Superiority of the new sex-adjusted models to remove the female disadvantage restoring equity in liver transplant allocation.

BACKGROUND AND AIMS: Model for End-stage Liver Disease (MELD) and MELDNa are used worldwide to guide graft allocation in liver transplantation (LT). Evidence exists that females are penalized in the present allocation systems. Recently, new sex-adjusted scores have been proposed with improved performance respect to MELD and MELDNa. GEMA-Na, MELD 3.0, and sex-adjusted MELDNa were developed to improve the 90-day dropout prediction from the list. The present study aimed at evaluating the accuracy and calibration of these scores in an Italian setting. METHODS: The primary outcome of the present study was the dropout from the list up to 90 days because of death or clinical deterioration. We retrospectively analysed data from 855 adults enlisted for liver transplantation in the Lazio region (Italy) (2012-2018). Ninety-day prediction of GEMA-Na, MELD 3.0 and sex-adjusted MELDNa with respect to MELD and MELDNa was analysed. Brier score and Brier Skill score were used for accuracy, and the Greenwood-Nam-D'Agostino test was used to evaluate the calibration of the models. RESULTS: GEMA-Na (concordance = .82, 95% CI = .75-.89), MELD 3.0 (concordance = .81, 95% CI = .74-.87) and sex-adjusted MELDNa (concordance = .81, 95% CI = .74-.88) showed the best 90-day dropout prediction. GEMA-Na showed a higher increase in accuracy with respect to MELD (p = .03). No superiority was shown with respect to MELDNa. All the tested scores showed a good calibration of the models. Using GEMA-Na instead of MELD would potentially save one in nine dropouts and could save one dropout per 285 patients listed. CONCLUSIONS: Validation and reclassification of the sex-adjusted score GEMA-Na confirm its superiority in predicting short-term dropout also in an Italian setting when compared with MELD.

"Real world" efficacy of bulevirtide in HBV/HDV-related cirrhosis including people living with HIV: Results from the compassionate use programme at INMI Spallanzani in Rome, Italy.

OBJECTIVES: We describe the preliminary results of bulevirtide compassionate use in patients with hepatitis B and delta virus (HBV/HDV)-related cirrhosis and clinically significant portal hypertension, including those living with HIV. METHODS: We conducted a prospective observational study of consecutive patients. Clinical evaluation, liver function tests, bile acid levels, HDV-RNA, HBV-DNA, hepatitis B surface antigen, and liver and spleen stiffness were assessed at baseline and after treatment months 1, 2, 3, 4, 6, 9, and 12. HIV-RNA and CD4+/CD8+ count were assessed in people living with HIV. The first drug injection was administered under nurse supervision, and counselling was provided and adherence reviewed at each visit. RESULTS: In total, 13 patients (61.5% migrants) were enrolled. The median treatment duration was 11 months. At month 6, mean alanine aminotransferase (ALT) levels fell by 64.5% and mean liver and spleen stiffness decreased by 8.6 and 0.9 kPa, respectively. The mean baseline HDV-RNA was 3.34 log IU/mL and 5.10 log IU/mL in people without and with HIV (n = 5) (p = 0.28), respectively. A similar mean decline was observed in both groups: -2.06 log IU/mL and -1.93 log IU/mL, respectively (p = 0.87). A combined response (undetectable HDV RNA or ≥ -2 log IU/mL decline vs. baseline, with ALT normalization) was achieved in 66% of subjects without and in 60% of patients with HIV. Patients with HIV showed persistently undetectable HIV-RNA and a progressive increase in CD4+/CD8+ cells during treatment. No patient discontinued bulevirtide because of adverse effects. CONCLUSIONS: Preliminary results suggest that bulevirtide is feasible and well-tolerated in populations with difficult-to-treat conditions, such as those with HIV/HBV/HDV co-infection and migrants, when special attention is given to patient education. HDV-RNA decline during treatment was similar in people living with and without HIV.

Third dose of SARS-CoV2 mRNA vaccination produces robust persistent cellular and humoral immune responses in liver transplant recipients.

