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Hugh James Freeman, Department of Medicine (Gastroenterology), University of British Columbia, Vancouver, British Columbia, Canada Correspondence to: Dr. Hugh J Freeman, MD, FRCPC, FACP, Professor, UBC Hospital, 2211 Wesbrook Mall, Vancouver, BC, V6T 1W5, Canada. hugfree@shaw.ca Telephone: +1-604-8227216 Fax: +1-604-8227236 Received: 2005-06-05 Accepted: 2005-07-20
Abstract A variety of hepatic and biliary tract disorders may complicate the clinical course of celiac disease. Some of these have been hypothesized to share common genetic factors or have a common immunopathogenesis, such as primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune forms of hepatitis or cholangitis. Other hepatic changes in celiac disease may be associated with malnutrition resulting from impaired nutrient absorption, including hepatic steatosis. In addition, celiac disease may be associated with rare hepatic complications, such as hepatic T-cell lymphoma. Finally, pancreatic exocrine function may be impaired in celiac disease and represent a cause of treatment failure.
� 2006 The WJG Press. All rights reserved.
Key words: Celiac disease; Liver disease; Cholangitis; Autoimmune hepatitis; Hepatic vein obstruction; Primary biliary cirrhosis
Freeman HJ. Hepatobiliary and pancreatic disorders in celiac disease. World J Gastroenterol 2006; 12(10): 1503-1508
http://www.wjgnet.com/1007-9327/12/1503.asp
INTRODUCTION A number of hepatobiliary and pancreatic disorders occur in celiac disease, a genetically-based small intestinal disorder that resolves with the complete restriction of dietary gluten[1]. Almost 3 decades ago, liver changes in celiac disease were first recognized by Hagander et al[2]. Later, Dickey et al[3] have confirmed these findings in a prospective evaluation of celiac disease patients and extended observations to results of gluten-free diet therapy. In some, these liver test changes are entirely reversible following administration of a gluten-free diet, while in others, clinically significant liver disease is not amenable to diet treatment alone[3]. Now, almost a decade after this report, recognition of celiac disease has been substantively improved, in part, a result of more modern serological assays for screening[4], the detection of tissue transglutaminase (tTG) as an autoantigen in celiac disease[5] and the increasingly widespread serological use of tTG ELISA to screen for celiac disease[6]. As a result of improved recognition of celiac disease, even more precise estimates of the overall disease burden related to hepatobiliary tract and pancreatic disorders will emerge. In patients with unexplained elevations of liver enzymes, several studies using serological screening methods have estimated that almost 10% will prove to have celiac disease[7,8]. For example, Volta et al[7] examined endomysial and gliadin antibodies in 55 patients with elevations of liver chemistry tests in the absence of a known cause. Five patients had positive serological studies and small intestinal biopsies showed changes of celiac disease that responded to a gluten-free diet. Liver biopsies done in some patients showed a nonspecific inflammatory process and liver chemistry tests normalized with a gluten-free diet. Bardella et al[8] screened 140 patients with chronically elevated transaminase values for gliadin and endomysial antibodies; of these, 13 were sero-positive. After 1 year on a gluten-free diet, 12 patients had normalization of liver enzyme tests. In patients with known celiac disease, abnormal liver enzyme tests also occur[2,9-11]. Hagander et al[2] described elevated liver enzymes in 30 of 75 (40%) patients, while Bonamico et al[9] showed increased levels in 39 of 65 (60%) children, and Jacobsen et al[10] documented almost 50% with increased liver enzymes. In some, liver biopsy showed a nonspecific inflammatory process, although a more specific �chronic active hepatitis� was detected in 5 of 37 (13.5%) patients. Bardella et al[11] evaluated 158 consecutive adults with celiac disease and showed that 42% had abnormal liver enzyme levels. A gluten-free diet for 1 to 10 years resulted in complete normalization of liver chemistry tests in 95% patients. In celiac disease, persistently abnormal liver chemistry tests may reflect the presence of a clinically occult hepatobiliary tract disorder with a possibly common immunopathogenesis. Specific examples of immune-mediated disorders include primary biliary cirrhosis, primary (lymphocytic, autoimmune) sclerosing cholangitis or autoimmune hepatitis. Alternatively, in some, a common genetically-based disorder, including altered control of small intestinal iron absorption resulting in a concomitant iron overload disorder, may be present, such as hemochromatosis. In addition, chronic changes in liver chemistry tests may reflect a direct effect of the celiac disease. For example, impaired absorption and resultant malnutrition may lead to deposition of fat in the liver, related, in part, to reduced fat mobilization from hepatocytes. Indeed, massive hepatic steatosis has occasionally been reported in celiac disease. Finally, but very rarely, patients may develop a specific complication of celiac disease that involves the liver, such as a T-cell form of lymphoma.
