Patient Selection For Liver Transplantation Research Articles

Imaging-based diagnosis of sarcopenia for transplant-free survival in primary sclerosing cholangitis

BackgroundImaging-based assessment of sarcopenia is a well-validated prognostic tool for patients with chronic liver disease. However, little is known about its value in patients with primary sclerosing cholangitis (PSC). This cross-sectional study aimed to investigate the predictive value of the cross-sectional imaging-based skeletal muscle index (SMI) for transplant-free survival (TFS) in patients with PSC.MethodsA total of 95 patients with PSC who underwent abdominal cross-sectional imaging between 2008 and 2022 were included in this retrospective study. SMI was measured at the third lumbar vertebra level (L3-SMI). The cut-off values to define sarcopenia were < 50 cm²/m² in male patients and < 39 cm²/m² in female patients. The primary outcome of this study was TFS, which was defined as survival without liver transplantation or death from any cause.ResultsOur study indicates that L3-SMI sarcopenia impairs TFS in patients with PSC (5-year TFS: 33.9% vs. 83.3%, p = 0.001, log-rank test). L3-SMI sarcopenia was independently associated with reduced TFS via multivariate Cox regression analysis (HR = 2.749; p = 0.028). Body mass index reduction > 10% at 12 months, which is used as MELD standard exception (SE) criterion in Eurotransplant (in Germany only until September 2023), was not significantly associated with TFS in the multivariate Cox regression analysis (HR = 1.417; p = 0.330). Substitution of BMI reduction with L3-SMI in the German SE criteria improved the predictive accuracy of TFS compared to the established SE criteria (multivariable Cox regression analysis: HR = 4.007, p < 0.001 vs. HR = 1.691, p = 0.141).ConclusionImaging-based diagnosis of sarcopenia via L3-SMI is associated with a low TFS in patients with PSC and may provide additional benefits as a prognostic factor in patient selection for liver transplantation.

Long-Term Impact of Direct-Acting Antivirals on Liver Fibrosis and Survival in HCV-Infected Liver Transplant Recipients.

(1) Background: Little is known about the long-term impact of sustained virological response (SVR) on fibrosis progression and patient survival in liver transplantation (LT) recipients treated with direct-acting antivirals (DAAs). We investigated liver fibrosis evolution and patient survival in hepatitis C virus (HCV)-infected patients receiving DAAs after LT. (2) Methods: All consecutive HCV-infected patients treated with DAAs after LT between May 2014 and January 2019 were considered. The clinical and virological features were registered at the baseline and during the follow-up. The liver fibrosis was assessed by liver biopsy and/or transient elastography (TE) at the baseline and at least 1 year after the end of treatment (EoT). (3) Results: A total of 136 patients were included. The SVR12 was 78% after the first treatment and 96% after retreatment. After the SVR12, biochemical tests improved at the EoT and remained stable throughout the 3-year follow-up. Liver fibrosis improved after the SVR12 (p < 0.001); nearly half of the patients with advanced liver fibrosis experienced an improvement of an F ≤ 2. The factors associated with lower survival in SVR12 patients were the baseline platelet count (p = 0.04) and creatinine level (p = 0.04). (4) Conclusions: The long-term follow-up data demonstrated that SVR12 was associated with an improvement in hepatic function, liver fibrosis, and post-LT survival, regardless of the baseline liver fibrosis. The presence of portal hypertension before the DAAs has an impact on patient survival, even after SVR12.

Portal Vein Thrombosis in Liver Transplantation: A Retrospective Cohort Study.

Portal vein thrombosis was considered a contraindication for liver transplantation. This study analyzes the perioperative complications and survival of liver transplant patients with portal vein thrombosis (PVT). A retrospective observational cohort study of liver transplant patients was conducted. The outcomes were early mortality (30 days) and patient survival. A total of 201 liver transplant patients were identified and 34 (17%) patients with PVT were found. The most frequent extension of thrombosis was Yerdel 1 (58.8%), and a portosystemic shunt was identified in 23 (68%) patients. Eleven patients (33%) presented any early vascular complication, PVT being the most frequent (12%). The multivariate regression analysis showed a statistically significant association between PVT and early complications (OR = 3.3, 95% confidence interval 1.4-7.7; p = 0.006). Moreover, early mortality was observed in eight patients (24%), of which two (5.9%) presented Yerdel 2. For Yerdel 1, patient survival according to the extent of thrombosis was 75% at 1 year and 3 years, while for Yerdel 2, it was 65% at 1 year, and 50% at 3 years (p = 0.04). Portal vein thrombosis significantly influenced early vascular complications. Furthermore, portal vein thrombosis Yerdel 2 or higher impacts the survival of liver grafts in the short and long term.

