Primary Biliary Cirrhosis

VS

Primary Sclerosing CholangitisDone By

Abdulwahab K Neyazi MBBS

(Cholangitis)

Content O Introduction

O Primary Biliary Cholangitis

O Primary Sclerosing Cholangitis

O Summary

O References

IntroductionO What are those ?!!

O Different !! Or Same

O Mixing Up

Primary Biliary Cholangitis

O Cholestatic hepatic disorder of unknown etiology with autoimmune feature

O T-lymphocyte-mediated attack on small intralobular bile ducts

Primary Biliary Cholangitis

O Associated disorders

O Sicca syndrome (Sjogren) 40%

O Thyroid dysfunction 10 -15%

O CREST  5 to 15

O Rheumatoid arthritis 5 to 10

Epidemiology O Geographical variation O Women > Men

O Middle aged women (30-65 y)

Pathophysiology

Pathophysiology

Pathophysiology

Clinical Presentation

O Asymptomatic

50-60 %

Clinical PresentationO Symptomatic

Clinical PresentationO Examination

Jaundice Itching marks

Hyperpigmentation

Clinical PresentationO Examination

Xanthelasma

Xanthomata

Clinical PresentationO Examination

Hepatosplenomegaly

Clinical Presentation

DiagnosisO Middle womenO FatigueO Unexplained itchingO Jaundice

Laboratory TestsO LFTBilirubinALTAST Alkaline phosphatase GGT

Laboratory TestsO Lipid profilemild elevations (LDL and VLDL) and striking elevations of HDL

O Serologic markersAntimitochondrial antibodies (AMA)  95 %

Antinuclear antibodies (ANA) 70 %

Criteria

O No extrahepatic biliary obstruction

O No comorbidity affecting the liver

CriteriaO With two of the following are

present:

O Alk-ph at least 1.5 times the upper limit of normal

O AMA titre of 1:40 or higher

O Histologic evidence of PBC

TreatmentO Ursodeoxycholic acid (13 to 15 mg/kg per day) (Grade 1A)

Treatment

O Methotrexate

(0.25 mg/kg body weight per week orally)

O ColchicineBUT

TreatmentO Randomized trials have not

demonstrated a benefit of methotrexate or colchicine 

O Thus, we suggest AGAINST routine use of methotrexate or colchicine given alone or in combination with UDCA (Grade 2B).

TreatmentO Liver Transplant

Serum bilirubin exceeding 6 mg/dL (103 micromol/L)

Decompensated cirrhosis with an unacceptable quality of life

TreatmentO Liver Transplant

treatment-resistant ascites and spontaneous bacterial peritonitis, recurrent variceal bleeding, encephalopathy, or hepatocellular carcinoma

TreatmentO Liver Transplant

Recurrence post transplantation is 30 percent after 10 years.

TreatmentO Emerging drugs for

the treatment of Primary Biliary Cholangitis.

Obeticholic Acid2016 Feb 22.

Primary Sclerosing Cholangitis

O Chronic liver disease characterized by a progressive course of cholestasis with inflammation and fibrosis of the intrahepatic and extrahepatic bile ducts

EpidemiologyO 6 0.77 per 100,000 person-years

O Men > Women 2:1

O Middle aged men around 40 years

Epidemiology

O High association with Inflammatory Bowel Disease (70% Ulcerative colitis)

O Cholangiocarcinoma 10-15%

ClassificationO Small Duct DiseaseTypical histologic feature with normal cholangiogram

O Classic PSC Strictures of biliary tree can be detected by cholangiogram

ClassificationO 75 % Involve both intra and

extrahepatic duct

O 15% intrahepatic duct only

O 10% Extrahepatic duct only

EtiologyO Immune mediated

O Infection

O Genetic predispositionHLA-B8, DR3, DR2, and DR4

O Environmental Factors

Pathophysiology

Pathophysiology

Clinical PresentationO Asymptomatic 50%

Clinical PresentationO Symptomatic

Weight loss

Fatigue

Acute cholangitis

DiagnosisO LFT Abnormal function mainly Alk-ph

O Hypergammaglobulinemia 30 %

O IgM levels 40-50 %

DiagnosisO Serology

p-ANCA 80%

ANA 50%

DiagnosisO Ultrasound

O CT

O MRI

DiagnosisO MRCP

O ERCP

O Percutaneous transhepatic cholangiography (PTC)

ERCP

Percutaneous transhepatic cholangiography

DiagnosisO Liver Biopsy

Histopathology

StagingStagingStage I – Enlargement, edema, and scarring of the portal triads, and mononuclear cell infiltration and damage to isolated bile ducts.

