Citations

The current system granting liver transplant candidates with hepatocellular carcinoma (HCC) additional Model for End‐Stage Liver Disease (MELD) points is controversial due to geographic disparity and uncertainty regarding optimal prioritization of candidates. The current national policy assigns a MELD exception score of 22 immediately upon listing of eligible patients with HCC. The aim of this study was to evaluate the potential effects of delays in granting these exception points on transplant rates for HCC and non‐HCC patients. We used Scientific Registry of Transplant Recipients data and liver simulated allocation modeling software and modeled (1) a 3‐month delay before granting a MELD exception score of 25, (2) a 6‐month delay before granting a score of 28, and (3) a 9‐month delay before granting a score of 29. Of all candidates waitlisted between January 1 and December 31, 2010 (n = 28,053), 2773 (9.9%) had an HCC MELD exception. For HCC candidates, transplant rates would be 108.7, 65.0, 44.2, and 33.6 per 100 person‐years for the current policy and for 3‐, 6‐, and 9‐month delays, respectively. Corresponding rates would be 30.1, 32.5, 33.9, and 34.8 for non‐HCC candidates. Conclusion: A delay of 6‐9 months would eliminate the geographic variability in the discrepancy between HCC and non‐HCC transplant rates under current policy and may allow for more equal access to transplant for all candidates. (Hepatology 2015;61:1643–1650)

Transarterial chemoembolization (TACE) is a common treatment for patients with hepatocellular carcinoma (HCC) who are awaiting liver transplantation (LT). The aim of this study was to assess the impact of multiple TACE treatments on tumor necrosis, tumor recurrence, and survival in these patients. A retrospective analysis was performed for 104 consecutive patients undergoing LT for HCC from January 2002 to December 2009 who were treated with TACE before LT. The number of TACE treatments was not associated with tumor necrosis in the explant. After a median follow‐up of 69 months (range = 0‐123 months), 14 of the 104 patients (13%) developed recurrent HCC after LT. Recurrence had a significant relationship with a short interval between the diagnosis of HCC and LT (≤6 months) in univariate and multivariate analyses [P = 0.029, odds ratio (OR) = 19.2]. Patients subjected to a single TACE treatment were more likely to experience recurrence, although this finding was not confirmed in the multivariate analysis. No significant relationship was observed between tumor necrosis in the explant and recurrence. The mean overall survival was 102.8 months (95% confidence interval = 94.9‐110.8 months) with 1‐, 3‐, and 5‐year survival rates of 91%, 89%, and 84% respectively. In the univariate survival analysis, the presence of ascites before TACE, a waiting time ≤ 9 months, and tumor characteristics at the pathological examination were statistically associated with shorter survival. In the multivariate analysis, only vascular invasion (P < 0.001, OR = 7.99) remained independently associated with shorter survival. The number of TACE treatments was not associated with survival. In conclusion, multiple TACE treatments were not associated with a higher risk of recurrence or shorter survival. Continued use of TACE should be considered as indicated if the patient and lesions are suitable for retreatment. A shorter waiting time before LT is related to an increased risk of recurrence and decreased survival after LT for HCC. These data could reflect the presence of more aggressive tumor biology and may be useful for guiding organ allocation policy to consider a minimum observation period before LT for regions with shorter wait times. Liver Transpl 21:248‐257, 2015. © 2014 AASLD.

Objectives: The aim of this was to determine survival after starting neoadjuvant therapy for patients who became ineligible for orthotopic liver transplantation (OLT). Methods and Materials: Since January 1993, 215 patients with unresectable cholangiocarcinoma began treatment with planned OLT. Treatment included external-beam radiation therapy (EBRT) with fluorouracil, bile duct brachytherapy, and postradiotherapy fluorouracil or capecitabine before OLT. Adverse findings at the staging operation, death, and other factors precluded OLT in 63 patients (29%), of whom 61 completed neoadjuvant chemoradiation. Results: By October 2012, 56 (89%) of the 63 patients unable to undergo OLT had died. Twenty-two patients (35%) became ineligible for OLT before the staging operation, 38 (60%) at the staging operation, and 3 (5%) after staging. From the date of diagnosis, median overall survival was 12.3 months. Survival was 17% at 18 months and 7% at 24 months. Median survival after fallout was 6.8 months. Median survival after the staging operation was 6 months. Two patients lived for 3.7 and 8.7 years before dying of cancer or liver failure caused by persistent biliary stricture at the site of the original cancer, respectively. Univariate analysis showed that time from diagnosis to fallout correlated with overall survival (P=0.04). Conclusions: In highly selected patients initially suitable for OLT, the mortality rate for cholangiocarcinoma was high in patients who became ineligible for OLT. Their survival, however, was comparable to expected survival for patients with locally advanced or metastatic disease treated with nontransplant therapies. The most common reason for patient fallout was adverse findings at the staging operation.

