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The COVID-19 pandemic declared in March 2020, has generated worldwide concern due to its effect on the health of the population and the potential health collapse. The strategy of "flattening the curve" through social distancing made it possible to adapt the resources of the health system to patients with COVID-19, but results in other areas of health could not be predicted. The objective of this work was to analyze the consequences of the pandemic on liver transplantation in general and for hepatocarcinoma (HCC). The following studies were carried out: a) a retrospective analysis using data from the CRESI / INCUCAI to compare admission to the waiting list, mortality on the list, donation and liver transplantation from 03/20 to 08/15, 2019 and the same period in 2020, and b) a survey of the transplant centers with the highest transplant activity to assess the effect of the measures taken in different institutional and regional situations. The first analysis showed a 55% decrease in liver transplants, with a similar reduction in donation and admission to the liver waiting list; while HCC transplantation rose from 10% in 2019 to 22% in 2020. The second analysis showed that the occupancy rate of beds by COVID-19 patients / week was variable: from 0.4% to 42.0%. The number of surgeries, hepato-bilio-pancreatic, resection of HCC and liver transplantation, were reduced by 47%, 49%, 31% and 36% respectively. The reduction in transplant activity mainly affected centers with high occupancy due to COVID-19. The final long-term outcome will need to be assessed.

Organ transplantation is the treatment of choice against terminal and irreversible organ failure. Optimal preservation of the graft is crucial to counteract cold ischemia effects. As we developed an N,N-bis-2-hydroxyethyl-2-aminoethanesulfonic acid-gluconate-polyethylene glycol (BGP)-based solution (hypothermic machine perfusion [HMP]), we aimed to analyze the use of this solution on static cold storage (SCS) of rat livers for transplantation as compared with the histidine tryptophan ketoglutarate (HTK) preservation solution. Livers procured from adult male Sprague Dawley rats were preserved with BGP-HMP or HTK solutions. Liver total water content and metabolites were measured during the SCS at 0°C for 24 hours. The function and viability of the preserved rat livers were first assessed ex vivo after rewarming (90 minutes at 37°C) and in vivo using the experimental model of reduced-size heterotopic liver transplantation. After SCS, the water and glycogen content in both groups remained unchanged as well as the tissue glutathione concentration. In the ex vivo studies, livers preserved with the BGP-HMP solution were hemodynamically more efficient and the O 2 consumption rate was higher than in livers from the HTK group. Bile production and glycogen content after 90 minutes of normothermic reperfusion was diminished in both groups compared with the control group. Cellular integrity of the BGP-HMP group was better, and the histological damage was reversible. In the in vivo model, HTK-preserved livers showed a greater degree of histological injury and higher apoptosis compared with the BGP-HMP group. In conclusion, our results suggest a better role of the BGP-HMP solution compared with HTK in preventing ischemia/reperfusion injury in the rat liver model., (Copyright © 2019 by the American Association for the Study of Liver Diseases.)

Portal vein malformations might occur during the embryonic period, as a consequence of abnormal remodeling of vitelline veins during embryonic life. Patients suffering from biliary atresia are particularly prone to have vascular malformations; although being the most frequent indication for liver transplantation in the pediatric age, portal vein duplication has not been so far associated with biliary atresia, and to the best of our knowledge, there is no-written evidence describing how to manage it when it is first diagnosed while performing a pediatric liver transplant. Therefore, we present a recent case from our group, describing the intraoperative diagnosis of a double portal system in a patient with biliary atresia and failed Kasai. We aim to describe its surgical management, understanding that it is a real challenge to find them unexpectedly during the surgical procedure in the setting of cirrhosis and portal hypertension, particularly in small patients; therefore, by reporting this case, we aim to make readers aware about the chance of finding it, and how to managed it, to include this approach as part of the surgical armamentarium., (© 2019 Wiley Periodicals, Inc.)