Comparing Long-Term Outcomes of Entecavir and Tenofovir Disoproxil Fumarate in Liver Transplant Patients

Objectives. There are no detailed reports on the long-term outcome of patients treated with tenofovir disoproxil fumarate (TDF) compared with entecavir (ENT) following liver transplantation. We aimed to assess the association between TDF use and long-term outcome compared to recipients using ENT. Methods. This retrospective observational study included patients who underwent liver transplantation between January 2015 and May 2019 at the First Affiliated Hospital of Zhejiang University School of Medicine and Hangzhou Shulan Hospital. Cox regression, propensity score matching (PSM), and inverse probability of treatment weighting (IPTW) were performed to assess HBV recurrence, renal dysfunction, and patient survival in liver transplant patients treated with TDF compared with ENT. Results. A total of 907 patients met the inclusion criteria and were included in the final analysis, among which, there were 109 (12.0%) patients treated with TDF and 798 (88.0%) patients treated with ENT. During the follow-up period, 166 patients died, 15 (13.8%) in the TDF group, and 151 (18.9%) in the ENT group. No significant association was found between TDF or ENT use and patient survival (HR, 0.72, 95% CI 0.41-1.23; P = 0.226 ) by PSM analysis. Similarly, differences in the antiviral agents were not significantly associated with hepatitis B recurrence (HR, 1.19, 95% CI 0.62-2.28; P = 0.603 ), but TDF use was significantly related to renal dysfunction after liver transplantation (HR 1.70, 95% CI, 1.21-2.37; P = 0.002 ). Similar results were obtained in subsequent sensitivity analyses. Conclusions. In this study, the results showed that the use of TDF after liver transplantation is as safe and effective as the use of ENT in preventing hepatitis B recurrence. However, renal function in recipients treated with TDF requires careful monitoring.

Temporary postoperative myocardial injury and long-term survival in liver transplant patients with coronary artery disease

Coronary artery disease (CAD) is increasing worldwide due to the aging population and cardiometabolic syndrome. However, the extent of postoperative myocardial injury, the most common cause of death during the 30 days after noncardiac surgery, remains unclear with respect to liver transplant (LT) patients with CAD. We examined the link between post-LT high sensitivity cardiac troponin I (hs_cTnI) and long-term survival according to liver disease severity. Consecutive patients who underwent LT (n = 3,220) from 2010 to 2020 were evaluated retrospectively. CAD was defined as a history of coronary artery bypass surgery or percutaneous intervention, or previous myocardial infarction. Peak hs_cTnI levels within 30 days post-transplant were compared in patients with and without CAD. The primary endpoint was defined as an all-cause mortality at 12 years following LT. Secondary endpoints include peak hs_cTnI level within post-transplant 30 days and 30-day mortality. Survival analysis was performed using the Kaplan-Meier method. CAD patients (n = 264, 8.2%) had higher peak hs_cTnI levels within 30 days post-LT than those without CAD (median [interquartile]: 0.068 [0.030-0.154] vs. 0.087 [0.037-0.203] ng/ml, respectively; P = 0.004); however, the mortality rate was comparable (14.7% vs. 14.8%, respectively, P = 0.999), at 12 years, and 1.9% vs. 1.1% (P = 0.522) at 30 days, respectively, at 30 days. Subgroup analysis with stratified liver disease severity identified a similar risk of long-term mortality. Although the peak hs_cTnI level within 30 days was higher in revascularized or treated CAD patients after LT compared those without CAD, long-term mortality rates at 12 years and 30-day mortality rate were comparable.

