Utility of FNAC in conjunction with cell block for diagnosing space-occupying lesion [SOL] of liver with emphasis on differentiating hepatocellular carcinoma from metastatic SOL: analysis of 61 cases

Objectives: To study the cytological patterns of fine-needle aspiration cytology [FNAC] obtained from space-occupying lesions [SOLs] of the liver with an aim to differentiate primary hepatocellular carcinoma from metastatic deposits and to evaluate the added advantage and efficacy of studying cell blocks in conjunction with smears for enhancing diagnostic accuracy

Methods: This prospective study took place over two years [September 2007 to 2009] and included 61 patients with cases of liver SOLs that were clinically or radiologically suspicious for malignancy and who were referred for computed tomography or ultrasonography-guided FNAC. Smears were prepared from the aspirated material, and any remainder was used to make the cell block [n = 55]. A final diagnosis was made after evaluating the smears and cell block sections

Results: On cytomorphology, a diagnosis of moderately differentiated hepatocellular carcinoma [HCC] and metastatic carcinoma was made in 10 [18.2%] and 25 [45.5%] cases, respectively, and were confirmed using cell block sections. In cases where it was difficult to differentiate between welldifferentiated HCC and regenerative nodules, and between poorly differentiated HCC and poorly differentiated metastatic carcinoma, a final diagnosis was made with the help of cell blocks sections. Cell blocks assisted in reaching a final diagnosis in 16 [29.1%] cases. Cases that were diagnosed using cytomorphology were confirmed by the cell block method. In these 39 [70.9%] cases we were able to render a diagnosis with much more confidence

Conclusion: In our experience, difficulties in diagnosing SOL liver are attributed to differentiation of the tumor. Cell block preparation gives an additional advantage as architectural details can be studied that help to reach an accurate diagnosis in problematic and challenging cases. Thus, we strongly recommend the use of the cell block technique in conjunction with cytosmears for the purpose of diagnosis

Mixed adenoneuroendocrine carcinoma of the gallbladder, histopathological features.

An unusual case of mixed adenoneuroendocrine carcinoma is described which posed a diagnostic challenge in view of neuroendocrine component mimicking signet ring cells of adenocarcinoma. Diagnostic criteria for these mixed tumors, their histogenesis and treatment modalities are highlighted.

Malignant Rhabdoid Tumor of Kidney and Brain in an Infant.

Background: Malignant rhabdoid tumors of kidney are associated with atypical teratoid rhabdoid tumors of brain, both being characterized genetically by deletion/ mutation of SMAR CBI/ INI gene. Case characteristics: 6-month-old male presented with a brain tumor and was subsequently found to have malignant rhabdoid tumor of kidney. Interventions: Surgical resection of brain tumor followed by chemotherapy and subsequently resection of renal tumor. Outcome: Child died seven months after initial presentation. Message: Children presenting with embroynal brain tumor, should be investigated for renal tumors and vice versa.

Predictors of histological activity and fibrosis in chronic Hepatitis C infection: A study from North India.

Background and Aims: The role of hepatitis C virus (HCV) genotypes in the severity of liver disease is still debatable and there is an occasional published report from India. The aim of this study is to assess the role of HCV genotypes in severity of liver disease in Indian patients. An attempt has also been made to perform a multivariate analysis to identify the predictors of severity of liver disease in chronic HCV infection. Materials and Methods: In this study, 31 newly diagnosed cases of chronic HCV infection over a period of two years were included. Age, sex and serum alanine transaminase (ALT) levels were recorded for each patient. HCV genotypes were identified using Line Probe assay (INNO-LiPA HCV II kit, Innogenetics, Belgium). Histological activity was graded and fibrosis was staged. Univariate and multivariate analysis was done to identify predictors of histological severity and fibrosis. Results: By univariate analysis, age of the patient, serum ALT levels and absence of genotype 3 (i.e., presence of HCV genotype other than genotype 3) showed association with histological activity score; whereas age and histological activity score showed association with fibrosis. However, on multivariate analysis, only serum ALT levels and absence of genotype 3 correlated well with activity score; while only activity score remained a significant predictor of stage of fibrosis. Conclusions: This study emphasizes the significant correlation of HCV genotype with severity of liver disease in chronic HCV infection. The stage of fibrosis showed correlation only with activity score as an independent factor. These results would further help in outlining algorithms for therapeutic stratification of patients with HCV infection.

