Low glomerular filtration rate is a risk factor for ribavirin-associated anaemia in old patients with chronic hepatitis C.

Elderly patients with chronic hepatitis C have a reduced responsiveness to antiviral therapy with Peg-interferon and ribavirin. The dose reduction or the discontinuation of ribavirin due to the occurrence of anaemia is one of the most important causes for the low sustained viral response observed in older patients. We aimed to evaluate the relationship between baseline renal function and the early onset of ribavirin-associated anaemia in older (≥60 years) patients. Using data from 348 patients with chronic hepatitis C consecutively treated with peg-interferon plus ribavirin, we investigated which factors were associated with the occurrence of anaemia in elderly patients (≥60 years). Ribavirin-induced anaemia occurred in 40.5% of patients. Older patients showed a rate of anaemia significantly higher than younger patients (51.5% vs 36.3%; P = 0.009). Consequently, the rate of ribavirin dose reduction or discontinuation due to anaemia was 35.1% in older patients and 23.5% in younger patients (P = 0.029). A significantly higher proportion of older patients had a low baseline glomerular filtration rate (GFR) compared with younger patients (56.7% vs 27.1%; P < 0.001). At the multivariate regression analysis, low baseline GFR (<70 mL/min) was associated with an increased risk of ribavirin-associated anaemia only in the older patients (OR: 3.526; 95% CI: 1.385-8.979; P = 0.008). In this subset, baseline GFR was significantly correlated with both absolute (r = -0.320; P < 0.001) and relative (r = -0.324; P < 0.001) haemoglobin decrease within the first 8 weeks of treatment. In patients aged >60 years, a low pre-treatment GFR was strongly associated with the risk to develop ribavirin-related anaemia with consequent reduction in ribavirin doses.

Resect and discard strategy in clinical practice: a prospective cohort study.

BACKGROUND AND STUDY AIMS: Narrow-band imaging (NBI) has shown promising results in discriminating adenomatous from non-adenomatous colonic polyps. In patients with small polyps (< 10  mm), the application of NBI within a "resect and discard" strategy, might allow post-polypectomy surveillance intervals to be determined independently from histopathology. The aim of the present study was to assess the feasibility and safety of this approach in routine clinical practice. PATIENTS AND METHODS: Consecutive colonoscopy outpatients with one or more polyps smaller than 10  mm were prospectively included. Each polyp was categorized by the endoscopist as adenoma or non-adenoma according to simplified NBI criteria, and future post-polypectomy surveillance interval was assigned accordingly. Following histopathology, post-polypectomy surveillance interval was subsequently re-assigned, and the accordance between endoscopy- and histology-directed surveillance strategies was calculated. RESULTS: Among 942 colonoscopy patients, 286 (30.4 %) with only small polyps were included. In total, 511 small polyps were evaluated; 350 (68.5 %) were adenomas and 18 of these (5.1 %) had histologic features of advanced neoplasia. For the in vivo diagnosis of adenoma, NBI sensitivity, specificity, accuracy, and positive and negative likelihood ratios were 94.9 %, 65.8 %, 85.7 %, 2.80, and 0.08, respectively. The endoscopy-directed surveillance strategy was in accordance with the histology-directed strategy in 237 of 286 patients (82.9 %). In 9.8 % and 7.3 % patients, the endoscopy-directed approach would have resulted in early and delayed surveillance, respectively. CONCLUSIONS: The resect and discard strategy seems to be a viable, safe, and cost-effective approach for the management of patients with small polyps. However, caution in the application of the strategy should be advocated for patients with polyps 6 - 9  mm in size and those with right-sided lesions, due to their malignant potential. The study was registered on Clinicaltrials.gov (NCT01462123).

Effectiveness of pegylated interferon/ribavirin combination in 'real world' patients with chronic hepatitis C virus infection.

