Prevalence of Acute on Chronic Liver Failure in Autoimmune Hepatitis, Treatment Response and Mortality Burden Assessment: A Region-Predominant Systematic Review and Meta-Analysis.

Acute-on-chronic liver failure (ACLF) is a global health problem. Little scientific evidence exists on its prevalence in autoimmune hepatitis. Treatment response and mortality outcomes have also been reported differently. The study was conducted to estimate the overall prevalence of ACLF among patients with autoimmune hepatitis (AIH) and determine the associated treatment response and mortality. We scrutinized wide literature in Scopus, PubMed, Embase, Web of Science, and Cochrane, and assessed published articles completely, studies performed and reported from around the globe, until December 07, 2023, according to the PROSPERO registered protocol (CRD42023412176). Studies (retrospective and prospective cohort study type) that stated the ACLF development among established AIH cases were considered. Features of the study, duration of follow-up, and numeric patient information were retrieved from the studies included. The research paper quality was checked for risk of bias. Random effect meta-analysis with metaregression and subsection scrutinies were performed with R. The main outcome was the collective prevalence of ACLF in the AIH patients, whereas treatment response and mortality in AIH-associated ACLF were secondary outcomes. Six studies were involved with confirmed diagnoses in 985 AIH patients for the data synthesis. The pooled prevalence of ACLF in the explored patients was 12% (95% CI: 8-17) ( P =0.01). Heterogeneity was found to be high in the present meta-analysis ( I2 =72%; P < 0.01). For the secondary endpoint analysis, the pooled prevalence of complete remission at 1-year follow-up was 71% (0.52; 0.85), and mortality from the ACLF-AIH patient population was 32% (95% CI: 18-50). Sensitivity analysis showed no influence on the overall estimations of the pooled prevalence of ACLF by omitting studies one by one. One in 10 AIH patients likely present with ACLF. The response to treatment is seen in two-thirds of patients, and mortality is high.

Autoimmune Hepatitis and Obstetrical Outcomes: A Nationwide Assessment.

INTRODUCTION: Previous research identified AIH as linked to unfavorable obstetrical outcomes in a US nationwide retrospective study from 2012-2016. Our aim is to update the literature and strengthen the AIH-pregnancy outcomes relationship. METHODS: Using the National Inpatient Sample database in the US, from 2016 to 2020, we compared pregnant females with a diagnosis of AIH to those with and without other chronic liver diseases (CLD), using ICD-10-CM codes. Baseline characteristics were analyzed using T-test and Chi-Square, and multivariate regression was used to estimate the differences in maternal outcomes adjusted for age, race, insurance status, geographical location, hospital characteristics, and comorbid conditions. RESULTS: Out of 19,392,328 hospitalizations for pregnant females ≥ 18 years old from 2016 to 2020, 1095 had AIH, 179,655 had CLD, and 19,206,696 had no CLD. No mortality was observed among individuals with AIH. When compared to individuals without CLD, AIH was associated with an 82% increase in the odds of preterm delivery (AIH: 8% vs. Without CLD: 5%, adjusted Odds Ratio = 1.82, 95% CI 1.06-3.14), with no significant differences in gestational diabetes mellitus, hypertensive complications, and postpartum hemorrhage, and a 0.6 day longer hospital stay. Furthermore, there were no significant differences in outcomes between AIH and CLD. CONCLUSIONS: Our study reinforces the association of AIH with adverse obstetrical outcomes (e.g., preterm delivery), however, we found that there is no difference in GDM and hypertensive complications, as suggested in prior studies. Therefore, further investigations are needed to clarify the association between AIH and these obstetrical complications.

[Assessment of the possible impact of hepatitis viruses on the development and course of autoimmune liver diseases].