HEPATOBILIARY TRACT DISEASES Primary biliary cirrhosis In 1978, Logan et al[12] described the first cases of primary biliary cirrhosis with celiac disease. Later, numerous additional cases have been reported[13-16]. In both disorders, other conditions having an immunological basis have been described, including diabetes and thyroiditis[16-19]. In addition, co-existence of primary biliary cirrhosis and celiac disease has not only been reported in Europe and the Americas, but also in migrants from South Asia[20] and the Coast Salish, an aboriginal population inhabiting the west coast of Canada thought to be of Asian descent[16]. To date, however, a definitive genetic predisposition or specific immunological alteration has not been clearly identified. Loss of weight, malabsorption, osteopenic bone disease, steatorrhea and elevated alkaline phosphatase activities are common features of both diseases, so that early in their coexistence, celiac disease or primary biliary cirrhosis may not be easily appreciated. In patients reported with both disorders, regardless of geographical origin or race, restriction of dietary gluten may have improved the diarrhea, but abnormal liver chemistry tests were usually not significantly altered with a gluten-free diet. Some more recent studies have explored serological testing in primary biliary cirrhosis or celiac disease. Kingham and Parker[21] used a patient registry in the United Kingdom and defined the prevalence of primary biliary cirrhosis in 143 celiac patients as 3%, while the prevalence of celiac disease in 67 primary biliary cirrhosis patients was 6%. As a result, screening with antimitochrondrial antibodies in celiac disease was recommended, while in primary biliary cirrhosis, serological screening with gliadin antibodies or small intestinal biopsy was suggested. Dickey et al[22] found similar findings of 7% (4/57) primary biliary cirrhosis patients based on initial evaluation using endomysial antibodies (11% positive), followed by later duodenal biopsy confirmation. Despite 12 to 24 mo on gluten-free diets, however, improvement in liver chemistry tests was not detected even though endomysial antibodies disappeared. Using Danish and Swedish registry data based on over 8 000 patients with celiac disease, Sorensen et al[23] also suggested an increased risk of primary biliary cirrhosis. Using stored sera from 378 Canadian patients with primary biliary cirrhosis, Gillett et al[24] found that screening for IgA antibodies to endomysium and primary biliary cirrhosis were both positive in 10 (2.6%) patients and 5 patients had small intestinal biopsies confirming celiac disease. Intertestingly, however, another 44 primary biliary cirrhosis patients had raised IgA tissue transglutaminase antibodies but were negative for IgA endomysium antibody. In 255 patients with autoimmune cholestatic liver disorders, including 173 with primary biliary cirrhosis, Volta et al[25] found 9 with celiac disease (including 7 in those with primary biliary cirrhosis, 4%). In some recent studies, however, the importance of biopsy confirmation in patients with primary biliary cirrhosis has been demonstrated in sero-positive patients as false-positive IgA or IgG tTG antibodies may occur in primary biliary cirrhosis[26,27]. In a recent study using a general practice longitudinal database from the United Kingdom[28], an overall 3-fold risk of primary biliary cirrhosis was demonstrated in 4 732 patients diagnosed with celiac disease as compared with 23 620 age- and sex-matched controls.
Primary sclerosing cholangitis Primary sclerosing cholangitis was first found to be associated with celiac disease in 1988 in 3 patients with diarrhea and steatorrhea[29]. Two also had concomitant �ulcerative colitis� (one with �inactive� quiescent disease and one with �mild� or �minimal change� colonic disease), a disorder known to be associated with primary sclerosing cholangitis. Although hepatobiliary tract changes were defined by cholangiography and liver biopsy, these did not respond to a gluten-free diet. Later, other cases were reported[10,25,30]. In one, the predominant lymphocytic nature of the portal inflammatory process was emphasized with increased intra-epithelial lymphocytes in biliary ductal epithelium[30], an observation also noted in gastric and colonic epithelium of celiac patients[31,33]. To date, despite some case report data[33], it has been difficult to show good evidence for a response of the hepatobiliary tract disease to a gluten-free diet. This may, in part, reflect sampling difficulties associated with liver biopsy as well as the response or lack of response of relatively non-specific liver chemistry test markers of cholestasis (e.g., serum alkaline phosphatase). Indeed, the origin of alkaline phosphatase activities measured in serum include the hepatobiliary tract and other tissues that may be substantially altered in celiac disease (i.e., bone and the intestine); conceivably all might be improved with a gluten-free diet.