BACKGROUND: Clinical trials have shown that the combination of pegylated interferon/ribavirin induces a sustained virological response in 54-63% of patients with chronic hepatitis C virus infection, but its effectiveness in day-to-day clinical practice is less clear. AIM: To verify if the efficacy of pegylated interferon/ribavirin combination in 'real world' patients is comparable to that observed in trials. Methods The medical records of 397 consecutive naïve patients with chronic hepatitis C virus infection treated with pegylated interferon/ribavirin combination in nontertiary hospital settings were reviewed in order to assess the response to anti-viral treatment. RESULTS: The sustained virological response rate achieved in this population was similar to that recorded in registration trials (total population: 64%; genotype 1: 46%; genotypes 2-3: 84%). Also, the premature discontinuation rate (15%) was similar to that observed in registration trials, but there were fewer dose reductions in one or both medications (26%). We confirmed the association between adherence and sustained virological response among the patients infected with hepatitis C virus genotype 1 who were treated for > or =80% of the planned duration of treatment. CONCLUSION: The effectiveness of pegylated interferon/ribavirin therapy and factors predicting an sustained virological response in everyday clinical practice mirror those reported in randomized-controlled studies.

Nutritional status and prognosis in cirrhotic patients.

BACKGROUND AND AIM: The potential prognostic value for survival of nutritional status in cirrhotics after adjusting Child-Pugh classification and Model for End-Stage Liver Disease has not been evaluated. METHODS: We used Kaplan-Meier and Cox proportional hazards regression models to identify factors associated with mortality in a cohort of 222 cirrhotics [M/F:145/77 median age 52 (18-68) years] with prospectively collected nutritional parameters as well as modified subjective global nutritional assessment, Royal Free Hospital-Subjective Global Assessment index. Follow-up was censored at the time of transplantation. Other variables were ones in Child-Pugh and Model for End-Stage Liver Disease scores, age, aetiology of cirrhosis and renal function. RESULTS: Pretransplant mortality (Kaplan-Meier) was 21% by 2 years (135 patients were transplanted). Among the nutritional parameters, only Royal Free Hospital-Subjective Global Assessment remained significantly associated with mortality in multivariable models (P = 0.0006). The final model included the following variables: urea (P = 0.0001), Royal Free Hospital-Subjective Global Assessment (P = 0.003), age (P = 0.0001), Child-Pugh grade (P = 0.009) and prothrombin time (P = 0.003). The results were similar when the Child-Pugh grade was replaced by the Model for End-Stage Liver Disease score in the model, and whether a competing risks model was used. CONCLUSIONS: Nutritional indices add significantly to both Child-Pugh grade and Model for End-Stage Liver Disease scores when assessing the patient prognosis.

Systematic review: The model for end-stage liver disease--should it replace Child-Pugh's classification for assessing prognosis in cirrhosis?

BACKGROUND: Prognosis in cirrhotic patients has had a resurgence of interest because of liver transplantation and new therapies for complications of end-stage cirrhosis. The model for end-stage liver disease score is now used for allocation in liver transplantation waiting lists, replacing Child-Turcotte-Pugh score. However, there is debate as whether it is better in other settings of cirrhosis. AIM: To review studies comparing the accuracy of model for end-stage liver disease score vs. Child-Turcotte-Pugh score in non-transplant settings. RESULTS: Transjugular intrahepatic portosystemic shunt studies (with 1360 cirrhotics) only one of five, showed model for end-stage liver disease to be superior to Child-Turcotte-Pugh to predict 3-month mortality, but not for 12-month mortality. Prognosis of cirrhosis studies (with 2569 patients) none of four showed significant differences between the two scores for either short- or long-term prognosis whereas no differences for variceal bleeding studies (with 411 cirrhotics). Modified Child-Turcotte-Pugh score, by adding creatinine, performed similarly to model for end-stage liver disease score. Hepatic encephalopathy and hyponatraemia (as an index of ascites), both components of Child-Turcotte-Pugh score, add to the prognostic performance of model for end-stage liver disease score. CONCLUSIONS: Based on current literature, model for end-stage liver disease score does not perform better than Child-Turcotte-Pugh score in non-transplant settings. Modified Child-Turcotte-Pugh and model for end-stage liver disease scores need further evaluation.