Stage II – Expansion of portal triads with fibrosis extending into the surrounding parenchyma.

Stage III – Bridging fibrosis.

Stage IV – Cirrhosis.

American College of Gastroenterology guideline 2015

American College of Gastroenterology guideline 2015

O MRCP is preferred over (ERCP) to establish a diagnosis of PSC.

(Strong recommendation, moderate quality of evidence)

American College of Gastroenterology guideline 2015

O Liver biopsy is not necessary to make a diagnosis in patients with suspected PSC based on diagnostic cholangiographic findings.

(Conditional recommendation, low quality of evidence)

American College of Gastroenterology guideline 2015

O Liver biopsy is recommended to make a diagnosis in patients with suspected small duct PSC or to exclude other conditions such as suspected overlap with autoimmune hepatitis.

(Conditional recommendation, moderate quality of evidence)

American College of Gastroenterology guideline 2015

O Liver biopsy is recommended to make a diagnosis in patients with suspected small duct PSC or to exclude other conditions such as suspected overlap with autoimmune hepatitis.

(Conditional recommendation, moderate quality of evidence)

American College of Gastroenterology guideline 2015

O Antimitochondrial autoantibody testing can help exclude primary biliary cirrhosis.

(Conditional recommendation, moderate quality of evidence)O Patients with PSC should be tested at

least once for elevated serum immunogloblulin G4 (IgG4) levels.

(Conditional recommendation, moderate quality of evidence)

American College of Gastroenterology guideline 2015

O Ursodeoxycholic acid (UDCA) in doses >28 mg/kg/day should not be used for the management of patients with PSC.

(Strong recommendation and high quality of evidence)

American College of Gastroenterology guideline 2015

O ERCP with balloon dilatation is recommended for PSC patients with dominant stricture and pruritus, and/or cholangitis, to relieve symptoms.

(Strong recommendation, low quality of evidence)

American College of Gastroenterology guideline 2015

O Liver transplantation, when possible, is recommended over medical therapy or surgical drainage in PSC patients with decompensated cirrhosis, to prolong survival.

(Strong recommendation, moderate quality of evidence)

American College of Gastroenterology guideline 2015

O Patients should be referred for liver transplantation when their Model for End-Stage Liver Disease (MELD) score exceeds 14.

(Conditional recommendation, moderate quality of evidence)

American College of Gastroenterology guideline 2015

O Annual colon surveillance preferably with chromoendoscopy is recommended in PSC patients with colitis beginning at the time of PSC diagnosis.

(Conditional recommendation, moderate quality of evidence)

American College of Gastroenterology guideline 2015

O full colonoscopy with biopsies is recommended in patients with PSC regardless of the presence of symptoms to assess for associated colitis at time of PSC diagnosis.

(Conditional recommendation, moderate quality of evidence)

American College of Gastroenterology guideline 2015

O Some advocate repeating the exam every 3–5 years in those without prior evidence of colitis.

(Weak recommendation, low quality of evidence)

American College of Gastroenterology guideline 2015

O Consider screening for cholangiocarcinoma with regular cross-sectional imaging with ultrasound or MR and serial CA 19-9 every 6–12 months.

(Conditional recommendation, very low quality of evidence)

American College of Gastroenterology guideline 2015

O Cholecystectomy should be performed for patients with PSC and gallbladder polyps >8 mm, to prevent the development of gallbladder adenocarcinoma.

(Conditional recommendation, very low quality of evidence)

Summary

RefrencesO Lindor, Keith D., et al. "Ursodeoxycholic acid

in the treatment of primary biliary cirrhosis." Gastroenterology 106.5 (1994): 1284-1290.

O Canadian liver foundationO American College of Gastroenterology

guideline 2015O Uptodate

Thanks

OGreetings people!Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC).. Because both have the word primary and

are associated with the hepatobiliary system, it's easy to mix em up.

Here's how I keep them straight -

The middle word is the key:

sclerOsing has an OO for onion

O looks like a bead

biliAry has an AA for autoimmune

A for antibodies

Periductal onion skin fibrosis on histology and beaded appearance (both strictures and dilation) on cholangiography is seen in primary sclerosing cholangitis.

Cholangitis and Colitis sound similar and that's how I make the Ulcerative colitis association with PSC!

Antimitochondrial antibodies are seen in primary biliary cirrhosis. It is autoimmune.

A also reminds me of the Attenuated bile duct epithelium due to destruction of interlobular bile ducts (those that course alongside the hepatic artery) by lymphocyte infiltration (Florid duct lesion).

Since autoimmune diseases are more commonly seen in females, PBC is also common in females.. So the other one, PSC, is seen in males!

Hope you all are doing awesome < 3