[Clinicopathological features of Sjogren's syndrome complicated with liver injury].

Objective: To study the clinicopathological features of Sjogren's syndrome (SS) with liver injury and to improve the understanding of this disease. Methods: Forty-nine patients with SS complicated with liver injury were collected from Beijing Ditan Hospital, Capital Medical University from October 2008 to January 2022. All patients underwent ultrasound-guided liver biopsy, and all specimens were stained with HE. The histopathologic characteristics were observed and the pathologic indexes were graded. Immunohistochemical stains for CK7, CK19, CD38, MUM1 and CD10 were performed by EnVision method; and special histochemical stains for reticulin, Masson's trichrome, Rhodanine, Prussian blue, periodic acid Schiff (PAS) and D-PAS stains were conducted. Results: The age of patients ranged from 31 to 66 years, including 3 males and 46 females. SS combined with drug-induced liver injury was the most common (22 cases, 44.9%), followed by autoimmune liver disease (13 cases, 26.5%, including primary biliary cholangitis in eight cases, autoimmune hepatitis in 3 cases, and PBC-AIH overlap syndrome in 2 cases), non-alcoholic fatty liver disease (NAFLD, 9 cases, 18.4%) and other lesions (5 cases, 10.2%; including 3 cases of nonspecific liver inflammation, 1 case of liver amyloidosis, and 1 case of porto-sinusoidal vascular disease). Among them, 28 cases (57.1%) were associated with obvious interlobular bile duct injury, mainly in SS combined with PBC group and drug-induced liver injury group. Twenty-three cases (46.9%) were associated with hepatocyte steatosis of varying degrees. In SS with autoimmune liver disease group, ISHAK score, degree of fibrosis bile duct injury, bile duct remodeling, lymphocyte infiltration of portal area, and plasma cell infiltration, MUM1 and CD38 expression; serum ALP and GGT, IgM; elevated globulin; positive AMA, proportion of AMA-M2 positive and IgM positive were all significantly higher than those in other groups(all P<0.05). Serum ALT, direct bilirubin and SSA positive ratio in SS combined with drug liver group were significantly higher than those in other groups(all P<0.05). The serum total cholesterol level in SS combined with PBC group (P=0.006) and NALFD group (P=0.011) were significantly higher than those in other groups (P<0.05). Conclusions: The pathologic manifestations of SS patients with liver injury are varied. The inflammatory lesions of SS patients with autoimmune liver disease are the most serious, and the inflammatory lesions of SS patients with non-alcoholic fatty liver disease and non-specific inflammation are mild. Comprehensive analysis of liver histopathologic changes and laboratory findings is helpful for the diagnosis of SS complicated with different types of liver injury.

Unprecedented complexity of six coexisting autoimmune diseases: A case report.

INTRODUCTION: Autoimmune disorders often exhibit interconnectedness, although encountering multiple autoimmune conditions in a single patient is uncommon. Multiple autoimmune syndrome is characterized by the presence of at least three distinct autoimmune diseases in an individual. This report outlines the case of a middle-aged woman diagnosed with autoimmune thyroiditis, Sjögren's syndrome, scleroderma, autoimmune hepatitis, primary biliary cirrhosis, and antisynthetase syndrome. Additionally, it includes a literature review encompassing multiple autoimmune syndromes involving five or more autoimmune diseases. OBSERVATION: A 57-year-old woman, with no previous medical history, presented with fever, extensive muscle weakness, progressive exertional dyspnea, inflammatory polyarthralgia, dysphagia, and dry mouth. Clinical examination revealed muscular deficit in the scapular and pelvic girdles, distal muscular deficit, synovitis in the wrists, and features indicative of "mechanic's hand". Laboratory examinations showed cytolysis, cholestasis, elevated muscle enzymes, hypergammaglobulinemia and elevated thyroid stimulating hormone. Immunoassays showed positive results for antinuclear antibodies, anti-histidyl-t-RNA synthetase, anti-Sjögren's-syndrome-related antigen A, anti-ribonucleic-acid-polymerase-III-RP155, anti-fibrillarin, anti-mitochondrial, anti-liver/kidney microsomal type 1, anti-glycoprotein 210, and anti-thyroid peroxidase antibodies. Further investigations led to the diagnosis of a multiple autoimmune syndrome involving autoimmune thyroiditis, Sjögren's syndrome, scleroderma, autoimmune hepatitis, primary biliary cirrhosis, and antisynthetase syndrome. The patient received treatment with intravenous immunoglobulins, corticosteroids, azathioprine, and ursodeoxycholic acid, which resulted in favorable clinical and biological outcomes. CONCLUSION: This patient presented with six concurrent distinct autoimmune disorders, categorizing this case as a type two multiple autoimmune syndrome. The identification of antisynthetase syndrome notably distinguishes this case.