AbstractBackground & AimsChronic kidney disease (CKD) after liver transplant (LT) is associated with increased long‐term mortality. The impact of gender on CKD before and after LT is unknown. To further define risk factors and analyse gender differences in the incidence and progression of CKD after liver transplant.MethodsFour hundred and fifty‐five consecutive adult primary solitary LT recipients were included. Iothalamate clearance tests performed over time were analysed.ResultsMean age was 51.4 ± 10.4 years with 63% males. A percentage of 29.1% of females and 21.1% of males had a GFR<60 ml/min/1.73 m2 and 10.2% of females and 5.9% of males had GFR<30 ml/min/1.73 m2 prior to transplant. At 1 year, 52.6% of recipients tested (69.6% females, 43.0% males) had GFR<60 ml/min/1.73 m2 and 7.3% (11.6% females, 4.9% males) had GFR<30 ml/min/1.73 m2. Pre‐LT GFR<60 ml/min/1.73 m2 [OR 3.28, (1.76–6.10), P ≤ 0.001], female gender (OR 2.96, (1.72–5.10), P < 0.001) and age [OR 1.09, (1.05–1.12), P < 0.001] were independently predictive of stage ≥3 CKD at 1 year post‐LT. Female gender [OR 2.52, (1.25–4.71), P = 0.004], age [OR 1.05, (1.02–1.08), P = 0.003] and NASH [OR 2.95, (1.06–8.21), P = 0.039] were independently predictive of ≥stage 3 CKD at 5 years post‐LT. Pre‐LT diabetes was associated with stage 4 CKD at 5 years [OR 2.91, (1.33–6.36), P = 0.008] post‐LT.ConclusionsIn addition to age and pre‐LT CKD, female gender and NASH are independent predictors of ≥stage 3 CKD post‐LT. Gender‐based approaches to optimize modifiable risk factors are needed to improved post‐transplant renal function.

OBJECTIVE Because direct adipose tissue free fatty acid (FFA) storage may contribute to body fat distribution, we measured FFA (palmitate) storage rates and fatty acid (FA) storage enzymes/proteins in omental and abdominal subcutaneous fat. RESEARCH DESIGN AND METHODS Elective surgery patients received a bolus of [1-14C]palmitate followed by omental and abdominal subcutaneous fat biopsies to measure direct FFA storage. Long chain acyl-CoA synthetase (ACS) and diacylglycerol acyltransferase activities, CD36, fatty acid-binding protein, and fatty acid transport protein 1 were measured. RESULTS Palmitate tracer storage (dpm/g adipose lipid) and calculated palmitate storage rates were greater in omental than abdominal subcutaneous fat in women (1.2 ± 0.8 vs. 0.7 ± 0.4 μmol ⋅ kg adipose lipid−1 ⋅ min−1, P = 0.005) and men (0.7 ± 0.2 vs. 0.2 ± 0.1, P &lt; 0.001), and both were greater in women than men (P &lt; 0.0001). Abdominal subcutaneous adipose tissue palmitate storage rates correlated with ACS activity (women: r = 0.66, P = 0.001; men: r = 0.70, P = 0.007); in men, CD36 was also independently related to palmitate storage rates. The content/activity of FA storage enzymes/proteins in omental fat was dramatically lower in those with more visceral fat. In women, only omental palmitate storage rates were correlated (r = 0.54, P = 0.03) with ACS activity. CONCLUSIONS Some adipocyte FA storage factors correlate with direct FFA storage, but sex differences in this process in visceral fat do not account for sex differences in visceral fatness. The reduced storage proteins in those with greater visceral fat suggest that the storage factors we measured are not a predominant cause of visceral adipose tissue accumulation.

Abstract Background The aim was to evaluate outcomes in patients with ulcerative colitis complicated by primary sclerosing cholangitis (PSC) who required ileal pouch–anal anastomosis (IPAA) and orthotopic liver transplantation (OLT). Methods A retrospective analysis was performed of 32 patients undergoing both IPAA and OLT between 1980 and 2006. Data were collected regarding demographics, indication for surgery, postoperative complications, and outcome of IPAA and OLT. Results Thirty-day mortality after either procedure was nil. The median preoperative Model for End-stage Liver Disease (MELD) score for the group with initial IPAA was 8 (range 6–20) and the postoperative score was 11 (range 6–19). At 1 and 10 years, 32 and 26 of the 32 liver grafts had survived, and 31 and 30 of the 32 pouches, respectively. Fourteen patients require daily medical therapy for chronic pouchitis. At a median follow-up of 3·6 (range 0·2–16·2) years after the second of two procedures, responding patients reported a median of 5·5 stools per day and 2 stools per night. Conclusion IPAA and OLT are feasible and safe in patients requiring both procedures for ulcerative colitis and PSC. Functional outcomes are stable over time, despite an increased risk of chronic pouchitis.