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Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) continues to have a devastating impact across the globe. However, little is known about the disease course in patients with autoimmune hepatitis (AIH). Methods Data for patients with AIH and SARS-CoV-2 infection were combined from three international reporting registries and outcomes were compared to those with chronic liver disease of other aetiology (non-AIH CLD) and to patients without liver disease (non-CLD). Results Between 25th March and 24th October 2020, data were collected for 932 patients with CLD and SARS-CoV-2 infection including 70 with autoimmune hepatitis (AIH). Fifty-eight (83%) of AIH patients were taking one or more immunosuppressive drug. There were no differences in rates of major outcomes between AIH and non-AIH CLD including hospitalization (76% vs 85%; p= 0.06), ICU admission (29% vs. 23%; p=0.240), and death (23% vs. 20%; p=0.643). Factors associated with death within the AIH cohort included age (OR 2.16/10 years; 1.07–3.81), Child-Turcotte-Pugh (CTP) class B (OR 42.48; 4.40–409.53), and CTP-C cirrhosis (OR 69.30; 2.83–1694.50), but not use of immunosuppression. Propensity score matched (PSM) analysis comparing AIH with non-AIH CLD demonstrated no increased risk adverse outcomes including death (+3.2%; -9.2%–15.7%). PSM analysis of AIH versus non-CLD patients (n=769) demonstrated increased risk of hospitalization with AIH (+18.4%; 5.6–31.2%), but equivalent risk of all other outcomes including death (+3.2%; -9.1%–15.6%). Conclusion AIH patients were not at increased risk of adverse outcomes despite immunosuppressive treatment compared to other causes of CLD and to matched cases without liver disease., Graphical abstract, Highlights • This is the largest cohort of patients with autoimmune hepatitis and laboratory proven SARS-COV-2 infection reported to date. • There were no differences in rates of major adverse COVID-19 outcomes including hospitalization, intensive care unit (ICU) admission, and death between AIH patients and those with other aetiologies of liver disease. • When compared to patients without liver disease in propensity score matched analysis, patients with AIH had higher rates of hospitalization but no increased risk of ICU admission or death despite potential reporting of AIH cases with more severe baseline liver disease. • Independent risk factors for death in AIH patients were age and baseline liver disease severity, but not the use of immunosuppression., Lay summary: Little is known about the outcomes of COVID-19 in patients with autoimmune hepatitis (AIH), a rare chronic inflammatory liver disease. This study combines data from three large registries to describe the course of COVID-19 in this patient group. We show that AIH patients do not appear to have an increased risk of death from COVID-19 compared to patients with other forms of liver disease and compared to patients without liver disease, despite the use of medications which suppress the immune system.

Autoimmune hepatitis (AIH) is an inflammatory disorder of the liver with a wide spectrum of disease presentation, from asymptomatic elevations in liver-associated enzymes to acute liver failure. AIH is classically associated with elevated immunoglobulins and autoantibodies, although approximately 20% of patients with features of AIH lack circulating antibodies. Recently, tumour necrosis factor alpha inhibitors have been implicated in several cases of drug-induced AIH which impact treatment regimens for patients with inflammatory bowel disease (IBD). We present a case of infliximab-induced seronegative AIH responding to budesonide therapy with successful alteration of IBD treatment regimen to vedolizumab.

Autoimmune hepatitis (AIH) is a chronic and progressive inflammatory process of the liver, with standard treatments including prednisone, azathioprine, and ultimately liver transplant. While there are many integrative and ayurvedic treatment options that have been shown to be helpful for other liver diseases, there are no studies that have been performed to evaluate these therapies particularly in AIH with cirrhosis. We detail the case of a 55-year-old female with cirrhosis in the setting of AIH placed on a liver transplant list after being treated with conventional therapies. She was started on various nutritional supplements and ayurvedic treatments which resulted in a significant decrease in her Model for End-Stage Liver Disease score, which was sustained at 7 months. This is the first case report to our knowledge detailing an integrative approach to cirrhosis in the setting of AIH showing such an improvement in liver function.

Background and aims Inflammatory bowel diseases (IBD) are chronic conditions that may be accompanied by autoimmune liver disease (AILD), most commonly primary sclerosing cholangitis (PSC). The objective of this study was to evaluate the behaviour of patients with IBD associated with AILD and compare a PSC group with a non-PSC group. Methods Medical records of patients with IBD associated with PSC, autoimmune cholangitis, primary biliary cholangitis, small-duct PSC, autoimmune hepatitis (AIH) and overlapping syndromes were assessed. Results Fifty-four patients were included: 48 (88.9%) had ulcerative colitis and six (11.1%) had Crohn's disease; 35 (64.8%) had PSC and 19 (35.2%) did not have PSC. There was no difference in outcomes (surgical treatment for IBD, liver transplantation or death) between the groups. Time since the diagnosis of IBD was associated with surgical treatment of IBD (p = 0.041; OR: 1.139, 95% CI: 1.006–1.255). Time since the diagnosis of AILD (p = 0.003; OR: 1.259, 95% CI: 1.1–1.396), as well as portal hypertension at diagnosis (p = 0.014; OR: 18.22, 95% CI: 1.815–182.96), were associated with liver transplantation. In addition, previous diagnosis of AIH was associated with de novo IBD (p = 0.012; OR: 7.1, 95% CI: 1.215–42.43). Conclusion Both groups had similar disease behaviour. A longer time since the diagnosis of IBD increased the risk for surgical treatment (13.9%/year). A 25.9%/year increase in liver transplantation was observed after the diagnosis of AILD, which was increased 18.22 times by the presence of portal hypertension. In addition, the diagnosis of AIH was associated with an increase in the number of diagnoses of de novo IBD (7.1).

The entry-inhibitor Bulevirtide (BLV) received conditional approval by EMA in July 2020 for the treatment of adult patients with compensated chronic hepatitis Delta. However, the effectiveness and safety of BLV administered as monotherapy beyond 48 weeks in difficult to treat HDV cirrhotic patients is presently unknown. Here we describe the first patients with HDV-related compensated cirrhosis who were treated with BLV (10 mg/day as a starting dose) for up to three years as compassionate use. Patients were also monitored for HBcrAg and HBV-RNA levels and HDV and HBV specific T-cells markers. In the patient who stopped BLV at week 48 after achieving a virological and biochemical response, the initial virological and biochemical rebound was followed by ALT normalization coupled with low HDV-RNA and HBsAg levels. In the two patients treated continuously for 3 years, virological and biochemical responses were maintained throughout the treatment period even after dose reduction. In a patient with advanced compensated cirrhosis, liver function tests significantly improved, esophageal varices disappeared, and histological/lab features of autoimmune hepatitis resolved. Overall, no safety issues were recorded, as bile salt increase was asymptomatic. While serum HBV-RNA levels remained undetectable in all patients, HBcrAg levels showed a progressive, yet modest decline during long-term BLV-treatment. No HDV-specific Interferon-γ producing T-cells were detected, neither after HDV reactivation (after BLV withdrawn in Patient 1) nor during 3 years of BLV treatment. In conclusion, this report shows that continuous administration of BLV monotherapy for three years provides excellent virological and clinical response in HDV cirrhotic patients who had contraindications to IFN-based therapies. LAY SUMMARY: HDV-RNA levels became undetectable, and ALT normalized in all three patients treated with Bulevirtide (BLV). Virological and biochemical responses were maintained even after dose reduction.- Improvement of liver function tests, regression of esophageal varices and recovery of HDV-related autoimmune disease were documented in the male cirrhotic patient long-term treated with BLV.- An asymptomatic increase of bile acids was the only drug-related clinical adverse event.

