Outline Figures (2) Extras (1)

762 Journal of Hepatology 2022 vol. 77 j 761–806

Table 3. Grades of recommendation. PSC is suspected in the presence of persistently elevated

Grade Wording Criteria serum liver tests in a cholestatic pattern. Most patients are
Strong Must, shall, should, is Evidence, consistency of studies, asymptomatic, but right upper quadrant abdominal pain, jaun-
recommended risk-benefit ratio, patient dice and/or pruritus may be present. Occasionally the initial
Shall not, should not, preferences, ethical obligations, presentation will be an episode of acute cholangitis, with right
is not recommended feasibility
upper quadrant abdominal pain, fever and jaundice. Secondary
Weak or Can, may, is suggested
open May not, is not suggested causes of sclerosing cholangitis should be excluded. Importantly,
50-80% of people with PSC also have IBD. Therefore, elevation in
serum liver tests, especially serum alkaline phosphatase (ALP),
The Delphi Panel agreement on each of the initial recommen- should raise suspicion for PSC and trigger further evaluation
dations is shown in the Appendix. (Fig.
Fig. 1
1). However, some rare patients may present with typical
findings of sclerosing cholangitis on cholangiography but
How is PSC diagnosed in adults? without elevation of serum ALP and gamma-glutamyltransferase
(GGT); such patients need careful follow-up.
Although MRCP can be used as a quick standalone non-
contrast test to diagnose PSC, performing a more complete,
Recommendations high-quality MRI evaluation will also provide information on bile
In adult patients presenting with elevated serum markers of duct thickness and enhancement, the status of hepatic paren-
cholestasis, a diagnosis of large duct PSC should be made in chyma and complications of liver disease including evidence of
the presence of typical findings of sclerosing cholangitis on portal hypertension.25,26
25 26 The classic features of PSC are multi-
high-quality cholangiography and after exclusion of sec- focal strictures and dilatations or ectasias involving the intra-
ondary causes. The preferred diagnostic test is magnetic and/or extrahepatic biliary tree. Other findings include ductal
resonance cholangiopancreaticography (MRCP) (LoE 2, thickening and pruning. In a meta-analysis, the pooled sensi-
strong recommendation, 93% consensus). tivity and specificity of MRCP for the diagnosis of PSC were 86%
and 94%, respectively.2727 Advantages of MRCP over endoscopic
A diagnosis of small duct PSC should be considered in retrograde cholangiopancreaticography (ERCP) include its non-
patients with elevated serum markers of cholestasis of invasive nature, lack of radiation use and lower cost, in addi-
unknown cause, normal high-quality cholangiography, tion to the potential to add MR elastography (MRE) for further
and compatible histology of PSC, particularly in those information on disease staging and prognosis.28,29
28 29 Limitations of
with concomitant inflammatory bowel disease (IBD) (LoE MRCP include poor visualisation of peripheral intrahepatic
3, strong recommendation, 88% consensus). branches, which limits the ability to diagnose very early intra-
Autoantibodies should not be used to diagnose or risk- hepatic PSC, and false-positive findings in cirrhosis of any aeti-
stratify people with PSC (LoE 4, strong recommenda- ology due to tapering and duct distortion.30,31
30 31 In a high-quality
tion, 100% consensus). MRCP, bile ducts up to third order are depicted without arti-
facts over the biliary tree and without motion blurring. For

Elevated ALP + GGT and/or bilirubin

Detailed history, physical examination

Ultrasound Dilated ducts, stones, tumor

Normal

AMA + ANA (sp100, gp210) PBC

Negative

MRCP PSC, SSC

Negative

Liver biopsy Parenchymal or biliary disease

Negative

Genetic analysis ABCB4 deficiency-(ABCB11, ATP8B1, etc.)

Fig. 1. Algorithm of diagnostic measures in chronic cholestasis (derived from20,51). 20 51 Once a positive finding has been achieved (right part of the figure),
additional diagnostic steps should be taken, if needed, according to relevant guidelines. ALP, alkaline phosphatase; AMA, anti-mitochondrial antibody; ANA, anti-
nuclear antibody; GGT, gamma-glutamyltransferase; MRCP, magnetic resonance cholangiopancreaticography; PBC, primary biliary cholangitits; PSC, primary
sclerosing cholangitis; SSC, secondary sclerosing cholangitis.

Journal of Hepatology 2022 vol. 77 j 761–806 763

Clinical Practice Guidelines

details on MRI in PSC and reporting standards please refer to the
recently published position statements.26,32
26 32
A liver biopsy it not mandatory for diagnosis in patients with
cholangiographic abnormalities compatible with PSC. However,
in roughly 10% of cases, PSC involvement is limited to the pe-
ripheral ductules and not visible in MRCP or ERCP images, so-
called small duct PSC.7 7 In these cases, a liver biopsy is required
perinuclear (p-ANCA), targeting another cytoplasmic protein,
myeloperoxidase. A third immunofluorescence pattern is called
atypical p-ANCA (perinuclear anti-neutrophil nuclear antibody),
directed against components of the nuclear envelope However,
these antibodies lack diagnostic specificity. Testing for anti-
nuclear antibody, smooth muscle antibody and anti-soluble
liver antigen is suggested when the diagnosis of overlapping