1. CHOLESTASIS Dr Mahsa Khodadoostan
Isfahan university of medical science
Department of Gastroentrology and Hepatology

2. Cholestasis is an impairment of bile formation and/or bile flow
Symptoms of fatigue, pruritus and in its most overt form, jaundice.
Early biochemical markers in often asymptomatic patients
increases in serum alkaline phosphatase (ALP)
γ -glutamyltranspeptidase (γGT)
Conjugated hyperbilirubinaemia at more advanced stages.
Cholestasis
classified as intra-hepatic or extra-hepatic

3. :Alkaline phosphatase
liver
Bones
Intestines
Pancreas
Kidneys
placenta

4. :Gamma-glutamyl transpeptidase
hepatocytes and biliary epithelial cells
Kidney
seminal vesicles
Pancreas
Spleen
Heart
brain

5. 5'-nucleotidase :
it is only released into serum by hepatobiliary tissue

11. Which of these tests is not LIVER FUNCTION TEST?
A: Bilirubin
B: Aminotransferase ( ALT and AST)
C: Albumin
D: INR

12. 1:Which of these tests in not LIVER FUNCTION TEST
1:Which of these tests in not LIVER FUNCTION TEST? A: Bilirubin B: Aminotransferase ( ALT and AST) C: Albumin D: INR

13. 2: A 46 year old man is consulted because of incidentaly discovered elevated alkaline phosphatase,
CBC: Normal
ALT= 20, AST= 16, ALP= 610
Bili= 1, INR= 1
Please select the next step?
A: Abdominal sonography
B: MRCP
C: serum GGT
D: AMA

14. 2: A 46 year old man is consulted because of incidentaly discovered elevated alkaline phosphatase, CBC: Normal ALT= 20, AST= 16, ALP= 610 Bili= 1, INR= 1 Please select the next step? A: Abdominal sonography B: MRCP C: serum GGT D: AMA

16. 3: Patient is a 52 year old lady who is admitted in ER because of RUQ pain, On PH/E she is icteric, febrile and has RUQ tenderness.
CBC : WBC= , neut= 80%, Hb= 13, Plt=
ALT= 73, AST= 60, ALP= 980, Bili. T= 3.1, D= 2.5
INR= 1
What do you order as the next test?
A: Abdominal sonography
B: MRCP
C: ERCP
D: GGT

17. 3: Patient is a 52 year old lady who is admitted in ER because of RUQ pain, On PH/E she is icteric, febrile and has RUQ tenderness.
CBC : WBC= , neut= 80%, Hb= 13, Plt=
ALT= 73, AST= 60, ALP= 980, Bili. T= 3.1, D= 2.5
INR= 1
What do you order as the next test?
A: Abdominal sonography
B: MRCP
C: ERCP
D: GGT

18. Abdominal sonography:
Liver has normal echotexture and intrahepatic bile ducts are dilated
CBD was measured up to 11mm in midpart and contained a 10mm stone in distal part
Gallbladder has normal wall thickness and contained two small stones
What’s the next step ?
A: MRCP
B: ERCP then cholecystectomy
C: Cholecystectomy and intraoperative CBD exploration
D: Cholecystectomy then ERCP

19. Liver has normal echotexture and intrahepatic bile ducts are dilated
CBD was measured up to 11mm in midpart and contained a 10mm stone in distal part
Gallbladder has normal wall thickness and contained two small stones
What’s the next step ?
A: MRCP
B: ERCP then cholecystectomy
C: Cholecystectomy and intraoperative CBD exploration
D: Cholecystectomy then ERCP

21. 4:Patient is a 56year old man who is referred because of icter, pruritus, abdominal pain and weight loss.
CBC: Normal
ALT= 70, AST= 67, ALP= 1090, Bili= 9
What is the next step?
A: Abdominal sonography
B: MRCP
C: ERCP
D: GGT

22. Patient is a 56year old man who is referred because of icter, pruritus, abdominal pain and weight loss.
CBC: Normal
ALT= 70, AST= 67, ALP= 1090, Bili= 9
What is the next step?
A: Abdominal sonography
B: MRCP
C: ERCP
D: GGT