Background & Aims Infliximab has been associated with drug-induced liver injury (DILI), particularly drug-induced autoimmune hepatitis (DIAIH). DIAIH is commonly treated with corticosteroids, but there is limited data on the efficacy of corticosteroids in infliximab-induced DILI. Methods Patients were included for assessment if they had been treated with infliximab between 2009-2020 in Iceland and had developed elevated liver tests. Other specific etiologies of liver enzyme elevations were excluded. Patients treated with corticosteroids were compared to patients not receiving corticosteroids. Results A total of 36 patients with infliximab-induced DILI were identified: median age was 46 years (IQR 32-54) and 28 (78%) were female. Type of liver injury was predominantly hepatocellular (64%). Median peak liver enzymes were: alanine aminotransferase (ALT) 393 (328-695) U/L, aspartate aminotransferase 283 (158-564) U/L, alkaline phosphatase 116 (83-205) U/L, and bilirubin (10-20) 13 μmol/L. A total of 25 (69%) were positive for anti-nuclear antibody and/or had elevated IgG. Corticosteroids were initiated in 17 (47%). Median time from onset of liver injury to peak ALT value was longer in patients treated with corticosteroids, 22 (12-59) vs. 0 (0-3) days (p = 0.001). Time from peak ALT to normalization of liver enzymes was 45 days in the corticosteroid group vs. 77 days in others (p = 0.062). Corticosteroids were tapered in all patients, with no cases of relapse during the follow-up period of 1,245 (820-2,698) days. Overall 75% received another biologic, mostly adalimumab, without evidence of liver injury. Conclusion Approximately half of patients with infliximab-induced liver injury had slow improvement in ALT despite cessation of therapy and were treated with corticosteroids. Treatment response was good with prompt resolution of liver test abnormalities. Relapse of liver injury was not observed after tapering of corticosteroids despite prolonged follow-up and no patients developed DILI due to a second biologic. Lay summary A rare side effect of infliximab, a biologic medicine used to treat multiple inflammatory diseases, is liver injury and liver inflammation. Steroid treatment has been used in some patients with liver injury caused by infliximab, but there have been few studies supporting this treatment. In this study of 36 patients with infliximab-induced liver injury, approximately half of patients were treated with steroids and the results suggest that patients receiving steroids recover more quickly.

BACKGROUND: Hyaline globules (HGs) in the cytoplasm of Kupffer cells (KCs) have been appraised for being a typical feature of autoimmune hepatitis (AIH). This study aimed to determine how useful Kupffer cell hyaline globules (KCHGs) are in diagnosing AIH vs. other causes of pediatric chronic liver diseases (PCLDs). MATERIALS AND METHODS: This retrospective study recruited 124 children; 58 with AIH, 50 with chronic hepatitis C virus (HCV) infection, and 16 with Wilson’s disease (WD). Two pathologists retrieved paraffin blocks of liver biopsies and prepared new cut sections for Periodic acid–Schiff–Diastase (PAS-D) stain. They independently examined liver biopsies before starting treatment. Two pediatricians reviewed medical records for demographic, clinical, laboratory, and serological findings. RESULTS: Females represented 48.6% of the studied children with a median age of 5.8 (4.9) years. Pathologists identified KCHGs in 67.24%, 12.5%, and 6.0% of AIH, WD, and HCV affected children respectively, P

In chronic hepatitis, a broad differential diagnosis should be considered to accurately identify the cause(s) of liver injury. Autoimmune liver diseases (autoimmune hepatitis, primary sclerosing cholangitis, overlap syndrome) can occur in the setting of limited symptoms; therefore, a high index of suspicion and appropriate diagnostic workup should be performed. Most children with autoimmune hepatitis achieve sustained remission with medical therapy; however, there are no equivalent therapies for primary sclerosing cholangitis that impact the progression of disease. Research should include biomarker studies to predict histologic remission in autoimmune hepatitis and mechanistic studies to define future treatment targets for primary sclerosing cholangitis.

BACKGROUND: Patients with autoimmune hepatitis (AIH) and primary or autoimmune sclerosing cholangitis are at nutritional risk; their body composition and has not been extensively studied. We aimed to describe their body composition and identify clinical links. METHODS: Using magnetic resonance imaging (MRI), two reviewers segmented total psoas muscle area (tPMSA), visceral fat area (VFA) and subcutaneous fat area (mm(2)) and measured visceral and subcutaneous thickness (mm). Clinical, laboratory and quality of life (QoL; using PedsQL) data were collected. Sarcopenia was defined as tPMSA ≤5th percentile. Analysis of variance, Wilcoxon rank test and multivariable modelling were performed. A paediatric cohort with non-alcoholic fatty liver disease (NAFLD) was used as a comparator following propensity score matching. RESULTS: Fifty-eight patients with autoimmune liver disease (AILD) (33 [57%] with AIH) were included: median age 16 years (interquartile range [IQR]: 13-18), 33 (57%) male. Median time from diagnosis to MRI was 15 months (IQR: 2-39 months). Two patients (3%) had a BMIz indicative of mild malnutrition. tPMSA was measurable in 52 subjects (90%). Of those, 25 (48%) had sarcopenia. Sarcopenic patients had a lower blood urea nitrogen compared to non-sarcopenic (median [IQR]: 9.5 [8.0, 12.0] vs 11 [10, 14] mg/dL; P = .023). There was no difference in corticosteroid use between groups. The VFA of sarcopenic patients was higher (3156 [2064, 7492]) vs 2084 [688, 3092]) mm(2); P = .005). Patient-reported QoL negatively associated with VFA and general health negatively associated with VFA. Compared with NAFLD, the odds ratio for sarcopenia with AILD was 14.5 (95% confidence interval: 2.3-90.7). CONCLUSION: In autoimmune liver diseases, sarcopenia is highly prevalent, associated with increased visceral fat and QoL.

Background and aims Neuropsychiatric symptoms in hepatitis C (HCV) patients resemble those of patients with autoimmune hepatitis (AIH) or primary biliary cholangitis (PBC), whilst the mechanisms behind them are unknown. Here we looked for cerebral metabolic and/or microstructural alterations in patients with HCV, AIH or PBC as possible causes behind these symptoms. Methods Patients with HCV infection (n = 17), AIH (n = 14) or PBC (n = 11) and age-adjusted healthy controls (n = 18) underwent brain magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) and psychometric assessment of memory and attention. Brain relative proton density (PD) and T2 relaxation time (T2) were determined in 17 regions of interest (ROIs), as were the concentrations of N-acetyl-aspartate, choline, creatine, myo-inositol and glutamine + glutamate in frontal- (fWM) and parietal white matter (pWM). One-way analysis of variance and Kruskal-Wallis tests were used for group comparison. Correlations between altered neuropsychological findings and MRI/MRS observations were estimated with the Spearman ρ test. Results HCV, AIH and PBC patients revealed similar alterations in brain PD and metabolites compared to controls: significantly decreased PD in 7/17 ROIs in the HCV group, 16/17 ROIs in the PBC group and 14/17 ROIs in the AIH group, significantly increased N-acetyl-aspartate in fWM in all patients, significantly increased choline in the PBC group in both fWM and pWM, in the AIH group only in pWM and with a trend in the HCV group in pWM. Correlation analysis did not reveal significant associations between MRI/MRS alterations and neuropsychological dysfunction. Conclusion The findings suggest similar pathophysiological mechanisms behind neuropsychiatric symptoms associated with HCV infection, AIH and PBC.

Very early onset inflammatory bowel disease, autoimmune hepatitis (AIH), or primary sclerosing cholangitis (PSC) alone is a rare condition in young children. The combination of all 3 autoimmune disorders in a 16-month-old child is even rarer. The onset and etiology of these diseases is multifactorial and typically unknown. However, when the children are diagnosed, the accepted view point is that the inflammation was likely present for months to years prior. This case is unique because the gastrointestinal problems started from infancy, and evolved to the development of Crohn’s disease, AIH, and PSC at a very early age. This case helps bring to light that very early onset autoimmune disorders may in fact present with symptoms of feeding difficulties, growth failure, and formula intolerance. Patients may be diagnosed initially with allergic enterocolitis in infancy. Although few children with these symptoms evolve to develop autoimmune diseases at an older age, clinicians should consider following these children more closely. This case also demonstrates how hard it is to diagnose very early onset autoimmune disorders, as they mimic other illnesses.

Autoimmune liver disease (AILD) spans a spectrum of chronic disorders affecting the liver parenchyma and biliary system. Three main categories of AILD are autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). This review condenses the presentation and discussions of the Single Topic Conference (STC) on AILD that was held in Ottawa, Ontario, in November 2019. We cover generalities regarding disease presentation and clinical diagnosis; mechanistic themes; treatment paradigms; clinical trials, including approaches and challenges to new therapies; and looking beyond traditional disease boundaries. Although these diseases are considered autoimmune, the etiology and role of environmental triggers are poorly understood. AILDs are progressive and chronic conditions that affect survival and quality of life. Advances have been made in PBC treatment because second-line treatments are now available (obeticholic acid, bezafibrate); however, a significant proportion still present suboptimal response. AIH treatment has remained unchanged for several decades, and data suggest that fewer than 50% of patients achieve a complete response and as many as 80% develop treatment-related side effects. B-cell depletion therapy to treat AIH is in an early stage of development and has shown promising results. An effective treatment for PSC is urgently needed. Liver transplant remains the best option for patients who develop decompensated cirrhosis or hepatocellular carcinoma within specific criteria, but recurrent AILD might occur. Continued efforts are warranted to develop networks for AILD aimed at assessing geo-epidemiological, clinical, and biochemical differences to capture the new treatment era in Canada.

