Subsequent Liver Transplantation Research Articles

Feasibility of Liver Transplantation after 90Y Radioembolization: Lessons from a Radiation Protection Incident.

Radioembolization using 90Y is a growing procedure in nuclear medicine for treating hepatocellular carcinoma. Current guidelines suggest postponing liver transplantation or surgical resection for a period of 14 to 30 d after radioembolization to minimize surgeons' exposure to ionizing radiation. In light of a radiation protection incident, we reevaluated the minimum delay required between radioembolization and subsequent liver transplantation. A patient with a hepatocellular carcinoma underwent a liver transplantation 44 h after undergoing radioembolization using 90Y (860 MBq SIR-Spheres). No specific radioprotection measures were followed during surgery and pathological analysis. We subsequently (1) evaluated the healthcare professionals' exposure to ionizing radiation by conducting dose rate measurements from removed liver tissue and (2) extrapolated the recommended interval to be observed between radioembolization and surgery/transplantation to ensure compliance with the radiation dose limits for worker safety. The surgeons involved in the transplantation procedure experienced the highest radiation exposure, with whole-body doses of 2.4 mSv and extremity doses of 24 mSv. The recommended delay between radioembolization and liver transplantation was 8 d when using SIR-Spheres and 15 d when injecting TheraSphere. This delay can be reduced further when considering the specific 90Y activity administered during radioembolization. This dosimetric study suggests the feasibility of shortening the delay for liver transplantation/surgery after radioembolization from the 8th or 15th day after using SIR-Spheres or TheraSphere, respectively. This delay can be decreased further when adjusted to the administrated activity while upholding radiation protection standards for healthcare professionals.

Transarterial Radioembolization (TARE) in Patients with Hepatocellular Carcinoma: A Comparison of Palliative with Bridging-to-Transplant Concepts.

We investigated transarterial radioembolization (TARE) as a palliative measure and bridging-to-transplant therapy in hepatocellular carcinoma (HCC) patients. A total of 167 patients (50 bridging, 117 palliative) with 245 TARE procedures were assessed. Fourteen patients underwent subsequent liver transplantation (LT). Patients undergoing LT exhibited significantly prolonged progression-free survival (PFS) compared to those with bridging-without-transplant (p = 0.033). No significant differences were observed between patients with bridging-without-transplant and palliative cases (p = 0.116). Median overall survival (OS) post-TARE was 16.6 months, with estimated OS rates at 6/12 months of 82.0%/60.5%, respectively. Patients who underwent LT demonstrated statistically significantly longer OS compared to those with bridging-without-transplant (p = 0.001). No marked outcome distinctions were found between bridging-without-transplant and palliative groups. The findings underscored the superiority of LT over alternative treatments. TARE served as an important component in non-LT scenarios, allowing for subsequent therapeutic options. The study reflected the highly variable and complex situations of patients with HCC, emphasizing the need for further investigations to define an optimal multimodal approach.

Maternal Prenatal Infections and Biliary Atresia in Offspring

Investigations into the association of antepartum maternal infections with the pathogenesis of biliary atresia (BA) in human offspring are insufficient. To examine the association between prenatal infections in mothers and the development of BA in their offspring. This population-based case-control study obtained administrative data from the Taiwan National Health Insurance Research Database with linkage to the Taiwan Maternal and Child Health Database, capturing demographic and medical information on nearly all 23 million of the Taiwan population. The cohort comprised 2 905 978 singleton live births among mother-infant dyads between January 1, 2004, and December 31, 2020, in Taiwan. The case group of infants with BA was identified from use of International Classification of Diseases diagnostic codes for BA and subsequent Kasai procedure or liver transplant. The control group was randomly selected from infants without BA, representing approximately 1 in 1000 study population. Data analyses were performed from May 1 to October 31, 2023. Prenatal maternal infections, including intestinal infection, influenza, upper airway infection, pneumonia, soft-tissue infection, and genitourinary tract infection. The main outcome was exposure to prenatal maternal infections. Inverse probability weighting analysis was performed by building a logistic regression model to estimate the probability of the exposure observed for a particular infant and using the estimated probability as a weight in subsequent analyses. The weighted odds ratio (OR) estimated by logistic regressions was then used to assess the risk of BA in offspring after prenatal maternal infections. Among the mother-infant dyads included, 447 infants with BA were cases (232 females [51.9%]) and 2912 infants without BA were controls (1514 males [52.0%]). The mean (SD) maternal age at childbirth was 30.7 (4.9) years. Offspring exposed to prenatal intestinal infection (weighted OR, 1.46; 95% CI, 1.17-1.82) and genitourinary tract infection (weighted OR, 1.22; 95% CI, 1.05-1.41) in mothers exhibited a significantly higher risk of BA. Furthermore, maternal intestinal infection (weighted OR, 6.05; 95% CI, 3.80-9.63) and genitourinary tract infection (weighted OR, 1.55; 95% CI, 1.13-2.11) that occurred during the third trimester were associated with an increased risk of BA in offspring. Results of this case-control study indicate an association between prenatal intestinal infection and genitourinary tract infection in mothers and BA occurrence in their offspring. Further studies are warranted to explore the underlying mechanisms of this association.

