Two hundred and fifty-one right hepatectomies for living donation: Association between preoperative risk factors, hepatic dysfunction, and complications.

BACKGROUND: Donor safety is essential in living donor liver transplantation. In this study we assessed the association among perioperative factors, liver dysfunction, and complications in 251 consecutives right hepatectomies for living donation. METHODS: Retrospectively collected data from a prospectively assembled cohort of 251 consecutive living donors who underwent right hepatectomy between 1999 and 2020 were evaluated. RESULTS: Median age was 36 years; 54% were men. There was a statistically significant relationship between standardized liver volume by body surface area and the volumes calculated by imaging, weighting, and volume displacement. (r2 = 0.40, r2 = 0.34, and r2 = 0.34, respectively), with the relationship between standardized liver volume and liver volume by imaging being the strongest. The median remnant liver volume was 35%. Fifty-eight donors (23%) developed postoperative hepatic dysfunction, which was associated with increased length of stay (P = .04), and complications (P < .01). Men had a 2.5 times higher chance of developing postoperative hepatic dysfunction. Age >50 years was an independent predictor of increased bilirubin at postoperative day 4 (P < .01), and remnant liver volume was inversely associated with higher peak international normalized ratio (P < .01). Eighty-one donors (32%) experienced complications. Postoperative hepatic dysfunction was associated with 2.4 times higher chances of complications (odds ratio = 2.4, P < .01). CONCLUSION: Early postoperative hepatic dysfunction is associated with the development of post-live liver donor complications. A thoughtful balancing of preoperative risk factors for postoperative hepatic dysfunction may indeed and by association reduce postoperative complications.

Recurrent Liver Allograft Injury in Patients With Donor-Derived Malignancy Treated With Immunosuppression Cessation and Retransplantation.

OBJECTIVES: Donor-derived malignancy of the liver allograft is a rare but serious condition in the setting of necessary immunosuppression. Retransplantation after abrupt immunosuppression cessation has been performed with durable cancer-free survival. METHODS: We present 2 cases of patients with donor-derived malignancy who were treated with complete immunosuppression cessation, which induced rapidly progressive liver allograft rejection and failure, with a need for subsequent retransplantation. We reviewed all serial liver biopsies and explants from both patients and performed C4d immunostaining. RESULTS: Initial explants of both patients showed severe allograft rejection, with unusual features of sinusoidal obstruction syndrome and C4d positivity. Malignant tumors in the explants were necrotic, related to rejection of donor-derived cancer cells and tissue. Follow-up of both patients has shown long-term cancer-free survival but issues with recurrent allograft failure requiring a third transplant. The reasons for retransplantation in both cases were related to allograft failure from antibody-mediated rejection. CONCLUSIONS: Clinicians should be aware of a potentially increased risk of rejection and recurrent allograft failure when strategizing treatment of donor-derived malignancy with immunosuppression cessation and retransplantation.

The International Liver Transplant Society Guideline on Living Liver Donation.

The following guideline represents the position of the International Liver Transplantation Society (ILTS) on key preoperative, operative, and postoperative aspects surrounding living liver donation. These recommendations were developed from experts in the field from around the world. The authors conducted an analysis of the National Library of Medicine indexed literature on "living donor liver transplantation" [Medline search] using Grading of Recommendations Assessment, Development and Evaluation methodology. Writing was guided by the ILTS Policy on the Development and Use of Practice Guidelines (www.ilts.org). ILTS members, and many more nonmembers, were invited to comment. Recommendations have been based on information available at the time of final submission (March 2016). The lack of randomized controlled trials in this field to date is acknowledged and is reflected in the grading of evidence. Intended for use by physicians, these recommendations support specific approaches to the diagnostic, therapeutic, and preventive aspects of care.

Utility of the low-accelerating-dose regimen in 182 liver recipients with recurrent hepatitis C virus.