Management of autoimmune hepatitis induced by hepatitis delta virus.

Approximately 12-72 million people worldwide are co-infected with hepatitis B virus (HBV) and hepatitis delta virus (HDV). This concurrent infection can lead to several severe outcomes with hepatic disease, such as cirrhosis, fulminant hepatitis, and hepatocellular carcinoma, being the most common. Over the past few decades, a correlation between viral hepatitis and autoimmune diseases has been reported. Furthermore, autoantibodies have been detected in the serum of patients co-infected with HBV/HDV, and autoimmune features have been reported. However, to date, very few cases of clinically significant autoimmune hepatitis (AIH) have been reported in patients with HDV infection, mainly in those who have received treatment with pegylated interferon. Interestingly, there are some patients with HBV infection and AIH in whom HDV infection is unearthed after receiving treatment with immunosuppressants. Consequently, several questions remain unanswered with the challenge to distinguish whether it is autoimmune or "autoimmune-like" hepatitis being the most crucial. Second, it remains uncertain whether autoimmunity is induced by HBV or delta virus. Finally, we investigated whether the cause of AIH lies in the previous treatment of HDV with pegylated interferon. These pressing issues should be elucidated to clarify whether new antiviral treatments for HDV, such as Bulevirtide or immu-nosuppressive drugs, are more appropriate for the management of patients with HDV and AIH.

The prevalence and disease course of autoimmune liver diseases in Greenland.

Autoimmune liver diseases are rare serious diseases causing chronic inflammation and fibrosis in the liver parenchyma and bile ducts. Yet, the prevalence and burden of autoimmune liver diseases are largely unexplored in Arctic native populations. We investigated the prevalence and management of autoimmune liver diseases in Greenland using nationwide cross-sectional register data and subsequent medical chart reviews validating diagnoses and extracting liver histology examinations and medical treatments. The overall prevalence of autoimmune liver diseases in Greenland was 24.6 per 100,000 (95% CI: 14.7-41.3). This was based on 7 patients with autoimmune hepatitis (AIH) (12.3 per 100,000), 3 patients with primary biliary cholangitis (PBC) (5.3 per 100,000), 4 patients with AIH/PBC overlap disease (7.0 per 100,000), and no patients with primary sclerosing cholangitis. All diagnoses were confirmed by liver histology examinations. Medical treatments adhered to internal recommendations and induced complete remission in most patients with AIH, and complete or partial remission in 1 patient with PBC and 3 patients with AIH/PBC overlap disease. One patient had established cirrhosis at the time of diagnosis, while 2 patients progressed to cirrhosis. In conclusion, the prevalence of autoimmune liver diseases was lower in Greenland than in Scandinavia and among Alaska Inuit.

