Primary sclerosing cholangitis (PSC) is a chronic inflammatory cholestatic disease characterized by the progressive destruction of bile ducts, often associated with inflammatory bowel disease, particularly ulcerative colitis. The condition has a male predominance and can present asymptomatically, with symptoms developing over time including jaundice and fatigue, and carries a lifetime risk of cholangiocarcinoma and other cancers. Management primarily involves liver transplantation as the only treatment shown to improve survival, while other medical therapies display inconsistent results.

1. Primary Sclerosing Cholangitis
Primary Sclerosing Cholangitis
HAMED RASHAD
HAMED RASHAD
Professor of surgery Banha faculty of medicine - Egypt
Professor of surgery Banha faculty of medicine - Egypt

2. Primary Sclerosing
Primary Sclerosing
Cholangitis PSC
Cholangitis PSC

3. Definition
Definition
A chronic inflammatory
A chronic inflammatory
cholestatic disease
cholestatic disease
Progressive destruction of bile
Progressive destruction of bile
ducts
ducts
May progress to cirrhosis
May progress to cirrhosis
Aetiology unknown
Aetiology unknown

4.  Rare disorder
Rare disorder
 Characterized by diffuse
Characterized by diffuse
inflammation of the biliary tract
inflammation of the biliary tract
leading to fibrosis and strictures of
leading to fibrosis and strictures of
the biliary system
the biliary system
 Most common - men aged 20-40
Most common - men aged 20-40
Primary Sclerosing
Primary Sclerosing
Cholangitis
Cholangitis

5. Epidemiology,Natural
Epidemiology,Natural
History and Prognosis
History and Prognosis
 Prevalence 6-8/100000
Prevalence 6-8/100000
 Usually diagnosed in 20s and 30s
Usually diagnosed in 20s and 30s
 Male predominance ~3:1
Male predominance ~3:1
 80% have IBD –usually UC
80% have IBD –usually UC
 ~44% asymptomatic at diagnosis
~44% asymptomatic at diagnosis
 Median survival ~ 12 years
Median survival ~ 12 years

6. IBD and PSC
IBD and PSC
 Mainly associated with UC ~85%-the
Mainly associated with UC ~85%-the
rest Crohns or indeterminate colitis
rest Crohns or indeterminate colitis
 4% UC patients will develop PSC
4% UC patients will develop PSC
 No correlation between activity of
No correlation between activity of
IBD and PSC
IBD and PSC

7. Aetiology and
Aetiology and
Pathogenesis
Pathogenesis
 Familial incidence
Familial incidence
 HLA associations-
HLA associations-
B8,DR3,DRw52a,DR2,DR4
B8,DR3,DRw52a,DR2,DR4
 Polymorphism of TNF gene
Polymorphism of TNF gene

8.  Associated with histocompatible
Associated with histocompatible
antigens HLA-B8 and -DR3 or -DR4 -
antigens HLA-B8 and -DR3 or -DR4 -
suggestive of genetic etiologic role
suggestive of genetic etiologic role
 Sclerosing cholangitis may occur in
Sclerosing cholangitis may occur in
AIDs patients from infections
AIDs patients from infections
caused by CMV, cryptosporidium, or
caused by CMV, cryptosporidium, or
microsporum
microsporum
Primary Sclerosing
Primary Sclerosing
Cholangitis
Cholangitis

9. Immune factors
Immune factors
 frequency autoimmune disorders
frequency autoimmune disorders
 T cells in blood and liver
T cells in blood and liver
 circulating immune complexes
circulating immune complexes

10. Autoantibodies
Autoantibodies
 95% patients with PSC have at least
95% patients with PSC have at least
one autoantibody
one autoantibody
 85% +ve ANCA
85% +ve ANCA
 50% +ve ANA
50% +ve ANA
 25% +ve SMA
25% +ve SMA