23. Abdominal sonography:
Dilated CBD without stone or sludge inside
What’s the next test?
A: MRCP+ MRI
B: Abdominal CT scan
C: Endoscopic ultrasonography
D: All of them

24. Dilated CBD without stone or sludge inside
What’s the next test?
A: MRCP+ MRI
B: Abdominal CT scan
C: Endoscopic ultrasonography
D: All of them

26. 6:Patient is a 30 year old man who is referred because of pruritus
ALT= 50, AST= 35, ALP= 890, Bili= 2
On sonography there was no intra or extrahepatic bile duct ectasia
What is the next step?
A: MRCP
B: ERCP
C: AMA
D: EUS

27. Patient is a 30 year old man who is referred because of pruritus
ALT= 50, AST= 35, ALP= 890, Bili= 2
On sonography there was no intra or extrahepatic bile duct ectasia
What is the next step?
A: MRCP
B: ERCP
C: AMA
D: EUS

28. AMA was negative
What do you order as the next test?
A: MRCP
B: ERCP
C: Biopsy
D: EUS

29. What do you order as the next test?
A: MRCP
B: ERCP
C: Biopsy
D: EUS

30. Primary sclerosing cholangitis
multifocal strictures, segmental dilations)

33. What’s the next diagnostic test in this PSC patient?
A: Upper gi endoscopy
B: Colonoscopy
C: Liver biopsy
D: Abdominal CT scan

34. What’s the next diagnostic test in this patient?
A: Upper gi endoscopy
B: Colonoscopy
C: Liver biopsy
D: Abdominal CT scan

35. Primary Sclerosing Cholangitis

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

37. Patients with PSC may be asymptomatic and diagnosed as part of the evaluation of abnormal laboratory tests, or they may have symptoms such as fatigue and pruritus.
Physical examination may reveal jaundice, hepatomegaly, splenomegaly, and excoriations, though it is often normal

38. complications Fat-soluble vitamin deficiencies (A, D, E, and K)
Metabolic bone disease
Dominant biliary strictures
Cholangitis and cholelithiasis
Cholangiocarcinoma
Gallbladder cancer
Hepatocellular carcinoma (in patients with cirrhosis)
Colon cancer (in patients with concomitant ulcerative colitis)

39. Relationship to IBD IBD in 60-90% of PSC patients
UC more common than Crohn’s (2:1)
PSC in Crohn’s disease almost always involves the colon
2-10% of UC patients have PSC

40. There are two major goals of treatment in primary sclerosing cholangitis (PSC):
Retardation and reversal of the disease process
Management of progressive disease and its complications

41. A variety of immunosuppressive and anti-inflammatory agents have been studied in patients with PSC, but none has shown a consistent benefit on overall or transplant- free survival
a role for any medical therapy is unproven

42. In patients who are already taking UDCA, we suggest stopping UDCA but reinstituting it at standard doses (13 to 15 mg/kg per day in divided doses) if:
they develop worsening pruritus or jaundice

43. given the uncertainty regarding its benefits, an alternative approach is to start (or continue) UDCA in patients who want to take it despite the uncertain benefits
After six months, if the alkaline phosphatase normalizes or is decreased by at least 40 percent, or if the patient experiences symptomatic improvement, UDCA can be continued. Otherwise, it is stopped

44. We suggest that patients with a dominant stricture and pruritus and/or cholangitis undergo endoscopic therapy to dilate and/or stent the stricture
Long-term prophylactic antibiotics are indicated for patients with recurrent cholangitis despite efforts to treat a dominant stricture

45. Mild pruritus: warm baths and emollients may help
Mild pruritus: warm baths and emollients may help. Antihistamines may also be helpful
Moderate to severe pruritus:
initially treat with a bile acid sequestrant such as cholestyramine (total daily dose of 4 to 16 grams)
does not provide adequate, relief we switch to rifampin (150 to 300 mg twice daily)
If symptoms persist, we then switch to an opioid antagonist, such as naltrexone (12.5 to 50 mg/day)
Switching to sertraline (75 to 100 mg daily) or phenobarbital 90 mg at bedtime can be tried if other measures fail

