We describe a case of a 23-year-old woman with a history of Crohn's disease (CD), who initially presented with sepsis-like symptoms, subsequently developed severe cholestasis and following extensive inpatient workup was found to have non-caseating granulomas on her liver biopsy. Infectious aetiologies were excluded and the patient was treated with oral corticosteroids, which ameliorated but did not completely reverse the cholestasis. We review the differential diagnosis of hepatic granulomas and discuss the potential difficulties in establishing their exact aetiology in patients with CD.

Inflammatory bowel diseases are associated with various hepatobiliary disorders, reported both in Crohn's disease and ulcerative colitis. They may occur at any moment in the natural course of the disease. The prevalence of liver dysfunction rises from 3% to 50% accordingly to definitions used in different studies. Fatty liver is considered as the most common hepatobiliary complication in inflammatory bowel diseases while primary sclerosing cholangitis is the most specific one. Less frequently, inflammatory bowel diseases-associated hepatobiliary disorders include: autoimmune hepatitis/ primary sclerosing cholangitis overlap syndrome, IgG4-associated cholangiopathy, primary biliary cholangitis, hepatic amyloidosis, granulomatous hepatitis, cholelithiasis, portal vein thrombosis and liver abscess. The spectrum of these manifestations varies according to the type of inflammatory bowel diseases. Treatments of inflammatory bowel diseases may cause liver toxicity, although incidence of serious complications remains low. However, early diagnosis of drug-induced liver injury is of major importance as it affects future clinical management. When facing abnormal liver tests, clinicians should undertake a full diagnostic work-up in order to determine whether the hepatic abnormalities are related to the inflammatory bowel diseases or not. Management of hepatic manifestations in inflammatory bowel diseases usually involves both hepatologists and gastroenterologists because of the complexity of some situations.

The present study investigated the antioxidant and anti-inflammatory effects of dietary protocatechuic acid (PCA), a simple hydrophilic phenolic compound commonly found in many edible vegetables, on dextran sulphate sodium (DSS)-induced ulcerative colitis and its associated hepatotoxicity in rats. PCA was administered orally at 10 mg kg(-1) to dextran sulphate sodium exposed rats for five days. The result revealed that administration of PCA significantly (p < 0.05) prevented the incidence of diarrhea and bleeding, the decrease in the body weight gain, shortening of colon length and the increase in colon mass index in DSS-treated rats. Furthermore, PCA prevented the increase in the plasma levels of pro-inflammatory cytokines, markers of liver toxicity and markedly suppressed the DSS-mediated elevation in colonic nitric oxide concentration and myeloperoxidase activity in the treated rats. Administration of PCA significantly protected against colonic and hepatic oxidative damage by increasing the antioxidant status and concomitantly decreased hydrogen peroxide and lipid peroxidation levels in the DSS-treated rats. Moreover, histological examinations confirmed PCA chemoprotection against colon and liver damage. Immunohistochemical analysis showed that PCA significantly inhibited cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein expression in the colon of DSS-treated rats. In conclusion, the effective chemoprotective role of PCA in colitis and the associated hepatotoxicity is related to its intrinsic anti-inflammatory and anti-oxidative properties.

Hepatic involvement is often encountered in gastrointestinal (GI) diseases, in part because of the close anatomic and physiologic relations between the liver and GI tract. Drainage of the mesenteric blood supply to the portal vein permits absorbed and/or translocated nutrients, toxins, bacterial elements, cytokines, and immunocytes to gain hepatic access. Liver problems in digestive disorders may range from nonspecific hepatocellular enzyme elevations to significant pathologic processes that may progress to end-stage liver disease. Hepatobiliary manifestations of primary GI diseases in childhood and adolescence are not uncommon and include several well-described associations, such as sclerosing cholangitis with inflammatory bowel disease. Liver damage may also result from the effects of drugs used to treat GI diseases, for example, the hepatotoxicity of immunomodulatory therapies. This review highlights the important features of the hepatic and biliary abnormalities associated with 3 common pediatric GI conditions: inflammatory bowel disease, celiac disease, and cystic fibrosis.

CYP3A and P-glycoprotein (P-gp) play important roles in drug metabolism and excretion; however, their functions in pathological conditions remain unclear. Hepatobiliary abnormalities have been described in patients with ulcerative colitis, which may affect drug metabolism and excretion in the liver and small intestine. We examined the functions of CYP3A and P-gp in the liver and small intestine of mice with dextran sodium sulfate (DSS)-induced colitis. Up to day 7, inflammatory markers were significantly increased in the livers of DSS-treated mice, accompanied by decreased CYP3A. Additionally hepatobiliary transporters and Pregnane X receptor, which regulates the transcriptional activation of CYP3A, were reduced. Both CYP3A and P-gp were significantly decreased in the upper small intestine of DSS-treated mice on day 7. This was associated with the increased expression of inducible nitric oxide synthase, but not changes in nuclear receptor expression. On day 7 of DSS treatment, the concentrations of cyclosporine A (CsA), a substrate of both CYP3A and P-gp, were significantly higher than controls. These results indicated the existence of a second inflammatory response in the liver and upper small intestine of mice with DSS-induced colitis, and bioavailability of CsA was increased by the dysfunction of CYP3A and P-gp in these organs.

