Cancer stem cells in hepatocellular carcinoma - an immuno- histochemical study with histopathological association.

Background & objectives: Cancer stem cells (CSCs) may be responsible for tumour recurrence and resistance to chemotherapy in hepatocellular carcinoma (HCC). This study was carried out to evaluate the association between histological parameters and liver CSCs (LCSC) in HCC, and to compare distribution of liver CSCs in HCC associated with and without hepatitis B virus (HBV) infection. Methods: Seventy nine tumours (49 surgical resections from 46 patients, and 30 from autopsy) were reviewed. Immunohistochemical staining for the LCSC marker EpCAM (epithelial cell adhesion molecule), liver progenitor cell (LPC) markers CK19 (cytokeratin 19) and neural cell adhesion molecule (NCAM) were performed and were associated with histological features of tumour behaviour. Results: Thirty three tumours (41.8%) showed positive staining for EpCAM. CK19 and NCAM expression were seen in 26 (32.9%) and four (5.1%) tumours, respectively. The expression of EpCAM and CK19 was significantly associated with each other (P<0.001). EpCAM expression was significantly associated with clinical and histological features indicating aggressive tumour behaviour, including younger age of onset, higher serum alpha foetoprotein (AFP) levels, tumour cell dedifferentiation, increased mitotic activity, and vascular invasiveness. There was no significant difference in expression of EpCAM, CK19 and NCAM between HBV positive and negative HCC. Interpretation & conclusions: The LCSC marker EpCAM was expressed in less than half of HCC, was independent of HBV aetiology, and was strongly associated with clinical and histological features of aggressive tumour behaviour. Positive staining for CK19 suggests a possible LPC origin of the EpCAM positive HCCs.

Hepatic angiomyolipoma: A case report with diagnostic challenge.

Angiomyolipomas are rare benign tumors derived from perivascular epithelioid cells that occur frequently in kidney and rarely in the liver. We present a case of hepatic angiomyolipma, with various clinical and radiological differential diagnoses. A 34-year-old male was found to have a palpable mass on the left side of the abdomen. Imaging showed heterogeneously enhancing mass lesion 15 cm × 7 cm, in the left lobe and segment 4 of the liver. Various benign and malignant diagnoses were entertained. The needle biopsy did not reveal any evidence of malignancy. Patient underwent resection of the lesion in view of the large size, which was diagnosed as angiomyolipoma. Angiomyolipoma is a benign tumor and accurate diagnosis is important to prevent overtreatment. Histology and immunohistochemisry may help in clinching the diagnosis, in proper clinical setting.

A study of aetiology of portal hypertension in adults (including the elderly) at a tertiary centre in southern India.

Background & objectives: There are only a few studies on aetiology of portal hypertension among adults presenting to tertiary care centres in India; hence we conducted this study to assess the aetiological reasons for portal hypertension in adult patients attending a tertiary care centre in southern India. Methods: Causes of portal hypertension were studied in consecutive new adult patients with portal hypertension attending department of Hepatatology at a tertiary care centre in south India during July 2009 to July 2010. Results: A total of 583 adult patients (>18 yr old) were enrolled in the study. After non-invasive testing, commonest causes of portal hypertension were cryptogenic chronic liver disease (35%), chronic liver disease due to alcohol (29%), hepatitis B (17%) or hepatitis C (9%). Of the 203 patients with cryptogenic chronic liver disease, 39 had liver biopsy - amongst the latter, idiopathic non cirrhotic intrahepatic portal hypertension (NCIPH) was seen in 16 patients (41%), while five patients had cirrhosis due to non alcoholic fatty liver disease. Fifty six (10%) adult patients with portal hypertension had vascular liver disorders. Predominant causes of portal hypertension in elderly (>60 yrs; n=83) were cryptogenic chronic liver disease (54%) and alcohol related chronic liver disease (16%). Interpretation & conclusions: Cryptogenic chronic liver disease was the commonest cause of portal hypertension in adults, followed by alcohol or hepatitis B related chronic liver disease. Of patients with cryptogenic chronic liver disease who had liver biopsy, NCIPH was the commonest cause identified. Vascular liver disorders caused portal hypertension in 10 per cent of adult patients. Cryptogenic chronic liver disease was also the commonest cause in elderly patients.

Idiopathic non-cirrhotic intrahepatic portal hypertension: common cause of cryptogenic intrahepatic portal hypertension in a Southern Indian tertiary hospital.

Background and aim Patients with intrahepatic portal hypertension and negative etiological work-up for liver disease are often labeled as having cryptogenic cirrhosis. The aim of this study was to evaluate causes of liver disease in patients with unexplained intrahepatic portal hypertension. Methods We retrospectively analyzed cause of liver disease in all patients with cryptogenic intrahepatic portal hypertension who underwent liver biopsies between June 2005 to June 2007 in our center. Results Five hundred and seventeen patients underwent liver biopsies of whom 227 had portal hypertension. Of these, the cause of liver disease could not be detected prior to liver biopsy in 62 patients. Causes of liver disease identified after liver biopsy in these 62 patients were: idiopathic non-cirrhotic intrahepatic portal hypertension (NCIPH) (30 patients, 48 ), cirrhosis (14), fatty liver disease (7) and other causes (11). Initial presentations in idiopathic NCIPH patients were splenomegaly and anemia (18 patients), variceal bleed (9) and ascites (3). Median age (range) of patients at first presentation was 32 (15-57) years, and 19 were male. Majority (90 ) were in Child’s class A. Hepatic vein pressure gradient was <5 mmHg in 2 of 7 NCIPH patients tested. Conclusions We identified 30 patients with idiopathic NCIPH at our center over the 2 year study period. The clinical presentation and investigations of NCIPH closely mimic cryptogenic cirrhosis. Idiopathic NCIPH should be considered as a differential diagnosis of cryptogenic cirrhosis in India.

