Autoimmune Liver Disease Flashcards
Features of autoimmune hepatitis
- Elevated transaminases (AST, ALT)
- Jaundice, anorexia, fatigue
- Females 4:1
- HYPERGAMMAGLOBULINEMIA
- Circulating autoantibodies
- HLADR3, DR4
- Requires LIVER BIOPSY
Plasma cell predominant inflammatory infiltrate
The portal tract is typically expanded by a lymphoplasmacytic infiltrate that
extends into the lobule causing hepatic necrosis with rosetting of liver cells
Types of autoimmune hepatitis
Type 1:
- Antinuclear
- Anti smooth muscle (most common)
- Anti-actin
- Anti-soluble liver antigen
- ANCA
- Association with HLA DR3, DR4, DR 13
Type 2:
- Anti-LKM1
- Anti-liver cytosol 1
- Association with HLADR3 and DR 7
Autoantibodies
- ANA not specific
- AMA common in type 1
- LKM-1 and LC-1 common in type 2
- SLA: highly specific for AIH
- pANCA: atypical pattern
Overlap Syndrome
PBC/AIH: antimitochondrial
PSC/AIH: none discriminatory, cholangiography indicated
Treatment of autoimmune hepatitis
- Pred +/- azathioprine
- Aim: complete normalisation of aminotransferases and IgG levels
Malignancy in autoimmune hepatitis
- Annual incidence of HCC in AIH with cirrhosis 1-2%
RF
- Longstanding cirrhosis (>10 years)
- Portal HTN
- Persistent liver inflammation
- Immunosuppressive therapy >3 years
Features of primary biliary cholangitis
-95% women
- Cholestatic disorder with serologic reactivation to antimitochondrial ab (AMA) or antinuclear ab (ANA)
AMA does not correlate with severity, stage or progression of disease
- Elevated IgM, elevated lipids, AMA +, ANA +
- AMA -ve PBC may have +ve anti-GP210 or other anti-SP100
- Histology: chronic non-suppurative, granulomatous, lymphocytic small bile duct cholangitis
Clinical Features
- Asymptomatic 50%
- Pruritus
- Hyperpigmentation
- Arthropathy (20-40%)
- Sjogrens (40-65%), scleroderma (5-15%)
Diagnosis
- In adults with cholestasis and no likelihood of systemic disease, an elevated ALP + AMA >1:40 is diagnostic of PBC
- Liver biopsy not required for diagnosis or staging
AMA + with normal LFTs
- Predicts eventual development of PNC
- Treatment not indicated until abnormal LFTS
Treatment for PBC
Complications of PBC
- Ursodeoxycholic acid
Improves liver biochem, delays histological progression as well as development of portal HTN and its complications
Pruritus occurs secondary to cholestasis leading to deposition of accumulated bile acids in tissues with exces histamine, substance P, autotaxin and lysophosphatidic acid (LPA)
- Cholestyramine
- Rifampicin
- Histamine
- Naltrexone
- Gabapentin
- Sertraline
Complications - OP - Fat soluble vitamin deficiency - Lipid issues - Other autoimmune problems (thyroid) -
Overlap syndrome: AIH/PBC
- 3-6 month trial of immunosuppression
Responders
- Higher ALT
- IgG
- Bridging necrosis
Non Responders
- Higher ALP
- IgM
- AMA titres
- No bridging necrosis
Features of primary sclerosing cholangitis
- Chronic cholestatic liver disease
- Intra and extrahepatic biliary strictures
- More common in men
- 90% will develop UC or crohn’s colitis
Should have colonoscopy with segmental biopsies - Poor prognosis, cirrhosis is common
- Pre-malignant condition
Increased risk of cholangiocarcinoma + gall bladder cancer
Significantly increased risk of colorectal cancer in PSC + IBD
Diagnosis
- MRCP
Treatment
- Ursodeoxycholic acid - controversial
Complications and Treatment of PSC
PSC complications - recurrent cholangitis, PSC cirrhosis and abscess formation
- Dominant stricture group - people with scheduled dilatation did better
- No medical therapy has been demonstrated to effectively alter the natural hx of PSC
- Majority of patients require liver transplant
- Focus on symptomatology
Symptomatic Treatments
- Pruritus
- Recurrent bacterial cholangitis
- Dominant strictures (dilatation, stenting)
- Portal HTN
Disease modifying
- ?Ursodeoxycholic acid
In relation to PBC, which of the following is correct?
A. Treatment is indicated only in patients with symptoms
B. Chenodeoxycholic acid delays disease progression and should be started at diagnosis
C. There is an increased prevalence of bowel cancer
D. Patients who have an elevated alkaline phosphatase after 12 months of ursodeoxycholic acid have a reduced survival
E. PBC does not recur after liver transplantation
D. Patients who have an elevated alkaline phosphatase after 12 months of ursodeoxycholic acid have a reduced survival
Drugs precipitating autoimmune hepatitis
Nitrofurantoin
Isoniazid
Propylthiouracil
Methyldopa
Complications of PSC
Recurrent cholangitis PSC cirrhosis Abscess formation Cholangiocarcinoma Colorectal cancer
PSC with dominant stricture on MRCP
Concerns of cholangiocarcinoma
PSC with dominant stricture on MRCP –> ERCP + cholangioscopy
In patients where it is isn’t a malignancy
- People with scheduled dilatation did better
