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1.
Transpl Int ; 36: 10954, 2023.
Article in English | MEDLINE | ID: mdl-36793896

ABSTRACT

The European Liver and Intestine Transplant Association, ELITA, promoted a Consensus Conference involving 20 experts across the world which generated updated guidelines on HBV prophylaxis in liver transplant candidates and recipients. This study explores the economic impact associated with the implementation of the new ELITA guidelines. To this aim, a condition-specific cohort simulation model has been developed to compare new and historical prophylaxis, including only pharmaceutical cost and using the European perspective. The target population simulated in the model included both prevalent and incident cases, and consisted of 6,133 patients after the first year, that increased to 7,442 and 8,743 patents after 5 and 10 years from its implementation. The ELITA protocols allowed a cost saving of around € 235.65 million after 5 years and € 540.73 million after 10 years; which was mainly due to early HIBG withdrawal either after the first 4 weeks or after the first year post Liver Transplantation (LT) depending on the virological risk at transplantation. Results were confirmed by sensitivity analyses. The money saved by the implementation of the ELITA guidelines would allow healthcare decision makers and budget holders to understand where costs could be reduced and resources re-allocated to different needs.


Subject(s)
Hepatitis B , Liver Transplantation , Humans , Antiviral Agents/therapeutic use , Hepatitis B/prevention & control , Drug Therapy, Combination
2.
J Hepatol ; 76(2): 364-370, 2022 02.
Article in English | MEDLINE | ID: mdl-34653592

ABSTRACT

BACKGROUND AND AIMS: The global impact of SARS-CoV-2 on liver transplantation (LT) practices across the world is unknown. The goal of this survey was to assess the impact of the pandemic on global LT practices. METHOD: A prospective web-based survey (available online from 7th September 2020 to 31st December 2020) was proposed to the active members of the EASL-ESOT/ELITA-ILTS in the Americas (including North, Central, and South America) (R1), Europe (R2), and the rest of the world (R3). The survey comprised 4 parts concerning transplant processes, therapy, living donors, and organ procurement. RESULTS: Of the 470 transplant centers reached, 128 answered each part of the survey, 29 centers (23%), 64 centers (50%), and 35 centers (27%) from R1, R2, and R3, respectively. When we compared the practices during the first 6 months of the pandemic in 2020 with those a year earlier in 2019, statistically significant differences were found in the number of patients added to the waiting list (WL), WL mortality, and the number of LTs performed. At the regional level, we found that in R2 the number of LTs was significantly higher in 2019 (p <0.01), while R3 had more patients listed, higher WL mortality, and more LTs performed before the pandemic. Countries severely affected by the pandemic ("hit" countries) had a lower number of WL patients (p = 0.009) and LTs (p = 0.002) during the pandemic. Interestingly, WL mortality was still higher in the "non-hit" countries in 2020 compared to 2019 (p = 0.022). CONCLUSION: The first wave of the pandemic differentially impacted LT practices across the world, especially with detrimental effects on the "hit" countries. Modifications to the policies of recipient and donor selection, organ retrieval, and postoperative recipient management were adopted at a regional or national level. LAY SUMMARY: The health emergency caused by the coronavirus pandemic has dramatically changed clinical practice during the pandemic. The first wave of the pandemic impacted liver transplantation differently across the world, with particularly detrimental effects on the countries badly hit by the virus. The resilience of the entire transplant network has enabled continued organ donation and transplantation, ultimately improving the lives of patients with end-stage liver disease.


Subject(s)
COVID-19/immunology , Liver Transplantation , SARS-CoV-2 , Cross-Sectional Studies , Global Health , Humans , Immunosuppression Therapy , Living Donors , Prospective Studies , Telemedicine , Tissue and Organ Procurement , Waiting Lists
3.
Aging Clin Exp Res ; 34(8): 1919-1923, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35380349

