Changing trends in the etiology of liver transplantation in Turkiye: A multicenter study.

Background and Aim: This study aimed to identify the indications for liver transplantation (LT) based on underlying etiology and to characterize the patients who underwent LT. Materials and Methods: We conducted a multicenter cross-sectional observational study across 11 tertiary centers in Turkiye from 2010 to 2020. The study included 5,080 adult patients. Results: The mean age of patients was 50.3±15.2 years, with a predominance of female patients (70%). Chronic viral hepatitis (46%) was the leading etiological factor, with Hepatitis B virus infection at 35%, followed by cryptogenic cirrhosis (24%), Hepatitis C virus infection (8%), and alcohol-related liver disease (ALD) (6%). Post-2015, there was a significant increase in both the number of liver transplants and the proportion of living donor liver transplants (p<0.001). A comparative analysis of patient characteristics before and after 2015 showed a significant decline in viral hepatitis-related LT (p<0.001), whereas fatty liver disease-related LT significantly increased (p<0.001). Conclusion: Chronic viral hepatitis continues to be the primary indication for LT in Turkiye. However, the proportions of non-alcoholic fatty liver disease (NAFLD) and ALD-related LT have seen an upward trend over the years.

Kidney and liver fat accumulation: from imaging to clinical consequences.

BACKGROUND: Recent studies indicate that accumulation of adipose tissue in various organs such as liver and kidney may contribute to the pathophysiology of metabolic syndrome. We aim to investigate the association between kidney and liver adipose tissue accumulation, assessed by the magnetic resonance imaging (MRI) proton density fat fraction technique, along with its relation to clinical and biochemical parameters. METHODS: We included 51 volunteers with phenotypical features of metabolic syndrome (mean age = 34 years, mean body-mass index = 26.4 kg/m2) in our study in which liver and kidney adipose tissue accumulation was assessed via MRI-proton density fat fraction along with multiple other clinical and biochemical parameters such as estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio, serum lipid profile, liver function tests and body-mass index (BMI). RESULTS: Our results from the univariate linear regression analysis indicate that both the kidney and liver scores were positively correlated with markers such as BMI, urine albumin-to-creatinine ratio, triglycerides (p < 0.001) and negatively correlated with eGFR (p < 0.05). In multivariate analysis, urine albumin-to-creatinine ratio (p < 0.05), triglycerides (p < 0.01), eGFR (p < 0.05) and BMI (p < 0.001) were found to be independently associated with kidney and liver fat accumulation, respectively (R2 = 0.64; R2 = 0.89). There was also a positive correlation between kidney and liver fat accumulation. CONCLUSION: We have found a significant association between adipose tissue accumulation in liver and kidney and the parameters of metabolic syndrome. Moreover, the presence of a strong association between kidney and liver fat accumulation and kidney function parameters such as urine albumin-to-creatinine ratio and eGFR may be an indicator of the clinical significance of parenchymal fat accumulation.

TASL Practice Guidance on the Clinical Assessment and Management of Patients with Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease and is significantly associated with obesity, insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease. NAFLD has become the most prevalent chronic liver disease in Western countries, and the proportion of NAFLD-related cirrhosis among patients on liver transplantation waiting lists has increased. In light of the accumulated data about NAFLD, and to provide a common approach with multi-disciplines dealing with the subject, it has become necessary to create new guidance for diagnosing and treating NAFLD. This guidance was prepared following an interdisciplinary study under the leadership of the Turkish Association for the Study of the Liver (TASL), Fatty Liver Special Interest Group. This new TASL Guidance is a practical application guide on NAFLD and was prepared to standardize the clinical approach to diagnosing and treating NAFLD patients. This guidance reflects many advances in the field of NAFLD. The proposals in this guidance are meant to aid decision-making in clinical practice. The guidance is primarily intended for gastroenterology, endocrinology, metabolism diseases, cardiology, internal medicine, pediatric specialists, and family medicine specialists.

The efficacy and tolerability of glecaprevir/pibrentasvir treatment in a real-world chronic hepatitis C patients cohort.