Onset of acute severe autoimmune hepatitis after severe acute respiratory syndrome coronavirus 2 infection: a case report.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can trigger autoimmune inflammation in the liver, leading to acute autoimmune hepatitis (AIH). We herein report a case involving a 39-year-old woman with a 23-day history of yellow skin and urine. Using the revised original scoring system of the International AIH Group, we definitively diagnosed the patient with acute severe AIH (AS-AIH). She began treatment with 80 mg/day intravenous methylprednisolone, which was gradually reduced and followed by eventual transition to oral methylprednisolone. The patient finally achieved a biochemical response after 30 days of therapy, and liver transplantation was avoided. Clinicians should be aware that the onset of AS-AIH after SARS-CoV-2 infection differs from the onset of conventional AIH with respect to its clinical and pathological features. Early diagnosis and timely glucocorticoid treatment are crucial in improving outcomes.

[Treatment of autoimmune hepatitis-First-line, second-line and third-line treatment]. / Therapie der Autoimmunhepatitis ­ Erst­, Zweit- und Drittlinientherapie.

Autoimmune hepatitis (AIH) is a rare autoimmune inflammation of the liver mostly with a chronic course, which can also be acutely manifested up to acute liver failure. It affects women 3-4 times more frequently than men and can be diagnosed in all age groups. In one third of the patients a liver cirrhosis is present at the time of diagnosis. It is characterized by a hepatic inflammation pattern, a polyclonal hypergammaglobulinemia of immunoglobulin G and the detection of autoantibodies. A liver biopsy is necessary to make the diagnosis. The AIH is histologically characterized in particular by a lymphoplasmacytic infiltrate in the portal fields. In cases with a relevant disease activity, AIH is typically treated by immunosuppression. The immunosuppressive treatment is associated with a prevention of disease progression to liver cirrhosis and a better survival. The success of treatment is measured by achieving biochemical remission, i.e., normalization of the transaminase and immunoglobulin G levels as a good noninvasive predictor of a histological remission. Another treatment target is an improvement of the symptoms of the patient. The first-line treatment consists of a glucocorticoid, mostly prednisolone or in cases without advanced fibrosis budesonide, and azothioprine. For reduction of steroid-specific treatment side effects the maintenance treatment should be carried out steroid-free whenever possible. In cases of insufficient response to azothioprine or side effects a treatment attempt using antimetabolites, such as 6­mercaptopurine or mycophenolate mofetil is primarily carried out as second-line treatment. For patients who do not achieve biochemical remission through first-line or second-line treatment, a variety of medications are available for third-line treatment, e.g., rituximab, calcineurin inhibitors or antitumor necrosis factor (anti-TNF) antibodies. Third-line treatment should be carried out in expert centers and registered in the European Reference Network for Rare Liver Diseases in order to improve the currently sparse database for these forms of treatment in the future.

Autoimmune liver disease triggered by SARS-CoV-2: a case report and review of the literature.

BACKGROUND: An increasing number of coronavirus disease 2019 (COVID-19) related autoimmune hepatitis (AIH) and autoimmune liver disease (AILD) has been already described so far in the last three years. This rise has set up some diagnostic and therapeutic concerns, although steroid therapy has mostly been efficient, avoiding main significant side effects. CASE REPORT: We report the case of a 52-year-old subject displaying liver function impairment at the laboratory tests while positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swab. Needle liver biopsy showed severe portal inflammation, interface hepatitis, lobular inflammation, abundant plasma cells, bridging necrosis, endothelialitis, bile duct vanishing disease, and ductular reaction. The diagnosis of autoimmune liver disease (AILD) was performed. After a month of steroid and ursodeoxycholic acid medications, liver function fully recovered. Azathioprine was introduced, and steroids were gradually reduced. CONCLUSIONS: Probably triggered by the SARS-CoV-2-induced cytokine storm, the association between COVID-19 and autoimmune-related inflammatory injury may display a particular paradigm of AILD pathogenesis.

The frequency and clinical significance of antibodies to soluble liver antigen/liver pancreas in autoimmune hepatitis: a prospective single-center study.

