Intrinsic factor antibody negative atrophic gastritis; is it different from pernicious anaemia.

Introduction: H. pylori gastritis and autoimmune gastritis are the two main types of chronic atrophic gastritis. Parietal cell antibody (PCA) and intrinsic factor antibody (IFA) are characteristic of autoimmune gastritis, of which IFA is more specific. Patients who are IFA negative are considered under the category of chronic atrophic gastritis. Aim: To differentiate IFA positive from IFA negative chronic atrophic gastritis. Methods: Fifty consecutive patients of biopsy proven chronic atrophic gastritis were included in this study. All patients underwent haematological and biochemical tests including serum LDH, vitamin B12 and fasting serum gastrin levels. PCA and IFA antibodies were tested in all patients. Multiple gastric biopsies from body and antrum of the stomach were taken and evaluated for presence of intestinal metaplasia, endocrine cell hyperplasia, carcinoid and H. pylori infection. Patients were grouped as group A (IFA positive) and group B (IFA negative). The mean laboratory values and histological parameters were compared between the two groups using appropriate statistical methods. Results: Eighteen patients were in group A (mean age 55.5±13 years, male: female = 16:2) and thirty-two in group B (mean age 49.7±13 years, male: female = 25:7). There was no statistically significant difference between median values of haemoglobin, MCV, LDH, Vitamin B12 and serum gastrin in both the groups. None of the histological parameters showed any significant difference. Conclusion: There was no statistically significant difference in haematological, biochemical and histological parameters in IFA positive and negative gastritis. These may be the spectrum of the same disease, where H. pylori may be responsible for initiating the process.

A retrospective clinico-pathological analysis of neuroendocrine tumors of the gastrointestinal tract.

Aim: Gastrointestinal tract is the commonest site for neuroendocrine tumors. Appendix, ileum and rectum were considered to be common sites for these tumors. However, there has been change in pattern of gastrointestinal neuroendocrine tumors over last few years. There is limited data available on epidemiology and patterns of these tumors in India. Methods: Analysis of 74 patients with gastrointestinal and pancreatic neuroendocrine tumors over a period of 7 years at a single center in Mumbai, India was done. Clinical details, surgical outcome with follow up and treatment were reviewed. All these patients were analyzed with special emphasis on the site of the tumor. Results: The results showed a male preponderance (ratio of 2.5:1) with a mean age of 53.01 ± 15.13 years. Of the 74 tumors, the commonest site was found to be stomach 22 (30.2%), followed by pancreas 17 (23.3%) and duodenum 14 (18.9%). Only 3 (4.1%) patients presented with carcinoid syndrome. The disease was localized in 46 (62.2%), regional spread was seen in 14 (18.9%) and distant spread in 14 (18.9%). Majority of gastric and duodenal tumors had localized disease while pancreatic NETs led to most of the cases with distant disease. Conclusion: This analysis showed that gastrointestinal and pancreatic neuroendocrine tumors are not rare. Pattern of these tumors has definitely changed over last few years. Stomach was found to be commonest site for gastrointestinal neuroendocrine tumors followed by pancreas and duodenum.

Utilization of antihepatocyte clone OCH1E5 (Hep Par 1) in histological evaluation of liver tumors.

