Combined Liver-Kidney Transplant for Juvenile Polycystic Kidney Disease and Concomitant Hereditary Factor V Deficiency.

Factor V deficiency is a congenital bleeding diathesis that, in selected cases, may be managed with liver transplant. In this case, we describe the treatment of an adult patient with kidney failure secondary to juvenile onset polycystic kidney disease who received a combined liver-kidney transplant as a method to manage the risks associated with the need for a kidney transplantin the setting of factorV deficiency and high sensitization.

MELD-GRAIL and MELD-GRAIL-Na Are Not Superior to MELD or MELD-Na in Predicting Liver Transplant Waiting List Mortality at a Single-center Level.

Background: Controversy exists regarding the best predictive model of liver transplant waiting list (WL) mortality. Models for end-stage liver disease-glomerular filtration rate assessment in liver disease (MELD-GRAIL) and MELD-GRAIL-Na were recently described to provide better prognostication, particularly in females. We evaluated the performance of these scores compared to MELD and MELD-Na. Methods: Consecutive patients with cirrhosis waitlisted for liver transplant from 1998 to 2017 were examined in this single-center study. The primary outcome was 90-d WL mortality. MELD, MELD-Na, MELD-GRAIL, and MELD-GRAIL-Na at the time of WL registration were compared. Model discrimination was assessed with area under the receiver operating characteristic curves and Harrell's C-index after fitting Cox models. Model calibration was examined with Grønnesby and Borgan's modification of the Hosmer-Lemeshow formula and by comparing predicted/observed outcomes across model strata. Results: The study population comprised 1108 patients with a median age of 53.5 (interquartile range 48-59) y and male predominance (74.9%). All models had excellent areas under the receiver operating characteristic curves for the primary outcome (MELD 0.89, MELD-Na 0.91, MELD-GRAIL 0.89, MELD-GRAIL-Na 0.89; all comparisons P > 0.05). Youden index cutoffs for 90-d mortality were as follows: MELD, 19; MELD-Na, 22; MELD-GRAIL, 18; and MELD-GRAIL-Na, 17. Variables associated with 90-d mortality on multivariable Cox regression were sodium, bilirubin, creatinine, and international normalized ratio. There were no differences in model discrimination using Harrell's C-index. All models were well calibrated; however, divergence between observed and predicted mortality was noted with scores ≥25. Conclusion: There were no demonstrable differences in discrimination or calibration of GRAIL-based models compared with MELD or MELD-Na in our cohort. This suggests that GRAIL-based models may not have meaningful improvements in discriminatory ability when applied to other settings.

Nature and outcomes of the increased incidence of colorectal malignancy after liver transplantation in Australasia.

OBJECTIVES: To examine whether incidence of colorectal malignancy is increased in Australasian liver transplant recipients compared with the general population of Australia, and to assess the characteristics and outcomes of colorectal malignancy in this patient group. DESIGN, SETTING AND PATIENTS: Data on patients who underwent orthotopic liver transplantation (OLTx) and had a diagnosis of de-novo colorectal malignancy after transplantation during the period 1985-2011 were obtained from the Australia and New Zealand Liver Transplant Registry, and these data were compared with colorectal malignancy data from the Australian Institute of Health and Welfare. MAIN OUTCOME MEASURES: Time from OLTx to diagnosis of colorectal malignancy, stage of colorectal malignancy at diagnosis, patient survival, and standardised incidence ratio (SIR) for colorectal malignancy. RESULTS: Forty-eight of 3735 recipients (1.3%) were diagnosed with colorectal malignancy at a median of 7.3 years after OLTx. More advanced colorectal malignancy (regional or metastatic disease) was evident at diagnosis in 20 of the 48 patients; these patients tended to be younger than patients with less advanced malignancy (P = 0.01) and diagnosed sooner after OLTx (P = 0.005). Despite treatment predominantly with surgery, 19 of the 48 patients died from the malignancy. The overall SIR for colorectal malignancy liver transplant recipients compared with the general population of Australia was 2.80 (95% CI, 2.06-3.71). CONCLUSIONS: The incidence of colorectal malignancy is increased in liver transplant recipients in comparison with the general population. Of concern is the tendency for advanced malignancy to be diagnosed in younger patients. These data highlight the importance of considering whether specific guidelines for colorectal malignancy screening in the Australasian adult liver transplant population are needed.

Early high peak hepatitis C viral load levels independently predict hepatitis C-related liver failure post-liver transplantation.

