F. Barbaria

Anti-tissue transglutaminase antibodies in patients with abnormal liver tests: is it always coeliac disease?

BACKGROUND:Coeliac disease (CD) is found in 5–10% of patients with chronically abnormal liver tests and no obvious cause of liver disease. In this population the efficacy of screening for CD by anti-tissue transglutaminase (anti-tTG) may be impaired by the high rate of positive anti-tTG found in chronic liver disease.AIMS:To evaluate the prevalence of coeliac disease and the role of anti-tTG in patients with non-viral, non-autoimmune chronic and no obvious cause of liver damage.METHODS:Out of 2,512 consecutive patients with abnormal liver tests, 168 (118 men, 50 women; mean age 40.7 ± 12.6 years) were defined, on the basis of clinical data and liver biopsy, as NAFLD or cryptogenic chronic hepatitis. All were tested by recombinant IgA and IgG anti-tissue transglutaminase. Patients with a positive serology underwent endoscopy with duodenal biopsies.RESULTS:NAFLD was diagnosed in 121 patients, in 6 associated with cirrhosis, while 47 patients were considered as cryptogenic hepatitis in the absence of steatosis. Anti-tTG were positive in 20/168 patients (3 IgA alone; 11 IgG alone; 6 both IgA and IgG). Coeliac disease was found at endoscopy and confirmed by histopathology only in the 6 patients (3.6%) with both IgA and IgG anti-tTG positivity. Four of the patients with CD had NAFLD (3.3%), in 2 of them associated with cirrhosis; while 2 of those with cryptogenic hepatitis (4.2%) had CD.CONCLUSIONS:The prevalence of CD in patients with chronically abnormal liver tests of unexplained etiology is 4%, with no relation with the degree of liver steatosis. Screening should be done by testing for IgA and IgG antibodies and then evaluating by endoscopy and biopsy only patients positive for both.

Retinol-binding protein 4: A new marker of virus-induced steatosis in patients infected with hepatitis c virus genotype 1†

Retinol‐binding protein 4 (RBP4) is an adipocytokine associated with insulin resistance (IR). We tested serum levels of RBP4 to assess its link with steatosis in patients with genotype 1 chronic hepatitis C (CHC) or nonalcoholic fatty liver disease (NAFLD). Nondiabetic patients with CHC (n = 143) or NAFLD (n = 37) were evaluated by liver biopsy and anthropometric and metabolic measurements, including IR by the homeostasis model assessment. Biopsies were scored by Scheuer classification for CHC, and Kleiner for NAFLD. Steatosis was tested as a continuous variable and graded as absent‐mild <30%, or moderate‐severe ≥30%. Thirty nondiabetic, nonobese blood donors served as controls. RBP4 levels were measured by a human competitive enzyme‐linked immunosorbent assay kit (AdipoGen). Mean values of RBP4 were similar in NAFLD and CHC (35.3 ± 9.3 μg/L versus 36.8 ± 17.6; P = 0.47, respectively), and both were significantly higher than in controls (28.9 ± 12.1; P = 0.02 and P = 0.01, respectively). RBP4 was higher in CHC patients with steatosis than in NAFLD (42.1 ± 19.7 versus 35.2 ± 9.3; P = 0.04). By linear regression, RBP4 was independently linked to steatosis only (P = 0.008) in CHC, and to elevated body mass index (P = 0.01) and low grading (P = 0.04) in NAFLD. By linear regression, steatosis was independently linked to homeostasis model assessment score (P = 0.03) and high RBP4 (P = 0.003) in CHC. By logistic regression, RBP4 was the only variable independently associated with moderate‐severe steatosis in CHC (odds ratio, 1.045; 95% confidence interval, 1.020 to 1.070; P = 0.0004), whereas waist circumference was associated with moderate‐severe steatosis in NAFLD (odds ratio, 1.095; 95% confidence interval, 1.007 to 1.192; P = 0.03). Conclusion: In nondiabetic, nonobese patients with genotype 1 CHC, serum RBP4 levels might be the expression of a virus‐linked pathway to steatosis, largely unrelated to IR. (HEPATOLOGY 2008.)