Routine versus "on demand" sedation and analgesia for colonoscopy: a prospective randomized controlled trial.

BACKGROUND: The safety and tolerance of routine sedation and analgesia versus "on demand" sedation were compared in patients undergoing colonoscopy. METHODS: Two hundred forty-nine outpatients were randomly assigned to one of two groups. Group A (n = 125) received midazolam, 0.07 mg/kg intravenously plus meperidine, 0.77 mg/kg intravenously immediately preceding the colonoscope insertion. Group B (n = 124) received the same medication upon request during the procedure. Tolerance was assessed 24 hours later by phone interview performed by a nurse blinded to the medication regimen administered. RESULTS: Eighty-three patients (66%) in Group B required sedation during colonoscopy. Among men in Group B more than 60 years of age, only 23% required sedation. The proportion of patients reporting moderate or severe pain (34% vs. 12.1%, p < 0.001) and of those stating they would not be willing to undergo colonoscopy again in the future (22% vs. 9.7%, p < 0.005) was significantly higher in the "on demand" sedation group. By multivariate analysis the randomization group was the single variable independently associated with both such outcomes. The frequency of side effects was similar in the two groups. CONCLUSIONS: Administration of sedative and analgesic drugs routinely before colonoscopy is superior to "on demand" sedation in terms of tolerance and is not associated with an increase in side effects.

Helicobacter pylori seroprevalence in hepatitis C virus positive patients with cirrhosis. The Como cross-sectional study.

BACKGROUND: Liver cirrhosis is a significant cause of death in Italy and one of the most frequent causes of hospitalization. Acute peptic ulcer and upper gastrointestinal bleeding reportedly occur in over 15% of cirrhotic patients. Since Helicobacter pylori (H. pylori) infection strongly correlates with peptic ulcer, we sought to ascertain the seroprevalence of H. pylori infection in cirrhotic patients. METHODS: In a cross-sectional study, we examined 52 consecutive patients (31 female and 21 male, age range 54-82, mean 68.7 years) suffering from hepatitis C virus (HCV)-related cirrhosis attending the Unit of Gastroenterology of the Valduce Hospital of Como (Italy). RESULTS: The prevalence of antibodies against H. pylori was 86.5% (45/52) in the cirrhotics. Of female patients 28/31 (90.3%) were seropositive as compared to 17 of 21 (80.9%) of male patients. CONCLUSIONS: The very high prevalence of H. pylori infection may explain the frequent occurrence of gastroduodenal ulcer in cirrhotic patients.

A randomized 4-arm multicenter study of interferon alfa-2b plus ribavirin in the treatment of patients with chronic hepatitis C not responding to interferon alone.

To determine whether a higher dosage of interferon (IFN) associated with ribavirin and/or prolonged time of administration may improve therapeutic efficacy, we conducted a 4-arm randomized trial on patients with chronic hepatitis C not responding to one or more previous treatment courses with IFN monotherapy. Group 1 (n = 139) received 3 million units (MU) IFN-alpha2b 3 times a week (t.i.w.) plus ribavirin 1,000 mg/d for 12 months; group 2 (n = 162) received 5 MU t.i.w. plus ribavirin for 12 months; group 3 (n = 142) received 3 MU t.i.w. plus ribavirin for 6 months; and group 4 (n = 151) received 5 MU t.i.w. plus ribavirin for 6 months. The primary end point was hepatitis C virus (HCV)-RNA clearance at the end of 6-month follow-up. HCV-RNA was negative in 15% of group 1, 23% of group 2, 11% of group 3, 16% of group 4 (group 2 vs. group 3, P =.04). Among patients with genotypes 1 and 4, sustained response was significantly higher in group 2 vs. group 3 (18% vs. 7%, P =.03; group 1 = 9%, group 4 = 12%, P = not significant [NS]). In patients with genotypes 2 and 3, sustained virologic response was not affected by the different regimens (group 1 = 32%, group 2 = 30%, group 3 = 30%, group 4 = 35%, P = NS). In conclusion, about 23% of nonresponders to IFN monotherapy may achieve a sustained response if re-treated by 5 MU t.i.w. IFN plus ribavirin 1,000 mg/d for 1 year. Patients with genotype 1 should receive a high dosage of IFN plus ribavirin for 12 months, whereas therapy for patients with genotype 2 or 3 should be less aggressive.

