Longitudinal Evaluation of Individuals With Severe Alpha-1 Antitrypsin Deficiency (Pi∗ZZ Genotype).

Background & Aims: Homozygous Pi∗Z mutation in alpha-1 antitrypsin (Pi∗ZZ genotype) predisposes to pulmonary loss-of-function and hepatic gain-of-function injury. To facilitate selection into clinical trials typically targeting only 1 organ, we systematically evaluated an international, multicenter, longitudinal, Pi∗ZZ cohort to uncover natural disease course and surrogates for future liver- and lung-related endpoints.

Methods: Cohort 1 recruited 737 Pi∗ZZ individuals from 25 different centers without known liver comorbidities who received a baseline clinical and laboratory assessment as well as liver stiffness measurement (LSM).

Long-term maternal outcomes of pregnancy after orthotopic liver transplantation in the Netherlands: A retrospective multicenter cohort study.

Pregnancy after orthotopic liver transplantation (OLT) puts the mother, child, and transplanted organ at risk. Little is known about long-term outcomes. We performed a nationwide retrospective cohort study to evaluate short-term and long-term outcomes of post-OLT pregnancies.

Incidence and prevalence of primary biliary cholangitis in the Netherlands - A nationwide cohort study.

Background & Aims: Although primary biliary cholangitis (PBC) is considered a rare disorder, accurate determination of its incidence and prevalence remains challenging due to limited comprehensive population-based registries. We aimed to assess the incidence and prevalence of PBC in the Netherlands over time through the nationwide Dutch PBC Cohort Study (DPCS).

Methods: DPCS retrospectively included every identifiable patient with PBC in the Netherlands from 1990 onwards in all 71 Dutch hospitals.

A deprescribing programme aimed to optimise blood glucose-lowering medication in older people with type 2 diabetes mellitus, the OMED2-study: the study protocol for a randomised controlled trial.

Background: Older patients with type 2 diabetes mellitus (T2D) have an increased risk of hypoglycaemic episodes when using sulphonylureas or insulin. In the Netherlands, guidelines exist for reducing glucose-lowering medication in older patients. However, evidence is lacking that a medication reduction in older patients can be safely pursued.

Diagnostic criteria and long-term outcomes in AIH-PBC variant syndrome under combination therapy.

Background & Aims: Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) can co-exist in AIH-PBC, requiring combined treatment with immunosuppression and ursodeoxycholic acid (UDCA). The Paris criteria are commonly used to identify these patients; however, the optimal diagnostic criteria are unknown. We aimed to evaluate the use and clinical relevance of both Paris and Zhang criteria.

Fazirsiran for Adults With Alpha-1 Antitrypsin Deficiency Liver Disease: A Phase 2 Placebo Controlled Trial (SEQUOIA).

Background & Aims: Homozygous ZZ alpha-1 antitrypsin (AAT) deficiency produces mutant AAT (Z-AAT) proteins in hepatocytes, leading to progressive liver fibrosis. We evaluated the safety and efficacy of an investigational RNA interference therapeutic, fazirsiran, that degrades Z-AAT messenger RNA, reducing deleterious protein synthesis.

Methods: This ongoing, phase 2 study randomized 40 patients to subcutaneous placebo or fazirsiran 25, 100, or 200 mg.

Autoimmune hepatitis displays distinctively high multi-antennary sialylation on plasma N-glycans compared to other liver diseases.

Background: Changes in plasma protein glycosylation are known to functionally affect proteins and to associate with liver diseases, including cirrhosis and hepatocellular carcinoma. Autoimmune hepatitis (AIH) is a liver disease characterized by liver inflammation and raised serum levels of IgG, and is difficult to distinguish from other liver diseases. The aim of this study was to examine plasma and IgG-specific N-glycosylation in AIH and compare it with healthy controls and other liver diseases.

Bacterial Infections After Liver Transplantation and the Role of Oral Selective Digestive Decontamination: A Retrospective Cohort Study.

Background: Bacterial infections are common after liver transplantation (LT) and cause serious morbidity and mortality. In our center, prolonged selective digestive decontamination (SDD) is the standard of care, which may lead to a reduced number and severity of bacterial infections. The aim of the current study was to investigate bacterial infection rates, the causative pathogens, localization, and the possible influence of SDD within the first year after LT.