There exists a close relationship between ulcerative colitis and various hepatic disorders. The present study was aimed to evaluate the hepatocellular damage in experimental colitis model. Ulcerative colitis was induced in Swiss mice by cyclic treatment with 3% w/v dextran sulfate sodium in drinking water. The severity of colitis was assessed on the basis of disease activity index and colon histology. The effect of ulcerative colitis on the liver was assessed using various biochemical parameters, histological evaluation, sirius red staining, immunohistochemical staining with peroxisome proliferator-activated receptor γ, 8-oxo-7,8-dihydro-2'-deoxyguanosine and placental glutathione S-transferase, comet assay (alkaline and modified), Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling assay and western blot analysis to detect the protein expression of nuclear factor kappa B, cyclooxygenase-2, nuclear erythroid 2-related factor 2 and NADPH: quinone oxidoreductase-1. Dextran sulfate sodium induced severe colitis in mice as evident from an elevated disease activity index and histological abnormalities. Ulcerative colitis increased the permeability of colon as apparent from a significant reduction in the expression of tight junction protein, occludin. Further, the bacterial translocation assay as well as the analysis of lipopolysaccharide level revealed the existence of various bacterial species in the liver of ulcerative colitis-induced mice. There was a significant increase in the plasma alanine and aspartate transaminases and liver triglyceride levels, expression of peroxisome proliferator-activated receptor γ, inflammatory markers, oxidative stress, fibrosis, oxidative DNA damage and apoptosis in the liver of mice. Moreover, there was an increase in the expression of nuclear factor kappa B and cyclooxygenase-2 and a reduction in the expression of nuclear erythroid 2-related factor 2 and NADPH: quinone oxidoreductase-1 in the liver of severe ulcerative colitis-induced mice. The results of the present study provide evidence that ulcerative colitis is accompanied with hepatic damage in mice.

Ulcerative colitis is an idiopathic, chronic and relapsing inflammatory bowel disease, which elicits the risk of colorectal cancer, the third most common malignancy in humans. It has been known for a long time that oxidative stress is a major pathogenic factor in the inflamed tissue that can pave the way towards DNA damage and carcinogenesis. However, the DNA damage produced due to oxidative stress in the inflamed tissue is not limited to the local site but extends globally, thereby augmenting the risk of global carcinogenesis. Targeting oxidative stress may provide an exciting avenue to combat inflammation-associated local as well as global DNA damage and the subsequent carcinogenesis. The present review portrays the role of oxidative stress in the pathogenesis of ulcerative colitis and the associated local as well as global DNA damage, which may lead to carcinogenesis.

The aim of the study was to estimate the frequency of primary sclerosing cholangitis (PSC)-type lesions in children with inflammatory bowel disease (IBD) by means of magnetic resonance cholangiopancreatography (MRCP), and to investigate the association between a series of easily applicable data on the one hand and the presentation of such lesions at MRCP on the other hand.

Collected demographic, laboratory, and magnetic resonance enterography data from the records of 73 children with IBD were cross-sectionally related to the MRCP-based diagnosis.

Around the time of MRCP, the distribution of IBD subtypes was 64.4%, 24.7%, and 11% for Crohn disease, indeterminate colitis, and ulcerative colitis, respectively. A total of 11 patients (15.1%) were identified with PSC-type lesions. Demographic and magnetic resonance enterography data were unrelated to the MRCP outcome. Biochemical abnormalities were of low prevalence (<50%) among patients with PSC. The abnormality prevalences of aspartate transaminase, alanine transaminase, and γ-glutamyl transferase were significantly higher in the PSC group, both at initial diagnosis of IBD and at the time of MRCP. Less-consistent results were documented for bilirubin and alkaline phosphatase, especially at initial diagnosis of IBD.

The abnormality prevalences of aspartate transaminase, alanine transaminase, and γ-glutamyl transferase were significantly higher in the PSC group. Nevertheless, PSC-type lesions frequently occur in pediatric IBD, even if the biochemical profile is hardly indicative of this probability.

There is a close relationship between inflammatory bowel disease (IBD) and various hepatobiliary disorders. The objective of this study was to determine whether hepatic leukocyte recruitment occurs in experimental colitis. We used the murine model of colitis induced by 2,4-dinitrobenezenesulfonic acid (DNBS). Male C57Bl/6 mice received an intrarectal injection of 4 mg DNBS in 100 microl 50% ethanol. Controls received 100 microl 50% ethanol. The hepatic microcirculation was examined at 3 and 14 days post-DNBS by intravital video microscopy. Three days post-DNBS, when mice had developed acute colitis, there was associated hepatic leukocyte recruitment. Within the postsinusoidal venules there was a fourfold increase in the flux of rolling leukocytes that was P-selectin dependent but not alpha(4)-integrin dependent. There was also an increase in stationary leukocytes within the sinusoids, although this was not associated with an increase in serum alanine transaminase. By 14 days post-DNBS when macroscopic evidence of colonic inflammation was resolved, rolling within the postsinusoidal venules had returned to control levels. In this murine model of colitis, we describe a link between acute colonic inflammation and remote hepatic leukocyte recruitment that is P-selectin dependent. Active IBD may lead to remote hepatic inflammation.