Celiac disease is a multisystem disorder. Celiac hepatitis characterized by gluten-responsive mild elevation of transaminases is the more common liver manifestation of celiac disease. Celiac disease may also be associated or coexist with other chronic liver disorders. Shared genetic risk and increased intestinal permeability have been suggested to be the most relevant events in the pathogenesis of liver injury in celiac disease. The aim of this article is to review the full spectrum of liver disorders in patients with celiac disease.

Coeliac disease (CD) is an immune-mediated disorder triggered by the ingestion of gluten in genetically susceptible individuals. However, only a small proportion of subjects harbouring CD-related genetic risk develop the disease. Among the environmental factors that may influence CD risk, pre- and perinatal factors, delivery methods, parental lifestyle, infant feeding practices, seasonality, dietary factors, drug use, childhood infections and variability in gut microbiota are those most widely studied regarding the risk to develop CD. Although for many of these external factors the exact mechanism of action is unknown, most of them are thought to act by disrupting the intestinal barrier, facilitating contact between potential antigens and the immune system effector cells. Management of CD is relatively easy in patients with a definite diagnosis and requires a strict, lifelong, gluten-free diet. Better knowledge of environmental exposures apart from gluten can facilitate understanding of the pathogenesis of the disorder and the wide heterogeneity of its clinical spectrum. The purpose of this review is to discuss current knowledge on environmental CD risk factors, as well as possible interaction between them, on the grounds of the reliable scientific evidence available. Key messages The risk of developing CD is influenced not only by gluten ingestion but also by a number of environmental factors including childhood infections and variability in gut microbiota, pre- and perinatal factors, infant feeding practices, delivery methods, parental lifestyle, seasonality, dietary factors and drug use, acting mainly by disrupting intestinal permeability. Better knowledge of exposure to these factors can facilitate their identification, and subsequent elimination, in the individual patient.

Celiac disease (CD) is a common autoimmune disorder induced by ingestion of gluten in genetically susceptible individuals. Despite the prerequisite for a genetic predisposition, only a minority of the 40% of the Caucasian population that has this genetic predisposition develops the disease. Thus, environmental and/or lifestyle factors play a causal role in the development of CD. The incidence of CD has increased over the last half-century, resulting in rising interest in identifying risk factors for CD to enable primary prevention. Early infant feeding practices have been suggested as one of the factors influencing the risk of CD in genetically susceptible individuals. However, recent large prospective studies have shown that neither the timing of gluten introduction nor the duration or maintenance of breastfeeding influence the risk of CD. Also, other environmental influences have been investigated as potential risk factors, but have not led to primary prevention strategies. Secondary prevention is possible through early diagnosis and treatment. Since CD is significantly underdiagnosed and a large proportion of CD patients are asymptomatic at the time of diagnosis, secondary prevention will not identify all CD patients, as long as mass screening has not been introduced. As following a gluten-free diet is a major challenge, tertiary prevention strategies are discussed as well.

Celiac disease (CD) is a systemic immune-mediated disorder triggered by dietary gluten in genetically predisposed individuals. The typical symptoms are anemia, diarrhea, fatigue, weight loss, and abdominal pain. CD has been reported in patients with primary sclerosing cholangitis, primary biliary cholangitis, autoimmune hepatitis, aminotransferase elevations, nonalcoholic fatty liver disease, hepatitis B, hepatitis C, portal hypertension and liver cirrhosis. We evaluate recommendations for active screening for CD in patients with liver diseases, and the effect of a gluten-free diet in these different settings. Active screening for CD is recommended in patients with liver diseases, particularly in those with autoimmune disorders, steatosis in the absence of metabolic syndrome, noncirrhotic intrahepatic portal hypertension, cryptogenic cirrhosis, and in the context of liver transplantation. In hepatitis C, diagnosis of CD can be important as a relative contraindication to interferon use. Gluten-free diet ameliorates the symptoms associated with CD; however, the associated liver disease may improve, remain the same, or progress.

Background. Patients treated with interferon (IFN) based therapies may develop exacerbation of autoimmune disease. We herein present the case of a 53-year-old female patient who developed celiac disease (CD) as a result of triple therapy (interferon, ribavirin, and boceprevir) for chronic HCV. Case. 53-year-old Caucasian female with past medical history of IV drug abuse was referred for abnormal LFTs. Laboratory data showed HCV RNA of 4,515,392 IU/mL, HCV genotype 1a, with normal LFTs. She was treated with 4 weeks of pegylated interferon alfa-2a plus ribavirin, followed by triple therapy using boceprevir for a total of 28 weeks. Approximately 4 weeks after initiation of triple therapy patient developed loose nonbloody bowel movements and was also found to have anemia. Biopsies from first and second portions of the duodenum were consistent with CD. The patient was treated with a gluten-free diet. Her intestinal symptoms improved and the hemoglobin returned to normal. Conclusion. Chronic HCV patients being treated with interferon alfa can develop celiac disease during or after therapy. For patients with positive autoantibodies, all-oral-IFN-free regimens should be considered. Celiac disease should be considered in patients who develop CD-like symptoms while on and shortly after cessation of interferon alfa therapy.