Pre-emptive transjugular intrahepatic portosystemic shunt in pediatric cystic fibrosis-related liver disease and portal hypertension: prospective long-term results.

Portal hypertension (PHT) and its sequelae are the most clinically important manifestations in cystic fibrosis-related liver disease (CFLD). This paper aimed to evaluate the safety and efficacy of a pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) to prevent PHT-related complications in pediatric patients with CFLD. This was a prospective single-arm study on pediatric patients with CFLD, signs of PHT, and preserved liver function who underwent a pre-emptive TIPS in a single tertiary CF center between 2007 and 2012. The long-term safety and clinical efficacy were assessed. A pre-emptive TIPS was performed on seven patients with a mean age of 9.2 years (± standard deviation: 2.2). The procedure was technically successful in all patients, with an estimated median primary patency of 10.7 years [interquartile range (IQR) 0.5-10.7)]. No variceal bleeding was observed during the median follow-up of 9 years (IQR 8.1-12.9). In two patients with advanced PHT and rapidly progressive liver disease, severe thrombocytopenia could not be stopped. Subsequent liver transplantation revealed biliary cirrhosis in both patients. In the remaining patients with early PHT and milder porto-sinusoidal vascular disease, symptomatic hypersplenism did not occur, and liver function remained stable until the end of the follow-up. Inclusion for pre-emptive TIPS was discontinued in 2013 following an episode of severe hepatic encephalopathy. TIPS is a feasible treatment with encouraging long-term primary patency to avoid variceal bleeding in selected patients with CF and PHT. However, as the progression of liver fibrosis, thrombocytopenia, and splenomegaly is inevitable, the clinical benefits due to pre-emptive placement appear to be minor.

Deep learning quantification reveals a fundamental prognostic role for ductular reaction in biliary atresia.

We aimed to quantify ductular reaction (DR) in biliary atresia using a neural network in relation to underlying pathophysiology and prognosis. Image-processing neural network model was applied to 259 cytokeratin-7-stained native liver biopsies of patients with biliary atresia and 43 controls. The model quantified total proportional DR (DR%) composed of portal biliary epithelium (BE%) and parenchymal intermediate hepatocytes (PIH%). The results were related to clinical data, Sirius Red-quantified liver fibrosis, serum biomarkers, and bile acids. In total, 2 biliary atresia biopsies were obtained preoperatively, 116 at Kasai portoenterostomy (KPE) and 141 during post-KPE follow-up. DR% (8.3% vs. 5.9%, p=0.045) and PIH% (1.3% vs. 0.6%, p=0.004) were increased at KPE in patients remaining cholestatic postoperatively. After KPE, patients with subsequent liver transplantation or death showed an increase in DR% (7.9%-9.9%, p = 0.04) and PIH% (1.6%-2.4%, p = 0.009), whereas patients with native liver survival (NLS) showed decreasing BE% (5.5%-3.0%, p = 0.03) and persistently low PIH% (0.9% vs. 1.3%, p = 0.11). In Cox regression, high DR predicted inferior NLS both at KPE [DR% (HR = 1.05, p = 0.01), BE% (HR = 1.05, p = 0.03), and PIH% (HR = 1.13, p = 0.005)] and during follow-up [DR% (HR = 1.08, p<0.0001), BE% (HR = 1.58, p = 0.001), and PIH% (HR = 1.04, p = 0.008)]. DR% correlated with Sirius red-quantified liver fibrosis at KPE (R = 0.47, p<0.0001) and follow-up (R = 0.27, p = 0.004). A close association between DR% and serum bile acids was observed at follow-up (R = 0.61, p<0.001). Liver fibrosis was not prognostic for NLS at KPE (HR = 1.00, p = 0.96) or follow-up (HR = 1.01, p = 0.29). DR predicted NLS in different disease stages before transplantation while associating with serum bile acids after KPE.