Collateral circulation secondary to liver cirrhosis may cause the development of large PSSs that may steal flow from the main portal circulation. It is important to identify these shunts prior to, or during the transplant surgery because they might cause an insufficient portal flow to the implanted graft. There are few reports of "steal flow syndrome" cases in pediatrics, even in biliary atresia patients that may have portal hypoplasia as an associated malformation. We present a 12-month-old female who received an uneventful LDLT from her mother, and the GRWR was 4.8. During the early post-operative period, she became hemodynamically unstable, developed ascites, and altered LFT. The post-operative ultrasound identified reversed portal flow, finding a non-anatomical PSS. A 3D CT scan confirmed the presence of a mesocaval shunt through the territory of the right gonadal vein, draining into the right iliac vein, with no portal inflow into the liver. The patient was re-operated, and the shunt was ligated. An intraoperative Doppler ultrasound showed adequate portal inflow after the procedure; the patient evolved satisfactorily and was discharged home on day number 49. The aim was to report a case of post-operative steal syndrome in a pediatric recipient due to a mesocaval shunt not diagnosed during the pretransplant evaluation., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Hepatocellular carcinoma (HCC) recurrence following liver transplantation is associated to bad prognosis. We retrospectively analyzed the data of 95 patients who underwent liver transplantation for HCC. Recurrence rate and variables associated with recurrence were reviewed. According to the findings on the explanted livers they were divided in two groups: Milan (M) 67% and non-Milan (NM) 33%. Global recurrence rate, and M-group and NM-group recurrence rates were 19%; 12% and 32%, respectively (P = 0.001). Although in the univariate analysis we found some factors associated to recurrence (hemocromathosis, year of transplant, bilobar distribution, vascular invasion and previous chemoembolization), they were not independent predictors of recurrence in the multivariate analysis. Actuarial survival in cirrhotic patients with and without HCC at 1, 3 and 5 years was 86% and 91% (NS), 77% and 88% (NS), and 67% and 86% (P = 0.002), respectively; whereas actuarial survival of the M and NM groups was 86% and 71%; 82% and 61%, and 78% and 58%, respectively (P = 0.02). We had a satisfactory five-year global survival in our series even though one third of our patients grafted for HCC were outside Milan criteria.

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., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: Donor outcome after living donor liver transplantation has not been examined extensively with regard to postoperative abdominal complaints. We wanted to examine the extent and type of abdominal complaints after removal of a part of the liver and gallbladder in living donors as well as potential similarities with known disorders., Methods: Twelve patients of mixed ethnicity, nine men, aged 18-45 years, and three women, aged 32-46 years, were enrolled in the study during a 3-year period and followed up at 6 and 12 months. Patients filled out questionnaires pertaining to functional abdominal complaints (FAC) using a recognized questionnaire, Rome II, as well as specific abdominal pain symptoms known from gallstone disease., Results: FAC occurred in 11 patients at 6 months and nine patients at 12 months while abdominal pain occurred in seven and six patients, respectively. Three patients had FAC but no abdominal pain while two patients had no complaints at 12 months. Irritable bowel syndrome (IBS) was found in the majority of patients., Conclusions: FAC and pain seemed to indicate a general postoperative disorder, of a psychosomatic character, and not connected with removal of part of the liver and gallbladder in particular. However, the occurrence of IBS and FD should merit attention, as they are known to impair quality of life.

An end-to-side portocaval shunt has been classically described as the standard procedure that needs to be performed to obtain adequate venous drainage of the foregut in combined liver-intestinal transplant. The transplanted organs are placed en bloc in a piggyback fashion on the recipient's vena cava, and graft's porto-mesenteric venous circulation is left intact. Recurrent portal hypertension with hemorrhage has been reported as a complication after such a procedure. In an effort to improve the technical aspects of this complex operation, we began to perform an end-to-end shunt from the recipient portal vein to the infrahepatic donor cava. Here, we describe this new surgical technique and discuss its potential advantages. The new technique is described in detail. Of the 70 intestinal transplants performed in 67 patients at The Mount Sinai Hospital from 1998 to December 2004, three were multivisceral transplants (MVTx) and 28 were combined liver intestine transplants (LITx), post-surgical outcome including recurrent portal hypertension and the presence of splenomegaly and significant thrombocytopenia was retrospectively review between the group that received the classic end-side vs. the new end-end portocaval shunt. Of the 28 LITx, 23 were done with the classic end-side portocaval shunt and in five (one adult, four pediatric) the end-to-end portocaval shunt described in the present study. One patient in this group died on post-operative day 31 (adult); after a mean follow up of 19.5 months there is a 100% patient and graft survival for the pediatric population. Post-operatively there have been no complications related to this technique. Few modifications have been made to the original description of MVTx. This is the first description of this technique that is relatively simple to perform, creating a large vascular conduit with high flow rates and theoretically less turbulence compared with the end-to-side shunt.

