Frequency of serological results of antibodies related to autoimmune hepatitis in Iranian patients with non-viral hepatitis

doi:10.21203/rs.3.rs-4300149/v1

Background

Autoimmune hepatitis as a chronic inflammatory disease of the liver can occur when the body's immune system is stimulated against liver cells, but its exact cause is unknown. Autoimmune hepatitis, if left untreated, leads to liver damage or cirrhosis over time, which can eventually cause liver failure.

Objective

This descriptive-analytical study was done to assess the frequency of serological results of autoimmune hepatitis-related antibodies in patients with non-viral hepatitis referring to an inpatient clinic in 2019 and provide basic information for future studies and assistance in localization of external guidelines performed to diagnose autoimmune hepatitis.

Methods

All patients were evaluated for age and sex, ANA, ASMA, and LKM antibodies, and immunoglobulin by preparing 5 cc of blood samples using laboratory techniques and electrophoresis. The collected data were recorded in the checklist created by the researcher.

Results

The total number of 209 patients with non-viral hepatitis, with a mean age of 37.98 years participated in this study. In patients with non-viral hepatitis, 50.2% of patients had polyclonal hypergammaglobulinemia, in 17.2% ANA was positive, in 16.3% ASMA was positive, and 1.9% LKM was positive.

Conclusion

hypergammaglobulinemia, ANA, and ASMA are suitable antibodies for autoimmune hepatitis. Moreover, laboratory results of ANA and ASMA in patients with autoimmune hepatitis indicate low levels of these antibodies in Iran and their deficiency in other countries. Conventional diagnostic methods can provide a definitive diagnosis. Therefore, it shows the need for further examination of laboratory instruments and wider use of other diagnostic methods, including biopsy and further assessments.

Serology

Autoimmune hepatitis

Epidemiology

Antibody

Autoimmune hepatitis as a chronic inflammatory disease of the liver can occur when the immune system of the body is stimulated against liver cells. Its exact cause is unknown, but genetic and environmental factors seem to work together over time to develop the disease. Autoimmune hepatitis, if left untreated, leads to liver damage or cirrhosis over time, which can eventually lead to liver failure. The presence of circulating autoantibodies as well as elevated serum globulin levels can be observed in this disease. The disease may have an acute onset and progress to chronic hepatitis and even cirrhosis of the liver (1). Rejection of viral and medicinal hepatitis and liver biopsy and laboratory findings are the main factors for diagnosing autoimmune hepatitis. One of the characteristic laboratory findings in autoimmune hepatitis is an increase in serum levels of globulins, which are associated with circulating autoantibodies and are of the IgG type (2).

Autoimmune hepatitis is classified into two types I and II according to the type of circulating antibodies: type I: ANA, ASMA, AAA, anti-SLA / LP, anti-dsDNA and anti-ssDNA or atypical p-ANCA and rarely AMA in the form of AIH-PBC overlap and type II: anti-LKM1 or ALC-1 in the bloodstream, and a titer of 1/80 for anti-LKM1 may be considered positive while a titer greater than 1/20 is positive for ANA and ASMA (3, 4). About 20% of patients with autoimmune hepatitis lack circulating antibodies, including ANA, ASMA, or anti-LKM1, known as autoantibody negative AIH or cryptogenic chronic hepatitis. In these patients, the therapeutic response to anti-inflammatory drugs may be the only clinical finding in favor of autoimmune hepatitis (3, 4).

Autoimmune hepatitis is diagnosed based on the rejection of other common diagnoses. According to a guideline by the American Association for the Study of Liver Disease (2010), in a person with increased serum concentrations of hepatic aminotransferases, at least twice the normal maximum after ruling out viral hepatitis, alcoholic liver disease, drug hepatitis, and measuring serum globulins and common antibodies including ANA, ASMA, LKM-1, AMA, gamma globin, and serum IgG is considered in the first stage.

If common antibodies are negative, other antibodies, including ALC-1, SLA/LPAb, and atypical p-ANCA, are tested and magnetic resonance cholangiopancreatography (MRCP) is performed in people with a history of inflammatory bowel disease (IBD) or increased ALK levels (5). Studies have shown low levels of antibodies in Iran compared to other communities, which has been attributed to different laboratory instruments. Diagnosis and treatment of autoimmune hepatitis patients should be based evidence-based, considering the prevalence of markers and antibodies.

