What is the recommended approach for diagnosing and managing Primary Sclerosing Cholangitis (PSC)?

PSC Evaluation: Diagnostic and Management Approach

Initial Diagnostic Workup

MRCP is the first-line imaging modality for diagnosing PSC, with 86% sensitivity and 94% specificity, and should be performed in any patient with unexplained cholestatic liver biochemistry, particularly those with inflammatory bowel disease. 1

When to Suspect PSC

• Unexplained cholestatic biochemistry (elevated alkaline phosphatase and γ-glutamyl transpeptidase) occurs in approximately 75% of PSC patients 1
• Young to middle-aged males with elevated alkaline phosphatase 1
• Patients with newly diagnosed or pre-existing inflammatory bowel disease (60-80% of PSC patients have concurrent IBD) 1
• Symptomatic presentations including jaundice, pruritus, right upper quadrant pain, or fatigue 1
• Acute cholangitis with Charcot's triad (fever, right upper quadrant pain, jaundice) 1

Imaging Strategy

Proceed directly to MRCP when cholestatic biochemistry suggests PSC, as it provides diagnostic accuracy comparable to ERCP (sensitivity 80-100%, specificity 89-100%) without procedural risks. 1

• MRCP shows characteristic beading appearance from multifocal short strictures 1
• Contrast-enhanced MRI provides additional information about liver parenchyma, varices, cholangiocarcinoma, and lymphadenopathy 1
• ERCP should be reserved exclusively for therapeutic intervention or tissue sampling of suspicious strictures, never for diagnosis alone 2, 1
• All patients undergoing ERCP must receive prophylactic antibiotics 2, 3
• ERCP should only be performed after expert multidisciplinary assessment 2

Histological Confirmation

• Liver biopsy is not routinely needed but should be reserved for small duct PSC, suspected overlap syndromes, or unclear diagnosis where histopathology would alter management 1
• The hallmark finding is concentric "onion skin" periductal fibrosis, though often absent on small specimens 1
• For suspicious strictures during ERCP, mandatory pathological sampling using brush cytology, FISH analysis, or cholangioscopy is required 2

Distinguishing IgG4-Related Sclerosing Cholangitis

Elevated serum IgG4 levels support the diagnosis of IgG4-related disease but cannot definitively distinguish IgG4-SC from PSC. 2

• Features favoring PSC: beading pattern, peripheral duct pruning, pseudodiverticula 1
• Features suggesting IgG4-SC: long biliary strictures with prestenotic dilatations, low common bile duct strictures 1
• Measure serum IgG4 levels and consider liver biopsy when IgG4-SC is suspected 2, 1
• Assess for other organ involvement, particularly pancreatic manifestations of IgG4-RD 2

Mandatory Baseline Screening

Colonoscopy for IBD

All patients with newly diagnosed PSC must undergo colonoscopy with colonic biopsies to identify concurrent IBD. 2, 1

• This is critical given the 60-80% prevalence of IBD in PSC patients 1
• Conversely, any patient with newly diagnosed or pre-existing IBD should be screened for PSC 1

Portal Hypertension Assessment

• Screen for oesophageal varices using endoscopy when cirrhosis or portal hypertension is present 2
• This follows international guidelines for variceal screening 2

Non-Invasive Risk Stratification

• Perform transient elastography to assess liver fibrosis stage, which correlates strongly with histological staging and has prognostic significance 1
• Enhanced liver fibrosis testing also correlates with elastography and helps stratify prognosis 1

Ongoing Surveillance Protocol

Cholangiocarcinoma Surveillance

When evaluating for cholangiocarcinoma in PSC patients with dominant strictures or clinical deterioration, obtain serum CA 19-9, perform contrast-enhanced cross-sectional imaging, and mandate pathological sampling of suspicious strictures during ERCP. 1

• CA 19-9 may support diagnosis of suspected cholangiocarcinoma but cannot be relied upon alone 2
• Annual ultrasound of the gallbladder should be performed to screen for polyps 2
• If polyps are identified, refer to specialist hepatopancreaticobiliary multidisciplinary team 2

Colorectal Cancer Surveillance

Patients with PSC who have coexistent colonic IBD require annual colonoscopic surveillance from the time of diagnosis of colitis. 2

• This follows British Society of Gastroenterology guidelines for IBD surveillance 2
• Those without IBD may benefit from 5-yearly colonoscopy or earlier with new symptoms 2, 1
• The risk of colorectal cancer is markedly enhanced in PSC-IBD patients 4, 5

Hepatocellular Carcinoma Surveillance

• In the presence of cirrhosis, perform hepatocellular carcinoma surveillance according to international guidelines 2

Monitoring for Disease Progression

Non-invasive investigations such as MRCP, dynamic liver MRI, and/or contrast CT should be performed in patients with new or changing symptoms or evolving laboratory abnormalities. 2

Medical Management

What NOT to Use

UDCA is not recommended for prevention of colorectal cancer or cholangiocarcinoma. 2

• Randomized controlled trials have not shown improvement in outcomes from UDCA 2, 6

Corticosteroids and immunosuppressants are not indicated for classic PSC. 2

• These may be indicated only in patients with additional features of autoimmune hepatitis or IgG4-SC 2

Symptom Management

For pruritus, cholestyramine is first-line medical treatment, with rifampicin and naltrexone as second-line agents. 2, 1

For fatigue, actively investigate and treat alternative causes including hypothyroidism, anemia, or depression. 2, 1

Nutritional Support

• Fat-soluble vitamin deficiency is relatively common in advanced PSC; maintain a low threshold for empirical replacement 2, 1

Bone Health

All patients with PSC should have risk assessment for osteoporosis, with treatment and follow-up according to national guidelines once detected. 2, 1

Management of Dominant Strictures

In patients undergoing ERCP for dominant strictures, biliary dilatation is preferred to insertion of biliary stents. 2

• Dominant strictures (≤1.5 mm in common bile duct or ≤1 mm in hepatic duct) occur in 45-58% of patients 1
• Balloon dilatation is preferred over stent placement when symptomatic strictures require intervention 1
• Pathological sampling of suspicious strictures is mandatory during ERCP 2

Care Coordination

Patients with symptomatic, evolving, or complex disease should be referred to expert multidisciplinary hepatology centers, while early stable disease can be managed in general gastroenterology clinics with specialist oversight. 2, 1

• Provision of care should involve partnership between patients, primary care, and hospital-led specialty medicine 2
• Patients meeting inclusion criteria should be offered referral to centers participating in clinical trials 2
• Encourage participation in patient support groups 2

Liver Transplantation

PSC is a well-recognized indication for liver transplantation with excellent outcomes (85% 5-year survival), and eligibility should be assessed early in the disease course according to national guidelines. 2, 1

• Time from diagnosis to death or liver transplantation is typically 12-18 years 6
• Recurrence of PSC after transplantation occurs in up to 20% of patients 4
• Risk of worsening IBD activity or de-novo IBD occurrence exists after liver transplantation 5

Pregnancy Considerations

Pregnancy in cirrhotic PSC patients carries higher risk of maternal and fetal complications; preconception counseling and specialist monitoring are essential. 2, 1

Common Pitfalls to Avoid

• Never perform ERCP without expert multidisciplinary assessment first 2
• Do not rely on CA 19-9 alone for cholangiocarcinoma diagnosis 2
• Do not use UDCA for disease modification or cancer prevention 2
• Do not overlook IBD screening in all PSC patients 2
• Do not delay biliary drainage in acute cholangitis—ERCP should be performed within 48 hours 3