Autoimmune hepatitis and cholangitis This has been evaluated in only a limited numbers of case reports and survey studies. Unfortunately, many appeared before hepatitis C testing[13,35]. Jacobsen et al[10] performed liver biopsies in 37 of 171 celiac patients and found changes of �chronic active hepatitis� in 5 (2.3%) patients. Using antibodies to endomysium and gliadin, Volta et al[36] surveyed 157 patients with type 1 autoimmune hepatitis and 24 with type 2 autoimmune hepatitis for celiac disease. They found that 8 of these 181 (4%) patients were positive for endomysial antibodies, including 6 (4%) with type 1 disease and 2 (8%) with type 2 disease. Five of the 8 patients had a duodenal biopsy, most being asymptomatic, and all showed changes of subtotal villous atrophy, consistent with untreated celiac disease. The effects of steroid with or without azothioprine treatment on the underlying small intestinal histological changes were considered and also may have masked intestinal symptoms. Unfortunately, in this study, the effects of gluten-free diet administration on the hepatic and intestinal changes were not reported. Recently, Villalta et al[37] evaluated 47 consecutive patients with autoimmune hepatitis, including 39 with type 1 disease and 8 with type 2 disease. Anti-IgA tissue transglutaminase and endomysial antibodies were positive in 3 (6.4%) patients and small intestinal biopsies confirmed the presence of the celiac disease histological changes[37]. Finally, celiac disease and other types of autoimmune liver and biliary tract disease may coexist. A case report of autoimmune cholangitis[38], a cholestatic liver disorder with biochemical evidence of cholestasis, histological evidence of inflammatory bile duct damage and an absence of anti-mitochondrial antibodies, was has been described in a patient with celiac disease. Interestingly, this patient�s small intestinal biopsies were reported to be normal without a gluten-free diet while being treated with steroids and azathioprine. In an another case, Sedlack et al[39] reported an improvement in hepatic biochemistries without use of immunosuppressive agents.
HEMOCHROMATOSIS OR IRON OVERLOAD LIVER DISEASE
Celiac
disease has been associated with hemochromatosis, which is not
surprising, since both are relatively common disorders based on a common
Celtic ancestry, so any association could be coincidental[40-42].
Iron absorption largely occurs in the proximal duodenum, the site most
often histologically altered in celiac disease. Indeed, �isolated� iron
deficiency with anemia may be the initial clinical manifestation of
clinically occult celiac disease. In contrast, in iron overload liver
disease, inappropriate iron absorption from the proximal small intestine
occurs as body iron stores are markedly increased. In one of these early
case reports, treatment of celiac disease and improvement in the
pathological small intestinal changes led to worsening liver chemisty
test values and recognition of occult iron overload liver disease
(C282Y-negative), presumably related to improved intestinal uptake of
dietary iron[41]. Another similar case of C282Y-positive
hemochromatosis presented with diarrhea, positive anti-gliadin and
endomysial antibodies. Subsequent small bowel biopsies showed villous
atrophy[42]. Interestingly, in this latter case, phlebotomy
therapy had to be terminated early because of an unexpectedly rapid fall
in the serum ferritin measurement. A genetically-based linkage was also
suggested since both diseases are associated with the HLA-region on
chromosome 6. Later investigations have sought to resolve this possible
relationship. Butterworth
OTHER LIVER DISORDERS IN CELIAC DISEASE Hepatic steatosis Common causes of hepatic steatosis include alcohol-induced steatosis, diabetes mellitus, NASH syndromes and some forms of drug therapy, including corticosteroids. In some countries, dietary protein deficiency and kwashiorkor are important causes. Intestinal malabsorption is often associated with hepatic steatosis in patients with a prior jejunoileal bypass procedure for morbid obesity[47,48] and, sometimes, in those with inflammatory bowel disease, particularly after extensive intestinal resections[49]. Because celiac disease is now frequently recognized in a clinically occult form before manifestations of marked nutrient depletion are detected, hepatic steatosis is probably less common than in other intestinal diseases. Several cases of fatty infiltration of the liver, often massive, have been described in adults with celiac disease[50-53]. Presumably, lesser degrees of hepatic fat deposition may occur. Most often if massive steatosis is evident, elevated transaminase and alkaline phosphatase activities have been documented along with alterations in coagulation. However, in most, clinical and biochemical changes attributed to the hepatic steatosis were improved with a gluten-free diet. In a patient with massive hepatic steatosis[52], a gluten-free diet for about 1 year also resulted in histological improvement in the fatty changes detected in the liver. The mechanisms involved in fat deposition in the liver are not defined. Interestingly, after jejunoileal bypass, reduced serum levels of some essential and nonessential amino acids may be observed[47,48]. In addition, changes in serum amino acids have been recorded in patients with starvation-associated kwashiorkor[54,55]. Based on these nutritional disorders, it has been suggested that malabsorption in celiac disease might lead to chronic deficiency of a lipotropic factor (e.g., choline), with an associated pyridoxine deficiency, hepatic steatosis might occur[52]. Further studies are needed to define the precise pathogenetic mechanism or mechanisms for fatty liver in celiac disease.
