Autoimmune Hepatitis. Dr. Stefania Casu Hepatology, UVCM, Inselspital Bern. November 14th, 2018

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Autoimmune Hepatitis Dr. Stefania Casu Hepatology, UVCM, Inselspital Bern November 14th, 2018

AIH - Definition Manns MP J Hepatol 2015, vol 62, P 100-111

AIH - Definition Autoimmune hepatitis (AIH) is a chronic selfperpetuating inflammatory disease with a female predominance occurring in all ages and races that may start with an episode of acute hepatitis and may lead to liver cirrhosis, liver cancer, liver transplantation or death Manns MP J Hepatol 2015, vol 62, P 100-111

AIH - Epidemiology Easl Clinical Practice Guideline 2017

AIH - Epidemiology 16 to 18 cases per 100,000 inhabitants in Europe - relatively rare Easl Clinical Practice Guideline 2017

AIH - Epidemiology 16 to 18 cases per 100,000 inhabitants in Europe - relatively rare marked increase in AIH incidence over time Easl Clinical Practice Guideline 2017

AIH - Epidemiology 16 to 18 cases per 100,000 inhabitants in Europe - relatively rare marked increase in AIH incidence over time affects mainly women Easl Clinical Practice Guideline 2017

AIH - Epidemiology 16 to 18 cases per 100,000 inhabitants in Europe - relatively rare marked increase in AIH incidence over time affects mainly women 25 30% of all AIH patients are male and may present at any age and in all ethnic groups Easl Clinical Practice Guideline 2017

AIH - Epidemiology 16 to 18 cases per 100,000 inhabitants in Europe - relatively rare marked increase in AIH incidence over time affects mainly women 25 30% of all AIH patients are male and may present at any age and in all ethnic groups Extrahepatic autoimmune disorders are common and occur in all stages of liver disease Easl Clinical Practice Guideline 2017

AIH Subclassification

AIH Subclassification AIH-1: (ca. 90% of AIH cases): ANA, SMA rare failure of treatment variable relapse rates after drug withdrawal variable need for long-term maintenance therapy

AIH Subclassification AIH-1: (ca. 90% of AIH cases): AIH-2: ANA, SMA rare failure of treatment variable relapse rates after drug withdrawal variable need for long-term maintenance therapy anti-lkm1, anti-lc1 and rarely anti-lkm3 onset usually in childhood and young adulthood clinical and histopathological severity commonly acute and advanced frequent failure of treatment frequent relapse rates after drug withdrawal need for long-term maintenance therapy very common

AIH Subclassification AIH-1: (ca. 90% of AIH cases): AIH-2: ANA, SMA rare failure of treatment variable relapse rates after drug withdrawal variable need for long-term maintenance therapy anti-lkm1, anti-lc1 and rarely anti-lkm3 onset usually in childhood and young adulthood clinical and histopathological severity commonly acute and advanced frequent failure of treatment frequent relapse rates after drug withdrawal need for long-term maintenance therapy very common AIH-3: SLA/LP positive

AIH Subclassification AIH-1: (ca. 90% of AIH cases): AIH-2: ANA, SMA rare failure of treatment variable relapse rates after drug withdrawal variable need for long-term maintenance therapy anti-lkm1, anti-lc1 and rarely anti-lkm3 onset usually in childhood and young adulthood clinical and histopathological severity commonly acute and advanced frequent failure of treatment frequent relapse rates after drug withdrawal need for long-term maintenance therapy very common AIH-3: SLA/LP positive

AIH

AIH ANA positivity: which pattern do you expect to find?

AIH Pathogenesis Manns MP J Hepatol 2015, vol 62, P 100-111

AIH Pathogenesis Genetic associatios genes of the human leukocyte antigen (HLA) region (the human major histocompatibility complex, MHC) located on the short arm of chromosome 6 involved in the presentation of antigenic peptides to T-cells Manns MP J Hepatol 2015, vol 62, P 100-111

AIH Pathogenesis Genetic associatios genes of the human leukocyte antigen (HLA) region (the human major histocompatibility complex, MHC) located on the short arm of chromosome 6 involved in the presentation of antigenic peptides to T-cells Strongest association: HLA-DR3 and HLA-DR4 susceptibility to AIH-1 HLA-DR7 and HLA-DR3 susceptibility to AIH-2 Manns MP J Hepatol 2015, vol 62, P 100-111

AIH Pathogenesis Genetic associatios genes of the human leukocyte antigen (HLA) region (the human major histocompatibility complex, MHC) located on the short arm of chromosome 6 involved in the presentation of antigenic peptides to T-cells Strongest association: HLA-DR3 and HLA-DR4 susceptibility to AIH-1 HLA-DR7 and HLA-DR3 susceptibility to AIH-2 Development of autoimmune diseases is favored by the breakdown of self-tolerance mechanisms Manns MP J Hepatol 2015, vol 62, P 100-111

AIH

AIH Is there a typical clinical presentation for AIH?