The onset of autoimmune hepatitis (AIH) during pregnancy is rare and often poses a diagnostic challenge. A 29-year-old Japanese woman experienced epigastric pain and nausea during the third trimester of her third pregnancy. Three days after the symptom onset, an emergency Caesarean section was performed because of suspected acute fatty liver of pregnancy; however, the patient's liver dysfunction worsened afterward. Despite normal serum IgG concentration and absence of autoantibodies, biopsy-proven severe hepatitis with centrilobular zonal necrosis and good biochemical response to corticosteroids led to a diagnosis of AIH. Therefore, AIH should be included in the differential diagnosis of liver dysfunction during pregnancy.

The purpose of this series is to highlight a range of rare health conditions. Rare health conditions are those that affect no more, and usually fewer, than 1 person in every 2000. Many healthcare assistants and nurses will encounter some of these conditions, given the high number of them. This 51st article will briefly explore four of these conditions: Aarskog syndrome, Adie syndrome, autoimmune hepatitis and Fowler's syndrome.

Immune checkpoint inhibitors (ICI) improve the prognosis of patients with advanced non-small cell lung cancer. However, clinicians should be aware of potentially life-threatening immune-related adverse events (irAEs). We report a case of a 67-year-old man with lung adenocarcinoma who developed an acute ischemic stroke after the second administration of pembrolizumab. The patient benefited from thrombolysis and mechanical thrombectomy with improved neurological outcome. An anti-phospholipid syndrome (APS) was diagnosed. Simultaneously, he developed a grade IV autoimmune hepatitis. Both manifestations were considered irAEs and the ICI treatment was discontinued. Steroids were initiated resulting in irAEs resolution. Remarkably, the patient achieved a complete oncological response and persistent remission after one year follow-up despite early discontinuation of pembrolizumab. Of note, APS is rarely reported as irAE. To our knowledge, this is the first case reported in the context of lung cancer. A systematic review of the literature is provided., SCOPUS: re.j, info:eu-repo/semantics/published

Purpose of review Liver test abnormalities in children with inflammatory bowel disease (IBD) are usually insidious in onset. By the time that symptoms referable to liver disease have appeared, the liver injury may be well advanced. It is, therefore, important that children with an incidental finding of abnormal liver tests are investigated in an appropriate and timely manner.Recent findings The most prevalent cause of liver test elevations in paediatric IBD is immune-related liver disease, including primary sclerosing cholangitis, autoimmune sclerosing cholangitis, and autoimmune hepatitis. Although less common, drugs used in the treatment of IBD can also cause liver injury. The diagnosis of drug-induced liver injury relies largely on excluding other causes of liver injury, such as viral hepatitis, nonalcoholic fatty liver disease, and biliary and vascular complications.Summary This review highlights an avenue to a step-wise approach for investigating children with IBD and silent liver test elevations. Central to the timing of diagnostic actions is grading the severity of liver test elevations.

Although various complex definitions of acute-on-chronic liver failure (ACLF) have been suggested in relation to adult patients, there is currently no universal definition of the syndrome in pediatric patients. In simplified terms, ACLF is characterized by the acute deterioration of the liver functions due to the effects of a precipitating factor on the basis of a chronic liver disease. Acute events and underlying liver diseases are very different in children from those seen in adults. Moreover, acute events and underlying chronic liver diseases vary among geographical regions, although it seems that the most common such diseases and acute events are autoimmune hepatitis, Wilson's disease, and their flares. ACLF is associated with a poor prognosis. While no scoring systems have been developed to predict the prognosis for children with ACLF, modified versions of the Asian Pacific Association for the Study of the liver's acute-on-chronic liver failure scoring system and the Chronic Liver Failure-Sequential Organ Failure Assessment criteria can be used in children until specific and validated scoring systems are available. Aside from liver transplantation, there is no proven treatment for ACLF. Thus, the early recognition of ACLF prior to the development of extrahepatic organ failure is important.

Background: The specialists should identify the features of Wilson disease and autoimmune hepatitis when both affect a patient to adopt appropriate treatment. Objectives: This study was conducted to determine features of the patient, disease, diagnostic studies, and therapeutic measures in cases of simultaneity of Wilson disease and autoimmune hepatitis. Methods: To find evidence related to the study objectives, we searched databases such as Barakat knowledge network system, SID, Magiran, Google Scholar, Web of Science, ProQuest, Springer, ScienceDirect, Medline via PubMed, and Scopus with specified Persian and English keywords, including “Wilson’s Disease”, “Autoimmune”, and “Hepatitis”. The inclusion criteria for the studies were 1) the study was observational and 2) the study was published in Persian or English. The exclusion criteria included low-quality studies based on the score obtained from the checklist. The obtained studies were screened in terms of titles, abstracts, and full text, and finally, the qualified studies entered the review process. The relevant data were extracted according to a designed checklist. Results: Finally, 10 studies were included in the review process. Information about 14 patients was reported. The Mean±SD age of the participants in the studies was 19±11 years. The direction of diagnosis was from autoimmune hepatitis to Wilson disease in 8 cases and from Wilson disease to autoimmune hepatitis in 3 cases. The simultaneity of autoimmune hepatitis and Wilson disease was considered in 3 patients with no primary and secondary diagnosis. Conclusions: The comorbidity of Wilson disease and autoimmune hepatitis is uncommon but is important. In the presence of relevant symptoms in these patients, the comorbidity of these two diseases should be considered. Accordingly, additional assessments such as serum ceruloplasmin, urinary 24-h copper, molecular genetic testing, MRI, serological tests, anti-nuclear antibody, anti-mitochondrial antibody, anti-smooth muscle antibody, complement level, gamma globulin, IgG, albumin, Kayser-Fleischer ring eye examination, and liver biopsy should be considered for correct diagnosis. If appropriate treatment was started for the disease with a diagnosis of Wilson disease or autoimmune hepatitis, but the response to treatment was insufficient, it is better to consider the simultaneous occurrence of two diseases or the initial misdiagnosis.

Genetic syndromes represent relevant and rare diseases. These conditions include a large amount of epidemiological, pathogenetic and clinical features. However, a systematic approach to genetic syndromes is often prevented by the rareness of these diseases. So, although clinical features are usually precisely defined, nowadays more uncommon associations between genetic syndromes and internal medicine related diseases have been insufficiently studied. Autoimmune hepatitis (AIH) is a chronic liver disease caused by loss of tolerance to hepatocyte-specific auto-antigens. Conversely, a better knowledge about specific genetic syndromes in which AIH is more frequent could be important in the clinical management of patients, both for an early diagnosis and for a prompt therapy. Furthermore, a systematic approach could explain if onset, clinical course, and response to treatment of AIH are typical for specific genetic syndromes. We took in consideration all the scientific articles reported in PubMed in the last 10 years, from 2010 to 2020. The purpose of this review is to explore the prevalence of AIH in genetic syndrome, but also to suggest new classification, that could be useful for pathogenetic hypothesis and clinical approach to genetic syndrome. From the 139 publications selected using keywords "autoimmune hepatitis" and "genetic syndrome", 30 papers (21.6%) respected the chosen inclusion criteria, reporting the association between AIH in patients with a genetic syndrome. We have collected in all 47 patients with AIH and genetic syndrome, and with median age of 12.6-year-old. We suggest that when a patient presents a clinical picture of cryptogenic chronic hepatitis, that is unexplained, it is useful to explore differential diagnosis of AIH associated with genetic syndrome. Given the clinical relevance of this topic, further reports are needed to demonstrate our hypothesis and collect new evidence in this field.