Background and Aim: The aims of the present study were to evaluate the real-life efficacy and tolerability of glecaprevir (GLE)/pibrentasvir (PIB) in the treatment of patients with chronic hepatitis C (CHC). Materials and Methods: Between May 2019 and May 2022, 686 patients with CHC, treated with GLE/PIB combination from 21 participating centers in Turkiye, were enrolled in the study. Results: All patients were Caucasian, and their median age was 56 years. At the start of GLE/PIB treatment, the median serum Hepatitis C virus RNA and serum alanine amino transaminase (ALT) levels were 6.74 log10 IU/mL and 47 U/L, respectively. Fifty-three percent of the patients were infected with genotype 1b, followed by genotype 3 (17%). Diabetes was the more common concomitant disease. The sustained virological response (SVR12) was 91.4% with intent-to-treat analysis and 98.5% with per protocol analysis. The SVR12 rates were statistically significant differences between the patients who were i.v. drug users and non-user (88.0% vs. 98.8%, p=0.025). From the baseline to SVR12, the serum ALT levels and Model for End-Stage Liver Disease score were significantly improved (p<0.001 and p=0.014, respectively). No severe adverse effect was observed. Conclusion: GLE/PIB is an effective and tolerable treatment in patients with CHC.

Complications of e-PTFE Grafts in LDLT; Evaluation of Case Series.

BACKGROUND: The expanded polytetrafluoroethylene (ePTFE) grafts are used to drain anterior sector veins during the living donor liver transplantation procedure. We aimed to analyze the potentially life-threatening complications, such as the infection and migration of ePTFE grafts. METHODS: A total of 1264 liver transplantations (LTs) were performed for 1097 adult and 167 pediatric liver failure cases. In total, 1169 living and 95 cadaveric liver transplantation procedures were performed between 2011 and 2021. Right liver transplantation was performed in 1016 cases, including 1002 living donors and 14 cadaveric split right livers. Cadaveric LT was performed in 81 cases. RESULTS: For 1002 right living liver grafts, 905 vascular grafts were used during the backtable for anterior sector outflow venoplasty. The most commonly drained segments were 5 and 8 (472 cases); there were isolated (5 or 8) and multiple drained segments. Vascular graft migration was described in 7 of 905 (0.77%) patients. CONCLUSIONS: Although complication rates regarding ePTFE grafts are low, there are serious life-threatening causes of morbidity and mortality. We recommend cushioning the vascular graft with the omentum, which is effective in preventing graft migration.

Graft versus host disease after liver transplantation: A case report.

Graft Versus Host Disease (GVHD) is a severe immunological-clinicopathological condition mediated by healthy T-lymphocytes in donor tissue against the immunosuppressed host tissue and rarely seen after solid organ transplantation (SOT). A 72-year old male patient underwent cadaveric liver transplantation. On day 34 of the postoperative follow-up, the patient developed fever, generalized skin rash and hemorrhagic lesions in the oropharynx. Skin biopsy was consistent with GVHD. Despite high-dose corticosteroid treatment, he died on postoperative day 51. Although it is seen rarely after liver transplantation, GVHD is an important clinical entity for which early diagnosis is critical due to its high rates of mortality.

Baseline characteristics associated with survival in patients with hepatocellular carcinoma.

Background and Aim: Hepatocellular carcinoma (HCC) is one of the most common and most lethal cancers worldwide. The objective of this study was to investigate the relationship between basal parameters and survival characteristics in patients with HCC. Materials and Methods: The records of 1447 HCC patients of a tertiary center during the period 2000-2017 were screened retrospectively. The demographic details; basal clinical, laboratory, and radiological characteristics; treatments; and survival time were recorded and prognostic scores were calculated. Results: A total of 788 patients with HCC (male/female: 623/165; mean age: 60.5±10.9 years) were included in the study. The median length of survival was 26.3 months (95% confidence interval [CI], 22.3-30.4 months). The 5-year survival rate was 28.1%. The number and diameter of the tumors; platelet count; platelet-to-lymphocyte ratio; level of aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase; portal and hepatic vein involvement; and an alpha-fetoprotein level of <9.6 ng/mL were found to be independently related to survival. Conclusion: The positive predictive value of the prognostic index derived from independent survival-related parameters for 5- and 10-year survival or overall survival was approximately 86%. Integration of this prognostic index to the criteria used in making treatment decisions for patients with HCC should be considered.

A single-center experience: Liver biopsy results during a year.