BACKGROUND: Despite the well-studied pathogenesis, the etiology of autoimmune liver disease (AILD) remains unknown. AIM: To determine the significance of hepatitis A, B, C and E viruses in the development and progression of AILD. MATERIALS AND METHODS: A single-center case-control study included 139 patients with AILD: autoimmune hepatitis - AIH (n=46), primary biliary cholangitis - PBS (n=74), primary sclerosing cholangitis - PSC (n=19). Median age 56 years, IQR 48-65 years. 125 patients - without liver disease - control group (median age 55 years, IQR 46-65 years). Testing of blood serum samples for anti-HAV IgG, anti-HEV IgG, HBsAg, anti-HBc IgG, anti-HCV was carried out by solid-phase ELISA. All patients underwent fibroelastography. Needle liver biopsy - 70 patients: AIH (n=37), PBC (n=28) and PSC (n=5). RESULTS: Ab(IgG) to HAV and HBV were detected in patients with AILD significantly more often than in the control group (74.8% vs 54.4%; p<0.001). An increased risk of developing AILD was established in patients with the presence of antibodies to HAV, HBV and HEV (OR 2.491, CI 95% [1.481-4.190]). The highest risk of developing PBC was found in patients with antibodies to HAV and HBV (OR 3.008, 95% CI [1.633-5.542] and OR 2.515, 95% CI [1.242-5.093]). In patients with severe liver fibrosis (F3-F4 according to METAVIR), antibodies to HAV and HBV were detected significantly more often than in patients with F0-F2 [85% vs 65%; p=0.008]. CONCLUSION: In our work, we have demonstrated the relationship of past hepatitis A, B, E and AILD, as well as the high risk of developing severe fibrosis in patients with AILD and markers of hepatitis A and B viruses indicates the possible involvement of these viruses in the pathogenesis of AILD.

We Are Not Immune: Racial and Ethnic Disparities in Autoimmune Liver Diseases.

Autoimmune liver diseases are attributed to a complex interplay of biologic, acquired, and environmental factors. Increased prevalence, later stage at presentation, worse response to standard therapy, and transplant-related disparities have all been reported in racial and ethnic minorities such as Black and Latinx patients with autoimmune liver diseases. While biology and inherited genetic predispositions may partly explain these disparities, definitive and universal genetic variations underlying these differences in outcomes have not been defined. Nonetheless, socioeconomic status, access to health care, environmental and societal factors, and implicit provider bias can all contribute to poor patient outcomes. There remains an unmet need to understand and mitigate the factors contributing to health inequity in autoimmune liver diseases. In this review, we summarize the data on racial and ethnic disparities in presentation, treatment response, and outcomes pertaining to autoimmune liver diseases in minority populations, on the premise that understanding disparities is the first step toward reaching health equity.

Autoimmune hepatitis in human immunodeficiency virus-infected patients: A case series and review of the literature.

BACKGROUND: Abnormal liver chemistry is a common problem in human immunodeficiency virus (HIV)-infected patients. Common causes of abnormal liver enzymes in this population include viral hepatitis B/C or opportunistic infection, drug toxicity, and neoplasm. Autoimmune hepatitis is a rare cause of hepatitis in HIV-infected individuals; however, this condition has been increasingly reported over the past few years. CASE SUMMARY: We present 13 HIV-infected patients (5 males and 8 females) who developed autoimmune hepatitis (AIH) after their immune status was restored, i.e. all patients had stable viral suppression with undetectable HIV viral loads, and median CD4+ counts of 557 cells/× 106 L. Eleven patients presented with chronic persistent elevation of aminotransferase enzyme levels. One patient presented with acute hepatitis and the other patient presented with jaundice. The median levels of aspartate aminotransferase and alanine aminotransferase enzymes were 178 and 177 U/mL, respectively. Elevation of immunoglobulin G levels was present in 11 (85%) patients. Antinuclear antibody and anti-smooth muscle antibody were positive in 11 (85%) and 5 (38%) patients. Liver biopsy was performed in all patients. They had histopathological findings compatible with AIH. The patients were started on prednisolone for remission induction, with good response. After improvement of the liver chemistry, the dose of prednisolone was tapered, and azathioprine was added as life-long maintenance therapy. At the last follow-up visit, all were doing well, without HIV viral rebound or infectious complications. CONCLUSION: This report underscores the emergence of autoimmune hepatitis in the context of HIV infection.

Association of Autoimmune Hepatitis and Cardiovascular Disease.

