Publications (9)15.13 Total impact
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Article: Etiologic types of end-stage chronic liver disease in adults: analysis of prevalence and their temporal changes from a study on native liver explants.
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ABSTRACT: Whole native livers from orthotopic liver transplant (LT) recipients provide an ideal resource material for the proper identification and etiologic evaluation of end-stage liver diseases in these patients. This study determined the etiologic types of chronic liver disease (CLD) in adults of our geographic region receiving living donor LT and projected approximate estimates of their current prevalence and temporal changes in these in the general population. The final etiologic categorization of CLD in 372 adult LT recipients was made only after correlating the morphologic findings on explanted whole native livers with all pre-LT data and diagnosis. The final etiologic categorizations of end-stage CLD in the majority (88.4%) of explanted livers in our series were as follows: hepatitis virus related - 48.6% [hepatitis C virus (HCV) - 31.1%, hepatitis B virus (HBV) - 15.9%, HCV and HBV - 1.6%]; alcohol related - 23.1%; and NALD related - 16.7%. Of 84 cases clinically considered as cryptogenic cirrhosis, 57 and nine were finally categorized as nonalcoholic fatty liver disease (NAFLD) cirrhosis and noncirrhotic portal fibrosis, respectively. Hepatocellular carcinoma (HCC) was found in 20.7% of all livers, 81.8% of these tumors developing in HBV-related and/or HCV-related CLD and 9.1% each in alcohol-related and NAFLD-related CLD. The etiology of end-stage CLD in adults of our region has changed over time. HCV, more than HBV, is now the major cause of both CLD and HCC; alcohol-related CLD has increased significantly and several cases of cirrhosis clinically considered as cryptogenic, some of them with HCC, evolve from NAFLD. A proportion of cryptogenic cirrhosis cases that require LT are constituted by the noncirrhotic disease noncirrhotic portal fibrosis.European journal of gastroenterology & hepatology 06/2012; 24(10):1199-208. · 1.66 Impact Factor -
Article: Hepatocellular carcinoma in nonalcoholic fatty liver cirrhosis and alcoholic cirrhosis: risk factor analysis in liver transplant recipients.
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ABSTRACT: Cirrhosis and hepatocellular carcinoma (HCC) evolving from nonalcoholic fatty liver disease (NAFLD) are being increasingly documented. However, clinicopathologic studies to support this are inadequate. Also, the pathogenesis of HCC in alcoholic cirrhosis (ALC) in which the pathologic and clinical features are very similar to those of nonalcoholic fatty liver cirrhosis (NAFLC) is unknown. A clinicomorphologic study on 47 confirmed NAFLC cases, with HCC in eight of them and 75 confirmed ALC cases with HCC in five from among orthotopic liver transplant recipients, was performed. Patients with NAFLC were older by about 9 years than those with ALC. HCC in NAFLC occurred almost exclusively in men. The presence of NAFLD risk factors, obesity and diabetes both together, was significantly higher in NAFLC than in ALC cases and within the latter, in those with HCC than in those without HCC, whereas in the NAFLC group, this was no different between those with and without the tumor. The steatohepatitic variant of HCC, consistently accompanied by similar histologic changes in the nontumor part of liver, which is a histologic hallmark of association with NAFLC risk factors, was much more frequent in the NAFLC group compared with the ALC group. Hepatic alterations induced by risk factors of NAFLD not only have cirrhogenic but also, very likely, a carcinogenic effect. The incidence of HCC in NAFLC seems higher than in ALC. These findings and their bases need to be established by further studies.European journal of gastroenterology & hepatology 04/2012; 24(7):840-8. · 1.66 Impact Factor -
Article: Bile duct changes in different etiologic types of end-stage chronic liver disease: a study on native explant livers.
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ABSTRACT: Bile duct changes in the form of intraepithelial neoplasia or dysplasia have been well studied in chronic biliary tract diseases. It is important to analyse the morphologic spectrum of bile duct changes in non-biliary diseases as a link has been reported between intrahepatic cholangiocarcinoma and chronic liver disease associated with viral hepatitis, metabolic syndromes and with alcohol abuse. The authors retrospectively reviewed liver explants of alcoholic liver disease (ALD)-, hepatitis C virus- and non-alcoholic fatty liver disease-related end-stage liver diseases to analyse morphologic changes in large intrahepatic bile ducts. Diagnostic criteria of biliary intraepithelial lesions at end-stage disease are discussed. Majority of explants exhibited reactive changes. Normal cuboidal epithelium of septal bile ducts was observed in minority of cases. Low-grade biliary intraepithelial neoplastic lesions were identified in all cases with variable frequency. None of the cases were associated with cholangiocarcinoma. Nuclear hyperchromasia, cellular polarity and presence o inflammation were considered as differentiating points between reactive and neoplastic lesions. At end stage of liver disease, large septal bile ducts rarely show normal morphology. Presence of low-grade biliary dysplasia at end stage signifies its frequent occurrence probably in response to alcohol/viral/metabolic syndrome-related injury. ADDITION TO LITERATURE: Observational analysis of large bile ducts in non-biliary diseases of varied aetiology has not been discussed from this part of world where incidence of cholangiocarcinoma is low. Identifying these lesions correctly is important. The frequency of these lesions is not uncommon especially at the end-stage liver disease.Journal of clinical pathology 12/2011; 65(4):348-51. · 2.43 Impact Factor -
Article: Non-cirrhotic portal fibrosis: one disease with many names? An analysis from morphological study of native explant livers with end stage chronic liver disease.
