Follow-up evaluation and management of anemia in inflammatory bowel disease: A study by the Italian Group for Inflammatory Bowel Diseases (IG-IBD).

BACKGROUND: The RIDART I study found a 13.6% prevalence of anemia in Italian patients with inflammatory bowel disease (IBD); most cases were due to iron-deficiency anemia (IDA). AIMS: To evaluate changes in hemoglobin concentration during a 24-week follow-up of anemic patients with IBD. METHODS: Follow-up laboratory and clinical data were obtained from RIDART I study patients with anemia. Factors affecting hemoglobin concentration, the impact of anemia on fatigue and quality of life (QoL), and its relationship with treatment, disease activity and disease complications were investigated. RESULTS: Hemoglobin was 108 g/L at baseline, increased to 121 g/L at follow-up week 12 (p < 0.001) and then stabilized until week 24, but most patients remained anemic, with IDA, throughout the study. Hemoglobin improvement was greater in patients receiving either oral or parenteral iron supplementation. Following hemoglobin normalization, anemia relapse rate during follow-up was 30%. Oral iron did not cause disease reactivation. Lower follow-up hemoglobin was associated with a higher probability of having active disease, clinical complications, increased fatigue and reduced QoL. CONCLUSIONS: In anemic patients with IBD, anemia represents a long-lasting problem, in most cases persisting for up to 24 weeks, with high relapse rate and a negative impact on fatigue and QoL.

A prospective, multicenter, three-cohort study evaluating contrast-induced acute kidney injury (CI-AKI) in patients with cirrhosis.

BACKGROUND & AIMS: Nephrotoxicity of intravenous iodinated contrast media (ICM) in cirrhosis is still a debated issue, due to scarce, low-quality and conflicting evidence. This study aims to evaluate the incidence and predisposing factors of acute kidney injury (AKI) in patients with cirrhosis undergoing contrast-enhanced computed tomography (CECT). METHODS: We performed a prospective, multicenter, cohort study including 444 inpatients, 148 with cirrhosis (cohort 1) and 163 without cirrhosis (cohort 3) undergoing CECT and 133 with cirrhosis (cohort 2) unexposed to ICM. Kidney function parameters were assessed at T0, 48-72 h (T1), 5 and 7 days after CECT/enrollment. Urinary neutrophil gelatinase-associated lipocalin (U-NGAL) was measured in 50 consecutive patients from cohort 1 and 50 from cohort 2 as an early biomarker of tubular damage. RESULTS: AKI incidence was not significantly increased in patients with cirrhosis undergoing CECT (4.8%, 1.5%, 2.5% in cohorts 1, 2, 3 respectively, p = n.s.). Most AKI cases were mild and transient. The presence of concomitant infections was the only independent predictive factor of contrast-induced AKI (odds ratio 22.18; 95% CI 2.87-171.22; p = 0.003). No significant modifications of U-NGAL between T0 and T1 were detected, neither in cohort 1 nor in cohort 2 (median ΔU-NGAL: +0.2 [-7.6 to +5.5] ng/ml, +0.0 [-6.8 to +9.5] ng/ml, respectively [p = 0.682]). CONCLUSIONS: AKI risk after CECT in cirrhosis is low and not significantly different from that of the general population or of the cirrhotic population unexposed to ICM. It mostly consists of mild and rapidly resolving episodes of renal dysfunction and it is not associated with tubular kidney injury. Patients with ongoing infections appear to be the only ones at higher risk of AKI. IMPACT AND IMPLICATIONS: Nephrotoxicity due to intravenous iodinated contrast media (ICM) in patients with cirrhosis is still a debated issue, as the available evidence is limited and based on very heterogeneous studies, often conducted on small and retrospective cohorts. In this prospective three-cohort study we found that intravenous administration of ICM was associated with a low risk of AKI, similar to that of the general population and to that of patients with cirrhosis unexposed to ICM. Patients with ongoing infections were the only ones to have a significantly increased risk of contrast-induced AKI. Therefore, the actual recommendations of performing contrast imaging studies cautiously in cirrhosis do not seem to be reasonable anymore, with the exception of infected patients, who have a significantly higher risk of contrast-induced AKI.

Prevalence, Pathogenesis and Management of Anemia in Inflammatory Bowel Disease: An IG-IBD Multicenter, Prospective, and Observational Study.

BACKGROUND: Anemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD), with a 6% to 74% prevalence and a negative impact on patient survival and quality of life, although the prevalence is apparently declining due to improved disease treatment. We aimed to investigate the prevalence, pathogenesis, and clinical correlates of anemia in Italian patients with IBD. METHODS: A multicenter, prospective, observational study, involving 28 Italian gastroenterology centers, was conducted to investigate the epidemiology and consequences of IBD-associated anemia. Clinical and laboratory data of anemic patients were obtained at study enrolment. RESULTS: Anemia was diagnosed in 737 of 5416 adult IBD outpatients (prevalence 13.6%); females were more commonly affected than males (odds ratio, 1.5; 95% confidence interval [CI], 1.2-1.7) and had more severe anemia. In the majority of cases, anemia was due to iron deficiency (62.5% of cases; 95% CI, 58.3%-66.6%), either isolated or in association with inflammation and/or vitamin deficiencies; anemia of inflammation accounted for only 8.3% of cases. More severe anemia was associated with increasing fatigue and worse quality of life. Only 68.9% of anemic patients with iron deficiency (95% CI, 63.4%-73.8%) and 34.6% of those with vitamin deficiencies (95% CI, 26.2%-44.2%) were properly treated with supplementation therapy. CONCLUSIONS: In Italy, the prevalence of IBD-associated anemia is lower than previously reported. Anemia of IBD is most commonly due to iron deficiency and contributes to fatigue and poor quality of life, but remains untreated in a large proportion of patients with iron and/or vitamin deficiencies. This study is registered at clinicaltrials.gov as NCT02872376.