Patients who had chronic hepatitis with raised serum transaminase levels for at least 6 months and positive serology for viral hepatitis A, B, and C, and those with a possibility of drug-induced, alcoholic, or fatty liver hepatitis, were evaluated based on their clinical history and paraclinical findings in their follow-up visit after examining the results of the tests. If the diagnosis of viral hepatitis was ruled out, patients were evaluated for a possible diagnosis of autoimmune hepatitis. All patients underwent a biopsy, and histopathologically, they had chronic hepatitis with or without specific changes of autoimmune hepatitis. Electrophoresis of serum proteins to check electrophoretic patterns and polyclonal hypergammaglobulinemia were requested. In addition, 5 cc of venous blood was taken from the patient for serological tests including ANA, ASMA, and LKM. To standardize the diagnostic process and improve diagnostic accuracy in autoimmune hepatitis (AIH), a scoring system based on antibody titer, IgG or gammaglobulin serum level, liver histopathology, and rejection of viral hepatitis was designed(1, 6, 18). The system assigned a score of 1 to ANA or ASMA titer of 1/40, and a score of 2 to ANA or ASMA titer of 1/80 or greater than or equal to 1/40 or positive SLA. A score of 1 was assigned if the level of serum IgG or gammaglobulin was higher than the maximum normal, and a score of 2 if it was more than 1.1 times the maximum normal. A score of 1 was assigned if the liver biopsy was compatible with AIH, and a score of 2 if it was typical of AIH(6, 7). Typical diagnostic findings included interface hepatitis, lymphoplasmacytic infiltration in the portal tract with extension to the hepatic lobule, emperipolesis (active infiltration of a larger intracellular cell), and hepatic rosette formation. Compatible diagnosis findings included chronic hepatitis with lymphocytic infiltration in the absence of all typical findings. The absence of viral hepatitis based on tests related to hepatitis B and C was assigned a score of 2, and other types of viral hepatitis was considered on a case-by-case basis based on clinical findings. A final score of 6 or more indicated a probable or definite diagnosis of autoimmune hepatitis, respectively.The descriptive statistics section included mean and standard deviation for quantitative variables with normal distribution, and frequency and percentage for qualitative variables in the form of frequency distribution tables and graphs. The Chi-square test was used to compare qualitative variables. The data were analyzed using SPSS version 22 software, and a statistical significance level of less than 5% was considered. The study was conducted in the gastroenterology clinic of Shahid Beheshti Medical Training Hospital in Hamadan in 2019. The study population included patients referred to the clinic for follow-up on the cause of liver inflammation, with an increase in the level of liver enzymes AST and ALT (at least 2 times the maximum normal), after ruling out viral hepatitis, drug-induced, alcoholic, or fatty liver hepatitis. The study sample included 209 patients under investigation for the diagnosis of autoimmune hepatitis. The sample size was calculated based on Czaja et al.'s study in 2012(3), titled "antibody-negative autoimmune hepatitis," which found the prevalence of antibody-negative autoimmune hepatitis in people with acute and severe hepatitis to be less than 7% and in people with reported chronic hepatitis between 1% and 34%. The minimum required sample size was calculated as 209 using the prevalence formula.

alfa = 0.05	Z1-a/2 = 1.961150826
d = 0.03
p = 0.07	n = 209

$$n=\frac{{Z}_{1-\frac{\alpha }{2}pq}^{2}}{{d}^{2}}$$

2.1.Exclusion criteria

Patients with positive serology for viral hepatitis A, B, and C, drug hepatitis and alcoholic hepatitis and history of the fatty liver based on the clinical history and paraclinical findings and Unwillingness of patients to participate in the study. To avoid bias, all the experiments related to this research were done with one kit and by a specific person. One of the things that can be considered as bias in this research is the presence of unknown non-hepatic autoimmune diseases that interfere with the results of electrophoresis.