Liver-Directed Combined Radiotherapy for Downstaging of the Milan Advanced Hepatocellular Carcinoma Converting to Liver Transplantation

Recent success of combined immunotherapy sheds a light to the future of advanced hepatocellular carcinoma patients but still remains as a palliative setting. The best oncologic outcome for HCC can be obtained by curative surgery either by resection or liver transplantation (LT). Efficacy of liver-directed combined radiotherapy (LD-CRT) for downstaging and subsequent surgical resection in locally advanced HCC had been reported earlier by our team. In this study, we investigated the role of LD-CRT as a downstaging strategy for converting advanced hepatocellular carcinoma to LT. We reviewed 55 hepatocellular carcinoma patients who had undergone downstaging LD-CRT and subsequent liver transplantation from January 2009 to February 2022. Patients within Milan criteria at the time of receiving radiotherapy were excluded and clinical characteristics and histopathology of explant liver were evaluated. The overall survival and disease-free survival were assessed using the Kaplan-Meier method RESULTS: The median follow-up period was 48.6 months (range 6.9 - 151.7 months). Of 55 patients, 24 (43.6%) were treatment naïve. At the time of RT, 36 patients presented large tumor (tumor diameter >5 cm) or multiple lesions (>3 lesions), 37 with major vessel involvement or portal vein tumor thrombosis, and 7 with extrahepatic lesion. LD-CRT was given as localized concurrent chemoradiation (CCRT) for 41 patients (74.5%) and transarterial chemoembolization (TACE) plus RT for 10 patents (18.2%). Substantial downstaging has been achieved in 38 (69%) patients with initially over the Milan to within Milan. Specifically, 29 of 37 patients initially with major vessel invasion or with tumor thrombosis were successfully converted to microscopic vessel invasion or tumor thrombus-free status in explant liver. 5-year overall survival was 68.1% and 2-year disease-free survival was 51%, respectively. Recurrence after transplantation was observed in 18 patients (4 intrahepatic recurrence and 14 extrahepatic metastasis) and the majority (14/18) occurred within 2 years. Liver-directed combined radiotherapy as a downstaging strategy for liver transplantation achieved favorable oncologic outcomes in advanced hepatocellular carcinoma patients. This study suggests that active adoption of radiotherapy needs full consideration for locally advanced HCC patients, opening a chance for curative LT.

Colonization of extended-spectrum β-lactamase-producing Enterobacteriaceae does not affect subsequent infection and liver transplant outcomes: a retrospective observational cohort study.

To investigate the colonization rate of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E), subsequent infections by ESBL-E and ESBL-producing gram-negative bacilli (ESBL-GNB), and the effect of ESBL-E colonization on clinical outcomes in liver transplantation (LT) recipients. This is a retrospective cohort study that included patients who underwent LT at Shanghai Renji Hospital between July 2016 and December 2017. Rectal swabs from LT patients at the postoperative ICU enrollment were screened anonymously for ESBL-E carriage. Demographics data, laboratory indexes, operative complications, and clinical course information were also obtained. The extent of ESBL-E colonization, the subsequent infection rates of ESBL-E and ESBL-GNB, and the clinical outcomes were compared between ESBL-E colonized and non-colonized patients. In total, 496 liver transplant recipients (387 males) were included in this study. ESBL-E colonization was detected in 240 patients (48.4%). There was no significant difference between the rates of ESBL-E infection (5.8 vs. 3.1%, p = 0.143), Ischemia-reperfusion ≥ 3 (27.9 vs. 24.6%, p = 0.403), acute kidney injury (39.6 vs. 38.7%, p = 0.835), acute rejection (2.1 vs. 1.6%, p = 0.664), graft versus host reaction (1.3 vs. 1.2%, p = 0.937), duration of hospitalization (22 vs. 23 days, p = 0.568), 90-day mortality (7.1 vs. 4.7%, p = 0.262) and 1-year mortality (12.9 vs. 9.3%, p = 0.265) in patients with and without ESBL-E colonization. Though the ESBL-GNB infection rate was higher in ESBL-E colonized patients (12.1 vs. 6.6%, p = 0.037), multivariate analysis showed that ESBL-E colonization did not increase the risk of ESBL-GNB infection (Model 1: aOR 1.755, 95% CI: 0.911-3.380, p = 0.093; Model 2: aOR 1.556, 95% CI: 0.761-3.181, p = 0.226). The ESBL-producing bacteria spectrum of colonization was significantly different from that of infections occurring after LT, with only three colonization events leading to infection by the same pathogen identified. ESBL-E colonization in liver transplant patients is not associated with ESBL-E infection, nor is it a risk factor for post-transplant ESBL-GNB infection. Additionally, ESBL-E colonization does not lead to worse prognoses when compared with non-colonized patients. Chinese Clinical Trial Registry, Identifier [ChiCTR2100043034].