Weaker responses have been described after two doses of anti-SARS-CoV2 vaccination in liver transplant recipients (LTRs). At the Italian National Institute for Infectious Diseases, 122 LTRs (84% males, median age 64 years) were tested for humoral and cell-mediated immune response after a third doses of anti-SARS-CoV2 mRNA vaccines. Humoral response was measured by quantifying anti-receptor binding domain and neutralizing antibodies; cell-mediated response was measured by quantifying IFN-γ after stimulation of T cells with SARS-CoV-2-specific peptides. Humoral and cellular responses improved significantly compared to the second vaccine dose; 86.4% of previous non-responders to the first 2 vaccine doses (N = 22) became responders. Mycophenolate mofetil-containing regimens were not associated with lower response rates to a third vaccine; shorter time since transplantation (<6 years) was associated with lower humoral and cellular responses to third vaccine. Protective antibodies against Omicron variant were detected in 60% of patients 12 weeks after third vaccine dose.

Coordinated cellular and humoral immune responses after two-dose SARS-CoV2 mRNA vaccination in liver transplant recipients.

Limited data are available on risks and benefits of anti-SARS-CoV2 vaccination in solid organ transplant recipients, and weaker responses have been described. At the Italian National Institute for Infectious Diseases, 61 liver transplant recipients underwent testing to describe the dynamics of humoral and cell-mediated immune response after two doses of anti-SARS-CoV2 mRNA vaccines and compared with 51 healthy controls. Humoral response was measured by quantifying both anti-spike and neutralizing antibodies; cell-mediated response was measured by PBMC proliferation assay with IFN-γ and IL-2 production. Liver transplant recipients showed lower response rates compared with controls in both humoral and cellular arms; shorter time since transplantation and multi-drug immunosuppressive regimen containing mycophenolate mofetil were predictive of reduced response to vaccination. Specific antibody and cytokine production, though reduced, were highly correlated in transplant recipients.

Sarco-Model: A score to predict the dropout risk in the perspective of organ allocation in patients awaiting liver transplantation.

BACKGROUND & AIMS: Sarcopenia in liver transplantation (LT) cirrhotic candidates has been connected with higher dropouts and graft losses after transplant. The study aims to create an 'urgency' model combining sarcopenia and Model for End-stage Liver Disease Sodium (MELDNa) to predict the risk of dropout and identify an appropriate threshold of post-LT futility. METHODS: A total of 1087 adult cirrhotic patients were listed for a first LT during January 2012 to December 2018. The study population was split into a training (n = 855) and a validation set (n = 232). RESULTS: Using a competing-risk analysis of cause-specific hazards, we created the Sarco-Model2 . According to the model, one extra point of MELDNa was added for each 0.5 cm2 /m2 reduction of total psoas area (TPA) < 6.0 cm2 /m2 . At external validation, the Sarco-Model2 showed the best diagnostic ability for predicting the risk of 3-month dropout in patients with MELDNa < 20 (area under the curve [AUC] = 0.93; P = .003). Using the net reclassification improvement, 14.3% of dropped-out patients were correctly reclassified using the Sarco-Model2 . As for the futility threshold, transplanted patients with TPA < 6.0 cm2 /m2 and MELDNa 35-40 (n = 16/833, 1.9%) had the worse results (6-month graft loss = 25.5%). CONCLUSIONS: In sarcopenic patients with MELDNa < 20, the 'urgency' Sarco-Model2 should be used to prioritize the list, while MELDNa value should be preferred in patients with MELDNa ≥ 20. The Sarco-Model2 played a role in more than 30% of the cases in the investigated allocation scenario. In sarcopenic patients with a MELDNa value of 35-40, 'futile' transplantation should be considered.

Cumulative incidence of solid and hematological De novo malignancy after liver transplantation in a multicentre cohort.

BACKGROUND: Recent innovations in the field of liver transplantation have led to a wealth of new treatment regimes, with potential impact on the onset of de novo malignancies (DNM). The aim of this multicenter cohort study was to provide contemporary figures for the cumulative incidences of solid and hematological DNM after liver transplantation. METHODS: We designed a retrospective cohort study including patients undergoing LT between 2000 and 2015 in three Italian transplant centers. Cumulative incidence was calculated by Kaplan-Meyer analysis. RESULTS: The study included 789 LT patients with a median follow-up of 81 months (IQR: 38-124). The cumulative incidence of non-cutaneous DNM was 6.2% at 5-years, 11.6% at 10-years and 16.3% at 15-years. Post-Transplant Lymphoproliferative Disorders (PTLD) were demonstrated to have a cumulative incidence of 1.0% at 5-years, 1.6% at 10-years and 2.2% at 15-years. Solid Organ Tumors (SOT) demonstrated higher cumulative incidences - 5.3% at 5-years, 10.3% at 10-years and 14.4% at 15-years. The most frequently observed classifications of SOT were lung (rate 1.0% at 5-years, 2.5% at 10-years) and head & neck tumors (rate 1.3% at 5-years, 1.9% at 10-years). CONCLUSIONS: Lung tumors and head & neck tumors are the most frequently observed SOT after LT.