Survival Rate of Liver Transplantation in Asia: A Systematic Review and Meta-Analysis.

Liver transplantation is one of the most effective treatments for acute liver failure, chronic liver cirrhosis, and hepatocellular carcinoma. This study was implemented to evaluate the survival rate of liver transplant in Asia. Studies that investigated the survival rate of liver transplant were selected using a systematic search strategy in the following databases: Medline, Embase, Scopus, ProQuest, ISI Web of Science, and Cochrane to Nov 30th, 2020. Pooled survival rate and 95% confidence intervals were calculated using Der-Simonian and Laird method. Stata 16.0 (Stata Corp, College Station, TX, USA) was used for analysis. One, 2, 3, 5, and 10-year survival rates of liver transplant were estimated to be 85%, 80%, 75%, 73%, and 71%, respectively. The results of the univariate meta-regression for defining the sources of heterogeneity for one-Year survival rate (SR) showed significant effects of bias (β high risk/moderate risk =0.059, 95% CI: 0.002, 0.115, P-Value=0.04) and follow up time (β= -0.0002, 95% CI: -0.0003, -0.00, P-Value=0.02) on heterogeneity. The survival rate of liver transplant in Asia is comparable with the corresponding rate reported in the United States and Europe. This study provides a better view of the efficiency of medical cares, regarding liver transplantation. Medical care be enhanced to increase the survival of liver transplant patients.

P9.11: Survival of Liver Transplant Patients From 2010 to 2022 Belonging to the Public Financing Program of CUCAIBA As an Institution of the Ministry of Health of Buenos Aires Argentina

P9.11: Survival of Liver Transplant Patients From 2010 to 2022 Belonging to the Public Financing Program of CUCAIBA As an Institution of the Ministry of Health of Buenos Aires Argentina

CAQ Corner: Psychosocial and ethical considerations in patient selection for liver transplantation.

-

Sarcopenia in high acuity liver transplantation: Does it predict outcomes?

Sarcopenia has gained momentum as a potential risk-stratification tool in liver transplantation (LT). While LT recipients recently have more advanced end-stage liver disease, the impact of sarcopenia in high acuity recipients with a high model for end-stage liver disease (MELD) score remains unclear. We retrospectively assessed sarcopenia by calculating skeletal muscle index (SMI) from cross-sectional area at third lumbar vertebra (cm2 ) and height (m2 ) in 296 patients with a CT ≤ 30 days prior to LT. Sex-specific SMI cut-offs were developed, and its impact was assessed in patients with MELD ≥ 35. In patients with MELD ≥ 35 (n=217), men with a SMI<30 cm2 /m2 had significantly higher rates of bacteremia (P=.021) and a longer hospital stay (P<.001). Women with a SMI<34 cm2 /m2 had a longer hospital stay (P=.032). There were no relationships between SMI and survival in men and women with MELD ≥ 35. This series examined sarcopenia with a focus on high MELD patients. Although decreased SMI contributed to higher post-LT hospital stay, it did not impact patient survival, suggesting that while SMI alone may not aid in patient selection for LT, it certainly may guide perioperative care-planning in this challenging patient population.

Clinical Utility of Protein Induced by Vitamin K Absence-II in Patients with Hepatocellular Carcinoma.

Objective:Despite moderate sensitivity, alpha fetoprotein (AFP) is widely used in screening and prognostication for hepatocellular carcinoma (HCC). The objective of the current study was to assess clinical utility of Prothrombin induced by Vitamin K absence-II (PIVKAII) in addition to AFP in patients with HCC. Methods:We retrospectively reviewed 244 patients with documented AFP, PIVKA II and dynamic imaging of the liver. Using ROC curves, cutoff values for AFP and PIVKAII for HCC detection, tumor grade and microvascular invasion (MVI) were assessed. In patients who underwent liver transplantation (LT) for HCC, survival was determined using Kaplan Meier curves. Results:The median PIVKAII in healthy living donors was 28.6mAU/ml (15.9-55). In cirrhotics, the sensitivity of an AFP cutoff of 7.6 ng/ml or PIVKAII cutoff of 250 mAU/ml for HCC detection was 91.7% (176/192) and specificity was 62.9%(68/108) (P<0.0001). In patients with HCC, PIVKAII values were significantly elevated with tumor size > 5 cm (P < 0.0001), tumor nodules > 3(P=0.01), and macrovascular invasion(P<0.0001). The high risk group (patients with AFP ≥ 40 ng/ml + PIVKAII ≥ 350 mAU/ml), had a sensitivity of (23/33) 69.6% and specificity of (22/22)100% for MVI (P <0.001). The estimated 3 year RFS after LT in the low risk group (AFP <40 ng/ml or PIVKAII< 350 mAU/ml) was 100% versus 63%(P=0.001). The estimated 3 year RFS based with and without MVI was 80% and 100% (P=0.03). Conclusion:PIVKAII in combination with AFP, appears to have a promising role in surveillance and prognostication for HCC. It also allows improved patient selection for liver transplantation.