AIH Diagnosis Presentation at onset Easl Clinical Practice Guideline 2017

AIH Diagnosis Presentation at onset Broad range from asymptomatic to acute/severe or even fulminant Easl Clinical Practice Guideline 2017

AIH Diagnosis Presentation at onset Broad range from asymptomatic to acute/severe or even fulminant 2/3 Patients: insidious onset with non-specific symptoms: fatigue, general ill health, right upper quadrant pain, lethargy, malaise, anorexia, weight loss, nausea, pruritus, fluctuating jaundice and polyarthralgia involving the small joints without arthritis, sometimes dating back years Easl Clinical Practice Guideline 2017

AIH Diagnosis Presentation at onset Broad range from asymptomatic to acute/severe or even fulminant 2/3 Patients: insidious onset with non-specific symptoms: fatigue, general ill health, right upper quadrant pain, lethargy, malaise, anorexia, weight loss, nausea, pruritus, fluctuating jaundice and polyarthralgia involving the small joints without arthritis, sometimes dating back years 25% of patients acute onset: acute exacerbation of chronic AIH true acute AIH without histological findings of chronic liver disease: centrilobular zone 3 necrosis (central perivenulitis) usually present in patients with acute presentation; autoantibodies or other classical features can be absent; not always responsiveness to corticosteroids Easl Clinical Practice Guideline 2017

AIH Diagnosis Presentation at onset Broad range from asymptomatic to acute/severe or even fulminant 2/3 Patients: insidious onset with non-specific symptoms: fatigue, general ill health, right upper quadrant pain, lethargy, malaise, anorexia, weight loss, nausea, pruritus, fluctuating jaundice and polyarthralgia involving the small joints without arthritis, sometimes dating back years 25% of patients acute onset: acute exacerbation of chronic AIH true acute AIH without histological findings of chronic liver disease: centrilobular zone 3 necrosis (central perivenulitis) usually present in patients with acute presentation; autoantibodies or other classical features can be absent; not always responsiveness to corticosteroids One third of patients at diagnosis have already developed cirrhosis irrespective of the presence of symptoms due to delay in diagnosis Easl Clinical Practice Guideline 2017

AIH Specific clinical features and presentations Overlap Syndromes (1) Easl Clinical Practice Guideline 2017

AIH Specific clinical features and presentations Overlap Syndromes (1) Lack of internationally agreed criteria defining these variant conditions difficult to give standardised recommendations Easl Clinical Practice Guideline 2017

AIH Specific clinical features and presentations Overlap Syndromes (1) Lack of internationally agreed criteria defining these variant conditions difficult to give standardised recommendations AIH-PBC: 8 10% of adult patients with either PBC or AIH in most cases, it is possible to define one primary disorder ( dominant disease), usually PBC Easl Clinical Practice Guideline 2017

AIH Specific clinical features and presentations Overlap Syndromes (1) Lack of internationally agreed criteria defining these variant conditions difficult to give standardised recommendations AIH-PBC: 8 10% of adult patients with either PBC or AIH in most cases, it is possible to define one primary disorder ( dominant disease), usually PBC AIH-PSC: Approximate prevalence of 7 14% patients with features of AIH and PSC require immunosuppression in AIH patients with remaining cholestasis despite adequate immunosuppression, MRCP for the detection of possible underlying or co-existent PSC is recommended Easl Clinical Practice Guideline 2017

AIH Specific clinical features and presentations Overlap Syndromes (2) Easl Clinical Practice Guideline 2017

AIH Specific clinical features and presentations Overlap Syndromes (2) AIH - IgG4: few and unclear data Easl Clinical Practice Guideline 2017

AIH Specific clinical features and presentations Overlap Syndromes (2) AIH - IgG4: few and unclear data DILI + AIH DILI with a strong immunoallergic component mimicking AIH AIH mimicking as DILI due to drug exposure in recent weeks and spontaneous improvement after cessation of drug exposure AIH triggered by an offending drug (DILI-induced AIH) nitrofurantoin, minocycline, statins, anti-tnfalpha Easl Clinical Practice Guideline 2017

AIH Laboratory findings What do you expect to find?