Non-organ-specific autoantibodies and thyroid autoantibodies have been frequently found in chronic carriers of hepatitis C virus (HCV). With respect to endomysial antibodies and tissue transglutaminase, it is controversial whether the prevalence of gluten-related seromarkers is higher in patients with HCV. In such cases, in addition to acknowledging any currently existing autoimmune disease, recognizing the risk of the patient developing an autoimmune disease during interferon (IFN)-based treatment must be a principle concern. From a clinical point-of-view, the presence of autoantibodies arouses suspicion that an autoimmune disease may be present or may be precipitated by IFN-based HCV treatment. In this paper, we review the prevalence of autoantibodies in individuals with hepatitis C, the clinical significance of these autoantibodies, and the approach recommended for such situations.

Celiac disease (CD) is defined as a permanent intolerance to ingested gluten. The intolerance to gluten results in immune-mediated damage of small intestine mucosa manifested by villous atrophy and crypt hyperplasia. These abnormalities resolve with initiationa gluten-free diet.

PubMed, Ovid, and Google were searched for full text articles published between 1963 and 2012. The associated keywords were used, and papers described particularly the impact of celiac disease on severity of liver disorder were identified.

Recently evidence has emerged revealingthat celiac disease not only is associated with small intestine abnormalities and malabsorption, but is also a multisystem disorder affecting other systems outside gastrointestinal tract, including musculo-skeletal, cardiovascular and nervous systems. Some correlations have been assumed between celiac and liver diseases. In particular, celiac disease is associated with changes in liver biochemistry and linked to alter the prognosis of other disorders. This review will concentrate on the effect of celiac disease and gluten-free diets on the severity of liver disorders.

Although GFD effect on the progression of CD associated liver diseases is not well defined, it seems that GFD improves liver function tests in patients with a hypertransaminasemia.

Autoantibodies are often produced during infection with chronic hepatitis C virus (HCV), but it remains controversial whether they influence the biochemical profile and histological features of this disease. Therefore, this current study sought to describe these autoantibodies and evaluate their impact on the clinical and histological presentation of hepatitis C.

This cross-sectional analytical study assessed patients with HCV (RNA+) from October 2011 to July 2012.

This study included 66 patients, with a mean age of 53.2±10.5 years. Of these patients, 60.6% were male, and 54.3% presented with genotype 1. Non-organ-specific autoantibodies (NOSA) were detected in 24% of the patients; of these, 7.6% were anti-mitochondrial antibodies (AMA+), 26.7% were anti-smooth muscle antibodies (SMA+) and 6.8% were liver kidney microsomal type 1 antibodies (LKM1+). With respect to the thyroid autoantibodies, 7.4% were anti-peroxidase (ATPO+) antibodies, and none were anti-thyroglobulin (ATG+) antibodies. Regarding celiac disease autoantibodies, 5.8% were endomysial antibodies (EMA+), and no transglutaminase (TTG+) antibodies were detected. Cryoglobulins were found in 2.1% of patients. When NOSA+ individuals were compared to patients without the presence of NOSAs, they exhibited higher median alkaline phosphatase (0.7 vs. 0.6 xULN; p=0.041), lower median platelet counts (141,500.0 vs. 180,500.0/mm 3 ; p=0.036), lower mean prothrombin activity (72.6±11.5% vs. 82.2±16.0%; p=0.012) and an increased prevalence of significant fibrosis (E≥2) (45.5% vs. 18.2%; p=0.012). There was also a tendency for a greater proportion of NOSA+ cases to have marked periportal activity (APP≥3) (44.5% vs. 15.6%; p=0.087).

In addition to the high prevalence of autoantibodies associated with HCV infection, it was observed that NOSA positivity was associated with a more severe histological and biochemical profile of hepatitis C infection.

A higher prevalence of coeliac disease has recently been reported among patients with HCV-related chronic hepatitis. Moreover, development of clinically overt coeliac disease has been described in a number of HCV-related chronic hepatitis patients during α-interferon therapy. This prospective study was designed to evaluate 1) the prevalence of coeliac disease in patients with HCV-related chronic hepatitis; 2) the prevalence of HCV infection in patients with coeliac disease; 3) whether PEG interferon-α treatment might favour the development of coeliac disease in patients with chronic hepatitis C.