Daclatasvir, sofosbuvir with or without ribavirin for 24 weeks in hepatitis C genotype 3 cirrhosis: A real-life study.

INTRODUCTION AND AIM: Cirrhotic patients with hepatitis C virus genotype 3 infection show unsatisfactory outcomes after 12 weeks' treatment with direct antiviral agents. The National Italian Drug Agency allows 24 weeks of therapy in difficult-to-treat patients, including genotype 3 cirrhotics. Aim of this study was to evaluate efficacy and safety of a 24-week course of sofosbuvir plus daclatasvir±ribavirin in this population. MATERIALS AND METHODS: 106 consecutive cirrhotics (70.8% males, mean age 55.3±7.6 years) in 8 tertiary hepatology centers received sofosbuvir plus daclatasvir for 24 weeks. Ribavirin was administered in 85 (80.2%) based expected tolerability, at a mean dose of 964±202mg/day. Baseline Child-Pugh class was A 91.5%, B 6.6%, C 1.9%; mean baseline MELD was 8.5±2.7. RESULTS: All patients completed 12-week follow-up post-treatment, and 104 (98.1%) obtained sustained virological response (100% in ribavirin -treated patients vs. 90.4% without ribavirin; p=0.04). No worsening in renal and liver function was observed, no serious adverse events occurred. Two virological failures showed resistance associated variants (Y93H and S282T). CONCLUSION: An extended 24-week treatment with sofosbuvir plus daclatasvir+ribavirin obtained 100% efficacy in genotype 3 hepatitis C cirrhosis, with very limited side effects. The role of ribavirin seems crucial in this setting and should be administered if clinically feasible.

Lack of reduction in serum alpha-fetoprotein during treatment with direct antiviral agents predicts hepatocellular carcinoma development in a large cohort of patients with hepatitis C virus-related cirrhosis.

Risk of hepatocellular carcinoma (HCC) in hepatitis C virus cirrhotic patients treated with direct-acting antiviral agents (DAA) is still debating. We investigated it in a large cohort. The cohort comprised 1045 cirrhotic patients who completed treatment with DAA, with a median follow-up of 17.3 months after end of treatment (EOT), including 943 patients without history of HCC and 102 previously treated for HCC. The majority were men (59.9%), with compensated cirrhosis (88.8%), genotype 1b (44.7%). Univariate, multivariate analysis and Kaplan-Meier curves were performed to detect predictors of HCC in patients with and without reduction in alpha-fetoprotein (AFP) during treatment. SVR12 was 95.6%. HCC developed in 95 (9.9%), including 54 of 943 (5.7%) occurrent and 41 of 102 (39%) recurrent tumours. De novo were more often unifocal (P = 0.01) and curable (P = 0.03). AFP decreased from 16.1 ± 36.2 mg/dL (baseline) to 11.4 ± 55 mg/dL (EOT). At univariate analysis, predictors were a previous HCC, older age, higher model for end-stage liver disease, prolonged INR, lower platelets, baseline and EOT AFP, virological failure and no reduction in AFP during treatment. Kaplan-Meier curves showed lower incidence of HCC in patients showing any reduction in AFP (P = 0.001). Those with AFP <6 ng/mL had the lowest risk (P = 0.0002). At logistic regression, platelets (P = 0.009, OR 0.99 CI: 0.99-1.00), previous HCC (P < 0.000 01, OR: 10.76, 95% CI: 5.89-19.34) and no reduction in AFP during treatment (P = 0.0005, OR: 2.98, CI: 1.60-5.54) were independent predictors of HCC. In conclusion, risk of HCC after DAA treatment remains substantial. It is higher among patients with previous HCC, low platelets and without reduction in AFP during treatment.

