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COVID-19 is associated with thrombotic complications and can result in hepatobiliary injury. Excellent early outcomes have been reported in recipients of solid non-lungs organs from SARS-CoV-2-infected donors, however longer follow-up data are lacking. We aimed to describe the medium-term outcome of our liver transplants (LT) from COVID-19 donors. From 11/2020 to 03/2022, we consecutively enrolled all patients who received a graft from COVID-19 donor in our Centre. Protocol liver biopsy and magnetic resonance cholangiopancreatography (MRCP) after 1-year from LT were reported. In the study period 12/213 (5.6%) adult LT patients received a COVID-19 donor (11 active, 1 resolved COVID-19)1. Eleven patients underwent end-to-end biliary anastomosis and 1 biliodigestive anastomosis. Recipients' and donors' characteristics are reported in table 1. Two recipients tested SARS-CoV-2 RNA positive on nasopharyngeal swab at LT and one was treated with sotrovimab on day-1 after LT. None of the patients developed COVID-19 after LT. One patient underwent hepatic artery thrombectomy at day-1 and died after 320 days for HCC recurrence. Until now: -10 patients underwent protocol MRCP (median time from LT 562 days, IQR 245-614), which showed: 7 no visible abnormalities, 1 donor-recipient's bile duct size discrepancy, 2 caliber changes <50% at the anastomotic level (untreated for the absence of cholestasis); -7 patients underwent protocol liver biopsy (median time from LT 553 days, IQR 311-557) which showed 1 acute cellular rejection (RAI 4/9) successfully treated with steroids; no signs of fibrosis, rejection or biliopathy in the other 6 patients. 11/12 patients who received a LT from COVID-19 donors are alive, without evidence of SARS-CoV-2 transmission. At a median follow-up of 1.5 years, protocol liver biopsy and MRCP did not show biliopathy, supporting the utilization of COVID-19 donors to expand the donor pool and reduce the waiting list mortality. [ABSTRACT FROM AUTHOR]

Liver transplantation(LT) remains the only therapeutic option for decompensated HDV-liver disease. We aimed to compare the characteristics of HBV- versus HBV/HDV-positive LT recipients in our high-volume Center in the last 12 years. All HBsAg+ patients who underwent LT in our Centre from January 2010 to December 2021 were included. Post-LT anti-HBV prophylaxis was performed with anti-HBs immunoglobulins and nucleos(t)idic analogues. Immunosuppression was based on calcineurin inhibitors, mycophenolate, and steroids (tapered to suspension in 6 months). In the study period, 1710 LTs were performed in our Centre. LT indication was HBsAg+ liver disease in 290 patients (17.0%). 147/290 patients (50.7%) were HBV monoinfected, while 143 (49.3%) were HBV/HDV coinfected. Median age was lower in HBV/HDV patients (55.2 years, IQR 49.1-60.2) compared to HBV patients (59.0 years, IQR 55.2-63.1), p<0.001. Female gender was more frequent in HBV/HDV group (28.7% vs. 11.6%, p<0.001). Median MELD was higher in HBV/HDV coinfected LT recipients (15 vs 11, p<0.001). Hepatocellular carcinoma (HCC) was the main LT indication in both groups, with higher prevalence in HBV monoinfected patients (74.1% vs 54.5%, p<0.001). The proportion of foreign-origin patients increased in the HBV/HDV group from 9.7% in 2010-2015 to 42.0% in 2016-2021 one (p<0.001), whereas it remained stable in the monoinfected group (9.9% vs 16.7%, p=0.22) (Table 1). Median post-LT follow-up time was 6.9 years (IQR 4.0-9.9). Overall 5-year survival was 92.2%: 95.5% in HBV/HDV and 88.9% in HBV group, p=0.009. All patients remained HBV-DNA negative after LT. Our experience shows that HDV still represents a noteworthy indication for LT, accounting for up to 50% of transplants performed for HBV, with a prevalence of 61.2% in the foreign subgroup. Coinfected patients need LT at a younger age and with higher MELD score compared with the HBV population, but they show an excellent 5-year post-LT survival. [ABSTRACT FROM AUTHOR]