46. 6:Patient is a 56 years old lady who is referred because of icter and pruritus since 2 years ago
CBC: WBC= 4200, HB= 12.5, PLt= 98000
ALT= 32, AST= 40, ALP= 1400
Bili.T= 4 , Bili.D= 3.5, INR= 1.5 , Alb= 3.2
On physical examination she is icteric and has splenomegaly

48. What’s the most common diagnosis:
A: Pancreatic cancer
B: CBD stone
C: PBC
D: PSC

49. What’s the most common diagnosis:
A: Pancreatic cancer
B: CBD stone
C: PBC
D: PSC

50. Primary biliary cholangitis (PBC) is rare,19 to 402 cases per million persons
The vast majority of patients (90 to 95 percent) are women
most patients are diagnosed between the ages of 30 and 65 years

51. Approximately 50 to 60 percent of patients with PBC are asymptomatic
Among patients with symptoms, fatigue and pruritus are most commonly seen

52. PBC is a progressive disease in most patients
PBC is a progressive disease in most patients. It eventually becomes irreversible, and therefore untreatable. The only widely accepted treatment is ursodeoxycholic acid (UDCA)
It is the only treatment aimed at modifying the natural history of the disease

53. A 23-year-old woman gravida 2 para 1 currently at 35 weeks with a singleton gestation is referred from a dermatologist for intractable itching
The itching is primarily on the palms of her hands and soles of her feet
It is present day and night, and keeps her from sleeping
The patient also had itching during her first pregnancy in which the fetus died in utero in the third trimester

54. What is your first diagnosis?

55. Intrahepatic cholestasis of pregnancy (ICP) occurs in the second and third trimester
is characterized by pruritus and an elevation in serum bile acid concentrations
For unknown reasons the disease is seen more commonly in the colder months

56. PATHOGENESIS
The cause of ICP is unknown but genetic, hormonal, and environmental factors are likely involved

57. Estrogens and progesterone
It is recommended that progesterone treatment be avoided in pregnant women with a previous history of ICP and immediately withdrawn when cholestasis occurs during pregnancy

58. CLINICAL MANIFESTATIONS
Pruritus may precede laboratory abnormalities
Abdominal pain is uncommon
Encephalopathy or other stigmata of liver failure are unusual
Physical examination is nonspecific
may show excoriations due to scratching
Jaundice occurs in less than 10 percent

59. Laboratory findings
Serum total bile acid concentrations increase in ICP, and may be the first or only laboratory abnormality

60. elevations in alkaline phosphatase, 5' nucleotidase, and total and direct bilirubin concentrations
Total bilirubin levels rarely exceed 6 mg/dL
gamma glutamyl transpeptidase (GGT) are normal or modestly elevated
aminotransferases may reach values greater than U/L
The prothrombin time is usually normal
prolonged prothrombin times reflect vitamin K deficiency due to cholestasis or to the use of bile acid sequestrants rather than liver dysfunction

61. ULTRASONOGRAPHY
the biliary ducts are not dilated and hepatic parenchyma appears normal

62. DIAGNOSIS
Most women are diagnosed during the second or third trimester
The diagnosis of ICP is based upon the presence of pruritus associated with elevated total serum bile acids levels and/or aminotransferases

63. TREATMENT
UDCA is considered as the first line treatment for ICP(500 BID or 300 TDS)
Hydroxyzine (25 to 50 mg/day)
Cholestyramine (8 to 16 g/day)

64. Cholestasis recurs during subsequent pregnancies in 60 to 70 percent
increased risk for gallstones
some women who develop ICP have underlying liver disease :
women in whom ICP is suspected and/or who have elevated serum aminotransferase during pregnancy should be tested for chronic hepatitis (especially hepatitis C)
liver function tests should be checked several months after the delivery

65. Hormonal contraception
contraceptives with a low dose of estrogen can be initiated after normalization of liver function tests
check liver function tests after three or six months of such contraception.

66. FETAL FOLLOW-UP AND OUTCOME
In contrast to the favorable prognosis for mothers, ICP carries significant risk for the fetus
fetal prematurity
meconium stained amniotic fluid
intrauterine demise
neonatal respiratory distress syndrome

67. Timing of delivery 37 wk 35-37 wk : Severe itching Jaundice
Prior fetal death