Steatosis in chronic hepatitis B: Prevalence and correlation with biochemical, histologic, viral, and metabolic parameters.

Background and Aims: Hepatic steatosis (HS) is highly prevalent in chronic hepatitis C and is an important variable predicting progression of histological injury, insulin resistance, and reduced response to antiviral therapy. There are limited data on HS in patients with chronic hepatitis B (CHB). This is relevant since response to current antiviral therapies for CHB is rather limited. We investigated the spectrum and predictors of HS in CHB patients. Materials and Methods: Liver biopsies of consecutive patients of chronic Hepatitis B Virus (HBV) infection were studied and were categorized as: Group I - hepatosteatosis (>5%) and Group II - no steatosis (£5%). Anthropometric, histological, biochemical, virological, and metabolic determinants were compared. Logistic regression analysis was applied to identify variables that were independently associated with the presence of steatosis. Results: Of the 350 patients, 118 (33.7%) liver biopsies showed steatosis (Group I); 65 (55.1%) had mild (6 to <25%) and 53 (44.9%) had moderate to severe steatosis (325%). Patients in group I, compared with group II, were older (35.5 ± 10.5 vs 27.9 ± 14.0 years, P < 0.01), predominantly male (M: F, 10.8: 1 vs 4.8: 1, P = 0.035), obese (75.0% vs 23.4%, P < 0.01), with higher body mass index (25.2 ± 4.8 vs 20.4 ± 3.5, P < 0.01), with higher triglycerides (138.8 ± 62.1 vs 88.0 ± 27.9, P = 0.02), with higher cholesterol (171.9 ± 43.5 vs 139.3 ± 37.6, P = 0.017), and with higher serum insulin (13.1 ± 9.1 vs 9.1 ± 6.0, P < .027) levels. HBV DNA level was significantly lower in group I than group II; however, HBV genotype did not influence HS. By multivariate regression analysis, only high serum triglyceride level was independent parameter associated with HS. Conclusions: Steatosis is seen in one-third cases with HBV-related chronic liver disease and is associated with host metabolic factors, especially serum triglyceride levels, whereas HBV DNA level negatively correlated with HS.

Adenomyoma of common bile duct arising in a type I choledochal cyst.

Adenomyoma can be misdiagnosed as an adenocarcinoma, leading to needless and extensive surgical resections. A 45-year-old woman presented with right hypochondrial pain. Magnetic resonance imaging showed a choledochal cyst. Excision of choledochal cyst with Roux-en-Y hepaticojejunostomy was performed. A segment of dilated common bile duct and an attached nodule was received. Sections from the choledochal cyst showed a cyst wall composed of dense fibrous tissue lined by partially ulcerated columnar epithelium. Sections from the nodule showed interlacing whorls of smooth muscle bundles with entrapped glands. The glands were lined by cuboidal to columnar cells without nuclear atypia. This was recognized as an adenomyoma. To the best of our knowledge, this is the first reported case in which an adenomyoma was found associated with a type 1 choledochal cyst. A review of the existing literature and discussion of theories of genesis and the diagnostic pitfalls are presented.

Evaluation of adefovir & lamivudine in chronic hepatitis B: correlation with HBV viral kinetic, hepatic-necro inflammation & fibrosis.

Background & objectives: Chronic hepatitis B is an important cause of morbidity and mortality. We conducted a study comparing the efficacy of adefovir and lamivudine with respect to their impact on serum and hepatic viral DNA clearance, and improvement in hepatic necro-inflammatory score, in naive patients of chronic hepatitis B. Methods: This prospective randomized pilot study was conducted in Lok Nayak Hospital, New Delhi, involving 30 patients of chronic hepatitis B (both e antigen positive and negative); 15 were randomly selected to receive either adefovir or lamivudine for a period of 6 months. Quantification of serum and hepatic HBV DNA levels was done by real time PCR and liver biopsy was done at the beginning and end of 6 months. Results: Serum ALT was elevated to 2 or more times normalized in both the groups. In the adefovir group, two patients became HBeAg negative. In the lamivudine group, one patient became HBeAg negative. After therapy HBV DNA was negative in 26.7 per cent patients from adefovir group and 13.3 per cent patients from lamivudine group. Serum HBV DNA levels were correlated with the hepatic levels before therapy (r=0.843; P<0.001) and after therapy (r=0.713, P<0.001) showing strong correlation. There was a median reduction of 1.92 and 2.06 log copies per ml in serum HBV DNA load after adefovir and lamivudine therapy, respectively. The mean reduction in the histotogy activity index (HAI) score was 2 and 1.53, fibrosis score was 2.33 and 3.06 after adefovir and lamivudine therapy respectively. Interpretation & conclusions: Adefovir and lamivudine treatment caused biochemical and serological improvement when administered for about 6 months with significant reduction in HBV DNA, serum and hepatic viral load without completely clearing the virus from either serum or liver. It also helped in reduction of the necro-inflammatory and fibrosis score of patients with chronic hepatitis B. Our study also showed significant correlation between serum and hepatic HBV DNA levels both before and after therapy. There was not enough evidence to show therapeutic advantage of one drug over the other in any of the parameters measured.