Liver disease in chelated transfusion-dependent thalassemics: the role of iron overload and chronic hepatitis C

This study shows that hepatitis C virus infection is the main risk factor for liver fibrosis in chelated transfusion-dependent thalassemic patients. See related perspective article on page 1121. Iron overload and hepatitis virus C infection cause liver fibrosis in thalassemics. In a monocentric retrospective analysis of liver disease in a cohort of 191 transfusion-dependent thalassemics, in 126 patients who had undergone liver biopsy (mean age 17.2 years; 58 hepatitis virus C-RNA positive and 68 hepatitis virus C-RNA negative) the liver iron concentration (median 2.4 mg/gr dry liver weight) was closely related to serum ferritin levels (R = 0.58; p<0.0001). Male gender (OR 4.12) and serum hepatitis virus C-RNA positivity (OR 11.04) were independent risk factors for advanced liver fibrosis. The majority of hepatitis virus C-RNA negative patients with low iron load did not develop liver fibrosis, while hepatitis virus C-RNA positive patients infected with genotype 1 or 4 and iron overload more frequently developed advanced fibrosis. Hepatitis virus C infection is the main risk factor for liver fibrosis in transfusion-dependent thalassemics. Adequate chelation therapy usually prevents the development of liver fibrosis in thalassemics free of hepatitis virus C-infection and reduces the risk of developing severe fibrosis in thalassemics with chronic hepatitis C.

Intrahepatic IgG/IgM plasma cells ratio helps in classifying autoimmune liver diseases

BACKGROUND/AIM Plasma cells infiltrate in the liver is a prototype lesion of autoimmune liver diseases. The possible role of plasma cells isotyping (IgM and IgG) in the liver in the diagnostic definition of autoimmune liver disease, and particularly in variant syndromes such as autoimmune cholangitis and the primary biliary cirrhosis/autoimmune hepatitis overlap syndrome, is less defined. METHODS We analysed the clinical, serological and histological features of 83 patients with autoimmune liver disease (40 primary biliary cirrhosis, 20 autoimmune hepatitis, 13 primary sclerosing cholangitis, 4 autoimmune cholangitis and 6 overlap syndrome) compared to 34 patients with chronic hepatitis C and evaluated the expression of IgM and IgG plasma cells in their liver by immunostaining. RESULTS By Spearmans correlation, the mean-counts of IgM plasma cells in portal tracts were significantly correlated with female gender, serum alkaline phosphatase, gamma-glutamyl transferase and IgM values, positivity for anti-mitochondrial antibody-M2 and, on liver biopsy, with bile duct changes, orcein-positive granules and granulomas. Whereas IgG plasma cells resulted more correlated with alanine aminotransferase levels. IgG/IgM ratio lower than 1 was found no only in primary biliary cirrhosis but also in all patients with autoimmune cholangitis. Conversely, all patients with overlap syndrome showed IgG/IgM ratio higher than 1. CONCLUSION Immunostaining for IgM and IgG plasma cells on liver tissue can be a valuable parameter for better diagnosis of autoimmune liver disease and also for variant or mixed syndromes.

Serum BLyS/BAFF predicts the outcome of acute hepatitis C virus infection

Summary.  B‐lymphocyte stimulator/B activating factor (BLyS/BAFF) is a tumour necrosis factor‐family cytokine that plays a key role in generating and maintaining the mature B‐cell pool. BLyS/BAFF expression by macrophages is stimulated by interferon‐γ and interleukin‐10, and its serum levels are increased in chronic hepatitis C (CHC). The aim of this study was to assess serum levels of BLyS/BAFF in patients with acute hepatitis C (AHC) and correlate them with disease outcome. We studied 28 patients with AHC (14 males, mean age 59.3 ± 15 years), followed for at least 7 months since onset, comparing them with 86 CHC patients and 25 healthy blood donors (HBD). BLyS/BAFF levels were assessed at baseline (within 4 weeks of onset) and during follow‐up. BLyS/BAFF median levels were significantly higher in AHC (1485 pg/mL) than in CHC (1058 pg/mL) and in HBD (980 pg/mL) (P < 0.001). BLyS/BAFF levels were higher in AHC patients evolving to chronicity (1980 pg/mL) than in those with a self‐limited course (1200 pg/mL), (P = 0.02). By logistic regression analysis, higher BLyS/BAFF levels were independently associated with persistence of HCV infection (OR 29.7; 95% CI: 1.73–508.20). High serum levels of BLyS/BAFF at onset of AHC can predict its evolution to chronic infection.

Oral mucosa of coeliac disease patients produces antiendomysial and antitransglutaminase antibodies: the diagnostic usefulness of an in vitro culture system.

Background  Antiendomysial (EmA) and antitransglutaminase (anti‐tTG) antibodies are the most specific indirect marker of coeliac disease (CD). It is not known whether the oral mucosa of patients with CD is able to produce these antibodies or not.