Significance of detectable HCV RNA below the limit of quantification in patients treated with DAAs using standard and ultrasensitive protocols.

Predictive factors of HCV relapse after treatment with DAAs are poorly understood. In this study, we aimed to assess whether the residual viral load positivity observed during or at the end of treatment (EOT) has an impact on viral outcome. Blood samples were collected from 337 patients with genotypes (GT) 1a, 1b, 2, 3, and 4 HCV chronic infection, treated with DAAs to determine HCV RNA load by the Abbott RealTime HCV (ART) assay at treatment week (W) 4, at EOT, and 4, 12, 24 weeks after discontinuation. EOT and other samples with "detected <12/mL" (DNQ) were retested by an ultrasensitive protocol (USP) to confirm the result. Frequency of DNQ was analyzed in subgroups of patients and clinical conditions to assess potential correlations. At W4, 22% and 30.9% of the samples were undetectable and DNQ by ART assay, respectively, but no correlation for achieving SVR was found. In contrast, an HCV RNA cut-off of ≥50/mL at W4 was a significant predictor of therapy failure (P = 0.036, univariate analysis). At EOT, DNQ was associated to 12W treatment duration (P < 0.001) and GT1a infection (P = 0.036). Overall, 20/41 (48.8%) of DNQ samples at EOT or post-treatment W4, were confirmed by USP but only in a single case the patient experienced viral relapse. HCV RNA at W4 can predict SVR, irrespective to genotype or DAA regimen. HCV RNA DNQ at EOT is associated to shorter treatment duration and to GT1a, but is not a predictor of therapy failure.

Sofosbuvir plus daclatasvir with or without ribavirin is safe and effective for post-transplant hepatitis C recurrence and severe fibrosis and cirrhosis: A prospective study.

BACKGROUND: In 2012, an Italian Named Patient Program began for hepatitis C virus (HCV)-infected liver transplant (LT) recipients with advanced fibrosis, before approval of direct antiviral agents (DAA), to benefit severely ill patients. The aim of this "real-life" study was to assess treatment efficacy and safety with an extended course of daclatasvir (DCV) plus sofosbuvir (SOF) with or without ribavirin (RBV). METHODS: All HCV LT recipients with severe fibrosis in 15 Italian transplant centers were treated with DCV+SOF±RBV for 24 weeks; sustained virological response was assessed at 12 weeks post-treatment (SVR12). RESULTS: Eighty-seven patients were enrolled (75.9% males, mean age 58.4 ± 7.2 years, 83.9% genotype 1, 81.6% cirrhosis); 52 (59.8%) received RBV. Overall, 79 obtained SVR12 (90.8%): 100% in F3 and 88.7% in cirrhotics (91.5% in Child-Pugh A, 83.3% in Child-Pugh B and C). According to the treatment group, SVR was 80% in DCV + SOF group and 98.1% in SOF + DCV + RBV. Two virological relapses occurred during follow-up in cirrhotic patients who received DCV + SOF. Four cirrhotic patients in DCV + SOF group and 1 in DCV + SOF + RBV group died on treatment. CONCLUSION: An extended course of SOF plus DCV for 24 weeks, with or without RBV, is effective and well tolerated for the treatment of post-LT HCV recurrence with severe fibrosis.

Dendritic cells activation is associated with sustained virological response to telaprevir treatment of HCV-infected patients.

First anti-HCV treatments, that include protease inhibitors in conjunction with IFN-α and Ribavirin, increase the sustained virological response (SVR) up to 80% in patients infected with HCV genotype 1. The effects of triple therapies on dendritic cell (DC) compartment have not been investigated. In this study we evaluated the effect of telaprevir-based triple therapy on DC phenotype and function, and their possible association with treatment outcome. HCV+ patients eligible for telaprevir-based therapy were enrolled, and circulating DC frequency, phenotype, and function were evaluated by flow-cytometry. The antiviral activity of plasmacytoid DC was also tested. In SVR patients, myeloid DC frequency transiently decreased, and returned to baseline level when telaprevir was stopped. Moreover, an up-regulation of CD80 and CD86 on mDC was observed in SVR patients as well as an improvement of IFN-α production by plasmacytoid DC, able to inhibit in vitro HCV replication.