Two hundred-ten consecutive patients (M/F = 140/70, range of age 35-58 years, median age 46.5 years) with biopsy proven chronic hepatitis C underwent serological screening for antiendomysial and tissue transglutaminase IgA antibodies. One hundred ninety-four coeliac patients (M/F = 52/142, range of age 18-74 years, median age 34 years) were screened for HCV antibodies. Positivity for HCV antibodies in coeliac disease patients was confirmed by detection of serum HCV-RNA by RT-PCR. This work was carried out in accordance to ethical guidelines of Declaration of Helsinki and was approved by Institutional Ethics Committee of the Second University of Naples. All patients gave informed written consent.

1) none of the 210 HCV-related chronic hepatitis patients were positive for coeliac disease serologic screening; 2) prevalence of HCV infection among coeliac patients was 1.54% (3/194) which is comparable to that reported in the Southern Italy population; 3) PEG interferon-α treatment was not associated with development of coeliac disease either clinical or serological.

1) coeliac disease is not associated with HCV infection; 2) PEG interferon-α does not trigger celiac disease.

Descriptive reports of liver histologic features in celiac disease (CD) are sparse, and the effect of a gluten-free diet (GFD) on the course of liver injury is poorly understood. We reviewed liver biopsy specimens in 30 patients with CD and performed immunostains for IgG, IgG4, IgM, and IgA. Subsequent liver biochemical tests and compliance with the GFD were recorded. Of the patients, 19 had autoimmune-mediated liver disease (AILD; autoimmune hepatitis, 9; primary sclerosing cholangitis, 7; and primary biliary cirrhosis, 3). The remaining 11 patients had cryptogenic hepatitis (5), hepatitis C (2), steatohepatitis (2), sarcoidosis (1), and T-cell lymphoma (1). The liver disease diagnosis preceded the CD diagnosis in all groups except steatohepatitis. Although 82% of patients without AILD had symptomatic CD, only 26% of patients with AILD had such symptoms. The pathology of the specific liver disease was not atypical in histologic features or IgG/IgM ratios. While GFD improved cryptogenic hepatitis, it did not seem to affect AILD. We propose that AILD and cryptogenic hepatitis in patients with CD represent distinct clinical, histologic, and immunohistochemical entities rather than 2 ends of a spectrum of liver injury.

Celiac disease affects the proximal small intestine and is caused by a local immune response to dietary gluten. Celiac disease usually presents with chronic diarrhea; however, presentations with elevated hepatic transaminase levels in blood or with iron-deficiency anemia have been described. Celiac disease has been reported to be associated with autoimmune liver diseases. Hepatitis C virus (HCV) can also initiate autoimmune disease process. Therefore, HCV infection and celiac disease may occur together. Here, we describe 4 cases of celiac disease associated with chronic hepatitis C. This small case series indicates that chronic HCV infection and celiac disease are not causally associated.

Many diseases with unknown etiology may be caused by unidentified viruses. Sequence-independent amplification revealed a new astrovirus, similar to VA1, in a 4-year-old male diagnosed with celiac disease. This expands the geographic range of this virus to include Europe and may associate astrovirus infection with the onset of celiac disease.

Lymphocytic gastritis (LG) is characterized by the presence of > or = 25 lymphocytes/100 epithelial cells in the gastric surface and pit epithelium. An association of LG with Helicobacter pylori infection or celiac disease (CD) has been suggested. The aim of this study was to verify the relation of LG with CD, with and without H pylori infection, in children.

A total of 164 children with CD diagnosed between June 2003 and October 2005, in whom gastric and duodenal biopsies were performed simultaneously, were enrolled prospectively. The control group was composed of 164 children without CD, matched for sex and age, who were undergoing upper digestive endoscopy. H pylori was searched for in gastric biopsy specimens sectioned and stained with hematoxylin and eosin, and a modified Giemsa stain for H pylori was performed for confirmation. The Student t test was used to compare quantitative measurements between groups.

LG was found in 69 (42.1%) patients with CD. Positive cases had a mean of 43.9 +/- 1.5 intraepithelial lymphocytes per 100 surface epithelial cells, compared with a mean of 13.4 +/- 0.4 in negative cases and 7.8 +/- 0.5 in non-CD control children (P<0.0001). Patients not showing LG did, however, show significantly increased gastric intraepithelial lymphocytes compared with the control children. Nine of 164 CD patients, and 4 of 69 patients with LG, had positive results for H pylori.