Gallstone disease Several studies have focused on gallbladder function in celiac patients. In some studies, slow emptying of the gallbladder has been documented[56,57], along with impaired contraction response to fat[56]. Studies of enteric endocrine cells showed significant quantitative changes in celiac patients, including complete absence of mucosal secretin cells[59]. In addition, studies with test meals have suggested impaired secretion of cholecystokinin in patients with celiac disease[59] or, possibly, impaired gallbladder responsiveness to cholecystokinin[56]. In spite of these physiological alterations, there does not appear to be a significant predisposition to gallstones in celiac disease. Only 9 of 350 patients had a cholecystectomy for gallstone disease[60]. However, in a survey of elderly celiacs initially diagnosed after the age of 60 years, 6 of 30 (20%) had gallstone disease[61].
Hepatic vein obstruction Although mesenteric vascular ischemia[62] and vasculitis[63-66] have been described in celiac disease, there are also reports of a unusual Budd-Chiari-like syndrome among celiac children from North Africa, particularly Tunisian and Algeria[67,68]. Hepatic vein obstruction has also been documented in 3 adults[69]. Deficiencies in protein C and antithrombin III are detected, and malabsorption of vitamin K in celiac disease has been proposed to cause transient protein C or protein S deficiencies. Further studies are needed to identify possible factors, either dietary or environmental agents, that may be important. More recently, a celiac patient with a Budd-Chiari syndrome associated with membranous obstruction of the inferior vena cava treated successfully with percutaneous balloon angioplasty has been reported[70].
Hepatic malignancies While hepatocellular cancer has been reported in 1 patient, cirrhosis was also present[71]. Occasionally, the liver may be involved with lymphoma, the most frequently detected malignant disorder in celiac disease patients[72]. In some patients with celiac disease, lymphomatous deposits have been detected in the liver, presumably as metastatic lesions[71]. For example, lymphoma in the liver is apparently secondary to jejunal lymphoma, complicating celiac disease[71]. In general, involvement of the liver in celiac disease patients with lymphoma is limited and overshadowed by the clinical course of the intestinal disease. However, a fulminant cholestatic syndrome has been described in a celiac disease patient, resulting in hepatic failure[73]. Later investigations have shown widespread hepatic involvement with an unusual lymphoid neoplasm classified as a hepatosplenic lymphoma, a rare type of peripheral T-cell lymphoma with rearrangement of the gamma-delta T-cell receptor[74,75].
Liver failure In patients with severe liver failure from a variety of causes in celiac disease, dietary treatment reverses hepatic dysfunction, even in patients with consideration for possible liver transplantation[76].
PANCREATIC DISEASE While celiac disease is associated with insulin-dependent diabetes[77], pancreatic exocrine insufficiency and celiac disease have only occasionally been recorded[78-84]. Pancreatic calcification is most often associated with chronic or persisting pancreatic inflammation which is usually due to excessive consumption of alcoholic beverages. Atophy, fibrosis and altered pancreatic function have been observed in experimental animals treated with diets deficient in protein, in adults with protein-energy malnutrition, in children with kwashiorkor and in some early autopsy studies of patients with celiac disease. In addition, pancreatic calcification has been reported with chronic protein malnutrition in the Indian subcontinent and in some African countries. Finally, a patient with celiac disease and pancreatitis with calcification has been described[83]. Although the frequency of pancreatic disease in celiac patients is not known, impaired pancreatic function occurs and may be a cause of persistently impaired nutrient assimilation and malnutrition. It has been estimated that over 20% of children with celiac disease have defective exocrine pancreatic function[85]. This may be related to several factors. Impaired secretion and/or release of pancreatic stimulating hormones from the diseased proximal small intestine may be important[60]. Immunohistochemical studies have demonstrated alterations in enteric endocrine cells, and in biopsies from patients with untreated celiac disease, an absence of secretin cells has been reported[59]. Studies with test meals in celiac patients have suggested impaired secretion of cholecystokinin-pancreozymin resulting in reduced pancreatic exocrine cell stimulation[81]. In addition, a deficiency of amino acids may result from impaired small intestinal amino acid uptake, leading to a reduction in precursors for pancreatic enzyme synthesis[55,80]. Also, protein malnutrition may lead to structural changes in the pancreas, including atrophy of acinar cells and pancreatic fibrosis[55], resulting in impaired pancreatic exocrine function. In a more recent study[86], pancreatic enzyme measurements were reduced with mucosal atrophy and could be inversely correlated with the degree of intestinal damage.