Prognostic Factors of Liver Transplantation for Hepatocellular Carcinoma: A Surveillance, Epidemiology, and End Results (SEER) Database Analysis

We aimed to identify new, more accurate risk factors of liver transplantation for liver cancer through using the Surveillance, Epidemiology, and End Results (SEER) database. Using the SEER database, we identified patients that had undergone surgical resection for non-metastatic hepatocellular carcinoma (HCC) and subsequent liver transplantation between 2010 and 2017. Overall survival (OS) was estimated using Kaplan-Meier plotter. Cox proportional hazards regression modelling was used to identify factors independently associated with recurrent disease [presented as adjusted hazard ratios (HR) with 95% CIs]. Totally, 1530 eligible patients were included in the analysis. There were significant differences in ethnicity (P=0.04), cancer stage (P<0.001), vascular invasion (P<0.001) and gall bladder involvement (P<0.001) between the groups that survived, died due to cancer, or died due to other causes. In the Cox regression model, there were no significant differences in OS at 5 years with different operative strategies (autotransplantation versus allotransplantation), nor at survival at 1 year with neoadjuvant radiotherapy. However, neoadjuvant radiotherapy did appear to improve survival at both 3 years (HR: 0.540, 95% CI: 0.326-0.896, P=0.017) and 5 years (HR: 0.338, 95% CI: 0.153-0.747, P=0.007) from diagnosis. This study demonstrated differences in patient characteristics between prognostic groups after liver resection and transplantation for HCC. These criteria can be used to inform patient selection and consent in this setting. Preoperative radiotherapy may improve long-term survival post-transplantation.

Liver-directed combined radiotherapy for downstaging of over the Milan advanced hepatocellular carcinoma converting to liver transplantation.

561 Background: Recent success of combined immunotherapy sheds a light to the future of advanced hepatocellular carcinoma patients but still remains as a palliative setting. The best oncologic outcome for HCC can be obtained by curative surgery either by resection or liver transplantation (LT). Efficacy of liver-directed combined radiotherapy (LD-CRT) for downstaging and subsequent surgical resection in locally advanced HCC had been reported earlier by our team. In this study, we investigated the role of LD-CRT as a downstaging strategy for converting advanced hepatocellular carcinoma to LT. Methods: We reviewed 55 hepatocellular carcinoma patients who had undergone downstaging LD-CRT and subsequent liver transplantation from January 2009 to February 2022. Patients within Milan criteria at the time of receiving radiotherapy were excluded and clinical characteristics and histopathology of explant liver were evaluated. The overall survival and disease-free survival were assessed using the Kaplan-Meier method. Results: The median follow-up period was 48.6 months (range 6.9 – 151.7 months). Of 55 patients, 24 (43.6%) were treatment naïve. At the time of RT, 36 patients presented large tumor (tumor diameter &gt;5 cm) or multiple lesions (&gt;3 lesions), 37 with major vessel involvement or portal vein tumor thrombosis, and 7 with extrahepatic lesion. LD-CRT was given as localized concurrent chemoradiation (CCRT) for 41 patients (74.5%) and transarterial chemoembolization (TACE) plus RT for 10 patents (18.2%). Substantial downstaging has been achieved in 38 (69%) patients with initially over the Milan to within Milan. Specifically, 29 of 37 patients initially with major vessel invasion or with tumor thrombosis were successfully converted to microscopic vessel invasion or tumor thrombus-free status in explant liver. 5-year overall survival was 68.1% and 2-year disease-free survival was 51%, respectively. Recurrence after transplantation was observed in 18 patients(4 intrahepatic recurrence and 14 extrahepatic metastasis) and the majority (14/18) occurred within 2 years. Conclusions: Liver-directed combined radiotherapy as a downstaging strategy for liver transplantation achieved favorable oncologic outcomes in advanced hepatocellular carcinoma patients. This study suggests that active adoption of radiotherapy needs full consideration for locally advanced HCC patients, opening a chance for curative LT.

What Makes A "Successful" Kasai Portoenterostomy "Unsuccessful"?

