Optimal Timing of Administration of Direct-acting Antivirals for Patients With Hepatitis C-associated Hepatocellular Carcinoma Undergoing Liver Transplantation.

OBJECTIVE: To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). SUMMARY OF BACKGROUND DATA: In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate. METHODS: The United States HCC LT Consortium (2015-2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS). RESULTS: Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01). CONCLUSIONS: The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results.

Recurrence of non-alcoholic steatohepatitis and cryptogenic cirrhosis following orthotopic liver transplantation in the context of the metabolic syndrome.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) and cryptogenic cirrhosis (CC) are increasing indications for orthotopic liver transplantation (OLT). The aim of this study is to describe our outcomes and delineate predictors of recurrence of NASH and CC after OLT. METHODS: This is a retrospective study from 1996 to 2008. Donor and recipient demographics, metabolic profile, insulin and steroid intake, immunosuppression regimen, operative factors, outcomes, and pathologies were reviewed. Fisher's exact test, Cox regression models, and Kaplan-Meier plots were used. RESULTS: A total of 83 patients were included. Recurrence occurred in 20 patients. Thirty-four percent of the patients with metabolic syndrome (MS) had recurrence of NASH or CC compared with 13% of the patients without MS (p = 0.05). Recurrence also occurred in 32% of the patients with hypertension (HTN) vs. 12% in those without HTN (p = 0.05). Thirty-seven percent of those on insulin had recurrence vs. 6% of those not on insulin (p = 0.05). Five-yr survival probability for patients with MS, HTN, and insulin use was 52%, 61%, and 58%, respectively. CONCLUSIONS: Higher recurrence of NASH and CC was associated with presence of MS, HTN and insulin use. Recurrence should be further evaluated in larger studies, with special emphasis on management of MS and prevention strategies.

A new vascular approach to the modified multivisceral graft procurement.

Modified multivisceral (MMV) transplantation including the stomach, pancreaticoduodenal complex and intestine requires preservation of the left gastric and splenic arteries. The previously described techniques require division of the hepatic artery proximal to the gastroduodenal artery leaving the liver transplant team with a very short and small caliber vessel. To increase MMV graft availability and provide the liver transplant team with an appropriate quality vessel, we developed the following technique. We also describe two cases where we used this method to support the technical feasibility of this procedure.

Massive Leiomyomatous Uterine Proliferation Following Kidney Transplantation: A Case Report and Literature Review.

Uterine fibroids are the most common benign uterine tumors affecting > 50% of premenopausal women. The incidence, burden and symptoms from uterine fibroids are higher in women of African descent compared to Caucasians. Despite increasing number of African American females being evaluated for and undergoing kidney transplantation (KT), perioperative management guidelines for uterine fibroids currently do not exist. We present a case of a 40 y/o African American female with known symptomatic uterine fibroids preoperatively and medically managed, who underwent a successful KT and 4 years later progressively developed massive leiomyomatous uterine proliferation, causing a complete lateral displacement of the transplanted kidney with severe hydronephrosis, transplant ureteral obstruction and secondary urinary tract infections with bacteremia. This obstruction required a percutaneous nephrostomy tube placement followed by an interval transabdominal hysterectomy, which was complicated by transplant ureteral transection requiring ureteral reimplantation, resulting in prolonged hospitalization, follow-up and outpatient antibiotic regimen. There is a need for management guidelines for uterine fibroids incidentally encountered during the KT evaluation process to avoid similar preventable post-KT complications in patient populations most commonly affected. Literature review and perioperative management/surveillance strategies are provided.

Intrahepatic Cholangiocarcinoma in the Liver Explant After Liver Transplantation: Histological Differentiation and Prognosis.

BACKGROUND: The aim of this study was to evaluate the outcome of patients with intrahepatic cholangiocarcinoma (ICCA) incidentally found in the explanted liver after liver transplantation. MATERIAL AND METHODS: We retrospectively reviewed 1188 recipients undergoing liver transplantation from August 2003 to August 2014; 13 patients were found to have ICCA (1.1%). Recurrence-free survival (RFS) rate was compared between ICCA patients and the matched cohort of 39 patients with hepatocellular carcinoma (HCC). We also investigate the relevance of clinical and pathological parameters in recurrence of ICCA. RESULTS: ICCA patients showed significantly higher recurrence rate with lower 1-year and 3-year RFS rates than HCC patients (recurrence rate, 12.8% vs. 54.8%; 1-year and 3-year RFS rates, 94% and 84% vs. 67% and 42%). Of the 13 ICCA patients, 4 were diagnosed with a well-differentiated ICCA and 9 with a moderately-differentiated ICCA. There was no recurrence among those with a well-differentiated ICCA, whereas 78% recurred in the moderately-differentiated group. The median RFS time for the moderately-differentiated group was 13.0 months, yielding RFS rates of 56% at 1 year and 22% at 3 years. CONCLUSIONS: Liver transplantation in patients with a well-differentiated ICCA yielded excellent outcomes as compared to patients with a moderately-differentiated ICCA. This may allow consideration of transplantation in the setting of a well-differentiated ICCA, and obviate the need for adjuvant systemic treatment. Conversely, a moderately-differentiated ICCA carries a poor prognosis with a prohibitively high recurrence rate and poor survival. Liver transplantation should remain a contraindication in this group.