AIM: To describe our experience using a low-accelerating-dose regimen (LADR) with pegylated interferon alpha-2a and ribavirin in treatment of hepatitis C virus (HCV) recurrence. METHODS: From 2003, a protocolized LADR strategy was employed to treat liver transplant (LT) recipients with recurrent HCV at our institution. Medical records of 182 adult patients with recurrent HCV treated with LADR between 1/2003 and 1/2011 were reviewed. Histopathology from all post-LT liver biopsies were reviewed in a blinded fashion. Paired recipient and donor IL28B status were assessed. A novel technique was employed to ascertain recipient and donor IL28B (rs12979860) Gt data using DNA extracted from archival FFPE tissue from explanted native livers and donor gallbladders respectively. The primary endpoint was SVR; secondary endpoints examined include (1) patient and graft survival; (2) effect of anti-viral therapy on liver histology (fibrosis and inflammation); (3) incidence of on-treatment development of ACR, CDR, or PCH; (4) association of recipient and donor IL28B genotype with SVR; and (5) incidence of anti-viral therapy-associated adverse events (anemia, leukopenia, thrombocytopenia, depression) and hepatic decompensation. RESULTS: The overall SVR rate was 38% (29% Gt1, 67% Gt2, 86% Gt3 and 58% Gt4). HCV Gt (P < 0.0001), donor age (P = 0.003), cytomegalovirus mismatch (P = 0.001), baseline serum bilirubin (P = 0.002), and baseline viral load (P = 0.04) were independent predictors for SVR. SVR rates were significantly higher in the recipient-CC/donor-non CC pairs (P = 0.007). Neither baseline fibrosis nor change in fibrosis stage after anti-viral therapy were associated with SVR. Fibrosis progressed in 72% of patients despite SVR. Median graft survival was 91 mo. Five-year patient survival was superior in patients who achieved SVR (97% vs 82%, P = 0.001). Pre-treatment ALP ≥ 150 U/L (P = 0.01), total bilirubin ≥ 1.5 mg/dL (P = 0.001) and creatinine ≥ 2 mg/dL (P = 0.001) were independently associated with patient survival. Only 13% of patients achieving SVR died during the follow-up period. Treatment discontinuation and treatment-related mortality occurred in 35% and 2.2% of patients, respectively. EPO, G-CSF and blood transfusion were needed in 89%, 40% and 23% of patients, respectively. Overall hospitalization rate for treatment-related serious adverse events was 21%. Forty-six (25%) of the patients were deceased; among those who died, 25 (54%) were due to liver-related complications, and 4 deaths (9%) occurred while receiving therapy (2 patients experienced hepatic decompensation and 2 sepsis). CONCLUSION: LADR strategy remains relevant in managing post-LT recurrent HCV where access to DAAs is limited. SVR is associated with improved survival, but fibrosis progression still occurs.

Tumors with intrahepatic bile duct differentiation in cirrhosis: implications on outcomes after liver transplantation.

BACKGROUND: The role of liver transplantation (LT) in the management of cirrhotic patients with tumors exhibiting intrahepatic bile duct differentiation remains controversial. The objective of this study was to characterize the spectrum of these tumors and analyze post-LT outcomes. METHODS: Retrospective pathology database search of explant histology analysis of liver transplants between April 1993 and November 2013. RESULTS: Thirty-two patients were analyzed, 75% were men with a mean age of 60 years. Seven patients had nodules demonstrating intrahepatic cholangiocarcinoma (I-CCA), nine had I-CCA nodules occurring concomitantly with hepatocellular carcinoma (HCC), and 16 had mixed HCC-CCA nodules. The median number of tumors was 1 and size was 2.5 cm. Overall patient survival post-LT at 1 and 5 years was 71% and 57%, respectively. Patients within Milan criteria, especially with I-CCA features, showed a 5-year tumor recurrence rate (10%) and 5-year survival rate (78%) comparable with other patients having HCC within Milan criteria. CONCLUSION: This series showed that patients with CCA within Milan criteria may be able to achieve acceptable long-term post-LT survival.

Right hepatectomy for living donation: role of remnant liver volume in predicting hepatic dysfunction and complications.