Celiac disease clinical presentation is constantly changing. We set to determine the prevalence of elevated transaminases in newly diagnosed celiac patients and to evaluate this sub-group of patients for associated clinical and laboratory findings and assess their natural course of disease following therapeutic diet initiation. We conducted a prospective-observational study of all newly diagnosed pediatric celiac patients, between August 2016 and April 2018, in a pediatric gastroenterology clinic. Clinical data, anthropometrics, and blood test results were recorded at diagnosis and at 3, 6, and 12 months, respectively, of follow-up. We compared patients with normal and elevated transaminases at diagnosis. ALT threshold was set at 24 U/l. Of 125 newly diagnosed celiac patients, 31 (24.8%) had elevated ALT at diagnosis; two (1.6%) with over 3 × ULN. Patients with elevated ALT at diagnosis were significantly younger (mean age 5.5 (SD 3.4) vs. 7.3 (SD 3.7) years, p

Recently, autoimmune hepatitis (AIH) is beco-ming more common; as stated in the EASL 2015 recommendation, it can occur in any population and in all age groups. The etiology of AIH is unknown, the pathogenesis is insufficiently studied. Factors that directly trigger the autoimmune process have not been established. They can belong to environmental and infectious agents. Autoimmune hepatitis is heterogeneous in both clinical and serological manifestations, is characterized by a wide range of clinical symptoms of the disease: from asymptomatic to severe course, with or without extrahepatic manifestations, which can affect almost all organs and systems. AIH has a variety of clinical manifestations, it is not a clinically stable process, it should be excluded in all patients with symptoms of liver damage. Own observations of children with AIH with atypical manifestations of the disease are presented. Positive autoantibodies and the use of a pediatric scale are the keys in AIH diagnosis. With the exception of the fulminant course of the disease, AIH responds well to immunosuppressive therapy regardless of the degree of liver dysfunction. In childhood, remission is achieved in 60–90 % of patients depending on the severity of the disease at its manifestation, speed and degree of response to treatment., В последнее время все чаще встречается аутоиммунный гепатит (autoimmune hepatitis; АІН), который, как указано в рекомендациях EASL 2015 года, может быть в любых популяциях и во всех возрастных группах. Этиология АІН неизвестна, патогенез изучен недостаточно. Триггерные факторы не установлены. Они могут относиться как к средовым, так и к инфекционным агентам. Аутоиммунный гепатит является гетерогенным как по клиническим, так и по серологическим проявлениям, характеризуется широким спектром клинической картины заболевания: от бессимптомного течения до тяжелого, с наличием внепеченочных проявлений, которые могут касаться многих органов и систем, или без них. Манифестация АІН имеет разнообразные клинические проявления, не является клинически стабильным процессом, его необходимо исключать у всех пациентов, имеющих симптомы поражения печени. Представлены собственные случаи АІН у детей с нетипичной манифестацией заболевания. Ключевыми в диагностике АІН являются обнаружение аутоантител и использование педиатрической балльной шкалы диагностики АІН. За исключением фульминантного течения заболевания, АІН хорошо реагирует на иммуносупрессивную терапию независимо от степени нарушения функций печени. В детском возрасте ремиссия достигается у 60–90 % пациентов в зависимости от тяжести заболевания при его манифестации, скорости и степени ответа на лечение., Останнім часом усе частіше зустрічається автоімунний гепатит (autoimmune hepatitis; АІН), який, як зазначено в рекомендаціях EASL 2015 року, може бути в будь-яких популяціях і в усіх вікових групах. Етіологія АІН невідома, патогенез вивчений недостатньо. Фактори, що безпосередньо запускають автоімунний процес, не встановлені. Вони можуть належати як до середовищних, так і до інфекційних агентів. Автоімунний гепатит є гетерогенним як за клінічними, так і за серологічними проявами, характеризується широким спектром клінічної картини захворювання: від безсимптомного перебігу до тяжкого, з наявністю позапечінкових проявів, що можуть стосуватися майже всіх органів і систем, або без них. Маніфестація АІН має різноманітні клінічні прояви, не є клінічно стабільним процесом, його необхідно виключати в усіх пацієнтів, що мають симптоми ураження печінки. Наведено власні спостереження дітей з АІН з нетиповою маніфестацією захворювання. Ключовими в діагностиці АІН є виявлення позитивних автоантитіл і користування педіатричною бальною шкалою діагностики АІН. За винятком фульмінантного перебігу захворювання, АІН добре реагує на імуносупресивну терапію незалежно від ступеня порушення функцій печінки. У дитячому віці ремісія досягається в 60–90 % пацієнтів залежно від тяжкості захворювання при його маніфестації, швидкості й ступеня відповіді на лікування.

The article presents data on the features of hepatitis A, B, C, D, E in pregnant women, methods for screening verification of liver pathology, clinical and laboratory signs of extrahepatic manifestations of chronic viral hepatitis B and C. Diagnostically significant laboratory parameters of hemochromatosis, autoimmune hepatitis, intrahepatic cholestasis of pregnanсy, pernicious vomiting of pregnancy, acute fatty liver of pregnancy, HELLP syndrome were determined in the pre­sent work. The article describes modern methods for conduc­ting a laboratory “puncture-free” liver biopsy to evaluate fibrosis, hepatitis activity and liver steatosis. The lecture is intended for infectious disease doctors, obstetricians, gynecologists, gastroenterologists, family doctors.

The gut-liver axis plays an important role in the pathogenesis of various liver diseases. Probiotics are living bacteria that may be used to correct disorders of this axis. Notable progress has been made in the study of probiotic drugs for the treatment of various liver diseases in the last decade. It has been proven that probiotics are useful for hepatic encephalopathy, but their effects on other symptoms and syndromes of cirrhosis are poorly studied. Their effectiveness in the treatment of metabolic associated fatty liver disease has been shown both in experimental models and in clinical trials, but their effect on the prognosis of this disease has not been described. The beneficial effects of probiotics in alcoholic liver disease have been shown in many experimental studies, but there are very few clinical trials to support these findings. The effects of probiotics on the course of other liver diseases are either poorly studied (such as primary sclerosing cholangitis, chronic hepatitis B and C, and autoimmune hepatitis) or not studied at all (such as primary biliary cholangitis, hepatitis A and E, Wilson's disease, hemochromatosis, storage diseases, and vascular liver diseases). Thus, despite the progress in the study of probiotics in hepatology over the past decade, there are many unexplored and unclear questions surrounding this topic.

Ascites is defined as the accumulation of intra-peritoneal fluid that can be caused by several diseases. We described a 47-year-old female presenting with low serum-ascites albumin gradient (SAAG) and a markedly high level of serum globulin. Serum protein electrophoresis revealed an M spike in the gamma region. Other laboratory results showed a marked increase in aspartate aminotransferase and alanine aminotransferase and predominantly conjugated hyperbilirubinemia without a sign of dilatation of bile ducts from abdominal ultrasonography examination. Furthermore, the follow-up showed a positive result for the anti-nuclear antibody test. The patient was assessed with autoimmune hepatitis, and the cause of ascites was suggested from portal hypertension although the level of SAAG was low. The ascites condition got improved after salt restriction, diuretics treatment, and abdominal paracentesis. However, the patient passed away because of the intracranial hemorrhage as a result of prolonged INR and APTT due to liver failure.

The article presents review of literature and observation of the clinical case of Wilson’s disease combined with autoimmune hepatitis in an adolescent. The questions of the diagnosis of autoimmune hepatitis and Wilson’s disease in children are considered in accordance with the recommendations of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition. The attention is focused on the difficulties of interpreting clinical data and evaluating the results of laboratory and instrumental examination of this group of patients. An algorithm for diagnosing Wilson’s disease and autoimmune hepatitis in children is presented., В статье приведены данные литературных источников и собственное наблюдение клинического случая сосуществования болезни Вильсона — Коновалова и аутоиммунного гепатита у подростка. Рассмотрены вопросы диагностики аутоиммунного гепатита и болезни Вильсона — Коновалова у детей в соответствии с рекомендациями Европейского общества детских гастроэнтерологов, гепатологов и нутрициологов. Акцентировано внимание на трудностях интерпретации клинических данных и оценки результатов лабораторно-инструментального обследования данной группы пациентов. Представлен алгоритм диагностики болезни Вильсона — Коновалова и аутоиммунного гепатита у детей., У статті наведені дані літературних джерел і власне спостереження клінічного випадку співіснування хвороби Вільсона — Коновалова та автоімунного гепатиту в підлітка. Розглянуто питання діагностики автоімунного гепатиту та хвороби Вільсона — Коновалова в дітей відповідно до рекомендацій Європейського товариства дитячих гастроентерологів, гепатологів та нутриціологів. Акцентовано увагу на труднощах інтерпретації клінічних даних та оцінки результатів лабораторно-інструментального обстеження даної групи пацієнтів. Наведено алгоритм діагностики хвороби Вільсона — Коновалова та автоімунного гепатиту в дітей.

