Summary Background The biological mechanism underlying the association between IFNL4/IFNL3 polymorphism and peginterferon/ribavirin (PR) response in HCV‐1 is thought to involve differential intrahepatic interferon‐stimulated gene expression. HCV‐3 is more sensitive to PR, but there are no studies of the association between IFNL4 polymorphism, PR treatment response and liver interferon‐stimulated gene expression in HCV‐3. Aim We evaluated the association between IFNL4/IFNL3 genotypes, PR treatment outcomes and intrahepatic interferon‐stimulated gene expression, according to HCV genotype. Methods HCV‐1 and HCV‐3 patients who received PR therapy were identified. IFNL3 (rs12979860) and IFNL4 genotype (rs368234815) were determined. A second cohort with stored liver specimens was identified. Expression of ISGs was measured by rt‐PCR. Results Two hundred and fifty‐nine patients were identified: 55% HCV‐1, 45% HCV‐3. IFNL4 genotype frequency was TT/TT 44%, TT/ΔG 42% andΔG/ΔG 14%. Linkage disequilibrium with IFNL3 genotype was high (r2 = 0.98). The association between IFNL4 genotype and PR response was attenuated in HCV‐3 vs. HCV‐1 (HCV‐3: SVR 89% vs. 76% vs. 72% for TT/TT vs. TT/ΔG vs. ΔG/ΔG, P = 0.09; HCV‐1: SVR: 82% vs. 29% vs. 24%, P < 0.001). Intrahepatic ISG expression was evaluated in 92 patients; 61% HCV‐1. The association between IFNL4 genotype and liver ISG expression was significantly different for HCV‐3 vs. HCV‐1 (P‐value for interaction = 0.046), with levels of interferon‐stimulated gene expression being highest in HCV‐1 patients who carried a poor‐response IFNL4 genotype. Conclusions The relationship between IFNL4 genotype and PR treatment response as well as intrahepatic interferon‐stimulated gene expression differs between HCV‐1 and HCV‐3. These data suggest fundamental differences in host–virus interactions according to HCV genotype.

SIRS, We read with interest the recent paper by FernandezBanares et al.1 detailing evidence-based recommendations for the management of microscopic colitis. Included in this paper was an overview of the conflicting evidence relating to methotrexate treatment of collagenous colitis. We have recently analysed the outcome of a series of patients with collagenous colitis who were treated with oral methotrexate. We retrospectively studied 20 consecutive patients (19 females, median age 66 years) who had been diagnosed with biopsy-proven collagenous colitis in a single gastroenterologist's practice between 1999 and 2013. Ten patients (all female, median age 62 years) were treated with oral methotrexate at an initial dose of 10 mg/week. Seven of these patients had previously been treated with loperamide, sulfasalazine or both without achieving clinical remission (defined as mean of <3 stools/day and mean <1 watery stool/day), and in the remaining three patients methotrexate was the first treatment commenced.All patients achieved clinical remission at first followup review. The median time to first review was 4 weeks post-methotrexate initiation (range 2-12 weeks). Histological remission of collagenous colitis was confirmed in the two patients who had repeat colonic biopsies while being treated with methotexate. No patients had a symptomatic relapse while continuing methotrexate therapy. No haematologic or hepatic toxicity was observed in any patient while being treated with methotrexate.

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