ABSTRACT

The majority of patients undergoing Orthotopic Liver Transplantation (OLT) have increased in age, therefore chronological age may have become an unreliable parameter for supporting clinical decisions. The age-related deficit accumulation model measuring frailty proposed by Rockwood et al., may propose an alternative in providing an estimate of an individual's biological age. No Frailty Index (FI) tailored specifically for OLT patients exists to date. Forty-three consecutive OLT patients with ≥ 20 years of survival with a functioning graft were included in our study. The FI was computed taking to account 39 items (FI-39), meeting the standard criteria for internal validation. Endpoints were polypharmacy, and recent Emergency Room admission. The mean age of our population was 69 (sd 9) years. The mean FI-39 was 0.23 (sd 0.1). The FI-39 was associated with polypharmacy [odds ratio (OR) 1.13; Confidence interval (95%CI) 1.03-1.24; p = 0.01], and recent Emergency Room admission [beta coefficient + 1.98; 95%CI + 0.26, + 3.70; p = 0.03], independent for age and sex. This study demonstrates that an FI can be derived from data collected during routine clinical follow-up and allows for improved differentiation related to the OLT clinical complexity in OLT patients, independent of chronological age. This may lead to the adoption of FI-39 to improve personalized OLT patient care.


Subject(s)
Frailty , Liver Transplantation , Aged , Frail Elderly , Frailty/diagnosis , Geriatric Assessment , Humans , Middle Aged , Treatment Outcome
4.
Gut ; 70(10): 1914-1924, 2021 10.
Article in English | MEDLINE | ID: mdl-34281984

ABSTRACT

OBJECTIVE: Explore the impact of COVID-19 on patients on the waiting list for liver transplantation (LT) and on their post-LT course. DESIGN: Data from consecutive adult LT candidates with COVID-19 were collected across Europe in a dedicated registry and were analysed. RESULTS: From 21 February to 20 November 2020, 136 adult cases with laboratory-confirmed SARS-CoV-2 infection from 33 centres in 11 European countries were collected, with 113 having COVID-19. Thirty-seven (37/113, 32.7%) patients died after a median of 18 (10-30) days, with respiratory failure being the major cause (33/37, 89.2%). The 60-day mortality risk did not significantly change between first (35.3%, 95% CI 23.9% to 50.0%) and second (26.0%, 95% CI 16.2% to 40.2%) waves. Multivariable Cox regression analysis showed Laboratory Model for End-stage Liver Disease (Lab-MELD) score of ≥15 (Model for End-stage Liver Disease (MELD) score 15-19, HR 5.46, 95% CI 1.81 to 16.50; MELD score≥20, HR 5.24, 95% CI 1.77 to 15.55) and dyspnoea on presentation (HR 3.89, 95% CI 2.02 to 7.51) being the two negative independent factors for mortality. Twenty-six patients underwent an LT after a median time of 78.5 (IQR 44-102) days, and 25 (96%) were alive after a median follow-up of 118 days (IQR 31-170). CONCLUSIONS: Increased mortality in LT candidates with COVID-19 (32.7%), reaching 45% in those with decompensated cirrhosis (DC) and Lab-MELD score of ≥15, was observed, with no significant difference between first and second waves of the pandemic. Respiratory failure was the major cause of death. The dismal prognosis of patients with DC supports the adoption of strict preventative measures and the urgent testing of vaccination efficacy in this population. Prior SARS-CoV-2 symptomatic infection did not affect early post-transplant survival (96%).


Subject(s)
COVID-19/mortality , Liver Transplantation , Pneumonia, Viral/mortality , Transplant Recipients , Cause of Death , Europe/epidemiology , Female , Humans , Male , Middle Aged , Pneumonia, Viral/virology , Registries , Risk Factors , SARS-CoV-2 , Waiting Lists
5.
J Hepatol ; 75(6): 1355-1366, 2021 12.
Article in English | MEDLINE | ID: mdl-34333100

