| What is autoimmune hepatitis? | Progressive chronic hepatitis of unknown cause occurs in children and adults of all ages, fluctuating w/ periods of increased or decreased activity.
dx based on histology, clinical and biochemical findings, abnormal globulin levels (Autoantibodies)
May be variant overlapping or mixed form |
| How is the pathogenesis of autoimmune hepatits? | Environmental agent triggers cascade of T cell events directed at liver Ag, there is a genetic predisposition leading to progressive necroinflammatory and fibrotic process in the liver
Potential triggers include (Viruses (Measles, Hep, CMV and EBV), drugs (methyldopa, nitrofuratonin, diclofenac, IFN, minocyclin, atorvastatin), herbal agents (black cohosh, dai-saiko-to) |
| What are the genetic components for getting AIH? | HLA haplotypes B8, B14, DR3, DR4, Dw3
C4A gene deletions (younger pt)
HLA DR3 (aggressive disease and less responsive to medicine and younger pt)
HLA DR4 has extrahepatic manifestations. |
| What are the classifications of AIH and differentiate between them? | . |
| How is the frequency of AIH? | Among chronic liver disease pt (11-23%), 6% of liver transplant pt (USA).
Type I AIH (0.1-1.9 of cases/ 100,000 / year in caucasian populations)
Female much more than males (70-80% females)
Type I AIH is bimodal age (10-30 yrs/ 40-50 yrs) |
| How is presentation of AIH? | Spectrum (asymptomatic to debilitating symptoms and fulminant hepatic failure)
Non specific symptoms (fatigue, malaise, anorexia, nausea, abdominal pain, itching, arthralgia (small joints)_
PE (Hepatomegaly (84%), Jaundice (70%), Spider angiomata (60%), splenomegaly (30%), ascites (20%), encephalopathy (10%) |
| What are diseases associated w/ AIH? | Hematologic (AI hemolytic anemia, pernicious anemia, idiopathic thrombocytopenic purpura, eosinophilia)
GI (IBD, celiac disease)
Proliferative glomerulonephritis, pericarditis and myocarditis.
Endocrino (Grave's (6%) and AI thyroiditis, juvenile DM)
Rheumato (RA and felty syndrome, Sjogren, systemic sclerosis, erythema nodosum) |
| What is overlap AIH syndrome? | 7% of AIH overlap w/PBC (primary biliary cirrhosis) (detectable AMA, histo injury of bile duct, may improve w/steroids)
6% of AIH overlap w/PSC (primary sclerosing cholangitis) (concurrent IBD, liver biopsy shows bile duct injury, abnormal cholangiograms, mixed hepatocellular and cholestatic liver chemistries, resistant to steroids, tx w/ ursodiol) |
| What is cryptogenic AIH? | Clinical picture indistinguishable from AIH, dx by liver biopsy, ANA- AMA and Anti-LKM-1 are negative at onset but may then become + late stages (like anti-SLA), responsive to steroids. |
| What are lab studies done in AIH? | Autoantibodies (90% of cases should be positive, for AIH Type I ASMA and ANA +, for Type II anti LKM 1 +)
Serum protein electrophoresis and quantitative Igs (IgG predominance polyclonal, gamma globulin from 3 to 6 g/dl, most of the cases we have hypergammaglobulinemia and we see the levels of them to see response to therapy)
Liver chemistries (AST-ALT elevated in all pt initial presentation (200-300 U/L) and can continue to increase w/inflammation, Serum Bi-ALP mild to moderate increase in 80-90% of pt, reflect PSC or onset of hepatocellular carcinoma due to cirrhosis)
Mild leukopenia, normochromic anemia, Coombs+ hemolytic anemia, thrombocytopenia, elevated ESR, eosinophilia (may also be present) |
| What are studies other than labs done for AIH? | Imaging (not useful, can confirm cirrhosis and rule out hepatocellular carcinoma)
ERCP (rules out coexisting PSC)
Liver biopsy (most important diagnostic procedure for AIH) |
| What are histologic findings in AIH? | Plasma cells increase, interface hepatitis (piecemeal necrosis), bridging necrosis (likely cirrhosis- which determines prognosis), lobular collapse and fibrosis.
Differentiate AIH from HCV, alcohol hep, drug-induced hep, PBC and PSC
We see conspicous plasma cell infiltrates. |
| How is dx of AIH done? | Scorring system
Gender (female +2), ALT (>3 -2, <1.5 +2), Serum glob (1-1.5 +1, 1.5-2 +2, >2 +3), Viral sero (+ -3, - +3), drug (+ -4, + +1), Alcohol intake (>60g/dl -2, <25 +2), AMA (+ -4), DR3/4 (+ +1), Histology (+3 if interface hep, +1 if lymphoplasmacytic infiltrate (+1 each), -3 if biliary change (-3 each), -5 if absence of all of the above)
ANA/SMA/LKM1 (1:40 +1, 1:80 +2, >1:80 +3)
other autoAb/autoimmune disease (+2 each), responsive to therapy (if complete +2 if relapse +3)
Total score of 10 or higher is positive result |
| How is the tx of AIH? | Prednisone and azathioprine (mainstays of therapy)
Absolute indications for therapy (serum AST >10x normal, or serum AST >5x normal +gamma globulin >2x normal, or bridging necrosis on histology)
Relative indications (symptoms, serum AST/globulin elevated less than absolute level, interface hepatitis)
We can give monotherapy of prednisone (cases of cytopenia, pregnancy, malignancy and short course- week 1 60, than 2 40, 3 30, 4 30, and maintenance at 20)
Or bitherapy (prednisone+aza, in cases of postmenopause, osteoporosis, DM, obesity, emotional lability, HTN, always give 50A, week 1 pred 30, 2 20, 3 15, 4 15, maintenance 10) |
| What are treatment endpoints for AIH? | Complete remission (absence of symptoms, AST<2x normal, histo improvement, discontinue azathioprine and be tapered off prednisone over a 6-week)
Treatment failure (deterioration of clinical, histo, or labs)
Incomplete remission (improvement insufficient to satisfy remission criteria, low immunosupression is needed) |
| How are treatment durations and results? | Immunosupressants improve 10-year life expectancy to 89%, continued for 1-2 years (65% remission in 18 months and 80% remission past 3 years, but histologic remission lags behind clinical by 3-6 months)
9% experience tx failure (resist steroids, treated w/other immunosupressants)
13% improve w/out complete remission (need low-dose long term prednisone) |
| How is use of liver transplant in AIH? | Indicated if we see decompensated liver cirrhosis (hypoalbuminemia, coagulopathy, variceal bleed, ascites, hepatic encephalopathy.
5-year survival 90%, positive autoantibodies disappear w/in 2 years, recurrence could occur post transplant for HLA DR3 +) |
| How is relapse after drug w/drawal occurring? | 50% of pt w/in 6 months, and 80% w/in 3 years.
So we use same original tx regimen although recurrence may occur again, if they relapse twice we give indefinite therapy w/either prednisone (7.5mg/day) or aza (2mg/kg/day) |
| How is the prognosis of AIH? | Spontaneous remission: 13-20% of patients -> an unpredictable event
Role of liver inflammation: severe initial presentation =worse long-term outlook than mild initial disease
Development of multiple relapses-> worse long-term prognosis
The role of HLA type: HLA DR3-positive patients are more likely to have active disease and are less responsive to therapy
Hepatocellular carcinoma (HCC)-> Surveillance abdominal imaging studies (eg, ultrasound, CT, MRI) +alpha-fetoprotein testing every 6 month |