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ABSTRACT: A group of non-cirrhotic chronic liver diseases, all with sustained portal hypertension and clinically mistaken as cirrhosis, have been described under various names, apparently because of differences in pathological features. The pathogenesis is uncertain and they were believed to have a good prognosis until it was recently shown, from study of explant livers, that they had progressed to end stage disease, needing liver transplantation. To describe detailed morphological features of such end stage non-cirrhotic disease and examine whether the diseases bearing various names are different or represent variable morphological expressions of one entity. Morphological features of 10 native explant livers from patients with pre-transplant diagnosis of end stage cirrhosis but finally categorised as non-cirrhotic portal fibrosis were analysed along with the relevant clinical information. Besides absence of criteria for cirrhosis, variable grades of obliterative changes in portal vein branches and portal fibrosis were consistently seen in all livers. Fibrous intimal thickening with luminal compromise in some medium and large sized portal veins was randomly distributed but appeared characteristic of this disease, very likely representing organised mural thrombi. Areas of closely placed nodular hyperplastic parenchyma separated by compressed hepatocytes, megasinusoids and peliotic changes were seen only in a proportion of cases. Non-cirrhotic portal fibrosis is a justifiable name for this disease that can progress to end stage liver disease. It represents a single entity that has been considered as different diseases and given various names on the basis of the dominant element in its heterogeneous morphological manifestation.Journal of clinical pathology 07/2011; 64(7):592-8. · 2.43 Impact Factor -
Article: Non-cirrhotic portal fibrosis related end stage liver disease in adults: evaluation from a study on living donor liver transplant recipients.
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ABSTRACT: BACKGROUND: That non-cirrhotic portal fibrosis (NCPF) can lead to end stage chronic liver disease (CLD) has been convincingly demonstrated only recently after the study of explant livers from clinically cirrhosis cases. AIMS: This study attempted to determine the frequency of NCPF among adults transplanted for end stage CLD and to identify parameters for a pre-transplant diagnosis of NCPF. METHODS: Several parameters were analyzed in three categories of cases: pure NCPF (n = 10), overlap NCPF (n = 10), and NAFLD cirrhosis controls (n = 44). Morphologic features of NCPF were looked for in explant livers of all these. RESULTS: Explant livers in the pure NCPF group were non-cirrhotic and showed histologic features of NCPF. These features were also present in all cases of overlap NCPF in the background of established cirrhosis of other etiologies but absent in the NAFLD cirrhosis controls. Values of seven objective and two subjective parameters showed significant differences between pure NCPF and NAFLD control groups. Compared to NAFLD controls, the model for end stage liver disease (MELD) score, body mass index (BMI), bilirubin, albumin, aspartate amino transferase (AST), and international normalized ratio (INR) were significantly less, whereas variceal grade was higher in the pure NCPF group. CONCLUSIONS: The study concludes that in our population, NCPF constitutes about 5% of the subset of end stage CLD considered eligible for liver transplantation (LT), presenting mostly as cryptogenic cirrhosis (CC). A diagnosis of NCPF should be considered when patients presumed to have cryptogenic or other cirrhosis become eligible for LT even in the presence of relatively well-preserved liver function and low MELD scores. End stage CLD manifests at earlier age, when cirrhosis of another etiology supervenes on pre-existent NCPF.Hepatology International 01/2011; · 2.64 Impact Factor -
Article: Hepatocellular carcinoma arising in association with von-Meyenburg's complexes: an incidental finding or precursor lesions? A clinicopatholigic study of 4 cases.
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ABSTRACT: Biliary hamartomas or von-Meyenburg complexes form part of a spectrum of ductal plate malformation that includes polycystic liver disease, congenital hepatic fibrosis, and Caroli disease. These lesions are known to have neoplastic transformation. Development of intrahepatic cholangiocarcinoma is well described in these complexes. Rarely, hepatocellular carcinomas (HCCs) have been seen in association with bile duct hamartomas, however; it is not clear whether development of HCC is an epiphenomenon unrelated to the precursor lesion or biliary hamartomas may progress to liver cancers. We herein report 4 interesting cases of hepatitis C virus-, alcohol-, and nonalcoholic fatty liver disease-associated end-stage liver disease with coexisting HCC and multiple large von-Meyenburg complexes.Annals of diagnostic pathology 10/2010; 14(5):317-20. -
Article: End-stage nonalcoholic fatty liver disease: evaluation of pathomorphologic features and relationship to cryptogenic cirrhosis from study of explant livers in a living donor liver transplant program.
