0.0002) only. There was no impact of induction in patients with HCV genotype 2 or 3. Efficacy of ribavirin: at week 24, 28 and 26 HCV-RNA negative patients were randomised to addition of ribavirin or not, respectively. Patients randomised to secondary additive ribavirin were more often HCV-RNA negative at the end of follow-up than patients treated with IFN-alpha alone: 18/28 (64%) vs 10/26 (39%); P=0.06. Among patients randomised to bitherapy, the relapse rate was significantly lower in patients with genotype 2 or 3 (0/12 vs 6/13, P=0.01) and not in those with genotype 1, 4 or 5 (5/11 vs 3/6, P=0.99). CONCLUSION: A 4 week IFN-alpha induction significantly increases the EVR rate in patients with HCV genotype 1, 4 or 5. Late secondary adjunction of ribavirin to IFN-alpha for 6 months in HCV-RNA negative patients after 6 months of IFN-alpha significantly decreases the relapse rate in patients with HCV genotype 2 or 3, but not in patients with genotypes 1, 4 or 5.