Treatment with interferon-alpha2b of naive non-cirrhotic patients with chronic hepatitis C according to viraemia and genotype. Results of a randomized multicentre study. The North West Italian Hepatological Group.

OBJECTIVE: To establish whether tailoring the dosage of interferon (IFN)-alpha2b in non-cirrhotic naive patients with chronic hepatitis C according to hepatitis C virus (HCV) genotype and viraemic level improves the rate of sustained response (normal alanine aminotransferase values and HCV-RNA negativity 6 months after the end of therapy). PATIENTS: A total of 538 consecutively collected HCV-positive patients with non-cirrhotic chronic hepatitis who had not been previously treated. METHODS: Quantitative viraemia and genotype were determined in each patient by a core laboratory. The patients were randomized to: Group 1, 86 patients with genotype non-1 and viraemia < 1,000,000 HCV genome equivalents/ml (GenEq/ml) treated with 3 Million Units (MU) IFN three times weekly (t.i.w.) for 1 year; Group 2, 42 patients with genotype 1 and viraemia < 1,000,000 GenEq/ ml treated with 3 MU IFN t.i.w. for 1 year; Group 3, 46 patients with genotype 1 and viraemia < 1,000,000 GenEq/ ml treated with 5 MU IFN t.i.w. for 1 year; Group 4, 85 patients with genotype non-1 and viraemia > 1,000,000 GenEq/ml treated with 3 MU IFN t.i.w. for 1 year; Group 5, 88 patients with genotype non-1 and viraemia > 1,000,000 GenEq/ml treated with 5 MU IFN t.i.w. for 1 year; Group 6, 94 patients with genotype 1 and viraemia > 1,000,000 GenEq/ml treated with 3 MU IFN t.i.w. for 1 year; Group 7, 97 patients with genotype 1 and viraemia > 1,000,000 GenEq/ml treated with 5 MU IFN daily for 2 months followed by 5 MU t.i.w. for a further 10 months. RESULTS: According to an intention-to-treat analysis, a sustained virological response (negative HCV-RNA by polymerase chain reaction 6 months after the end of therapy) was observed in 42% of Group 1 patients, in 21% of Group 2 patients versus 24% of Group 3 patients [P = not significant (NS)], in 28% of Group 4 patients versus 35% of Group 5 patients (P = NS), and in 8.5% of Group 6 patients versus 12% of Group 7 patients (P = NS). CONCLUSIONS: Even though a trend towards a therapeutic improvement is observed, the adoption of more aggressive IFN protocols, such as induction therapy, does not appear to significantly improve the rate of sustained response in patients with chronic hepatitis C associated with HCV genotype 1 and highly viraemic levels compared with standard therapy. Moreover, patients with only one unfavourable predictive factor (genotype 1 or high viraemia) do not gain major therapeutic benefits when treated with high doses of IFN.

Acute self-limiting jejunitis as the first manifestation of microscopic polyangiitis associated with Sjogren's disease: report of one case and review of the literature.

We report a case of acute self-limiting ulcerative jejunitis of unknown aetiology in a 72-year-old female patient in which a subsequent diagnosis of microscopic polyangiitis and Sjogren's syndrome was made. All known causes of jejunal ulceration and inflammation were excluded. Previously reported cases of acute self-limiting jejunitis are reviewed and the possibility that acute jejunitis in this patient had been the first manifestation of systemic vasculitis is discussed.