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.

Portopulmonary hypertension in a case of non-cirrhotic portal fibrosis.

Portopulmonary hypertension (PPHT) is the unusual association of portal hypertension (HT) with pulmonary HT. We report a case of noncirrhotic portal fibrosis (NCPF) leading to PPHT which is exceedingly rare with only very few cases reported in the literature. This is an autopsy report of a 30 years old man, a known case of portal HT who died suddenly due to a syncopal attack. Autopsy revealed massive pulmonary thromobembolism with pulmonary HT. Liver showed changes of NCPF. The rarity of NCPF causing PPHT prompted this case report.

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.

Gastric lipoma presenting with dyspepsia.

Gastric lipoma is one of the rare benign gastric tumors. Its preoperative diagnosis obviates the need of an extended gastrectomy. We report a case of gastric lipoma who presented with symptoms of dyspepsia and was treated by surgical gastrectomy and tumour enucleation.

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.

Chronic liver disease in diabetes mellitus.

BACKGROUND: The association of diabetes with liver disease is well known. AIM: To study the spectrum of liver disease in patients of chronic liver disease (CLD) with diabetics and compare it with age and sex matched patients of CLD without diabetes. METHODS: We studied the patients of chronic liver disease presenting over a period of one year and their diagnosis were established by biochemical studies, imaging, endoscopic examination and liver biopsy when required. They were evaluated for the aetiological causes of liver diseases. RESULTS: A total of 53 patients of CLD with diabetes, M:F 43:8, with an age range of 35-70 years, median age of 51 years were taken as study group. Demographic picture of control group was n = 115, with M:F = 100: 15, age range of 37-68 years, with a median age of 52 years. Spectrum of liver disease in diabetic group were as follows: 56.6% cirrhosis, 15.1% chronic hepatitis, 22.6% fatty liver, 5.7% cirrhosis + hepatocellular carcinoma (HCC). The spectrum in control group was as follows, cirrhosis 46.1%, chronic hepatitis 36.5%, fatty liver 14.8%, cirrhosis and HCC 2.6%. Aetiology of chronic liver disease in diabetic group was as follows: Non-alcoholic steatohepatitis (NASH) with cirrhosis 11.3%, NASH 18.9%, cryptogenic cirrhosis 22.6%, hepatitis B virus (HBV) 17%, hepatitis C virus (HCV) 13.2%, alcohol 17%. Aetiology of chronic liver disease in nondiabetic group was as follows: NASH with cirrhosis 1.7%, NASH 13.0%, cryptogenic cirrhosis 7.8%, HBV 30.43%, HCV 13%, alcohol 29.6% and autoimmune in 4.3%. Incidence of NASH with cirrhosis and cryptogenic cirrhosis were found to be statistically significantly high in diabetic group. Incidence of diabetes in cryptogenic cirrhosis was found to be 57% versus 30% in noncryptogenic cirrhosis. CONCLUSION: NASH, NASH with cirrhosis and cryptogenic cirrhosis are the major causes of chronic liver disease in patients with diabetes mellitus. Alcohol and viral causes are found to be important aetiologies in nondiabetic control group. Diabetes mellitus is an important risk factor for chronic liver disease and progression of NASH to cirrhosis, which may present as cryptogenic cirrhosis.

Prevalence of hepatitis C genotypes in Indian patients and their clinical significance.

AIM: To study the significance of hepatitis C genotypes in relation to severity of liver disease, progression of liver disease and response to treatment. METHODS: Sixty one consecutive patients with hepatitis C infection were evaluated with detailed history, clinical examination, biochemical, imaging and virological profile, liver histology whenever feasible. Hepatitis C infection was confirmed with AntiHCV third generation ELISA assay. HCVRNA by PCR and HCV genotyping by direct sequencing. RESULTS: Demographic profile of patients was as M:F 36:25, mean age 46.3 +/- 13.6 years (range 10 to 70 years). Clinical presentations of these patients were as cirrhosis 23, cirrhosis with HCC 3, chronic hepatitis 22, acute hepatitis 4, asymptomatic with normal enzymes nine. Distribution of genotypes was as follows; 13/61 (21%) genotype I, 15/61 (25%) genotypes II and 33/61 (54%) genotype III. Cirrhosis was significantly common in genotype I (77%) when compared to genotype II and III (33%); p < 0.001. Mean time of presenting as cirrhosis was much faster in genotype I (8.7 +/- 6.7 years) as compared to other genotypes (type II 12.8 +/- 4.2 years and genotype III 15.8 +/- 6.9 years). Genotype distribution in CRF and renal transplant patient was genotype I 8/23 (35%), genotype II 5/23 (22%) and genotype III 10/23 (43%). Fourteen patients were treated with interferon and ribavarine combination for one year. Sustained response seen in 8/14 (57%). All these patients had genotype non 1. All the four patients with Genotype I were non-responders. CONCLUSION: Hepatitis C genotype III is common in India, Genotype I runs a more severe course, faster progression and non responders to interferon as compared with genotype II and III.

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.

Hepatocellular carcinoma in association with membranous obstruction of inferior vena cava.

We report a patient with hepatocellular carcinoma (HCC) with membranous obstruction of the inferior vena cava (IVC). He underwent balloon dilatation of the IVC with good results. The HCC was managed by chemoembolization followed by resection. At follow up of eleven months the patient is asymptomatic.

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.