BACKGROUND AND AIMS: Soluble liver antigen/liver pancreas antibodies (anti-SLA/LP) are specific markers for autoimmune hepatitis (AIH) that have been associated with a distinct clinical phenotype and a more aggressive form of AIH. We prospectively evaluated the frequency and clinical significance of anti-SLA/LP in Turkish patients with AIH. MATERIAL AND METHODS: We prospectively included patients diagnosed with AIH between January 2018 and May 2023. Autoantibodies were detected using by immunofluorescence and immunoblot. RESULTS: We included 61 (80%, female) AIH patients with a median age of 31 years (15-78) at the time of diagnosis. Anti-SLA/LP was detected in 20% ( n  = 12) of the patients. Baseline characteristics, treatment responses and outcomes were similar among anti-SLA/LP-positive and anti-SLA/LP-negative AIH patients. Anti-SLA/LP-positive patients had significantly higher biochemical response rates after 4 weeks (100 vs. 67%, P  = 0.027), 3 months (100 vs. 39%, P  < 0.001), 6 months (100 vs. 69%, P  = 0.041) of therapy but not after 12 months (100 vs. 76%, P  = 0.103) and at the end of follow-up (100 vs. 91%, P  = 0.328). Relapse rates following treatment response were similar in patients with and without anti-SLA/LP (22 vs. 23%, P  = 0.956). Second-line therapies (tacrolimus and mycophenolate mofetil) were given to seven (11%) patients, all were anti-SLA/LP-negative. Two of these progressed into end-stage liver disease and both underwent liver transplantation. CONCLUSION: Our study results suggest that anti-SLA/LP positivity does not entail clinically distinct or severe features in AIH. In our cohort, anti-SLA/LP-positive patients showed a quicker response to immunosuppressive therapy.

[Drug-induced autoimmune-like liver injury]. / Arzneimittelinduzierte immunvermittelte Leberschädigung.

Drug-induced liver injury (DILI) is a rare yet potentially life-threatening disease. Besides intrinsic DILI, which is mainly caused by paracetamol overdosing and which is dose-dependent and predictable, there is idiosyncratic DILI-an unpredictable and dose-independent injury of the liver caused by certain medications that only occurs in a minority of patients taking this drug. The reason why some patients react with DILI towards a specific drug is still unknown. However, the immune system plays a central role, which is underlined by the association of certain human leukocyte antigen (HLA) polymorphisms and DILI caused by specific drug classes. Due to the immunological processes that lead to the liver injury in DILI, there are great overlaps regarding laboratory and histological parameters between DILI and autoimmune hepatitis (AIH). Differentiating DILI and AIH can therefore be challenging, especially at the time of presentation. In addition, there are other immunologically mediated DILI phenotypes, in particular the newly defined drug-induced autoimmune-like hepatitis (DI-ALH) and liver injuries caused by checkpoint inhibitors (CPI). DI-ALH is characterized by autoimmune features and good responses towards corticosteroids, with the difference that DI-ALH mostly does not relapse after discontinuation of corticosteroids. CPI-induced liver injury has become more frequent with the rising use of those drugs and is characterized by a distinct histopathological pattern with granulomatous hepatitis and infiltration dominated by cytotoxic T cells. Similarly, the recently recognized liver injury following vaccinations also shows an autoimmune phenotype; however, in contrast to AIH, cytotoxic T cells seem to dominate the inflammatory infiltrates in the liver.

Retrospective, single-center analysis of autoimmune hepatitis in Jordanian children: clinical features, treatments, and outcomes.

