Biopsy Proven Fibrosis in Non-Alcoholic Fatty Liver Disease: An Analysis of Risk Factors.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is emerging as an important cause of liver disease in India. NAFLD is characterized by hepatic steatosis in absence of a significant alcohol use or other known liver disease. Non-alcoholic steatohepatitis (NASH) is a progressive form of NAFLD which deserves particular attention because it is more prone for development of fibrosis. Liver biopsy is the gold standard for diagnosis of NASH by evaluating necroinflammatory activity and stages of fibrosis. The aim of the study was to analyze liver biopsy specimens and identify risk factors associated with fibrosis in patients of NAFLD in eastern coastal India. METHODS: A total of 216 subjects with fatty liver in ultrasonography (USG) were selected for needle biopsy. Those NAFLD cases showing fibrosis in biopsy were analyzed for risk factors association. RESULTS: Definite NASH was diagnosed in 50 (23.14%), borderline NASH in 66 (30.55%) and not NASH in 100 (46.39%) of cases. Those patients with fibrosis (22%) were taken as cases and those without fibrosis (78%) were taken as controls for risk factor analysis. Age > 40 [odds ratio (OR) 2.01 (1.09-4.04)], female gender [OR 2.74 (1.24-6.05)], body mass index (BMI) > 23 [OR 15.36 (4.59-51.37)] and moderate fatty change in USG [OR 1.89 (1.01-3.62)] were observed as risk factors for progression to fibrosis in NAFLD cases. CONCLUSION: Older age, females, obesity and moderate fatty liver on USG are risk factors for development of fibrosis in patients with NAFLD. Patients with these risk factors should be selected for liver biopsy and to be kept for close follow-up.

Biochemical Profile of Nonalcoholic Fatty Liver Disease Patients in Eastern India with Histopathological Correlation.

Aminotransferase assay is often used as a screening test as well as an endpoint for resolution of disease in nonalcoholic fatty liver disease (NAFLD). Aim of the study was to evaluate the relationship of transaminase level with metabolic variables and histology in NAFLD. Single center observational study was conducted in a gastroenterology clinic at Cuttack in coastal Odisha. Subjects were consecutive patients presenting with functional bowel disease and undergoing abdominal sonography. All participants were evaluated for the presence of metabolic syndrome (MS), insulin resistance, liver function test and lipid profile. Various parameters were compared between NAFLD subjects and controls. 53.5 % of NAFLD had normal serum transaminases, whereas 20.8 % of healthy controls had transaminitis. NAFLD patients had significantly higher BMI, fasting plasma glucose, serum transaminases, serum triglycerides, serum insulin and homeostatic model assessment (HOMA) IR than controls. NAFLD patients who had transaminitis had significantly higher incidence of MS and higher mean HOMA IR than those without. There was no significant difference in histopathological features between NAFLD with and without transaminitis. To conclude, over half of NAFLD subjects do not have transaminitis while transaminitis is present in a fifth of healthy people without fatty liver. Hence serum transaminase should not be used as screening test for NAFLD. NAFLD patients with transaminitis had a higher incidence of MS and insulin resistance than those without. However, there was no significant difference in histopathological features between these two groups.

Histological Evaluation of Non-alcoholic Fatty Liver Disease and Its Correlation with Different Noninvasive Scoring Systems with Special Reference to Fibrosis: A Single Center Experience.

BACKGROUND: Although liver biopsy remains the gold standard for the diagnosis of non-alcoholic fatty liver disease [NAFLD], many non-invasive markers of liver fibrosis have recently been proposed and assessed as surrogates of liver biopsy. AIMS AND OBJECTIVE: To evaluate the degree of liver fibrosis by different non-invasive fibrosis scoring systems and to compare each non-invasive fibrosis scoring system with histological fibrosis stage. MATERIALS AND METHODS: The study population consists of consecutive patients with biopsy proven NAFLD. Complete medical history was taken and physical examination was done in all patients along with appropriate biochemical evaluations. NAFLD fibrosis score, BARD score, BAAT score and APRI score were calculated and each score was compared with histological fibrosis staging. RESULTS: The study population consisted of 60 patients having mean age 39.73 years (SD 9.62, range 17-63 years) including 51 (85%) males and 9 (15%) females. On histology fibrosis was present in 68.3% (41/60) patients. Out of 60 patients 41 had fibrosis and among them 17, 22, 2 patients had grade 1, 2, 3 fibrosis respectively and no one had grade 4 fibrosis. 61.67% (37/60) had definite NASH. Comparing the fibrosis of histology with the noninvasive scoring systems, the sensitivity and specificity of NAFLD fibrosis score were 5.56% and 100% respectively. BARD score had 45.83% sensitivity and 80.55% specificity. The sensitivities of BAAT score and APRI score were 0% and 29.16% respectively and the specificities were 100% and 97.22% respectively. CONCLUSION: The noninvasive scoring systems like NFS, BARD, BAAT, and APRI are not sensitive enough to detect fibrosis but highly specific to include fibrosis if scores are more than cut-off values in our cohort, however they cannot replace liver biopsy. Newer more efficient non-invasive scoring systems have to be devised for the Indian NAFLD population.