BACKGROUND: Extensive attention has been placed on remnant liver volume (RLV) above other factors to ensure donor safety. METHODS: We performed a retrospective review of 137 right hepatectomies in live donors between June 1999 and November 2010. RESULTS: Median right lobe volume was 1,029 cm(3), which correlated with its actual weight (r = 0.63, P < .01); median RLV was 548 cm(3). Of the donors, 32 (24%) developed postoperative hepatic dysfunction (bilirubin >3 mg/dL or prothrombin time >18 s on postoperative day 4). RLV did not predict postoperative hepatic dysfunction (P = .9), but it was associated with peak international normalized ratio (INR) (P = .04). Donor age and male gender were predictors of increased bilirubin at postoperative day 4 (age, P = .03; gender, P = .02). Of the donors, 45 (33%) experienced complications, and 24 donors had RLVs <30%; 42% experienced complications compared to 31% of donors whose RLVs were greater than 30% (P = .3). Cell-saver utilization and aspartate-aminotransferase (AST) levels (OR = 3) were associated with complications. Volumetric assessment can predict RLV accurately. CONCLUSION: Although no demonstrable association between RLV <30% and complications was found, an RLV of 30% should remain the threshold for donor safety. Age and gender should be balanced in donors with a near threshold RLV of 30%. Surgical complexity, suggested by the need for intraoperative autoinfusion of blood and postoperative levels of AST, remained the independent predictor of complications.

Liver transplantation for hepatocellular carcinoma: defining the impact of using extended criteria liver allografts.

BACKGROUND: This series compares outcomes of patients with hepatocellular carcinoma (HCC) listed for orthotopic liver transplantation (OLT) within and outside Milan criteria, and determines the impact of extended criteria liver allografts (ECD). METHODS: Records of patients listed for liver transplantation at a single center from 1998 to 2007 were reviewed retrospectively. RESULTS: Ninety-seven HCC patients were listed for OLT, 77 underwent transplantation; 47 received ECDs and 30 standard organs. ECDs were more frequently allocated to outside Milan recipients. Wait time for OLT was shorter for outside Milan patients (4 vs. 7 months P=0.04) but hazard rate of dropout was higher (26%, 46%, and 73% at 6,12, and 24 months compared with 2%, 14%, and 60% P<0.01). Tumor size more than 3 cm (P=0.02) and model for end-stage liver disease score at listing more than 11 (P=0.04) were independent predictors of dropout. Hazard rate of OLT was similar within and outside Milan (61%, 80%, and 90% at 6, 12, and 24 months vs. 60%, 70%, and 86% P=0.38). Post-OLT survival at 1 year and 4 years were 88% and 63% within Milan compared with 79% and 62% among Milan out recipients (P=0.95). No significant post-OLT survival predictor was found. CONCLUSION: The use of ECD organs provided patients with HCCs outside Milan criteria access to liver transplant at a rate comparable to patients within Milan and model for end-stage liver disease HCC priority. Similar patient survival post-OLT can be achieved using standard or ECD organs. The higher risk of drop out in patients outside Milan, and even within Milan, with tumors more than 3 cm justifies the use of ECD organs for timely transplantation.

Massive pulmonary and intracardiac embolism during liver transplantation.

Despite prolonged coagulation times and thrombocytopenia associated with end-stage liver disease, formation of thrombi in the circulation seems to occur more frequently during liver transplant than during any other type of major surgery. Here, we report a case of massive pulmonary and intracardiac embolism that resulted in cardiac arrest and intraoperative death. This was diagnosed by transesophageal echocardiography and occurred shortly after induction of anesthesia and initiation of continuous veno-venous hemofiltration without the concomitant use of antifibrinolytic drugs. We discuss the physiologic changes associated with cirrhosis and liver transplant, and review the literature.

Surgical dilemma: liver resection or liver transplantation for hepatocellular carcinoma and cirrhosis. Intention-to-treat analysis in patients within and outwith Milan criteria.