ABSTRACT

BACKGROUND & AIMS: Although the discriminative ability of the model for end-stage liver disease (MELD) score is generally considered acceptable, its calibration is still unclear. In a validation study, we assessed the discriminative performance and calibration of 3 versions of the model: original MELD-TIPS, used to predict survival after transjugular intrahepatic portosystemic shunt (TIPS); classic MELD-Mayo; and MELD-UNOS, used by the United Network for Organ Sharing (UNOS). We also explored recalibrating and updating the model. METHODS: In total, 776 patients who underwent elective TIPS (TIPS cohort) and 445 unselected patients (non-TIPS cohort) were included. Three, 6 and 12-month mortality predictions were calculated by the 3 MELD versions: discrimination was assessed by c-statistics and calibration by comparing deciles of predicted and observed risks. Cox and Fine and Grey models were used for recalibration and prognostic analyses. RESULTS: In the TIPS/non-TIPS cohorts, the etiology of liver disease was viral in 402/188, alcoholic in 185/130, and non-alcoholic steatohepatitis in 65/33; mean follow-up±SD was 25±9/19±21 months; and the number of deaths at 3-6-12 months was 57-102-142/31-47-99, respectively. C-statistics ranged from 0.66 to 0.72 in TIPS and 0.66 to 0.76 in non-TIPS cohorts across prediction times and scores. A post hoc analysis revealed worse c-statistics in non-viral cirrhosis with more pronounced and significant worsening in the non-TIPS cohort. Calibration was acceptable with MELD-TIPS but largely unsatisfactory with MELD-Mayo and -UNOS whose performance improved much after recalibration. A prognostic analysis showed that age, albumin, and TIPS indication might be used to update the MELD. CONCLUSIONS: In this validation study, the performance of the MELD score was largely unsatisfactory, particularly in non-viral cirrhosis. MELD recalibration and candidate variables for an update to the MELD score are proposed. LAY SUMMARY: While the discriminative performance of the model for end-stage liver disease (MELD) score is credited to be fair to good, its calibration, the correspondence of observed to predicted mortality, is still unsettled. We found that application of 3 different versions of the MELD in 2 independent cirrhosis cohorts yielded largely imprecise mortality predictions particularly in non-viral cirrhosis. Thus, we propose a recalibration and suggest candidate variables for an update to the model.


Subject(s)
End Stage Liver Disease/classification , End Stage Liver Disease/etiology , Mortality/trends , Adult , Aged , Cohort Studies , End Stage Liver Disease/mortality , Follow-Up Studies , Humans , Italy , Middle Aged , Models, Biological , Prognosis , Severity of Illness Index , Time Factors , Validation Studies as Topic
6.
Clin Gastroenterol Hepatol ; 19(8): 1688-1697.e14, 2021 08.
Article in English | MEDLINE | ID: mdl-32777554

ABSTRACT

BACKGROUND & AIMS: Gamma-glutamyltransferase (GGT) is a serum marker of cholestasis. We investigated whether serum level of GGT is a prognostic marker for patients with primary biliary cholangitis (PBC). METHODS: We analyzed data from patients with PBC from the Global PBC Study Group, comprising 14 centers in Europe and North America. We obtained measurements of serum GGT at baseline and time points after treatment. We used Cox model hazard ratios to evaluate the association between GGT and clinical outcomes, including liver transplantation and liver-related death. RESULTS: Of the 2129 patients included in our analysis, 281 (13%) had a liver-related clinical endpoint. Mean age at diagnosis was 53 years and 91% of patients were female patients. We found a correlation between serum levels of GGT and alkaline phosphatase (ALP) (r = 0.71). Based on data collected at baseline and yearly for up to 5 years, higher serum levels of GGT were associated with lower hazard for transplant-free survival. Serum level of GGT at 12 months after treatment higher than 3.2-fold the upper limit of normal (ULN) identified patients who required liver transplantation or with liver-related death at 10 years with an area under the receiver operating characteristic curve of 0.70. The risk of liver transplantation or liver-related death in patients with serum level of GGT above 3.2-fold the ULN, despite level of ALP lower than 1.5-fold the ULN, was higher compared to patients with level of GGT lower than 3.2-fold the ULN and level of ALP lower than 1.5-fold the ULN (P < .05). Including information on level of GGT increased the prognostic value of the Globe score. CONCLUSIONS: Serum level of GGT can be used to identify patients with PBC at risk for liver transplantation or death, and increase the prognostic value of ALP measurement. Our findings support the use of GGT as primary clinical endpoint in clinical trials. In patients with low serum level of ALP, a high level of GGT identifies those who might require treatment of metabolic disorders or PBC treatment escalation.


