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Background The PNPLA3/Adiponutrin rs738409 C/G single nucleotide polymorphism is associated with the severity of steatosis, steatohepatitis and fibrosis in patients with non-alcoholic fatty liver disease, as well as the severity of steatosis and fibrosis in patients with chronic hepatitis C ( CHC). Aim To test in genotype 1(G1)- CHC patients, the putative association between the PNPLA3 variant and histological features of steatohepatitis, as well as their impact on the severity of fibrosis. Methods Four hundred and thirty-four consecutively biopsied Caucasian G1- CHC patients were genotyped for PNPLA3 rs738409, its effect evaluated by using an additive model. Histological features of steatohepatitis in CHC were assessed using the Bedossa classification. Hepatic expression of PNPLA3 mRNA was evaluated in 63 patients. Results The prevalence of steatohepatitis increased from 16.5% in patients with PNPLA3 CC, to 23.2% in CG and 29.2% in the GG genotype ( P = 0.02). By multiple logistic regression, PNPLA3 genotype ( OR 1.54, 95% CI 1.03-2.30, P = 0.03), together with age ( OR 1.03, 95% CI 1.00-1.05, P = 0.02), BMI ≥ 30 ( OR 2.06, 95% CI 1.04-4.10, P = 0.03) and homoeostasis model assessment ( HOMA, OR 1.18, 95% CI 1.04-1.32, P = 0.006) were independently linked to steatohepatitis. When stratifying for obesity, PNPLA3 was associated with NASH in non-obese patients only (12.0% in CC vs. 18.3% in CG vs. 27.3% in GG, P = 0.01), including after correction for metabolic confounders ( OR 2.06, 95% CI 1.26-3.36, P = 0.004). We showed an independent association between steatohepatitis ( OR 2.05, 95% CI 1.05-4.02, P = 0.003) and severe fibrosis. Higher liver PNPLA3 mRNA was associated both with the severity of steatosis (adjusted P = 0.03) and steatohepatitis after adjusting for gender, age, BMI and HOMA ( P = 0.002). Conclusion In patients with genotype 1 hepatitis C, the PNPLA3 G variant is associated with a higher risk of steatosis severity and steatohepatitis, particularly among non-obese subjects. [ABSTRACT FROM AUTHOR]

Lower 25-hydroxyvitamin D [25( OH) D] serum levels have been associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients ( G1 CHC). In addition, a recent genome-wide study identified genetic variants (rs12785878, near dehydrocholesterol reductase, DHCR7; rs10741657, near CYP2R1; and rs7041, near vitamin D-binding protein, GC) affecting 25( OH) D serum levels in healthy populations. We aimed to assess the association between vitamin D serum levels and its genetic determinants, with the severity of liver fibrosis. Two hundred and sixty patients with biopsy-proven G1 CHC were consecutively evaluated. The 25( OH) D serum levels were measured by high-pressure liquid chromatography. All patients were genotyped for DHCR7 rs12785878, CYP2R1 rs10741657 and GC rs7041 single nucleotide polymorphisms. DHCR7 GG genotype ( P = 0.003) and the severity of fibrosis ( P = 0.03) were independent factors associated with lower 25( OH) D serum levels in multiple linear regression analysis. Interestingly, 53.8% (7/13) of patients with DHCR7 GG genotype had severe liver fibrosis, compared to 27.1% (67/247) of those with DHCR7 TT/ TG genotype ( P = 0.03). By multivariate logistic regression analysis, severe fibrosis was independently associated with older age ( OR, 1.056; 95% CI, 1.023-1.089, P = 0.001), low cholesterol ( OR, 0.984; 95% CI, 0.974-0.994, P = 0.002), high triglycerides ( OR, 1.008; 95% CI, 1.002-1.015, P = 0.01), low 25( OH)D ( OR, 0.958; 95% CI, 0.919-0.999, P = 0.04), DHCR7 GG genotype ( OR, 4.222; 95% CI, 1.106-16.120; P = 0.03), moderate-severe steatosis ( OR, 2.588; 95% CI, 1.355-4.943; P = 0.004) and moderate-severe necroinflammatory activity (grading) ( OR, 2.437; 95% CI, 1.307-4.763; P = 0.001). No associations were found between liver fibrosis and both CYP2R1 and GC genotypes. In patients with G1 CHC, GG homozygosis for DHCR7 gene and lower 25( OH) D levels are independently associated with the severity of liver fibrosis. [ABSTRACT FROM AUTHOR]

. Soluble CD36 (sCD36) plasma levels, a known marker of cardiometabolic disorders, are associated with surrogate markers of steatosis, while experimental and human studies show a link between CD36 expression in the liver and steatosis. In a cohort of patients with genotype 1 chronic hepatitis C (G1 CHC), we tested the association of sCD36 plasma levels with host and viral factors and sustained virological response (SVR). One hundred and seventy-five consecutive biopsy-proven patients were studied. sCD36 plasma levels were assessed by an in-house ELISA. All biopsies were scored by one pathologist for staging and grading (Scheuer) and graded for steatosis, which was considered moderate-severe if ≥20%. Patients underwent standard of care therapy with pegylated interferon and ribavirin. The severity of steatosis progressively increased according to sCD36 quartiles ( P = 0.02); total and low-density lipoprotein (LDL) cholesterol levels were significantly higher in patients in the lower quartile compared to all the others. Gamma-glutamyl transferase ( P = 0.02), homoeostasis model assessment (HOMA) score ( P = 0.002) and sCD36 ( P = 0.04) were independently associated with the severity of steatosis as continuous variable. Multivariate logistic regression analysis showed that HOMA (OR 1.243, 95% CI 1.04-1.484, P = 0.01) and sCD36 (OR 1.445, 95%CI 1.135-1.839, P = 0.003) were independently linked to steatosis ≥20%. No association was found between sCD36 and SVR. CD36 is linked to steatosis and insulin resistance in patients with G1 CHC, but does not predict response to treatment. The potential of sCD36 as a surrogate marker of steatosis should be further investigated. [ABSTRACT FROM AUTHOR]

The article focuses on the effectiveness of adalimumab (ADA) and golimumab (GOL) for treating moderate to severe ulcerative colitis (UC). Topics discussed include clinical remission of patients naïve and non-naïve to anti-TNF α treatment; rate of clinical remission with ADA and GOL; and older age people associated with higher remission rate.

A letter to the editor is presented in response to the article on the effectiveness and safety of a second anti-tumor necrosis factor (TNF) agent after primary or secondary failure or intolerance to a first drug.