BACKGROUND: The optimal role of surgery in the management of hepatocellular carcinoma (HCC) is in continuous evolution. OBJECTIVE: The objective of this study was to analyse survival rates after liver resection (LR) and orthotopic liver transplantation (OLT) for HCC within and outwith Milan criteria in an intention-to-treat analysis. METHODS: During 1997-2007, 179 patients with cirrhosis and HCC either underwent LR (n= 60) or were listed for OLT (n= 119). Patients with incidental HCC after OLT, preoperative macrovascular invasion before LR, non-cirrhosis and Child-Pugh class C cirrhosis prior to OLT were eliminated, leaving 51 patients primarily treated with LR and 106 patients listed for primary OLT (84 of whom were transplanted) to be included in this analysis. A total of 66 patients fell outwith Milan criteria (26 LR, 40 OLT) and 91 continued to meet Milan criteria (25 LR, 66 OLT). RESULTS: The median length of follow-up was 26 months. The mean waiting time for OLT was 7 months. During that time, 21 patients were removed from the waiting list as a result of tumour progression. Probabilities of dropout were 2% and 13% at 6 and 12 months, respectively, for patients within Milan criteria, and 34% and 57% at 6 and 12 months, respectively, for patients outwith Milan criteria (P < 0.01). Tumour size >3 cm was found to be the independent factor associated with dropout (hazard ratio [HR] 6.0). Postoperative survival was slightly higher after OLT, but this was not statistically significant (64% for OLT vs. 57% for LR). Overall survival from time of listing for OLT or LR did not differ between the two groups (P= 0.9); for patients within Milan criteria, 1- and 4-year survival rates after LR were 88% and 61%, respectively, compared with 92% and 62%, respectively, after OLT (P= 0.54). For patients outwith Milan criteria, 1- and 4-year survival rates after LR were 69% and 54%, respectively, compared with 65% and 40%, respectively, after OLT (P= 0.42). Tumour size >3 cm was again found to be an independent factor for poor outcome (HR 2.4) in the intention-to-treat analysis. CONCLUSIONS: Survival rates for patients with HCC are similar in LR and OLT. Liver resection can potentially decrease the dropout rate and serve as a bridge for future salvage LT, particularly in patients with tumours >3 cm.

Surgical treatment of hepatocellular carcinoma beyond Milan criteria. Results of liver resection, salvage transplantation, and primary liver transplantation.

BACKGROUND: There is no clear consensus regarding the best treatment strategy for patients with advanced hepatocellular carcinoma (HCC). METHODS: Patients with cirrhosis and HCC beyond Milan who had undergone liver resection (LR) or primary orthotopic liver transplantation (OLT) between November 1995 and December 2005 were included in this study. Pathological tumor staging was based on the American Liver Tumor Study Group modified Tumor-Node-Metastasis classification. RESULTS: A total of 23 HCC patients were primarily treated by means of LR, 5 of whom eventually underwent salvage OLT. An additional 32 patients underwent primary OLT. The overall actuarial survival rates at 3 and 5 years were 35% after LR, and 69% and 60%, respectively, after primary OLT. Recurrence-free survival at 5 years was significantly higher after OLT (65%) than after LR (26%). Of the patients who underwent LR, 11 (48%) experienced HCC recurrence only in the liver; 6 of these 11 presented with advanced HCC recurrence, poor medical status, or short disease-free intervals and were not considered for transplantation. Salvage OLT was performed in 5 patients with early stage recurrence (45% of patients with hepatic recurrence after LR and 22% of all patients who underwent LR). At a median of 18 months after salvage OLT, all 5 patients are alive, 4 are free of disease, and 1 developed HCC recurrence 16 months after salvage OLT. CONCLUSION: For patients with HCC beyond Milan criteria, multimodality treatment-including LR, salvage OLT, and primary OLT-results in long-term survival in half of the patients. When indicated, LR can optimize the use of scarce donor organs by leaving OLT as a reserve option for early stage HCC recurrence.