Clinicopathological features and genotype distribution in patients with hepatitis C virus chronic liver disease.

Background and Objective Hepatitis C virus (HCV) genotype influences the severity of disease and response to therapy. This retrospective study examined the clinical and histological features and the genotype distribution in biopsied patients with HCV related chronic liver disease. Methods Of 105 biopsies from patients with HCV infection, 96 from patients with chronic liver disease were reviewed. The Ishak scoring system was used for histological analysis. Results Genotype 3 was most common accounting for 77.1%, and genotype 1 for 9.4% of cases. There was no significant association of transaminase levels, viral load or necroinflammatory activity score with genotype. A severe degree of fibrosis was seen in 77.8% cases of genotype 1 and in 63.5% of genotype 3 (p=0.76). Variable degrees of steatosis were noted in 68.8% of cases. However, severe steatosis was noted only in genotype 3 (7 cases). Serum transaminase levels did not correlate with either histological activity (p=0.43) or degree of fibrosis (p=0.72). Severe fibrosis / cirrhosis was seen in 74.24% of patients above 40 years of age as compared to 33.3% of patients below 40 years (p=0.001). The frequency of Mallory hyaline was significantly different between genotypes 1 and 3 infection (P<0.001). Conclusions This study confirms the preponderance of genotype 3 in Indian patients with HCV related chronic liver disease. Severe steatosis was seen only in genotype 3 and Mallory hyaline was very common in genotype 1. The small numbers of patients in non genotype 3 could be a reason for the apparent lack of histological differences between different HCV genotypes. Severe fibrosis seen in older age groups confirms that HCV infection is progressive and major acceleration of the disease process occurs after 40 years of age.

Liver histology and immunohistochemical findings in asymptomatic Indians with incidental detection of hepatitis B virus infection.

BACKGROUND AND OBJECTIVES: The relationship between hepatocyte expression of hepatitis B virus (HBV) antigens, liver histology and viral replication in asymptomatic subjects with incidental detection of hepatitis B surface antigen (HBsAg) remains unclear. We evaluated the histological activity index (HAI) and hepatocyte expression of viral antigens with replicative status in asymptomatic chronic HBV infection. METHODS: Asymptomatic subjects with incidental detection of HBsAg and ALT levels less than twice the upper limit of normal were grouped as follows: Group A - negative for HBeAg and HBV DNA (no HBV replication); B - HBeAg negative, HBV DNA positive (low HBV replication or pre-core mutant); C - positive HBeAg and HBV DNA (high viral replication). Liver biopsies were assessed for HAI (Ishak's scoring system). These were also subjected to immunohistochemistry for expression of HBsAg and hepatitis B core antigen (HBcAg); distribution, staining pattern and quantitative measurement of antigen expression were assessed. RESULTS: Median HAI was similar in the three groups (1.0, 2.0 and 2.0 in groups A, B and C, respectively). All subjects in Group C showed discrete cytoplasmic expression of HBsAg, whereas the other two groups showed heterogeneity in distribution and pattern of HBsAg staining. Quantitative measurement of cytoplasmic HBsAg revealed similar results in the three groups. Core antigen (nuclear) was detected in 4 of 5 subjects in Group C and none of those in Groups A and B. Ground-glass hepatocytes were seen in 20 and orcein-positive cells in 26 cases. HBsAg was detected by immunohistochemistry in 37 biopsies. CONCLUSIONS: Among asymptomatic subjects with chronic HBV infection, those with high rate of viral replication had discrete cytoplasmic HBsAg expression and nuclear expression of core antigen; these findings were uncommon in subjects with low or no viral replication.

Acute fatty liver of pregnancy: a report of two cases.

Acute fatty liver of pregnancy is an uncommon, potentially fatal disorder. Between 1998 and 2000, two patients with acute fatty liver of pregnancy presented at the Christian Medical College Hospital, Vellore. Both patients were in the thirty-sixth week of pregnancy. jaundice and encephalopathy were the predominant symptoms. Both the mothers died after they delivered a stillborn Infant each. The maternal deaths were due to multiorgan failure and/or postpartum haemorrhage and sepsis. The route of delivery was vaginal in both the patients. Extrahepatic and metabolic complications in both cases Included renal failure, sepsis, hypoglycaemia, disseminated intravascular coagulation and gastrointestinal bleeding. Liver biopsy done in both patients was consistent with the diagnosis of acute fatty liver of pregnancy. To the best of our knowledge, this is the first report from India on acute fatty liver of pregnancy.

Epithelioid haemangioendothelioma of the liver.

Epithelioid haemangioendothelioma is a well-recognized vascular neoplasm but can be mistaken for metastatic adenocarcinoma or other primary liver tumors. We present a case of epithelioid haemangioendothelioma of the liver in a 62 year old woman, in whom the diagnosis was missed by various pathologists. This patient presented with loss of appetite and weight, and fever. She rapidly deteriorated and died presumably of liver cell failure. The characteristic histological features and the positive immunostaining for endothelial markers (CD31 & Ulex europaeus) confirmed the diagnosis.