REFERENCES 1 Freeman HJ. Adult celiac disease and the severe �flat� small bowel biopsy lesion. Dig Dis Sci 2004; 49: 535-545 PubMed 2 Hagander B, Berg NO, Brandt L, Norden A, Sjolund K, Stenstam M. Hepatic injury in adult coeliac disease. Lancet 1977; 2: 270-272 PubMed 3 Dickey W, McMillan SA, Collins JS, Watson RG, McLoughlin JC, Love AH. Liver abnormalities associated with celiac sprue. How common are they, what is their significance, and what do we do about them? J Clin Gastroenterol 1995; 20: 290-292 PubMed 4 Gillett HR, Freeman HJ. Serological testing in screening for adult celiac disease. Can J Gastroenterol 1999; 13: 265-269 PubMed 5 Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken EO, Schuppan D. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med 1997; 3: 797-801 PubMed 6 Freeman HJ. Inflammatory bowel disease with cytoplasmic-staining antineutrophil cytoplasmic antibody and extensive colitis. Can J Gastroenterol 1998; 12: 279-282 PubMed 7 Ishiyama Y. The present and future of neurophysiological examination. Rinsho Byori 1998; 46: 879-886 PubMed 8 Bardella MT, Vecchi M, Conte D, Del Ninno E, Fraquelli M, Pacchetti S, Minola E, Landoni M, Cesana BM, De Franchis R. Chronic unexplained hypertransaminasemia may be caused by occult celiac disease. Hepatology 1999; 29: 654-657 PubMed 9 Signoretti A, Roggini M, Bonamico M, Nigro G, Lionetti P, Falconieri P. Interstitial pneumonitis during Kawasaki disease associated with herpes simplex infection. Minerva Pediatr 1986; 38: 589-593 PubMed 10 Jacobsen MB, Fausa O, Elgjo K, Schrumpf E. Hepatic lesions in adult coeliac disease. Scand J Gastroenterol 1990; 25: 656-662 PubMed 11 Bardella MT, Fraquelli M, Quatrini M, Molteni N, Bianchi P, Conte D. Prevalence of hypertransaminasemia in adult celiac patients and effect of gluten-free diet. Hepatology 1995; 22: 833-836 PubMed 12 Logan RF, Ferguson A, Finlayson ND, Weir DG. Primary biliary cirrhosis and coeliac disease: an association? Lancet 1978; 1: 230-233 PubMed 13 Behr W, Barnert J. Adult celiac disease and primary biliary cirrhosis. Am J Gastroenterol 1986; 81: 796-799 PubMed 14 Olsson R, Kagevi I, Rydberg L. On the concurrence of primary biliary cirrhosis and intestinal villous atrophy. Scand J Gastroenterol 1982; 17: 625-628 PubMed 15 Iliffe GD, Owen DA. An association between primary biliary cirrhosis and jejunal villous atrophy resembling celiac disease. Dig Dis Sci 1979; 24: 802-806 PubMed 16 Freeman HJ. Celiac disease associated with primary cirrhosis in a Coast Salish native. Can J Gastroenterol 1994; 8: 105-108 PubMed 17 Whitehead EM, Daly JG, Hayes JR. Renal tubular acidosis in association with Sjogren�s syndrome, primary biliary cirrhosis and coeliac disease. Ir J Med Sci 1987; 156: 124-125 PubMed 18 Weetman AP. Non-thyroid autoantibodies in autoimmune thyroid disease. Best Pract Res Clin Endocrinol Metab 2005; 19: 17-32 PubMed 19 Fracchia M, Galatola G, Corradi F, Dall�Omo AM, Rovera L, Pera A, Vitale C, Bertero MT. Coeliac disease associated with Sjogren�s syndrome, renal tubular acidosis, primary biliary cirrhosis and autoimmune hyperthyroidism. Dig Liver Dis 2004; 36: 489-491 PubMed 20 Anand AC, Elias E, Neuberger JM. End-stage primary biliary cirrhosis in a first generation migrant south Asian population. Eur J Gastroenterol Hepatol 1996; 8: 663-666 PubMed 21 Kingham JG, Parker DR. The association between primary biliary cirrhosis and coeliac disease: a study of relative prevalences. Gut 1998; 42: 120-122 PubMed 22 Dickey W, McMillan SA, Callender ME. High prevalence of celiac sprue among patients with primary biliary cirrhosis. J Clin Gastroenterol 1997; 25: 328-329 PubMed 23 Sorensen HT, Thulstrup AM, Blomqvist P, Norgaard B, Fonager K, Ekbom A. Risk of primary biliary liver cirrhosis in patients with coeliac disease: Danish and Swedish