This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

Combination therapy with PEG IFN alpha-2b plus RBV is more effective in patients who relapsed after combination standard IFN plus RBV than in nonresponders to either combination therapy or IFN monotherapy. There was no significant effect of dosing regimen.

No abstract

Estimation of glomerular filtration rate (eGFR) in patients with liver disease is suboptimal in the presence of renal dysfunction. We developed a model for GFR assessment in liver disease (GRAIL) before and after liver transplantation (LT). GRAIL was derived using objective variables (creatinine, blood urea nitrogen, age, gender, race, and albumin) to estimate GFR based on timing of measurement relative to LT and degree of renal dysfunction (www.bswh.md/grail). The measured GFR (mGFR) by iothalamate clearance (n = 12,122, 1985‐2015) at protocol time points before/after LT was used as reference. GRAIL was compared with the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) and Modification of Diet in Renal Disease (MDRD‐4, MDRD‐6) equations for mGFR < 30 mL/min/1.73 m2. Prediction of development of chronic kidney disease (mGFR < 20 mL/min/1.73 m2, initiation of chronic dialysis) and listing or receipt of kidney transplantation within 5 years was examined in internal cohort (n = 785) and external validation (n = 68,217, 2001‐2015). GRAIL had less bias and was more accurate and precise as compared with CKD‐EPI, MDRD‐4, and MDRD‐6 at time points before/after LT for low GFR. For mGFR < 30 mL/min/1.73 m2, the median difference (eGFR–mGFR) was GRAIL: 5.24 (9.65) mL/min/1.73 m2 as compared with CKD‐EPI: 8.70 (18.24) mL/min/1.73 m2, MDRD‐4: 8.82 (17.38) mL/min/1.73 m2, and MDRD‐6: 6.53 (14.42) mL/min/1.73 m2. Before LT, GRAIL correctly classified 75% as having mGFR < 30 mL/min/1.73 m2 versus 36.1% (CKD‐EPI), 36.1% (MDRD‐4), and 52.8% (MDRD‐6) (P < 0.01). An eGFR < 30 mL/min/1.73 m2 by GRAIL predicted development of CKD (26.9% versus 4.6% CKD‐EPI, 5.9% MDRD‐4, and 10.5% MDRD‐6) in center data and needing kidney after LT (48.3% versus 22.0% CKD‐EPI versus 23.1% MDRD‐4 versus 48.3% MDRD‐6, P < 0.01) in national data within 5 years after LT. Conclusion: GRAIL may serve as an alternative model to estimate GFR among patients with liver disease before and after LT at low GFR.

The use of hepatitis C virus (HCV)-positive organs in liver transplantation (LT) has increased in the era of direct-acting antiviral therapy. A rising demand for organs, the increased ability to effectively treat HCV infection in the transplant setting, and an unprecedented increase in HCV-positive donors have all contributed to this trend. A recent abrupt rise in opioid use in the United States has resulted in a surge of injection drug use, transmission of HCV, and opioid-related overdose deaths. Geographical areas most affected by the opioid epidemic have experienced a rapid increase in recovery and utilization of HCV-positive donor organs, in which the proportion of deceased donor LTs in the United States from donors who are HCV positive has increased nearly 2-fold within the last 3 years. The prospect of expanding the organ donor pool with HCV-positive donors and achieving acceptable posttransplant outcomes has generated much interest in the areas of liver, kidney, and thoracic transplantation, including the potential for transplanting organs from HCV positive donors into HCV-negative recipients. Developing strategies to ensure appropriate selection of potential recipients of HCV-positive organs, initiating timely antiviral therapy, and defining associated risks will be critical in achieving optimal posttransplant outcomes in this setting. (Hepatology 2018;67:1600-1608).