Long-term follow-up of HCV-infected patients with end-stage chronic kidney disease after sustained virological response with direct-acting antiviral therapy.

BACKGROUND AND AIM: Patients with chronic kidney disease (CKD) and hepatitis C infection can be safely and effectively treated with direct-acting antivirals (DAAs). However, there is scarce data on the long-term impact of hepatitis C cure on CKD. The aim of this study was to assess the long-term mortality, morbidity and hepatic/renal function outcomes in a cohort of HCV-infected individuals with CKD treated with DAAs. METHODS: 135 HCV patients with CKD stage 3b-5 who received ombitasvir/paritaprevir/ritonavir±dasabuvir in a multicenter study were evaluated for long-term hepatic and renal outcomes and their associated mortality. RESULTS: 125 patients achieved SVR and 66 were included. Prior to SVR, 53 were under renal replacement therapy (RRT) and 25 (37.8%) had liver cirrhosis. After a follow-up of 4.5 years, 25 (38%) required kidney transplantation but none combined liver-kidney. No changes in renal function were observed among the 51 patients who did not receive renal transplant although eGFR values improved in those with baseline CKD stage 3b-4. Three (5.6%) subjects were weaned from RRT. Eighteen (27.3%) patients died, mostly from cardiovascular events; 2 developed liver decompensation and 1 hepatocellular carcinoma. No HCV reinfection was observed. CONCLUSIONS: Long-term mortality remained high among end-stage CKD patients despite HCV cure. Overall, no improvement in renal function was observed and a high proportion of patients required kidney transplantation. However, in CKD stage 3b-4 HCV cure may play a positive role in renal function.

A pharmacogenetics study of TPMT and ITPA genes detects a relationship with side effects and clinical response in patients with inflammatory bowel disease receiving Azathioprine.

BACKGROUND AND AIMS: Pharmacogenetic studies in inflammatory bowel diseases (IBD) are mainly focused on genes involved in the metabolism of Azathioprine (AZA). Use of AZA is limited by its toxicity, which occurs in 20-30% of patients. Variants in the Thiopurine S-methyltransferase (TPMT) and Inosine triphosphate pyrophosphatase (ITPA) genes have been associated with AZA toxicity, but also can contribute to the lack of response. The aims of this study were to determine the contribution of TPMT and ITPA variants in the development of AZA-related toxicity and response. METHODS: Variants associated with the decrease of enzyme activity in TPMT and ITPA genes were genotyped with the Snapshot system in 232 IBD patients treated with AZA, and correlated with the clinical response and development of adverse drug reactions in a retrospective case-control study. RESULTS: Genotypic analysis showed that there is a statistical significance between c.94C > A variant on ITPA gene with non response to AZA treatment (p=0.005) and arthralgia (OR 8.2353; 95%CI 1.752-38.87, p=0.0041), as well as between mutant TPMT alleles and myelosuppression (OR 7.5; 95%CI 1.4456-38.91, p=0.0304). CONCLUSIONS: There is a positive correlation between c.94C > A variant on ITPA with clinical response. Mutant alleles on TPMT and the variant c.94C > A on ITPA gene predict side effects induced by AZA in our population (myelosuppression and arthralgia).