Nonalcoholic steatohepatitis--a histological perspective.

Nonalcoholic Steatohepatitis (NASH) is a progressive liver disease that has gained recognition in the last two decades. It may even account for some of the cases previously diagnosed as cryptogenic cirrhosis. Association of this entity,with obesity, insulin resistance and type II diabetes is well documented. In this review we clarify the terminology and describe the histological features associated with NASH. Criteria for diagnosis, grading and staging systems and role of liver biopsy is also discussed.

Reversible cholestatic hepatitis due to carbamazepine in an adolescent.

We report a 13-year-old boy who developed fever, rash and hepatitis with cholestasis (on biochemistry and liver histology) after 10 weeks' use of carbamazepine. Recovery of liver biochemistry occurred 4 months after discontinuing the drug.

Distribution of hepatitis C virus genotypes in patients with chronic hepatitis C infection in India.

BACKGROUND & OBJECTIVES: Hepatitis C virus (HCV), an important cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma, shows a considerable genetic heterogeneity among hepatitis C virus isolates from all over the world. At least six main groups of sequence variants are recognized. The natural history of disease and response to treatment may be related to the genotype of HCV in a particular patient. Antigenic differences between genotypes also have implications for optimal design of serological sequencing and confirmatory assays for HCV. The present study was undertaken with the objective to find out various genotypes of hepatitis C virus prevalent in Indian patients with chronic hepatitis C infection. METHODS: Thirty six consecutive newly diagnosed patients with chronic hepatitis C infection were included in the study. HCV RNA was extracted from the serum by standard guanidinium thiocyanate method. Following reverse transcription and amplification, the HCV genotypes were determined by line probe assay (INNO-LiPA HCV II). RESULTS: Of the 36 patients, genotype 3 was found in 24 (66.6%). Of these 24 patients, 3a was seen in 5 patients (13.8%), 3b in two (5.5%) and mixed subtype 3a and 3b in 17 patients (47.2%). Genotype 1 was found in 5 patients (13.8%), with 1b in 1 and 1a in rest four cases. Two patients (5.5%) were infected with genotype 2 (subtype 2a and mixed subtype 2a, 2b respectively). One (2.7%) was infected with genotype 4 (4a). Mixed genotype infection was found in 4 patients (11.1%). INTERPRETATION & CONCLUSION: The present findings showed that genotype 3 of hepatitis C virus was the most prevalent genotype in patients with chronic hepatitis C in this part of India.

Histological profile of liver disease in patients with dual hepatitis B and C virus infection.

There is limited information on the histological profile of chronic liver disease due to dual infection with hepatitis B virus and hepatitis C virus infection. Few studies have indicated higher histological activity with dual infection as compared to HBV and HCV infection present alone. This study aims at reviewing the histological profile of liver biopsies in the three groups. Liver biopsies of 25 patients serologically diagnosed as HBV and HCV dual infection (Group I), were compared with 25 age and sex matched cases of HBV infection (Group II) and HCV infection (Group III). RESULTS: Mean Histological Activity Score in group I was 8, which was higher than the scores of group II (6.2) and group III (7.3). The mean stage of fibrosis was also slightly higher in group I (2.3) as compared to group II (1.9) and group III (1.7). However, when stage 3 and 4 fibrosis (extensive fibrosis) were combined and compared with the number of patients with stage 1 and 2 fibrosis in each group, we found Group I (dual infection) had larger number of patients with extensive fibrosis (48%) than in Groups II and III (20% and 36% respectively). In addition, there was no significant difference in presence of features like fatty change, bile duct injury and lymphoid aggregates in the three groups. CONCLUSION: Patients with dual HBV and HCV infection are more likely to have an advanced stage of disease than those with a single infection, however there is no significant difference in histologic activity or any other histological parameter between these groups.

Prevalence of hepatitis B infection within family contacts of chronic liver disease patients--does HBeAg positivity really matter?