Comparison of clinical, biochemical and histological features of alcoholic steatohepatitis and non-alcoholic steatohepatitis in Asian Indian patients.

Background: Alcoholic steatohepatitis (ASH) and non-alcoholic steatohepatitis (NASH) are significant forms of liver disease and may progress to end-stage liver disease, cirrhosis and potentially malignant complications. The most difficult aspect of establishing a diagnosis of NASH is distinguishing it from ASH. Laboratory markers such as AST, ALT and GGT lack sufficient sensitivity and specificity. Aim: To study the clinical, biochemical and histological differences between non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH). Materials and Methods: Sixty histologically confirmed cases of non-alcoholic steatohepatitis and 38 cases of alcoholic steatohepatitis were included in the study. A modified form of scoring system proposed by Yip and Burt was used to grade histological features of NASH and ASH. Results: Mean age was 42.85 ± 12.36 years in ASH group and 35.07 ± 8.06 years for NASH group. Male: Female ratio was 37:1 in ASH and 4:1 in NASH. The mean ALT (P = 0.012), SAP (P = 0.003), serum bilirubin (P = 0.001), AST/ALT ratio (P = 0.03), steatosis (P < 0.001), ballooning degeneration of hepatocytes (P < 0.001), portal inflammation (P < 0.001), Mallory hyaline (P = 0.001), ductular proliferation and fibrosis (P < 0.001) showed a significant difference between ASH and NASH cases. Discussion: Older age, male sex, larger derangement of serum biochemistry, high serum bilirubin, AST/ALT > 1, more ballooning degeneration, portal inflammation, Mallory's hyaline, hepatocytic and ductular cholestasis, ductular proliferation and higher stage of fibrosis favors a diagnosis of ASH. Younger age, high ALT, AST/ALT < 1, higher grade of steatosis and absence of extensive neutrophilic portal inflammation favors a diagnosis of NASH.

Florid xanthogranulomatous cholecystitis masquerading as invasive gallbladder cancer leading to extensive surgical resection.

Xanthogranulomatous inflammation of gallbladder wall can extend and infiltrate adjacent organs which can be mistaken for malignancy on preoperative investigations and, intraoperatively, often leads to extensive surgical resections. Only the histopathologic examination of the specimen allows correct diagnosis. We hereby review clinicopathologic findings of six cases which underwent extensive surgeries on clinical, radiological and intraoperative suspicion of gallbladder carcinoma which turned out to be xanthogranulomatous cholecystitis (XGC). There was no evidence of malignancy on histopathologic examination. Xanthogranulomatous inflammation extended into liver, duodenum, colon and stomach in case 1; liver and colon in case 2; liver, duodenum, colon in case 3; stomach, duodenum, colon in case 4; stomach and duodenum in case 5 and duodenum and colon in case 6. Lymph nodes in all the six cases showed reactive hyperplasia. We present here the clinico-radiologic findings of these cases, techniques which may help differentiate between an XGC and a gallbladder carcinoma and also discuss the management of these cases.

Making and using inexpensive manually constructed tissue micro-array: Experience of a tertiary care hospital in India.

Background: Tissue micro-array enables the analysis of a large number of tissues simultaneously. Widespread use of this technology is hampered by the high cost of commercial array instruments. We describe our experience of constructing tissue micro-array in a simple method using easily available and inexpensive instruments. Materials and Methods: We used an 11-19 gauge (G) bone marrow trephine biopsy needle/ small sized slotted screwdriver to punch holes in the wax blocks. Cores were taken from donor tissue blocks using a bone marrow trephine biopsy needle and arrayed into host paraffin wax blocks. A detailed database was constructed for each array constructed. Results: The array blocks were used over a period of one year as internal control for immunohistochemistry (IHC), quality control and research. It took about 10 minutes to construct a nine-dot array and about one hour for a 56-dot array. During IHC, the average loss of control dots was less than one per cent. We did not see any loss of antigenicity in the control sections even after four weeks storage. Discussion: Tissue array construction by the technique described here is inexpensive and reliable alternative to automated instruments. Because it is easy to modify the arrays by varying the core size, it is easy to adapt this to individual labs and requirements. We recommend using blocks with cores in 3 × 3 to 5 × 4 grids as controls in IHC and for standardizing antibodies and array blocks with a larger number of cores for research.

