Screening for primary sclerosing cholangitis (PSC)-associated malignancies will likely approve patient outcomes, according to John E. Eaton, MD, gastroenterologist and internist at the Mayo Clinic, Rochester.
Dr. Eaton discussed PSC as part of Sunday morning’s Hepatology Associates Course. PSC is an inflammation and structuring of the intrahepatic and/or extrahepatic bile ducts that occurs in six to 13 people per 100,000 in the United States. It can lead to liver failure and increases the risk of colorectal cancer (CRC) associated with irritable bowel disease (IBD), cholangiocarcinoma (CCA), gallbladder cancer (GBC) and hepatocellular carcinoma (HCC).
“CCA is one of the most dreaded complications of this disease, especially in terms of mortality, with about a third of all deaths” Dr. Eaton said, adding that PCS increases the CCA risk 400-fold compared with the general population.
Neither AASLD nor EASL recommends for or against CCA screening for PSC patients. One recent retrospective single-center study suggests that five-year survival increased by 48 percent using screening with abdominal imaging and lab tests versus no screening, but Dr. Eaton pointed out that high-quality data supporting or refuting screening is lacking, and many studies involving PSC screening have been underpowered.
Screening methods include CA 19-9 testing, MRI/MRCP and ultrasound.
“Many experts will routinely screen for PSC-related complications,” Dr. Eaton said. “This is my practice, and the practice of many of my colleagues.”
CRC is the second-leading cause of malignancy-associated deaths in PSC patients, and IBD in PSC can be clinically and endoscopically quiescent. PSC patients have between a 70 and 80% incidence of IBD. Dr. Eaton recommended full colonoscopies plus biopsies at the time of PSC diagnosis for patients without IBD and full colonoscopies and biopsies every one to two years for those patients with IBD.
AASLD and EASL do recommend annual ultrasound screening for GBC. The rationale, Dr. Eaton said, was because GBC and polyps are common and early detection and surgical resection offer the only chance for a cure.
As for PSC treatment itself, effective medical treatment remains lacking. No official guidelines for or against using ursodeoxycholic acid (UDCA) exist from either AASLD or EASL, but adverse outcomes have been found in those taking >28 mg/kg/day.
If attempting UDCA treatment, discuss with the patient the therapeutic and symptomatic benefits and risks and begin with doses between 17-23 mg/kg/day and monitor closely for patient tolerance, ALK normalization or greater than 40 percent reduction from baseline along with symptomatic improvement at six months. At any point these criteria are not met, or there is greater than 40 percent reduction but still 1.5 times ULN and/or just partial symptomatic improvement, stop UDCA treatment and consider additional, novel experimental therapies by enrolling patients in clinical trials, Dr. Eaton said.
Several clinical trials open to PSC patients are available, including phase II trials involving the agents vancomycin, all-trans retinoic acid, HTD1801, DUR-928 and BTT1023. Obeticholic acid, nor-UDCA and simtuzumab are also being investigated for efficacy in PSC.