H.R. van Buuren

Sclerosing pancreato-cholangitis responsive to steroid therapy

Four patients with weight loss, jaundice, a sonolucent swelling of the pancreas, and multiple bile-duct strictures are described. These cases of sclerosing pancreato-cholangitis responded to steroid therapy.

Budesonide or prednisone in combination with ursodeoxycholic acid in primary sclerosing cholangitis: a randomized double-blind pilot study

Budesonide or prednisone in combination with ursodeoxycholic acid in primary sclerosing cholangitis: a randomized double-blind pilot study

More Right-sided IBD-associated Colorectal Cancer in Patients with Primary Sclerosing Cholangitis

Background: Patients with inflammatory bowel disease (IBD) and concurrent primary sclerosing cholangitis (PSC) have a higher risk of developing colorectal cancer (CRC) than IBD patients without PSC. The aim of this study was to investigate potential clinical differences between patients with CRC in IBD and those with CRC in IBD and PSC, as this may lead to improved knowledge of underlying pathophysiological mechanisms of CRC development. Methods: The retrospective study from 1980–2006 involved 7 Dutch university medical centers. Clinical data were retrieved from cases identified using the national pathology database (PALGA). Results: In total, 27 IBD‐CRC patients with PSC (70% male) and 127 IBD‐CRC patients without PSC (59% male) were included. CRC‐related mortality was not different between groups (30% versus 19%, P = 0.32); however, survival for cases with PSC after diagnosing CRC was lower (5‐year survival: 40% versus 75% P = 0.001). Right‐sided tumors were more prevalent in the PSC group (67% versus 36%, P = 0.006); adjusted for age, sex, and extent of IBD, this difference remained significant (odds ratio: 4.8, 95% confidence interval [CI] 2.0–11.8). In addition, tumors in individuals with PSC were significantly more advanced. Conclusions: The right colon is the predilection site for development of colonic malignancies in patients with PSC and IBD. When such patients are diagnosed with cancer they tend to have more advanced tumors than patients with IBD without concurrent PSC, and the overall prognosis is worse. Furthermore, the higher frequency of right‐sided tumors in patients with PSC suggests a different pathogenesis between patients with PSC and IBD and those with IBD alone. (Inflamm Bowel Dis 2009)

ACYCLOVIR ENHANCES THE ANTIVIRAL EFFECT OF INTERFERON IN CHRONIC HEPATITIS B

Patients with chronic hepatitis B with active viral replication had a significantly greater fall in DNA polymerase and hepatitis-Be antigen when treated with interferon and acyclovir together than when treated with either interferon or acyclovir alone. Apart from fatigue and thrombophlebitis, tolerance of the combination therapy was excellent. The combination therapy appears the most promising for conversion of a state of active viral replication into virus latency.

Jaundice in non-cirrhotic primary biliary cirrhosis: the premature ductopenic variant

The clinical and pathological findings of four females with primary biliary cirrhosis (PBC) with an unusual and hitherto not well recognised course are reported. Patients suffered severe pruritus and weight loss with progressive icteric cholestasis which did not respond to such treatments as ursodeoxycholic acid and immunosuppressives. In all cases liver histology revealed marked bile duct loss without however significant fibrosis or cirrhosis. Further diagnostic studies and repeat biopsies confirmed the absence of liver cirrhosis as well as other potential causes of hyperbilirubinaemia. Comparison of the fibrosis-ductopenia relationship for our cases with that for a group of 101 non-cirrhotic PBC patients indicated that in the former the severity of bile duct loss relative to the amount of fibrosis was significantly higher. The proportion of portal triads containing an interlobular bile duct was 3%, 4%, 6%, and 10% compared with 45% (median; range 8.3–100%) for controls (p<0.001). Three patients received a liver transplant 6–7 years after the first manifestation of PBC because of progressive cholestasis, refractory pruritus, and weight loss, while the fourth patient is considering this option. In one case cirrhosis had developed at the time of transplantation while the others still had non-cirrhotic disease. These cases suggest that cholestatic jaundice in non-cirrhotic PBC may be secondary to extensive “premature” or accelerated intrahepatic bile duct loss. Although the extent of fibrosis may be limited initially, progression to cirrhosis appears to be inevitable in the long run. Despite intact protein synthesis and absence of cirrhotic complications, liver transplantation in the pre-cirrhotic stage for preventing malnutrition and to improve quality of life should be considered for these patients.