Clinical case S. G., 63 year-old woman Rheumatoid Arthritis diagnosed in 2007 Previous treatment: Hydroxychloroquine (suspended for intolerance); Leflunomide (supended for Pancytopenia) since August 2016 under Methotrexate Bronchial asthma

Clinical case Since January 2017 progressive elevation of transaminases (up to 2 times ULN) MTX suspended on February 6th Asymptomatic Ongoing therapy: Metotrexate 15 mg/week Ipratropium 250 mcg (max 4 times/day) Salbutamol as-needed basis No new medication No history of alcohol or drug consumption No transfusions No recent trips Negative family history for liver disease

Clinical case February 2017: Hospitalization in the Rheumatology Department ACUTE HEPATITIS

Clinical case February 2017: Hospitalization in the Rheumatology Department Hb 133 g/l (121-154) ACUTE HEPATITIS Leuco 4.48 G/l (3.00-10.5) PLT 214 (140-380) CRP 6 mg/l (<5) Glucose 6.05 mmol/l (4.56-6.38) Creatinine 65 µmol/l (45-84) Bilirubin 32 µmol/l (<17) Albumin 30 g/l (35-52) AST 2336 U/l (<35) ALT 2892 U/l (<35) ALP 348 U/l (35-105) ɣgt 370 U/l (5-36) PT INR 1.07 (0.8-1.2)

Clinical case February 2017: Hospitalization in the Rheumatology Department Hb 133 g/l (121-154) Leuco 4.48 G/l (3.00-10.5) PLT 214 (140-380) CRP 6 mg/l (<5) Glucose 6.05 mmol/l (4.56-6.38) Creatinine 65 µmol/l (45-84) Bilirubin 32 µmol/l (<17) Albumin 30 g/l (35-52) AST 2336 U/l (<35) ALT 2892 U/l (<35) ALP 348 U/l (35-105) ɣgt 370 U/l (5-36) PT INR 1.07 (0.8-1.2) ACUTE HEPATITIS Viral serologies: anti-hbs and anti-hbc positivity (HBsAg neg) HCV neg HAV IgM neg, IgG pos HEV (IgG+IgM+PCR) neg CMV IgM neg, IgG pos EBV neg

Clinical case February 2017: Hospitalization in the Rheumatology Department Hb 133 g/l (121-154) Leuco 4.48 G/l (3.00-10.5) PLT 214 (140-380) CRP 6 mg/l (<5) Glucose 6.05 mmol/l (4.56-6.38) Creatinine 65 µmol/l (45-84) Bilirubin 32 µmol/l (<17) Albumin 30 g/l (35-52) AST 2336 U/l (<35) ALT 2892 U/l (<35) ALP 348 U/l (35-105) ɣgt 370 U/l (5-36) PT INR 1.07 (0.8-1.2) ACUTE HEPATITIS Total IgG: 12 g/l Autoantibodies: ANA 1:80 (< 1:80) LKM-1 < 1:80 SLA < 1:80 SMA pending Viral serologies: anti-hbs and anti-hbc positivity (HBsAg neg) HCV neg HAV IgM neg, IgG pos HEV (IgG+IgM+PCR) neg CMV IgM neg, IgG pos EBV neg

AIH

AIH Next step?

AIH Histology Are the histological findings alone enough to establish the diagnosis?

AIH Histology Easl Clinical Practice Guideline 2017 Manns Journal Hep 2015

AIH Histology no morphological feature is pathognomonic of AIH Easl Clinical Practice Guideline 2017 Manns Journal Hep 2015

AIH Histology no morphological feature is pathognomonic of AIH Interface hepatitis (hepatitis at the portal-parenchymal interface) with dense plasma cell-rich lymphoplasmocytic infiltrates, hepatocellular rosette formation, emperipolesis (active penetration by one cell into and through a larger cell) and hepatocyte swelling and/or pycnotic necrosis typical hallmarks of AIH Easl Clinical Practice Guideline 2017 Manns Journal Hep 2015