OBJECTIVES: This study describes clinical, biochemical, and histological features and long-term outcomes in pediatric patients diagnosed with autoimmune hepatitis (AIH) at King Abdullah University Hospital, Jordan. DESIGN: Retrospective, single-center study. SETTING: King Abdullah University Hospital, Jordan. PARTICIPANTS: Inclusion of all pediatric patients with AIH diagnosed at our hospital from 2015 to 2023. Exclusion criteria was patients aged over 18 at time of diagnosis and those diagnosed elsewhere. OUTCOME MEASURES: Understanding clinical, biochemical, and histological AIH features in children, evaluating treatment responses, and reporting short- and long-term complications, including mortality. RESULTS: Sixteen pediatric cases were diagnosed, with an average age of 9.84 ± 4.13 years. Females comprised 75% of patients, and 31.3% presented with acute liver failure. Jaundice was the most common symptom, and hepatosplenomegaly was observed in 18% of cases. Most patients had elevated transaminase levels, along with positive anti-smooth muscle antibody (ASMA) and antinuclear antibodies (ANA). Common hematological abnormalities included anemia (56.3%) and thrombocytopenia (37.5%). All patients underwent liver biopsy, with interface hepatitis present in 81.3% of cases. Treatment mainly involved prednisone and azathioprine. Three patients died, one discontinued therapy, two patients were lost to follow-up, and 10 remained on treatment. CONCLUSION: Autoimmune hepatitis affects Jordanian children, primarily female children. Jaundice is the most common presenting symptoms. Only Type I AIH occurred in our cohort. Although of good response to conventional treatment with steroids and immunosuppression, mortality reached 18.8%.

Liver Transplant in Patients With Autoimmune Hepatitis: A Large Single-Center Study.

OBJECTIVES: Autoimmune hepatitis is a rare indication for liver transplant in Western countries. Our goal was to identify characteristics and long-term outcomes of patients who underwent liver transplant for autoimmune hepatitis-related end-stage liver disease at our center. MATERIALS AND METHODS: Adult patients who underwent primary liver transplant from January 2007 to March 2022 at Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran, were enrolled in our study. RESULTS: Among 1107 patients enrolled in our study, mean age was 45.94 ± 12.43 years (range, 16-73 years) and 423 (38.2%) female patients were included. Autoimmune hepatitis was the underlying cause of cirrhosis in 177 patients (experimental group); the other 930 patients did not have autoimmune hepatitis (control group). All patients were followed for a median of 60 ± 40.3 months (range, 3-187 months) after transplant. In the experimental group, patient survival rates at 1 month, 1 year, and 3 years were 87%, 81%, and 78%, which were not significantly different between the 2 groups (P = .445). Recurrence of autoimmune hepatitis was detected in 8 patients (4.5%) in the experimental group. Acute allograft rejection was more significantly detected in the patients with recurrence of autoimmune hepatitis than in patients without recurrence of autoimmune hepatitis. CONCLUSIONS: Liver transplant in patients with autoimmune hepatitis is safe and is associated with good outcomes.

Advances in the evaluation and treatment of autoimmune hepatitis.

PURPOSE OF REVIEW: The primary therapy of autoimmune hepatitis (AIH) has been established for over three decades. This review focuses on updates in the evaluation and management of patients with AIH. RECENT FINDINGS: The evaluation of patients has recently been updated to include more definitive screening for other autoimmune diseases, including thyroid disease and celiac disease. Antibody detection by ELISA, an easier and more commonly available method, has been incorporated into the latest iteration of the AIH scoring system. Corticosteroids and AZA remain the backbone of AIH treatment, but there is growing evidence for mycophenolate mofetil as both first-line and second-line therapy, and growing inquiry into calcineurin inhibitors. Noninvasive markers of liver disease have now been validated in AIH, with the strongest evidence for VCTE in patients with minimal hepatic inflammation. SUMMARY: Recent research of alternative immunosuppressant therapies, noninvasive markers of fibrosis, and updated society guidelines, have improved our ability to evaluate, treat, and follow patients with AIH.