BACKGROUND: Autoimmune Hepatitis is a chronic liver disease while Cardiovascular Disease is seen in inflammatory states. This study sought to determine if Cardiovascular Disease was associated with Autoimmune Hepatitis. METHODS: The National Inpatient Sample selected patients with a primary diagnosis of Autoimmune Hepatitis and secondary diagnosis of Cardiovascular Disease in 2014. The primary outcome was the association of Autoimmune Hepatitis with Cardiovascular Disease. Secondary outcomes evaluated the hospital burden with Cardiovascular Disease. RESULTS: 16,375 patients with Autoimmune Hepatitis were included in the study. There was a decreased association between Autoimmune Hepatitis and Cardiovascular Disease (aOR 0.77, 95% CI 0.69-0.85, p < 0.00), Coronary Artery Disease, (aOR 0.75, 95% CI 0.67-0.85, p < 0.00), and Peripheral Vascular Disease (aOR 0.75, 95% CI 0.60-0.93, p = 0.01). Moreover, Coronary Artery Disease comprises 84% of the overall Cardiovascular Disease cohort and did not demonstrate significantly increased length of stay (aOR -0.53, 95% CI -1.16 to 0.12, p = 0.11) or hospitalization cost (aOR -6711, 95% CI -14336 to 912, p = 0.08). DISCUSSION: The decreased association between Autoimmune Hepatitis and Cardiovascular Disease is likely multifactorial in etiology. Consequently, this observation requires further examination with prospective trials.

Inequity of care provision and outcome disparity in autoimmune hepatitis in the United Kingdom.

BACKGROUND: Treatment paradigms in autoimmune hepatitis (AIH) have remained largely unchanged for decades. Studies report ≤20% of patients have sub-optimal treatment response with most requiring long-term therapy. AIM: The United Kingdom Autoimmune Hepatitis (UK-AIH) study was established to evaluate current treatment practice and outcomes, determine the unmet needs of patients, and develop and implement improved treatment approaches. METHODS: The United Kingdom Autoimmune Hepatitis study is a cross-sectional cohort study examining secondary care management of prevalent adult patients with a clinical diagnosis of autoimmune hepatitis. Enrolment began in March 2014. Prevalent cases were defined as having been diagnosed and treated for >1 year. Demographic data, biochemistry, treatment history and response, and care location were collected. RESULTS: In total, 1249 patients were recruited; 635 were cared for in transplant units and 614 in non-transplant centres (81% female with median age at diagnosis 50 years). Overall, 29 treatment regimens were reported and biochemical remission rate was 59%. Remission rates were significantly higher in transplant compared to non-transplant centres (62 vs 55%, P = 0.028). 55% have ongoing corticosteroid exposure; 9% are receiving prednisolone monotherapy. Those aged ≤20 years at diagnosis were more likely to develop cirrhosis and place of care was associated with an aggressive disease phenotype. CONCLUSIONS: There are significant discrepancies in the care received by patients with autoimmune hepatitis in the UK. A high proportion remains on corticosteroids and there is significant treatment variability. Patients receiving care in transplant centres were more likely to achieve and maintain remission. Overall poor remission rates suggest that there are significant unmet therapeutic needs for patients with autoimmune hepatitis.

Race/ethnicity is an independent risk factor for autoimmune hepatitis among the San Francisco underserved.

Although autoimmune hepatitis (AIH) is more common in women and affects people of all races/ethnicities, there is currently limited information regarding the relationship between race/ethnicity and AIH, especially in the context of underserved populations. We aim to evaluate the relationship between race/ethnicity and AIH and better characterize its clinical features among different racial groups. We conducted a 15-year retrospective analysis, from January 2002 to June 2017, of patients seen at Zuckerberg San Francisco General Hospital (ZSFG). Sixty-three AIH patients and 2049 non-AIH controls were eligible for the study. The main predictor of interest was race/ethnicity, and the main outcome of interest was AIH diagnosis; other secondary measures recorded include clinical features such as ALT, bilirubin, and biopsy fibrosis at presentation. In a multivariable model adjusting for age and sex, we found that black (OR 9.6, 95% CI 1.8-178), Latino (OR 25.0, 95% CI 5.3-448), and Asian/Pacific Islander (API) (OR 10.8, 95% CI 2.2-196) race/ethnicity were associated with increased odds of an AIH diagnosis compared to the white reference group. Among people of colour with AIH, there were no significant differences in baseline ALT (p = .45), total bilirubin at presentation (p = .06), fibrosis at presentation (p = .74), and hospitalization (p = .27). Race/ethnicity is an independent risk factor for AIH. The clinical features of AIH did not differ significantly among black, Latino, and API patients.