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ABSTRACT: In a proportion of liver cirrhosis, the etiology continues to remain elusive. It is uncertain whether and to what extent cirrhosis evolving from nonalcoholic fatty liver disease contributes to this group of cryptogenic cirrhosis because the clinicopathologic features of nonalcoholic fatty liver disease cirrhosis are largely unknown. We explored these facets by examining the explant livers and clinical data in living donor liver transplant recipients. Among 103 adult liver transplant recipients with different types of chronic liver disease, 30 had a pre-liver transplant diagnosis of cryptogenic cirrhosis. A final categorization of the native liver disease was attempted in these cases on the basis of detail pathomorphological findings in adequately sampled explant liver correlated with careful review of pre-liver transplant clinical data. Of the 30 cryptogenic cirrhosis cases, 19 (63.3%) finally labeled as nonalcoholic fatty liver disease cirrhosis showed histologic features in several respects different from those reported for the early and established phases of nonalcoholic fatty liver disease. Steatosis was infrequent and focal or even absent, whereas variable grades of Mallory hyaline and inflammation were consistently present. Ductular proliferation and hydropic change of hepatocytes were also frequent. Only 9 (47%) of the 19 cases had nonalcoholic fatty liver disease associated risk factors like diabetes and obesity. It was concluded that appreciation of quantitative and qualitative differences in hepatic morphology between the cirrhotic and the early/established stage of nonalcoholic fatty liver disease will help in making a correct diagnosis of nonalcoholic fatty liver disease cirrhosis in the proper clinical setting. When appropriate criteria are used, nonalcoholic fatty liver disease appears to account for close to two thirds of cases currently labeled as cryptogenic cirrhosis.Human pathology 11/2009; 41(3):425-30. · 3.03 Impact Factor -
Article: CD99 expression in hepatocellular carcinoma: an immunohistochemical study in the fibrolamellar and common variant of the tumour.
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ABSTRACT: Histological diagnosis of hepatocellular carcinoma (HCC) in biopsy and fine needle aspiration material can pose difficult problems. This is particularly so in the fibrolamellar variant of the tumour (FLHCC) which has biological features distinctly different from those of common HCC (CHCC). Expression of CD99, a membrane localised glycoprotein which is known to be a feature of diagnostic importance in several malignant neoplasms was looked for in immunohistochemical preparation of tissue material from 18 cases of HCC, 6 FLHCC and 12 CHCC accessioned in our department. Positive staining of variable degrees and intesity was observed in all 18 cases. Non-neoplastic hepatocytes, normal or others and all the 18 other cases of non-HCC cancers outside the liver or metastatic within the liver were negative. In some cases, mostly of FLHCC, a definitive diagnosis could be suggested on the basis of CD99 positivity. It is concluded that in cases of HCC, particularly in small specimens and in FLHCC, immunostaining for CD99 will be of significant help in diagnosis.Indian Journal of Pathology and Microbiology 11/2003; 46(4):625-9. · 0.68 Impact Factor -
Article: Spectrum of histological features in non-alcoholic fatty liver disease.
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ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) has become an Important entity globally, including in India and other Asian countries. Morphological evaluation of a liver biopsy is necessary for the diagnosis, staging and possibly management of this disease. However, the spectrum of changes in the liver, their evolution, Interrelationships and implications are incompletely understood. We aimed to study the spectrum of histological abnormalities in NAFLD. The study material was drawn from a pool of 80 liver biopsies diagnosed in our laboratory as NAFLD, 67 retrieved retrospectively from our records and 13 obtained prospectively with complete clinical data. After comprehensive histological assessment, a detailed analysis was done of 32 of those categorized as definitive NAFLD on the basis of a dependable history of no alcohol Intake and seronegativity for hepatitis virus B and C Infections. Fatty change was preferentially seen in acinar zones 2 and 3, more so in the former. Steatotic cells varied in size; some large ones were non-spherical. Steatosis alone was present in more than a quarter of the cases and steatosis along with inflammation was present in half. The magnitude of steatosis correlated with inflammation, while both these seemed to correlate with hepatocyte Injury and fibrosis. A proportion of patients with NAFLD show only hepatic steatosis. An Increasing grade of steatosis is associated with greater Inflammation, hepatocyte injury and acinar fibrosis. Preferential involvement of acinar zone 2 by steatosis, the morphology of the steatotic cells, and nature and location of inflammation are important in the diagnosis of NAFLD and its differentiation from other causes of fatty liver.The National medical journal of India 20(6):282-7. · 0.60 Impact Factor
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2003–2009
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Sir Ganga Ram Hospital
New Delhi, NCT, India
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