cohort data. 1999; 44: 736-738 PubMed 24 Gillett HR, Cauch-Dudek K, Jenny E, Heathcote EJ, Freeman HJ. Prevalence of IgA antibodies to endomysium and tissue transglutaminase in primary biliary cirrhosis. Can J Gastroenterol 2000; 14: 672-675 PubMed 25 Volta U, Rodrigo L, Granito A, Petrolini N, Muratori P, Muratori L, Linares A, Veronesi L, Fuentes D, Zauli D, Bianchi FB. Celiac disease in autoimmune cholestatic liver disorders. Am J Gastroenterol 2002; 97: 2609-2613 PubMed 26 Floreani A, Betterle C, Baragiotta A, Martini S, Venturi C, Basso D, Pittoni M, Chiarelli S, Sategna Guidetti C. Prevalence of coeliac disease in primary biliary cirrhosis and of antimitochondrial antibodies in adult coeliac disease patients in Italy. Dig Liver Dis 2002; 34: 258-261 PubMed 27 Bizzaro N, Villalta D, Tonutti E, Doria A, Tampoia M, Bassetti D, Tozzoli R. IgA and IgG tissue transglutaminase antibody prevalence and clinical significance in connective tissue diseases, inflammatory bowel disease, and primary biliary cirrhosis. Dig Dis Sci 2003; 48: 2360-2365 PubMed 28 Lawson A, West J, Aithal GP, Logan RF. Autoimmune cholestatic liver disease in people with coeliac disease: a population-based study of their association. Aliment Pharmacol Ther 2005; 21: 401-405 PubMed 29 Hay JE, Wiesner RH, Shorter RG, LaRusso NF, Baldus WP. Primary sclerosing cholangitis and celiac disease. A novel association. Ann Intern Med 1988; 109: 713-717 PubMed 30 Freeman HJ, Kwan WC. Occult celiac disease associated with lymphocytic sclerosing cholangitis. Can J Gastroenterol 1994; 8: 249-252 PubMed 31 Wolber R, Owen D, DelBuono L, Appelman H, Freeman H. Lymphocytic gastritis in patients with celiac sprue or spruelike intestinal disease. Gastroenterology 1990; 98: 310-315 PubMed 32 Wolber R, Owen D, Freeman H. Colonic lymphocytosis in patients with celiac sprue. Hum Pathol 1990; 21: 1092-1096 PubMed 33 Venturini I, Cosenza R, Miglioli L, Borghi A, Bagni A, Gandolfo M, Modonesi G, Zeneroli ML. Adult celiac disease and primary sclerosing cholangitis: two case reports. Hepatogastroenterology 1998; 45: 2344-2347 PubMed 34 Lindberg J, Ahren C, Iwarson S. Intestinal villous atrophy in chronic active hepatitis. Scand J Gastroenterol 1979; 14: 1015-1018 PubMed 35 Swarbrick ET, Fairclough PD, Campbell PJ, Levison DA, Greenwood RH, Baker LR. Coeliac disease, chronic active hepatiti, and mesangiocapillary glomerulonephritis in the same patient. Lancet 1980; 2: 1084-1085 PubMed 36 Volta U, De Franceschi L, Molinaro N, Cassani F, Muratori L, Lenzi M, Bianchi FB, Czaja AJ. Frequency and significance of anti-gliadin and anti-endomysial antibodies in autoimmune hepatitis. Dig Dis Sci 1998; 43: 2190-2195 PubMed 37 Villalta D, Girolami D, Bidoli E, Bizzaro N, Tampoia M, Liguori M, Pradella M, Tonutti E, Tozzoli R. High prevalence of celiac disease in autoimmune hepatitis detected by anti-tissue tranglutaminase autoantibodies. J Clin Lab Anal 2005; 19: 6-10 PubMed 38 Gogos CA, Nikolopoulou V, Zolota V, Siampi V, Vagenakis A. Autoimmune cholangitis in a patient with celiac disease: a case report and review of the literature. J Hepatol 1999; 30: 321-324 PubMed 39 Sedlack RE, Smyrk TC, Czaja AJ, Talwalkar JA. Celiac disease-associated autoimmune cholangitis. Am J Gastroenterol 2002; 97: 3196-3198 PubMed 40 Morris WE Jr. Hemochromatosis and celiac sprue. Case report. J Fla Med Assoc 1993; 80: 243-245 PubMed 41 Heneghan MA, Feeley KM, Stevens FM, Little MP, McCarthy CF. Precipitation of iron overload and hereditary hemochromatosis after successful treatment of celiac disease. Am J Gastroenterol 2000; 95: 298-300 PubMed 42 Turcu A, Leveque L, Bielefeld P, Besancenot JF, Hillon P. Adult celiac disease and hemochromatosis. Am J Gastroenterol 2000; 95: 3661-3662 PubMed 43 Butterworth JR, Cooper BT, Rosenberg WM, Purkiss