This study supports a pathogenetic relation between CD and LG. CD without LG also showed increased gastric intraepithelial lymphocytes. H pylori infection may be another cause of LG in children.

Considering that celiac disease (CD) is an autoimmune-based entity and the hepatitis C virus is suspected of being able to trigging autoimmune reactions, it has been hypothesized that hepatitis C virus infection might predispose to CD. The aim of this study was to investigate CD-related antibodies in a large series of hepatitis C virus-infected subjects that were also tested for non-organ-specific autoantibodies (NOSA) as indirect marker of autoimmune disorders.

Two hundred and forty-four patients with chronic hepatitis C virus infection (HCV-patients) and 121 patients with HCV-negative liver disease (non-HCV-patients) underwent NOSA determination and celiac serology (firstly, anti-tissue transglutaminase antibodies, then the cases which tested positive were subsequently evaluated for the presence of antiendomysial antibodies). Serum samples from 42 of the HCV-patients who underwent interferon-alpha therapy after enrollment were tested for celiac antibodies and NOSA even after stopping treatment. Additionally, sera from 1,230 blood donors were assayed for celiac serology as healthy control population.

Positive anti-endomysial antibodies (AEA) were found in 5/244 (2%) HCV-patients, 1/121 (0.8%) non-HCV-patients and 2/1,230 (0.16%) blood donors, with a significant difference between HCV-patients and blood donors (P = 0.02; Odds ratio 12.8; 95% Confidence Interval 2.4-66). NOSA were found in 51 HCV-patients but only one of them had positive AEA. Eight out of 42 HCV-patients treated with interferon-alpha developed NOSA under therapy and none of them had CD antibodies.

AEA occur in 2% of HCV-patients and their presence is independent of other patterns of autoimmunity.

Celiac disease (CD) is an autoimmune enteropathy triggered by gluten ingestion in genetically susceptible individuals. Hypertransaminasemia has been observed in up to 40% of untreated celiac patients and is usually resolved by a gluten-free diet. The most common type of liver disease associated with CD is non-specific reactive hepatitis, while association with viral hepatitis or autoimmune-mediated liver diseases such as autoimmune hepatitis, primary biliary cirrhosis or primary sclerosing cholangitis is less frequent. Therefore, a practical recommendation would be to look for liver disfunction in patients with CD as well as to perform diagnostic tests for CD in patients with hypertransaminasemia or cholestasis of unknown etiology.

Celiac disease (CD) has been epidemiologically associated with chronic hepatitis C (HCV), and CD activation after the initiation of interferon (IFN-alpha) in patients with HCV is documented. However, clear association of CD and HCV is lacking. A prospectively maintained database of 878 CD patients showed a prevalence of 0.68% (six patients). Symptoms of diarrhea, weight loss, and depression prompted the diagnosis of CD during or after IFN-alpha therapy in four cases. Also, 294 subjects with liver disease (195 with HCV, 80 normal controls and 19 disease controls) were prospectively screened for CD. The mean age of the subjects was 50.1 years (SD 12.3), 58% males:42% females. A total of 30% received IFN-alpha therapy (16% at the time of testing for CD). Two HCV patients (1%) had positive tTG-IgA but these had negative endomysial antibody (EMA) and normal duodenal biopsies. CD prevalence is not increased in patients with HCV. Routine screening of CD in HCV patients is not warranted, however, the presence of CD should be considered in the setting of clinical deterioration during or after IFN-alpha therapy.

A prevalence of 1.2% of coeliac disease (CD) in patients with chronic hepatitis C was recently reported, suggesting a possible epidemiological link between these two diseases. However, other studies have not found this relationship.

To conduct a French multicentre prospective study to assess the prevalence of CD in hepatitis C virus (HCV)-infected patients.

Between June 2003 and November 2005, 624 consecutive HCV-positive out-patients were tested for antiendomysial IgA antibodies (AEA), antigliadin IgA and IgG antibodies (AGA). Patients with positive AEA or IgA AGA and positive IgG AGA in a context of a high suspicion of CD were asked to undergo gastroscopy with duodenal biopsies.

Isolated IgA AEA, IgA AGA and IgG AGA were 0.16%, 5.7% and 4.4%, respectively. Gastroscopy was required for 39 patients, 31 were performed (eight refusals), but only 25 duodenal biopsies were performed as six patients had cirrhosis. CD was never detected.

The prevalence of CD in HCV-positive patients was 0% (95% confidence interval: 0-0.59%), but there is a low prevalence of CD in the whole French population.

