Liver histology and HBV DNA levels in chronically HBV infected patients with persistently normal alanine aminotransferase.

BACKGROUND: Data on histological activity and HBV DNA levels in patients with chronic HBV infection and persistently normal alanine aminotransferase levels are sparse. We aimed to investigate the histological activity and HBV DNA levels in these patients. METHODS: There were 132 patients with HBeAg negative chronic HBV infection and persistently normal alanine aminotransferase levels that were included prospectively. Data were dichotomized according to the median levels. Associations of histology with HBV DNA and other variables were assessed. RESULTS: A total of 80 patients were male. The median age was 36 years. The median baseline HBV DNA was 2.9Log10 IU/mL. There were 50 cases (38%) with a total score > or = 5, 53 cases (40.2%) had grade > or = 4 and 40 cases (30.3%) had stage > or = 2. A baseline HBV DNA <2000 IU/mL was seen in 24 cases (48%) of those with total score > or = 5, 28 cases (53%) of those with grade > or = 4 and 9 cases (22.5%) with stage > or = 2. Multivariate analysis of baseline HBV DNA above the median level significantly predicted the total score, grade and stage with an adjusted odds ratio of 5.43, 3.47, and 4.23, respectively when compared to below median values. A second liver biopsy was performed in 61 patients. The median time interval between the two biopsies was 40 months. Total scores of 23 cases (38%) progressed by > or = 2 scores and the HBV DNA of 18 cases (22.5%) increased by > or = 1 Log10 IU when compared to baseline values. CONCLUSION: HBeAg negative chronic HBV infection with persistently normal alanine aminotransferase is not a silent disease. Active liver disease may be seen in such patients with viral loads less than 2000 IU/mL.

Expression of EGFRvIII in thyroid carcinoma: immunohistochemical study by camel antibodies.

Patients with poor prognosis in thyroid cancers resistant to currently available therapeutic modalities are often in search of a new treatment. The epidermal growth factor receptor (EGFR) vIII, a ligand-independent, constitutively active, mutated form of EGFR has been shown to play a role in the pathogenesis of some cancers. Consequently, the immunohistochemical detection of EGFRvIII with novel camel antibodies, which are valuable for their ability to interact with less antigenic epitopes in contrast to the conventional antibodies, might be worthy in diagnostic techniques of thyroid neoplasms. EGFRvIII was evaluated on paraffin-embedded tissue specimens of 40 samples of follicular carcinomas, papillary carcinomas, medullary carcinomas, follicular adenomas, and goiter of the thyroid gland by immunohistochemistry. Positive immunostaining of neoplastic tissues with camel and rabbit polyclonal, as a control, were 81.3% and 39.1%, respectively. No goiter tissue was stained with either antibody preparation. Also, the results showed that the sensitivity of camel heavy chain antibodies (65%) is higher in contrast to conventional rabbit under the same conditions (39.1%). Considering the results of this study, exploiting the smaller heavy chain antibodies of camels against EGFRvIII seems promising in the diagnosis procedures of thyroid neoplasms.

Gluten sensitive enteropathy in patients with iron deficiency anemia of unknown origin.

AIM: To determine the prevalence of gluten sensitive enteropathy (GSE) in a large group of patients with iron deficiency anemia (IDA) of obscure origin. METHODS: In this cross-sectional study, patients with IDA of obscure origin were screened for GSE. Anti-endomysial antibody (EMA) and tissue transglutaminase antibody (tTG) levels were evaluated and duodenal biopsies were taken and scored according to the Marsh classification. The diagnosis of GSE was based on a positive serological test and abnormal duodenal histology. Gluten free diet (GFD) was advised for all the GSE patients. RESULTS: Of the 4120 IDA patients referred to our Hematology departments, 206 (95 male) patients were found to have IDA of obscure origin. Thirty out of 206 patients (14.6%) had GSE. The mean age of GSE patients was 34.6 +/- 17.03 (range 10-72 years). The female to male ratio was 1.3:1. Sixteen patients had Marsh 3, 12 had Marsh 2, and 2 had Marsh 1 lesions. The severity of anemia was in parallel with the severity of duodenal lesions. Twenty-two GSE patients (73.3%) had no gastrointestinal symptoms. Fourteen GSE patients who adhered to GFD without receiving iron supplementation agreed to undergo follow up visits. After 6 mo of GFD, their mean hemoglobin levels (Hb) increased from 9.9 +/- 1.6 to 12.8 +/- 1.0 g/dL (P < 0.01). Interestingly, in 6 out of 14 patients who had Marsh 1/2 lesions (e.g. no villous atrophy) on duodenal biopsy, mean Hb increased from 11.0 +/- 1.1 to 13.1 +/- 1.0 g/dL (P < 0.01) while they did not receive any iron supplementation. CONCLUSION: There is a high prevalence (e.g. 14.6%) of GSE in patients with IDA of obscure origin. Gluten free diet can improve anemia in GSE patients who have mild duodenal lesions without villous atrophy.

Immunohistochemical analysis of survivin expression in thyroid follicular adenoma and carcinoma.