Minimization of Immunosuppressive Therapy Is Associated with Improved Survival of Liver Transplant Patients with Recurrent Hepatocellular Carcinoma.

Simple SummaryLiver transplantation is a curative treatment option for a subset of patients with hepatocellular carcinoma (HCC). However, about twenty percent of patients develop recurrence in the graft or at extrahepatic sites, which is associated with limited therapeutic options and poor survival. To date, management of the immunosuppressive regimen after recurrence and its impact on survival are unknown. In this retrospective study, we analyzed a cohort of liver recipients with HCC recurrence. Our findings indicate that reduction of immunosuppressive therapy after diagnosis of recurrence has a beneficial impact on patient survival. Therefore, we propose further investigation into the management of immunosuppressive therapy following recurrence.Introduction: Recurrence of hepatocellular carcinoma (rHCC) after liver transplantation (LT) is associated with limited survival. Therefore, identification of factors that prolong survival in these patients is of great interest. Surgical resection, radiotherapy, and transarterial chemoembolization (TACE) are established interventions to improve outcomes in these patients; however, the impact of immunosuppression is unknown. Methods: All patients diagnosed with rHCC in the follow-up after LT were identified from a database of liver recipients transplanted between 1988 and 2019 at our institution (Charité Universitätsmedizin Berlin, Germany). Based on the immunosuppressive regimen following diagnosis of rHCC and the oncological treatment approach, survival analysis was performed. Results: Among 484 patients transplanted for HCC, 112 (23.1%) developed rHCC in the follow-up. Recurrent HCC was diagnosed at a median interval of 16.0 months (range 1.0–203.0), with the majority presenting early after transplantation (63.0%, <2 years). Median survival after rHCC diagnosis was 10.6 months (0.3–228.7). Reduction of immunosuppression was associated with improved survival, particularly in patients with palliative treatment (8.4 versus 3.0 months). In addition, greater reduction of immunosuppression seemed to be associated with greater prolongation of survival. Graft rejection after reduction was uncommon (n = 7, 6.8%) and did not result in any graft loss. Patients that underwent surgical resection showed improved survival rates (median 19.5 vs. 8.7 months). Conclusion: Reduction of immunosuppressive therapy after rHCC diagnosis is associated with prolonged survival in LT patients. Therefore, reduction of immunosuppression should be an early intervention following diagnosis. In addition, surgical resection should be attempted, if technically feasible and oncologically meaningful.

Retrospective-prospective study of safety and efficacy of sofosbuvir-based direct-acting antivirals in HIV/HCV-coinfected participants with decompensated liver disease pre- or post-liver transplant.