Population-based prevalence, incidence, and disease burden of autoimmune hepatitis in South Korea.

BACKGROUND AND AIM: Little is known about population-based epidemiology and disease burden of autoimmune hepatitis (AIH). The aim of this study was to investigate the prevalence, incidence, comorbidity and direct medical cost of AIH in South Korea. METHODS: The data was from the nationwide, population-based National Health Insurance Service claims database and the Rare Intractable Disease registration program. Age and gender-specific prevalence rates were calculated, and data on comorbidity, diagnostic tests, prescribed drugs, and medical costs were retrieved for patients registered under the disease code K75.4 (AIH) from 2009 to 2013. RESULTS: A total of 4,085 patients with AIH were identified between 2009 and 2013 with a female-to-male ratio of 6.4. The age-adjusted prevalence rate was 4.82/100,000 persons and gender adjusted prevalence rates were 8.35 in females and 1.30 in males. The age-adjusted calculated incidence rate was 1.07/100,000 persons (gender-adjusted 1.83 in females and 0.31 in males). Ascites, variceal bleeding, and hepatocellular carcinoma were found in 1.4%, 1.3%, and 2.2% of the patients, respectively. Forty-six patients (1.1%) underwent liver transplantation during the study period. Case-fatality was 2.18%. Corticosteroid and azathioprine were prescribed in 44.1% and 38.0% of prevalent patients with AIH in 2013, respectively. The nationwide total direct medical cost was less than 4.0 million USD, and the average cost for each patient was 1,174 USD in 2013. CONCLUSION: This is the first report on the nationwide epidemiology of AIH in Korea, and it showed a lower prevalence than that of Western countries with considerable disease burden.

Global Disparities and Their Implications in the Occurrence and Outcome of Autoimmune Hepatitis.

Autoimmune hepatitis has a variable occurrence, clinical phenotype, and outcome, and the factors contributing to this variability are uncertain. The goals of this review are to examine the global disparities in the occurrence and outcome of autoimmune hepatitis, suggest bases for these disparities, and encourage investigations that extend beyond single-center experiences. Disparities in the incidence and prevalence of autoimmune hepatitis in different age groups, genders, ethnicities, and geographical regions suggest that factors other than genetic predisposition are involved. Age- and gender-related antigen exposures from the external (infections, toxins, and medications) and internal (intestinal microbiome) environment may affect the incidence of the disease, and the timeliness and nature of treatment may influence its prevalence. The increasing incidence of autoimmune hepatitis in Spain, Denmark, and the Netherlands suggests that a new etiological trigger has been introduced or that the susceptible population has changed. Variations in mortality between Western and Asian-Pacific countries may result from differences in disease detection or management, and variations in gender predilection, peak age of onset, frequency of concurrent immune diseases, and serological profile may reflect gender-biased and age-related antigen exposures and genetic predispositions. Global collaborations, population-based epidemiological studies that identify case clustering, and controlled interview-based surveys are mechanisms by which to understand these disparities and improve management. In conclusion, autoimmune hepatitis has a rising incidence in some countries and variable occurrence, phenotype, and outcome between countries and subgroups within countries. These disparities suggest that unrecognized population-based environmental, infectious, or socioeconomic factors are affecting its character.

Transient elastography as a noninvasive assessment tool for hepatopathies of different etiology in pediatric type 1 diabetes mellitus.

AIM: To identify the prevalence and effect of hepatopathies of different etiologies among pediatric patients with type 1 diabetes mellitus (T1DM) using transient elastography (TE) and its relation to glycemic control. METHODS: One hundred T1DM patients were studied focusing on liver functions, fasting lipid profile, hemoglobin A1c (HbA1c), hepatitis C virus (HCV), serum immunoglobulins, autoimmune antibodies; anti-nuclear antibody (ANA), anti-smooth muscle antibody (ASMA), and anti-liver kidney microsomal antibody (anti-LKM). Abdominal ultrasound was performed and TE was done for patients with HCV, positive autoimmune antibody and/or abnormal ultrasound findings. RESULTS: Thirty-one patients were found to have one or more hepatic abnormalities; clinical hepatomegaly in 8%, elevated alanine aminotransferase (ALT) in 10%, HCV in 6%, autoimmune hepatitis (AIH) in 11% (10 were positive for ASMA and 2 were positive for ANA while anti-LKM antibodies were negative) and abnormal hepatic ultrasound in 20% (12 non-alcoholic fatty liver disease, 5 AIH, 2 HCV, 1 Mauriac syndrome). Mean liver stiffness in those 31 patients was 7.0±2.1kPa (range, 3.1-11.8kPa); 24 were Metavir F0-F1, 7 were F2-F3 while none was F4. Type 1 diabetic patients with abnormal hepatic ultrasound had higher fasting blood glucose, HbA1c and total cholesterol than those with normal findings. Liver stiffness was significantly higher in patients with abnormal liver ultrasound compared with normal sonography. Liver stiffness was positively correlated to HbA1c and ALT. CONCLUSIONS: Hepatic abnormalities are prevalent in T1DM and related to poor metabolic control. TE provides a non-invasive method for detection of hepatopathy-induced fibrosis.

