management of autoimmune hepatitis - aphc.info · pierre-emmanuel rautou inserm u970, parcc@hegp,...
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Pierre-Emmanuel RAUTOUInserm U970, PARCC@HEGP, Paris
Service d’hépatologie, Hôpital Beaujon, Clichy, France
Management of autoimmune hepatitis
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Case 1
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52 year-old woman, referred for liver blood tests abnormalities for 2 years
● Medical history● Type 2 diabetes (Metformin)● Arterial hypertension (Perindopril, Amlodipine)● No alcohol
● Physical examination● 108 kg; 1.62 m (BMI 41.0 kg/m²)
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Laboratory results
22/01/2013
AST (IU/L) (< 31) 165
ALT (IU/L) (<34) 70
ALK (IU/L) (<100) 94
GGT (IU/L) (<38) 25
Bilirubin (µmol/L) 25
Albumin (g/L) 35
Prothrombin time (%) 65%
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● Work-up for causes:● HBs Ag undetectable● Anti-HCV Ab undetectable● IgG 19 g/L (<16g/L)● Anti-antinuclear Ab: 1/320
● Ultrasound: steatosis, no thrombosis
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Liver blood tests abnormalities in this patients can be due to:
A- Non alcoholic steatohepatitis
B- Autoimmune hepatitis
Question
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Liver blood tests abnormalities in this patients can be due to:
A- Non alcoholic steatohepatitis
B- Autoimmune hepatitis
Question
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NASH and auto-antibodies864 patients with
biopsy proven NASH
Significant autoantibodies* N=182 (21%)
No significant autoantibodies N=682 (79%)
* ANA ≥1:160 or SMA ≥ 1:40 or both
No difference in:● age, gender, race, BMI, HOMA-IR or history of diabetes ● lobular inflammation, ballooning, advanced fibrosis
Less steatosis
Vuppalanchi, Hepatology 2009Vuppalanchi, Hepatol Int 2011
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Liver biopsy
Courtesy Pr P Bedossa
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How would you manage that patient?
A- No treatment
B- Prednisolone alone
C- Prednisolone + Azathioprine
D- Budesonide alone
E- Budesonide + Azathioprine
Question
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How would you manage that patient?
A- No treatment
B- Prednisolone alone
C- Prednisolone + Azathioprine
D- Budesonide alone
E- Budesonide + Azathioprine
Question
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Laboratory results
01/2013 06/2013
AST (IU/L) (< 31) 165 62
ALT (IU/L) (<34) 70 51
ALK (IU/L) (<100) 94 90
GGT (IU/L) (<38) 25 24
Bilirubin (µmol/L) 25 20
Albumin (g/L) 35 36
PT (%) 65% 70
IgG (g/L) 19 16
Prednisolone + Azathioprine
But, poor diabetes control and intolerance to azathioprine
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What would you then propose to this patient?
A- No treatment (stop immunosupression)
B- Prednisolone alone
C- Mycophenolate mofetil alone
D- Tacrolimus alone
Question
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What would you then propose to this patient?
A- No treatment stop (immunosupression)
B- Prednisolone alone
C- Mycophenolate mofetil alone
D- Tacrolimus alone
Question
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Second line for azathioprine-intolerant patients: MMF
Efe, CGH 2017Roberts, CGH 2017
N= Biochemical remission maintenance
Efe, CGH 2017 74 92%
Roberts, CGH 2017 63 62%
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Laboratory results
01/2013 06/2013 01/2014
AST (IU/L) (< 31) 165 62 60
ALT (IU/L) (<34) 70 51 53
ALK (IU/L) (<100) 94 90 85
GGT (IU/L) (<38) 25 24 27
Bilirubin (µmol/L) 25 20 19
Albumin (g/L) 35 36 36
PT (%) 65% 70 71
IgG (g/L) 19 16 15
Prednisolone + AZA
Weight loss, good diabetes control
MMF 2g/day
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Laboratory results
01/2013 06/2013 01/2014 12/2014
AST (IU/L) (< 31) 165 62 60 29
ALT (IU/L) (<34) 70 51 53 30
ALK (IU/L) (<100) 94 90 85 70
GGT (IU/L) (<38) 25 24 27 20
Bilirubin (µmol/L) 25 20 19 15
Albumin (g/L) 35 36 36 43
PT (%) 65% 70 71 86
IgG (g/L) 19 16 15 13
Prednisolone + AZA
Weight loss, good diabetes control
MMF 2g/day
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The patient asks you if you will consider stopping MMF. What would you answer?A- Now, since biochemical remission is obtainedB- After � 2 years of normal AST and ALTC- After � 2 years of normal AST, ALT + IgGD- Never (lifelong treatment)
Question
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The patient asks you if you will consider stopping MMF. What would you answer?A- Now, since biochemical remission is obtainedB- After � 2 years of normal AST and ALTC- After � 2 years of normal AST, ALT + IgGD- Never (lifelong treatment)
Question
But relapse � 50%, typically within 12 months
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Question
2017: AST, ALT and IgG strictly normal since 2014
You consider interrupting MMF
Do you perform a liver biopsy?
