Hanne Prytz

Hepatic and extrahepatic malignancies in primary sclerosing cholangitis

BACKGROUND/AIMS To assess the risk of hepatic and extrahepatic malignancies in a large cohort of Swedish primary sclerosing cholangitis (PSC) patients compared with that of the general Swedish population. METHODS The study cohort comprised 604 PSC patients identified between 1970 and 1998. Follow-up was provided through linkages to the Swedish Cancer and Death registries. Cumulative incidence of malignancies and standard incidence ratio were calculated with the incidence rates in the Swedish population, taking into account: sex, age and calendar year as comparison group. RESULTS Median time of follow-up was 5.7 years (range 0-27.8). Seventy-nine percent had concomitant inflammatory bowel disease. The cause of death was cancer in 44%. The frequency of hepatobiliary malignancies was 13.3% (81/604). Thirty-seven percent (30/81) of all hepatobiliary malignancies were diagnosed less than 1 year after the diagnosis of PSC. The risk for hepatobiliary malignancy was increased 161 times, for colorectal carcinoma 10 times and for pancreatic carcinoma 14 times, compared with that of the general population. CONCLUSIONS In this national-based study including the largest cohort of PSC patients ever presented, the frequency of cholangiocarcinoma is 13%. The risk of hepatobiliary carcinoma is constant after the first year after PSC diagnosis with an incidence rate of 1.5% per year. The risk of pancreatic carcinoma is increased 14 times compared with the general Swedish population. These results are suggestive of an increased risk of pancreatic carcinoma in patients with PSC.

Increased risk of primary sclerosing cholangitis and ulcerative colitis in first-degree relatives of patients with primary sclerosing cholangitis

BACKGROUND & AIMS The importance of genetic factors for the development of primary sclerosing cholangitis (PSC) is incompletely understood. This study assessed the risk of PSC and inflammatory bowel disease (IBD) among first-degree relatives of patients with PSC, compared with the first-degree relatives of a cohort without PSC. METHODS Subjects from the national Swedish cohort of PSC patients (n = 678) were matched for date of birth, sex, and region to up to 10 subjects without a diagnosis of PSC (n = 6347). Linkage through general population registers identified first-degree relatives of subjects in both the PSC and comparison cohorts (n = 34,092). Diagnoses among first-degree relatives were identified by using the Inpatient Register. RESULTS The risk of cholangitis was statistically significantly increased in offspring, siblings, and parents of the PSC patient cohort, compared with relatives of the comparison cohort, with the hazard ratios and 95% confidence intervals, 11.5 (1.6-84.4), 11.1 (3.3-37.8), and 2.3 (0.9-6.1), respectively. The hazard ratios for ulcerative colitis (UC) among first-degree relatives of all PSC patients was 3.3 (2.3-4.9) and for Crohns disease 1.4 (0.8-2.5). The risk of UC for relatives of PSC patients without IBD was also increased, 7.4 (2.9-18.9). CONCLUSIONS First-degree relatives of patients with PSC run an increased risk of PSC, indicating the importance of genetic factors in the etiology of PSC. First-degree relatives of PSC patients without IBD are also at an increased risk of UC, which might indicate shared genetic susceptibility factors for PSC and UC.

Epidemiology and the initial presentation of autoimmune hepatitis in Sweden: A nationwide study

Objective. Autoimmune hepatitis (AIH) is a chronic liver disease, which if untreated can lead to cirrhosis and hepatic failure. The aim of the study was to investigate the incidence, prevalence, diagnostic tradition and clinical initial presentation of AIH. Material and methods. Analyses were performed in 473 patients identified as having probable or definite AIH. Results. The incidence of AIH was 0.85/100,000 (95% CI 0.69–1.01) inhabitants, which is somewhat lower than reported previously. The point prevalence amounted to 10.7/100,000 (95% CI 8.8–13.1), and 76% of the cases were females. The age-related incidence curve was bimodal but men were found to have only one incidence peak in the late teens, whereas women had a peak after menopause. AIH was presented as a spectrum of clinical settings from detected “en passant” to acute liver failure. Almost 30% of patients already had liver cirrhosis at diagnosis. Autoantibodies indicative of AIH type 1 were found in 79% of cases. Other concomitant autoimmune diseases were frequently found (49%). Conclusions. The incidence and prevalence figures confirm that AIH is a fairly uncommon disease in the Swedish population. Symptoms at presentation were unspecific, but almost half of the patients were jaundiced, with around 30% having liver cirrhosis. The majority of Swedish AIH patients had AIH type 1.

Colchicine treatment of primary sclerosing cholangitis

BACKGROUND/AIMS There is no medical treatment of documented benefit in primary sclerosing cholangitis (PSC). Colchicine has been observed to reduce mortality in primary biliary cirrhosis in one study. The aim of this study was to examine the effect of colchicine in PSC. METHODS Eighty-four patients with PSC were randomized to receive 1 mg of colchicine daily (n = 44) or placebo (n = 40) in a double-blind 3-year study. The effect of treatment was evaluated through blind scoring of 10 variables in prestudy and poststudy liver biopsy specimens, daily recording of symptoms, and biochemical tests (serum bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, albumin, immunoglobulins, ceruloplasmin, alpha 1-antitrypsin, and plasma prothrombin levels) at 6-month intervals. RESULTS There was no evidence of a favorable effect of colchicine on survival, symptoms, serum biochemistry, or liver histology in patients with PSC. CONCLUSIONS One milligram of colchicine daily is ineffective in PSC.