Women with Cirrhosis: Prevalence, Natural History, and Management.

Cirrhosis is less frequent in women than in men, in large part due to the lower prevalence of hepatitis B, hepatitis C, and alcohol use in women. The most common causes of cirrhosis among women are hepatitis C, autoimmune etiologies, nonalcoholic steatohepatitis, and alcoholic liver disease. For most chronic liver diseases, the risk of progression to cirrhosis and rates of liver failure and hepatocellular carcinoma are lower in women than in men. Pregnancy is very infrequent in women with cirrhosis due to reduced fertility, but when it occurs, requires specialized management.

The impact of race/ethnicity on the clinical epidemiology of autoimmune hepatitis.

GOALS: To evaluate race/ethnicity-specific variations in autoimmune hepatitis (AIH) with a focus on Asians and Hispanics, the fastest growing populations in the United States. BACKGROUND: AIH is a chronic inflammatory disease in which race/ethnicity-specific variations in clinical epidemiology have been reported. However, earlier studies were small or did not include a comprehensive analysis of Asians and Hispanics, the 2 fastest growing population cohorts in the United States. STUDY: A retrospective study analyzing patient data from 1999 to 2010 in a large tertiary-care community hospital to assess AIH epidemiology among a racially diverse population. RESULTS: One hundred eighty-three patients with AIH were included in the study with 81 patients having "definite" AIH by International Autoimmune Hepatitis Group criteria and 63 were diagnosed with overlap syndromes. Women and whites were the largest cohorts. The average age of diagnosis was similar among all groups. Biopsy-confirmed cirrhosis was present in 34% of AIH patients with Hispanics demonstrating the highest prevalence of cirrhosis (55%). When compared with whites, Asians had higher international normalized ratio (INR) (1.4 U vs. 1.1 U, P<0.01), and Hispanics had lower serum albumin (3.3 g/dL vs. 3.7 g/dL, P<0.001) and platelets (123.8 thousand/mcL vs. 187.5 thousand/mcL, P<0.001) and higher international normalized ratio (1.5 U vs. 1.1 U, P=0.05). Kaplan-Meier survival analysis demonstrated a trend toward worse outcomes among Asians. CONCLUSIONS: Among AIH patients, Hispanics had the highest prevalence of cirrhosis, and Asians had poorer survival outcomes. Race/ethnicity-specific disparities in AIH epidemiology may reflect underlying genetic differences, contributing to variations in disease severity, response to therapy, and overall mortality.

Epidemiological assessment of liver disease in northeastern Brazil by means of a standardized liver biopsy protocol.

BACKGROUND/AIM: The main objective of this study was to describe the profile of patients who were benefitted in a collective effort to perform liver biopsies in Bahia, Brazil. METHOD: A cross-sectional study was conducted with a sample composed of all the patients who were submitted to liver biopsy during a collective effort carried out in Bahia between July 2007 and November 2009. At the time of the procedure, date on the age and gender of patients and the reason for performing the biopsy were recorded. Data on the degree of fibrosis and the presence of co-morbidities. Following statistical analysis, the frequency of the liver diseases that led to the biopsy procedure was described, and the profile of the patients was stratified into groups according to the most prevalent etiologies. RESULTS: Of the 550 patients evaluated, 55.3% were men and 44.7% women. Mean age was 46.63 ± 11.59 years and there was no statistically significant difference in age between males and females. Of the 550 patients, 72% had hepatitis C and the mean age of these patients was 48.49 ± 10.1 years, significantly higher than the mean age of the patients with hepatitis B (40.41 ± 12.43 years). Furthermore, 70.7% of the patients with hepatitis C were between 41 and 60 years of age. The most frequent fibrosis grade was F2 (44%) and the prevalence of advanced fibrosis was 27.7%. Overall, 85 patients, most of them men, had some degree of iron overload. With respect to the safety of the biopsy procedure, severe complications occurred in only two patients. CONCLUSION: Hepatitis C is the predominant liver disease that demanded liver biopsy. The profile of the patients who benefitted from this collective effort is similar to that of patients in the rest of the country. Moreover, non-Ultrasonography guided liver biopsy is safe and the collective effort to carry out liver biopsies in Bahia was found to be a viable venture.