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

BACKGROUND: Autoimmune hepatitis (AIH) is a rare, chronic inflammatory disease of the liver. The treatment goal is reaching complete biochemical response (CR), defined as the normalisation of aspartate and alanine aminotransferases and immunoglobulin gamma. Ongoing AIH activity can lead to fibrosis and (decompensated) cirrhosis. Incomplete biochemical response is the most important risk factor for liver transplantation or liver-related mortality. First-line treatment consists of a combination of azathioprine and prednisolone. If CR is not reached, tacrolimus (TAC) or mycophenolate mofetil (MMF) can be used as second-line therapy. Both products are registered for the prevention of graft rejection in solid organ transplant recipients. The aim of this study is to compare the effectiveness and safety of TAC and MMF as second-line treatment for AIH. METHODS: The TAILOR study is a phase IIIB, multicentre, open-label, parallel-group, randomised (1:1) controlled trial performed in large teaching and university hospitals in the Netherlands. We will enrol 86 patients with AIH who have not reached CR after at least 6 months of treatment with first-line therapy. Patients are randomised to TAC (0.07 mg/kg/day initially and adjusted by trough levels) or MMF (max 2000 mg/day), stratified by the presence of cirrhosis at inclusion. The primary endpoint is the difference in the proportion of patients reaching CR after 12 months. Secondary endpoints include the difference in the proportion of patients reaching CR after 6 months, adverse effects, difference in fibrogenesis, quality of life and cost-effectiveness. DISCUSSION: This is the first randomised controlled trial comparing two second-line therapies for AIH. Currently, second-line treatment is based on retrospective cohort studies. The rarity of AIH is the main issue in clinical research for alternative treatment options. The results of this trial can be implemented in existing international clinical guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT05221411 . Retrospectively registered on 3 February 2022; EudraCT number 2021-003420-33. Prospectively registered on 16 June 2021.

The evolving phenotype of autoimmune hepatitis across the millennium: The 40-year experience of a referral centre in Italy.

BACKGROUND AND AIMS: During recent years, there have been major insight into the pathogenesis, diagnosis and treatment of autoimmune hepatitis (AIH). We aim to evaluate modifications of the clinical-epidemiological phenotype of AIH patients from 1980 to our days. METHODS: Single-centre, tertiary care retrospective study on 507 consecutive Italian patients with AIH. Patients were divided into four subgroups according to the decade of diagnosis: 1981-1990, 1991-2000, 2001-2010 and 2011-2020. We assessed clinical, laboratory and histological features at diagnosis, response to treatment and clinical outcomes. Acute presentation is defined as transaminase levels >10-fold the upper limit and/or bilirubin >5 mg/dL. Complete response is defined as the normalization of transaminases and IgG after 12 months. Clinical progression is defined as the development of cirrhosis in non-cirrhotic patients and hepatic decompensation/hepatocellular carcinoma development in compensated cirrhosis. RESULTS: Median age at diagnosis increased across decades (24, 31, 39, 52 years, p < .001). Acute onset became more common (39.6%, 44.4%, 47.7%, 59.5%, p = .019), while cirrhosis at diagnosis became less frequent (36.5%, 16.3%, 10.8%, 8.7%, p < .001). Complete response rates rose (11.1%, 49.4%, 72.7% 76.2%, p < .001) and clinical progression during follow-up decreased (54.3%, 29.9%, 16.9%, 11.2%, p < .001). Anti-nuclear antibodies positivity increased (40.7%, 52.0%, 73.7%, 79.3%, p < .001), while IgG levels/upper limit progressively decreased (1.546, 1.515, 1.252, 1.120, p < .001). Liver-related death and liver transplantation reduced from 17.1% to 2.1% (p < .001). CONCLUSIONS: In the new millennium, the typical AIH patient in Italy is older at diagnosis, more often presents with acute hepatitis, cirrhosis is less frequent and response to treatment is more favourable.

Could a reduced hemoglobin, albumin, lymphocyte, and platelet (HALP) score predict autoimmune hepatitis and degree of liver fibrosis?

