Multicenter experience using simeprevir and sofosbuvir with or without ribavirin to treat hepatitis C genotype 1 in patients with cirrhosis.

UNLABELLED: Interferon (IFN)-free regimens are needed to treat hepatitis C virus (HCV) infection. Combined simeprevir (SMV) and sofosbuvir (SOF) with or without ribavirin (RBV) results in high sustained virological response (SVR) rates along with minimal adverse events (AEs) in patients with hepatitis C genotype 1 (HCV GT1). The aim of this study was to report on the virological response, safety, and tolerability of SOF and SMV with or without RBV in compensated and decompensated patients with cirrhosis with HCV GT1 infection. Patients treated with standardized clinical protocol utilizing SMV+SOF with or without RBV at three transplant centers were retrospectively reviewed. A total of 119 patients (61% male, 87% white, 69% subtype 1a, 30% Child-Pugh-Turcott [CPT]-B liver cirrhosis [LC], and 82% were treatment experienced) received treatment and were followed for a median of 38 weeks (range, 12-58). Sustained virological response (SVR) at week 12 (SVR12) was achieved in 78% (92 of 118) of patients (95% confidence interval: 69-85). Lower pretreatment Model for End Stage Liver Disease (MELD) score was a predictor of SVR12 (P = 0.018). Baseline viral load, previous treatment status, RBV use, or GT1 subtype did not impact SVR 12. The majority of patients with SVR12 showed stability or improvement in MELD score. Treatment was very well tolerated with mild degrees of AEs. CONCLUSIONS: The regimen of SMV+SOF with or without RBV for 12 weeks was very well tolerated and resulted in high SVR12 rates (78%) in HCV GT1 patients with LC. SVR12 was inversely related to pretreatment MELD. SVR12 had favorable short-term impact on MELD score. Long-term impact on disease stability is yet to be determined. Longer treatment duration or the use of different regimen may still be needed in this population.

Multicenter experience using simeprevir and sofosbuvir with or without ribavirin to treat hepatitis C genotype 1 after liver transplant.

UNLABELLED: Treatment with an all-oral interferon-free antiviral regimen using simeprevir and sofosbuvir with or without ribavirin (RBV) for 12 weeks resulted in high sustained virologic response (SVR) rates along with minimal adverse events in non-liver transplant (LT) patients with hepatitis C virus (HCV) genotype 1 infection. This is the first multicenter report on the efficacy, safety, and tolerability of this regimen in LT recipients. A total of 123 patients (76% male, 74% white, 60% genotype 1a, 30% METAVIR F3-F4, 4% decompensation, 11% cholestatic recurrence, 7% had kidney transplant, and 82% previously failed pegylated interferon/RBV-based regimens) received treatment and were followed for a median of 30 weeks (range 12-53 weeks). The median time from LT to treatment was 32 months (range 2-317 months). Tacrolimus was the primary immunosuppression in 91% of patients. Minimal immunosuppression dose adjustments were required. An SVR 12 weeks after treatment completion (SVR12) was achieved in 90% of patients (95% confidence interval 84%-96%). In patients with genotype 1a infection, the SVR12 rate was significantly lower in those with METAVIR F3-F4 (71%) compared to those with F0-F2 (91%). Half of the patients achieved undetected HCV RNA at treatment week 4, and their SVR12 rate was significantly higher (96%) compared to those with detectable HCV RNA (83%). Treatment was very well tolerated with mild degrees of adverse events, except for one death possibly due to drug-induced lung injury. In the 25 patients who received RBV, 72% developed anemia requiring intervention. CONCLUSION: An all-oral interferon-free antiviral regimen using simeprevir and sofosbuvir with or without RBV for 12 weeks was very well tolerated and resulted in excellent SVR12 rates in LT recipients with HCV genotype 1 infection.

Acute liver failure associated with Garcinia cambogia use.

Millions of Americans regularly use herbal supplements, but many are unaware of the potential hidden dangers. Numerous supplements have been associated with hepatotoxicity and, indeed dietary/herbal supplements represent an increasingly common source of acute liver injury. We report a case of acute liver failure requiring liver transplantation associated with the use of Garcinia cambogia, a supplement widely promoted for weight loss. When patients present with acute hepatitis or liver failure from an unknown etiology, a careful history of supplement use should be performed.

Comparison of post-transplantation diabetes mellitus incidence and risk factors between kidney and liver transplantation patients.

BACKGROUND: Most prior studies characterizing post-transplantation diabetes mellitus (PTDM) have been limited to single-cohort, single-organ studies. This retrospective study determined PTDM across organs by comparing incidence and risk factors among 346 liver and 407 kidney transplant recipients from a single center. METHODS: Univariate and multivariate regression-based analyses were conducted to determine association of various risk factors and PTDM in the two cohorts, as well as differences in glucometrics and insulin use across time points. RESULTS: There was a higher incidence of PTDM among liver versus kidney transplant recipients (30% vs. 19%) at 1-year post-transplant. Liver transplant recipients demonstrated a 337% higher odds association to PTDM (OR 3.37, 95% CI (1.38-8.25), p<0.01). 1-month FBG was higher in kidney patients (135 mg/dL vs 104 mg/dL; p < .01), while 1-month insulin use was higher in liver patients (61% vs 27%, p < .01). Age, BMI, insulin use, and inpatient FBG were also significantly associated with differential PTDM risk. CONCLUSIONS: Kidney and liver transplant patients have different PTDM risk profiles, both in terms of absolute PTDM risk as well as time course of risk. Management of this population should better reflect risk heterogeneity to short-term need for insulin therapy and potentially long-term outcomes.

Hyperglycemia during the immediate period following liver transplantation.

AIM: High blood glucose levels in the hospital are common among transplant recipients. METHODS: Retrospective analysis, stratified by diagnosis of pretransplant diabetes mellitus (DM). RESULTS: Of 346 patients, 96 had pretransplant DM (insulin, n = 60; no insulin, n = 36) and 250 did not. Patients with pretransplant DM had higher inpatient mean glucose levels and more hyperglycemia and hypoglycemia (all p < 0.01). For patients without pretransplant DM, the need for insulin at discharge increased 23% for every 5-year age increase (odds ratio: 1.23; 95% CI: 1.06-1.44; p = 0.007) and 51% for every five units of glucose measurements >180 mg/dl (OR: 1.51; 95% CI: 1.23-1.95; p < 0.01). CONCLUSION: Inpatient hyperglycemia was common in liver transplant recipients. Hospital practitioners must anticipate the need to teach self-management skills to liver transplant recipients.