Background: : Due to ongoing organ donor shortage, an increasing number of adult live-donor liver transplants (LDLT) are being performed. The aims of this study were to compare the incidence of ACR between recipients of live- and deceased-donor liver transplants, and to note any differences in ACR among related and unrelated living-donor recipients., Methods: : Sixty-four adults undergoing LDLT between 1998-2001 were closely matched with a deceased recipient. Statistical comparisons in ACR between the live- and deceased-donor groups were based on the differences between the ACR rates of each LDLT patient and the corresponding matched deceased recipient. Analyses were performed separately for pairs in which the living donor was not related to the recipient, was a nonsibling relative, or was a sibling., Results: : Live- and deceased-donor recipients underwent a similar number of liver biopsies. In all, 16/50 (32%) of the biopsied LDLT patients had ACR compared to 36/49 (73%) of the deceased-donor recipients. ACR rates of living donors and their deceased-donor matches did not differ significantly for the unrelated living donors, but did differ for the nonsibling related (P=0.03) and the sibling LDLT (P=0.03). The results were similar when comparing rates of high-degree ACR for unrelated, nonsibling related, and sibling pairs. High-degree ACR differences in the sibling LDLT group were significantly greater than in the nonsibling group (P=0.05)., Conclusions: : Rates of ACR and high-degree ACR are decreased in living-related liver transplant recipients. This difference is likely genetically related as ACR rates are lower in recipient-donor pairs of increasing genetic similarity.

The demand for pediatric solid organs for transplantation exceeds the available supply. Transplant surgeons may elect to use organs from a donor whose cause of death is uncertain, especially when the recipient is deteriorating. In such circumstances, it is possible that organs from a patient with a systemic metabolic disorder may be transplanted into the recipient, leading to an adverse outcome. We report the first case in which liver and small bowel were procured from a donor with an unsuspected mitochondrial respiratory transport chain defect (succinate cytochrome C reductase deficiency). We describe the subsequent course of the recipient, who died 10 weeks later of multiorgan failure, and unusual findings at autopsy. In the absence of a clear cause of death in a potential pediatric organ donor, factors such as parental consanguinity should prompt physicians to acknowledge the increased possibility of an inherited metabolic disorder and to take this into consideration before proceeding with the transplant procedure.

Background: Biliary reconstruction represents one of the most challenging parts of right lobe (RL) living donor liver transplantations (LDLTs). Different causes, surgical techniques, and treatments have been suggested but are incompletely defined., Methods: Between June 1999 and January 2002, 96 RL LDLTs were performed in our center. We reviewed the incidence of biliary complications in all the recipients., Results: Roux-en-Y reconstruction was performed in 53 cases (55.2%) and duct-to-duct was performed in 39 cases (40.6%). Both procedures were performed in 4 cases (4.2%). Multiple ducts (> or =2) were found in 58 grafts (60.4%). Thirty-nine recipients (40.6%) had 43 biliary complications: 21 had bile leaks, 22 had biliary strictures, and 4 had both complications. Patients with multiple ducts had a higher incidence of bile leaks than those patients with a single duct (P=0.049). No significant differences in complications were found between Roux-en-Y or duct-to-duct reconstructions. Freedom from biliary complications was 59% at 1 year and 55% at 2 years. The overall 1-year and 2-year survival rates for patients were 86% and 81%, respectively. The overall 1-year and 2-year survival rates for grafts were 80% and 77%, respectively. Occurrence of bile leaks affected patient and graft survival (76% and 65% 2-year patient and graft survival, respectively, vs. 89% and 85% for those without biliary leaks, P=0.07)., Conclusions: Despite technical modifications and application of various surgical techniques, biliary complications remain frequent after RL LDLT. Patients with multiple biliary reconstructions had a higher incidence of bile leaks. Patients who developed leaks had lower patient and graft survival rates.