In this study, the serological findings of 209 patients with non-viral hepatitis referring to the internal clinic were evaluated. The mean (standard deviation) age of the patient with non-viral hepatitis participating in the present study was 37.98 years (14.5). Among 209 patients, 56.9% were female and the remaining 43.1% were male. Most patients were 31–40 years (28.1%) and 21–30 years old (25.2%) and the lowest number of patients was in the age group of 70 years (2.4%) (Table 2) (Fig. 1).

Table 2

Frequency of age group in patients with non-viral hepatitis referring to the Hamadan internal clinic in 2019
Age category	frequency	percent
10–20	19	9
21–30	53	25.2
31–40	59	28.1
41–50	36	17.1
51–60	27	12.9
61–70	10	4.8
> 70	5	2.4
Total	209	100

According to the epidemiological studies on autoimmune hepatitis, it seems that patients with this complication in our country are similar in age and sex to studies in other countries (8, 9). However, other studies have been performed on children at younger ages (10–11).

In terms of ANA-positive serology, 17.2% of patients had positive serology and the remaining 82.8% had negative serology. Regarding ANA-positive serology, in patients with non-viral hepatitis with polyclonal hypergammaglobulinemia, 24.8% had positive serology and the remaining 75.2% had negative serology. As shown in Table 3, the prevalence of ANA-positive serology in non-viral hepatitis cases with hypergammaglobulinemia was higher than those without hypergammaglobulinemia, which was significantly based on the Chi-square test results (p = 0.005). Regarding ASMA-positive serology, 16.3% of patients had positive serology and the remaining 83.7% had negative serology. Regarding ASMA-positive serology in patients with non-viral hepatitis with polyclonal hypergammaglobulinemia, 23.81% of patients had positive serology and the remaining 76.19% had negative serology. The prevalence of ASMA-positive serology as shown in Table 4 was higher in non-viral hepatitis patients with hypergammaglobulinemia than those without hypergammaglobulinemia. According to the Chi-square test results, this difference was statistically significant. (P = 0.003). Regarding positive-LKM serology in patients with non-viral hepatitis, 1.9% of patients had LKM-positive and others had 98.1% negative serology. Regarding LKM-positive serology in patients with non-viral hepatitis with polyclonal hypergammaglobulinemia, 3.8% of patients had LKM-positive and 96.2% had negative serology. As shown in Table 5, the prevalence of LKM-positive serology in people with non-viral hepatitis with hypergammaglobulinemia was higher than those without hypergammaglobulinemia, but according to the Chi-square test results, this difference was not significant (p = 0.062). Regarding positive serology cases (ANA/ASMA/LKM) in patients with non-viral hepatitis, 28.7% of patients had positive serology and the remaining 71.3% had negative serology. Regarding positive serology (ANA/ASMA/LKM) in patients with non-viral hepatitis with polyclonal hypergammaglobulinemia, 40% had positive serology and the remaining 60% had negative serology. The prevalence of positive serology (ANA/ASMA/LKM) in the people with non-viral hepatitis with hypergammaglobulinemia was higher than those without hypergammaglobulinemia, and based on the Chi-square test results, this difference was significant (p = 0.001) (Table 3)

Table 3. Comparison of the prevalence of ANA-positive cases in individuals with and without polyclonal hypergammaglobulinemia in non-viral hepatitis, Comparison of the prevalence of ASMA positive serology in individuals with and without polyclonal hypergammaglobulinemia in non-viral hepatitis. Comparison of the prevalence of LKM positive serology in individuals with and without hypergammaglobulinemia in non-viral hepatitis, Comparison of the prevalence of positive antibody (ANA or ASMA or LKM) in patients with and without hypergammaglobulinemia in non-viral hepatitis

Serology status	Blood globulin protein levels		P-value
Serology status	Hypergammaglobulinemia	No hypergammaglobulinemia	P-value
*Positive LKM*	4(3.8%)	0(0%)	0.062
*Negative LKM*	101(96.2%)	104(100%)
*total*	105(100%)	104(100%)
*Positive ANA*	26(24.48%)	10(9.6%)	0.005
*Negative ANA*	36(75.2%)	94(90.4%)
*total*	105(100%)	104(100%)
*Positive ASMA*	25(23.8%)	9(8.7%)	0.003
*Negative ASMA*	80(76.2%)	95(91.3%)
*Total*	105(100%)	104(100%)
*Positive serology (ANA/ASMA/LKM)*	42(40%)	18(17.3%)	0.001
*Negative serology (ANA/ASMA/LKM)*	63(60%)	86(82.7%)
Total	105(100%)	104(100%)