M, Jobson S, Hathaway M, Briggs D, Howell WM, Wood GM, Adams DH, Iqbal TH. The role of hemochromatosis susceptibility gene mutations in protecting against iron deficiency in celiac disease. Gastroenterology 2002; 123: 444-449 PubMed 44 Bowlus CL, Lie BA. Discussion of the role of hemochromatosis susceptibility gene mutation in protecting against iron deficiency in celiac disease. Gastroenterology 2003; 124: 1562-1563 PubMed 45 Barisani D, Ceroni S, Del Bianco S, Meneveri R, Bardella MT. Hemochromatosis gene mutations and iron metabolism in celiac disease. Haematologica 2004; 89: 1299-1305 PubMed 46 Geier A, Gartung C, Theurl I, Weiss G, Lammert F, Dietrich CG, Weiskirchen R, Zoller H, Hermanns B, Matern S. Occult celiac disease prevents penetrance of hemochromatosis. World J Gastroenterol 2005; 11: 3323-3326 PubMed 47 Holzbach RT. Hepatic effects of jejunoileal bypass for morbid obesity. Am J Clin Nutr 1977; 30: 43-52 PubMed 48 Moxley RT 3rd, Pozefsky T, Lockwood DH. Protein nutrition and liver disease after jejunoileal bypass for morbid obesity. N Engl J Med 1974; 290: 921-926 PubMed 49 Kern F Jr. Hepatobiliary disorders in inflammatory bowel disease. Prog Liver Dis 1976; 5: 575-589 PubMed 50 van Tongeren JH, Breed WP, Corstens FH, Driessen WM, Flendrig JA, Laar A van�t, Schillings PH. Fatty liver and malabosprtion. Folia Med Neerl 1972; 15: 246-258 PubMed 51 Capron JP, Sevenet F, Quenum C, Doutrellot C, Capron-Chivrac D, Delamarre J. Massive hepatic steatosis disclosing adult celiac disease. Study of a case and review of the literature. Gastroenterol Clin Biol 1983; 7: 256-260 PubMed 52 Naschitz JE, Yeshurun D, Zuckerman E, Arad E, Boss JH. Massive hepatic steatosis complicating adult celiac disease: report of a case and review of the literature. Am J Gastroenterol 1987; 82: 1186-1189 PubMed 53 Sood A, Midha V, Sood N. Nonalcoholic steatohepatitis, obesity and celiac disease. Indian J Gastroenterol 2003; 22: 156 PubMed 54 Padilla H, Sanchez A, Powell RN, Umezawa C, Swendseid ME, Prado PM, Sigala R. Plasma amino acids in children from Guadalajara with kwashiorkor. Am J Clin Nutr 1971; 24: 353-357 PubMed 55 Freeman HJ, Kim YS, Sleisenger MH. Protein digestion and absorption in man. Normal mechanisms and protein-energy malnutrition. Am J Med 1979; 67: 1030-1036 PubMed 56 Low-Beer TS, Heaton KW, Read AE. Gallbladder inertia in adult coeliac disease. Gut 1970; 11: 1057-1058 PubMed 57 Low-Beer TS, Heaton KW, Heaton ST, Read AE. Gallbladder inertia and sluggish enterohepatic circulation of bile-salts in coeliac disease. Lancet 1971; 1: 991-994 PubMed 58 Low-Beer TS, Harvey RF, Davies ER, Read AF. Abnormalities of serum cholecystokinin and gallbladder emptying in celiac disease. N Engl J Med 1975; 292: 961-963 PubMed 59 Buchan AM, Grant S, Brown JC, Freeman HJ. A quantitative study of enteric endocrine cells in celiac sprue. J Pediatr Gastroenterol Nutr 1984; 3: 665-671 PubMed 60 DiMagno EP, Go WL, Summerskill WH. Impaired cholecystokinin-pancreozymin secretion, intraluminal dilution, and maldigestion of fat in sprue. Gastroenterology 1972; 63: 25-32 PubMed 61 Freeman H, Lemoyne M, Pare P. Coeliac disease. Best Pract Res Clin Gastroenterol 2002; 16: 37-49 PubMed 62 Upadhyay R, Park RH, Russell RI, Danesh BJ, Lee FD. Acute mesenteric ischaemia: a presenting feature of coeliac disease? Br Med J (Clin Res Ed) 1987; 295: 958-959 PubMed 63 Does WF, Evans D, Hobbs JR, Booth CC. Celiac disease, vasculitis, and cryoglobulinemia. Gut 1972; 13: 112-123 PubMed 64 Meyers S, Dikman S, Spiera H, Schultz N, Janowitz HD. Cutaneous vasculitis complicating coeliac disease. Gut 1981; 22: 61-64 PubMed 65 Alegre VA, Winkelmann RK, Diez-Martin JL, Banks PM. Adult celiac disease, small and medium vessel cutaneous necrotizing vasculitis, and T cell lymphoma. J Am Acad Dermatol 1988; 19: 973-978 