Natural history and outcome in 32 Swedish patients with small duct primary sclerosing cholangitis (PSC)

BACKGROUND/AIMS This study aims at describing the natural history and outcome of small duct primary sclerosing cholangitis (PSC). METHODS Thirty-two patients with small duct PSC were studied. The average time taken for diagnosis was 69 (1-168) months. The median follow-up time was 63 (1-194) months. RESULTS All patients including one who underwent liver transplantation because of end-stage liver disease and hepatocellular carcinoma were alive at follow-up. None developed cholangiocarcinoma. In 27 patients repeated cholangiographic examinations were done after a median time of 72 (12-192) months from first ERCP. Four developed features of large duct PSC. CONCLUSIONS Small duct PSC rarely progresses to large bile duct PSC and it seems to have a benign course in most patients and no development of cholangiocarcinoma was found.

Acute liver failure in Sweden: etiology and outcome.

Objective.  To determine the causes and outcome of all patients with acute liver failure (ALF) in Sweden 1994–2003 and study the diagnostic accuracy of Kings College Hospital (KCH) criteria and the model for end‐stage liver disease (MELD) score with transplant‐free deaths as a positive outcome.

Dynamic FDG-PET is useful for detection of cholangiocarcinoma in patients with PSC listed for liver transplantation.

Five to 15% of patients with primary sclerosing cholangitis (PSC) develop cholangiocarcinoma (CC) with a median survival of 5 to 7 months, an outcome not significantly improved by liver transplantation. However, if CC is found incidentally during the procedure or in the explanted liver, 5‐year survival rates of 35% are reported. A noninvasive method to detect CC small enough to allow for intended curative surgery is needed. Unfortunately, computed tomography (CT) and ultrasonography (US) have poor sensitivity for detection of CC in PSC; however, positron emission tomography (PET) using 2‐[18F]fluoro‐2‐deoxy‐D‐glucose (FDG) differentiates well between CC and nonmalignant tissue. We examined whether PET findings are valid using a blinded study design comparing pretransplantation FDG‐PET results with histology of explanted livers. Dynamic FDG‐PET was performed in 24 consecutive patients with PSC within 2 weeks after listing for liver transplantation and with no evidence of malignancy on CT, magnetic resonance imaging, or ultrasonography. The PET Center staff was blinded to clinical findings, and surgeons and pathologists were blinded to the PET results. Three patients had CC that was correctly identified by PET. PET was negative in 1 patient with high‐grade hilar duct dysplasia. In 20 patients without malignancies, PET was false positive in 1 patient with epitheloid granulomas in the liver. In conclusion, dynamic FDG‐PET appears superior to conventional imaging techniques for both detection and exclusion of CC in advanced PSC. FDG‐PET may be useful for screening for CC in the pretransplant evaluation of patients with PSC. (HEPATOLOGY 2006;44:1572–1580.)

High dose ursodeoxycholic acid in primary sclerosing cholangitis does not prevent colorectal neoplasia

Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) have a high risk of developing colorectal cancer and dysplasia. Ursodeoxycholic acid (UDCA) has been suggested to have chemopreventive effects on the development of colorectal cancer and dysplasia but long‐term data and larger trials are lacking.

Hepatic and extrahepatic malignancies in autoimmune hepatitis. A long-term follow-up in 473 Swedish patients

BACKGROUND/AIMS Autoimmune Hepatitis (AIH) is a liver disease which may lead to liver cirrhosis. Cirrhosis is a well-known risk factor for hepatocellular cancer. Lymphoma is a disease, where immune modulating drugs as well as the autoimmune disease itself may contribute to the elevated risk. The aim was to investigate the risks of malignancies in a large cohort of AIH patients. METHODS Four hundred and seventy-three patients with AIH were matched to the Swedish national cancer register as well as to the death cause register. RESULTS We found an overall higher risk of malignancies in the cohort of AIH patients from the date of diagnosis with a SIR of 1.51 (95% CI 1.10-2.03). SIR in the subpopulation of well defined catchment areas and complete case finding was 23.28 (95% CI 7.5-54.34) for HCC. Lymphomas were found a SIR of 13.09 (95% CI 4.22-30.56). CONCLUSIONS There was an overall increased risk of malignancies in a cohort of AIH patients, which manly was caused by hepatobiliary cancers. However, the true risk of HCC in an AIH cirrhotic cohort has yet to be investigated. A significantly higher risk of lymphomas was also found, but no clear cut association to the use of immune modulators.

Ursodeoxycholic acid treatment in patients with primary biliary cirrhosis. A Swedish multicentre, double-blind, randomized controlled study.

BACKGROUND Ursodeoxycholic acid (UDCA) has been shown to improve serum levels of liver enzymes and bilirubin in primary biliary cirrhosis (PBC). However, it is still uncertain whether UDCA treatment also improves symptoms, liver histology, and survival without liver transplantation. METHODS We randomized 116 patients with PBC to receive 0.5 g UDCA (n = 60) or placebo (n = 56) daily for 2 years. During the next 2 years, 80% of the UDCA-treated patients and 65% of the placebo-treated patients continued to take UDCA. RESULTS UDCA improved serum enzyme values but not survival, symptoms, serum bilirubin levels, or liver histology. There was no significant difference in response between initially symptomatic and asymptomatic patients. CONCLUSIONS UDCA in a dosage of 7.7 mg/kg body weight is of little benefit in PBC. This does not exclude the possibility that larger doses have beneficial effects.