Diagnosis of hepatocellular carcinoma (HCC) is not always easy on simple hematoxylin and eosin (H&E) stain. The diagnostic problems arise when tumor shows pseudoglandular, pleomorphic or clear cell differentiation. Various tumors markers have been described with varying sensitivity and specificity. Monoclonal antibody Hep Par 1 (OCH1E5) which is specific for hepatocytes offers great help in separation of these tumors. The aim of the present study was to determine utility of Hep Par 1 (OCH1E5) in differentiating HCC from metastatic tumors and cholangiocarcinoma. Total of 62 cases of liver tumors obtained from biopsies, resected or autopsy specimens were included in the study. Slides having representative sections were subjected to immunohistochemistry with monoclonal antibody Hep Par 1 (Dako Corp) using avidin biotin technique with primary antibody dilution of 1:40. Adjacent nontumorous hepatocytes were taken as positive control. Slides were examined by experienced pathologist without any information of clinical or H&E diagnosis. Cases were considered positive for Hep Par 1 if tumor cells showed cytoplasmic brown colored granules. The intensity and distribution (diffuse/ focal) of immunoreactivity was noted. Subsequently immunohistochemistry results were correlated with histology and clinical diagnosis. Hep Par 1 antibody was positive in 26 (42 %) and negative in 36 (58 %) liver tumors. On correlating with H&E sections, out of 26 positive cases, 25 (89.2%) were HCC and one was the case of metastasis of mucin secreting adenocarcinoma. From 36 tumors with negative staining 3 were cases of HCC, 27 metastatic adenocarcinomas and 6 cholangiocarcinomas. Only one case of liver metastasis of mucin secreting adenocarcinoma showed positivity. None of the cases of cholangiocarcinoma showed positivity for Hep Par 1. The three HCCs which did not take up staining for Hep Par 1 were 2 cases of moderately differentiated HCC having pseudoglandular pattern and a case of well differentiated HCC with trabecular arrangement. In 11(44%) cases staining was diffuse while in 14 (56%) it was focal but intense. Hep Par 1 is a useful marker in differentiating HCC from metastaic tumors and cholangiocarcinoma with sensitivity and specificity of 89 % and 97 % respectively and positive predictive value of 96 %. However one should be aware of limitations of immunohistochemistry.

Tissue polymerase chain reaction in diagnosis of intestinal tuberculosis and Crohn's disease.

AIMS AND OBJECTIVES: 1) To evaluate the utility of PCR in differentiating intestinal tuberculosis from Crohn's disease. 2) To compare histological features of tuberculosis and Crohn's disease. MATERIAL AND METHODS: A total of 60 cases of diagnosed intestinal tuberculosis and 20 Crohn's disease were included in the study. Clinical data, radiological and endoscopic findings and response to treatment were taken into consideration. Endoscopic biopsies from affected areas were subjected to histopathological examination and polymerase chain reaction (PCR) assay. Acid fast staining on tissue and culture was done whenever possible. RESULTS: Clinical symptoms, radiological and endoscopic findings were almost similar between intestinal tuberculosis and Crohn's disease. PCR was positive in 21.6% cases of intestinal tuberculosis and 5% Crohn's disease. Nine out of 42 cases (21.4%) without granuloma were also positive by PCR. There was no statistical difference for PCR positivity between patients with intestinal tuberculosis with or without granuloma on histology and also between caseating and non-caseating granuloma. CONCLUSION: PCR assay showed high specificity (95%) for the diagnosis of intestinal tuberculosis hence may be valuable method to differentiate intestinal tuberculosis from Crohn's disease.

Gastric antral vascular ectasia (GAVE) syndrome.

Gastric antral vascular ectasia (GAVE) syndrome is an uncommon cause of chronic gastrointestinal bleeding and iron deficiency anaemia. We describe two cases of GAVE, one pernicious anaemia related and the other portal hypertension related. In both the cases, progressive mucosal changes, which lead to development of GAVE, were documented. Those changes were progression of multiple antral erythematous spots into linear configuration and lastly to watermelon stomach. One of the cases was treated with tranexamic acid with good response.

Management of large hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. There is increasing incidence of HCC in India. More than 70% of HCC are not suitable for curative treatment. Majority of the HCCs are large when diagnosed all over the world. There is no standard treatment for large HCCs. Different palliative treatments like arterial embolization/chemoembolization, intraarterial lipoidol chemotherapy, hormonal compounds like tamoxifene, octerotide systemic chemotherapy, immuno therapy with interferon, internal radiation with 131I or 99Yttrium. Arterial chemoembolization is the treatment of choice with proved efficacy in selected group of patients. The newer modalities and strategies need to be tried in controlled randomized trials.

HLA genotyping in type-I autoimmune hepatitis in Western India.

OBJECTIVES: To analyze association of different HLA genotypes for predisposition to type-I autoimmune hepatitis in Western India. METHODS: This study was undertaken on patients of type-I autoimmune hepatitis (defined by international criteria by IAHG, 1999). HLA genotyping for class I and II was done in 20 patients of autoimmune hepatitis and 100 healthy controls. Statistics were done using Halden's modification of Woolfs formula. RESULT: Significant association of autoimmune hepatitis was found amongst class I antigens--HLA B27 [20 vs. 0 %] & HLA cw4 [40 vs. 15 %] and amongst class II antigens--DRBI*01XX [25 vs. 2%], DRB1*14XX [30 vs. 12%], DRB1*15XX [40 vs. 25%] and DRB1*07XX [20 vs. 9 %] at DRB1 locus. Stronger association was found with HLA B27, cw4 & HLA DRB1 *01XX. CONCLUSION: Our data indicate that predisposition to autoimmune hepatitis is different in Indian patients and not associated with HLA DRB1*03XX or *04XX, as seen in Western world.