Cystic ductal adenocarcinoma of pancreas: an unusual variant.

Cystic lesions of the pancreas are usually pseudocysts (90%); only 10% of them are cystic tumors. These cystic tumors constitute less than 10% of all pancreatic neoplasms, making them an extremely uncommon type of pancreatic malignancy. What is more important is that these tumors are very easily misdiagnosed as pseudocysts because their characteristics are very similar to those of the benign pseudocysts. This gains importance as the cystic tumors have a high cure rate and good prognosis if diagnosed and treated on time. Of all the cystic tumors, the most common are the benign serous cystadenomas, mucinous cystic tumors, intraductal papillary mucinous neoplasms etc. Ductal adenocarcinoma of pancreas presenting in cystic form is an uncommon type of cystic tumor, making it extremely rare among all pancreatic malignancies (solid or cystic). We present the following case report. The review of literature concerning the diagnosis and management has also been discussed.

Infant gastroesophageal reflux disease score: reproducibility and validity in a developing country.

A 25-point infant gastro-oesophageal reflux disease (GERD) score based on 11 signs and symptoms of gastrooesophageal reflux (GER), to diagnose GERD has been suggested in infant. We carried out this study to test the reproducibility and validity of this scoring system in the cross-cultural settings of Indian infants. Caretakers of 610 apparently healthy infants, between the ages of 1 month and 24 months were administered the Orenstein's infant GER questionnaire and assigned a GERD score. Of these, 95 infants were taken up for a 24-hours oesophageal pH monitoring study. Before the pH study, each subject was again tested by the infant GER questionnaire by another independent observer and assigned an infant GERD score. The 24-hours oesophageal pH study was done using the Synectics Digitrapper MK III portable pH recording device. Reflux index (RI) >10% in infants up to 1 year of age and >5% in children more than 1 year of age was taken as pathological. Upper gastrointestinal endoscopy and oesophageal biopsies were performed in 35 cases, after taking informed consent. A good correlation was seen between the scores evaluated independently by the two workers, with a Pearson correlation coefficient of 0.906. The mean GERD score in infants with GER (as diagnosed by pH-metry) was 4.64 +/- 3.99 compared to 3.54 +/- 3.96 in those with no documented GER (p>0.05). A GERD score of 5 had a sensitivity of 43% and specificity of 79%, compared to 86% and 85% observed by Orenstein et al. in their series. The infant GER Questionnaire is easily adaptable and reproducible in the settings of developing countries. However, its diagnostic validity appears to be much less than that obtained by Orenstein et al. in their study on American infants.

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.

Surgical management of obstructive gastroduodenal tuberculosis.

BACKGROUND: Gastroduodenal tuberculosis is a rare but potentially curable condition. The aim of the present study was to evaluate the clinical presentation, pre-operative status, management and outcome in patients with histologically proven diagnosis of gastroduodenal obstruction due to tuberculosis. METHODS: We retrospectively reviewed the records of 17 patients managed surgically for gastroduodenal obstruction due to tuberculosis. RESULTS: The site of obstruction was the pyloroduodenal canal in 53% of patients, second part of the duodenum in 24%, third part of the duodenum in 12% and duodenjojejunal flexure in 12%. The obstruction was caused by fibrotic stricture formation in 59% of patients and extrinsic compression by a lymph nodal mass in 41%. Endoscopic biopsy was diagnostic in only 29% of the patients in whom it was performed. Overall, a pre-operative diagnosis of gastroduodenal tuberculosis was suspected in only 35% of patients. All the patients underwent surgical drainage procedures and the diagnosis was confirmed by histopathological examination of biopsies taken at the time of laparotomy. CONCLUSIONS: In view of its rarity and non-specific findings on clinical, radiological and endoscopic evaluation, tuberculosis as a cause of gastroduodenal obstruction is seldom diagnosed pre-operatively. Hence, a high index of suspicion is required in young patients residing in endemic areas. Surgical intervention helps not only in relieving obstruction but also in confirming the diagnosis.