Clearance of jaundice (CoJ) is the first key objective of Kasai portoenterostomy (KPE) for biliary atresia (BA) and its achievement is by far the best index of long-term prognosis. We sought to identify the reasons for failure [subsequent liver transplant (LT)] in this cohort. Review of single-center prospective BA database. Successful KPE was defined by achieving a postoperative bilirubin of ≤20 µmol/L. Pre-KPE and post-KPE variables were identified together with a multivariate logistic regression model to identify those observable at 3 months post-KPE. Data are quoted as median (range). A P value of ≤0.05 was significant. One hundred thirty-five infants underwent KPE between January 2012 and December 2018, of which 90 (67%) achieved CoJ. From these 20 (22%) (Cohort A) underwent LT with the remainder continuing with native liver (Cohort B) (median follow-up of 4.15 years). There was no difference in age at KPE ( P = 0.41), APRi (aspartate aminotransferase-to-platelet ratio) ( P = 0.07), associated anomalies ( P = 0.7), and cytomegalovirus status ( P = 0.7) between the 2 groups. Postoperatively, both cholangitis [any episode, 18/20 (90%) vs 15/70 (21%); P < 0.0001] and portal hypertension (PHT) [gastrointestinal (GI) bleed, 10/20 (50%) vs 2/70 (2.8%); P < 0.0001] were significantly more common in cohort A. Univariate analysis showed that the most significant predictive values at 3 months for LT by 2 years were high APRi, bilirubin, international normalized ratio, and ultrasound (US)-detected ascites with multivariate logistic modeling confirming these variables with predictive values of r2 = 0.79, AUROC = 0.98. Failure is not preordained at KPE but due to recurrent cholangitis and/or symptoms of PHT.

Magnetic Resonance Imaging Predictors of Hepatocellular Carcinoma Progression and Dropout in Patients in Liver Transplantation Waiting List.

Background.With the rising incidence of hepatocellular carcinoma (HCC), more patients are now eligible for liver transplantation. Consequently, HCC progression and dropout from the waiting list are also anticipated to rise. We developed a predictive model based on radiographic features and alpha-fetoprotein to identify high-risk patients.Methods.This is a case-cohort retrospective study of 76 patients with HCC who were listed for liver transplantation with subsequent liver transplantation or delisting due to HCC progression. We analyzed imaging-based predictive variables including tumor margin (well- versus ill-defined), capsule bulging lesions, volumetric analysis and distance to portal vein, tumor numbers, and tumor diameter. Volumetric analysis of the index lesions was used to quantify index tumor total volume and volumetric enhancement, whereas logistic regression and receiver operating characteristic curve (ROC) analyses were used to predict the main outcome of disease progression.Results.In univariate analyses, the following baseline variables were significantly associated with disease progression: size and number of lesions, sum of lesion diameters, lesions bulging the capsule, and total and venous-enhancing (viable) tumor volumes. Based on multivariable analyses, a risk model including lesion numbers and diameter, capsule bulging, tumor margin (infiltrative versus well-defined), and alpha-fetoprotein was developed to predict HCC progression and dropout. The model has an area under the ROC of 82%, which was significantly higher than Milan criteria that has an area under the ROC of 67%.Conclusions.Our model has a high predictive test for patient dropout due to HCC progression. This model can identify high-risk patients who may benefit from more aggressive HCC treatment early after diagnosis to prevent dropout due to such disease progression.

Liver Transplantation for Metamizole induced Acute Liver Failure

Metamizole, or dipyrone, is a frequently prescribed analgetic drug that can cause drug-induced liver injury (DILI). Still, there are only a few metamizole-associated DILI cases (n=61, including our study) described in the literature. So far liver transplantation has been reported in 6 patients with metamizole-induced acute liver failure. In 2020, a German group described a bigger cohort (n=23) of metamizole-related DILI. Shortly thereafter, this issue gained wider attention as the German Federal Institute for Drugs and Medical Devices published a Direct Healthcare Professional Communication, emphasizing DILI as a potential adverse event caused by metamizole. We herein report 2 patients that were admitted to our liver transplant center due to acute liver failure (ALF) in April and May 2021. Both patients reported intake of metamizole as pain medication over a few weeks. After ruling out alternative reasons for ALF and fulfilling the King's College criteria both patients received emergency liver transplantations in our center. Pathology assessment of both explants were consistent with metamizole-associated DILI. As illustrated by our 2 cases of metamizole-induced liver failure with subsequent liver transplantation, this rare but presumably often overlooked adverse drug effect of metamizole should be considered as differential diagnosis in cases of cryptogenic liver failure.

Optimal imaging criteria and modality to determine Milan criteria for the prediction of post-transplant HCC recurrence after locoregional treatment.