Very little is known about the natural history, effects of therapy, and survival after recurrence of hepatocellular carcinoma (HCC) after liver transplantation. All adult patients undergoing liver transplant from September 19, 1988, until September 19, 2002, were reviewed. Only patients with histologically proven HCC in the explant who subsequently developed recurrence were included in further analysis. The endpoints analyzed were survival from time of transplant and survival from time of recurrence. Recipient demographics and laboratory values, technique of transplant (whole cadaver, split, or living donor), and tumor characteristics were analyzed. The time to, location of, and any medical or surgical treatment of recurrences also were considered. Of the 311 patients with HCC in the explant, 57 (18.3%) eventually were diagnosed with recurrent tumor after transplant. Median time to recurrence was 12.3. Five-year survival was significantly lower for patients with recurrence (22%) than for patients without recurrence (64%)(P < 0.0001). Multivariate analysis demonstrated that the size and differentiation of the original tumor, as well as the presence of bone recurrence, were independently associated with survival from transplant in patients with recurrence. When survival from the time of recurrence was analyzed, multivariate analysis showed that the absence of bone metastases, recurrence more than 12 months from transplant, and surgical treatment of the recurrence were independently associated with significantly longer survival. In conclusion, recurrence of HCC significantly shortens survival after transplant. Nonetheless, some patients with recurrence can be expected to live for a considerable period of time. Recurrent disease should be treated surgically when possible, because surgery is independently associated with longer survival.

Objective: Nonadherence to medications is a leading cause of morbidity in children and adolescents who have had a transplant, yet there are no published data about the use of different methods for detecting whether these children are taking their medications. There are also no published data about the age of transition at which a child assumes responsibility over taking the medications. This information is important if interventions to improve adherence are contemplated., Methods: We present an analysis of data obtained in the first year of the implementation of an adherence assessment protocol at a pediatric liver transplant clinic in a tertiary medical care center. Data were obtained for children and adolescents who had a liver transplant at least 1 year before the assessments took place. We used 5 adherence detection methods. The 4 subjective methods were self-reported, scaled questionnaires answered by nurses, physicians, caregivers, and patients. For the objective method, a standard deviation (SD) was calculated for tacrolimus blood levels obtained from each patient over time. A higher SD suggests increased variation among patients' blood levels and hence more erratic medication taking. We also asked the patients and caregivers who is responsible for taking the medications and what are the reasons for not taking them. The medical outcome measures were biopsy-proven rejection episodes, number of biopsies regardless of the results, number of hospital admissions, and number of in-patient days., Results: An analysis of 81 cases (258 assessments) revealed that the only method that predicted the medical outcome variables (biopsy-proven rejection and number of biopsies) was the SD of medication blood levels. Patients', clinicians', and caregivers' reports were not predictive. Clinicians' ratings of adherence were not correlated with patients' or caregivers'. The transition of responsibility for medication taking occurred approximately at the age of 12 years. Forgetfulness was cited as the most common reason for nonadherence by patients and caregivers; medication side effects were not frequently cited., Conclusions: Our results indicate that clinical impression is not sufficient to determine whether children and adolescents are taking their medications after they have had a liver transplant. An objective assessment method should be used. Interventions targeting adherence should address the child's increasing role beginning in early adolescence. A clinical protocol incorporating objective assessments of adherence could potentially be implemented in other settings. It could form the basis for the evaluation of efficacy of interventions seeking to improve adherence to medications.

Background: Anatomic knowledge is crucial in right liver living donor transplantation., Study Design: We reviewed radiologic and surgical findings in right liver donors. Arterial and portal anatomy was assessed in 96 donors, biliary anatomy in 77, and hepatic venous anatomy in 65., Results: Portal vein (PV): 86.4% had classic anatomy; 6.3% had a trifurcated PV; 7.3% had a right anterior PV taken off the left PV. Hepatic artery (HA): 70.8% had classic anatomy; 12.5% had a left HA arising from the left gastric artery; 13.5% had a right HA arising from the superior mesenteric artery; 2.1% had a double replaced left HA and right HA; and in 1.0% the common HA arose from the superior mesenteric artery. Biliary tree: 55.8% had normal anatomy; 14.3% had a trifurcated biliary anatomy; in 5.2% the right anterior bile duct and in 15.6% the right posterior bile duct opened into the left bile duct; in 2.6% the right anterior and in 6.5% the right posterior ducts opened into the common bile duct. Hepatic veins: S5 and S8 accessory hepatic veins had incidences of 43% and 49%, respectively. The incidence of S6 or S7 short hepatic vein was 38%., Conclusions: Anatomic variations are common but do not contraindicate donation; surgeons should be prepared to recognize and manage them.