Аутоиммунный гепатит (АИГ) — редкая патология печени, но в последние годы количество больных увеличивается. Нет однозначного определения и четких патогномоничных критериев АИГ, отличительными признаками являются наличие аутоантител, значительная гипергаммаглобулинемия, характерные морфологические изменения и хороший ответ на иммуносупрессивную терапию. Иммуносупрессивная терапия при АИГ направлена на купирование аутоиммунного процесса, ликвидацию воспалительного синдрома, уменьшение прогрессирования фиброза, торможение развития цирроза. Препаратами первой линии являются кортикостероиды и азатиоприн, эффективность которых значительно превышает плацебо. Преднизолон назначают в среднем 40–60 мг/сут, в дозе 0,5–1 мг/кг/сут. Чем выше активность цитолиза, тем большая доза преднизолона необходима. При уменьшении цитолиза, по данным печеночных проб, соответственно уменьшается доза преднизолона. В практике чаще используется метилпреднизолон. Азатиоприн назначают или сразу, или через 2 недели приема преднизолона в дозе 50 мг/сут с возможным повышением до 100 мг/сут, в индивидуальной дозе — 1–2 мг/кг/сут. В настоящее время преимущество отдают комбинированной терапии преднизолоном и азатиоприном. Оценка эффективности лечения АИГ предусматривает контроль уровня аминотрансфераз (прежде всего аланинтрансферазы) и IgG, желательна их полная нормализация. Для оценки фиброза применяется эластография печени. К сожалению, лечение фактически назначается пожизненно. К препаратам второй линии относятся микофенолата мофетил, циклоспорин, такролимус, сиролимус, эверолимус и другие. Из них наиболее изученным считается микофенолата мофетил. Продолжаются поиски эффективной терапии АИГ, разрабатываются методы клеточной, антицитокиновой, антифибротической терапии. Приведены клинические примеры из собственного опыта. Выводы. Лечение АИГ является сложным процессом. В решении данной проблемы значительно помогают современные рекомендации, данные проведенных исследований и накопленный опыт. Выбор терапии требует индивидуального подхода с учетом особенностей клинического течения и ответа на терапию.

Non-alcoholic fatty liver disease includes hepatic steatosis, steatohepatitis and fibrosis, which can progress to cirrhosis. In view of the prevalence of this disease, the deterioration of the quality of life of patients, mortality from complications, the development of methods for accurate and timely assessment of the severity of fatty liver and progression of fibrosis are becoming of greater interest. Purpose. The study of diagnostic potential of transient elastography in patients with idiopathic transaminase elevations. Methods. In 52 patients (20 men and 32 women) with idiopathic increased transaminases without signs of hepatic steatosis according to sonographic study, controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) were performed using FibroScan with M probe. Exclusion criteria from the study were the presence of chronic viral, autoimmune hepatitis and alcohol abuse. Results. Forty one patients (78.8 %) had fatty liver disease according to CAP. The analysis of the data of transient elastography demonstrated that 63.4 % had fibrosis F0–F1, 29.3 % — F1–F2 and in 7.3 % — F3. In terms of the CAP there were significant differences between the group with severe fibrosis (F3) and groups with minimal fibrosis (F0–F1) ((203.0 ± 5.1) vs. (243.0 ± 10.1), p < 0.05). The analysis of biochemical parameters demonstrated significant differences in terms of gamma-glutamyltransferase in the groups with severe fibrosis (F3) and minimal fibrosis ((40.2 ± 5.7) vs. (26.4 ± 3.7), p < 0.05). Thus, the results obtained in the study indicate that a significant proportion of patients with idiopathic transaminase elevations inflammation factor is fatty liver disease, which is not detected at routine ultrasound examination. In the group with more expressed fibrosis reduction of fat in the liver and increased activity gamma glutamyltransferase were determined, that indicated the cholestasis deterioration in the liver in these patients. Consequently, patients with idiopathic transaminase increase, even with the absence of signs of steatosis according to sonography need CAP measurement using FibroScan, which is more sensitive in identifying fatty liver disease than ultrasound.

Background . The article deals with the chronic inflammatory bowel diseases, in particular, the attention is paid to ulcerative colitis (UC). UC proceeds with the development of a number of extraintestinal lesions, among which a special place is given to the changes in the liver and bile ducts. In connection with this, a study was conducted to assess the prevalence, nature and clinical features of liver damage in patients with UC. Materials and methods. Under observation, there were 180 patients with UC confirmed endoscopically and morphologically. All patients underwent multimodal ultrasound examination of the liver, study of the biochemical signs of cytolysis and/or cholestasis with negative serological markers of viral hepatitis B, C, D and autoimmune hepatitis. Also, a biochemical study of the lipid spectrum of the blood was performed, and in patients with suspected autoimmune lesions of the liver — an analysis of the spectrum of the corresponding antibodies. Results. In 180 patients with UC, a liver damage was detected in 58 (32.2 %) persons. Parenchymal lesions of the liver were diagnosed in 40 (22.2 %) UC patients, and changes in the bile ducts — in 18 (10.0 %) patients with UC. Nonalcoholic steatohepatitis (NASH), autoimmune hepatitis (AH) and primary biliary cirrhosis (PBC) of the liver were detected in 40 (69.0 %) patients with UC, and lesions of extra- and intrahepatic bile ducts and gall bladder — in 18 (31.0 %). Among the parenchymal lesions of the liver, NASH dominated (53.5 %). AH was diagnosed in 8.6 % of patients, PBC — in 5.2 % of patients with UC. All patients with UC and NASH, in addition to the basic UC therapy, received the preparation of essential phospholipids in a daily dose of 1,800 mg (2 capsules 3 times a day) for three months. After the end of treatment, only 2 (6.5 %) patients had minor complaints. Prior to treatment, a significant increase in aspartate aminotransferase and alanine aminotransferase by 2.3 and 2.2 times, respectively, was observed in all the examined patients, in combination with 3.7 times increase in gamma-glutamyl transpeptidase compared with the norm, which may indicate a moderate cytolysis syndrome. After the treatment, patients showed a tendency to normalize the enzymatic status, although the indices remained elevated in comparison with the norm. Conclusions. Thus, liver damage was detected in 32.2 % of patients, predominantly in the advanced forms, with a moderate and severe course and high activity of UC. For the treatment of NASH in patients with UC, it is advisable to use essential phospholipids.

Recent studies have identified an increased risk of hepatocellular carcinoma (HCC) in autoimmune hepatitis (AIH). Sex and regional disparities in incidence of HCC in AIH continue to be reported worldwide. Nevertheless, the magnitude of this gap remains unknown. We searched several databases including PubMed, Embase, Web of Science, Cochrane Library, Wanfang Data, CNKI and SinoMed. Incidence rates of HCC in AIH were combined and analyzed following the EBayes method. Incidence rate ratios were pooled to assess the sex differences. The impact of population difference, sex, age, cirrhotic condition was further analyzed with subgroup analysis and linear regression analysis. 39 studies meeting our eligibility criteria were chosen for the analysis. The pooled incidence rate of HCC in AIH was 3.54 per 1000 person years (95% CI 2.76–4.55). Pooled IRR for the risk of HCC in male AIH patients compared to female was 2.16 (95% CI 1.25–3.75), with mild heterogeneity among studies. The pooled HCC incidence rate in AIH by continents was as follows: Europe 2.37 per 1000 person-years (95% CI 1.45–3.88), Asia 6.18 per 1000 person-years (95%CI 5.51–6.93), North America 2.97 per 1000 person-years (95%CI 2.40–3.68), Oceania 2.60 (95%CI 0.54–7.58). The pooled HCC incidence rate in AIH-related cirrhosis by continent was as follows: Europe 6.35 per 1000 person-years (95%CI 3.94–10.22), Asia 17.02 per 1000 person-years (95%CI 11.18–25.91), North America 10.89 per 1000 person-years (95%CI 6.69–17.74). A higher HCC incidence in AIH was observed among male and in Asian populations. Cirrhosis status at AIH diagnosis is significantly associated with an increased incidence rate for HCC, and routine HCC surveillance is recommended for patients with AIH cirrhosis, especially for those in Asia.

Hepatitis A virus immunoglobulin M (HAV-IgM) is often used to diagnose acute hepatitis A virus (HAV) infection serologically. However, false-positive test results can interfere with the diagnosis. A 56-year-old woman was readmitted to the hospital owing to abnormal liver function tests for the last 18 months. She had been diagnosed with acute HAV and was hospitalized in isolation based on a positive HAV-IgM test 18 months ago. Regular follow-up after discharge showed abnormal liver function and an elevated level of antinuclear antibodies and immunoglobulin G. For the last 15 days, the patient had fatigue, decreased appetite, and yellow urine, signaling recrudescence. Liver function tests were also abnormal. Liver biopsy revealed histological changes consistent with typical autoimmune hepatitis. After 2 months of methylprednisolone treatment, liver function returned to normal, and HAV-IgM turned negative. The diagnosis of acute HAV in nonendemic areas requires a comprehensive analysis of epidemic history, clinical characteristics, etiology, etc.