Hepatic sarcoidosis.

We describe six cases of hepatic sarcoidosis. Clinical presentation was with weight loss, hepatomegaly and abnormal liver function tests. In addition there was fever, itching, splenomegaly and abdominal lymphadenopathy in some. CT scan revealed mediastinal lymphadenopathy in all. Liver biopsy showed noncaseating epithelioid granulomas. Serum angiotensin converting enzyme was elevated in four cases. All patients had received anti-tuberculosis treatment with clinical diagnosis of hepatic tuberculosis. None of them improved, while some showed clinical deterioration. All patients responded to corticosteroids with disappearance of symptoms and normalization of liver function tests.

Profile of hepatitis B e antigen-negative chronic hepatitis B.

BACKGROUND: Although chronic hepatitis B occurs in hepatitis B e antigen (HBeAg)-negative patients, its prevalence and clinical significance are not known. AIM: To determine the prevalence and profile of HBeAg-negative chronic hepatitis B virus (HBV) infection. METHODS: A retrospective analysis of 363 consecutive patients (mean age 36 y; 288 men) with chronic HBV infection was performed. All patients were HBsAg-positive. Tests for liver profile, HBeAg and anti-HBe antibody were performed in all patients. Serum HBV DNA was tested using branched DNA assay in 245 patients. The patients were classified into three groups: no cirrhosis with normal ALT levels, no cirrhosis with elevated ALT levels, and clinical or histological evidence of cirrhosis. RESULTS: Of 363 patients, 141 (39%) were HBeAg-positive and 222 (61%) HBeAg-negative. Of HBeAg-negative patients, 120 (54%) had normal ALT, 45 (20%) had elevated ALT and 57 (26%) had evidence of cirrhosis; corresponding figures in the HBeAg-positive patients were 40 (28%), 66 (47%) and 35 (25%). HBV DNA was positive in 53 of 131 (40%) HBeAg-negative patients tested; of these 53 patients, 9 (17%) had normal ALT, 20 (38%) had elevated ALT and 24 (45%) had cirrhosis. Thus, 72% of HBeAg-positive and 46% of HBeAg-negative patients had elevated ALT and/or cirrhosis. Among the latter group, 83% of HBV DNA-positive patients had elevated ALT and/or cirrhosis. Overall, 18% of HBsAg-positive patients had HBeAg-negative, HBV DNA-positive liver disease. CONCLUSION: HBeAg-negative chronic hepatitis B is not an uncommon and benign entity and chronic liver disease develops in a significant proportion of such patients.

Role of autoimmunity in nonviral chronic liver disease.

OBJECTIVE: To evaluate the prevalence and clinical profile of autoimmune hepatitis (AIH) in patients with chronic liver disease. METHODS: Four hundred and thirty five consecutive patient with chronic liver disease seen in our department from January 1997 to December 1998 were studied with detailed history and clinical examination. All the patients underwent liver function tests, ultrasonography, isotope liver scanning, viral markers, autoimmune markers ANA, ASMA, LKM1 and AMA (by immunofluorescence technique) and liver histology whenever permissible. Appropriate work up for Wilson's disease was done whenever suspected clinically. Diagnosis of autoimmune hepatitis was made by the composite scoring system by international autoimmune hepatitis group. Twenty out of the 435 patients met the criteria of definite autoimmune hepatitis and seven patient had probable autoimmune hepatitis. Forty out of 408 patients showed markers of autoimmunity positive but did not qualify diagnosis of AIH on composite scores. RESULTS: Demographic profile of 27 patients with autoimmune hepatitis was as follows; male:female ratio 1:8, mean age 39.8 +/- 13 years (Range 4-65 years); mode of presentation as cirrhosis 11/27 (40.7%), chronic hepatitis 12/27 (44.4%) and acute hepatitis 4/27 (14.8%). Elevated serum bilirubin levels were seen in 12 (44.4%) patients while mean serum aminotransferases levels were 249 +/- 343 and 262 +/- 418 respectively. Other disease associations seen were as follows: diabetes in 4 (14.8%), rheumatoid arthritis in 3 (11%), hypothyroidism in 2 (7.4%) and ulcerative colitis in 1 (3.7%). The pattern of autoimmune markers was ANA +ve 23/27 (85%) (+ve titres of ANA > 1:80 in adults and 1:20 in children), ASMA +ve in 16/27 (59.2%) (+ve titres of ASMA > 1:40) and LKM1 in 3 patients. AMA in tires less than 1:80 was found in 3 patients. Liver histology changes seen were lymphoplasmacytic infiltrates (100%), bridging necrosis (93%), liver cell rossetting (80%) and fibrosis with or without cirrhosis (50%). CONCLUSION: Autoimmune liver disease is not uncommon in India and should be suspected in all patients with chronic liver disease, especially in non-viral, non-alcoholic, female patients. The diagnosis of AIH should however be made on the composite scoring system given by international group and not only on the presence or absence of autoimmune markers.