Direct-acting antiviral (DAA) therapy has transformed the management of human immunodeficiency virus (HIV) and hepatitis C (HCV) coinfected patients with advanced liver disease. STOP-Coinfection was a multicenter prospective and retrospective, open-label study using sofosbuvir-based DAA therapy to treat HIV/HCV-coinfected participants pre- or post-liver transplant (LT). Sixty-eight participants with end-stage liver disease (Child-Turcotte-Pugh score ≥7 and Model for End-Stage Liver Disease score 6-29) were enrolled, 26 had hepatocellular carcinoma. Forty-two participants were treated pre-LT and 26 post-LT. All participants completed therapy without need for dose reduction or transfusion; eight required two or more courses of therapy. Ninety-three percent achieved a sustained virologic response and DAA therapy was well tolerated. Despite HCV cure, 12 end-stage liver disease participants required subsequent LT, 7 for decompensated liver disease. Thirteen participants died, 10 with decompensated liver disease pre-LT and three post-LT. Overall, transplant free survival was 42.8% at 4years and post-LT survival was 87.9% at 5years. We conclude that sofosbuvir-based DAA therapy is safe and highly effective in HCV-HIV patients with decompensated liver disease and post-LT, with post-LT survival rates comparable to other indications. This removes one of the last barriers to liver transplantation in this challenging cohort of recipients.

Patient selection in liver transplantation for hepatocellular carcinoma

: Liver transplantation is the best therapy for selected patients with unresectable hepatocellular carcinoma (HCC). The worldwide incidence of the disease and the success of liver transplantation have produced a high demand, which has led different countries to adopt heterogeneous policies to allocate deceased donor livers for these patients. Even though tumor burden is the criteria with strongest evidence, there is continuous evolution of the interaction of factors that can improve the prediction of disease recurrence and long-term survival, such as tumor size, number of nodules, tumor volume, cancer-related symptoms, alpha fetoprotein serum level, imaging studies, pretransplant biopsy, response to liver-directed therapies and waiting time. In this manuscript, we summarize recent literature on the selection criteria of candidates with HCC undergoing liver transplant evaluation around the world. We review the evidence behind deceased donor liver allocation systems in different countries and the current role of living donor liver transplantation (LDLT). The largest studies come from United Network for Organ Sharing (UNOS) and European databases, however, there is high-impact data coming from Eastern countries with high HCC incidence and high-volume transplant centers, such as China, India, Japan, and South Korea. Soon, a slow shift towards transplant survival benefit in combination with overall survival may be observed in the allocation policies around the world.

S2434 Post Liver Transplant Appendicitis: Be Vigilant for Appendiceal Tumors!

INTRODUCTION: De novo malignancies in post-transplant patients are a sequel of immunosuppression and have an incidence between 3 and 26%. They are one of the most common cause of morbidity and mortality in long term survival of liver transplant patients with risk almost four times greater than general population. While case reports of appendiceal tumors have been documented in renal transplant patients, there is not much literature for liver transplant patients. Also, fewer than 30 cases of appendicitis in post liver transplant setting have been reported in literature till date. We present a very rare case of mucinous appendiceal adenocarcinoma that presented as appendicitis within three years of liver transplant. CASE DESCRIPTION/METHODS: A 32-year-old Caucasian female with decompensated autoimmune cirrhosis underwent liver transplant in 2017 after detailed transplant evaluation. Post-transplant she was kept on protocol-based immunosuppression consisting of tacrolimus, mycophenolic acid and prednisolone with acceptable therapeutic drug monitoring. She presented in June 2019 with acute onset abdominal pain and was diagnosed with acute appendicitis on clinical examination and imaging. A laparoscopic appendicectomy was performed but complicated by intra-operative appendiceal rupture. Postoperative course was uneventful. Interestingly, final pathology revealed low-grade appendiceal mucinous neoplasm. Considering mandatory immunosuppressive state and peritoneal rupture of appendiceal malignancy, with extensive literature review and team discussions, patient underwent right hemicolectomy followed by intra-operative hyperthermic intraperitoneal chemotherapy (HIPEC) in July 2019. The patient recovered well with no disease recurrence till her last follow up on May 2020. DISCUSSION: Appendiceal malignancies are difficult to diagnose and found in 2% of appendectomy specimens. Mucinous appendiceal cancers are an even rarer subset with incidence of only 0.2%. The reported survival rate is <10% over 10 years. It is extremely rare for GI malignancy to present within 3 years of transplant since detailed cancer screening is part of transplant evaluation which includes abdominal imaging and colonoscopy. Here we report early presentation of a very rare appendiceal carcinoma in post liver transplant setting with excellent response to right hemicolectomy and HIPEC despite continued immunosuppression, which has never been reported. The case also stresses the need for detailed cancer screening in this special population.