Tacrolimus versus mycophenolate for AutoImmune hepatitis patients with incompLete response On first-line therapy (TAILOR study): a study protocol for a phase III, open-label, multicentre, randomised controlled trial.

Background: Autoimmune hepatitis (AIH) is a rare, chronic inflammatory disease of the liver. The treatment goal is reaching complete biochemical response (CR), defined as the normalisation of aspartate and alanine aminotransferases and immunoglobulin gamma. Ongoing AIH activity can lead to fibrosis and (decompensated) cirrhosis.

An open-label randomised-controlled trial of azathioprine vs. mycophenolate mofetil for the induction of remission in treatment-naive autoimmune hepatitis.

Background & Aims: Patients with autoimmune hepatitis (AIH) almost invariably require lifelong immunosuppressive treatment. There is genuine concern about the efficacy and tolerability of the current standard combination therapy of prednisolone and azathioprine. Mycophenolate mofetil (MMF) has emerged as an alternative option.

Survival benefit from liver transplantation for patients with and without hepatocellular carcinoma.

Background & Aims: In the USA, inequal liver transplantation (LT) access exists between patients with and without hepatocellular carcinoma (HCC). Survival benefit considers survival without and with LT and could equalise LT access. We calculated bias-corrected LT survival benefit for patients with(out) HCC who underwent a transplant, based on longitudinal data in a recent United States cohort.

Health-related Quality of Life and Fatigue in Liver Transplant Recipients Receiving Tacrolimus Versus Sirolimus-based Immunosuppression: Results From a Randomized Trial.

Background: The impact of different immunosuppression regimes on the health-related quality of life (HRQoL) and the severity of fatigue in liver transplant recipients is largely unknown. We investigated the impact of a sirolimus-based regimen compared with a tacrolimus (TAC)-based regimen on the HRQoL and the severity of fatigue.

Methods: In this multicenter, open-label, randomized, controlled trial, 196 patients were randomized 90 d after transplantation to (1) once daily normal-dose TAC or (2) once daily combination therapy of low-dose sirolimus and TAC.

Incidence and predictors of hepatocellular carcinoma in patients with autoimmune hepatitis.

Background And Aims: Autoimmune hepatitis (AIH) is a rare chronic liver disease of unknown aetiology; the risk of hepatocellular carcinoma (HCC) remains unclear and risk factors are not well-defined. We aimed to investigate the risk of HCC across a multicentre AIH cohort and to identify predictive factors.

Methods: We performed a retrospective, observational, multicentric study of patients included in the International Autoimmune Hepatitis Group Retrospective Registry.

Prevalence of non-alcoholic fatty liver in the general Dutch population and in groups at increased risk.

Background And Aim: Non-alcoholic fatty liver disease (NAFLD) is defined as a liver fat content ≥5.56%. It is of clinical interest to know the prevalence of NAFLD in people with a combination of metabolic risk factors.

Primary sclerosing cholangitis and other risk factors for post-transplant lymphoproliferative disease after liver transplantation in adults.

Post-transplant lymphoproliferative disease (PTLD) is a rare but serious complication of liver transplantation (LT) with morbidity and mortality. The risk factors for PTLD in adults are ill-defined. This study aimed to assess the risk factors for PTLD after LT in adults.

Antibodies against multiple post-translationally modified proteins aid in diagnosis of autoimmune hepatitis and associate with complete biochemical response to treatment.

Background: (Auto)immune mediated and cholestatic liver disease (AILD) includes autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Especially AIH is characterized by the presence of autoantibodies and elevated serum immunoglobulins. In rheumatoid arthritis, autoantibodies against post-translational modifications (PTMs) such as citrullination (Cit) and carbamylation (CarP) are used as diagnostic and prognostic markers, respectively.

Randomized Trial of Ciclosporin with 2-h Monitoring vs. Tacrolimus with Trough Monitoring in Liver Transplantation: DELTA Study.

Background And Aims: Previous trials comparing cyclosporine and tacrolimus after liver transplantation (LT) showed conflicting results. Most used trough monitoring for cyclosporine (C0), leading to less accurate dosing than with 2-h monitoring (C2). Only one larger trial compared C2 with tacrolimus based on trough level (T0) after LT, with similar treated biopsy-proven acute rejection (tBPAR) and graft loss, while a smaller trial had less tBPAR with C2 compared to T0.