[ALT screening for chronic liver diseases: scrutinizing the evidence]. / ALT als Screeningparameter für Lebererkrankungen: eine kritische Evaluation der Evidenz.

Elevated serum amino-transferase levels may be associated with liver injury. Testing for aspartate aminotransferase (AST) or alanine aminotransferase (ALT) is part of many routine screening approaches. The aim of this manuscript was to scrutinize the evidence for using ALT testing as a primary screening parameter for liver diseases. We conclude that (i) elevated serum ALT levels indicate a high specificity and a reasonable sensitivity liver injury, (ii) 10 - 25 % of German adults have elevated ALT levels, (iii) ALT values are increased in the majority but not all patients with acute and chronic liver disease (iv) elevated ALT-values are associated with an increased risk of liver-specific mortality, (v) elevated ALT values are also a risk factor for non-hepatic diseases including diabetes mellitus type 2, metabolic syndrome, cardiovascular diseases and malignancies, (vi) many liver diseases identified by an ALT screening can be treated successfully including prevention of development of clinical endpoints, (vii) an ALT-screening is very likely to be cost-effective although studies are needed for Germany to support this conclusion.

[Incidence and prevalence of autoimmune hepatitis in the area of the Hospital de Sagunto (Spain)]. / Incidencia y prevalencia de hepatitis autoinmune en el área sanitaria del Hospital de Sagunto.

Thirteen cases of autoimmune hepatitis (AIH) were diagnosed from 1990 to 2003 in the area of the Hospital de Sagunto (Valencia, Spain), which attends a population of 112,003 inhabitants aged more than 14 years (54,622 males and 57,381 females). The diagnostic criteria of the International Autoimmune Hepatitis Group were used and patients who, despite having a probable diagnosis of AIH, presented hepatitis C virus infection were excluded. The diagnosis was probable in one patient and definitive in 12. All patients, 11 females and two males aged 45.9 12.2 years (range: 28-66), were classified as AIH type 1. Among the population aged more than 14 years, the mean annual incidence of AIH was 0.83 cases/100,000 inhabitants (95% CI, 0.44-1.42) (range: 0-2.68), showing a significant trend to increase (b = 0.132; p = 0.019). The incidence was higher in women than in men (RR = 5.24; 95% CI, 1.16-23.62). The mean annual incidence was 1.37 (95% CI, 0.68-2.46) (range: 0-3,49) in women and was 0.26 (95% CI, 0.02-0.96) (range: 0-1.83) in men. By age, the maximum mean annual incidence was observed in the group aged 55-64 years (1.6 cases/100,000 inhabitants). The prevalence of AIH in September 2003 was 11.61 cases/100,000 inhabitants aged more than 14 years (95% CI, 6.78-19.86). The prevalence was 3.66 (95% CI, 1-13.35) in men and was 19.17 (95% CI, 10.70-34.33) in women.

Medical and economic impact of autoimmune hepatitis.

AIH is a chronic liver disease that has been associated with hepatic failure and death in the absence of liver transplantation. As a result, AIH imparts significant medical and economic burdens on affected patients and health care delivery systems, respectively. The use of accepted methodologies for outcomes and health services research has identified emerging information on the epidemiology and natural history, HRQoL, and resource utilization for similar autoimmune chronic liver diseases such as PBC and PSC. Similar efforts are needed in AIH, and they are supported on the basis of existing data which suggest similar levels of disease burden compared to PBC and PSC. As a result, the ability to plan for disease management strategies in AIH that require the allocation of scarce resources will be feasible.