Malatya and Other Criteria for Liver Transplantation in Hepatocellular Carcinoma.

Liver transplantation is a curative treatment option for hepatocellular carcinoma. In this review, we aimed to review liver transplantation criteria for hepatocellular carcinoma and patient survivals. We reviewed literature in terms of liver transplant criteria for hepatocellular carcinoma. Patient eligibility criteria, post-transplant survivals, tumor recurrence and expansion of Milan criteria rates were analyzed. The Milan criteria, after being published in 1996, have become for deceased donor liver transplantation in hepatocellular carcinoma worldwide. Later, many transplant centers published their own liver transplant criteria. Most of the criteria consisted of morphological tumor characteristics based on tumor size and number. The newest published one is Malatya criteria. The 5-year overall survival according the all of the criteria is greater than 50%. There were just one paper which compare criteria according to survival and Malatya criteria were the best amongst extended criteria with 5-year OS 79.7% in that study. It is clear that morphological criteria consisting only of tumor size and number are insufficient in patient selection for liver transplantation and should thus be combined with biological, inflammatory, radiological, pathological and genetic markers that predict the biological behavior of the tumor. Efforts to find the best criteria are still ongoing and 5-year overall survival should be greater than 60%.

Influence of postoperative complications on long-term survival in liver transplant patients.

BACKGROUNDLiver transplant (LT) is a complex procedure with frequent postoperative complications. In other surgical procedures such as gastrectomy, esophagectomy or resection of liver metastases, these complications are associated with poorer long-term survival. It is possible this happens in LT but there are not enough data to establish this relationship.AIMTo analyze the possible influence of postoperative complications on long-term survival and the ability of the comprehensive complication index (CCI) to predict this.METHODSRetrospective study in a tertiary-level university hospital. The 164 participants were all patients who received a LT from January 2012 to July 2019. The follow-up was done in the hospital until the end of the study or death. Comorbidity and risk after transplantation were calculated using the Charlson and balance of risk (BAR) scores, respectively. Postoperative complications were graded according to the Clavien-Dindo classification and the CCI. To assess the CCI cut-off value with greater prognostic accuracy a receiver operating characteristic (ROC) curve was built, with calculation of the area under the curve (AUC). Overall survival was estimated according to the Kaplan-Meier test and log-rank test. Groups were compared by the Mann-Whitney test. For the multivariable analysis the Cox regression was used.RESULTSThe mean follow-up time of the cohort was 37.76 (SD = 24.5) mo. A ROC curve of CCI with 5-year survival was built. The AUC was 0.826 (0.730-0.922), P < 0.001. The cut-off was calculated by means of the Youden index with a result of 35.95. The sensitivity was 84.6% and the specificity 61.3%. Survival curves for comparison of patients with CCI score < 36 vs ≥ 36 were calculated. The estimated 5-year survival was 57.65 and 43.95 months, respectively (log-rank < 0.001). This suggests that patients with more severe complications exhibit worse long-term survival. Other cut-off values were analysed. Comparison between patients with CCI < 33.5 vs > 33.5 (33.5 = median CCI value) showed estimated 5-year survival was 57.4 and 45.71 months, respectively (log-rank < 0.0001). Dividing patients according to the mode CCI value (20.9) showed an estimated 5-year survival of 60 mo for a CCI below 20.9 vs 57 mo for a CCI above 20.9 (log-rank = 0.147). The univariate analysis did not show any association between individual complications and long-term survival. A multivariate analysis was carried out to analyse the possible influence of CCI, Charlson comorbidity index, BAR and hepatocellular carcinoma on survival. Only the CCI score showed significant influence on long-term survival.CONCLUSIONA complicated postoperative period – well-defined by means of the CCI score – can influence not only short-term survival, but also long-term survival.

Liver Transplantation for Colorectal and Neuroendocrine Liver Metastases and Hepatoblastoma. Working Group Report From the ILTS Transplant Oncology Consensus Conference.