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Hartl, J Hepatol 2018
Histological remission
Mild histological disease activity
High histological disease activity
Normal IgGNormal ALT
N=22
↑ IgGAnd/or ↑ ALT
N=38
Biochemical vs. histological remission
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Liver biopsy
Courtesy Pr P Bedossa
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Liver biopsy
Courtesy Pr P Bedossa
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Question
You propose withdrawal of MMF. How?
A- Complete interruption (biochemical + histo remission)
B- Stepwise reduction every 6-8 weeks
C- Stepwise reduction every year
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Question
You propose withdrawal of MMF. How?
A- Complete interruption (biochemical + histo remission)
B- Stepwise reduction every 6-8 weeks
C- Stepwise reduction every year
AASLD guidelines 2010
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Question
How frequently do you perform blood tests during MMF withdrawal?
A- Every week
B- Every 3 weeks
C- Every 3 months
D- Every year
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Question
How frequently do you perform blood tests during MMF withdrawal?
A- Every week
B- Every 3 weeks
C- Every 3 months
D- Every year
AASLD guidelines 2010
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Question
Do you think that liver stiffness could be of interest?
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Hartl, J Hepatol 2016
Liver stiffness in AIH: first 6 monthsALT (IU/L)
Liver stiffness
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Liver stiffness in AIH: long-term
Hartl, J Hepatol 2018
F4 (n=11)
F3 (n=18)
F2 (n=50)
F0-F1 (n=46)
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• Liver stiffness: 5.9 kPa• Hepatic venous pressure gradient: 7 mm Hg
Liver biopsy vs. liver stiffness
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Case 2
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15 year-old man, referred for liver blood tests abnormalities discovered at the time of the diagnosis of ulcerative colitis (pancolitis)
● Medical history● none
● Physical examination● 53 kg; 1.76m
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Laboratory results
AST (IU/L) (< 35) 89
ALT (IU/L) (<45) 246
ALK (IU/L) (<150) 235
GGT (IU/L) (<55) 81
Bilirubin (µmol/L) 7
Albumin (g/L) 35
Prothrombin time (%) 76
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● Work-up for causes:● HBs Ag undetectable● Anti-HCV Ab undetectable● IgG 28 g/L (<16g/L)● Anti-antinuclear Ab: 1/1280
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Question
This presentation is consistent with:
A- Autoimmune hepatitis (AIH)
B- Primary sclerosing cholangitis (PSC)
C- Overlap syndrome (AIH-PSC)
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Question
This presentation is consistent with:
A- Autoimmune hepatitis (AIH)
B- Primary sclerosing cholangitis (PSC)
C- Overlap syndrome (AIH-PSC)
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• Among children with PSC: ● 33% have autoimmune hepatitis● 25% have normal ALK levels
• Overestimation due to fibrosis
Feldstein, Hepatology 2003Deneau, Hepatology 2017
AIH, PSC in children
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Lewin, Hepatology 2009
Extensive liver fibrosis induces mild intrahepatic bile duct abnormalities in AIH
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Liver biopsy
Courtesy Pr V Paradis
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Liver biopsy
Courtesy Pr V Paradis
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Well-controlled liver disease with MMF 2 g/day (relapse when withdrawal tested). He married and wants children. What would you suggest?A- Maintain MMFB- Stop all immunosuppressive therapyC- Low dose prednisolone
Question
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Well-controlled liver disease with MMF 2 g/day (relapse when withdrawal tested). He married and wants children. What would you suggest?A- Maintain MMFB- Stop all immunosuppressive therapyC- Low dose prednisolone
Question