Subject(s)
Cholestasis , Liver Cirrhosis, Biliary , Liver Transplantation , Female , Humans , Prognosis , gamma-Glutamyltransferase
7.
Liver Transpl ; 26(4): 507-516, 2020 04.
Article in English | MEDLINE | ID: mdl-31901209

ABSTRACT

Wilson's disease (WD) is a rare genetic disorder with protean manifestations. Even if liver transplantation (LT) could represent an effective therapeutic option for patients with end-stage liver disease, it has remained controversial in the presence of neuropsychiatric involvement. This study aimed to examine the frequency of adult LT for WD in Italy, focusing on the disease phenotype at the time of LT. A retrospective, observational, multicenter study was conducted across Italy exploring the frequency and characteristics of adults transplanted for WD between 2006 and 2016. A total of 29 adult WD patients underwent LT during the study period at 11 Italian LT centers (accounting for 0.4% of all LTs performed), and 27 of them were considered in this analysis (male/female, n = 9/18; age at LT, 29 years [19-60 years]; median Model for End-Stage Liver Disease score at LT, 27 [6-49]). Isolated hepatic phenotype was the indication for LT in 17 (63%) patients, whereas 2 (7%) patients underwent LT for neurological impairment on compensated liver disease. Overall 1- and 5-year patient survival was excellent (88% and 83%, respectively). Neuropsychiatric symptoms early after LT completely recovered in only a few patients. In conclusion, WD remains an uncommon, unusual indication for LT in Italy, displaying good post-LT graft and patient survival. Because isolated neuropsychiatric involvement represents a rare indication to LT, more data are needed to properly assess the value of LT for WD in this subset of patients.


Subject(s)
End Stage Liver Disease , Hepatolenticular Degeneration , Liver Transplantation , Adult , End Stage Liver Disease/surgery , Female , Hepatolenticular Degeneration/surgery , Humans , Italy/epidemiology , Liver Transplantation/adverse effects , Male , Retrospective Studies , Severity of Illness Index , Treatment Outcome
8.
J Hepatol ; 69(4): 810-817, 2018 10.
Article in English | MEDLINE | ID: mdl-29940268

ABSTRACT

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) have dramatically improved the outcome of patients with hepatitis C virus (HCV) infection including those with decompensated cirrhosis (DC). We analyzed the evolution of indications and results of liver transplantation (LT) in the past 10 years in Europe, focusing on the changes induced by the advent of DAAs. METHODS: This is a cohort study based on data from the European Liver Transplant Registry (ELTR). Data of adult LTs performed between January 2007 to June 2017 for HCV, hepatitis B virus (HBV), alcohol (EtOH) and non-alcoholic steatohepatitis (NASH) were analyzed. The period was divided into different eras: interferon (IFN/RBV; 2007-2010), protease inhibitor (PI; 2011-2013) and second generation DAA (DAA; 2014-June 2017). RESULTS: Out of a total number of 60,527 LTs, 36,382 were performed in patients with HCV, HBV, EtOH and NASH. The percentage of LTs due to HCV-related liver disease varied significantly over time (p <0.0001), decreasing from 22.8% in the IFN/RBV era to 17.4% in the DAA era, while those performed for NASH increased significantly (p <0.0001). In the DAA era, the percentage of LTs for HCV decreased significantly (p <0.0001) from 21.1% (first semester 2014) to 10.6% (first semester 2017). This decline was more evident in patients with DC (HCV-DC, -58.0%) than in those with hepatocellular carcinoma (HCC) associated with HCV (HCV-HCC, -41.2%). Conversely, three-year survival of LT recipients with HCV-related liver disease improved from 65.1% in the IFN/RBV era to 76.9% in the DAA era, and is now comparable to the survival of recipients with HBV infection (p = 0.3807). CONCLUSIONS: In Europe, the number of LTs due to HCV infection is rapidly declining for both HCV-DC and HCV-HCC indications and post-LT survival has dramatically improved over the last three years. This is the first comprehensive study of the overall impact of DAA treatment for HCV on liver transplantation in Europe. LAY SUMMARY: After the advent of direct-acting antivirals in 2014, a dramatic decline was observed in the number of liver transplants performed both in patients with decompensated cirrhosis due to hepatitis C virus (HCV), minus 60%, and in those with hepatocellular carcinoma associated with HCV, minus 41%. Furthermore, this is the first large-scale study demonstrating that the survival of liver transplant recipients with HCV-related liver disease has dramatically improved over the last three years and is now comparable to the survival of recipients with hepatitis B virus infection. The reduction in HCV-related indications for LT means that there is a greater availability of livers, at least 600 every year, which can be allocated to patients with indications other than HCV.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/complications , Liver Transplantation , Carcinoma, Hepatocellular/mortality , Cohort Studies , Female , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/mortality , Humans , Liver Cirrhosis/mortality , Liver Neoplasms/mortality , Male , Middle Aged , Registries
9.
Clin Gastroenterol Hepatol ; 16(7): 1153-1162.e7, 2018 07.
Article in English | MEDLINE | ID: mdl-29378312