Nonalcoholic steatohepatitis: clinicopathological profile.

AIMS: To evaluate clinicopathological spectrum of nonalcoholic steatohepatitis (NASH) METHODOLOGY: Total 210 patients with chronic liver disease were evaluated. Detailed history has taken with clinical examination, laboratory investigations, radiological findings and liver biopsy whenever possible. RESULTS: From 210 patients of chronic liver disease, 13 (6.19%) were diagnosed to have NASH (M:F = 9:4, age range 37-72 years, mean age 55.4 +/- 9 years). Of 13 patients, four were referred for asymptomatic enzyme elevation, nine had right hypochondriac pain. Risk factors were diabetes in four cases, obesity four, steroid treatment two and hyperlipidemia in three cases. Laboratory investigations showed abnormal liver enzymes in all the cases. Ultrasonography and CT scan was helpful in predicting fatty liver. Liver biopsy showed steatosis with inflammation in all, fibrosis in two and cirrhosis in one patient. CONCLUSION: NASH is an important form of chronic liver disease, and is characterised by hepatomegaly, elevated liver enzymes. It is essential to diagnose this condition due to its progression to liver fibrosis and cirrhosis in some patients.

Spectrum of liver diseases in HIV infection.

BACKGROUND: Most earlier reports on the spectrum of liver diseases in HIV-infected individuals originated from the West. OBJECTIVE: To study the spectrum of liver diseases in HIV-infected individuals. METHODS: Seventy four consecutive HIV-positive patients (57 men; age range 23-75 years, mean 34) were studied prospectively with clinical evaluation, liver function tests, ultrasonography, radioisotope liver scan, markers of hepatitis B (HBV) and C (HCV) viruses, and liver histology whenever necessary. RESULTS: Thirty four patients (45%) were chronic alcoholics. Mean (SD) absolute lymphocyte count was 2521 (1271)/mm3; count < 2000/ mm3 was present in 20 patients. Serum bilirubin, transaminases and alkaline phosphatase levels were elevated in 13%, 13% and 24% of patients, respectively. Ultrasonography detected an abscess in two patients (tuberculous-1, amebic-1). Evidence of exposure to HBV was present in 81% (HBsAg-12, hepatitis B core and/or surface antibody-48); anti-HCV antibody was positive in 29.7%. Five patients with liver tuberculosis (granuloma-4, abscess-1) had AFB either in liver tissue or lymph nodes. CONCLUSION: Chronic alcoholism, HBV and HCV infection, hepatic tuberculosis, and evidence of other liver disease were common in patients with HIV infection.

Histological spectrum of lymphoid follicles and aggregates in Helicobacter pylori gastritis.

Seventy three patients of non ulcer dyspepsia underwent upper gastrointestinal endoscopy with biopsy from antrum and body of stomach. The tissue was stained with hematoxylin eosin and warthin starry stain. The severity of gastritis was correlated with the presence of Helicobacter pylori and lymphoid follicles and aggregates. The incidence of chronic atrophic gastritis and Helicobacter pylori were found to be 97% and 64.1% respectively. Lymphoid follicles and aggregates were seen in 32.9% of chronic atrophic gastritis. Severity of gastritis with activity correlates with Helicobacter pylori colonisation and the presence of lymphoid follicles and aggregates. We have found that there is no difference between presence of lymphoid follicles and aggregates in Helicobacter pylori positive and negative gastritis. The development of lymphoid follicles probably represents an immune response to the colonisation of gastric mucosa by Helicobacter pylori.

