Primary sclerosing cholangitis and Biliary cirrhosis associated with Ulcerative colitis

Abstract

Primary sclerosing cholangitis and Ulcerative colitis are caused by progressive inflammation of the bile duct and large intestine respectively. The existence of any plausible association between Primary sclerosing cholangitis and Ulcerative colitis remains highly elusive. Little is known about the incidence and prevalence of primary sclerosing cholangitis with concomitant Ulcerative colitis in the Indian subcontinent. We report a case of Primary sclerosing cholangitis with long standing Ulcerative colitis which later also developed Primary biliary cirrhosis. [PUBLICATION ABSTRACT]

Headnote

Abstract

Primary sclerosing cholangitis and Ulcerative colitis are caused by progressive inflammation of the bile duct and large intestine respectively. The existence of any plausible association between Primary sclerosing cholangitis and Ulcerative colitis remains highly elusive. Little is known about the incidence and prevalence of primary sclerosing cholangitis with concomitant Ulcerative colitis in the Indian subcontinent. We report a case of Primary sclerosing cholangitis with long standing Ulcerative colitis which later also developed Primary biliary cirrhosis.

Key words: Primary sclerosing cholangitis, Ulcerative colitis, Primary biliary cirrhosis

© 2011 Deccan College of Medical Sciences. All rights reserved.

Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by obliter-ative inflammation and fibrosis which usually involves the whole biliary tree1. PSC causes dam-age to the bile ducts both inside and outside the liv-er, resulting in scarring of the bile ducts and block-age of bile flow, causing cholestasis. Chronic biliary obstruction causes portal tract fibrosis and ultimate-ly biliary cirrhosis and liver failure. It is reported that almost 70% of patients suffering from PSC present with concomitant idiopathic Ulcerative colitis (UC)2. UC, one of the two most common manifestations of inflammatory bowel disease (IBD) is usually charac-terized by mucosal inflammation limited to the colon, always involving the rectum and a variable extent of the more proximal colon in a diffuse or continuous manner. The extent of disease varies from isolated proctitis to extensive disease i.e. pancolitis3.

The incidence of UC is approximately 10-20 per 100,000 per year with a reported prevalence of 100-200 per 100,0004. The incidence remains stable, but the prevalence is likely to be an underestimate be-cause this implies average disease duration (preva-lence/incidence) of 10 years for a condition that is known to last for life5. There are marked differences between ethnic groups with some (such as Ashke-nazi Jews) having a particularly high incidence3. It is reported that annual frequency of PSC is 0.9-1.31/100,000 with point prevalence of 8.5-13.6/100,000 and this appears to be growing6. PSC is twice more frequent in men than in women (men constitute 2/3 of all cases). PSC occurs in 5% of patients with UC and UC occurs in 60-75% of pa-tients affected with PSC6.

We present a rarely-reported case, of an Indian eth-nic male with typical presentation of primary scleros-ing cholangitis with long standing ulcerative colitis.

Case Report

In January 2005, a 44 year old male patient pre-sented with jaundice, profuse bleeding per rectum, and frequency of stools [8-10/day]. The patient also suffered with fever, chills, rigors and severe abdo-minal pain over the preceding 10 days. Jaundice was found to be progressive and accompanied by pruritus.

His past record revealed that he had presented with complaint of blood in stools for about a year, occur-ring about 4-5 times per day, in 1993. The patient had been advised regular surveillance and follow-up for 6 months, but he had not returned for any medi-cal visit subsequently. He had no history or evidence of other extra-intestinal manifestations, such as in joints or skin. The patient had no history of smoking or use of alcohol.

At this visit, tests for coronary artery disease (CAD), diabetes mellitus (DM), hypertension (HTN), and chronic obstructive airways disease (COAD), were found to be negative. Colonoscopic examination, followed by histopathology, revealed pancolitis with discrete multiple ulcers, MELD Mayo score of 10.

The patient was started on Salazopyrine (3000 mg / daily) and oral corticosteroids (Prednisolone, 30mg) with 5mg tapering per week.

The patients liver function tests (LFT) performed in January 2005 showed: Bilirubin - 9.5/7.0mg/dL, se-rum glutamic oxaloacetic transaminase (SGOT) - 605U/L, serum glutamic pyruvate transaminase (SGPT) - 235U/L, serum alkaline phosphatase (SAP) - 1400U/L, thymidine phosphorylase (TP) - 6.4U/mL, albumin (Alb) - 3.0 g/dl, haemoglobin (Hb)- 12gm%, total leucocyte count (TLC) - 20,400 cu.mm. All viral markers were found to be negative.

The endoscopic retrograde cholangiopancreatogra-phy (ERCP) report indicated mildly dilated common bile duct CBD with multiple filling defects. The pa-tient also underwent sphincterotomy, followed by balloon trawl, at this time, and multiple pigment stones were extracted. Cholangiogram revealed primary sclerosing cholangitis.

The patient was started on: Tab. Ursodeoxycholic acid (300 mg, twice daily), Tab. Mesalamine (800 mg, thrice daily), Proton pump inhibitor (PPI), Vita-min E and Vitamin B12 support.