Significant coronary artery disease (CAD) should be treated with percutaneous revascularization in pre-liver transplant (LT) work-up. New-generation drug-eluting stents (DES) allow early discontinuation of dual antiplatelet therapy (DAPT). We aimed to describe pre-LT management and early post-LT outcome of our patients with CAD who underwent Percutaneous Coronary Intervention (PCI). We enrolled all patients transplanted in our Centre from 01/2018 to 04/2022 who underwent pre-LT cardiac catheterization (CATH). Stenosis ≥50% in a major-vessel or stenosis ≥70% in a moderate-sized branch vessel indicated significant CAD. Among 638 adult patients who received LT, 33 underwent pre-LT CATH (5%) due to previous history of obstructive CAD (18%), positive noninvasive stress-test (61%), inconclusive noninvasive test (15%) or CAD symptoms (6%). CATH showed normal coronaries in 6/33 (18%), non-obstructive CAD in 15/33 (46%) and significant CAD in 12/33 (36%). These 12 patients were all male, median age 64 years, 75% diabetics, 83% smokers, median BMI 26kg/m2 and underwent PCI with single (6/12) or ≥ 2 coronary arteries stenting (6/12). Patients received 31 days (IQR 31-41) of DAPT (clopidogrel+cardioaspirin), followed by aspirin monotherapy; anemia was a concern, without pre-LT major bleeding. Registration on the LT waiting list and LT occurred after 14 days (7-87) and 77 days (12-172) respectively from DAPT discontinuation. The median number of red blood cell units transfused during LT was 5 (2-7). At the end of LT, median arterial lactate and noradrenaline requirement were 1.9 mmol/L and 0.13 γ/Kg/min (Table 1). After a median follow-up of 321 days from LT: patient #1 experienced acute heart failure at month 4th (EF 35%), following major gastrointestinal bleeding (hemoglobin 4.2 g/dL); CATH was unchanged; patient improved with blood transfusion (EF at discharge 45%). Coronary DES revascularization and early clopidogrel discontinuation was safe in cirrhotic patients with significant CAD and allowed timely LT. [ABSTRACT FROM AUTHOR]

In the current era of pulmonary arterial hypertension (PAH) therapy (tx), patients (pts) affected by liver disease with mild portopulmonary hypertension (POPH) can experience significant improvement after liver transplant (LT). We described characteristics of POPH pts who underwent LT in our Center. Among 1135 LT performed between 05/2013-05/2021 in our Center, we enrolled 10 cirrhotics with POPH. Diagnosis was made accordingto right heart catheterization (RHC) criteria: mean PA pressure(mPAP) >25 mmHg, PA wedge pressure(CAP)≤ 15 mmHg, pulmonary vascular resistance(PVR)>3WU. To achieve LT criteria (mPAP<35 mmHg, PVR<5 WU or mPAP 35-44 mmHg and PVR<3 WU) pts received phosphodiesterase-5-inhibitors(P-5i) and/or endothelin-receptor antagonists(ERA) and/or prostacyclin receptor-agonists. Follow-up was closed on 30/11/2022. Recipients (Table 1): median age 53 years, 80% male, BMI 26Kg/m2, 100% HCV cirrhosis, 20% HCC, 60% with large portosystemic-shunt, MELD 12. PAH-tx: pts#1-5 underwent ERA-tx; pts#6-8 ERA+P-5i; pt#9 and#10 prostacyclin+P-5i+ERA. Six pts (#1,#2,#4,#5,#9,#10) achieved POPH LT criteria after 4 mo of PAH-tx; 2 pts (#3,#6) after 8 mo, pt #8 after 12 mo.The 10 pts were transplanted after 0.3 y from registration on LT waiting list. Donors: median age 49 y, DRI 1.6. Post-LT: 3 pts developed early allograft dysfunction. All except pt #7 were extubated within day 2 post-LT; median hospital length of stay was 16 days. Pt#7 died after 18 days for cardiac failure.At a median follow-up of 2.9 y, 7 patients persistently discontinued PAH-tx. In our high-volume LT center, in the last 8 y we transplanted 10 cirrhotic pts affected by POPH and responsive to targeted therapy. LT offered a POPH resolution in 78% of the pts who were weaned off all PAH-tx without RHC evidence of POPH recurrence. One pt died early post-LT for cardiac failure. Careful patient and donor selection and proper timing of LT remain pivotal to obtain good outcomes. [ABSTRACT FROM AUTHOR]