PubMed 66 Simila S, Kokkonen J, Kallioinen M. Cutaneous vasculitis as a manifestation of coeliac disease. Acta Paediatr Scand 1982; 71: 1051-1054 PubMed 67 Gentil-Kocher S, Bernard O, Brunelle F. Budd-Chiari syndrome in children: report of 22 cases. J Pediatr 1988; 113: 30-38 PubMed 68 Hamdi A, Ayachi R, Saad H, Gargouri R, Zouari K, Chebbah MS. Hemiplegie relevant un syndrome de Budd-Chiari associe a une maladie coeliaque chez un nourrisson. Presse Med 1990; 19: 1011-1012 PubMed 69 Marteau P, Cadranel JF, Messing B, Gargot D, Valla D, Rambaud JC. Association of hepatic vein obstruction and coeliac disease in North African subjects. J Hepatol 1994; 20: 650-653 PubMed 70 Martinez F, Berenguer M, Prieto M, Montes H, Rayon M, Berenguer J. Budd-Chiari syndrome caused by membranous obstruction of the inferior vena cava associated with coeliac disease. Dig Liver Dis 2004; 36: 157-162 PubMed 71 Pollock DJ. The liver in coeliac disease. Histopathology 1977; 1: 421-430 PubMed 72 Freeman HJ. Lymphoproliferative and intestinal malignancies in 214 patients with biopsy-defined celiac disease. J Clin Gastroenterol 2004; 38: 429-434 PubMed 73 Freeman HJ. Fulminant liver failure with necrotizing foci in the liver, spleen and lymph nodes in celiac disease due to malignant lymphoma. Can J Gastroenterol 1996; 10: 225-229 PubMed 74 Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 1994; 84: 1361-1392 PubMed 75 Farcet JP, Gaulard P, Marolleau JP, Le Couedic JP, Henni T, Gourdin MF, Divine M, Haioun C, Zafrani S, Goossens M. Hepatosplenic T-cell lymphoma: sinusal/sinusoidal localization of malignant cells expressing the T-cell receptor gamma delta. Blood 1990; 75: 2213-2219 PubMed 76 Kaukinen K, Halme L, Collin P, Farkkila M, Maki M, Vehmanen P, Partanen J, Hockerstedt K. Celiac disease in patients with severe liver disease: gluten-free diet may reverse hepatic failure. Gastroenterology 2002; 122: 881-888 PubMed 77 Gillett PM, Gillett HR, Israel DM, Metzger DL, Stewart L, Chanoine JP, Freeman HJ. High prevalence of celiac disease in patients with type 1 diabetes detected by antibodies to endomysium and tissue transglutaminase. Can J Gastroenterol 2001; 15: 297-301 PubMed 78 Benson GD, Kowlessar OD, Sleisenger MH. Adult celiac disease with emphasis upon response to the gluten-free diet. Medicine (Baltimore) 1964; 43: 1-40 PubMed 79 Pink IJ, Creamer B. Response to a gluten-free diet of patients with the celiac syndrome. Lancet 1967; 1: 300-304 PubMed 80 Weinstein LD, Herskovic T. Rectal seepage of oil in a patient with celiac disease and secondary pancreatic insufficiency. Am J Dig Dis 1968; 13: 762-765 PubMed 81 Regan PT, DiMagno EP. Exocrine pancreatic insufficiency in celiac sprue: a cause of treatment failure. Gastroenterology 1980; 78: 484-487 PubMed 82 Pitchumoni CS, Thomas E, Balthazar E, Sherling B. Chronic calcific pancreatitis in association with celiac disease. Am J Gastroenterol 1977; 68: 358-361 PubMed 83 Freeman HJ, Whittaker SJ. Nonalcoholic chronic pancreatitis with pancreatic calcification: presenting manifestation of occult celiac disease. Can J Gastroenterol 1994; 8: 319-322 PubMed 84 Pitchumoni CS. Pancreas in primary malnutrition disorders. Am J Clin Nutr 1973; 26: 374-379 PubMed 85 Carroccio A, Iacono G, Montalto G, Cavataio F, Di Marco C, Balsamo V, Notarbartolo A. Exocrine pancreatic function in children with coeliac disease before and after a gluten free diet. Gut 1991; 32: 796-799 PubMed 86 Nousia-Arvanitakis S, Karagiozoglou-Lamboudes T, Aggouridaki C, Malaka-Lambrellis E, Galli-Tsinopoulou A, Xefteri M. Influence of jejunal morphology changes on exocrine pancreatic function in celiac disease. J Pediatr Gastroenterol Nutr 1999; 29: 81-85 PubMed S- Editor Wang J L- Editor Zhang JZ E- Editor Liu WF
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