Effectiveness of Paritaprevir/Ritonavir/Ombitasvir/Dasabuvir in Hemodialysis Patients With Hepatitis C Virus Infection and Advanced Liver Fibrosis: Case Reports.

Hepatitis C virus infection is common among patients on hemodialysis therapy and is an important cause of morbidity and mortality. We investigated the safety and effectiveness of a paritaprevir/ritonavir/ombitasvir/dasabuvir regimen in a group of 10 patients on hemodialysis therapy with genotype 1a, 1b, or 4 hepatitis C virus infection who had predictors of unfavorable response, such as compensated cirrhosis (7 patients) or advanced fibrosis and failure of previous therapy (3 patients). The treatment, with or without ribavirin, was administered daily for 12 or 24 weeks. Clinical and virologic assessment was performed every 4 weeks during the treatment and at posttreatment weeks 4 and 12. All patients achieved a sustained virologic response at posttreatment week 12. 80% of patients reported at least one adverse event: fatigue and anemia of mild intensity were the most common; a single episode of moderate liver decompensation was observed. The paritaprevir/ritonavir/ombitasvir/dasabuvir antiviral regimen is effective and well tolerated in genotype 1 or 4 hepatitis C virus-infected patients on hemodialysis therapy with compensated cirrhosis and/or failure of previous treatments.

The Italian compassionate use of sofosbuvir observational cohort study for the treatment of recurrent hepatitis C: clinical and virological outcomes.

Direct antivirals are available for treating recurrent hepatitis C (RHC). This study reported outcomes of 424 patients with METAVIR F3-F4 RHC who were treated for 24 weeks with sofosbuvir/ribavirin and followed for 12 weeks within the Italian sofosbuvir compassionate use program. In 55 patients, daclatasvir or simeprevir were added. Child-Pugh class and model of end stage liver disease (MELD) scores were evaluated at baseline and 36 weeks after the start of therapy. The sustained viral response (SVR) was 86.7% (316/365) in patients who received sofosbuvir/ribavirin and 98.3% (58/59) in patients who received a second antiviral (P < 0.01). In patients treated with sofosbuvir/ribavirin, a significant difference in SVR was observed between patients diagnosed with METAVIR F4 (211/250; 84.4%), METAVIR F3 (95/105; 90.5%) and fibrosing cholestatic hepatitis (10/10; 100%) (P = 0.049). A significant association was found between patients who worsened from Child-Pugh class A and who experienced viral relapse (4/26 vs. 8/189, P = 0.02). In patients with a baseline MELD score <15, a significant association was found between maintaining a final MELD score <15 and the achievement of SVR (187/219 vs. 6/10, P = 0.031). This real-world study indicates that sofosbuvir/ribavirin treatment for 24 weeks was effective, and the achievement of SVR was associated with a reduced probability of developing worsening liver function.

Yttrium-90 Radioembolization for Hepatocellular Carcinoma Prior to Liver Transplantation.

BACKGROUND: Liver transplantation (LT) is a well-established procedure for hepatocellular carcinoma (HCC) within the Milan criteria. Yttrium-90 microspheres radioembolization (Y90-RE) has shown to be an effective and safe treatment of primary liver tumors. We retrospectively evaluate the efficacy of the Y90-RE in patients with HCC prior to LT. METHODS: From January 2002 to December 2015, 365 patients were transplanted at the San Camillo Hospital Center. One hundred forty-three patients were transplanted for HCC, and in 22 cases the patients were treated with Y90-RE before LT. RESULTS: Three patients were treated with Y90-RE within the Milan criteria, and 19 patients were out of criteria before Y90-RE. Four patients had an increasing MELD score between Y90-RE and LT. On the other hand, alpha-fetoprotein decreases after Y90-RE treatment in all cases. No patient death was observed in Y90-RE procedure or at LT. In 78.9 % of cases, a successful downstaging was observed, and in 100 % of cases bridging was achieved. From Y90-RE treatment overall survival was 43.9 months. From LT, overall mean survival was 30.2 months with a free survival of 29.6 months. The overall survival after LT analysis between the patients treated with Y90-RE and patients without was not significant (p = 0.113). Free survival analysis was not significant (p = 0.897) between the two populations. CONCLUSIONS: We successfully performed LT in patients after Y90-RE treatment both as bridging and downstaging for HCC and obtained a similar overall and free survival of LT for HCC within Milan criteria. Y90-RE becomes a real option to provide curative therapy for patients who traditionally are not considered eligible for surgery.