The present report describes a young woman with no previous gastrointestinal complaints who was initially diagnosed with postinfective irritable bowel syndrome (IBS) after a confirmed case of Campylobacter jejuni enteritis. However, because of persistent diarrhea, new-onset bloating and the development of iron and vitamin deficiencies, serological markers for celiac disease (CD) were evaluated. A positive tissue transglutaminase immunoglobulin A antibody test and repeat endoscopy with duodenal biopsy showing a Marsh IIIa lesion confirmed the diagnosis of CD. Infectious gastroenteritis is a well-established risk factor for the development of IBS, and there is recent evidence that it could play a role in the initiation and exacerbation of inflammatory bowel disease. The present case suggests that the clinical expression of CD can be unmasked by an acute gastrointestinal infection and supports the hypothesis that environmental factors other than gliadin may play a role in the clinical onset of CD in a genetically susceptible host. The increasing availability of serological testing and upper endoscopy has led to increasingly frequent diagnoses of CD and recognition that it may mimic IBS. The present case findings suggest that CD should be considered in the differential diagnosis of persistent IBS-like symptoms after an episode of infectious gastroenteritis.

Hepatitis C virus (HCV) infection is associated with various autoimmune disorders and can mimic systemic lupus erythematosus (SLE) clinically and serologically. There are few reports of prevalence of HCV infection in patients with SLE. The aim of this study was to determine the prevalence of HCV viremia by polymerase chain reaction (PCR) in patients with SLE.

We tested sera from 40 consecutive patients with SLE collected from 1993 to 2000. All of the patients had HCV viral load measured by PCR. The results were compared with the prevalence of HCV viremia in a control group of blood donors in our geographic area as well as in United States general population.

HCV was detected in 4 of 40 patients (10%). The prevalence of HCV in our area blood donors is 130 cases per 100,000 persons (0.13%; P<0.0001). The prevalence of HCV infection in the United States general population, screened by PCR, is 1330 cases per 100,000 people (1.33%; P=0.002). The prevalence of HCV infection was significantly higher in our SLE patients than in our area blood donors. The frequency of HCV infection was also higher than that of the United States general population.

Our observations support those of other investigators who have reported an increased prevalence of HCV infection in SLE patients. Further detailed investigation of this association may help in understanding the pathogenesis of SLE. HCV infection should be tested when the diagnosis of SLE is considered.

The prevalence of celiac disease (CD) and the prevalence and clinical significance of anti-tissue transglutaminase (tTG) antibodies (tTGAbs) in a large series of patients with chronic liver diseases were assessed. We studied 738 patients (462 with chronic viral hepatitis, 117 with autoimmune liver diseases, 113 with alcoholic or nonalcoholic fatty liver disease, and 46 with other liver disorders) and 1,350 healthy controls (HC). Immunoglobulin A (IgA) tTGAbs were measured by enzyme-linked immunosorbent assay and a microsphere-based flow cytometric assay. Positive sera were investigated for IgA antiendomysial antibodies (EmA). IgA tTGAb-positive subjects were invited to undergo a small-intestinal biopsy and HLA-DQ allele typing. Four of 1,350 HC (0.3%) tested tTGAb(+) EmA(+) and underwent a biopsy (CD confirmation in all). Four of 738 liver disease patients tested tTGAbs(+) EmA(+) (0.54%; not statistically significant). Two were HCV infected (1.24%; not statistically significant), and two had transaminasemia of unknown origin. Forty-three patients tested tTGAbs(+) EmA(-) (5.8%; P<0.001 compared to HC). Inhibition experiments verified the existence of specific IgA anti-tTG reactivity. Twenty-six of 43 patients underwent a biopsy (all negative for CD). Binary logistic regression analysis revealed age (P=0.008), cirrhosis (P=0.004), alkaline phosphatase (P=0.026), and antinuclear antibodies (P=0.012) as independent risk factors for tTGAb reactivity among the patients. It was concluded that CD prevalence is the same in HC and patients with chronic liver diseases. The prevalence of tTGAbs is higher in hepatic patients compared to HC, but their specificity for CD diagnosis in this group of patients is low. tTGAbs in patients appear to be associated with the presence of autoimmunity, cirrhosis, and cholestasis, irrespective of the origin of the liver disease.

