Immunosuppression in adult liver transplant recipients: a 2024 update from the Italian Liver Transplant Working Group.

PURPOSE: Advances in surgical procedures and immunosuppressive therapies have considerably improved the outcomes of patients who have undergone liver transplantation in the past few decades. In 2020, the Italian Liver Transplant Working Group published practice-oriented algorithms for immunosuppressive therapy (IT) in adult liver transplant (LT) recipients. Due to the rapidly evolving LT field, regular updates to the recommendations are required. This review presents a consensus- and evidence-based update of the 2020 recommendations. METHODS: The Italian Liver Transplant Working Group set out to address new IT issues, which were discussed based on supporting literature and the specialists' personal experiences. The panel deliberated on and graded each statement before consensus was reached. RESULTS: A series of consensus statements were formulated and finalized on: (i) oncologic indications for LT; (ii) management of chronic LT rejection; (iii) combined liver-kidney transplantation; (iv) immunosuppression for transplantation with an organ donated after circulatory death; (v) transplantation in the presence of frailty and sarcopenia; and (vi) ABO blood group incompatibility between donor and recipient. Algorithms were updated in the following LT groups: standard patients, critical patients, oncology patients, patients with specific etiology, and patients at high immunologic risk. A steroid-free approach was generally recommended, except for patients with autoimmune liver disease and those at high immunologic risk. CONCLUSION: The updated consensus- and evidence-based 2024 recommendations for immunosuppression regimens in adult patients with ABO-compatible LT address a range of clinical variables that should be considered to optimize the choice of the immunosuppression treatment in clinical practice in Italy.

Trends in liver transplantation for primary sclerosing cholangitis.

BACKGROUND: Primary sclerosing cholangitis is a cholestatic disease with a low prevalence in Italy. Indications for liver transplantation and the time of listing are not stated. AIM: We performed a national survey to investigate the listing criteria, comorbidities, and outcomes. METHODS: In April 2022, we surveyed liver transplantation in primary sclerosing cholangitis nationwide for the last 15 years. RESULTS: From 2007 to 2021, 445 patients were included on waiting lists, and 411 had undergone liver transplants. The median age at transplantation was 46 years (males 63.9%); 262 patients (59%) presented an inflammatory bowel disease. Transplants increased over the years, from 1.8 % in 2007 to 3.0 % in 2021. Cholangitis (51%) and hepatic decompensation (45%) were the main indications for listing. The disease recurred in 81 patients (20%). Patient survival after the first transplant was 94 %, 86% and 84% at one, five, and ten years. Twenty-four died in the first year (50% surgical complications, 25% infections); 33 between one to five years (36% recurrence, 21% cholangiocarcinoma recurrence) and nine after five years (56% de novo cancer, 44% recurrence). CONCLUSIONS: Primary sclerosing cholangitis has been an increasing indication for transplantation in Italy. Cholangitis and decompensation were the main indications for listing. Recurrence and cancer were the leading causes of death.

Role of sex in liver tumor occurrence and clinical outcomes: A comprehensive review.

Clinical research on sex-based differences in the manifestations, pathophysiology, and prevalence of several diseases, including those affecting the liver, has expanded considerably in recent years. Increasing evidence suggests that liver diseases develop, progress, and respond to treatment differently depending on the sex. These observations support the concept that the liver is a sexually dimorphic organ in which estrogen and androgen receptors are present, which results in disparities between men and women in liver gene expression patterns, immune responses, and the progression of liver damage, including the propensity to develop liver malignancies. Sex hormones play protective or deleterious roles depending on the patient's sex, the severity of the underlying disease, and the nature of precipitating factors. Moreover, obesity, alcohol consumption, and active smoking, as well as social determinants of liver diseases leading to sex-related inequalities, may interact strongly with hormone-related mechanisms of liver damage. Drug-induced liver injury, viral hepatitis, and metabolic liver diseases are influenced by the status of sex hormones. Available data on the roles of sex hormones and gender differences in liver tumor occurrence and clinical outcomes are conflicting. Here, we critically review the main gender-based differences in the molecular mechanisms associated with liver carcinogenesis and the prevalence, prognosis, and treatment of primary and metastatic liver tumors.

Safe pregnancy after liver transplantation: Evidence from a multicenter Italian collaborative study.

BACKGROUND: Women who have undergone liver transplantation (LT) enjoy better health, and possibility of childbearing. However, maternal and graft risks, optimal immunosuppression, and fetal outcome is still to clarify. AIM: Aim of the study was to assess outcomes of pregnancy after LT at national level. METHODS: In 2019, under the auspices of the Permanent Transplant Committee of the Italian Association for the Study of the Liver, a multicenter survey including 14 Italian LT-centers was conducted aiming at evaluating the outcomes of recipients and newborns, and graft injury/function parameters during pregnancy in LT-recipients. RESULTS: Sixty-two pregnancies occurred in 60 LT-recipients between 1990 and 2018. Median age at the time of pregnancy was 31-years and median time from transplantation to conception was 8-years. During pregnancy, 4 recipients experienced maternal complications with hospital admission. Live-birth-rate was 100%. Prematurity occurred in 25/62 newborns, and 8/62 newborns had low-birth-weight. Cyclosporine was used in 16 and Tacrolimus in 37 pregnancies, with no different maternal or newborn outcomes. Low-birth-weight was correlated to high values of AST, ALT and GGT. CONCLUSION: Pregnancy after LT has good outcome; however, maternal complications and prematurity may occur. Compliance with the immunosuppression is fundamental to ensure the stability of graft function and prevent graft-deterioration.

Early Introduction of Subcutaneous Hepatitis B Immunoglobulin Following Liver Transplantation for Hepatitis B Virus Infection: A Prospective, Multicenter Study.