OBJECTIVE: Autoimmune hepatitis is a rare inflammatory disease of the liver that is characterized by elevated liver enzymes. The hemoglobin, albumin, lymphocyte, and platelet score, which is derived from hemoglobin, serum albumin, circulating lymphocyte count, and platelet count, is also associated with inflammatory conditions. The aim was to examine the hemoglobin, albumin, lymphocyte, and platelet score of patients with autoimmune hepatitis and to compare it to that of healthy individuals in this retrospective analysis. METHODS: Subjects diagnosed with autoimmune hepatitis were enrolled in the study, and healthy individuals were enrolled as controls. Moreover, autoimmune hepatitis subjects were grouped into mild or moderate/advanced fibrosis. Furthermore, aspartate to platelet ratio index, Fibrosis-4, and hemoglobin, albumin, lymphocyte, and platelet scores of the autoimmune hepatitis patients and controls were compared. In addition, the hemoglobin, albumin, lymphocyte, and platelet score of the autoimmune hepatitis patients with mild fibrosis is compared to that of those with moderate/advanced fibrosis. RESULTS: The mean hemoglobin, albumin, lymphocyte, and platelet score of the autoimmune hepatitis patients was 44.2±14.5 while this value was 76.8±15.5 in control subjects. The hemoglobin, albumin, lymphocyte, and platelet score was significantly reduced in autoimmune hepatitis patients than healthy controls (p<0.001). The hemoglobin, albumin, lymphocyte, and platelet score was significantly and negatively correlated with C-reactive protein, aspartate, alanine transaminase, gamma glutamyl transferase, aspartate to platelet ratio index, and Fibrosis-4 values. A hemoglobin, albumin, lymphocyte, and platelet score that was lower than 52.3 had 83% sensitivity and 73% specificity in predicting autoimmune hepatitis. The sensitivity and specificity of the hemoglobin, albumin, lymphocyte, and platelet score were higher than the Fibrosis-4 score in predicting moderate/advanced fibrosis in autoimmune hepatitis. CONCLUSION: We suggest that the hemoglobin, albumin, lymphocyte, and platelet score be used as an additional noninvasive diagnostic tool for autoimmune hepatitis and to predict moderate/advanced liver fibrosis in patients with autoimmune hepatitis.

Evaluation of autoimmune liver disease natural history in patients referred to Middle East Liver Diseases (MELD) center.

BACKGROUND: Autoimmune liver diseases (AILD) are increasing and common forms of chronic liver disease (CLD) with different clinical responses and characteristics which can result in cirrhosis. This study aimed to investigate the natural history and characteristics of AILD in an Iranian population. METHODS: Patients with AILD [Autoimmune Hepatitis (AIH), Primary Biliary Cholangitis (PBC), Primary Sclerosing Cholangitis (PSC) and Overlap Syndrome (OS)] referred to Middle East Liver Diseases (MELD) center, Tehran, Iran, between January 2002 and December 2022 were included in this retrospective cohort study. The main features of natural history (the trends of liver functional tests (LFT), Auto-Antibodies, response to treatment and cirrhotic status) along with demographic data were studied. RESULTS: Two hundred sixty-five patients (160 (60.4%) AIH, 37 (14.0%) PBC, 20 (7.5%) PSC, 48 (18.1%) overlap syndrome) with a median follow-up time of 5 years (IQR 4 to 8 years) were included. Baseline laboratory tests revealed that patients with AIH exhibit elevated transaminase levels. However, patients suffering from PBC and PSC displayed increased alkaline phosphatase levels. Conversely, in overlap syndrome patients, both transaminases and alkaline phosphatase were observed at high levels. Autoantibodies represented themselves as important diagnostic markers for the AIH and PBC but not for PSC. The complete response occurred in 112 (70%) of and 28 (58.4%) patients with AIH and overlap syndrome respectively and 21 patients 11 (6.9%) of AIH and 10 (20.8%) of overlap syndrome) were non-responders. Other patients in these two categories were considered as insufficient responders. On the other side, 32 (91.9%) and 8 (40%) of patients with PBC and PSC biochemically responded to Ursodeoxycholic Acid (UDCA). Unpredictably, cirrhosis regression was observed in some AIH and PBC patients. CONCLUSION: Appropriate medication management for AILD patients may leads to regression from cirrhosis and improvement of manifestations; while discontinuation of medication may cause relapses. However, patient suffering from PSC showed limited response to treatment.