We aimed to investigate the optimal radiologic method to determine Milan criteria (MC) for the prediction of recurrence in patients who underwent locoregional treatment (LRT) for hepatocellular carcinoma (HCC) and subsequent liver transplantation (LT). This retrospective study included 121 HCC patients who underwent LRT and had both liver dynamic CT and MRI. They were classified with MC using four cross combinations of two imaging modalities (CT and MRI) and two diagnostic criteria (modified Response Evaluation Criteria in Solid Tumors [mRECIST] and Liver Imaging Reporting and Data System treatment response algorithm [LI-RADS TRA]). Competing risk regression was performed to analyze the time to recurrence after LT. The predictive abilities of the four methods for recurrence were evaluated using the time-dependent area under the curve (AUC). Competing risk regression analyses found that beyond MC determined by MRI with mRECIST was independently associated with recurrence (hazard ratio, 6.926; p = 0.001). With mRECIST, MRI showed significantly higher AUCs than CT at 3 years and 5 years after LT (0.597 vs. 0.756, p = 0.012 at 3 years; and 0.588 vs. 0.733, p = 0.024 at 5 years). Using the pathologic reference standard, MRI with LI-RADS TRA showed higher sensitivity (61.5%) than CT with LI-RADS TRA (30.8%, p < 0.001) or MRI with mRECIST (38.5%, p < 0.001). MRI with mRECIST was the optimal radiologic method to determine MC for the prediction of post-LT recurrence in HCC patients with prior LRT. • MRI with modified RECIST (mRECIST) is the optimal preoperative method to determine Milan criteria for the prediction of post-transplant HCC recurrence in patients with prior locoregional treatment. • With mRECIST, MRI was better than CT for the prediction of post-transplant recurrence.

Abstract No. 184 Pre-operative portal vein recanalization-transjugular intrahepatic portosystemic shunt for chronic, obliterative portal vein thrombosis: outcomes following liver transplantation

High-grade portal vein thrombosis (PVT) is often considered to be a relative contraindication for liver transplantation (LT). This study compares patients with chronic, obliterative PVT, who underwent portal vein recanalization-transjugular intrahepatic portosystemic shunt (PVR-TIPS) and subsequent LT, to those with partial, non-occlusive PVT who underwent LT without an intervention.

Liver Transplantation After Organ Donation Due to Hydrogen Sulfide Intoxication: Report of the First Case.

The discrepancy of patients on the waiting list and the availability of organs suitable for transplantation continues to represent a relevant problem in transplantation medicine. Regarding liver transplantation, the increasing use of organs from donors with so-called extended criteria meanwhile has become daily practice in many countries.1 Consequently, every potential donor reported is carefully evaluated for suitability for organ donation. When a liver from a young brain-dead donor after hydrogen sulfide (H2S) intoxication was offered for a high-urgency listed patient, research of the literature did not provide any help for decision making in organ allocation. Herewith, we want to share our experience following the successful use of this donor liver for transplantation. A 60-y-old female patient with acute liver failure caused by an autoimmune hepatitis was transferred to our center and eventually listed for high-urgency liver transplantation following biopsy-proven diagnosis and rapid worsening of the clinical condition despite thorough intensive medical treatment (see Figure 1). Within 5 h after approval of high-urgency status, we were offered a liver from a 19-y-old female brain-dead donor following H2S intoxication in suicidal intent. Apart from depression, the donor was in excellent general condition before intoxication and had no other known illnesses. Despite recently promoted organ protective effects in experimental studies,2 inhalation of H2S in higher concentrations is highly toxic and eventually led to cardiac arrest in this patient.3 Following a short period of resuscitation, the donor was admitted to an intensive care unit and eventually diagnosed brain dead. Within 24 h, severe lung edema and subsequently respiratory failure developed as signs of multiorgan failure. Regarding the liver, apart from an initial peak of transaminases (peak AST and ALT levels of 357 and 438 U/L, respectively), the laboratory findings were all unremarkable. Because of the severe condition of our recipient with severe hepatic encephalopathy, we thus accepted the organ after intense interdisciplinary discussion despite the lack of any data on successful use of organs for transplant under these conditions. Upon arrival of the organ at our center, histological work-up of the liver by frozen section was performed despite excellent macroscopic appearance, which did not reveal any signs of acute liver injury or chronic alterations‚ such as steatosis or fibrosis (see Figure 2). Subsequent liver transplantation was completely uneventful. The patient’s clinical condition improved rapidly, with discharge at day 15 after transplantation (see Figure 1). During follow-up of 6 mo, no irregularities were observed, with excellent graft function and medical condition of the recipient at last visit. In conclusion, to our knowledge‚ this is the first report of a liver transplant from a brain-dead donor after hydrogen sulfide intoxication. Based on this single-case experience, potential donors after hydrogen sulfide intoxication should be carefully evaluated and considered for organ donation. Particularly evaluation of potential grafts applying normothermic machine perfusion might represent another valuable option in case of less urgent conditions of the recipients.4FIGURE 1.: Course of laboratory parameters (AST, ALT [both U/L], bilirubin [µmol/L], and INR) of the recipient before and after LTx, with time points of liver biopsy, PE and steroid therapy‚ and day of transplantation indicated by gray bars. ALT, alanine aminotransferase; AST, aspartate aminotransferase; INR, international normalized ratio; LTx, liver transplantation; PE, plasmapheresis.FIGURE 2.: Histopathology of liver wedge biopsy: hematoxylin and eosin staining shows no steatosis, fibrosis, or cirrhosis ([A] ×40 magnification and [B] ×100 magnification), and Elastica van Gieson staining highlights absence of fibrosis within the liver parenchyma ([C] ×40 magnification and [D] ×100 magnification).