ABSTRACT

BACKGROUND & AIMS: Portosystemic encephalopathy (PSE) is a major complication of trans-jugular intrahepatic porto-systemic shunt (TIPS) placement. Most devices are self-expandable polytetrafluoroethylene-covered stent grafts (PTFE-SGs) that are dilated to their nominal diameter (8 or 10 mm). We investigated whether PTFE-SGs dilated to a smaller caliber (under-dilated TIPS) reduce PSE yet maintain clinical and hemodynamic efficacy. We also studied whether under-dilated TIPS self-expand to nominal diameter over time. METHODS: We performed a prospective, non-randomized study of 42 unselected patients with cirrhosis who received under-dilated TIPS (7 and 6 mm) and 53 patients who received PTFE-SGs of 8 mm or more (controls) at referral centers in Italy. After completion of this study, dilation to 6 mm became the standard and 47 patients were included in a validation study. All patients were followed for 6 months; Doppler ultrasonography was performed 2 weeks and 3 months after TIPS placement and every 6 months thereafter. Stability of PTFE-SG diameter was evaluated by computed tomography analysis of 226 patients with cirrhosis whose stent grafts increased to 6, 7, 8, 9, or 10 mm. The primary outcomes were incidence of at least 1 episode of PSE grade 2 or higher during follow up, incidence of recurrent variceal hemorrhage or ascites, incidence of shunt dysfunction requiring TIPS recanalization, and reduction in porto-caval pressure gradient. RESULTS: PSE developed in a significantly lower proportion of patients with under-dilated TIPS (27%) than controls (54%) during the first year after the procedure (P = .015), but the proportions of patients with recurrent variceal hemorrhage or ascites did not differ significantly between groups. No TIPS occlusions were observed. These results were confirmed in the validation cohort. In an analysis of self-expansion of stent grafts, during a mean follow-up period of 252 days after placement, none of the PTFE-SGs self-expanded to the nominal diameter in hemodynamically relevant sites (such as portal and hepatic vein vascular walls). CONCLUSIONS: In prospective, non-randomized study of patients with cirrhosis, we found under-dilation of PTFE-SGs during TIPS placement to be feasible, associated with lower rates of PSE, and effective.


Subject(s)
Fibrosis/complications , Hepatic Encephalopathy/epidemiology , Hepatic Encephalopathy/prevention & control , Portasystemic Shunt, Transjugular Intrahepatic/adverse effects , Portasystemic Shunt, Transjugular Intrahepatic/methods , Aged , Fibrosis/surgery , Humans , Incidence , Italy/epidemiology , Male , Middle Aged , Prospective Studies , Treatment Outcome
10.
Biochim Biophys Acta Mol Basis Dis ; 1864(4 Pt B): 1415-1422, 2018 04.
Article in English | MEDLINE | ID: mdl-28844954