Background and Aim: Liver biopsy is the gold standard method for the diagnosis and treatment of liver diseases. In this study, we aimed to evaluate the results of liver biopsies performed in a year in our clinic. In addition, we also aimed if these liver biopsies could reveal the etiology of liver disease in patients with elevations of transaminases or/and alkaline phosphatase levels or liver masses. Materials and Methods: Patients who had liver biopsies for persistently elevated transaminases or/and alkaline phosphatase levels, protocol biopsies after liver transplantation, or liver masses in our hepatology clinic between 2011 and 2012 were included in the study. Liver biopsy decisions were made by experts during the hepatology council. Liver biopsies were previously performed using classical percutaneous liver biopsy or ultrasonography-guided Sonocan® liver biopsy sets. The pathology results of liver biopsies and clinical data of the matching patients were obtained from the liver biopsy record archives and patient files, respectively. Results: Totally, 479 liver biopsy results (male=252, 52.6%, mean age 49±14.5 years) were evaluated in the study. Of these patients, 432 (male=228) underwent percutaneous liver biopsy and 47 (male=24) underwent Sonocan® needle biopsy. The most common histopathologic diagnoses in the percutaneous liver biopsy group were chronic hepatitis B (n=127, 29.4%), normal histopathological findings (n=50, 11.6% and 32 of them were protocol biopsies after liver transplantation), and nonalcoholic steatohepatitis (NASH, n=41, 9.5%). The most common histopathologic diagnoses in the Sonocan® group were 25 liver metastasis out of 29 liver tumors (n=25, 53.2% of all) chronic hepatitis B (n=5, 10.6%), and NASH (n=3, 6.4%). Conclusion: In this study, diversity in liver biopsy results indicates the importance of histopathological evaluation. The most prevalent pathology in the liver biopsies was chronic hepatitis B, which is the most common chronic liver disease in Turkey. The metastatic liver tumor was the most common among the liver masses.

Liver transplantation in hepatic myelopathy.

Hepatic myelopathy (HMy) is a rare neurological complication of liver cirrhosis that involves spastic paraplegia caused by lateral cord demyelination especially due to the accumulation of some metabolites such as ammonia and manganese. We report a young adult woman presenting with spasticity and paraparesis in extremities after intrahepatic portosystemic shunting (TIPS) application and underwent deceased liver transplantation (LT). A 39-year-old woman underwent deceased LT because of cryptogenic liver cirrhosis. She underwent a TIPS procedure 5 years ago. After that, hepatic encephalopathy and spasticity appeared. She was on the waiting list for 3 years. Neurological findings after LT significantly decreased, but did not return to normal. After the emergence of neurological findings, the earlier LT can provide improvement in neurological findings.

Liver injury after SARS-CoV-2 vaccination: Features of immune-mediated hepatitis, role of corticosteroid therapy and outcome.

BACKGROUND AND AIMS: A few case reports of autoimmune hepatitis-like liver injury have been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We evaluated clinical features, treatment response and outcomes of liver injury following SARS-CoV-2 vaccination in a large case series. APPROACH AND RESULTS: We collected data from cases in 18 countries. The type of liver injury was assessed with the R-value. The study population was categorized according to features of immune-mediated hepatitis (positive autoantibodies and elevated immunoglobulin G levels) and corticosteroid therapy for the liver injury. We identified 87 patients (63%, female), median age 48 (range: 18-79) years at presentation. Liver injury was diagnosed a median 15 (range: 3-65) days after vaccination. Fifty-one cases (59%) were attributed to the Pfizer-BioNTech (BNT162b2) vaccine, 20 (23%) cases to the Oxford-AstraZeneca (ChAdOX1 nCoV-19) vaccine and 16 (18%) cases to the Moderna (mRNA-1273) vaccine. The liver injury was predominantly hepatocellular (84%) and 57% of patients showed features of immune-mediated hepatitis. Corticosteroids were given to 46 (53%) patients, more often for grade 3-4 liver injury than for grade 1-2 liver injury (88.9% vs. 43.5%, p = 0.001) and more often for patients with than without immune-mediated hepatitis (71.1% vs. 38.2%, p = 0.003). All patients showed resolution of liver injury except for one man (1.1%) who developed liver failure and underwent liver transplantation. Steroid therapy was withdrawn during the observation period in 12 (26%) patients after complete biochemical resolution. None had a relapse during follow-up. CONCLUSIONS: SARS-CoV-2 vaccination can be associated with liver injury. Corticosteroid therapy may be beneficial in those with immune-mediated features or severe hepatitis. Outcome was generally favorable, but vaccine-associated liver injury led to fulminant liver failure in one patient.

Risk factors and outcomes associated with recurrent autoimmune hepatitis following liver transplantation.

