Primary sclerosing cholangitis K83.0

Primary sclerosing cholangitis (PSC) is a chronic, cholestatic liver disease characterized by non-purulent cholangitis with progressive destruction of the intra- and/or extrahepatic bile duct system (Lindor K et al. 2015).

PSC is more common in patients with chronic inflammatory bowel disease and is associated with an increased risk of various malignancies (13-14%), especially cholangiocellular carcinoma, colorectal carcinoma and pancreatic carcinoma.

Incidence: 1:100 000 inhabitants; prevalence: 4-16/100 000 (EASL 2009). The incidence has increased over the last 20 years (> 35% increase in 10 years).

The etiology and pathogenesis of PSC are unknown. Increased risk of disease in first-degree relatives and proven HLA association (B8, DR2, DR3 or DR3w52a). Incidence of the disease in Scandinavian countries.

Predominantly middle-aged men (62-70 %) are affected (m: w=2:1); but may also occur in children < 10 years and older patients > 70 years. The diagnosis is made on average between 36 and 52 years of age.

In the early stages mostly asymptomatic; not infrequently accidental laboratory findings; up to 50% of patients are symptom-free at the initial diagnosis of PSC. Otherwise unspecific symptoms such as fatigue and exhaustion, weight loss, itching, icterus or right-sided upper abdominal pain. Later tormenting itching (20-70%, usually well before the onset of jaundice), icterus. With the progressive destruction of the bile ducts, there is a progression of the liver disease, development of fibrosis or cirrhosis. The individual course of the disease is very different

PSC and CED: PSC is strongly associated with chronic inflammatory bowel disease (CED). In data from Northern Europe and North America, the prevalence of CEDs is 60-80% (Broome U et al. 1996). In particular, there are associations with ulcerative colitis (60-80% in the presence of PSC) and Crohn's disease (7-21% in the presence of PSC).

PSC and cholangiocellular carcinoma (CCC): In addition to the development of (biliary) cirrhosis, cholangiocellular carcinoma (C22.1) is a serious complication associated with a poor prognosis. PSC patients have a 13-14% risk of developing CCC. Important: In up to 50% of cases, CCC is diagnosed when PSC is first diagnosed or within the first year. The CA 19-9 provides a tumour marker for CCC (Lutz H et al. 2013).

PSC and gallbladder carcinoma: PSC patients have an increased risk of gallbladder polyps and gallbladder carcinoma. The prevalence of carcinomas with unclear gallbladder structures is high (> 50%) in PSC patients (Lutz H et al. 2013).

Increased cholestasis parameters, PSC-specific antibodies are not known. ANA and antineutrophil cytoplasmic antibodies(pANCA) are detectable in 60% of cases. CA 19-9 as tumor marker for CCC.

In the case of cholestatic hepatopathy of unclear etiology, PSC should be considered. If cholestasis is detected, further diagnostic or therapeutic steps are taken. According to the current guidelines of the professional societies, magnetic resonance cholangiopancreaticography (MRCP) with a sensitivity > 80 % and specificity > 90 % is considered to play the decisive role (Dave M et al.2010).

In cases of sonographically proven bile duct dilatation, endoscopic retrograde cholangiography (ERC) should be performed directly. Additionally: intraductal ultrasound, ductal cholangioscopy and endosonography of the extrahepatic bile ducts.

A liver biopsy is not routinely required. It is indicated if the visualization of the bile ducts is without significant findings and if there is still a need for clarification of cholestatic liver disease (e.g. in suspected overlap syndrome with autoimmune hepatitis or primary biliary cirrhosis (PBC).

The drug therapy options are limited, and an improvement in prognosis due to ursodeoxycholic acid (UDCA) could not be shown in randomized controlled trials. ERCP is used for balloon dilatation of dominant stenoses and for the treatment of cholangitides (Lutz H et al. 2013).

Due to the high risk of recurrence, liver transplantation is only possible in a very selected group of patients. Prerequisites for this are, among other things, the absence of distant metastases and the exclusion of lymphatic filiarisation through abdominal lymphadenectomy. A 10-year survival rate of 80 % can be achieved with a liver transplantation.

Causal therapy is not known (Karlsen TH et al. 2014). Omission of all potential liver noxae (alcohol, drugs); all patients should be vaccinated against HA/HB if the virus status is negative. Additional hepatitis infections lead to a severe course with increased mortality.

Drug treatment of PSC is a problem because there is neither a specific nor an effective treatment option. Immunosuppressants, immunomodulators and also antifibrotic therapy approaches do not show any significant effect and are therefore not used in clinical routine (Williamson KD et al. 2015).

Ursodeoxycholic acid (UDCA: 17-23 mg/kg bw, 10-30 mg/kg bw), a hydrophilic bile acid, has a long tradition in the drug treatment of PSC. However, the clinical benefit (in contrast to primary biliary cirrhosis) is controversially discussed (Williamson KD et al. 2015).

Treatment of pruritus: The opioid antagonist naltrexone showed a moderate positive effect on pruritus intensity in placebo-controlled, randomized studies (Tandon P et al. (2007). The role of UDCA in the prevention of both CCC and colorectal cancer is controversially discussed in PSC patients. As a consequence of various negative studies, the American Association for the Study of Liver Diseases (AASLD) has come out against the use of UDCA in PSC.

Liver transplantation (LTx): Liver transplantation is the only curative treatment option for PSC patients (Hirschfield GM et al. 2013). However, the optimal time for LTx should be based on the individual prognosis of each patient. Progressive severe liver disease with persistent elevation of bilirubin or recurrent cholangitis with or without development of dominant stenoses despite optimal endoscopic therapy as well as a reduction of BMI of > 10% in 12 months should be reasons for LTx listing.

For biliary tract infections: use of antibiotics (e.g. Ceftriaxone i.v.)

PSC is a chronic insidious disease that often remains clinically undetected for years. Cure is not achievable under drug therapy. After diagnosis, the time to death or liver transplantation is 12-18 years. The risk of dying from the consequences of a malignoma with a complicating appearance is 40-58 %.

An early form of PSC is possibly the so-called "small-duct PSC", a liver disease with histologically PSC-typical findings but inconspicuous cholangiogram, whereby about 20% of patients develop a progression to classic PSC. However, the majority of these patients do not develop destructive biliary tract disease and are not at increased risk of malignancy.

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