Background Hepatitis B virus recurrence after liver transplantation (LT) has practically disappeared with a prophylaxis combining anti–hepatitis B surface antigen Immunoglobulins (HBIg) and antiviral drugs. Recently, cost-saving requirements pushed us to move from a fixed schedule of 50,000 IU intravenous HBIg in the first month after LT to an “on demand” administration guided by close monitoring of HBV surface antigen (HBsAg) and anti-HBV surface Antigen antibody (HBsAb) with a serological target of HBsAg negative and HBsAb >300 mIU/mL. In this context, we investigated the meaning of HBsAg quantitative determination at LT in predicting the need of HBIg in the first month after LT. Methods From February 2012 to July 2013, we performed 35 LTs in HBsAg-positive patients, 18 of whom had hepatitis Delta virus coinfection (Delta-positive). Anti-HBV prophylaxis was based on nucleos(t)ide analogues from day 1 post-LT and intravenous HBIg (10,000 IU intraoperatively and, in the following days, 5,000 IU and 2,500 IU pulses to reach and maintain the serological target). Results The HBsAg quantitative level at LT was significantly higher in Delta-positive recipients. Complete negativization of HBsAg and HBsAb serum level >300 mIU/mL was achieved on day 3 in Delta-positive and on day 2 in Delta-negative. A positive linear correlation between HBsAg quantitative level at LT and HBIg administered in the first month after LT was observed ( RHO = .788), with a total of 32,500 IU HBIg used in HDV-positive and 22,000 IU in HDV-negative recipients ( P = .0016). Compared to the old schedule, we saved a median of 14,750 IU in HDV-positive and 28,000 IU in Delta-negative. No HBV recurrence was observed in a median follow-up of 10.5 months. Conclusions Delta-positive patients need higher doses of HBIg to reach the serological target after LT because they have greater HBsAg quantitative levels at LT. In future studies, pre-LT HBsAg quantitative determination will be helpful to predict the actual need of HBIg early after LT. [ABSTRACT FROM AUTHOR]

Abstract: Background: Liver transplantation (OLT) is the gold standard therapy for patients with cirrhosis complicated by hepatocellular carcinoma (HCC) within Milan Criteria (MC). We evaluated the impact of the etiology of the underlying liver disease on long-term outcomes of patients undergoing OLT for HCC within MC having a Model for End-stage Liver Disease (MELD) score < 15. Methods: From November 2002 to December 2009, we performed 203 primary OLTs from brain-dead donors in recipients with HCC and cirrhosis with biochemical MELD scores below 15. We excluded 31 patients outside MC on the explant pathology of the native liver. The remaining 172 were divided into 3 groups according to the etiology of the underlying cirrhosis: hepatitis C virus-positive (HCV+; n = 78; 45%), hepatitis B virus-positive (HBV+; n = 65; 38%) and other indications (n = 29; 17%). The groups were compared for donor and recipient features, donor-recipient match, and transplant variables. The study endpoint was long-term patient survival. Results: The groups were similar, except for a greater prevalence of hepatitis B core antibody-positive grafts in the HBV+ group and less frequent HCC bridging procedures in the other indications group. After a median follow-up of 72 months, HCC recurrence was observed in 8 (4.7%) patients (6 HCV+, 2 other indications), 5 of whom died. Overall 5-year patient survival of 82%, revealed significant differences among groups: 98.3% in HBV+, 67.1% in HCV+, and 85.8% in other indications (HBV+ vs other indications: P = .01; HBV+ vs HCV+: P = .0001; HCV+ vs other indications: P = NS). In the HCV+ group, recurrent HCV hepatitis was the most frequent cause of death. Upon multivariate analysis, HBV positivity in the recipient was an independent predictor of better patient survival (hazard ratio = 0.10, 95% confidence interval 0.02–0.64, P = .013). Conclusions: Etiology of the underlying cirrhosis significantly influenced the long-term survival after OLT of patients with HCC within MC and MELD < 15. It should be taken into account in estimation of survival benefit. [Copyright &y& Elsevier]

Background After introduction of the Model for End-Stage Liver Disease (MELD) score in 2002, a worldwide increasing number of simultaneous liver–kidney transplantations (SLKTx) has been observed. However, organ shortage puts into question the allocation of 2 grafts to 1 recipient. This retrospective, single-center study compared SLKTx results with isolated liver transplantation (LTx). Methods Between 1995 and 2013, 37 SLKTx were performed in adult recipients. Every SLKTx was matched by donor age (±5 years) and transplantation date with 2 LTx (n = 74). Pretransplant, intraoperative, and post-transplant variables were collected; liver graft and patient survivals were calculated. Results As expected, donor age was similar in the 2 groups (median, 39.7 years), whereas serum creatinine level, glomerular filtration rate, and MELD and D-MELD (donor age*MELD) scores were significantly higher in the SLKTx group. SLKTx had longer waiting list time ( P = .0034) as well as higher surgical difficulty, testified by more blood transfusions ( P = .0083), increased use of classic caval reconstruction ( P = .0024), and more frequent need of abdominal packing for bleeding control ( P = .0003). In addition, duration of hospital stay ( P < .0001), second-look surgery ( P = .0082), post-transplant dialysis ( P < .0001), and post-transplant infections ( P = .04) were significantly greater in SLKTx group. Acute rejection episodes involving the liver were significantly less in SLKTx than in LTx (14% vs 41%; P = .0045). Liver graft and patient survival at 10 years after transplantation was similar in the 2 groups (liver graft: SLKTx, 80% vs LTx, 77% [ P = .85]; patient: SLKTx, 86% vs LTx, 79% [ P = .56]). Conclusions Despite being technically challenging, SLKTx provided excellent long-term results and was shown to be an effective use of liver grafts. [ABSTRACT FROM AUTHOR]