BACKGROUND & AIMS: Autoimmune hepatitis can recur after liver transplantation (LT), though the impact of recurrence on patient and graft survival has not been well characterized. We evaluated a large, international, multicenter cohort to identify the probability and risk factors associated with recurrent AIH and the association between recurrent disease and patient and graft survival. METHODS: We included 736 patients (77% female, mean age 42±1 years) with AIH who underwent LT from January 1987 through June 2020, among 33 centers in North America, South America, Europe and Asia. Clinical data before and after LT, biochemical data within the first 12 months after LT, and immunosuppression after LT were analyzed to identify patients at higher risk of AIH recurrence based on histological diagnosis. RESULTS: AIH recurred in 20% of patients after 5 years and 31% after 10 years. Age at LT ≤42 years (hazard ratio [HR] 3.15; 95% CI 1.22-8.16; p = 0.02), use of mycophenolate mofetil post-LT (HR 3.06; 95% CI 1.39-6.73; p = 0.005), donor and recipient sex mismatch (HR 2.57; 95% CI 1.39-4.76; p = 0.003) and high IgG pre-LT (HR 1.04; 95% CI 1.01-1.06; p = 0.004) were associated with higher risk of AIH recurrence after adjusting for other confounders. In multivariate Cox regression, recurrent AIH (as a time-dependent covariate) was significantly associated with graft loss (HR 10.79, 95% CI 5.37-21.66, p <0.001) and death (HR 2.53, 95% CI 1.48-4.33, p = 0.001). CONCLUSION: Recurrence of AIH following transplant is frequent and is associated with younger age at LT, use of mycophenolate mofetil post-LT, sex mismatch and high IgG pre-LT. We demonstrate an association between disease recurrence and impaired graft and overall survival in patients with AIH, highlighting the importance of ongoing efforts to better characterize, prevent and treat recurrent AIH. LAY SUMMARY: Recurrent autoimmune hepatitis following liver transplant is frequent and is associated with some recipient features and the type of immunosuppressive medications use. Recurrent autoimmune hepatitis negatively affects outcomes after liver transplantation. Thus, improved measures are required to prevent and treat this condition.

Multiomics Analysis Reveals the Impact of Microbiota on Host Metabolism in Hepatic Steatosis.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a complex disease involving alterations in multiple biological processes regulated by the interactions between obesity, genetic background, and environmental factors including the microbiome. To decipher hepatic steatosis (HS) pathogenesis by excluding critical confounding factors including genetic variants and diabetes, 56 heterogenous MAFLD patients are characterized by generating multiomics data including oral and gut metagenomics as well as plasma metabolomics and inflammatory proteomics data. The dysbiosis in the oral and gut microbiome is explored and the host-microbiome interactions based on global metabolic and inflammatory processes are revealed. These multiomics data are integrated using the biological network and HS's key features are identified using multiomics data. HS is finally predicted using these key features and findings are validated in a follow-up cohort, where 22 subjects with varying degree of HS are characterized.

Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis.

BACKGROUND: We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH). PATIENTS AND METHODS: Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication. The clinical courses of COVID-19 were classified as (i)-no hospitalization, (ii)-hospitalization without oxygen supplementation, (iii)-hospitalization with oxygen supplementation by nasal cannula or mask, (iv)-intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v)-ICU admission with invasive mechanical ventilation or (vi)-death and analysed using ordinal logistic regression. RESULTS: We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17-85) years. At the onset of COVID-19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12-25.89) and thiopurines (aOR 4.78, 95% CI 1.33-23.50) for AIH was associated with worse COVID-19 severity, after adjusting for age-sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76-20.56) and tacrolimus (aOR 4.09, 95% CI 0.69-27.00) were also associated with more severe COVID-19 courses in a smaller subset of treated patients. CONCLUSION: Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID-19 was significantly associated with COVID-19 severity in patients with AIH.

Standard immunosuppressive treatment reduces regulatory B cells in children with autoimmune liver disease.