11. Pathogenesis
Pathogenesis
 Association between PSC and UC
Association between PSC and UC
suggests a pathogenic interaction
suggests a pathogenic interaction
 ?bacteria or toxic substances
?bacteria or toxic substances
absorbed via inflammed mucosa
absorbed via inflammed mucosa
 Bile duct injury suggest ischaemic
Bile duct injury suggest ischaemic
injury ?immune complex mediated
injury ?immune complex mediated

12. Clinical Manifestations
Clinical Manifestations
 44% asymptomatic but most
44% asymptomatic but most
develop symptoms over time
develop symptoms over time
 Pruritis,jaundice,pain and fatigue
Pruritis,jaundice,pain and fatigue
are common symptoms
are common symptoms
 Later on develop symptoms of
Later on develop symptoms of
cirrhosis and portal hypertension
cirrhosis and portal hypertension

13.  Symptoms -
Symptoms -
– progressive obstructive jaundice
progressive obstructive jaundice
frequently associated with:
frequently associated with:
 malaise, pruritus,anorexia and
malaise, pruritus,anorexia and
indigestion
indigestion
 Early detection in presymptomatic
Early detection in presymptomatic
phase may occur due to elevated
phase may occur due to elevated
alkaline phosphatase level
alkaline phosphatase level
Primary Sclerosing
Primary Sclerosing
Cholangitis
Cholangitis

14. Cholangiocarcinoma
Cholangiocarcinoma
 Lifetime prevalence of 10-30%
Lifetime prevalence of 10-30%
 Annual risk 1.5% per year
Annual risk 1.5% per year
 Difficult to diagnose
Difficult to diagnose
 Patients also have late risk of HCC
Patients also have late risk of HCC

15. PSC and Bowel cancer
PSC and Bowel cancer
 25% PSC develop cancer or dysplasia
25% PSC develop cancer or dysplasia
cf 5.6% with UC alone
cf 5.6% with UC alone
 Cancers associated with PSC tend to
Cancers associated with PSC tend to
be more proximal,are more
be more proximal,are more
advanced at diagnosis and mre likely
advanced at diagnosis and mre likely
to be fatal
to be fatal
 Need aggressive colonoscopic
Need aggressive colonoscopic
surveillance
surveillance

16. Diagnosis
Diagnosis
 Cholangiography-either MRCP or
Cholangiography-either MRCP or
ERCP
ERCP
 Clinical,biochemical and histological
Clinical,biochemical and histological
features
features

17. ERCP and MRCP
ERCP and MRCP
 Typical features:-
Typical features:-
multifocal strictures and dilatation
multifocal strictures and dilatation
usually affects both intra and
usually affects both intra and
extrahepatic ducts
extrahepatic ducts

18. MRCP image of PSC
MRCP image of PSC

19. ERCP image
ERCP image

20. MRCP-PSC
MRCP-PSC

21. ERCP-PSC
ERCP-PSC

22. Pus exuding from the papilla
Pus exuding from the papilla

23. Liver biopsy
Liver biopsy
 Useful for staging disease
Useful for staging disease
 “
“Onion skin fibrosis” only in ~10%
Onion skin fibrosis” only in ~10%
biopsies
biopsies
 ~5% patients have typical biopsy
~5% patients have typical biopsy
features with a normal
features with a normal
cholangiogram
cholangiogram

24. PSC-onion skin
PSC-onion skin
appearance
appearance

25. PSC-cirrhosis
PSC-cirrhosis

26. Lab tests
Lab tests
 LFTs-cholestatic pattern:ALP 3-5x
LFTs-cholestatic pattern:ALP 3-5x
ULN
ULN
-AST/ALT slightly elevated only
-AST/ALT slightly elevated only
-raised bilirubin may occur with
-raised bilirubin may occur with
advanced disease,dominant
advanced disease,dominant
stricture,cholangioca,stones,cholan
stricture,cholangioca,stones,cholan
gitis
gitis

27. Management
Management
 Many strategies tried but only
Many strategies tried but only
transplantation shown to improve
transplantation shown to improve
survival
survival