We herein report two cases of thrombotic thrombocytopenic purpura (TTP) complicated by other autoimmune disorders, autoimmune hepatitis and immune thrombocytopenia, respectively. In both cases, corticosteroids were continuously administered for the treatment of preceding autoimmune disorders. However, a sufficient objective response for TTP was not obtained by plasma exchange and corticosteroid treatment. Once a week rituximab (375 mg/m2) treatment for 4 times was initiated within 2 weeks from the diagnosis. Both patients achieved a sufficient response, and have never had any recurrence as of the last follow-up dates. The early introduction of rituximab could be an effective treatment option in TTP patients complicated with other autoimmune disorders.

Background Liver transplantation is a life-saving and successful therapeutic procedure which is more and more frequent worldwide, also among women of reproductive age. Consequently, there is an increasing number of reports of pregnancy following liver transplantation, but doubts still exist regarding preconception counseling and the optimal method of managing pregnancy. The aim of this study was to report and evaluate pregnancy outcomes in women who had undergone liver transplantation. Methods We retrospectively analyzed female patients after orthotopic liver transplantation who reported pregnancy and were under medical care of a single transplant center. Results We identified 14 pregnancies in 10 women who had undergone liver transplantation (12 childbirths, one induced abortion due to fetal death in the first trimester, one pregnancy is still ongoing). Causes of transplantation include congenital or acquired disorders and the most common indication was autoimmune hepatitis (50%). The mean age at the point of transplantation was 28.5 (range 21–36), mean maternal age at pregnancy was 32 (range 26–43), and transplant-to-pregnancy interval was 4.07 years (range 1.5–7). The mean gestational week was 36.67 (range 31–40). Immunosuppression was maintained with combinations of prednisone (n = 11), tacrolimus (n = 13), and azathioprine (n = 8) prior to and during pregnancy. Two pregnancies were unintended, so women took mycophenolate mofetil in the first weeks of gestation. Another two women stopped taking azathioprine due to increasing anemia. Maternal complications included increase of aspartate transaminase and alanine transaminase (n = 2), anemia (n = 4) and hyperthyroidism (n = 2). Among the 12 childbirths, five (41.67%) were preterm. Only five women entered labor spontaneously, while seven (58,33%) had cesarean delivery. Conclusions Pregnancy after liver transplantation can achieve relatively favorable outcomes. Liver transplantation does not influence women’s fertility and, during pregnancy, we report low rates of minor graft complications. A multidisciplinary team should be involved in contraceptive, fertility and consequently pregnancy counseling of female transplant recipients.

Purpose of the study.To investigate the features of lesions of the gastrointestinal tract in diff erent variants of the course of COVID-19 in children.Materials and methods.A single-center prospective study was carried out to study the clinical and laboratory manifestations of gastrointestinal tract (GIT) lesions in different variants of the course of COVID-19 in children. The study was carried out in the following groups: group No. 1 — pediatric patients with a verified diagnosis (according to ICD 10) “U07.1. COVID-19 virus identified, confirmed by laboratory tests, regardless of the severity of clinical signs or symptoms ”, n = 524; group No. 2 — pediatric patients with a verified diagnosis (according to ICD 10) “U10.9 Multisystem inflammatory syndrome associated with COVID-19, unspecified”, n = 46. The article provides a brief description of the observations of the development of autoimmune pathologies (ulcerative colitis, autoimmune hepatitis) in pediatric patients, for whom a postponed COVID-19 infection could be a probable trigger.Results.The leading symptoms of the gastrointestinal tract in patients of group No. 1 were symptoms of acute gastroenteritis, registered in 37.6% of cases. Diarrhea was detected in 21.2% of cases, vomiting — in 16.5%; abdominal pain syndrome — 9.2%. These manifestations were statistically more significant in patients under one year of age, as well as in children of the first three years of life (p≤0.05). Gastrointestinal syndrome in patients of group No. 2 was registered in 67.4% of cases, with vomiting — 60.9% of cases, diarrheal syndrome — 23.9% of cases, abdominal pain syndrome — 82.6%. Other manifestations of the gastrointestinal tract in patients of this group were: reactive hepatitis — 69.6% of cases (average ALT — 98 (47; 347); AST — 107 (34; 347)), reactive pancreatitis — 60.8% of cases (average values of amylase — 127 (28; 269); lipase — 196 (47; 107)). These lesions were of a reactive inflammatory nature, with a probable immune development mechanism.

Background. Liver transplantation is indicated in end-stage liver disease due to autoimmune diseases. The liver allocation system can be affected by disparities such as decreased liver transplant referrals for racial minorities, especially African Americans that negatively impact the pre- and posttransplant outcomes. Aim. To determine differences in waitlist survival and posttransplant graft survival rates between African American and Caucasian patients with autoimmune liver diseases. Study. The United Network for Organ Sharing database was used to identify all patients with autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis who underwent liver transplant from 1988 to 2019. We compared waitlist survival and posttransplant graft survival between Caucasians and African Americans using Kaplan–Meier curves and Cox regression models. We also evaluated the cumulative incidence of death or delisting for deterioration and posttransplant incidence of death and retransplantation using competing risk analysis. Results. African Americans were more likely to be removed from the waitlist for death or clinical deterioration (subdistribution hazard ratio (SHR) 1.26, 95% CI 1–1.58, P = 0.046 ) using competing risk analysis. On multivariate Cox regression analysis, there was no difference in posttransplant graft survival among the two groups (hazard ratio (HR) 1.10, 95% CI 0.98–1.23, P = 0.081 ). Conclusions. Despite the current efforts to reduce racial disparities, we found that African Americans are more likely to die on the waitlist for liver transplant and are less likely to be transplanted, with no differences in graft survival rates. The persistence of healthcare disparities continues to negatively impact African Americans.

Introduction and objectives It has been proposed that non-invasive methods may replace liver biopsy for the diagnosis of tissue damage in patients with autoimmune liver disease (ALD). The aim of this study was to determine diagnostic performance and degree of concordance between the APRI index and liver biopsy for diagnosing cirrhosis in these patients. Material and methods In a cohort of patients with ALD, the value of the APRI index and liver biopsy results were determined according to the METAVIR score. The AUC and the degree of concordance between an APRI value >2 and a METAVIR score of F4 were evaluated as markers of liver cirrhosis, through a kappa statistic. Results In total, 70 patients (age 51 ± 13 years) were included. The most common autoimmune liver diseases were primary biliary cirrhosis (PBC) (40%), autoimmune hepatitis (AIH) (24.3%) and AIH-PBC overlap syndrome (32.9%). Cirrhosis was confirmed by biopsy in 16 patients (22.9%). 15 patients (21.4%) had an APRI index >2 (Cirrhosis) and only six met both criteria. The AUC of the APRI was 0.77 (95% CI 0.65−0.88). The degree of concordance between the tests was low for an APRI cut-off point >2 (kappa 0.213; 95% CI 0.094−0.332), as well as for cut-off points >1.5, >1 and >0.5 (kappa 0.213, 0.255, 0.257, respectively) Conclusion Our results suggest that there is little concordance between APRI and liver biopsy for the diagnosis of cirrhosis in patients with ALD. It should therefore not be used as a single diagnostic method to determine cirrhosis.

Background Nogo-B is one of the members of the reticulon family. Nogo-B influences the proliferation of the hepatic stellate cells inducing liver fibrotic changes. We aimed at measuring the serum levels of Nogo-B in patients with chronic liver disease (CLD) with different etiologies. Ninety subjects were included, 18 of them were normal healthy individuals and 72 had liver disease (fibrosis/cirrhosis) with different etiologies: post-hepatitis C infection, post-hepatitis B infection, NASH, and autoimmune hepatitis. Serum Nogo-B was assessed using ELISA. Patients were subdivided according to the Child-Pugh score into 3 groups: group 1—Child A (24 patients); group 2—Child B (24 patients); and group 3—Child C (24 patients). Results Serum Nogo-B levels were found to be significantly higher in patients (1477.92 ± 1113.50) when compared with healthy control (301.28 ± 180.87) (p < 0.001). There was a statistically significant difference in serum Nogo-B level between the three sub-groups of patients (p < 0.001). A positive correlation was found between serum Nogo-B and MELD score (r = 0.46, p-value < 0.001). However, there was no correlation found between Nogo-B and FIB-4 index or APRI score. There was a significant positive correlation between serum Nogo-B level and coagulation profile and serum bilirubin. An inverse correlation was found between serum Nogo-B with serum albumin. A ROC curve was done to examine the validity of Nogo-B in the diagnosis of liver cirrhosis, and the area under the curve was found to be 0.979, a cutoff value of 600 with a sensitivity of 97.2% and a specificity of 94.4% (p-value < 0.001). Conclusion Nogo-B had a high value in the identification of patients with any severity of CLD. There is a highly significant correlation between Nogo-B and the synthetic function of the liver; it could be used as a measure of hepatic functional reserve.