Introduction: Autoimmune hepatitis (AIH) is a chronic liver disease caused by a perturbed immune system. The scarcity of short- and long-term immune monitoring of AIH hampered us to comprehend the interaction between immunosuppressive medication and immune homeostasis. Methods and patients: We recruited children with AIH at the time of diagnosis and at the 1st, 3rd, 6th, 12th, 18th, and 24th months of immunosuppression (IS). We also enrolled children with AIH being on IS for >2 years. Children with drug-induced liver injury (DILI), and those receiving tacrolimus after liver transplantation (LT), were enrolled as disease/IS control subjects. Healthy children (HC) were also recruited. Peripheral blood mononuclear cells (PBMCs) were isolated from all participants. Healthy liver tissue from adult donors and from livers without inflammation were obtained from children with hepatoblastoma. By using flow cytometry, we performed multi-parametric immune profiling of PBMCs and intrahepatic lymphocytes. Additionally, after IS with prednisolone, tacrolimus, rapamycin, or 6-mercaptopurine, we carried out an in vitro cytokine stimulation assay. Finally, a Lifecodes SSO typing kit was used to type HLA-DRB1 and Luminex was used to analyze the results. Results: Untreated AIH patients had lower total CD8 T-cell frequencies than HC, but these cells were more naïve. While the percentage of naïve regulatory T cells (Tregs) (CD4+FOXP3lowCD45RA+) and regulatory B cells (Bregs, CD20+CD24+CD38+) was similar, AIH patients had fewer activated Tregs (CD4+FOXP3highCD45RA - ) compared to HC. Mucosal-associated-invariant-T-cells (MAIT) were also lower in these patients. Following the initiation of IS, the immune profiles demonstrated fluctuations. Bregs frequency decreased substantially at 1 month and did not recover anymore. Additionally, the frequency of intrahepatic Bregs in treated AIH patients was lower, compared to control livers, DILI, and LT patients. Following in vitro IS drugs incubation, only the frequency of IL-10-producing total B-cells increased with tacrolimus and 6MP. Lastly, 70% of AIH patients possessed HLA-DR11, whereas HLA-DR03/DR07/DR13 was present in only some patients. Conclusion: HLA-DR11 was prominent in our AIH cohort. Activated Tregs and MAIT cell frequencies were lower before IS. Importantly, we discovered a previously unrecognized and long-lasting Bregs scarcity in AIH patients after IS. Tacrolimus and 6MP increased IL-10+ B-cells in vitro.

Combined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients.

Nonalcoholic fatty liver disease (NAFLD) refers to excess fat accumulation in the liver. In animal experiments and human kinetic study, we found that administration of combined metabolic activators (CMAs) promotes the oxidation of fat, attenuates the resulting oxidative stress, activates mitochondria, and eventually removes excess fat from the liver. Here, we tested the safety and efficacy of CMA in NAFLD patients in a placebo-controlled 10-week study. We found that CMA significantly decreased hepatic steatosis and levels of aspartate aminotransferase, alanine aminotransferase, uric acid, and creatinine, whereas found no differences on these variables in the placebo group after adjustment for weight loss. By integrating clinical data with plasma metabolomics and inflammatory proteomics as well as oral and gut metagenomic data, we revealed the underlying molecular mechanisms associated with the reduced hepatic fat and inflammation in NAFLD patients and identified the key players involved in the host-microbiome interactions. In conclusion, we showed that CMA can be used to develop a pharmacological treatment strategy in NAFLD patients.

Recommendations for Hepatitis B Immunoglobulin and Antiviral Prophylaxis Against Hepatitis B Recurrence After Liver Transplantation.

The combination of hepatitis B immunoglobulin and potent nucleos(t)ide analogs after liver transplantation is considered as the standard of care for prophylaxis against hepatitis B virus recurrence. However, the recommended doses, route of administration, and duration of HBIG administration remain unclear. Moreover, hepatitis B immunoglobulin-free prophylaxis with potent nucleos(t)ide analogs has shown promising disease outcomes in preventing hepatitis B virus recurrence. The current recommendations, produced by the Turkish Association for the Study of the Liver, Acute Liver Failure and Liver Transplantation Special Interest Group, suggest a reduced need for hepatitis B immunoglobulin administration with effective long-term suppression of hepatitis B virus replication using potent nucleos(t) ide analogs after liver transplantation.

Determination of Turkish norms of psychometric tests for diagnosing minimal hepatic encephalopathy and proposal of a high sensitive screening test battery.