According to the results of the Chi-square test, patients with non-viral hepatitis with low albumin (alpha 1 or low alpha 2) and high gamma globulin protein levels were significantly different in terms of positive serology (ANA/ASMA/LKM) compared to patients who did not have this feature (P = 0.004), which indicates the significantly higher prevalence of positive serology of common antibodies in people with electrophoretic patterns in favor of liver failure compared to those without this pattern in patients with non-viral hepatitis. According to the Chi-square test results, patients with non-viral hepatitis with high gamma globulin protein levels (alpha 1 or alpha 2) were not significantly different from serologically positive patients (ANA/ASMA/LKM) (p=0.090). In other words, the positive prevalence of common antibodies in people with non-viral hepatitis with an electrophoretic pattern in favor of chronic active hepatitis was higher in patients with non-viral hepatitis than in those without this pattern, but this difference was not significant. According to the results of the Chi-square test, patients with non-viral hepatitis with low albumin (alpha 1 or alpha 2) and high gamma globulin protein levels had no statistically significant difference with patients with this characteristic (ANA/ASMA/LKM) (p=0.200). The positive prevalence of common antibodies in patients with non-viral hepatitis with electrophoretic patterns in favor of chronic hepatitis was higher than in non-viral hepatitis patients without this pattern, but this difference was not significant (Table 4).

Table 4. Comparison of the prevalence of positive antibody (ANA or ASMA or LKM) in patients with non-viral hepatitis with the electrophoretic pattern including low albumin and low alpha1 or alpha 2 and high gamma compared to patients without this pattern, Comparison of the prevalence of positive antibody (ANA or ASMA or LKM) in patients with non-viral hepatitis with the electrophoretic pattern including high alpha 1 or alpha 2 and high gamma compared to patients without this pattern, Comparison of the prevalence of positive antibody (ANA or ASMA or LKM) in patients with non-viral hepatitis with the electrophoretic pattern including low alpha 1 or alpha 2 and high gamma compared to patients without this pattern

Serologic status	Low albumin (low alpha 1 or low alpha 2) and high gammaglobulin protein levels		P-value	Low albumin (Alpha 1 or Alpha 2) High and high gammaglobulin protein levels		P-value	Low albumin (Alpha 1 or alpha 2) and gammglobulin protein levels		P-value
Serologic status	Yes	No	P-value	yes	No	P-value	yes	No	P-value
Positive serology (ANA/ASMA/LKM)	11(61.1%)	49(25.7%)	0.004	17(39.5%)	43(25.9%)	0.090	12(38.7%)	48(27%)	0.200
Negative serology ((ANA/ASMA/LKM)	7(38.9%)	142(74.3%)		26(60.5%)	123(74.1%)		19(61.3%)	130(73%)
Total	18(100%)	191(100%)		43(100%)	166(100%)		31(100%)	178(100%)

According to Table 5, the prevalence of positive serology (ANA/ASMA/LKM) in cases with non-viral hepatitis increases with an increasing score in the diagnostic scoring system, and this increase is statistically significant according to the Chi-square test results (p =0.001).

Table 5. Comparison of the prevalence of positive antibody (ANA or ASMA or LKM) with diagnostic scoring system scoring in patients with non-viral hepatitis

Diagnostic score	Positive serology (ANA/ASMA/LKM)		Total
Diagnostic score	Yes	No	Total
2	8(8.5%)	86(91.5%)	94(100%)
3	8(20%)	32(80%)	40(100%)
4	17(35.4%)	31(64.6%)	48(100%)
5	15(100%)	0	15(100%)
6	12(100%)	0	12(100%)
P-value	0.001	209