The aim of this study was to examine the importance of the serum hepatitis C viral load within the first year post-liver transplant in determining posttransplant survival. A retrospective analysis of 118 consecutive hepatitis C virus-positive liver transplant recipients who received an allograft from January 1997 to September 2005 was undertaken with a median duration of follow-up of 32.4 months. Univariate and multivariate analyses were used to examine the effects of recipient, donor, surgical, and viral factors on posttransplant outcomes. A total of 620 viral load estimations were undertaken in the first 12 months following transplantation. Patient and graft survival rates at 1, 3, and 5 years were 87.8%, 79.9%, and 70.1% and 87.0%, 79.2%, and 68.2%, respectively. According to multivariate analysis, a peak viral load > or = 10(7) IU/mL (P = 0.004; hazard ratio, 8.68; 95% confidence interval, 2.04-37.02) and exposure to antirejection therapy (P = 0.05; hazard ratio, 2.26; 95% confidence interval, 1.01-5.38) were both independent predictors of diminished patient and graft survival and hepatitis C-related allograft failure. The only other independent predictor of hepatitis C virus-related outcome after transplant was azathioprine use, which was associated with improved outcomes (P = 0.04; hazard ratio, 0.25; 95% confidence interval, 0.07-0.91). A peak viral load in the first year after transplant of >10(8), 10(7) to 10(8), and <10(7) IU/mL was associated with a mean survival of 11.8, 70.6, and 89.1 months respectively (P < or = 0.03). The results emphasize the importance of high viral loads in the early posttransplant period as an independent predictor of recipient outcomes.

Cadaveric liver transplant from older donors.

OBJECTIVE: To examine the effects of cadaveric donor age on outcomes following orthotopic liver transplantation OLT. METHODS: Data were collected on all patients who underwent OLT between January 1997 and December 2004 at the Royal Prince Alfred Hospital, Sydney, New South Wales, Australia. During this period, 313 OLTs were performed: 51 patients 16% received older donor livers OD; 60 or more years old, and 262 84% received younger donor livers YD; less than 60 years old. RESULTS: In the study group 313 patients, we found significantly more recipients of OD liver with blood group O: 51% versus 33% p=0.025 and with fulminant hepatic failure: 9.8% versus 5% p=0.018 compared to YD recipients. No difference between OD and YD liver recipients was found in initial poor graft function: 16/51 31% versus 74/262 28%, primary non-functioning: 6.5% versus 6.5%, the overall graft loss: 15/51 29% versus 62/262 24%, post-revascularization liver biopsy steatosis: 14/40 35% versus 82/232 36% or hepatic artery thrombosis: 1/51 2% versus 8/262 3%. There was no difference in graft actuarial survival between OD and YD recipients at 1, 3, and 5 years, 82% versus 87%, 75% versus 81%, and 75% versus 77% p=0.27 log rank or patient actuarial survival, 86% versus 89%, 79% versus 83%, and 79% versus 80% p=0.336 log rank. CONCLUSION: Orthotopic liver transplantation can be achieved with acceptable outcomes using selected livers from older deceased donors.

Laparoscopic hepatectomy, a systematic review.

This systematic review was undertaken to assess the published evidence for the safety, feasibility and reproducibility of laparoscopic liver resection. A computerized search of the Medline and Embase databases identified 28 non-duplicated studies including 703 patients in whom laparoscopic hepatectomy was attempted. Pooled data were examined for information on the patients, lesions, complications and outcome. The most common procedures were wedge resection (35.1%), segmentectomy (21.7%) and left lateral segmentectomy (20.9%). Formal right hepatectomy constituted less than 4% of the reported resections. The conversion and complication rates were 8.1% and 17.6%, respectively. The mortality rate over all these studies was 0.8% and the median (range) hospital stay 7.8 days (2-15.3 days). Eight case-control studies were analysed and although some identified significant reductions in-hospital stay, time to first ambulation after surgery and blood loss, none showed a reduction in complication or mortality rate for laparoscopically carried out resections. It is clear that certain types of laparoscopic resection are feasible and safe when carried out by appropriately skilled surgeons. Further work is needed to determine whether these conclusions can be generalized to include formal right hepatectomy.

Outcome of patients with hepatocellular carcinoma referred to a tertiary centre with availability of multiple treatment options including cadaveric liver transplantation.

UNLABELLED: Hepatocellular carcinoma (HCC) is a primary cancer of the liver with an established causal link to viral hepatitis and other forms of chronic liver disease. AIMS: The aim of this study was to analyse the determinants of outcome in patients with HCC referred to a tertiary centre for management. METHOD: Two hundred and thirty-five prospective patients with HCC and minimum 12-month follow-up were studied. RESULTS: The cohort was heterogeneous, with 52% Caucasian, 40% Asian and 5% of Middle-Eastern origin. Independent predictors of outcome included tumour size and number, the presence of ascites or portal vein thrombosis, alpha-foetoprotein >50 U/L and an impaired performance status. Treatment was determined on an individual case basis by a multidisciplinary tumour team. Surgical resection was primary treatment in 43 patients, liver transplantation in 40 patients, local ablation (percutaneous radiofrequency ablation or alcohol injection) in 33 patients, transarterial chemoembolisation in 33 patients, chemotherapy or other systemic therapy in 30 patients and no treatment in 56 patients. After adjustment for significant covariates, both liver transplantation (P<0.001) and surgical resection (P=0.029) had a significant effect on patient survival compared with no treatment, but local ablation (P=0.410) and chemoembolisation (P=0.831) did not. Liver transplantation resulted in superior overall and, in particular, disease-free survival compared with surgical resection (disease-free survival 84 vs 15% at 5 years). CONCLUSION: In conclusion, both surgical resection and liver transplantation significantly improve the survival of patients with HCC, but improvements need to be made to the delivery of loco-regional therapy to enhance its effectiveness.