28.  Tx w/corticosteroids and broad spectrum
Tx w/corticosteroids and broad spectrum
antimicrobial agents yields inconsistent
antimicrobial agents yields inconsistent
and unpredictable results
and unpredictable results
 Episodes of acute bacterial cholangitis
Episodes of acute bacterial cholangitis
may be treated with ciprofloxacin
may be treated with ciprofloxacin
 high dose ursodeoxycholic acid
high dose ursodeoxycholic acid
(20mg/kg/d) may reduce
(20mg/kg/d) may reduce
cholangiographic progression and liver
cholangiographic progression and liver
fibrosis
fibrosis
Primary Sclerosing
Primary Sclerosing
Cholangitis
Cholangitis

29.  In patients with ulcerative colitis,
In patients with ulcerative colitis,
primary sclerosing cholangitis is an
primary sclerosing cholangitis is an
independent risk factor for
independent risk factor for
development of colorectal dysplasia
development of colorectal dysplasia
and cancer- routine colonoscopic
and cancer- routine colonoscopic
surveillance is advised
surveillance is advised
Primary Sclerosing
Primary Sclerosing
Cholangitis
Cholangitis

30. Ursodeoxycholic acid
Ursodeoxycholic acid
 Causes significant biochemical
Causes significant biochemical
improvement
improvement
 Little symptomatic or clinical benefit
Little symptomatic or clinical benefit
 May need high doses
May need high doses
 Major role may be to reduce bowel
Major role may be to reduce bowel
cancer risk in patients with PSC/UC
cancer risk in patients with PSC/UC
 Not funded in NZ !
Not funded in NZ !

31. Steroids
Steroids
 No long term data
No long term data
 Serious risk of bone disease
Serious risk of bone disease
 Colchicine, D-Penicillamine, Nicotine of no
Colchicine, D-Penicillamine, Nicotine of no
benefit
benefit
 Combination Rx with UDCA Aza and
Combination Rx with UDCA Aza and
steroids showed clinical and biochemical
steroids showed clinical and biochemical
improvement in a small trial
improvement in a small trial

32. Endoscopic treatment
Endoscopic treatment
 Direct injection of steroids into
Direct injection of steroids into
biliary tree ineffective
biliary tree ineffective
 Balloon dilation or stenting can
Balloon dilation or stenting can
improve clinical,biochemical and
improve clinical,biochemical and
cholangiographic appearances
cholangiographic appearances
 Some reports of survival advantages
Some reports of survival advantages
and delay to liver transplantation
and delay to liver transplantation

33.  For patients with cirrhosis and
For patients with cirrhosis and
clinical decompensation, liver
clinical decompensation, liver
transplantation is the procedure of
transplantation is the procedure of
choice
choice
Primary Sclerosing
Primary Sclerosing
Cholangitis
Cholangitis

34. Liver Transplant
Liver Transplant
 Only treatment to improve overall
Only treatment to improve overall
survival
survival
 Improves quality of life in 80%
Improves quality of life in 80%
patients
patients
 10 year survival post OLT ~70%
10 year survival post OLT ~70%
 Aim to transplant before cholangica
Aim to transplant before cholangica
 Recurrent PSC in ~ 4% of grafts
Recurrent PSC in ~ 4% of grafts

35.  Survival of patients with primary sclerosing
Survival of patients with primary sclerosing
cholangitis averages 10 years once symptoms
cholangitis averages 10 years once symptoms
appear
appear
 Adverse prognostic factors:
Adverse prognostic factors:
– increased age
increased age
– increased serum bilirubin
increased serum bilirubin
– increased aspartate aminotransferase levels
increased aspartate aminotransferase levels
– low albumin levels
low albumin levels
– history of variceal bleeding
history of variceal bleeding
Primary Sclerosing
Primary Sclerosing
Cholangitis
Cholangitis

36. THANK YOU
THANK YOU