This study investigated the serological findings of 209 patients with non-viral hepatitis who were referred to the internal clinic. The mean age of the patients with non-viral hepatitis who participated in the study was 37.98 years (SD = 14.5), with 56.9% being women and 43.1% being men. Most of the patients were in the age group of 31–40 years (28%) and 21–30 years (25%), while the least number of patients were in the age group of 70 years (2.4%).According to previous epidemiological studies on autoimmune hepatitis disease(8, 9), it appears that the patients with this condition in our country are similar to those in other countries in terms of age and gender(10, 11). However, other studies have focused on children in younger age groups.The results of this study showed that in 209 patients with non-viral hepatitis suspected to be autoimmune hepatitis, 50.2% had hypergammaglobulinemia, 17.2% were ANA positive, 16.3% were ASMA positive, 1.9% were LKM positive, and 28.7% had at least one positive antibody among the common antibodies (ANA-ASMA-LKM). Furthermore, in 105 patients with non-viral hepatitis and hypergammaglobulinemia suspected to be autoimmune hepatitis, 24.8% were ANA positive, 23.8% were ASMA positive, and 8.3% were LKM positive. Additionally, 40% of patients had at least one positive antibody among the common antibodies (ANA-ASMA-LKM). The prevalence of positive serology of antibodies in people with polyclonal hypergammaglobulinemia was significantly higher than those without polyclonal hypergammaglobulinemia, except for Anti-LKM. However, due to the small number of positive cases, LKM positivity was not statistically significant.A study conducted by Liang et al. in 2018 examined patients with autoimmune hepatitis in terms of serological results of antibodies related to autoimmune hepatitis(12). The results of their study showed that 76.7% of ANA patients and 67% of ASMA patients were positive, and the average blood gamma globulins of the patients were higher than the normal range. The difference between the results of Liang's study and the present study may be due to the examination of patients diagnosed with autoimmune hepatitis, while in the present study, patients with non-viral hepatitis suspected of autoimmune hepatitis were examined(12).In a study carried out by Aghazadeh et al. in 2003, they examined the epidemiological indicators and the response to treatment of autoimmune hepatitis in Taleghani Hospital in Iran(8). The results showed that the prevalence of positive cases of autoantibodies (ASMA) and ANA in patients were 54.8% and 38%, respectively. The results of this study were similar to the results of the present study, and the higher rate of antibody positivity in Aghazadeh's study may be due to the examination of antibodies in patients with a definitive diagnosis of autoimmune hepatitis(8). In their 2000 study, Dariani et al. evaluated the epidemiological indicators of autoimmune hepatitis patients in Imam Khomeini Hospital in Iran. They found that 43.6% of patients were positive for ASMA, and 35.9% were positive for ANA (13). Unlike the present study, they found a higher prevalence of positive ASMA than positive ANA. In 2008, Stefan Luth and colleagues examined the serological markers of autoimmune hepatitis patients (14). They found that ASMA and ANA were equally positive in 43% of patients. Both markers were simultaneously positive in 21% of patients, while only 1% of patients had positive LKM. Hypergammaglobulinemia was found to be a useful diagnostic criterion for autoimmune hepatitis in this study (14). While Luth's study found more ANA and ASMA positive cases than the present study, it showed a low prevalence of LKM and a high prevalence of hypergammaglobinemia, similar to the present study. In 2009, Muratori et al. found that 75% of patients with autoimmune hepatitis type 1 were ASMA positive, 63% were ANA positive, and none were positive for LKM. Several studies have indicated a low prevalence of LKM in autoimmune hepatitis patients (15). The present study differs from Muratori's study in terms of diagnostic certainty. Somroo et al. investigated the serological status of children with autoimmune hepatitis in 2018. They found that all patients had hypergammaglobulinemia, and 55% of patients had positive ANA (16). The difference between Somroo's study and the present study is likely due to age and diagnostic differences. In 2017, Taubert et al. reported high levels of ASMA and ANA in autoimmune hepatitis patients and considered hypergammaglobulinemia a predictor of treatment status and a diagnostic factor for the disease (17).The present study found differences in serological criteria compared to other studies, including lower percentages of positive cases of ANA and ASMA in Iran than in other countries. This difference may be due to differences in laboratory methods or racial differences.In addition to hypergammaglobulinemia, the present study found a higher prevalence of positive serology in people with electrophoresis patterns indicative of chronic liver inflammation and liver inflammation leading to liver failure than in those without these patterns. However, this difference was significant only in the group with liver inflammation leading to liver failure.The study also found that the prevalence of positive serology in people with non-viral hepatitis increased with an increase in the score in the scoring system designed to diagnose autoimmune hepatitis, which was statistically significant. All subjects had non-viral hepatitis and received at least 2 points from the scoring system, with 50% also having polyclonal hypergammaglobulinemia, which earned them an additional point. The lack of liver biopsy results resulted in a loss of 2 points for all subjects. In the group with possible and close to probable scores, all patients had positive serology, indicating a probable or definitive diagnosis of autoimmune hepatitis. The possibility of suppressed common antibodies and the delayed appearance of common antibodies should be considered, and over time, serological tests should be repeated. In addition, the possibility of unknown antibodies should also be considered, and biopsy should be performed to add points for people with scores of 4 and 5. The measurement of uncommon serological markers may also improve the diagnostic score and determine the patient's assignment. The prevalence of antibody-negative autoimmune hepatitis in previous studies has been reported between 1 and 34%, with an average of 20% (3, 4).