Survivin is one of the 8 members of human inhibitor of apoptosis , which is differentially expressed in cancerous/transformed cells versus normal differentiated tissues. This retrospective study of thyroid histologic samples aimed to assess the clinical usefulness of survivin immunostaining for discrimination between follicular adenoma and carcinoma of thyroid. Immunohistochemical staining for survivin was performed on 41 lesions from patients who had undergone surgery for either follicular adenoma or carcinoma of thyroid. Survivin expression was significantly (P < 0.005) higher in the cases that received a diagnosis of carcinoma in comparison with follicular adenomas cases. Odds ratio of follicular carcinoma for survivin expression was 21.375 (95% CI: 3.283 to 139.177). Our results showed potential value of survivin in discrimination between follicular thyroid adenoma and follicular thyroid carcinoma. We conclude that survivin is a potential candidate for further investigation in the proper histologic diagnosis of thyroid cancers.

Noninvasive markers of liver fibrosis and inflammation in chronic hepatitis B-virus related liver disease.

BACKGROUND/AIMS: Noninvasive markers for predicting significant fibrosis and inflammation have not yet been validated in an unselected group of chronic hepatitis B virus (HBV) carriers. The aim of this study was to create noninvasive models to predict significant fibrosis and inflammation in chronic HBV carriers. METHODS: A total of 276 (229 HBeAg negative, 47 HBeAg positive) unselected consecutive treatment naïve patients chronically infected with HBV who attended our center over a 36-month period underwent liver biopsy. HBeAg negative patients were randomly divided into two cohorts: training group (N = 130) and validation group (N = 99). HBeAg positive patients were analyzed as a whole without separation. Thirteen parameters were analyzed separately in HBeAg negative and HBeAg positive patients to predict significant fibrosis (Ishak stage >or=3) and inflammation (Ishak grade >or=7). RESULTS: In HBeAg negative patients significant liver fibrosis was best predicted using the variables HBV DNA levels, alkaline phosphatase, albumin, and platelet counts with an area under ROC curve (AUC) of 0.91 for the training group and 0.85 for the validation group. Using the low cutoff probability of 4.72, significant fibrosis could be excluded with negative predictive value of 99% in the entire cohort, and liver biopsy would have been avoided in 52% of patients. The best model for predicting significant inflammation included the variables age, HBV DNA levels, AST, and albumin with an AUC of 0.93 in the training and 0.82 in the validation group. In HBeAg positive patients no factor could predict accurately stages of liver fibrosis, but the best factor for predicting significant inflammation was AST with an AUC of 0.87. CONCLUSIONS: Significant hepatic fibrosis and necroinflammation can reliably be predicted using routinely checked tests and HBV DNA levels.

Impact of immunosuppressive treatment on liver fibrosis in autoimmune hepatitis.

The impact of treatment on progression of fibrosis in autoimmune hepatitis (AIH) is unknown. We assessed the changes in liver fibrosis before and after treatment among these patients. Nineteen AIH patients who had paired liver biopsies were studied. Of these, seven had been treated with 6 months of cyclosporine A and the rest with 6 months of prednisolone for induction of remission. Thereafter all had been maintained on azathioprine. Biopsy specimens before and after treatment were reviewed by one pathologist and scored by the Ishak method. Mean fibrosis stages before and after treatment were compared. Also, factors predicting significant fibrosis (stage > or =3) and cirrhosis (stage > or =5) at presentation were assessed. Mean interval between biopsies was 3.38 years. Mean fibrosis stage decreased from 4.53 to 2.16 following treatment (P < 0.001). Mean decrement in inflammatory grade was 8 scores (range, 4-10) in patients in whom fibrosis improved, and 2 scores (range, 0-4) in patients in whom fibrosis did not decrease after treatment (P < 0.001). ALT-to-platelet ratio was the best predictor of significant fibrosis and also cirrhosis. Fibrosis commonly improves after immunosuppressive treatment in AIH. ALT-to-platelet ratio can predict accurately the presence of significant fibrosis and cirrhosis in AIH.

Reversibility of cirrhosis in chronic hepatitis B.

BACKGROUND & AIMS: Hepatic fibrosis and cirrhosis are the consequences of many types of chronic liver disease, and, at its final stage when liver nodule and scarring develop, they are generally considered to be irreversible. METHODS: Here we describe 3 patients with chronic hepatitis B with clinical, biochemical, and histologic evidence of cirrhosis. They underwent treatment with interferon-alpha or lamivudine and had follow-up liver biopsy while in clinical, biochemical, and virologic remission. Biopsy specimens were randomly coded in unpaired manner according to patient, and they were read independently by 2 pathologists using the modified hepatitis activity index (with a maximum stage of 6). The mean interval between biopsies was 5.5 years. RESULTS: The mean ALT level decreased from 113.7 to 28.3 U/L. The mean bilirubin level decreased from 2.4 to 0.9 mg/dL, and the mean prothrombin time decreased from 16.3 to 12.3 seconds. The mean Child-Pugh score decreased from 8 to 5. The mean fibrosis score decreased from 5.8 to 0.5 (P = 0.004), and the mean grading score decreased from 10.8 to 3.2 (P = 0.017). CONCLUSIONS: Cirrhosis due to chronic hepatitis B might be reversible in some patients who respond to antiviral therapy.

Adenocarcinoma of the colon associated with sarcoidosis.

Lymph node swelling in the setting of malignancy generally suggests metastasis of the primary tumor. Here, we describe a patient with adenocarcinoma of the colon with regional and systemic lymph node enlargement that resulted from sarcoid reaction, not metastasis. Interestingly, sarcoidosis regressed after treatment of colon cancer. The literature is reviewed and possible mechanisms are explained.