Clinical and virological predictors of sustained response with an interferon-based simeprevir regimen for patients with chronic genotype 1 hepatitis C virus infection.

Simeprevir plus peg-interferon/ribavirin (PR) is approved to treat chronic hepatitis C (HCV) genotype 1 (GT1) and GT4 infection. This study aimed to assess baseline and on-treatment the factors predictive of sustained virologic response 12-weeks post-treatment (SVR12) in patients receiving 12 weeks of simeprevir plus PR followed by 12 or 36 weeks of PR. Data from participants in four studies (QUEST-1, QUEST-2, ATTAIN and PROMISE) were pooled to examine the efficacy and safety of simeprevir+PR in HCV GT1 patients. The predictive power of baseline variables for SVR12 was assessed using univariate and multivariate logistic regression models while the relationship between early (Week 4) on-treatment response and SVR12 was analyzed by GT1 subtype and treatment experience. Data for 1160 patients were analyzed (overall SVR12: 71%). Baseline factors predictive of SVR12 were: IL28B CC genotype, GT1a/Q80K-negative, treatment-naïve/prior relapser, no cirrhosis, HCV-RNA ≤2,000,000IU/mL, albumin >42g/L, platelets >200x109 /L. Patients with HCV GT1b (86%), IL28B CC genotype (87%), and treatment-naïve patients (83%) were predicted to achieve the highest SVR12 rates and rates of rapid virologic response. Week 4 early on-treatment response identified treatment-naïve and prior relapse patients likely to achieve SVR12. Patients likely to respond to simeprevir+PR can be identified using baseline factors. Early on-treatment response predicts treatment success.

Daclatasvir combined with sofosbuvir or simeprevir in liver transplant recipients with severe recurrent hepatitis C infection.

Daclatasvir (DCV) is a potent, pangenotypic nonstructural protein 5A inhibitor with demonstrated antiviral efficacy when combined with sofosbuvir (SOF) or simeprevir (SMV) with or without ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection. Herein, we report efficacy and safety data for DCV-based all-oral antiviral therapy in liver transplantation (LT) recipients with severe recurrent HCV. DCV at 60 mg/day was administered for up to 24 weeks as part of a compassionate use protocol. The study included 97 LT recipients with a mean age of 59.3 ± 8.2 years; 93% had genotype 1 HCV and 31% had biopsy-proven cirrhosis between the time of LT and the initiation of DCV. The mean Model for End-Stage Liver Disease (MELD) score was 13.0 ± 6.0, and the proportion with Child-Turcotte-Pugh (CTP) A/B/C was 51%/31%/12%, respectively. Mean HCV RNA at DCV initiation was 14.3 × 6 log10 IU/mL, and 37% had severe cholestatic HCV infection. Antiviral regimens were selected by the local investigator and included DCV+SOF (n = 77), DCV+SMV (n = 18), and DCV+SMV+SOF (n = 2); 35% overall received RBV. At the end of treatment (EOT) and 12 weeks after EOT, 88 (91%) and 84 (87%) patients, respectively, were HCV RNA negative or had levels <43 IU/mL. CTP and MELD scores significantly improved between DCV-based treatment initiation and last contact. Three virological breakthroughs and 2 relapses occurred in patients treated with DCV+SMV with or without RBV. None of the 8 patient deaths (6 during and 2 after therapy) were attributed to therapy. In conclusion, DCV-based all-oral antiviral therapy was well tolerated and resulted in a high sustained virological response in LT recipients with severe recurrent HCV infection. Most treated patients experienced stabilization or improvement in their clinical status.

Endoscopic management with multiple plastic stents of anastomotic biliary stricture following liver transplantation: long-term results.