BACKGROUND: Psychometric hepatic encephalopathy score (PHES) needs local standardization. AIMS: This study aimed at standardizing PHES for Turkish patients and compare them with German norms; to determine minimal hepatic encephalopathy (mHE) prevalence with two different methods [PHES battery and Critical Flicker Frequency (CFF)] and to assess whether sub-tests of the battery can be used for screening for mHE. METHODS: Healthy volunteers (n = 816; 400 male) and cirrhotics (n = 124; 58 male) were included. For mHE diagnosis PHES score threshold was set at ≤ - 5 points and that of CFF at < 39 Hz. For comparing German and Turkish norms, datasets were combined. Multiple backward procedure was applied to assess effects of age, sex and education on single tests of the battery. Receiver operating characteristic (ROC) curves were created for assessing diagnostic capabilities of subtests of the battery. RESULTS: PHES norms for Turks were developed. MHE prevalence in compensated cirrhotics was 29.8% and 27.4% with PHES and CFF tests, respectively, with low compatibility (kappa coefficient 0.389); mHE prevalence decreased to 16% when both tests were combined. Turks performed worse vs Germans in the digit symbol (DS) and serial dotting (SD) subtests but performed better in other subtests. In ROC analyzes of subtests, the combination of DS + SD tests achieved an AUROC of 0.974 versus PHES. CONCLUSIONS: Use of two methods for diagnosing mHE is important for research purposes. From a clinical perspective, sensitivity with acceptable specificity may suffice for screening instruments for mHE. Combined use of DS and SD subtests of the PHES battery appears suitable for this purpose.

Course of vitamin D levels before and after liver transplantation in pediatric patients.

BACKGROUND: 25-hydroxy VD insufficiency is known in children undergoing LT but the serial post-transplant VD course and supplementation modalities in the peri-transplant period are lacking. We aimed to determine the pre-VD status and the post-transplant VD status course following VD supplementation and to elucidate its relationship with post-transplant outcome parameters such as infection and survival. METHODS: Pre- and post-VD levels were monitored in parallel with interventions to adjust VD levels in LT patients. VD status was categorized as circulating levels <30-21 ng/ml (insufficiency), 20-10 ng/ml (deficiency), and <10 ng/ml (severe deficiency). Patients received stoss (300000IU) VD3 within the pretransplant period if serum levels were <20 ng/ml. RESULTS: 135 transplanted children were included. The age at LT was 22 months (IQR: 8-60). The pretransplant median VD level was 14 ng/ml. Despite stoss dose, post-transplant median VD level was 1.8 ng/ml (day one), 4 ng/ml (week one), 19 ng/ml (month one), 33 ng/ml (month three), 38 ng/ml (months 6-12), and 40 ng/ml (month 24). After 6 months, VD status reached >30 ng/ml in 98% of patients. Only at pre-LT, higher infection rate (18.7%) in the severe VD deficiency group was observed compared to the VD deficiency group (2.9%, p = .04). Survival was not affected by serum VD levels. CONCLUSION: VD levels fell substantially after LT but are rectifiable by stoss dose, which was well tolerated. Only the infection rate was associated with the VD status.

Outcome of COVID-19 in Patients With Autoimmune Hepatitis: An International Multicenter Study.

BACKGROUND AND AIMS: Data regarding outcome of COVID-19 in patients with autoimmune hepatitis (AIH) are lacking. APPROACH AND RESULTS: We performed a retrospective study on patients with AIH and COVID-19 from 34 centers in Europe and the Americas. We analyzed factors associated with severe COVID-19 outcomes, defined as the need for mechanical ventilation, intensive care admission, and/or death. The outcomes of patients with AIH were compared to a propensity score-matched cohort of patients without AIH but with chronic liver diseases (CLD) and COVID-19. The frequency and clinical significance of new-onset liver injury (alanine aminotransferase > 2 × the upper limit of normal) during COVID-19 was also evaluated. We included 110 patients with AIH (80% female) with a median age of 49 (range, 18-85) years at COVID-19 diagnosis. New-onset liver injury was observed in 37.1% (33/89) of the patients. Use of antivirals was associated with liver injury (P = 0.041; OR, 3.36; 95% CI, 1.05-10.78), while continued immunosuppression during COVID-19 was associated with a lower rate of liver injury (P = 0.009; OR, 0.26; 95% CI, 0.09-0.71). The rates of severe COVID-19 (15.5% versus 20.2%, P = 0.231) and all-cause mortality (10% versus 11.5%, P = 0.852) were not different between AIH and non-AIH CLD. Cirrhosis was an independent predictor of severe COVID-19 in patients with AIH (P < 0.001; OR, 17.46; 95% CI, 4.22-72.13). Continuation of immunosuppression or presence of liver injury during COVID-19 was not associated with severe COVID-19. CONCLUSIONS: This international, multicenter study reveals that patients with AIH were not at risk for worse outcomes with COVID-19 than other causes of CLD. Cirrhosis was the strongest predictor for severe COVID-19 in patients with AIH. Maintenance of immunosuppression during COVID-19 was not associated with increased risk for severe COVID-19 but did lower the risk for new-onset liver injury during COVID-19.