Liver transplantation (LT) for unresectable colorectal liver metastases has long been abandoned because of dismal prognoses. After the dark ages, advances in chemotherapy and diagnostic imaging have enabled strict patient selection, and the pioneering study from the Oslo group has contributed to the substantial progress in this field. For unresectable neuroendocrine liver metastases, LT for patients who met the Milan criteria was able to achieve excellent long-term outcomes. The guidelines further adopted in the United States and Europe were based on these criteria. For hepatoblastoma, patients with unresectable and borderline-resectable disease are considered good candidates for LT; however, the indications are yet to be defined. In the budding era of transplant oncology, it is critically important to recognize the current status and unsolved questions for each disease entity. These guidelines were developed to serve as a beacon of light for optimal patient selection for LT and set the stage for future basic and clinical studies.

Serum MicroRNA Signatures in Recovery From Acute and Chronic Liver Injury and Selection for Liver Transplantation.

We previously demonstrated a distinct hepatic microRNA (miRNA) signature (down-regulation of miRNA-23a, -150, - 200b, -503, and -663 and up-regulation of miRNA-20a) is associated with successful regeneration in auxiliary liver transplantation (ALT). This study aimed to evaluate whether the serum expression of this regeneration-linked miRNA signature is associated with clinical outcomes in acute and chronic liver disease. These were represented by patients with acetaminophen-induced acute liver failure (ALF; n=18) and patients with hepatitis C virus (HCV) undergoing treatment with direct-acting antivirals (n=56), respectively. Patients were grouped depending on their clinical outcome. Global serum miRNA expression was analyzed using polymerase chain reaction (PCR) arrays and selected miRNA expression using targeted PCR. We demonstrate that specific regeneration-linked miRNAs discriminate outcomes in both clinical scenarios. We further show that miRNA-20a, -23a, -150, -200b, -503, and -663 undergo concordant changes in expression in 3 distinct clinical settings: liver regeneration accompanying successful ALT, clinical recovery after ALF, and clinical recompensation after cure of HCV. This miRNA signature represents a potentially novel biomarker to predict outcome and optimize patient selection for liver transplantation in both acute and chronic liver disease.

The impact of the COVID-19 outbreak on liver transplantation programs in Northern Italy.

In January 2020, Novel Coronavirus Disease 2019 (COVID‐19) resulted in a global pandemic, creating uncertainty toward the management of liver transplantation (LT) programs. Lombardy has been the most affected region in Italy: the current mortality rate of COVID‐19 patients is 18.3% (10 022 deaths; April 10th) with hospitals in Lombardy having to expand the total number of ICU beds from 724 to 1381 to accommodate infected patients. There has been a drastic decrease in liver donors. From February 23rd until April 10th, 17 LTs were performed in Lombardy. Mean donor age was 49 years (range 18‐74) whereas mean recipient age was 55 (13‐69); mean MELD score was 12 (6‐24). All donors underwent screening for SARS‐CoV‐2 prior to LT. Two patients tested positive after LT, and one patient died for COVID on POD 30. Sixteen patients are alive after an average of 30 days post‐LT (range 3‐46). 10 patients have been discharged. This study has found no specific reason concerning the safety of recipients, to stop LT programs. Several key lessons from our experience are reported. However, due to the complex circumstances which surround the viral outbreak, the cessation or a reduction in LT activity is a pragmatic requirement.

Essential updates 2018/2019: Liver transplantation.

Among the recent topics in the field of liver transplantation (LT), one of the significant therapeutic breakthroughs is the introduction of direct‐acting antiviral agents (DAAs) against hepatitis C virus (HCV) infection. With cure rates close to 100%, a better proportion of LT candidates and recipients can be cured of HCV infection by DAA therapies that are simple and well‐tolerated. Other critical topics include the issue of indication of LT for patients with hepatocellular carcinoma, which has been continuously studied. Several expanded criteria beyond the Milan criteria with acceptable results have been recently reported. The role of donor‐specific antibodies (DSAs) in intractable rejection is also an important matter that has been studied. Although long recognized as an important factor in antibody‐mediated rejection and even graft survival in renal transplantation, the impact of DSAs on graft and patient survival in LT remains to be elucidated. Including the issues described above, this article focuses on recent advances in LT, management to avoid recurrence of primary diseases, optimization of immunosuppressive treatment, and extended donor criteria.