ABSTRACT

BACKGROUND: Autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis represent the three major autoimmune liver diseases (AILDs). Their management is highly specialized, requires a multidisciplinary approach and often relies on expensive, orphan drugs. Unfortunately, their treatment is often unsatisfactory, and the care pathway heterogeneous across different centers. Disease-specific clinical outcome indicators (COIs) able to evaluate the whole cycle of care are needed to assist both clinicians and administrators in improving quality and value of care. Aim of our study was to generate a set of COIs for the three AILDs. We then prospectively validated these indicators based on a series of consecutive patients recruited at three tertiary clinical centers in Lombardy, Italy. METHODS: In phase I using a Delphi method and a RAND 9-point appropriateness scale a set of COIs was generated. In phase II the indicators were applied in a real-life dataset. RESULTS: Two-hundred fourteen patients were enrolled and followed-up for a median time of 54months and the above COIs were recorded using a web-based electronic medical record program. The COIs were easy to collect in the clinical practice environment and their values compared well with the available natural history studies. CONCLUSIONS: We have generated a comprehensive set of COIs which sequentially capture different clinical outcome of the three AILDs explored. These indicators represent a critical tool to implement a value-based approach to patients with these conditions, to monitor, compare and improve quality through benchmarking of clinical performance and to assess the significance of novel drugs and technologies. This article is part of a Special Issue entitled: Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.


Subject(s)
Autoimmune Diseases/therapy , Cholangitis, Sclerosing/therapy , Hepatitis, Autoimmune/therapy , Outcome Assessment, Health Care/methods , Quality Indicators, Health Care , Adult , Aged , Autoimmune Diseases/epidemiology , Cholangitis, Sclerosing/epidemiology , Critical Pathways/organization & administration , Delphi Technique , Female , Follow-Up Studies , Hepatitis, Autoimmune/epidemiology , Humans , Incidence , Italy/epidemiology , Male , Middle Aged , Prospective Studies , Survival Analysis , Tertiary Care Centers/statistics & numerical data
12.
J Hepatol ; 65(3): 524-31, 2016 09.
Article in English | MEDLINE | ID: mdl-27212241

ABSTRACT

BACKGROUND & AIMS: All oral direct acting antivirals (DAA) have been shown to improve the liver function of patients with decompensated cirrhosis but it is presently unknown whether this clinical improvement may lead to the delisting of some patients. The aim of this study was to assess if and which patients can be first inactivated due to clinically improvement and subsequently delisted in a real life setting. METHODS: 103 consecutive listed patients without hepatocellular carcinoma were treated with different DAA combinations in 11 European centres between February 2014 and February 2015. RESULTS: The cumulative incidence of inactivated and delisted patients by competing risk analysis was 15.5% and 0% at 24weeks, 27.6% and 10.3% at 48weeks, 33.3% and 19.2% at 60weeks. The 34 patients who were inactivated showed a median improvement of 3.4 points for MELD (delta MELD, p<0.0001) and 2 points for Child-Pugh (CP) (delta-CP, p<0.0001). Three variables emerged from the most parsimonious multivariate competing risk model as predictors of inactivation for clinical improvement, namely, baseline MELD classes (MELD 16-20: HR=0.120; p=0.0005, MELD >20:HR=0.042; p<0.0001), delta MELD (HR=1.349; p<0.0001) and delta albumin (HR=0.307; p=0.0069) both assessed after 12weeks of DAA therapy. CONCLUSIONS: This study showed that all oral DAAs were able to reverse liver dysfunction and favoured the inactivation and delisting of about one patient out-of-three and one patient out-of-five in 60weeks, respectively. Patients with lower MELD scores had higher chances to be delisted. The longer term benefits of therapy need to be ascertained. LAY SUMMARY: The excellent efficacy and safety profile of the new drugs against Hepatitis C virus, "direct acting antivirals" or DAAs, have made antiviral therapy possible also for patients with advanced liver disease and for those on the waiting list for liver transplantation (LT). This study shows for the first time that the DAAs may lead to a remarkable clinical improvement allowing the delisting of one patient out of 5.


Subject(s)
Liver Transplantation , Carcinoma, Hepatocellular , Hepatitis C, Chronic , Humans , Liver Neoplasms , Waiting Lists
13.
Clin Transplant ; 29(2): 161-6, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25522890

