Abstract
Although rare, hepatobiliary involvement in IBD can be diagnosed with a high index of suspicion. Advances in diagnosis and treatment over the past few years have helped in offering treatment to these patients which can improve their quality of life and life expectancy.

Inflammatory bowel diseases (ulcerative colitis and Crohn’s disease) have extraintestinal manifestations which involve various systems. From 1950 onwards involvement of the liver and the biliary tract has been reported. Although the best known and studied association has been Primary Sclerosing Cholangitis (PSC) various other forms of involvement have been described (Table 1).

Suspicion of hepatobiliary involvement
The diagnosis requires a high index of suspicion. Rarely primary sclerosing cholangitis may be the first manifestations of inflammatory bowel disease. It is therefore desirable to evaluate all patients with this diagnosis for the presence of inflammatory bowel disease.

In patients diagnosed as having inflammatory bowel disease, liver involvement can be suspected if the patient develops symptoms of hepatocellular failure or cholestasis or if the liver biochemistry shows an abnormality (either raised bilirubin or transaminases or a raised alkaline phosphatase). An abnormal liver imaging could also suggest hepatic involvement. There is no routine screening recommendation for hepatobiliary involvement in these patients.

Diagnosis of hepatobiliary involvement
Liver function tests are generally the starting point in a symptomatic or an asymptomatic patient. Raised transaminases suggest hepatic parenchymal involvement while raised alkaline phosphatase suggests biliary involvement. The elevations are generally modest (less than 3 times normal).
Confirmation of the exact type of involvement requires a liver biopsy or imaging of the biliary tree. An MRC (Magnetic Resonance Cholangiography) may make diagnosing primary sclerosing cholangitis easier.

Liver Parenchymal Involvement
Fatty liver
Fatty liver has been reported in upto 80% patients with IBD with a mean of 33%. Most of the studies have been before reported, before the entity of Non alcoholic fatty liver disease (NAFLD) became established. Although it is believed that fatty liver in IBD is the result of protein energy malnutrition the exact pathogenesis is not clear. Most patients with fatty liver are asymptomatic. No specific treatment other than correction of protein calorie malnutrition is recommended. Treatment of IBD does not directly improve this condition.

Autoimmune Hepatitis
Association of autoimmune hepatitis (AIH) and IBD has been long recognized. In the earlier reports the prevalence was probably overestimated as many of these patients could have had chronic Hepatitis B or C. Also, it is now recognized that AIH may have an overlap with PSC. Probably only type 1 AIH is associated with IBD. A biopsy and appropriate serology for viruses and autoimmune markers is required for the diagnosis of AIH. The condition responds to steroids and immunosuppressants. In a study reported in 1992 by Czaja’s group about 16% of patients with severe AIH had ulcerative colitis and about half of these had evidence of PSC on ERCP (Endoscopic Retrograde Cholangiopancreatography). From a practical standpoint all patients with IBD with persistently raised transaminases should be tested for autoimmune markers. Those with positive markers should be evaluated with the possibility of AIH, and AIH and PSC overlap in mind. Treatment is along standard lines. The course of IBD and AIH is independent of each other but AIH can progress to cirrhosis. Some reports with small numbers of patients (six) reported an improvement in AIH after colectomy.

Cirrhosis
Cirrhosis and fibrosis has been reported in about 1-5% patients with both types of IBD. It is more common in patients with severe and extensive disease. The pathogenesis is not known. The earlier described entity of “pericholangitis” was believed to be a precursor of cirrhosis in the earlier literature. It is now considered that in most of these patients cirrhosis results from AIH or PSC or an overlap.

Other parenchymal involvement
Other types of involvement (Table 1) are rare and poorly studied. Amyloidosis should be suspected if there is associated proteinuria. Granulomas have been described in patients with Crohn’s disease. Pyogenic liver abscess was a common complication before the advent of broad spectrum antibiotics but is rarely seen now.

Biliary Involvement of IBD
This is the most well studied complication of IBD. The maximum recent literature has been on PSC.

Pericholangitis
This term describes inflammation around the small bile ducts and was amongst the earliest and commonest associations with IBD. As per current understanding this term has been abandoned from literature. It is likely that it may proceed to development of PSC. However it has been found that the number of patients who have PSC is far less than the number of patients who have pericholangitis. The significance of this finding is unclear and it has been suggested that patients with this finding on biopsy should have an ERCP. MRC may have an evolving role in this condition.

As it is believed that some of these patients represent a phase in the development of PSC. There is also a belief that this is a small duct variant of PSC.

Primary sclerosing cholangitis (PSC)
PSC has been described in patients with extensive ulcerative colitis and patients with Crohn’s disease who have colonic or ileocolonic involvement. It is not seen in patiens with small bowel Crohn’s disease.

Diagnostic criteria
The four standard diagnostic criteria include:

1. No history of biliary surgery
2. No cholelithiasis
3. Multiple strictures in the biliary tree (Diffuse involvement)
4. Exclusion of cholangiocarcinoma

Recently there has been a proposal to include patients with cholelithiasis if the cholangiogram is quite suggestive.

Course
The course is generally indolent and the average life expectancy has been about 12 to 21 years between diagnosis and death or liver transplantation. The studies on natural history have been important in devising prognostic models and scoring systems for this condition.

Diagnosis
The gold standard for diagnosis of this condition has been ERCP. A recent study evaluated the role of MRC in this condition and showed that it was as sensitive and specific as ERCP.¹

Medical treatment
Agents which have been tried include Ursodeoxycholic acid (UDCA), Steroids, Methotrexate, D Penicillamine, more recently tacrolimus and pentoxyfylline have been used. High dose UDCA (20-25 mg/kg body weight) has been shown to improve liver biochemistry. This has been confirmed by a recent Cochrane review (2003). Cholestyramine is beneficial for symptomatic treatment of pruritus.

Endoscopic Therapy
Endoscopic therapy is used mainly for dominant strictures and palliation of cholangiocarcinoma in patients with PSC. Endoscopy is also useful in diagnosing cholangiocarcinoma with the use of brush cytology.

Orthotopic Liver Transplantation
For advanced PSC the only treatment which offers a survival in excess of 75% at 5 years. In fact after an OLT deaths in patients with PSC occur because of colonic malignancy.

Colectomy
It does not cure PSC. In fact patients who have a colectomy for control of ulcerative colitis should have an ideal pouch anal anastomosis rather than a stoma to prevent the development of peristomal varices.

Reference
1. Angulo P, Pearce DH, Johnson CD, et al. Magnetic resonance cholangiography in patients with biliary disease, its role in PSC. J Hepatol 2000; 33 :
659-60.

Chief Gastroenterologist and Hepatologist, Jehangir Hospital, Pune - 1.