| What are chronic cholestatic liver diseases? | Most common ones are primary biliary cirrhosis and PSC in adults, clinically distinct diseases, maybe autoimmune, progressive destruction of bile ducts leading to chronic cholestasis and biliary cirrhosis.
Complications such as portal HTN and liver failure may occur
These are rare diseases. |
| What is primary biliary cirrhosis? | Ongoing inflammatory destruction of interlobular and septal bile ducts leading to biliary cirrhosis
Occurs mostly for middle-aged women of most racial groups |
| How is epidemiology of PBC? | Women: Men 9:1, median age is 50 years, but wide range (21-91 years, not seen in under 20)
19-240 cases/million population (more in england), annual incidence is 2-22/million population
Increasing prevalence over time. |
| What are genetic components of PBC? | Class 11 HLA contribute to it, HLA DR8 is most observed link found.
HLA 1 no link at all. |
| How is pathogenesis of PBC? | Autoimmune maybe, AMAs, triggered by immune response to an alloantigen/autoantigen lead to destruction of duct, chronic cholestasis and biliary cirrhosis. |
| What are clinical features of PBC? | Asymptomatic (30% of pt, elevated ALP and AMA, hyperlipidemia)
Symptomatic (fatigue 90%, pruritis 70%, hyperpigmentation 55%, hepatomegaly 50%, jaundice and splenomegaly 30%, xanthelasma 20%)
Associated diseases include (keratoconjunctivitis 72-100%, CREST 78%, Cutaneous disorders (lichen, lupus, pemphigoid 50-80%), arthritis 4-42%, scleroderma 20%, raynaud disease 20%, AI thyroiditis 11%, renal acidosis gallstones 33%) |
| How is dx of PBC done? | Labs (ALP and GGT increase 3-4 x normal, AST and ALT mild elevation (<3x), Bi normal early stages but may reach 20mg/dl, low serum albumin and prolonged prothrombin time (poor prognosis and advanced disease), 90% have + AMA (sens 98% spec 96%), RF (70%), Anti smooth muscle (66%), ANA (30%)..)
Liver histology (Biopsy for final dx and exclusion of other causes, damage to epithelium in small bile ducts (initial), may be ductopenia (absence of interlobular bile ducts in more than 50% of portal tracts) |
| How is the tx of PBC? | Specific therapy (corticosteroid, cyclosporin, azathioprine, chlorambucil, D-pencillamine, methotrixate, Colchicine, Tacrolimus, Ursodeoxycholic acid (improves survival slightly) |
| What are complications of PBC? | Chronic cholestasis causes bone disease, fat-soluble vitamin deficiency, hypercholesterolemia and hyperlipidemia, pruritis and steatorrhea. |
| How is liver transplant in case of PBC? | Best therapy for end-stage disease, used w/development of major complications of portal HTN, but have poor QoL due to disabling fatigue, intractable pruritis and severe muscle wasting.
We may have persistent increase in serum Bi w/out hepatic malignancy, 1-year survival >90%, 5-year survival >80%, AMA may persist after transplant. |
| What is primary sclerosing cholangitis? | Chronic cholestatic syndrome of unknown etiology, associated w/IBD, diffuse fibrosing inflammatory destruction of intra/extrahepatic biliary duct system.
follows progression of biliary cirrhosis, and get complications of portal HTN and liver failure unless a transplant is done. |
| How is epidemiology of PSC? | Male:Female 2:1, median age 40 years, range from 1-90 years, 70% pt w/PSC get ulcerative colitis, 3-7.5% of pt w/ulcerative colitis have PSC, 2-7 cases/100,000 in USA. |
| How is pathogenesis of PSC? | Unknown cause, factors propsed: immune and genetics (CD4+ T cells, HLA DRBI - 0301 (DR3) and DRw52a alleles 149-150-151)
Non-immune (Chronic portal bacteremia caused by IBD leads to chronic biliary tract infection, inflammation, portal fibrosis, and ultimately PSC. |
| How is dx of PSC? | Clinical (fatigue, pruritis, jaundice, weight loss, fever, hepatomegaly, splenomegaly, hyperpigmentation, IBD (ulcerative colitis and crohns less likely))
Labs (elevated ALP 3-5 x normal, mild ALT/AST elevation, serum Bi fluctuates (complications like cholangiocarcinoma, strictures) non-organ specific autoantibodies)
Radio (ERCP (first choice) if unsuccessful percutaneous transhepatic cholangiography), MRCP)
We see diffuse multifocal annular strictures extra and intrahepatic bile ducts, short bandlike strictures, diverticulum like out pouchings, pancreatic duct involvement causes chronic pancreatitis)
Histology (4 stages: periductal fibrosis, bile duct proliferation, ductal obliteration and ductopenia) |
| What are complications associated w/PSC? | Malignancy (most lethal one, cholangiocarcinoma, older age, long duration IBD, smoking, brushing ERCP biliary stricture, CA19-9 tells about it)
Chronic cholestasis (same as above) |
| What is the medical therapy of PSC? | UDCA (imp)
Colchicine
Cyclosporin
Methotrexate (imp)
D-penicillamine
Tacrolimus (imp)
Corticosteroids (imp)
Azathioprine
Pentoxifylline
Nicotine
UDCA + Methotrexate
Corticosteroids + Colchicine (imp) |
| What is liver transplant use in PSC? | PSC is one of the most common indications for transplant in USA, 1 year survival 90-97%, similar indications as PBC |
| What is autoimmune cholangitis? | AKA AMA Ab - PBC, Clinically, biochemically, and histologically appear to have the classical features of PBC
Most of these patients have antinuclear or antismooth muscle antibodies
Therapeutic response to UDCA similar to that of AMA-positive, Different genetic susceptibility for the development of these two conditions
When features in the liver biopsy suggest superimposed autoimmune hepatitis the combination of corticosteroids and UDCA should be considered |