Rosuvastatin-associated hepatitis with autoimmune features

Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands. Correspondence and requests for reprints to L. M. M. Wolters, Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 40, room Ca 413, 3015 GD Rotterdam, The Netherlands. Tel: + 31 10 4633793; fax: + 31 10 4365916; e-mail: l.m.m.wolters@erasmusmc.nl

Review article: management of ascites and associated complications in patients with cirrhosis

Background  Ascites is the most common complication of cirrhosis, associated with an expected survival below 50% after 5 years. Prognosis is particularly poor for patients with refractory ascites and for those developing complications, including spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome (HRS).

Anticoagulant therapy in patients with non-cirrhotic portal vein thrombosis: Effect on new thrombotic events and gastrointestinal bleeding

It remains unclear when anticoagulant therapy should be given in patients with non‐cirrhotic portal vein thrombosis (PVT). The aim of this study was to assess the effect of anticoagulation on recurrent thrombotic events and gastrointestinal bleeding in non‐cirrhotic PVT patients.

HLA-DRB1*03:01 and HLA-DRB1*04:01 modify the presentation and outcome in autoimmune hepatitis type-1

The classical human leukocyte antigen (HLA)-DRB1*03:01 and HLA-DRB1*04:01 alleles are established autoimmune hepatitis (AIH) risk alleles. To study the immune-modifying effect of these alleles, we imputed the genotypes from genome-wide association data in 649 Dutch AIH type-1 patients. We therefore compared the international AIH group (IAIHG) diagnostic scores as well as the underlying clinical characteristics between patients positive and negative for these HLA alleles. Seventy-five percent of the AIH patients were HLA-DRB1*03:01/HLA-DRB1*04:01 positive. HLA-DRB1*03:01/HLA-DRB1*04:01-positive patients had a higher median IAIHG score than HLA-DRB1*03:01/HLA-DRB1*04:01-negative patients (P<0.001). We did not observe associations between HLA alleles and alanine transaminase levels (HLA-DRB1*03:01: P=0.2; HLA-DRB1*04:01; P=0.5); however, HLA-DRB1*03:01 was independently associated with higher immunoglobulin G levels (P=0.04). The HLA-DRB1*04:01 allele was independently associated with presentation at older age (P=0.03) and a female predominance (P=0.04). HLA-DRB1*03:01-positive patients received immunosuppressive medication and liver transplantation. In conclusion, the HLA-DRB1*03:01 and HLA-DRB1*04:01 alleles are both independently associated with the aggregate diagnostic IAIHG score in type-1 AIH patients, but are not essential for AIH development. HLA-DRB1*03:01 is the strongest genetic modifier of disease severity in AIH.

PROPRANOLOL INCREASES ARTERIAL AMMONIA IN LIVER CIRRHOSIS

Propranolol (20 mg 4 times a day) was given to patients with liver cirrhosis or fatty infiltration of the liver. In six patients with cirrhosis and a stable arterial plasma ammonia concentration before treatment, blood ammonia was increased significantly on day 3 of propranolol treatment. Arterial plasma ammonia concentration was still high on day 6 of propranolol. Individual percentage change in arterial ammonia ranged from 8% to 66%. After propranolol had been discontinued ammonia concentration returned to pretreatment concentrations in 3 to 6 days. In 3 patients with fatty livers and normal pretreatment ammonia concentrations no change was detected in arterial plasma ammonia while they were on propranolol.