Preoperative portal vein recanalization-transjugular intrahepatic portosystemic shunt for chronic obliterative portal vein thrombosis: Outcomes following liver transplantation.

High‐grade portal vein thrombosis (PVT) is often considered to be a technically challenging scenario for liver transplantation (LT) and in some centers a relative contraindication. This study compares patients with chronic obliterative PVT who underwent portal vein recanalization–transjugular intrahepatic portosystemic shunt (PVR‐TIPS) and subsequent LT to those with partial nonocclusive PVT who underwent LT without an intervention. This institutional review board‐approved study analyzed 49 patients with cirrhosis with PVT from 2000 to 2020 at our institution. Patients were divided into two groups, those that received PVR‐TIPS due to anticipated surgical challenges from chronic obliterative PVT and those who did not because of partial PVT. Demographic data and long‐term outcomes were compared. A total of 35 patients received PVR‐TIPS while 14 did not, with all receiving LT. Patients with PVR‐TIPS had a higher Yerdel score and frequency of cavernoma than those that did not. PVR‐TIPS was effective in decreasing portosystemic gradient (16 down to 8 mm HG; p < 0.05). Both groups allowed for end‐to‐end anastomoses in >90% of cases. However, veno–veno bypass was used significantly more in patients who did not receive PVR‐TIPS. Additionally, patients without PVR‐TIPS required significantly more intraoperative red blood cells. Overall survival was not different between groups. PVR‐TIPS demonstrated efficacy in resolving PVT and allowed for end‐to‐end portal vein anastomoses. PVR‐TIPS is a viable treatment option for chronic obliterative PVT with or without cavernoma that simplifies the surgical aspects of LT.

Combined treatment of unresectable hilar cholangiocarcinoma with subsequent liver transplantation

Objective: to demonstrate the experience of unresectable hilar cholangiocarcinoma treatment using neoadjuvant therapy followed by liver transplantation (LT).Materials and methods. From 2017 to 2021, six patients were included in the treatment protocol for unresectable Klatskin tumor followed by liver transplantation at Granov Russian Scientific Center for Radiology and Surgical Technology. The neoadjuvant therapy included endobiliary photodynamic therapy (PDT), as well as regional and systemic chemotherapy. Each method was used at least three times for 4 to 5 months with radiological evaluation and measurement of CA 19-9 levels. Patients were placed on the waiting list when the tumor marker reduced, or when there were no radiological signs of disease progression and there was no acute cholangitis. The recipients underwent laparoscopic abdominal revision for carcinomatosis and assessment of lymph nodes in the hepatoduodenal ligament with urgent morphological examination. Where there was no extrahepatic spread, LT was performed according to the classical technique with paracaval, para-aortic and hepatoduodenal lymphodissection, biliodigestive anastomosis by an isolated Roux loop of small intestine. The operation was performed in three patients, all of them were men aged 40 to 55 years (mean 48). The mean time from the start of treatment to transplantation was 9.3 months (range 6 to 14). Mean CA 19-9 level at the time of intervention was 81.3 IU/mL (8 to 212).Results. In three patients, CA 19-9 levels more than doubled on average over four months despite treatment. According to data from computed tomography RECIST assessment, two of the patients showed disease progression. In one patient, carcinomatosis was detected by diagnostic laparoscopy. In three patients, CA 19-9 levels decreased more than fourfold. Two of these patients were radiologically confirmed to have the disease stabilized, and one had a partial response. One patient died from sepsis three years after transplantation as a result of secondary biliary cirrhosis and biliary abscesses without signs of progression. Two patients are still alive after 6 and 21 months without signs of tumor progression.Conclusion. LT for unresectable Klatskin tumor is effective in controlling the bioactivity of the tumor through the use of neoadjuvant therapy

[The use of immuno-oncologic therapy in hepatocellular carcinoma in the context of liver transplantation. An interdisciplinary benefit/risk assessment].