A 69-year-old man presented with jaundice and appetite loss. Blood analyses showed elevated aminotransferase levels, hyperbilirubinemia, positivity for antinuclear antibody, elevated immunoglobulin (Ig) G4 levels, and negativity for hepatitis virus markers. Additionally, computed tomography revealed a focal enlargement of the pancreatic body and enhancement of the peripheral bile ducts. Liver biopsy showed interface hepatitis, supporting a clinical diagnosis of autoimmune hepatitis (AIH). Immunohistochemistry revealed that IgG4-bearing plasma cells accounted for more than 60% of the IgG-bearing plasma cells in the portal area. Then, we started oral prednisolone therapy. After tapering, serum transaminase levels became elevated again, and we had to adjust the dose. Azathioprine maintenance therapy was necessary to prevent relapse. We herein report a case of IgG4-hepatopathy with a clinical course similar to that of AIH with acute onset.

Background & Aims Patients with autoimmune hepatitis (AIH) usually receive maintenance therapy with thiopurines, such as azathioprine (AZA) or mercaptopurine. Genetic polymorphisms in AZA metabolism can lead to variations in thioguanine nucleotide (TGN) and 6-methylmercaptopurine, both of which can cause adverse drug reactions (ADRs). In inflammatory bowel disease, a therapeutic TGN range (225–450 pmol/8x108 erythrocytes) has been identified to optimise effectiveness. We evaluated the benefits of a personalised medicine approach to thiopurine dosing, in comparison to standard weight-based dosing. Methods A retrospective matched cohort study of 214 patients with AIH who were seen at King’s College between 1999-2019 was performed. Metabolite levels were measured in 109 patients. The control group included 105 patients on weight-based thiopurine dosing with no metabolite monitoring. Results Biochemical response (BR) occurred more frequently at 6-month follow-up in patients with metabolite monitoring compared to those on a weight-based regimen (77% vs. 60%, p = 0.008). This remained true with data analysis based on clinicians who measure metabolites and those who do not (BR at 6 months: 84% vs. 64%, p = 0.016). Patients with BR had TGN levels within the therapeutic range of 225–450 pmol/8x108 erythrocytes significantly more often than those who failed to achieve or lost BR (40% vs. 13%, p Conclusion A strategy of personalised medicine using metabolite levels can optimise treatment regimens in AIH, resulting in fewer ADRs whilst maintaining BR. Lay summary This study looked to see if measuring the breakdown products of a medication used in autoimmune hepatitis increases the chances of gaining good control of the disease, when compared to a group of patients who were on a dose of this medication based on their weight. A group of 214 patients with autoimmune hepatitis were split into 2 groups: roughly half had their medication dose adjusted according to measurements of breakdown products in the blood, whilst the other half received their weight-based dose as normal. The results confirmed that using a personalised approach and checking drug breakdown products resulted in fewer side effects and potentially improved control of disease.

Acute liver injury (ALI) has been rarely reported as a clinical finding of adult T-cell leukemia/lymphoma (ATLL). A 74-year-old Japanese female patient who was histologically diagnosed as having autoimmune hepatitis (AIH) one year earlier, showed elevations in her aminotransferase and total bilirubin levels, and this was considered to be an exacerbation of AIH. Liver biopsy revealed interface hepatitis. Because atypical lymphocytes and human T-cell leukemia virus 1 immunoglobulin G antibody were positive, the patient was diagnosed to have ATLL. The biopsy revealed CD4+ and CD8+, but not CD20+ lymphocytes. Thus, the ALI in the patient was due to T-cell infiltration into the liver, and not due to an exacerbation of AIH.

BACKGROUND Previous studies investigating the prevalence of celiac disease (CD) in individuals with autoimmune hepatitis (AIH) have shown highly variable results. We therefore aimed to examine the prevalence of CD in individuals with AIH. METHODS Two professional librarians searched PubMed, EMBASE, Cochrane and Web of Science Core Collection up until 7 February 2020. The search terms included 'celiac disease', 'celiac', 'transglutaminases', 'gluten', 'gliadin', 'EMA', 'TTG' and 'villous' combined with 'autoimmune', 'hepatitis', 'ANA', 'SMA' and 'LKM'. This search yielded 2419 unique publications. A systematic review based on the PRISMA guidelines resulted in 31 articles eligible for full text review. Fifteen articles were deemed relevant, with 8 being included in our main analysis. A fixed-effect inverse variance-weighted model was used, and heterogeneity was calculated. RESULTS Our main analysis included 567 individuals with AIH from eight studies, where biopsy-verified CD (equivalent to Marsh III) was seen in 23 individuals (4.1%). The pooled prevalence of CD in AIH was 3.5% (95% CI = 1.6%-5.3%) (heterogeneity: P = .874; I2 = 0.0%), which is clearly higher than the 1% CD seen in most general populations. When also including studies where CD had been diagnosed through positive serology without biopsy (15 studies: n = 1817 individuals with AIH), the pooled prevalence of CD was 2.9% (95% CI = 2.1%-3.8%) (heterogeneity: P

Traditionally, inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn’s disease (CD). At the same time, there are a number of lesions of the gastrointestinal tract, which can proceed for a long time under the guise of IBD, masking the true cause of the disease. This leads to late diagnosis and, quite often, fatal consequences. These diseases include autoimmune enteropathy (AIE). It is a fairly rare disease characterized by severe diarrhea and immune- mediated damage to the intestinal mucosa.The aim is to describe the criteria of diagnosis, etiology, pathogenesis, epidemiology, clinic and treatment of AIE in children based on an analysis of modern literature.Results. Diagnostic criteria for AIE include chronic diarrhea (lasting more than 6 weeks), malabsorption syndrome, specific histological findings from small bowel biopsy with the exclusion of other causes of villous atrophy. An additional criterion is the presence of antibodies against enterocytes or goblet cells. There are: (1) AIEs associated with syndromes such as IPEX and APECED; (2) an isolated form of GI AIE with antibodies against enterocytes without diseases of the digestive system; and (3) any form of AIE in girls associated with any other autoimmune phenomena. To date, at least five subtypes of AIE are known: Primary AIE (pediatric); Syndromic AIE (pediatric); Primary (sporadic) EIA of adults; Secondary (iatrogenic) AIE of adults; Paraneoplastic AIE. Patients with AIE may have associated autoimmune diseases, including diabetes mellitus, autoimmune hepatitis, alopecia, hypothyroidism, and interstitial nephritis. AIE. is a complex disease and potentially life-threatening, the mortality rate reaches 30% in pediatric practice. The prognosis depends on the age of onset of the disease, the severity of symptoms and the degree of histological damage to the gastrointestinal tract. Along with nutritional support, immunosuppressive therapy, the use of therapy based on modern knowledge in the field of molecular biology can help control the disease.

The impact of acute liver failure (ALF) etiology on waitlist (WL) and posttransplantation outcomes, independent of severity of illness, is incompletely characterized. All adults (n = 1691) listed for primary liver transplantation (LT) between 2002 and 2019 with ALF due to acetaminophen toxicity (APAP), drug-induced liver injury (DILI), autoimmune hepatitis (AIH), and hepatitis B virus (HBV) were identified in the United Network for Organ Sharing database. ALF etiology was evaluated as an independent predictor of WL mortality and spontaneous survival (SS; versus outcome of LT), as well as post-LT overall survival, graft survival, and in-hospital mortality using multivariable models accounting for differences in clinical parameters at listing. Accounting for severity of illness at listing, WL mortality and SS for DILI, AIH, and HBV were each lower than those for APAP toxicity (adjusted relative risk ratio

Autoimmune liver diseases are chronic inflammatory hepatobiliary disorders that when classically defined encompass three distinctive clinical presentations; primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH). Meaningful changes in disease epidemiology are reported, with increasing incidence and prevalence of AIH and PSC in Europe, and rising prevalence of PBC across Europe, North America and the Asia-Pacific region. However, there appears to be very significant global variation with contemporary incidence rates of disease per 100 000 ranging from 0.84 to 2.75 for PBC, 0.1 to 4.39 for PSC and 0.4 to 2.39 for AIH. Prevalence corresponds, and per 100 000 estimates for PBC range from 1.91 to 40.2, for PSC between 0.78 and 31.7 and for AIH from 4.8 to 42.9. Population-based studies and multicentre observational cohort series provide improved understanding of the clinical course that patients experience, highlighting variations in presenting phenotypes geographically and temporally. Collectively, while autoimmune liver diseases are rare, the clinical burden is disproportionately high relative to population incidence and prevalence. Age, sex and race also impact clinical outcomes, and patient morbidity and mortality are reflected by high need for gastroenterology, hepatology and organ transplant services.