Abstract: Background: Liver transplantation (LT) with grafts from hepatitis B core antibody (HBcAb)–positive donors has been the object of recent studies, suggesting different outcomes depending on the etiology of viral cirrhosis in the recipient. Methods: From November 2002 to December 2009, we transplanted 124 livers from hepatitis B surface antigen (HBsAg)–negative HBcAb-positive deceased heart-beating donors to adult recipients with viral cirrhosis, classified as: HBsAg positive (group 1; n = 63); hepatitis C virus (HCV) RNA positive (group 2; n = 52); and simultaneously HBsAg and HCV-RNA positive (group 3; n = 9). Immunosuppression included a calcineurin inhibitor, mycophenolate, and steroids (tapered to suspension in 6 months). In all groups, anti-HBV prophylaxis was performed with anti-HBs immunoglobulins and nucleos(t)idic analogues. Results: The groups were similar regarding donor, recipient, donor-recipient match, transplant procedure, variables, and treatment of acute rejection, except for younger recipient age in group 1 (P = .009), lower recipient body mass index in group 3 (P = .03), and longer cold ischemia time in group 2 (P = .003). Median follow-up for surviving grafts was 63 (range, 16–102) months. No case of recurrent or de novo hepatitis B occurred. The prevalence of histologically proven recurrent HCV hepatitis was similar in groups 2 and 3 (65% vs 78%). Graft survival at 5 years was 86% in group 1, 35% in group 2, and 31% in group 3 (P < .0001 for group 1 vs 2; P < .01 for group 1 vs 3). On multivariate analysis, independent predictors of worse graft survival were HCV infection in the recipient (HR 8.08, 95% CI 3.36–17.97; P < .0001) and MELD at LT ≥25 (HR 3.72, 95% CI 1.12–12.37; P = .032). Conclusions: The presence of HCV infection in the recipient is the factor which most negatively influenced the outcome of LT using grafts from HBcAb-positive donors. Allocation of such grafts should consider the type of viral cirrhosis among LT candidates. [Copyright &y& Elsevier]

Abstract: Background: Recent data from Italian studies have shown excellent results of liver transplantation (LT) in hepatitis B virus (HBV)–infected patients with grafts from hepatitis B core antibody (HBcAb)—positive donors, whereas such grafts in hepatitis C virus (HCV)–infected recipients have displayed poorer outcomes. We investigated the results of LT with HBcAb-positive grafts in patients with ongoing HBV and HCV coinfections. Methods: From August 1999 to December 2009, we performed 27 adult primary LTs from deceased heart-beating donors into recipients showing hepatitis B surface antigen (HBsAg)- and HCV-RNA-positivity simultaneously: 12 patients received a graft from an HBsAg-negative HBcAb-positive donor (core+D group) and 15 from an HBcAb-negative donor (core−D group). Immunosuppression included a calcineurin inhibitor, antimetabolite and steroids which were suspended at 6 months. Anti-HBV prophylaxis was always perfomed with anti-HBs immunoglobulins and nucleos(t)idic analogues. Results: The groups were similar regarding variables of donor, recipient, donor-recipient match, LT procedure, and acute rejection treatment. Median follow-up for surviving grafts was 67 months (range, 16–141). Among all patients, HCV-RNA remained positive after LT. The prevalence of histologically proven recurrent HCV hepatitis was similar in the 2 groups: 83% core+D vs 73% core−D. No recurrent HBV hepatitis occurred during the follow-up. Graft survival at 5 years was significantly lower in the core+D group (core+D 48% vs core−D 87%; P = .018), in which a significantly higher prevalence of graft loss was caused by HCV recurrence (core+D 5/12, 42% vs core−D 1/15, 7%; P = .03). All of the 5 core+D patients who lost their grafts due to HCV recurrence did not receive anti-HCV therapy (4 owing to an aggressive disease and 1 because of patient refusal). Conclusions: Outcomes of LT in patients with ongoing HBV and HCV coinfection are adversely affected by donor HBcAb positivity, an effect that is mainly mediated by the dismal course of HCV recurrence after LT. [Copyright &y& Elsevier]