Our findings indicated the importance of hypergammaglobulinemia and positive serology of at least one of the three common antibodies, including ANA, ASMA, and LKM in people with suspected non-viral hepatitis and autoimmune hepatitis for diagnosis because 40% of suspected patients had serological hypergammaglobulinemia. Positive, common antibodies (ANA/ASMA/LKM) were observed, and in line with most studies, the prevalence of ANA-positive serology was higher than ASMA and LKM-positive serology. Despite the difference in our study population’s certainty in diagnosis compared to other studies, the prevalence of autoimmune antibody-negative hepatitis in probable and near probable individuals was zero. Serology of uncommon antibodies was strongly felt in low-scoring cases to determine patients' tasks, as 94% of people suspected of having autoimmune hepatitis remained undecided in this cross-sectional study. These findings can provide basic information for future studies and are effective in localizing external guidelines for the diagnosis of autoimmune hepatitis.

The patient's non-cooperation and giving false information, which seems to have been solved by justifying them and not disclosing the information related to the patients.

Ethics approval and consent to participate:

This study was approved by the Research Ethics Committees of the Hamadan University of Medical Science with the ethics code: IR.UMSHA.REC.1398.455. Informed consent was obtained from all participating patients/their legal guardians in this study after fully explaining the study method, the study was fully explained to the patients, and the questions and doubts of the patients were fully answered. It was also explained to the patients that for any reason, they wanted to continue participating in the study. do not have, they can withdraw, and this study will not interfere with their treatment. Also, all patients are assured that all their information is confidential and that only the collective information of the entire investigation is available. All methods were carried out in accordance with relevant guidelines and regulations.

Consent for publication

Not applicable.

Availability of data and materials

All data generated or analyzed during this study are included in this published article.

Competing interests:

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Funding:

The funding source of this research is Hamadan University of Medical Sciences.

Authors' contributions:

Study concept and design: Hamid Reza Ghasemi Basir.

Data acquisition: Alireza Khalilian. Data analysis and interpretation: Hamid Reza Ghasemi Basir.

Drafting of the manuscript; critical revision of the manuscript for important intellectual content: Anahita Eslami-Ghayour.

Scientific advisor: Mehdi Ghobakhlou

Acknowledgements:

We thank all the people who have helped us in this way

Author information

Hamid Reza Ghasemi Basir, MD, Associate Professor of Pathology ,Department of Pathology, School of Medicine,Sina (Farshchian) Educational and Medical Center, Hamadan University of Medical Sciences, Hamadan, Iran

Alireza Khalilian , MD, Assistant Professor of Gastroenterology and Hepatology ,Department of Internal Medicine, School of Medicine, Shahid Beheshti Medical Educational Center, Hamadan University of Medical Sciences, Hamadan, Iran

Anahita Eslami-Ghayour, MD, corresponding author' ³, ([email protected] )

Mehdi Ghobakhlou,MD, Assistant Professor of Gastroenterology and Hepatology ^{4 (}[email protected])

