Effects of ethnicity and socioeconomic status on survival and severity of fibrosis in liver transplant recipients with hepatitis C virus.

The ethnicity and socioeconomic status of the host may affect the progression of hepatitis C virus (HCV). We aimed to compare survival and fibrosis progression in Hispanic white (HW) and non-Hispanic white (NHW) recipients of liver transplantation (LT) with HCV. All HW and NHW patients with HCV who underwent transplantation between January 2000 and December 2007 at 2 centers were retrospectively assessed. The primary outcomes were the time to death, death or graft loss due to HCV, and significant fibrosis [at least stage 2 of 4]. Five hundred eleven patients were studied (159 HW patients and 352 NHW patients), and the baseline demographics were similar for the 2 groups. NHW patients were more likely to be male, to have attended college, and to have private insurance, and they had a higher median household income (MHI). The unadjusted rates of survival (log-rank P = 0.93), death or graft loss due to HCV (P = 0.89), and significant fibrosis (P = 0.95) were similar between groups. In a multivariate analysis controlling for center, age [hazard ratio (HR) per 10 years = 1.43, P = 0.01], donor age (HR per 10 years = 1.25, P < 0.001), and rejection (HR = 1.47, P = 0.048) predicted death, whereas HW ethnicity (HR = 1.06, P = 0.77) was not significant. Independent predictors of significant fibrosis were HW ethnicity (HR = 2.42, P = 0.046), MHI (HR per $10,000 = 1.11, P = 0.01), donor age (HR per 10 years = 1.13, P = 0.02), cold ischemia time (HR = 1.06, P = 0.03), and the interaction between ethnicity and MHI (HR = 0.82, P = 0.03). In conclusion, there is no difference in post-LT survival or graft loss due to HCV between HW patients and NHW patients. Socioeconomic factors may influence disease severity; this is suggested by our findings of more significant fibrosis in HW patients with a low MHI.

Prevention of de novo hepatitis B with adefovir dipivoxil in recipients of liver grafts from hepatitis B core antibody-positive donors.

Lamivudine has been shown to prevent de novo hepatitis B virus (HBV) infections in liver transplantation (LT) patients receiving hepatitis B core antibody-positive (HBcAb(+)) grafts, but it may produce long-term resistance. Adefovir dipivoxil (ADV) might be effective in preventing de novo hepatitis and resistance. A single-center, prospective trial was conducted with 16 adults (10 men and 6 women, mean age = 54 ± 11 years) who underwent LT with HBcAb(+) grafts between September 2007 and October 2009. After LT, patients were given ADV [10 mg daily (adjusted for renal function)]. No hepatitis B immune globulin was administered. At LT, all graft recipients were hepatitis B surface antigen-negative (HBsAg(-)), 38% were surface antibody-positive (HBsAb(+)), and 50% were HBcAb(+). The median follow-up after LT was 1.8 years (range = 1.0-2.6 years). All recipients had undetectable HBV DNA (<40 IU/mL) after LT until the end of follow-up. One recipient (6%) who was HBsAb(-) and HBcAb(-) before LT became HBsAg(+) after 52 weeks. One recipient was switched from ADV to entecavir for chronic renal insufficiency, and 19% of the patients had renal dose adjustments. There was a nonsignificant trend of increasing creatinine levels over time (1.2 mg/dL at LT, 1.3 mg/dL 1 year after LT, and 2.0 mg/dL 2 years after LT, P = 0.27). A comparison with a control cohort of LT recipients with hepatitis C virus who did not receive ADV showed no difference in the creatinine levels at LT or 1 year after LT. In conclusion, ADV prophylaxis prevents HBV replication in recipients of HBcAb(+) livers but does not fully protect recipients from de novo HBV. Long-term follow-up is needed to better determine the risk of de novo infection.

Urinary neutrophil gelatinase-associated lipocalin predicts mortality and identifies acute kidney injury in cirrhosis.