The multiplexed particle-based flow cytometric technology proposes a new approach for the diagnosis of autoimmune diseases combining the advantages of conventional methods with the ability to quantitatively determine multiple autoantibodies in the same sample, simultaneously and rapidly. Recently, a commercial kit (FIDIS Celiac, Biomedical Diagnostics, Mane la Vallé, France) was introduced for the simultaneous detection of IgA anti-tissue transglutaminase (anti-tTG), IgG, and IgA anti-gliadin antibodies (AGA). This study was undertaken to evaluate and compare the FIDIS Celiac kit with standardized commercial ELISAs (QUANTA Lite, INOVA Diagnostics Inc., San Diego, CA). A disease group consisted of 21 samples from untreated patients with biopsy confirmed celiac disease (CD), and two control groups of historical sera (207 from regular blood donors and 181 from chronically infected hepatitis patients) were studied. All control sera were negative for IgA anti-endomysial antibodies (EmA) and had an IgA concentration above the lower normal limit. Concerning the reproducibility, intra- and inter-assay coefficients of variation (CVs) ranging between 2% and 12%, and between 3% and 21%, respectively, were observed. Regarding the diagnostic quality, each assay was compared to the disease diagnosis using the McNemar test and the kappa (K) parameter, while ROC analysis was applied. Generally, the performance of FIDIS assay was proved almost equally adequate to that of ELISA in the detection of IgA anti-tTG antibodies, IgA and IgG AGA. However, the performance of FIDIS assay was found surmounting that of ELISA among hepatitis patients, possibly due to the avoidance of debris and unbound cross contaminants and, hence, the "noise" of such materials in samples under analysis. Taking our results together with the simplicity and the high throughput of FIDIS assay, its overall performance in the diagnosis of CD seems better than that of ELISA.

Population data supporting an association between the autoimmune cholestatic liver diseases, primary biliary cirrhosis and primary sclerosing cholangitis and coeliac disease, is limited and at times contradictory.

To explore the relationship between coeliac disease and both primary biliary cirrhosis and primary sclerosing cholangitis within the General Practice Research Database, a UK-based longitudinal primary care database.

We identified 4732 people with diagnosed coeliac disease and 23 620 age- and sex-matched controls within the General Practice Research Database. We calculated the prevalence of primary biliary cirrhosis and primary sclerosing cholangitis for both the coeliac disease and control group.

There was a higher prevalence of primary biliary cirrhosis in adults with coeliac disease, compared with controls [0.17% vs. 0.05%, odds ratio 3.63 (95% confidence interval: 1.46-9.04)]. Primary sclerosing cholangitis was also more common in the coeliac disease group [0.04% vs. 0%, fishers exact test (P = 0.03)].

There was a threefold or greater increase in risk of both primary biliary cirrhosis and primary sclerosing cholangitis in people with coeliac disease compared with the general population. The association with primary biliary cirrhosis was weaker than in some reports and it is difficult on the basis of this study to justify screening patients with coeliac disease for either primary biliary cirrhosis or primary sclerosing cholangitis.

To assess the impact of interferon treatment on celiac disease onset in hepatitis C patients and to clarify its clinical relevance and outcome.

Hepatitis C is associated with autoimmunity, which can be exacerbated by interferon treatment. Cases of celiac disease activation during interferon treatment have been reported.

Retrospective evaluation of 534 hepatitis C patients with or without symptoms compatible with celiac disease onset during interferon treatment and 225 controls. Anti-transglutaminase antibodies were assayed. HLA-DQA1 and -B1 loci were typed. Upper gastrointestinal endoscopy was applied to confirm the diagnosis in antibody-positive patients.

Anti-transglutaminase antibodies were detected before treatment in 1.3% of hepatitis C patients and in 0.4% of controls (not significant). Eighty-six percent of patients with anti-transglutaminase antibodies showed activation of celiac disease while on interferon. Symptoms ranged from mild to severe, and interferon had to be discontinued in 2 of 7 (29%) patients. Symptoms disappeared in 6 of 7 patients after interferon withdrawal. Onset of symptoms compatible with celiac disease during interferon therapy was significantly associated with the presence of anti-transglutaminase antibodies (OR 53).

In hepatitis C patients, the activation of silent celiac disease during interferon treatment is almost universal and should be suspected, but it uncommonly requires interferon treatment discontinuation. Symptoms subside after interferon withdrawal.

Report of a case of a woman patient who developed celiac disease after pegylated interferon alpha-2a and ribavirin use for chronic hepatitis C.

A 34-year-old woman with chronic hepatitis C, genotype 3, receiving pegylated interferon alpha-2a and ribavirin for 6 months, developed progressive malaise and anemia 6 months after the end of treatment.

Additional investigation revealed duodenal villous atrophy and positivity for anti-endomysium and anti-gliadin antibodies. Celiac disease diagnosis was performed and symptoms and laboratory abnormalities improved after gluten-free diet.

Celiac disease must be ruled out in patients with malabsorption complaints in or after interferon (or pegylated interferon) therapy. Screening for celiac disease with detection of anti-endomysium antibodies would be done in susceptible patients.