Defining characteristics and long-term prognosis of drug-induced autoimmune-like hepatitis: A retrospective cohort study.

BACKGROUND: Drug-induced autoimmune-like hepatitis (DI-AILH) is poorly defined and more data are required to better characterise and manage this disease entity. OBJECTIVES: The aim of this study was to evaluate the clinical characteristics, histology and long-term outcomes of DI-AILH compared with idiopathic autoimmune hepatitis (AIH). METHODS: This retrospective cohort study reviewed 28 DI-AILH and 39 AIH patients in a single centre. The new (2022) and simplified (2008) AIH histology criteria were used to assess DI-AILH. RESULTS: DI-AILH were more likely to present with jaundice (p = 0.004) and higher bilirubin levels (p = 0.04) than AIH. AIH patients had higher rate of immunosuppression (IS) use including second- and third-line agents, though the time to reach biochemical remission were comparable. AIH patients had more advanced fibrosis than DI-AILH (Ishak fibrosis score 3.5 vs. 1.9, p < 0.0001). DI-AILH more commonly had eosinophilic aggregates (18% vs. 3%, p = 0.031) and less commonly showed plasma cell aggregates (61% vs. 97%, p < 0.001) than AIH. The simplified AIH histology criteria identified 1 atypical histology within the DI-AILH cohort, although this patient required long-term IS. The new AIH histology criteria classified 23 (82%) as likely AIH and 5 (18%) as possible AIH. Two of the possible DI-AILH did not require IS and one patient had successful IS withdrawal. Four DI-AILH patients with fibrosis stage ≤3 had successful IS withdrawal compared with none in the AIH group. Four patients underwent liver transplantation (LT) in both cohorts with significantly shorter time to LT in DI-AILH as the indication was for (sub)acute liver failure. Two DI-AILH patients died within 60 days of LT. CONCLUSION: The new AIH histology criteria may be better at identifying DI-AILH. Immunosuppression withdrawal in those without significant fibrosis may be considered. DI-AILH is at risk of (sub)acute liver failure and early discussions with a transplant centre would be desirable.

Comparison of four histological scoring systems for autoimmune hepatitis to improve diagnostic sensitivity.

BACKGROUND/AIMS: The histological criteria in the 1999 and 2008 scoring systems proposed by the International Autoimmune Hepatitis Group (IAIHG) have their inherent limitations in diagnosing autoimmune hepatitis (AIH). In this study, we evaluated the histology components of four scoring systems (1. revised original scoring system ["1999 IAIHG"], 2. simplified scoring system ["2008 IAIHG"], 3. modified histologic criteria ["2017 UCSF"], and 4. a new histologic criteria proposed by the International AIH Pathology Group ["2022 IAHPG"]) in AIH patients. METHODS: Medical records and liver biopsies were retrospectively reviewed for 68 patients from two independent medical institutions, diagnosed with AIH based on the 1999 IAIHG system between 2006 and 2016. The histological features were reviewed in detail, and the four histological scoring systems were compared. RESULTS: Out of the 68 patients, 56 (82.4%) patients met the "probable" or "definite" AIH criteria of the 2008 IAIHG system, and the proportion of histologic score 2 (maximum) was 40/68 (58.8%). By applying the 2017 UCSF criteria, the number of histology score 2 increased to 60/68 (88.2%), and "probable" or "definite" AIH cases increased to 61/68 (89.7%). Finally, applying the 2022 IAHPG histology score resulted in the highest number of cases with histologic score 2 (64/68; 94.1%) and with a diagnosis of "probable" or "definite" AIH (62/68; 91.2%). CONCLUSION: The recently proposed UCSF/IAHPG histological criteria increased the histology score of AIH. Substituting the histology component of the 2008 IAIHG system with the 2022 IAHPG criteria increased the sensitivity for diagnosing AIH (≥"Probable AIH") from 82.4% to 91.2%.