Johnson PJ, McFarlane IG, Convenors OBotP. Meeting report: international autoimmune hepatitis group. Hepatology. 1993;18(4):998-1005.
Manns MP, Lohse AW, Vergani D. Autoimmune hepatitis–update 2015. Journal of hepatology. 2015;62(1):S100-S11.
Czaja AJ. Autoantibody-negative autoimmune hepatitis. Digestive diseases and sciences. 2012;57(3):610-24.
Heneghan MA, Yeoman AD, Verma S, Smith AD, Longhi MS. Autoimmune hepatitis. The Lancet. 2013;382(9902):1433-44.
Binicier ÖB, Günay S. The efficacy and adverse effects of budesonide in remission induction treatment of autoimmune hepatitis: a retrospective study. Croatian medical journal. 2019;60(4):345.
Frenzel C, Herkel J, Lüth S, Galle PR, Schramm C, Lohse AW. Evaluation of F-actin ELISA for the diagnosis of autoimmune hepatitis. The American journal of gastroenterology. 2006;101(12):2731.
. Hennes EM, Zeniya M, Czaja AJ, Parés A, Dalekos GN, Krawitt EL, et al. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology. 2008;48(1):169-76.
Epidemiological indices of 31 patients with autoimmune hepatitis and their response to treatment. Pejouhesh dar Pezeshki (Research in Medicine). 2003;27(1):53-6.
Othman AM, Hamzah EA, Almughales JA, Al-Mikhlafy A. SERUM POSITIVITY OF ANA AND ASMA AMONG KHAT AND NONKHAT CHEWERS AS MARKERS FOR AUTOIMMUNE HEPATITIS TYPE. Universal J Pharm Res. 2017;2(4):20-4.
Farid E, M Isa H, Al Nasef M, Mohamed R, Jamsheer H. Childhood autoimmune hepatitis in Bahrain: a tertiary center experience. Iranian Journal of Immunology. 2015;12(2):141-8.
Karakoyun M, Ecevit CO, Kilicoglu E, Aydogdu S, Yagci RV, Ozgenc F. Autoimmune hepatitis and long-term disease course in children in Turkey, a single-center experience. European journal of gastroenterology & hepatology. 2016;28(8):927-30.
Liang M, Liwen Z, Yun Z, Yanbo D, Jianping C. Serum levels of IL-33 and correlation with IL-4, IL-17A, and hypergammaglobulinemia in patients with autoimmune hepatitis. Mediators of inflammation. 2018;2018.
Ebrahimi Daryani N, Mir momen SH,Bahrami H, Mohammadi H, Evaluation epidemiologic factors in Autoimmune hepatitis patients and their response to treatment in Emam Khomaini Hospital.2000;5(29-30)
Lüth S, Herkel J, Kanzler S, Frenzel C, Galle PR, Dienes HP, et al. Serologic markers compared with liver biopsy for monitoring disease activity in autoimmune hepatitis. Journal of clinical gastroenterology. 2008;42(8):926-30
Muratori P, Granito A, Pappas G, Pendino GM, Quarneti C, Cicola R, et al. The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. The American journal of gastroenterology. 2009;104(6):1420.
Somroo GB, Rai AA, Luck NH, Abbas Z. Clinical presentation of autoimmune hepatitis in Pakistani children. The Pan African medical journal. 2018;30.
Taubert R, Hardtke-Wolenski M, Noyan F, Lalanne C, Jonigk D, Schlue J, et al. Hyperferritinemia and hypergammaglobulinemia predict the treatment response to standard therapy in autoimmune hepatitis. PloS one. 2017;12(6):e0179074-e.
Hennes EM, Zeniya M, Czaja AJ, Parés A, Dalekos GN, Krawitt EL, et al. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology. 2008;48(1):169-76.

No competing interests reported.

Frequency of serological results of antibodies related to autoimmune hepatitis in Iranian patients with non-viral hepatitis

Status:

Version 1

Abstract

Background

Objective

Methods

Results

Conclusion

Figures

1. Introduction

2. Methods

2.1.Exclusion criteria

3. Results

4. Discussion

5. Conclusion

Limitation

Declarations

References

Additional Declarations

Status:

Version 1