Cutaneous eruptions related to hepatitis C virus (HCV), a major cause of hepatitis in the setting of blood transfusion, intravenous drug abuse, organ transplantation, and hemodialysis, are typically reported as isolated cases. We encountered 35 cases of HCV infection associated with cutaneous eruptions. The present study evaluates paraffin-embedded, formalin-fixed tissue sections stained with hematoxylin and eosin from biopsy specimens of skin lesions from 35 patients seropositive for HCV. In 20 cases, reverse transcriptase polymerase chain reaction (RT-PCR) was performed using a probe for HCV RNA; the RNA was detected through the action of alkaline phosphatase on the chromogen nitroblue tetrazolium and bromochloroindolyl phosphate. The clinical spectrum comprised dermatomyositis-like photodistributed eruptions, palpable purpura, folliculitis, violaceous and perniotic acral lesions, ulcers, nodules, and urticaria. Lesions were also classified histopathologically by the dominant reaction pattern: vasculopathies of neutrophilic, lymphocytic, and granulomatous vasculitis and pauci-inflammatory subtypes (15 patients); palisading granulomatous inflammation (3 patients); sterile neutrophilic folliculitis (5 patients); dermatitis herpetiformis (1 patient); lobular panniculitis composed of neutrophilic lobular panniculitis in 2 patients and benign cutaneous polyarteritis nodosa in 1 patient; neutrophilic dermatoses, including neutrophilic urticaria, neutrophilic eccrine hidradenitis, and pyoderma gangrenosum (3 patients); interface dermatitis (3 patients); and low-grade lymphoproliferative disease of B-cell lineage representing marginal zone lymphoma in 1 patient and a clonal plasmacellular infiltrate in another patient. In most cases, whereas 1 of the aforementioned disorders defined the dominant reaction pattern, there was an accompanying secondary reaction pattern, defining a hybrid picture. Endothelial changes including endothelial cell enlargement and effaced heterochromatin with margination of the chromatin to the nuclear membrane were seen in several cases; in some cases similar cytopathic changes also involved the supporting pericytes, eccrine ductular cells, or keratinocytes. The RT-PCR analyses in 8 of 20 cases examined revealed HCV RNA expression in a focal, weak fashion in endothelia and perivascular inflammatory cells in those cases showing vasculopathic changes. Viral parasitism of endothelia may be important in cutaneous lesional propagation in the setting of HCV infection. Cross-reactivity between endogenous and viral antigens, leading to cellular and/or type II immune reactions; viral tropism to B lymphocytes, resulting in B cell expansion with resultant autoantibody production; and circulating immune complexes containing monoclonal cryoglobulins may also be of pathogenetic importance. Tropism of the virus to B lymphocytes provides a mechanism for the development of low-grade clonal B cell lymphoproliferative disease in this setting.

Functional dyspepsia, unexplained chronic hypertransaminasaemia (CHT) and hepatitis C virus (HCV) are common gastrointestinal situations that have been related to coeliac disease. Antibodies to tissue transglutaminase (tTG) have been claimed recently to be highly effective as a screening method for coeliac disease.

To assess the prevalence of coeliac disease by means of detection of antibodies against human tTG in the above-mentioned groups of patients.

A control group consisted of 165 normal blood donors. Patient groups comprised 90 CHT patients, 102 HCV patients and 92 functional dyspepsia patients. All patients were tested for anti-tTG (immunoglobulin A, IgA) antibodies. Anti-endomysium (IgA) antibodies (AEA) and antigliadin (IgA) antibodies (AGA) and antigliadin (immunoglobulin G, IgG) antibodies (AGG) were also tested. When anti-tTG or AEA was positive, a duodenal biopsy was recommended.

One of 165 blood donors, three of 92 functional dyspepsia patients, four of 90 CHT patients and none of 102 HCV patients were positive for anti-tTG antibodies. In the anti-tTG-positive group, all but one were AEA-positive. There were no AEA- or AGA IgA-positives that revealed a negative anti-tTG test. Duodenal biopsy confirmed a diagnosis of coeliac disease in all the cases. Statistically significant differences were found between the controls and the functional dyspepsia group and between the controls and the CHT group, but not between the controls and the HCV group.

Both CHT and functional dyspepsia may represent a true oligosymptomatic form of coeliac disease. In such conditions, the detection of anti-tTG antibodies is useful as a screening method. Coeliac disease is not an autoimmune manifestation of HCV, so screening for coeliac disease in HCV patients cannot be recommended.

The aims of this study were to evaluate the following: 1) the prevalence of hypertransaminasemia (HT) in a pediatric celiac disease (CD) and its relation with clinical parameters; 2) the frequency of HT as the only manifestation of pediatric CD; and 3) the evolution of HT after a gluten free diet.