AIH Histology no morphological feature is pathognomonic of AIH Interface hepatitis (hepatitis at the portal-parenchymal interface) with dense plasma cell-rich lymphoplasmocytic infiltrates, hepatocellular rosette formation, emperipolesis (active penetration by one cell into and through a larger cell) and hepatocyte swelling and/or pycnotic necrosis typical hallmarks of AIH Panlobular hepatitis, bridging necrosis and massive necrosis signs of severe inflammatory activity (acute disease onset). The characteristic histological pattern is panacinar hepatitis (parenchymal collapse) especially in biopsies performed during an acute onset and closely resembles drug-induced hepatitis. Easl Clinical Practice Guideline 2017 Manns Journal Hep 2015

AIH Histology no morphological feature is pathognomonic of AIH Distinction from DILI can be very difficoult Interface hepatitis (hepatitis at the portal-parenchymal interface) with dense plasma cell-rich lymphoplasmocytic infiltrates, hepatocellular rosette formation, emperipolesis (active penetration by one cell into and through a larger cell) and hepatocyte swelling and/or pycnotic necrosis typical hallmarks of AIH Panlobular hepatitis, bridging necrosis and massive necrosis signs of severe inflammatory activity (acute disease onset). The characteristic histological pattern is panacinar hepatitis (parenchymal collapse) especially in biopsies performed during an acute onset and closely resembles drug-induced hepatitis. Easl Clinical Practice Guideline 2017 Manns Journal Hep 2015

AIH Histology no morphological feature is pathognomonic of AIH Distinction from DILI can be very difficoult Interface hepatitis (hepatitis at the portal-parenchymal interface) with dense plasma cell-rich lymphoplasmocytic infiltrates, hepatocellular rosette formation, Bile-duct damage is typically not a feature of AIH, but in severe emperipolesis (active penetration by one cell into and through a larger cell) and hepatocyte swelling and/or pycnotic necrosis typical hallmarks of AIH Panlobular hepatitis, bridging necrosis and massive necrosis signs of severe inflammatory activity (acute disease onset). The characteristic caseshistological it can also pattern be is panacinar hepatitis (parenchymal collapse) especially in biopsies oserved performed during an acute onset and closely resembles drug-induced hepatitis. Easl Clinical Practice Guideline 2017 Manns Journal Hep 2015

AIH Histology Histologic hallmarks of autoimmune hepatitis: 1) Interface hepatitis (A) occurs when the lymphocytes in the portal triad invade the limiting plate spilling around the hepatocytes 2) Lymphocytic infiltrate accumulates in the portal triad (B). Manns MP J Hepatol 2015, vol 62, P 100-111

Clinical case Histological findings compatible with DILI but: Mixed inflammatory cell infiltration (plasma cells and eosinophils) Interphase inflammation Focal apoptosis and necrosis

Clinical case Histological findings compatible with DILI but: Mixed inflammatory cell infiltration (plasma cells and eosinophils) Interphase inflammation Focal apoptosis and necrosis

Clinical case Histological findings compatible with DILI but: Mixed inflammatory cell infiltration (plasma cells and eosinophils) Interphase inflammation No steatosis Focal apoptosis and necrosis No steatohepatitis

Clinical case Liver histology Immunihistochemestry

AIH DILI

AIH DILI

AIH Diagnostic criteria Simplified scoring system for autoimmune hepatitis of the International Autoimmune Hepatitis Group (IAHG) Autoantibodies ANA or SMA or LKM > 1:40 ANA or SMA or LKM > 1:80 SLA/LP Positive (>20 units) Points 1 2 IgG Liver histology Absence of viral hepatitis Upper normal limit > 1.10 times normal limit Compatible with AIH Typical for AIH Yes No 1 2 1 2 2 0 6 probable AIH; 7 definite AIH J Hepatol 2011 55, P 171 182 Hennes et al. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology 2008. 48:169-176

AIH Diagnostic criteria Simplified scoring system for autoimmune hepatitis of the International Autoimmune Hepatitis Group (IAHG) Autoantibodies ANA or SMA or LKM > 1:40 ANA or SMA or LKM > 1:80 SLA/LP Positive (>20 units) Points 1 2 IgG Liver histology Absence of viral hepatitis Upper normal limit > 1.10 times normal limit Compatible with AIH Typical for AIH Yes No 1 2 1 2 2 0 6 probable AIH; 7 definite AIH J Hepatol 2011 55, P 171 182 Hennes et al. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology 2008. 48:169-176