Fulminant and fatal gas gangrene of the stomach in a healthy live liver donor.

A 57-year-old male with a history of hypercholesterolemia and anxiety but otherwise in good health volunteered to donate the right lobe of his liver to his brother. The operation was performed uneventfully, without transfusion. Postoperatively he did well, until he developed tachycardia, profound hypotension, and coffee ground emesis on postoperative day 3. Despite resuscitative measures, he arrested and expired. Autopsy demonstrated gas gangrene of the stomach as the underlying cause of the hemorrhage and numerous colonies of Gram-positive bacilli were identified. Subsequent polymerase chain reaction (PCR) analysis identified these bacteria to be Clostridium perfringens (C. perfringens) type D. This patient's death was devastating, both to his family and his medical team. The impact of his death has transcended that of an individual occurrence. In conclusion, herein we present the facts and discuss this extraordinary example of florid clostridial infection and toxin-mediated shock. It was completely unexpected and probably unpreventable, and its cause was almost inconceivable.

Unresectable squamous cell carcinoma of donor origin treated with immunosuppression withdrawal and liver retransplantation.

Posttransplantation allograft malignancy of donor origin is a rare complication after liver transplantation. In the case described, subjective fevers and nonspecific abdominal complaints nearly 6 months following cadaveric liver transplantation in a young woman prompted an evaluation which was remarkable for a large central liver mass. A poorly differentiated squamous cell carcinoma was diagnosed, but was unresectable at exploration. The tumor was confined to the liver. Histocompatibility testing using polymerase chain reaction (PCR) amplification techniques identified both donor and recipient HLA alleles. The patient was treated with chemoembolization, systemic chemotherapy and cessation of immunosuppression. Repeat biopsy 2 months later showed the tumor to be completely necrotic. With decompensated liver disease, she was relisted and retransplanted. More than 2 years later she remains disease-free with complete pathological remission. This is the only reported case of squamous cell carcinoma of donor origin arising in a transplanted liver.

Adult living donor liver transplantation for patients with hepatocellular carcinoma: extending UNOS priority criteria.

INTRODUCTION: For patients with hepatocellular carcinoma (HCC) in particular, living donor liver transplant (LDLT) improves access to transplant. We report our results in 36 patients with HCC who underwent LDLT with a median follow-up >1 year. METHODS Underlying diagnoses included: hepatitis C (24), hepatitis B (9), cryptogenic cirrhosis (1), hemochromatosis (1), and primary biliary cirrhosis (1). Patients with tumors >or= 5 cm received IV doxorubicin intraoperatively and 6 cycles of doxorubicin at 3-week intervals. Patients were followed with CT scan and alpha-fetoprotein levels every 3 months for 2 years posttransplant. Mean waiting time, pretransplant treatment, tumor variables, and survival were analyzed. Univariate and multivariate analysis were done to analyze tumor variables; Kaplan-Meier and log rank were used to compare survivals. P < 0.05 was considered significant. RESULTS Mean wait for LDLT was 62 days, compared with 459 days in 50 patients with HCC transplanted with cadaveric organs during the same time period (P = 0.0001). At median follow-up of 450 days, there have been 10 deaths due to non-tumor-related causes and 3 deaths from recurrence; recurrence has also been observed in 3 other patients. On univariate and multivariate analysis, bilobar distribution was the only significant tumor variable (P = 0.03, log rank = 0.02). Fifty-three percent of patients exceeded UNOS priority criteria. One- and two-year patient survivals were 75% and 60%, respectively. Freedom from recurrence at 365 and 730 days was 82% and 74%, respectively. Overall and in patients with HCC > 5 cm (n = 12), there were no statistically significant differences in survival or in freedom from recurrence between recipients of living donor and cadaveric grafts. CONCLUSION Although one third of patients had tumors > 5 cm, the incidence of recurrence as well as patient survival and freedom from recurrence are comparable to results after cadaveric transplant. LDLT allows timely transplantation in patients with early or with large HCC.