Background: Acute renal failure (ARF) occurs in 5-50% of patients undergoing orthotopic liver transplantation (OLT). The aim of this study was to determine factors that might predict the development of end stage renal disease (ESRD) in patients who had ARF after OLT., Methods: We studied all OLT recipients between 9/1/1988 through 12/31/2000., Results: A total of 1602 patients underwent OLT during the study period. About 350 patients (22%) developed ARF requiring dialysis post-operatively. One hundred and twenty-three (39.8%) died within a year after OLT. Median follow up was 5.8 yr (range 1-12 yr). Forty-three patients (23%) developed ESRD over median of 3.79 yr (range 1-8 yr). Multivariate logistic regression analysis revealed creatinine levels > 1.7 mg/dL at 1 yr (p < 0.001), cyclosporine as immunosuppression (p = 0.026), and the presence of diabetes pre-OLT (p < 0.001) to be associated with the development of ESRD. The development of ESRD did not decrease patient survival (p = 0.111). ESRD patients who received subsequent kidney transplantation had significantly improved survival rates (p = 0.005)., Conclusions: Serum creatinine levels at 1 yr, cyclosporine as immunosuppression, and the presence of diabetes pre-OLT are independent predictive factors for the development of ESRD. ESRD patients who received kidney transplantation had higher 10-yr survival rates when compared with patients maintained on dialysis.

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.

Background: Liver transplantation is the best therapeutic option for patients with end-stage liver disease from primary sclerosing cholangitis. Primary sclerosing cholangitis is associated with a markedly increased risk of cholangiocarcinoma, which adversely affects survival. Approximately 20% to 30% of cholangiocarcinomas are localized in the distal bile duct. Pancreatoduodenectomy is the curative therapy for cholangiocarcinomas in this location., Study Design: We reviewed our data on a patient with primary sclerosing cholangitis-related end-stage liver disease and a simultaneous distal bile duct tumor, which was treated with a combined right-lobe, living-donor liver transplantation and pancreatoduodenectomy., Results: The patient was discharged 32 days post-transplantation. He is currently alive 1 year after the procedure with no evidence of recurrent cancer., Conclusions: Combined living-donor liver transplantation and pancreatoduodenectomy is feasible and allows timely and elective surgical control of carefully selected distal bile duct tumors in the setting of end-stage liver disease.

We evaluated the influence of portal and hepatic venous hemodynamics on the immediate and 3-month postoperative function of living donor right lobe grafts. Portal velocity was measured prospectively by ultrasound in 14 consecutive donor/recipient pairs. Velocity was converted to flow with the Moriyasu formula. Measurements were taken in donors in the operating room and in recipients at 1 hour after reperfusion and 3 months after transplant. Recipient liver function tests were measured postoperatively. Prereperfusion and postreperfusion liver biopsies were evaluated and correlated with the hemodynamic and biochemical results. There were 11 male (78.6%) and 3 female donors (mean age, 38.9 +/- 9.8 years) for 10 male (71.4%) and 4 female recipients (mean age, 49.3 +/- 14 years). The mean graft/recipient weight ratio was 1.22 +/- 0.3. The mean right portal vein pressure was 8 +/- 1.8 mm Hg in donors versus 13 +/- 4.7 mm Hg in recipients (P < .05). The mean peak flow velocity (Vmax) in the portal vein in donors was 47.6 +/- 12.8 cm/sec (normal, 44 cm/sec). One hour after graft reperfusion in the recipient, the mean portal Vmax was significantly higher at 94.7 +/- 28.4 cm/sec (P = .004), but by 3 months follow-up, mean portal Vmax had fallen to 58.8 +/- 37.8 (P = .01). Recipient portal vein Vmax highly correlated with portal flow (r = 0.7, P = .01). Increased recipient total bilirubin on postoperative day 2 correlated highly with higher recipient portal flow one hour after transplant (r = 0.6; P =.03). Portal vein velocity/flow dramatically increases after reperfusion, returning to baseline about 3 months after transplant. Evaluation of hepatic and portal venous flow is a relatively easy skill to acquire. Intraoperative ultrasound may enable the surgeon to predict graft dysfunction and possibly, may be used to implement pre-emptive therapies.

The article discusses the successful human liver transplant. Topic include the on the study of the IL-33/ST2 axis during allograft rejection, fibrosis and liver injury in the transplant context as part of our translational research program manuscript in preparation, adverse effects caused by the long-term use of immunosuppression and the lack of new drugs in the pipeline.

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