BACKGROUND: The risk of infectivity is known to be high in contacts of HBeAg positive chronically infected patient. We investigated and compared the frequency and significance of transmission of HBV infection from chronic liver disease patients (CLD) with HBeAg or anti-HBe and HBV DNA positive status. MATERIAL AND METHODS: Four hundred and seventy nine contacts [first degree blood relatives (n=278), second degree contacts (n=139) and sexual contacts (n=62)] of 92 HBV-related, liver biopsy proven, CLD patients were studied. Three hundred and seventy three belonged to 65 index patients with HBsAg+ve, HBeAg+ve, HBV DNA+ve, HBV DNA+ve infection and 106 belonged to 27 index patients with (HBsAg+ve, HBeAg-ve, anti-HBe+ve, HBV DNA+ve infection). One hundred and seventy six family members, age and sex matched, belonging to 38 healthy individuals, with no history of liver disease or HBV positivity, served as controls. Viral serology and quantitative DNA estimation was done in index patients. RESULTS: Forty nine of 65 (75.4%) families of HBeAg+ve and 63% families of HBeAg-ve index patients had one or more family member exposed to HBV (positive family, p=ns). The chronic HBV infection (HBsAg+ve) and past-exposure (only IgG anti-HBc+ve) rates in the contacts of HBeAg+ve and HBeAg-ve index patients were 17.4% and 19.8% (p=ns), and 31% and 14.2% respectively, both being significantly higher (P < 0.01) than the prevalence rates in the control group (chronic HBV infection 2.3%, past-exposure 10.2%). Overall, 48.5% and 34% (p < 0.05) of contacts in the HBeAg+ve and HBeAg-ve groups had markers of HBV infection. The quantitative HBV DNA levels were comparable between HBeAg+ve and HBeAg-ve index patients (1712 +/- 356 pg/ml vs 1802 +/- 812 pg/ml). First degree relatives had higher chronic HBV infection rates than second degree contacts (29% vs. 0%, p < 0.05). The duration of symptomatic illness of HBeAg+ve index patients was longer than HBeAg-ve (p < 0.05). A significant proportion of HBsAg+ve first degree relatives of HBeAg+ve (33%) and HBeAg-ve (40%) patients, had evidence of CLD. CONCLUSIONS: (i) The frequency of transmission of HBV infection is nearly similar in contacts of HBeAg+ve and HBeAg-ve infected patients, more so in first degree relatives, (ii) these observations make family contacts a very high risk group, requiring priority screening and vaccination against HBV.

Profile of asymptomatic chronic HBV infection in India.

BACKGROUND & OBJECTIVES: In India, horizontal transmission in early childhood has been shown to be a significant mode of transmission of hepatitis B virus (HBV). This prospective, cross-sectional study was undertaken to study the biochemical, serological and histological profile of incidentally detected asymptomatic HBsAg positive subjects (IDAHS) picked up at a tertiary care referral centre. METHODS: In 157 (M:F::123:34) HBsAg positive subjects, clinical, biochemical, virological and histological assessment was done. The histological activity index (HAI) of > 3 was considered as chronic hepatitis. Serum was tested for HBsAg, HBeAg, HBeAb, HBV DNA and alanine transaminase (ALT). RESULTS: Seventy (45%) subjects were HBeAg and 83 (53%) anti-HBe positive. While 71 per cent of the subjects with elevated ALT had an HAI > 3, only 36 per cent with normal ALT showed significant histological changes (P < 0.001). Significant histopathological lesions in the liver biopsy were seen in 92 (59%) subjects, with moderate to severe lesions in 14. IDAHS who were HBeAg +ve were more likely to have significant histological lesion than those who were anti-HBe +ve (P < 0.01). In the anti-HBe +ve group, 35 of 57 (61%) subjects for whom HBV-DNA was available, were HBV-DNA positive. Anti-HBe+ve, HBV-DNA+ ve IDAHS with elevated ALT were more likely to have chronic hepatitis vis-a-vis those subjects in this group who had a normal ALT (P < 0.001). INTERPRETATION & CONCLUSION: ALT is a reliable discriminant of significant histological lesion in IDAHS. The relatively young mean age of Anti-HBe +ve IDAHS suggests an early age of infection and hence, early seroconversion or mutant virus infection in this cohort. A significant proportion of these IDAHS have HBV-DNA positivity and HAI > 3. Our results clearly demonstrate ongoing liver disease in asymptomatic, so-called "HBV carriers". We propose that the term hepatitis B 'carrier' should be abandoned and replaced by 'chronic HBV infection'.