BACKGROUND: Subcutaneous administration of hepatitis B immunoglobulin (HBIg) is effective in preventing hepatitis B virus (HBV) recurrence after liver transplantation, but early conversion to subcutaneous administration is undocumented. METHODS: In a prospective study, patients transplanted for terminal liver disease due to HBV infection who were HBV DNA-negative at transplant were switched by week 3 posttransplantation from intravenous to subcutaneous HBIg (500 or 1000 IU weekly or fortnightly, adjusted according to serum anti-HBs trough level) if they were HBsAg- and HBV-DNA negative at time of switch. All patients concomitantly received nucleos(t)ide analogue antiviral therapy. Primary endpoint was failure rate by month 6, defined as serum anti-HBs of 100 IU/L or less or HBV reinfection despite serum anti-HBs greater than 100 IU/L. RESULTS: Of 49 patients treated, 47 (95.9%) continued treatment until month 6. All patients achieved administration by a caregiver or self-injection by week 14. No treatment failures occurred. Mean anti-HBs declined progressively to month 6, plateauing at a protective titer of approximately 290 IU/L. All patients tested for HBV DNA remained negative (45/45). Only 1 adverse event (mild injection site hematoma) was assessed as treatment-related. CONCLUSIONS: Introduction of subcutaneous HBIg administration by week 3 posttransplantation, combined with HBV virostatic prophylaxis, is effective and convenient for preventing HBV recurrence.

[Clinical pattern of celiac disease in a population residing in North Sardinia (Italy)]. / Quadro clinico della malattia celiaca in una popolazione residente nel Nord Sardegna.

Celiac disease (CD) was first described by Aretaeus from Cappadocia in II century after C. The impressive clinical picture of a patient with life-threatening diarrhea, malabsorption, weight loss, neurologic disorders and osteopenia is now often replaced by the mostly atypical symptoms or an asymptomatic presentation. When unrecognized and untreated, the celiac disease is associated with increased mortality. In order to collect information on the clinical presentation of celiac disease in North Sardinia, Italy, data on 287 patients with biopsy examination-proven celiac disease were obtained. Women predominated (87%). Overall 78,2%, 53,2% and 44,7% of patients showed classical, subclinical/silent or atypical, and no gastrointestinal features of celiac disease, respectively. Anemia was the main mode of presentation, occurring in 53% of patients. Diarrhea was less frequent (41,5%), although never severe. In conclusion, in North Sardinia a significant proportion of patients with CD are seen more commonly with non-diarrheal presentations than those with diarrhea. To recognize atypical symptoms could be the most important step in the diagnosis and further treatment.

Evidence for preferences of Italian patients for physician attire.

BACKGROUND: The relationship between patient and physician is a complex interaction that includes multiple factors. The objective of this study was to explore Italian patients' preferences regarding physician appearance. METHODS: A questionnaire was developed to survey patients in different medical and surgical settings; each subject was asked to choose one picture of either a male or female physician from a selection of different attires (professional, casual, surgical scrubs, trendy, and careless). Patients were also surveyed about issues such as the presence of a name tag, hair length, trousers on women, amount of makeup, presence of tattoos, and body piercing. Statistical analysis was performed using a Chi-square test. RESULTS: A total of 765 questionnaires (534 completed from patients waiting for an internal medicine visit and 231 for other subspecialties) were completed. The majority (45%) of patients preferred the gastroenterologist to wear a surgical scrub with a white coat. For the other specialists, patients accepted either scrubs or formal dress under a white coat (P ≤ 0.05), with a name tag. Trendy attire was preferred by nine patients (1.1%). The entire sample judged it inappropriate for clinicians to have long hair, visible tattoos, body piercing, and, for women, to wear trousers and use excessive makeup. CONCLUSION: This is the first study conducted in Italy regarding physician attire. As in other Western countries, Italian patients favor physicians in professional attire with a white coat. Wearing professional dress is part of "etiquette based medicine" and may favorably influence clinician-patient relationships and patient compliance.

Twice-a-day bismuth-containing quadruple therapy for Helicobacter pylori eradication: a randomized trial of 10 and 14 days.

BACKGROUND: Bismuth-containing quadruple therapy given twice a day for 14 days has been shown to be an excellent first-line H. pylori eradication therapy. AIM: To compare the efficacy and tolerability of twice-a-day bismuth-containing quadruple H. pylori eradication therapy for 10 versus 14 days in a noninferiority trial. METHODS: Dyspeptic patients with H. pylori infection and naïve to H. pylori treatment were randomly assigned to: pantoprazole 20 mg, tetracycline 500 mg, metronidazole 500 mg, and bismuth subcitrate caplets 240 mg given b.i.d. (with the midday and evening meals) for 10 or 14 days. Eradication was defined by negative UBT and/or histology 4-6 weeks posttherapy. Efficacy and side effects were determined. RESULTS: A total of 417 patients were randomized (153 men, 264 women; median age 52). Per protocol (PP) treatment success with 14 and 10 days was essentially identical [i.e., 96% (95% CI: 92-98) vs 95% (95% CI: 91-98) for 14 days versus 10 days, respectively. Results with intention-to-treat (ITT) analysis were also similar (92% (95% CI, 87-95) vs 92% (95% CI, 88-96)) for 14 and 10 days, respectively. Compliance was excellent in both groups. Side effects were generally mild and similar between groups. Fatigue, discomfort, and vomiting were more common in those in the 14-day group. The 10-day regimen costs € 17.65 (ie, approximately 25%) less than the 14-day regimen. CONCLUSIONS: Bismuth-containing quadruple therapy remained highly effective (i.e., ≥95% PP and >90% ITT) despite reducing the duration from 14 to 10 days.