He was discharged 3 days later with the diagnosis of UC with hepato-biliary complications and common bile duct (CBD) calculi causing obstructive jaundice.

In March 2005, the patient was reviewed. At this time the lab results were as follows: Bilirubin - 2.1mg/dl, SGOT - 38U/L, SGPT - 52U/L, SAP -421U/L, Alb - 3.6g/dl, TP - 7.2 U/mL. The ultra sound (US) abdomen showed subtle intrahepatic biliary dilatation (IHBD) in both the lobes of liver, a CBD of 4 mm, and sludge in the gall bladder.

In September 2005, the patient came back with re-current jaundice, fever, abdominal pain, but with UC in remission. The LFT results showed - Bilirubin 6.8mg/dl, SGOT - 362U/L, SGPT - 334U/L, SAP - 745U/L, Alb - 3.5g/dl, TP - 7.8U/mL. The ultrasound abdomen tested positive for IHBD and showed a mild dilation in CBD with multiple calculi. Again ERCP was performed, and after the balloon trawl test and extending the sphicterotomy, some pig-mented calculi were extracted.

After 15 days the LFT showed normal results: Biliru-bin - 0.9mg/dl, SAP - 451U/L). Colonoscopy showed pancolitis and in the biopsy (Bx) - Lamina propria showed diffuse infiltrates of plasma cells, lympho-cytes and neutrophils; some of the glands showed degenerative changes. Granulomata and dysplasia were consistent with chronic UC in remission.

In May 2007, the patient presented with progressive abdominal distension and bilateral pedal edema since 3 months, and UC in remission. He had no fever, gastrointestinal (GI) tract bleeding, jaundice with pruritus, abdominal pain or alteration in senso-rium. But the patient had generalized weakness, anorexia with fatigue & lethargy, and had ascites. Lab reports were as follows: Hb - 7.5gm%, TLC - 8,100 cu.mm; Platelets were adequate, bilirubin- 1.4/0.3mg/dl, SGOT - 38U/L, SGPT -24U/L, SAP - 841U/L, Alb - 2.6g/dl and TP - 5.9U/mL. Ultrasound abdomen showed cirrhosis of liver with portal hyper-tension; upper gastrointestinal endoscopy indicated Grade II- Grade III esophageal varices.

The magnetic resonance cholangiopancreatography (MRCP) showed (Fig. 1 A & B) intrahepatic sectoral and segmental ducts which showed multifocal ste-nosis with minimum proximal dilation. A short seg-ment with high grade stenosis of proximal left main hepatic duct was seen with moderate dilation of left hepatic ductal system. CBD involved two short seg-ment high grade structures with smooth margins. Choledocholelithiasis was positive. No hepatic en-cephalopathy or hepato-renal syndrome was found. All the findings were consistent with sclerosing cho-langitis, and our final diagnosis was established as primary sclerosing cholangitis with biliary cirrhosis and long standing ulcerative colitis.

Discussion

Primary sclerosing cholangitis is a chronic cholesta-sis with progressive bile duct obliteration7 but the root cause remains largely unknown and it is more frequent in men. Primary sclerosing cholangitis has been considered to be a rare disease associated with inflammatory bowel disease, mainly ulcerative colitis and seems to be a risk factor for colon can-cer2.

Although the symptoms of UC usually develop be-fore those of PSC, in some subset of patients, PSC may precede colitis by 4-5 years. It has been found that clinical outcome of hepatobiliary disease is completely independent of the activity, severity or clinical course of colitis, and vice versa.

The first study to assess the prevalence of PSC in a large series of patients with UC was performed in South America2. Studies from Scandinavian coun-tries, England and North America have shown that 2 to 3.7% of patients with UC have, or will have, PSC8. The main risk factors include disease extent, duration, coexistent PSC, and a family history of colorec-tal cancer9. Although several therapeutic trials have been conducted, effective medical therapy has not been shown to alter the progressive course of PSC. A steady increase in the serum alkaline phospha-tase has been reported to be a better marker to identify patients with PSC10. There are at least two possible mechanisms underlying the improvement of PSC associated in this patient. One possibility is that PSC may have improved via a mechanism similar to that underlying the improvement of UC11. Recently, several studies have reviewed the role of PSC in the development of colorectal cancer in patients with UC1. The risk of colorectal cancer as well as the probability of developing this complication was sig-nificantly higher in patients with UC and PSC. Liver transplant for PSC patients increases the probability for developing colorectal cancer. It has been dem-onstrated that in UC patients, liver transplants may worsen the colitis activity. More than a few mechan-isms exist, to deal with patients with UC, PSC and liver transplants. Ursodeoxycholic acid has been definitively shown to reduce the risk of developing colorectal dysplasia and cancer in patients with UC and PSC12. Recently, primary biliary cirrhosis (PBC) has also been reported in patients with UC13 and it should be differentiated from the more common find-ing of PSC. In addition to the characteristic feature of PSC in our patient, there was also PBC which developed at a later stage.

Conclusion

In this case study, we report a patient with typical Primary sclerosing cholangitis associated with pro-longed Ulcerative colitis, which later developed Cho-ledocholithiasis and Biliary cirrhosis.

Acknowledgments: None

Conflict of interest: None

References

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