Multiple systemic therapy options have been recently approved for the treatment of hepatocellular carcinoma (HCC). In particular, immuno-oncology combination therapies can now achieve impressive response rates and significantly prolonged survival with good tolerability. These immuno-oncology (IO)-based combinations are currently not only evaluated for the therapy of advanced HCC, but increasingly also in earlier stages in terms of peri-interventional therapy concepts and also for down-sizing to local therapies. In the context of liver transplantation (LTx), a particularly critical benefit/risk assessment must be made before the use of immunotherapeutics in the context of multimodal concepts, since the risk of a potentially lethal rejection can be significantly increased by immunotherapy. This review is based on a selective literature search performed between December 2020 and April 2021 in the PubMed and Cochrane Library databases. Guidelines, expert opinions, and recommendations from professional societies were given special consideration. Nearly one in five LTx in Germany are performed due to HCCs. In this context, LTx is a curative therapy option not only for the underlying liver disease but also for the malignant tumor. Individual case reports indicate that IO therapy prior to LTx may increase the risk of rejection or liver failure after subsequent liver transplantation. Since 2015, immunotherapeutics have also been widely used for tumor therapy in patients after LTx. In small case series, rejection rates of 36%, associated with rejection-related mortality of 20% of treated patients, have been described. A similar incidence of rejection has also been described following the use of immunotherapeutics in patients after other organ transplantations. In the context of organ transplantation, IO therapy carries the risk of graft rejection, which can lead to graft loss and also patient death. However, from today's point of view, IO-based therapy can be considered in the context of organ transplantation with a careful benefit/risk assessment.

LI-RADS Treatment Response Algorithm: Performance and Diagnostic Accuracy With Radiologic-Pathologic Explant Correlation in Patients With SBRT-Treated Hepatocellular Carcinoma

Our purpose was to evaluate the accuracy of LI-RADS Treatment Response Algorithm (LR-TRA) for assessing the viability of hepatocellular carcinoma (HCC) treated with stereotactic body radiation therapy (SBRT), using explant pathology as the gold standard. This retrospective study included patients who underwent SBRT for locoregional treatment of HCC between 2008 and 2019 with subsequent liver transplantation. Five radiologists independently assessed all treated lesions by using the LR-TRA. Imaging and posttransplant histopathology were compared. Lesions were categorized as either completely (100%) or incompletely (<100%) necrotic, and performance characteristics and predictive values for the LR-TR viable and nonviable categories were calculated for each reader. Interreader reliability was calculated using the Fleiss kappa test. A total of 40 treated lesions in 26 patients (median age, 63 years [interquartile range, 59.4-65.5]; 23 men) were included. For lesions treated with SBRT, sensitivity for incomplete tumor necrosis across readers ranged between 71% and 86%, specificity between 85% and 96%, and positive predictive value between 86% and 92%, when the LR-TR equivocal category was treated as nonviable, accounting for subject clustering. When the LR-TR equivocal category was treated as viable, sensitivity of complete tumor necrosis for lesions treated with SBRT ranged from 88% to 96%, specificity from 71% to 93%, and negative predictive value from 85% to 96%. Interreader reliability was fair (k=0.22; 95% confidence interval, 0.13-0.33). Although a loss of arterial phase hyperenhancement (APHE) was highly correlated with pathologically nonviable tumor on explant, almost half of the patients with APHE had pathologically nonviable tumor on explant. LR-TRA v2018 performs well for predicting complete and incomplete necrosis in HCC treated with SBRT. In contrast to other locoregional therapies, the presence of APHE after SBRT does not always indicate viable tumor and suggests that observation may be an appropriate strategy for these patients.

Combined Heart and Liver Transplantation for Uhl's Anomaly: A Case Report

Uhl's anomaly is an extremely rare congenital heart defect characterized by absence of the right ventricle myocardium and preserved left ventricular myocardium. Although the disease has a poor prognosis and is generally fatal in the perinatal period, some patients may reach adulthood. We describe a case of Uhl's anomaly complicated with heart failure and decompensated cardiac cirrhosis in a 42-year-old man treated by combined heart-liver transplant. The patient underwent heart transplant using the bicaval technique followed by subsequent liver transplant with the piggyback technique without venovenous bypass. Total ischemia time was 108 minutes for the heart and 360 and 25 minutes of cold and warm ischemia, respectively, for the liver. No intraoperative complications occurred. The patient was discharged without severe complications on postoperative day 22. Pathologic examination of the organs reported advanced cirrhosis of the liver and severe dilated myocardiopathy of right ventricle with absence of myocardium and a normal left ventricle. Twenty-seven months after the transplant the patient has been free from hospital admissions, with normal function of both transplanted organs. We report the first successful combined heart-liver transplant for Uhl's anomaly indication in an adult patient. Despite of the insufficient knowledge of natural history of this exceptional disease, we successfully apply the management principles of other end-stage right heart disorders complicated with liver failure.