Early kidney dysfunction post liver transplantation predicts late chronic kidney disease.

BACKGROUND: Acute and chronic renal dysfunction (ARD, CRD) are common complications after liver transplantation and are associated with poor outcome. METHODS: We reviewed the results of 181 liver transplants performed in our institution between January 1, 1998 and December 31, 2000 in which the recipients were alive with good liver function at the end of the follow-up period (mean 2.7 years). Renal dysfunction was defined as a serum creatinine (Cr) greater than or equal to 2 mg/dL in both acute and chronic settings. RESULTS: The incidence of ARD during the first posttransplant week was 39.2% (n=71), whereas late CRD occurred in 6.0% (n=11) of the patients by the end of the follow-up period. Among the variables we examined for association with CRD, five factors were found to be statistically significant in univariate analysis: pretransplant diabetes (PRTDM) (0.000), Cr greater than or equal to 2 during the first postoperative week (0.003), posttransplant diabetes (POTDM) (0.014), age greater than 50 (0.025), and tacrolimus level greater than 15 ng/mL at postoperative day 15 (0.058). In binary logistic regression analysis, PRTDM (odds ratio [OR]=5.7, 95% confidence interval [CI]) and early postoperative ARD (OR=10.2 95% CI) remained consistently significant. Nine of 11 patients with CRD also had a history of ARD during the first postoperative week. These patients progressed to CRD despite the fact that seven of nine had normalized their renal function by day 90 posttransplant. CONCLUSION: We suggest that a combination of events during the first postoperative week after liver transplant serve as a physiologic "stress test" for the kidneys. Patients who fail the test (peak Cr >/=2 mg/dL during the first postoperative week) as well as the patients with diabetes mellitus are at increased risk of CRD. In such cases, conversion to a less nephrotoxic regimen may be beneficial.

Predicting outcome after liver transplantation: utility of the model for end-stage liver disease and a newly derived discrimination function.

BACKGROUND: The Model for End-Stage Liver Disease (MELD) has been found to accurately predict pretransplant mortality and is a valuable system for ranking patients in greatest need of liver transplantation. It is unknown whether a higher MELD score also predicts decreased posttransplant survival. METHODS: We examined a cohort of patients from the United Network for Organ Sharing (UNOS) database for whom the critical pretransplant recipient values needed to calculate the MELD score were available (international normalized ratio of prothrombin time, total bilirubin, and creatinine). In these 2,565 patients, we analyzed whether the MELD score predicted graft and patient survival and length of posttransplant hospitalization. RESULTS: In contrast with its ability to predict survival in patients with chronic liver disease awaiting liver transplant, the MELD score was found to be poor at predicting posttransplant outcome except for patients with the highest 20% of MELD scores. We developed a model with four variables not included in MELD that had greater ability to predict 3-month posttransplant patient survival, with a c-statistic of 0.65, compared with 0.54 for the pretransplant MELD score. These pretransplant variables were recipient age, mechanical ventilation, dialysis, and retransplantation. Recipients with any two of the three latter variables showed a markedly diminished posttransplant survival rate. CONCLUSIONS: The MELD score is a relatively poor predictor of posttransplant outcome. In contrast, a model based on four pretransplant variables (recipient age, mechanical ventilation, dialysis, and retransplantation) had a better ability to predict outcome. Our results support the use of MELD for liver allocation and indicate that statistical modeling, such as reported in this article, can be used to identify futile cases in which expected outcome is too poor to justify transplantation.

Survival following liver transplantation from non-heart-beating donors.

OBJECTIVE: To determine whether patient and graft survival following transplantation with non-heart-beating donor (NHBD) hepatic allografts is equivalent to heart-beating-donor (HBD) allografts. SUMMARY BACKGROUND DATA: With the growing disparity between the number of patients awaiting liver transplantation and a limited supply of cadaveric organs, there is renewed interest in the use of hepatic allografts from NHBDs. Limited outcome data addressing this issue exist. METHODS: Retrospective evaluation of graft and patient survival among adult recipients of NHBD hepatic allografts compared with recipients of HBD livers between 1993 and 2001 using the United Network of Organ Sharing database. RESULTS: NHBD (N = 144) graft survival was significantly shorter than HBD grafts (N = 26856). One- and 3-year graft survival was 70.2% and 63.3% for NHBD recipients versus 80.4% and 72.1% (P = 0.003 and P = 0.012) for HBD recipients. Recipients of an NHBD graft had a greater incidence of primary nonfunction (11.8 vs. 6.4%, P = 0.008) and retransplantation (13.9% vs. 8.3%, P = 0.04) compared with HBD recipients. Prolonged cold ischemic time and recipient life support were predictors of early graft failure among recipients of NHBD livers. Although differences in patient survival following NHBD versus HBD transplant did not meet statistical significance, a strong trend was evident that likely has relevant clinical implications. CONCLUSIONS: Graft and patient survival is inferior among recipients of NHBD livers. NHBD donors remain an important source of hepatic grafts; however, judicious use is warranted, including minimization of cold ischemia and use in stable recipients.