Efficacy of Interferon A-2b monotherapy in Β-thalassemics with chronic hepatitis C.

BACKGROUND & AIMS: Monotherapy with standard or pegylated interferon (PegIFN) remains the first-line treatment for HCV infection in patients with thalassemia major (ßTM), although its long-term impact is still unknown. We aimed to assess the efficacy of IFN-a2b/PegIFN-a2b (one or multiple treatment sessions) and the predictors for sustained virological response (SVR) in HCV-infected ßTM patients. METHODS: Between 11/1992 and 12/2013 [median follow-up: 165.5 months (8-237)], 48 ßTM HCV-infected patients [19 males, median age: 22 years (12-45)], received IFN-a2b (n=34) or PegIFN-a2b (n=14). Twenty-three patients (47.9%) had a previous splenectomy; 13/40 (32.5%) patients had Ishak stage >/=4 and 21/40 (52.5%) had siderosis grade 3-4. HCV-genotype was available in 36 patients (genotype 1: 47.2%, 2: 5.6%, 3: 25%, and 4: 22%). IL28B genotype was determined in 37 patients by means of in-house real-time PCR (CC: 27%, CT: 62.2%, TT: 10.8%). RESULTS: Totally, 15/48 (31.3%) achieved SVR following the first treatment and 18/48 (37.5%) after multiple courses. Splenectomy (p=0.01) and fibrosis grade >/=4 (p<0.05) were negative predictors for SVR (first course), whereas splenectomy (p<0.05) and age >18 (p<0.02) for SVR after multiple courses. In HCV-genotype 1/4 (n=25), none of the patients with CT or TT IL28B genotype achieved SVR compared to 50% of the CC patients (p=0.004). CONCLUSIONS: Interferon is an effective therapeutic option in HCV-infected ßTM patients. IL28B genotype was a strong predictor for SVR, together with splenectomy, age and fibrosis.

Critical illness-related corticosteroid insufficiency in patients with cirrhosis and variceal bleeding.

BACKGROUND & AIMS: Relative adrenal insufficiency (AI) occurs in patients with cirrhosis with sepsis, but not with variceal bleeding. We evaluated adrenal function in cirrhotic patients with and without bleeding. METHODS: Twenty cirrhotic patients with variceal bleeding were evaluated using the short synacthen test (SST) and 10 using the low-dose synacthen test (LDSST) followed by SST. The control group included 60 stable cirrhotic patients, assessed by LDSST (n = 50) or SST (n = 10), and 14 healthy volunteers. AI was diagnosed using SST, based on peak cortisol levels ≤ 18 µg/dL in nonstressed patients or Δmax <9 µg/dL or a total cortisol level <10 µg/dL in stressed patients with variceal bleeding-the current criteria for critical illness-related corticosteroid insufficiency. Using LDSST, diagnosis was based on peak concentrations of cortisol ≤ 18 µg/dL in nonstressed patients and <25 µg/dL (or Δmax <9 µg/dL) in patients with variceal bleeding. We evaluated patients with levels of serum albumin >2.5 g/dL, to indirectly assess cortisol binding. RESULTS: All healthy volunteers had normal results from LDSSTs and SSTs. Patients with variceal bleeding had higher median baseline concentrations of cortisol (15.4 µg/dL) than stable cirrhotic patients (8.7 µg/dL, P = .001) or healthy volunteers (10.1 µg/dL, P = .01). Patients with variceal bleeding had higher median peak concentrations of cortisol than stable cirrhotic patients (SST results of 32.7 vs 21 µg/dL, P = .001; LDSST results of 9.3 vs 8.1 µg/dL; nonsignificant), with no differences in Δmax in either test. These differences were greater with variceal bleeding than in stable cirrhotic patients with AI. Subanalysis of patients with albumin levels >2.5 g/dL did not change these differences. CONCLUSIONS: Cirrhotic patients with variceal bleeding have AI. Despite higher baseline concentrations of serum cortisol and subnormal Δmax values, they did not have adequate responses to stress, and therefore had critical illness-related corticosteroid insufficiency.