BACKGROUND: Kidney failure predicts mortality in patients with cirrhosis. Identification of kidney failure etiology and recognition of those at the highest mortality risk remains a challenge. AIMS: We hypothesized that urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts mortality and identifies hepatorenal syndrome (HRS) in patients with cirrhosis. METHODS: Prospectively enrolled patients with cirrhosis were investigated by uNGAL immunoblot upon hospital admission. Kidney failure type was determined blinded to NGAL measurements. RESULTS: One hundred eighteen patients were enrolled. Fifty-two (44 %) patients had normal kidney function, 14 (12 %) stable chronic kidney disease, 17 (14 %) prerenal azotemia, 20 (17 %) HRS, and 15 (13 %) intrinsic acute kidney injury (iAKI). Patients with HRS had uNGAL levels intermediate between prerenal azotemia [median (IQR) 105 (27.5-387.5) vs. 20 (15-45) ng/mL, p = 0.004] and iAKI [325 (100-700), p < 0.001]. Fifteen (13 %) patients died. In unadjusted analysis, uNGAL predicted inpatient mortality (OR 2.00, 95 % CI 1.36-2.94) and mortality or liver transplantation (OR 2.01, 95 % CI 1.42-2.85). In multiple regression models, uNGAL > 110 ng/mL (OR 6.05, 95 % CI 1.35-27.2) and HRS (OR 6.71, 95 % CI 1.76-25.5) independently predicted mortality, adjusting for age and serum creatinine >1.5 mg/dL. CONCLUSIONS: uNGAL strongly predicts short-term inpatient mortality in both unadjusted and adjusted models. Patients with HRS may have uNGAL levels intermediate between those with prerenal azotemia and iAKI. Further studies are needed to determine if uNGAL can improve discrimination of HRS from other types of acute kidney injury and predict short- and long-term cirrhosis outcomes.

Prevention of de novo hepatitis B in recipients of core antibody-positive livers with lamivudine and other nucleos(t)ides: a 12-year experience.

BACKGROUND: Lamivudine (LAM) has been shown to prevent de novo hepatitis B virus (HBV) infection in recipients of hepatitis B core antibody (HBcAb)-positive liver transplants (LT) but primarily in small studies with limited follow-up. METHODS: We conducted a retrospective cohort study of HBcAb+ graft recipients at our institution from October 1999 to August 2008. RESULTS: One hundred nineteen recipients without prior HBV were identified (median age, 54 years; 70% male), of which 62 received LAM. The median follow-up was 2.6 years overall and 5.3 years in the LAM group. Among LAM recipients, 44% were HBV naïve (HBsAb-/HBcAb-) at LT, of which 6% developed HBsAb+ and 3% developed HBcAb+ after LT. Eight percent developed de novo HBV: two recipients became hepatitis B surface antigen positive at 70 and 23 months and three experienced breakthrough with HBV DNA more than 2000 IU at 1 to 9 months after LT. Sixty percent (3 of 5) were HBV naïve. Four (6%) other recipients also had transiently detectable HBV less than 2000 IU, which did not require any changes to their prophylaxis regimen. When compared with recipients who received other nucleos(t)ide analogues, there was no difference in de novo rates: LAM 8% (5 of 62), adefovir 15% (5 of 33), tenofovir 0% (0 of 3), entecavir 0% (0 of 1), and 5% (1 of 20) for those not given prophylaxis (P=0.59). CONCLUSIONS: LAM monoprophylaxis was effective in preventing de novo HBV in the vast majority of recipients over long-term follow-up. Adefovir had a higher rate of de novo infections numerically, whereas tenofovir and entecavir had no cases and may be more effective, but this was limited by a small sample size.

Basiliximab induction and delayed calcineurin inhibitor initiation in liver transplant recipients with renal insufficiency.

BACKGROUND: Renal insufficiency (RI) is common after liver transplantation (LT) and may worsen due to calcineurin inhibitor (CNI) use. We compared LT outcomes using basiliximab induction and delayed CNI initiation to controls with a standard CNI regimen in patients with peri-LT RI. METHODS: All adults transplanted January 2004 to December 2007 with peri-LT RI (hemodialysis or creatinine ≥1.5 within 1 week of LT) were included in a retrospective nonrandomized cohort. Outcomes including 30-day and 1-year patient and graft survival and renal function were compared between basiliximab and control groups. RESULTS: Two hundred twenty-nine patients (102 basiliximab, 127 controls) were analyzed, mean age 54 years, 72% men, 54% with hepatitis C virus. Mean model for end-stage liver disease (28.2 vs. 20.0; P<0.001) and creatinine (1.9 vs. 1.6; P=0.001) were higher and more patients were on hemodialysis at LT (29% vs. 6%; P<0.001) in the basiliximab group. 30-day patient (99% vs. 97%; P=0.26) and graft survival (98% vs. 95%; P=0.17), 1-year patient (87% vs. 87%; P=0.89) and graft survival (86% vs. 82%; P=0.37), mean creatinine at 1-year (1.5 vs. 1.5 mg/dL; P=0.82), and treated acute rejection (6% vs. 6%; P=0.90) were similar between basiliximab and control groups, respectively. In multivariable logistic regression, basiliximab was not significantly associated with 30-day (odds ratio, 0.10; P=0.11) or 1-year (odds ratio, 0.97; P=0.94) survival, controlling for age, previous LT, model for end-stage liver disease, and hepatitis C virus. CONCLUSIONS: Basiliximab induction resulted in 30-day and 1-year patient, graft and renal outcomes comparable with a control group receiving standard CNI-based immunosuppression. Antibody induction with delayed CNI should be further studied prospectively.