AIH Diagnostic criteria Simplified scoring system for autoimmune hepatitis of the International Autoimmune Hepatitis Group (IAHG) Autoantibodies ANA or SMA or LKM > 1:40 ANA or SMA or LKM > 1:80 SLA/LP Positive (>20 units) Points 1 2 IgG Liver histology Absence of viral hepatitis Upper normal limit > 1.10 times normal limit Compatible with AIH Typical for AIH Yes No 1 2 1 2 2 0 6 probable AIH; 7 definite AIH J Hepatol 2011 55, P 171 182 Hennes et al. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology 2008. 48:169-176

AIH Diagnostic criteria Simplified scoring system for autoimmune hepatitis of the International Autoimmune Hepatitis Group (IAHG) Autoantibodies ANA or SMA or LKM > 1:40 ANA or SMA or LKM > 1:80 SLA/LP Positive (>20 units) Points 1 2 IgG Liver histology Absence of viral hepatitis Upper normal limit > 1.10 times normal limit Compatible with AIH Typical for AIH Yes No 1 2 1 2 2 0 6 probable AIH; 7 definite AIH J Hepatol 2011 55, P 171 182 Hennes et al. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology 2008. 48:169-176

AIH Diagnostic criteria Simplified scoring system for autoimmune hepatitis of the International Autoimmune Hepatitis Group (IAHG) Autoantibodies ANA or SMA or LKM > 1:40 ANA or SMA or LKM > 1:80 SLA/LP Positive (>20 units) Points 1 2 IgG Liver histology Absence of viral hepatitis Upper normal limit > 1.10 times normal limit Compatible with AIH Typical for AIH Yes No 1 2 1 2 2 0 6 probable AIH; 7 definite AIH J Hepatol 2011 55, P 171 182 Hennes et al. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology 2008. 48:169-176

AIH Treatment

AIH Treatment Who to treat and how to treat

AIH Treatment Manns MP J Hepatol 2015, vol 62, P 100-111 Easl Clinical Practice Guideline 2017

AIH Treatment aim of treatment in AIH is to obtain complete remission of the disease and to prevent further progression of liver disease Manns MP J Hepatol 2015, vol 62, P 100-111 Easl Clinical Practice Guideline 2017

AIH Treatment aim of treatment in AIH is to obtain complete remission of the disease and to prevent further progression of liver disease Remission induction: start with steroids predniso(lo)ne monotherapy (up to 1 mg/kg/day) oder Budesonide 9 mg/d (only in non-cirrhotic patients!) Manns MP J Hepatol 2015, vol 62, P 100-111 Easl Clinical Practice Guideline 2017

AIH Treatment aim of treatment in AIH is to obtain complete remission of the disease and to prevent further progression of liver disease Remission induction: start with steroids predniso(lo)ne monotherapy (up to 1 mg/kg/day) oder Budesonide 9 mg/d (only in non-cirrhotic patients!) Add azathioprine gradually up to 1-2 mg/kg/d Manns MP J Hepatol 2015, vol 62, P 100-111 Easl Clinical Practice Guideline 2017

AIH Treatment aim of treatment in AIH is to obtain complete remission of the disease and to prevent further progression of liver disease Remission induction: start with steroids predniso(lo)ne monotherapy (up to 1 mg/kg/day) oder Budesonide 9 mg/d (only in non-cirrhotic patients!) Add azathioprine gradually up to 1-2 mg/kg/d Delaying introduction of azathioprine (usually by about two weeks) can be pragmatically helpful in managing patients with AIH help to resolve diagnostic uncertainties avoids the diagnostic dilemma of discrimination between azathioprine-induced hepatotoxicity from primary non-response. Manns MP J Hepatol 2015, vol 62, P 100-111 Easl Clinical Practice Guideline 2017

AIH Treatment aim of treatment in AIH is to obtain complete remission of the disease and to prevent further progression of liver disease Remission induction: start with steroids predniso(lo)ne monotherapy (up to 1 mg/kg/day) oder Budesonide 9 mg/d (only in non-cirrhotic patients!) Add azathioprine gradually up to 1-2 mg/kg/d Delaying introduction of azathioprine (usually by about two weeks) can be pragmatically helpful in managing patients with AIH help to resolve diagnostic uncertainties Second line Therapy: MMF, Infliximab, Rituximab avoids the diagnostic dilemma of discrimination between azathioprine-induced hepatotoxicity from primary non-response. Manns MP J Hepatol 2015, vol 62, P 100-111 Easl Clinical Practice Guideline 2017