ABSTRACT

Autoantibodies are frequently detected after liver transplantation (LT), but their role is unclear. This study was designed to address three points: autoantibody prevalence pre-LT and over time up to five yr after LT, identification of possible predictors of autoantibody formation, and correlation between autoantibodies and graft dysfunction. To these aims, we retrospectively evaluated 92 consecutive LT recipients for whom prospectively stored frozen sera were available for autoantibodies assessment by immunofluorescence. The overall autoantibody prevalence resulted significantly higher after LT than before LT (64% vs. 27%, p < 0.001 and 35.9% vs. 8.7%, p < 0.001 considering cutoff titer of ≥ 1:80 and ≥ 1:160, respectively). Recipient gender, donor age and gender, and indication for LT and main immunosuppressant (cyclosporine vs. tacrolimus) were not associated with the presence of autoantibodies. Patients with graft dysfunction had a significantly higher autoantibody prevalence irrespective of the etiology of liver injury as compared to those patients with persistently normal liver biochemistry, but only for cutoff titers ≥ 1:160 (p = 0.004). No cases of de novo autoimmune hepatitis were observed. In conclusion, autoantibodies are very frequently detected after LT also at high titers and their association with graft dysfunction likely represents an aspecific indicator of liver injury.


Subject(s)
Autoantibodies/blood , Autoimmune Diseases/immunology , Autoimmunity , Liver Transplantation , Autoimmune Diseases/blood , Autoimmune Diseases/etiology , Female , Follow-Up Studies , Humans , Italy/epidemiology , Male , Middle Aged , Postoperative Complications , Prevalence , Retrospective Studies , Risk Factors
14.
Dig Liver Dis ; 55(2): 268-275, 2023 02.
Article in English | MEDLINE | ID: mdl-35644890

ABSTRACT

BACKGROUND: Liver transplantation (LT) represents the best therapeutic option for hepatocellular carcinoma (HCC) and end-stage liver disease (ESLD). Although HIV infection does not seem to lower survival rates, HCV and HCC recurrence appear more harmful. AIMS: To compare the overall survival after LT; evaluate the impact of anti-HCV direct-acting agents (DAA); assess the rate of HCC recurrence in HIV-positive and negative patients. METHODS: Subjects with HCV/HBV infection who underwent LT for HCC or ESLD from 2012 to 2019 were retrospectively evaluated. RESULTS: Study population included 299 individuals, 31 (10.4%) were HIV-positive. Overall mortality was similar (16.1% versus 19.0%, p = 0.695). HCC recurrence was observed in 6 HIV-positive (19.4%) and in 17 negative subjects (6.3%, p = 0.022). Time to relapse was 831 days in HIV-positive and 315 days in negative patients (p = 0.046). Cox model found a significant role for HIV in univariate analysis but, after adjusting for variables, extra-hepatic tumor was the only factor associated to recurrence (aHR 56.379, p < 0.001). CONCLUSIONS: Post-LT survival improved after DAA availability and HIV has no impact on mortality. A higher and delayed rate of HCC recurrence was observed in co-infected individuals: surveillance protocols should be strengthened along time in this population.


Subject(s)
Carcinoma, Hepatocellular , End Stage Liver Disease , HIV Infections , Hepatitis C , Liver Neoplasms , Liver Transplantation , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , HIV Infections/complications , HIV Infections/drug therapy , Retrospective Studies , Antiviral Agents/therapeutic use , Neoplasm Recurrence, Local/pathology , Hepatitis C/drug therapy , Liver Cirrhosis/complications , Liver Cirrhosis/drug therapy
15.
Front Transplant ; 2: 1332616, 2023.
Article in English | MEDLINE | ID: mdl-38993892

ABSTRACT

Background: Despite the WHO's report of 24 available SARS-CoV-2 vaccines, limited data exist regarding vaccination policies for liver transplant (LT) patients. To address this, we conducted a global multi-society survey (EASL-ESOT-ELITA-ILTS) in LT centers. Methods: A digital questionnaire assessing vaccine policies, safety, efficacy, and center data was administered online to LT centers. Results: Out of 168 responding centers, 46.4%, 28%, 13.1%, 10.7%, and 1.8% were from European, American, Western Pacific, Southeast Asian, and Eastern Mediterranean Regions. Most LT centers prioritized COVID-19 vaccine access for LT patients (76%) and healthcare workers (86%), while other categories had lower priority (30%). One-third of responders recommended mRNA vaccine exclusively, while booster doses were widely recommended (81%). One-third conducted post-vaccine liver function tests post COVID-19 vaccine. Only 16% of centers modified immunosuppression, and mycophenolate discontinuation or modification was the main approach. Side effects were seen in 1 in 1,000 vaccinated patients, with thromboembolism, acute rejection, and allergic reaction being the most severe. mRNA showed fewer side effects (-3.1, p = 0.002). Conclusion: COVID-19 vaccines and booster doses were widely used among LT recipients and healthcare workers, without a specific vaccine preference. Preventative immunosuppression adjustment post-vaccination was uncommon. mRNA vaccines demonstrated a favorable safety profile in this population.