A total of 114 consecutive pediatric CD patients were studied (60% with classical and 40% with atypical forms). Antiendomisyum antibodies and anti-tissue transglutaminase antibodies were determined in patients with a clinical suspicion of CD (including unexplained chronic HT), in patients at risk, and in patients with preoperative increased ALT activity for minor surgery. CD was confirmed by duodenal biopsy. At baseline, the relationship between clinical factors and aminotransferase status was univariately and multivariately assessed. After starting a gluten free diet, patients were followed up, until serological markers cleared and serum aminotransferase normalized.

HT occurred in 32% of patients (37 of 114) at diagnosis. HT was the only manifestation of CD in five patients (4.3%). Patients with HT were younger (2.9 +/- 0.4 yr) than patients with normal aminotransferases (5.1 +/- 0.5 yr) (p = 0.007). A higher percentage of patients with classical CD tend to have abnormal aminotransferases (73%; 95% CI = 65-81%) than do patients with atypical CD (27%; 95% CI = 19-35%) (p = 0.068). Logistic regression analysis showed that only younger age was significantly associated with HT (p = 0.039; OR = 0.8; 95% CI = 0.71-0.99). Aminotransferases normalized with a gluten free diet in all 35 patients who were followed-up, either before (n = 18) or at the same time (n = 17) as serological markers cleared.

HT is a frequent finding in pediatric CD patients and, in a substantial proportion, may be the only manifestation of CD. Thus, serological markers of CD should be introduced in the first step of the diagnostic workup of liver diseases in pediatric patients.

The spectrum and pathogenesis of liver dysfunction in coeliac disease (CD) is reviewed. CD and liver disease share common risk factors, and consequences of CD may cause liver dysfunction. Liver dysfunction should be sought in CD, and its aetiology explored when abnormalities persist after gluten exclusion. CD should be excluded in patients with unexplained liver dysfunction before being labelled "cryptogenic".

This study demonstrates the dynamics in the epidemiology of hepatitis C virus subtypes. Subtypes 3a and 4a have become increasingly prevalent in patients where an infection within recent years can be assumed. Evidence is presented that the subtypes observed among younger patients can spread rapidly and lead to significant changes in the subtype distribution.

Patients with Crohn's disease (CD) are at higher risk of hepatitis C (HCV) and B virus (HBV) infection, because of surgical and/or endoscopic procedures. However, the prevalence of HCV and HBV infection in CD is unknown. This issue may be relevant because of the growing use of immunomodulatory drugs in CD. The purpose of this study was to assess, in a multicenter study, the prevalence and risk factors of HCV and HBV infection in CD. The effect of immunomodulatory drugs for CD on the clinical course of hepatitis virus infections and of interferon-alpha (IFN-alpha) on the course of CD was examined in a small number of patients. Sera from 332 patients with CD and 374 control subjects (C) were tested for the following: hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), HBcAb, HBeAg, HBeAb, anti-HCV, and HCV-RNA. An additional 162 patients with ulcerative colitis (UC) were tested as a disease control group. Risk factors were assessed by multivariate statistical analysis. Infection by either HCV or HBV was detected in 24.7% of patients with CD. In the age groups younger than 50 years, HCV prevalence was higher in CD than in C (p = 0.01). HCV infection in CD was associated with surgery (OR 1.71; 95% CI 1.00-2.93; p = 0.04), blood transfusions (OR 3.39; 95% CI 1.04-11.04; p = 0.04), and age (OR 2.3; 95% CI 1.61-3.56; p < 0.001). The event CD-related surgery appeared to be the main risk factor for HCV infection in CD. HCV prevalence was higher in CD (7.4%) than in UC (0.6%) (p = 0.001). HBcAb positivity was higher in CD (10.9%) and UC (11.5%) than in C (5.1%) (CD vs. C: p = 0.016; UC vs. C: p = 0.02), associated with age (OR 2.08; 95% CI 1.37-3.17; p = 0.001) and female gender (OR 2.68; 95% CI 1.37-3.17; p = 0.001) in CD and to UC duration (OR 1.20; 95% CI 1.06-1.36; p = 0.002). Immunomodulatory drugs did not influence the course of HBV or HCV infection in seven patients with CD, and IFN-alpha for chronic hepatitis C did not affect CD activity in six patients with CD. It is concluded that HBV prevalence is higher in CD than in C at all ages, whereas HCV prevalence is increased in young patients with CD, because of a greater need for surgery. The higher HCV (but not HBV) prevalence in CD than in UC suggests that the host immune response may influence the risk of HCV infection. Although a relatively high proportion of patients with CD showed HBV and/or HCV infections, this should not influence treatment strategies for CD.