AIH Treatment Easl Clinical Practice Guideline 2017

AIH Treatment Treatment requires: induction of remission (steroids) prolonged maintenance therapy (thiopurines) Laboratory endpoints: normalization of IgG and ALT Therapy is aimed to obtain complete biochemical and histological remission Easl Clinical Practice Guideline 2017

AIH Treatment When to stop therapy

AIH Treatment Easl Clinical Practice Guideline 2017

AIH Treatment Treatment should be continued for at least three years and for at least 24 months after complete normalization of serum transaminases and IgG levels (biochemical remission) Easl Clinical Practice Guideline 2017

AIH Treatment Treatment should be continued for at least three years and for at least 24 months after complete normalization of serum transaminases and IgG levels (biochemical remission) Longer treatments may decrease the frequency of relapse. Easl Clinical Practice Guideline 2017

AIH Treatment Treatment should be continued for at least three years and for at least 24 months after complete normalization of serum transaminases and IgG levels (biochemical remission) Longer treatments may decrease the frequency of relapse. Patients with severe initial presentation and low tolerance of induction treatment should undergo to liver biopsy prior to treatment withdrawal Easl Clinical Practice Guideline 2017

AIH Treatment Treatment should be continued for at least three years and for at least 24 months after complete normalization of serum transaminases and IgG levels (biochemical remission) Longer treatments may decrease the frequency of relapse. Patients with severe initial presentation and low tolerance of induction treatment should undergo to liver biopsy prior to treatment withdrawal In patients with continued histological disease activity (HAI >3) immunosuppressive treatment should not be discontinued (high risk of relapse) Easl Clinical Practice Guideline 2017

AIH Treatment Treatment should be continued for at least three years and for at least 24 months after complete normalization of serum transaminases and IgG levels (biochemical remission) Longer treatments may decrease the frequency of relapse. Patients with severe initial presentation and low tolerance of induction treatment should undergo to liver biopsy prior to treatment withdrawal In patients with continued histological disease activity (HAI >3) immunosuppressive treatment should not be discontinued (high risk of relapse) Flares of AIH activity during maintenance therapy or following treatment reduction require increased doses of immunosuppression and preclude complete drug withdrawal Easl Clinical Practice Guideline 2017

AIH Treatment Liver Transplantation Ultimate rescue treatment 4% of OLT are due to AIH (Fulminant AIH and end stage liver cirrhosis) Particular risk of infection early after surgery Acute rejection episodes occur more frequently Manns MP J Hepatol 2015, vol 62, P 100-111

AIH Follow up Patients initiated on prednisolone/azathioprine combination therapy should have baseline clinical and laboratory parameters monitored during the first four weeks As the steroid dose is tapered monitoring intervals can be extended to 1-3 months During maintenance treatment patients should be seen in three- to six-month intervals Relapse after treatment withdrawal occurs commonly within 12 months closely monitoring after treatment withdrawal Lifelong monitoring disease flares and relapses are frequent even after complete remission Easl Clinical Practice Guideline 2017 Manns MP J Hepatol 2015, vol 62, P 100-111

Summary

Summary The diagnosis of Autoimmune Hepatitis is often challenging and it is made based on clinical and laboratory criteria including specific circulating antibodies

Summary The diagnosis of Autoimmune Hepatitis is often challenging and it is made based on clinical and laboratory criteria including specific circulating antibodies The liver histology is important for diagnosis and needs to be carefully evaluated in the context. The histology evaluate also grading and staging

Summary The diagnosis of Autoimmune Hepatitis is often challenging and it is made based on clinical and laboratory criteria including specific circulating antibodies The liver histology is important for diagnosis and needs to be carefully evaluated in the context. The histology evaluate also grading and staging SOC: corticosteroids alone or in combination with azathioprine

Summary The diagnosis of Autoimmune Hepatitis is often challenging and it is made based on clinical and laboratory criteria including specific circulating antibodies The liver histology is important for diagnosis and needs to be carefully evaluated in the context. The histology evaluate also grading and staging SOC: corticosteroids alone or in combination with azathioprine Lifelong monitoring of clinical and laboratory parameters

Thank you for your attention