Ultrasonic evaluation of portosystemic collateral circulation in portal hypertension.

The aim of the study was to evaluate portosystemic collateral circulation in relation to (1)individual etiological groups of portal hypertension., (2) Presence and size of esophageal varices, (3) esophageal sclerotherapy and (4) ascites. A prospective study of 101 patients of portal hypertension was carried out. Patients were divided into 4 etiological groups: Alcoholic cirrhosis (ALD) (38), Non-alcoholic cirrhosis (NALD) (35), non cirrhotic portal fibrosis (NCPF) (14) and extrahepatic portal vein obstruction (EHPVO) (14). Esophageal varices were assessed and graded endoscopically into 3 categories: no varix, small varices and large varices. Evaluation of portosystemic collateral circulation, other than esophageal varices was done ultrasonically. "Other" portosystemic collaterals (lienorenal, gastrorenal, dilated paraumbilical and umbilical veins, paraduodenal and gall bladdes varices) were seen in 26 out of 101 patients and more commonly in the non-cirrhotic groups (50%) [NCPF: 57.14%, EHPVO: 42.86%] than in the cirrhotic group (16.44%) [ALD: 13.5%, NALD: 20%]. Gall bladder varices were the only form of ectopic (extra esophagogastric) varices visualised with an overall incidence of 3.96%. Collateral shunts were seen more frequently in patients without varices (100%), than in patients with small varices (34.88%) or large varices (7.84%), and in patients having undergone esophageal sclerotherapy (57.14%). Collateral circulation did not contribute to the development of ascites. 37 patients with ascites did not have collateral shunts. We conclude portosystmic circulation plays a decompressive role in portal hypertension and prevents formation of esophageal varices or prevents them from increasing in size. It is seen more frequently in noncirrhotic patients and in those having undergone sclerotherapy and does not contribute to development of ascites.

Significance of radioisotope bone marrow uptake on 99m technetium sulphocolloid scan in portal hypertension.

A prospective study of 101 consecutive patients of portal hypertension was carried out to study the possible relationships between bone marrow activity on 99m technetium labelled sulphocolloid scan and severity of liver disease, etiology of portal hypertension and cirrhosis, as well as presence and extent of collateral circulation, including esophageal varices. The patients were divided into 4 etiological groups: alcoholic cirrhosis (ALD), (38) non-alcoholic cirrhosis (NALD) (35) non-cirrhotic portal fibrosis (NCPF) (14) and extrahepatic portal vein obstruction (EHPVO) (14). Patients of cirrhosis were categorised according to modified Child-Pugh's classification. Esophageal varices were graded endoscopically as (1) no varix (2) small varices (< 5mm) (3) large varices (> 5mm). All patients underwent radionuclide imaging using 99m Technetium labelled sulphocolloid and bone marrow activity was studied. Evaluation of portasystemic collaterals was done ultrasonically. We found that 16.6%, 44.6% and 72.72% patients with Child A, B and C cirrhosis respectively, had increased marrow activity (p < 0.05). There was no significant difference between marrow activity of patients with ALD (52.6%) and NALD (40%). None of the non-cirrhotic patients demonstrated bone marrow uptake of radioisotope. There was no significant difference between bone marrow uptake presence of lienorenal collaterals and presence or size of esophageal varices. We thus conclude the bone marrow activity on radioisotope scanning depends only on the severity of liver disease and does not vary a according to the etiology of cirrhosis, or presence and extent of portasystemic collaterals, including esophageal varices.

Acute pancreatitis in hepatitis A infection.

A 13 year old boy who was admitted for acute viral hepatitis due to hepatitis A virus developed acute pancreatitis which resolved completely with conservative treatment. Extensive evaluation did not reveal any other cause of pancreatitis and it was presumed that hepatitis A may result in acute pancreatitis.

Tuberculous abscess of the liver associated with HIV infection.

Tuberculosis is an AIDS-defining illness in HIV-seropositive patients. Though disseminated tuberculosis is common in HIV-seropositive patients, hepatic involvement in the form of abscess formation is rare. We report such a patient.