The prevalence of inflammatory bowel disease­associated anemia is 13.6%. The prevalence is higher among females younger than 50. Anemia is usually due to iron deficiency and adversely affects fatigue and quality of life. Many patients with iron or vitamin deficiency (31% and 65%, respectively) remain untreated.

Short duration treatment in genotype 1 chronic hepatitis C patients with rapid virologic response to pegylated interferon plus ribavirin.

BACKGROUND: In patients with chronic hepatitis C, rapid HCV-RNA clearance under treatment might allow shorter treatment duration without modifying the sustained virological response (SVR) rate. This study evaluated the impact of rapid virological response (RVR) in HCV genotype 1b infection management. METHODS: In an open-label trial, 180 patients received standard doses of peginterferon alfa-2a plus ribavirin. Those with undetectable serum HCV-RNA at week 6 (RVR) received 24-week short-course treatment; patients with undetectable HCV-RNA at week 12 (early responders [ER]) received 48-week "standard of care" treatment; patients with positive HCV-RNA at week 12 (non-responders [NR]) stopped the treatment. Study end-point was to determine SVR rate at week 24. RESULTS: The following responses were observed: 24% RVR, 44% ER, 32% NR. Among RVR subjects, HCV-RNA baseline levels and age were significantly lower (P=0.038 and 0.035 respectively) than in non-RVR patients. At follow-up, 91% of RVR and 33% of ER patients achieved SVR. Among those with RVR, patients experiencing post-therapy relapse were older than those who achieved a SVR (P=0.028). CONCLUSIONS: Chronic HCV-1b patients, achieving RVR with a 24-week treatment regimen, attained excellent SVR rates. In a cost-effective therapeutic approach, all HCV-1b patients eligible for therapy may have a short duration therapy on the basis of RVR.

Long-term follow-up of previous hepatitis C virus positive nonresponders to interferon monotherapy successfully retreated with combination therapy: are they really cured?

OBJECTIVES: To evaluate whether in chronic hepatitis C-positive patients who failed to respond to interferon (IFN) monotherapy a sustained response obtained with retreatment using the combination therapy of IFN + ribavirin can be safely considered to reflect eradication of the infection. METHODS: Prospective follow-up of a cohort of 97 patients who responded to retreatment with different regimens of IFN + ribavirin after failing to respond to a first IFN monotherapy course. The patients were followed throughout 7 yr of follow-up with determinations of HCV viremia every 6 months. RESULTS: At the end of the follow-up, 11 patients (11.3%) showed a viremic reappearance. HCV late relapse rates were 0%, 13%, 20%, and 12% in patients retreated, respectively, with 3 MU IFN + ribavirin for 12 months (Group 1), 5 MU IFN + ribavirin for 12 months (Group 2), 3 MU IFN + ribavirin for 6 months (Group 3), and 5 MU IFN + ribavirin for 6 months (Group 4) (Group 2 vs Group 3, p= 0.005). The virologic relapses occurred within 2 yr from therapy withdrawal. Among patients with genotype 1 and 4, the long-term response was significantly higher in Group 2 than in Group 3 (15%vs 3%, p= 0.03). In patients with genotype 2 and 3, the long-term virological response was not affected by the different regimens. CONCLUSIONS: Nonresponders to IFN monotherapy who achieve a sustained virologic response after retreatment with IFN + ribavirin stand a discrete risk of HCV reactivation within 2 yr after therapy.

A randomized 4-arm multicenter study of interferon alfa-2b plus ribavirin in the treatment of patients with chronic hepatitis C relapsing after interferon monotherapy.

To determine whether a higher dosage of interferon (IFN) and/or a prolonged time of administration may improve the efficacy of combination therapy, we conducted a 4-arm randomized trial on patients with chronic hepatitis C relapsing after 1 or more previous treatment courses with IFN monotherapy. Group A (n = 70) received 3 MU IFN alfa-2b 3 times per week plus ribavirin 1,000 mg/d for 12 months; group B (n = 70) received 5 MU 3 times per week plus ribavirin for 12 months; group C (n = 82) received 3 MU 3 times per week plus ribavirin for 6 months, and group D (n = 73) received 5 MU 3 times per week plus ribavirin for 6 months. The primary end point was the clearance of viremia at the end of 6-month follow-up: test results for hepatitis C virus (HCV)-RNA were negative in 54% of group A, 56% of group B, 40% of group C, and 49% of group D patients (P = NS). Among patients with genotype 1 and 4, the sustained response was significantly higher in groups A and B than in group C (45%, 49% vs. 22%, P =.03; group D = 33%, P = NS). In patients with genotype 2 and 3, the sustained virologic response was not affected by the different regimens (group A = 69%, group B = 68%, group C = 62%, group D = 71%, P = NS). In conclusion, duration of therapy rather than IFN dosage is more important in increasing the sustained virologic rate among HCV-positive patients with genotype 1 and 4 relapsing after IFN monotherapy; patients with genotypes 2 and 3 can be effectively retreated with a 6-month course of combination therapy, avoiding unnecessary side effects and waste of resources.