BACKGROUND AND AIMS: Anastomotic biliary stricture (ABS) is the most common biliary complication after orthotopic liver transplantation (OLT) and can be successfully managed endoscopically. The long-term results of a protocol using placement of multiple plastic stents to treat ABS following OLT were analyzed. METHODS: All patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for OLT-related biliary complications at our Endoscopy Unit between July 1994 and March 2012 were retrospectively identified from the ERCP database. Patients with an ABS treated with an increasing number of plastic stents were included in the study. Follow-up after stent removal was obtained by telephone contact with the patient and/or referring physician and by liver function tests (LFTs) evaluation. RESULTS: 56 patients, treated with an increasing number of plastic stents until resolution of the stricture, were included. Five patients were then excluded (unrelated death during treatment, n = 3; incomplete treatment because of poor compliance, n = 2), and 51/56 patients reached study end points and were included in the analysis. Resolution of ABS was obtained in 50/51 patients; 1 patient required hepaticojejunostomy because of failure to pass the stricture with the guidewire (per protocol resolution, 98 %). Mean duration of endoscopic treatment was 11.5 months, with a median 4 ERCPs per patient. Immediate ERCP-related adverse events occurred in 3/56 patients (5.4 %). After a median follow-up of 5.8 years from stent removal, 3/50 patients (6 %) had recurrence of ABS. These 3 patients were successfully treated again endoscopically and are asymptomatic after a further median follow-up of 5.6 years. CONCLUSIONS: At long-term follow-up, endoscopic treatment with multiple plastic stents of ABS following OLT appeared to be effective in most patients. Stricture recurrence is rare and can be successfully treated again endoscopically.

Rapid and preemptive evaluation of individual anti-hepatitis C virus treatment outcome capability by a short-term autologous liver tissue culture system.

Hepatitis C virus (HCV) standard of care (SOC) therapy is not effective in a large percentage of patients and its efficacy may be evaluated only after several weeks. The aim of this work was to set up an in vitro liver culture assay able to preemptively predict SOC outcome by using residual liver samples from HCV patients. The in vitro response to SOC was found associated with the in vivo treatment outcome with a concordance of 100%. A wider clinical trial on a larger patient group is necessary to fully evaluate the impact of this procedure on the clinical management of untreated HCV patients.

Humoral Immune Response after COVID-19 mRNA Vaccination in Patients with Liver Cirrhosis: A Prospective Real-Life Single Center Study.

Coronavirus-disease-2019 (COVID-19) mRNA vaccination effectively reduces mortality and morbidity in cirrhotic patients, but the immunogenicity and safety of vaccination have been partially characterized. The study aimed to evaluate humoral response, predictive factors, and safety of mRNA-COVID-19 vaccination in cirrhotic patients compared to healthy subjects. A prospective, single-center, observational study enrolled consecutive cirrhotic patients who underwent mRNA-COVID-19 vaccination from April to May 2021. Anti-spike-protein (anti-S) and nucleocapsid-protein (anti-N) antibodies were evaluated before the first (T0) and the second (T1) doses and 15 days after completing the vaccination. An age and sex-matched healthy reference group was included. The incidence of adverse events (AEs) was assessed. In total, 162 cirrhotic patients were enrolled, 13 were excluded due to previous SARS-CoV-2 infection; therefore, 149 patients and 149 Health Care Workers (HCWs) were included in the analysis. The seroconversion rate was similar in cirrhotic patients and HCWs at T1 (92.5% vs. 95.3%, p = 0.44) and T2 (100% in both groups). At T2, anti-S-titres were significantly higher in cirrhotic patients compared to HCWs (2776.6 vs. 1756 BAU/mL, p < 0.001]. Male sex (ß = -0.32 [-0.64, -0.04], p = 0.027) and past-HCV-infection (ß = -0.31 [-0.59, -0.04], p = 0.029) were independent predictors of lower anti-S-titres on multiple-gamma-regression-analysis. No severe AEs occurred. The COVID-19-mRNA vaccination induces a high immunization rate and anti-S-titres in cirrhotic patients. Male sex and past-HCV infection are associated with lower anti-S-titres. The COVID-19-mRNA vaccination is safe.

Lymphofollicular lesions associated with monkeypox (Mpox) virus proctitis.

In the recent 2022 monkeypox (Mpox) global outbreak, cases have been mostly documented among men who have sex with men. Proctitis was reported in almost 14% of cases. In this study, four Mpox-confirmed cases requiring hospitalizations for severe proctitis were characterized by clinical, virological, microbiological, endoscopic, and histological aspects. The study showed the presence of lymphofollicular lesions associated with Mpox virus rectal infection for the first time.