Autoimmune hepatitis (AIH) is an immune-mediated chronic liver disease that affects all ages, including women of childbearing age. Optimal management during pregnancy is poorly defined. We aimed to explore the clinical and biochemical course of AIH in the antenatal and postpartum periods, and assess factors associated with premature birth and postpartum flares. Pregnant women with AIH reviewed in the autoimmune liver disease clinic at the Queen Elizabeth Hospital Birmingham between 2009 and 2020 were identified retrospectively, and clinical, biochemical, and immunological data 1 year before conception to 1 year postpartum were collected. Analysis was performed to identify trends in blood markers over the antenatal period, with an interrupted time series approach used to assess postpartum trends. Data were available for n = 27 pregnancies (n = 20 women), with median gestation of 38 weeks (30% premature) and most having type 1 AIH (78%) and delivering via caesarean section (63%). Levels of alanine transaminase, aspartate transaminase, and immunoglobulin G all declined significantly during gestation, followed by significant step-change increases after delivery. Postpartum flare developed in 58% of pregnancies. AIH type 2 was associated with a higher rate of premature births (67% vs. 19%, P = 0.044), and a trend toward a higher rate of postpartum flare (100% vs. 48%, P = 0.053). Although not significant, medication nonadherence was associated with almost double the risk of prematurity (40% vs. 24%, P = 0.415) and postpartum flare (80% vs. 44%, P = 0.109). Conclusion: Biochemical and immunological remission of AIH occurs during pregnancy, although subsequent postpartum flare is common. Type 2 AIH is associated with a higher risk of premature birth and postpartum flare, although further research is required to validate and explain this finding.

Objectives Acute-on-chronic liver failure and its outcomes have not yet been evaluated in detail in children. We aimed to evaluate the etiology, acute events, and prognostic factors of acute-on-chronic liver failure in children. Materials and methods Pediatric patients (age 2-18 years) diagnosed with acute-on-chronic liver failure between April 2014 and April 2020 were evaluated retrospectively. Acute-on-chronic liver failure was defined as the presence of acute hepatic insult in previously diagnosed or undiagnosed chronic liver disease causing jaundice (total serum bilirubin ≥5 mg/dL) and coagulopathy (international normalized ratio of ≥2.0) and clinical and/or radiological ascites and/or hepatic encephalopathy within 4 weeks. Acute-on-Chronic Liver Failure Research Consortium and Chronic Liver Failure-Sequential Organ Failure Assessment scores were calculated for patients at first admission and at end of day 5 or before liver transplant. Results Our study included 29 patients. Underlying chronic liver diseases were mostly autoimmune hepatitis (51.72%) and Wilson disease (27.58%), with flare-ups of these diseases also the most common acute events (48.28% and 27.58%, respectively). Seven patients (24.14%) received liver transplants. At first admission, Acute-on-Chronic Liver Failure Research Consortium and Chronic Liver Failure-Sequential Organ Failure Assessment cut-off scores to predict liver transplant were 7.5 and 6.5; at end of day 5 or before transplant, cut-off scores were 8.5 and 7.5, respectively. The 8.5 cut-off score on day 5 was the most specific and sensitive to predict liver transplant. International normalized ratio cut-off of 3.04 predicted transplant requirement with maximum sensitivity and specificity. Conclusions Wilson disease and autoimmune hepatitis were the most common underlying chronic and acute events of acute-on-chronic liver failure in children. Although an Acute-on-Chronic Liver Failure Research Consortium score ≥ 8.5 best predicted liver transplant, for patients with scores ≥ 7.5 and being followed in a nontransplant center, patient referral to a transplant center is appropriate.

The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health crisis causing major challenges for clinical care in patients with gastrointestinal diseases. Although triggering of anti-viral immune responses is essential for clearance of infection, some patients have severe lung inflammation and multiorgan failure due to marked immune cell dysregulation and cytokine storm syndrome. Importantly, the activation of cytotoxic follicular helper T cells and a reduction of regulatory T cells have a crucial, negative prognostic role. These findings lead to the question of whether immunosuppressive and biologic therapies for gastrointestinal diseases affect the incidence or prognosis of COVID-19 and, thus, whether they should be adjusted to prevent or affect the course of the disease. In this Review, data on the use of such therapies are discussed with a primary focus on inflammatory bowel disease, autoimmune hepatitis and liver transplantation. In particular, the roles of corticosteroids, classic immunosuppressive agents (such as thiopurines and mycophenolate mofetil), small molecules (such as Janus kinase (JAK) inhibitors), and biologic agents (such as tumour necrosis factor (TNF) blockers, vedolizumab and ustekinumab) are reviewed. Finally, the use of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines for the prevention of infection in patients with gastrointestinal diseases and concomitant immunosuppressive or biologic therapy will be discussed., In this Review, Neurath discusses the implications of COVID-19 on immunosuppressive and biologic therapies as well as those of vaccination in gastrointestinal contexts such as inflammatory bowel disease, autoimmune hepatitis and liver transplantation., Key points The coronavirus disease 2019 (COVID-19) pandemic is a global health threat caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which binds to cellular angiotensin-converting enzyme 2 (ACE2) and cell surface-associated transmembrane serine protease 2 (TMPRSS2). As ACE2 and TMPRSS2 are expressed on the surface of several cell subsets in the gastrointestinal tract (such as intestinal epithelial cells), COVID-19 frequently causes gastrointestinal manifestations of disease. Patients with gastrointestinal disorders, such as inflammatory bowel disease (IBD), and liver transplant recipients should be encouraged to follow strict hygiene and social distancing measures. In patients with IBD, high-dose corticosteroid treatment before SARS-CoV-2 infection has been identified as a risk factor for aggravated outcomes, suggesting that corticosteroid therapy should be reduced if possible. Although systemic corticosteroids are recommended for the treatment of patients with severe COVID-19 in intensive care units, these drugs might augment mortality in non-severe COVID-19 cases. Immunosuppression in IBD and liver transplant recipients appears not to induce aggravated outcomes and might even exert a protective effect against severe COVID-19; patients should consider vaccination whenever available.

Background: Oral cladribine is an approved disease-modifying drug for the treatment of relapsing multiple sclerosis. In controlled clinical trials as well as in post marketing safety assessments, autoimmune conditions have not yet been reported as a specific side effect of cladribine. Objective and Results: Here, we report a case of anti-glomerular basement membrane antibody-mediated glomerulonephritis that occurred shortly after the fourth cladribine treatment cycle. Conclusion: Neurologists should be attentive to the development of secondary autoimmunity in cladribine-treated patients.

Complementary and alternative medicine (CAM) use has become increasingly common. It is also prevalent in patients with chronic liver disease, but the scope, depth, and safety of use is not well known. This study aimed to evaluate the prevalence and patterns of CAM use in autoimmune hepatitis (AIH) patients. Electronic invitation to complete a 22 item CAM-specific questionnaire was posted weekly to well-established AIH Facebook communities (combined membership of 4700 individuals) during a 6-week study period. Age ≥ 18 years and AIH diagnosis made by a treating physician were the eligibility criteria. The prevalence of ever CAM use among participants was 56.4%, and nearly 42% used CAM after AIH diagnosis. Among those reporting CAM use after diagnosis, 53.7% (51/95) indicated CAM was used to mitigate AIH-related phenomenon, most often targeting liver inflammation/fibrosis (67.7%), fatigue (51%), joint pain (47.1%), and sleep issues (45.1%). Most frequent physical CAM strategies were exercise (49.5%) and yoga (34%), whereas most frequent consumable CAM included healthier eating (45.3%), cannabidiol preparations (45.3%), and probiotics (44.3%). Seventy-five percent reported that CAM improved AIH symptoms and no severe adverse events were reported. CAM use in AIH patients is prevalent, yet providers have historically failed to document their patient’s CAM strategies. Beyond inherent drug-induced liver injury risk, drug-drug interactions remain a concern and could alter baseline immunosuppression levels in AIH. Despite a majority found CAM approaches that improved targeted symptoms, all were unable to alter the course of chronically prescribed medications by physicians.