18.
Liver Transpl ; 15(4): 390-9, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19326408

ABSTRACT

In 20% to 30% of infected individuals, hepatitis C virus (HCV) can cause cirrhosis and hepatocellular carcinoma, for which liver transplantation is the best treatment available. HCV re-infection is universal, and hepatitis disease recurrence occurs in most cases with a 30% probability of progression to graft cirrhosis at 5 years post-transplant. The immunological response to HCV involves natural killer (NK) cells and killer cell immunoglobulin-like receptors (KIRs), which specifically recognize human leukocyte antigen (HLA) class I antigens present on target cells. The effector functions of NK cells are influenced by inhibitory KIR interaction with self-HLA class I ligands, with HLA-C being the most predominant. This study examines the roles of KIR genotypes and their HLA ligands in both HCV disease recurrence and its progression. A total of 151 patients were included in the cohort, and their clinical details were recorded. Liver biopsies were used to define the absence/presence of recurrent hepatitis, the degree of fibrosis, and the progression to cirrhosis over a 10-year period. Mismatching of KIR-HLA-C ligands between donor-recipient pairs was associated with the recurrence of hepatitis (P = 0.008). The presence of KIR2DL3 in the recipient correlated with progression to liver fibrosis (P = 0.04). The mismatching of HLA-KIR ligands favored the progression of the recurrent hepatitis to fibrosis only in the presence of KIR2DL3 (P = 0.04). These preliminary results indicate that the KIR genotype and KIR-HLA-C ligand compatibility play roles in the recurrence and progression of hepatitis C disease in liver transplant recipients.


Subject(s)
Carcinoma, Hepatocellular/surgery , HLA-C Antigens/immunology , Hepatitis C, Chronic/complications , Killer Cells, Natural/immunology , Liver Cirrhosis/surgery , Liver Neoplasms/surgery , Liver Transplantation , Receptors, KIR/genetics , Adult , Biopsy , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/virology , Disease Progression , Female , Gene Frequency , Genotype , Graft Rejection/immunology , Graft Rejection/virology , Graft Survival , Hepatitis C, Chronic/immunology , Hepatitis C, Chronic/surgery , Histocompatibility , Humans , Italy , Killer Cells, Natural/virology , Ligands , Liver/immunology , Liver/pathology , Liver/virology , Liver Cirrhosis/immunology , Liver Cirrhosis/virology , Liver Neoplasms/immunology , Liver Neoplasms/virology , Male , Middle Aged , Receptors, KIR/immunology , Receptors, KIR2DL3/genetics , Recurrence , Retrospective Studies , Risk Assessment , Risk Factors , Severity of Illness Index , Time Factors , Transplantation, Homologous , Treatment Outcome
20.
Dig Liver Dis ; 49(3): 241-253, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28096056

ABSTRACT

The present document contains the recommendations of an expert panel of transplant hepatologists, appointed by the Italian Association for the Study of the Liver (AISF), on how to manage the most common aspects of liver transplantation: the topics covered include: new treatments for HCV in patients on the waiting list for liver transplantation; antiviral treatments in patients with HCV recurrence after liver transplantation; prophylaxis for HBV recurrence after liver transplantation; indications for liver transplantation in alcoholic liver disease; and Immunosuppressive therapy. The statements on each topic were approved by participants at the AISF Transplant Hepatologist Expert Meeting (organized by the Permanent Committee on Liver Transplantation in Mondello on 4-5 October 2015), and are graded according to the Oxford classification of levels of evidence.


Subject(s)
Antiviral Agents/therapeutic use , Disease Management , Hepatitis C, Chronic/therapy , Liver Diseases, Alcoholic/complications , Liver Transplantation , Waiting Lists , Hepatitis C, Chronic/surgery , Humans , Italy , Liver Diseases, Alcoholic/surgery , Recurrence , Societies, Medical
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