Oxidative stress in murine Theiler's virus-induced temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common form of acquired epilepsy that can be caused by several inciting events including viral infections. However, one-third of TLE patients are pharmacoresistant to current antiepileptic drugs and therefore, there is an urgent need to develop antiepileptogenic therapies that prevent the development of the disease. Oxidative stress and redox alterations have recently been recognized as important etiological factors contributing to seizure-induced neuronal damage. The goal of this study was to determine if oxidative stress occurs in the TMEV (Theiler's murine encephalomyelitis virus) model of temporal lobe epilepsy (TLE). C57Bl/6 mice were injected with TMEV or with PBS intracortically and observed for acute seizures. At various time points after TMEV injection, hippocampi were analyzed for levels of reduced glutathione (GSH), oxidized glutathione (GSSG) and 3-nitrotyrosine (3 NT). Mice infected with TMEV displayed behavioral seizures between days 3 and 7 days post-infection (dpi). The intensity of seizures increased over time with most of the seizures being a stage 4 or 5 on the Racine scale at 6 days p.i. Mice exhibiting at least one seizure during the observation period were utilized for the biochemical analyses. The levels of GSH were significantly depleted in TMEV infected mice at 3, 4 and 14 days p.i. with a concomitant increase in GSSH levels as well as an impairment of the redox status. Additionally, there was a substantial increase in 3 NT levels in TMEV infected mice at these time points. These redox changes correlated with the occurrence of acute seizures in this model. Interestingly, we did not see changes in any of the indices in the cerebellum of TMEV-infected mice at 3 dpi indicating that these alterations are localized to the hippocampus and perhaps other limbic regions. This is the first study to demonstrate the occurrence of oxidative stress in the TMEV model of infection-induced TLE. The redox alterations were observed at time points coinciding with the appearance of acute behavioral seizures suggesting that these changes might be a consequence of seizure activity. Our results support the hypothesis that redox changes correlate with seizure activity in acquired epilepsies, regardless of the inciting insults, and suggest oxidative stress as a potential therapeutic target for their treatment.

Risk Factors Associated With Non-Alcoholic Fatty Liver Disease in Indians: A Case-Control Study.

BACKGROUND/AIMS: NAFLD has today emerged as the leading cause of liver disorder. There is scanty data on risk factors associated with NAFLD emanating from India. The present study was conducted to identify the risk factors associated with NAFLD. METHODS: 464 consecutive NAFLD patients and 181 control patients were subjected to detailed questionnaire regarding their lifestyle and dietary risk factors. Anthropometric measurements were obtained and biochemical assays were done. Comparison of different variables was made between NAFLD patients and controls using principal component analysis (PCA). RESULTS: NAFLD patients had higher BMI [26.25 ± 3.80 vs 21.46 ± 3.08 kg/m(2), P = 0.000], waist-hip ratio [0.96 ± 0.12 vs 0.90 ± 0.08, P = 0.000] and waist-height ratio [0.57 ± 0.09 vs 0.50 ± 0.06, P = 0.000] compared to controls. Fasting blood sugar [101.88 ± 31.57 vs 90.87 ± 10.74 mg/dl] and triglyceride levels [196.16 ± 102.66 vs 133.20 ± 58.37 mg/dl] were significantly higher in NAFLD group. HOMA-IR was also higher in NAFLD group [2.53 ± 2.57 vs 1.16 ± 0.58, P = 0.000]. Majority (90.2%) of NAFLD patients were sedentary. Family history of metabolic syndrome (MS) was positively correlated with NAFLD. Dietary risk factors associated with NAFLD were non-vegetarian diet [35% vs 23%, P = 0.002], fried food [35% vs 9%, P = 0.000], spicy foods [51% vs 15%, P = 0.001] and tea [55% vs 39%, P = 0.001]. Diabetes, hypertension, snoring and sleep apnoea syndrome were common factors in NAFLD. On multivariate PCA, waist/height ratio and BMI were significantly higher in the NAFLD patients. CONCLUSION: The risk factors associated with NAFLD are sedentary lifestyle, obesity family history of MS, consumption of meat/fish, spicy foods, fried foods and tea. Other risk factors associated with NAFLD included snoring and MS.

Nonalcoholic fatty liver disease (NAFLD) without insulin resistance: Is it different?

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of insulin resistance [IR]. However, a significant proportion of NAFLD patients are devoid of IR. Is NAFLD sans IR a different entity? The aim of the study was to compare the anthropometric, metabolic, biochemical, ultrasonography, and histological profile of NAFLD patients with and without IR. METHODS: Retrospective analyses of 336 NAFLD patients diagnosed during the last two years was done. Patients without IR were compared with those with IR. RESULTS: Out of 336 patients, 153 [45.53%] were without IR. Although age, gender, BMI and transaminase levels were comparable, significantly higher proportion of patients in non-IR group were non-obese [43.14% vs. 25/14%; P=0.0005], and had mild fatty change on ultrasonography; [78.43% vs. 67.21%; P=0.022]. Higher proportion of them had elevated transaminases; [67.97% vs. 56.83%; P=0.036]. Serum triglyceride [178.52±78.78 vs. 204.86±94.72 mg/dl; P=0.02], FBG [85.39±13.80 vs. 98.93±31.56 mg/dl; P=0.00], PGBG [123.76±36.77 vs. 148.07±64.67m g/dl; P=0.00], and serum insulin [6.33±2.18 vs. 15.39±12.56 µIU/ml; P=0.00] were significantly lower in patients without IR. Although there was no difference in histology, interestingly fibrosis was seen in one third of patients despite absence of IR. CONCLUSION: Nearly half of our NAFLD population was without IR; one third of them had significant fibrosis. NAFLD is probably a heterogeneous disease and IR is not the sole factor responsible for NAFLD; further studies are needed to find out other possible etiological factors.

Cryptococcal lymphadenitis in HIV: a chance diagnosis by FNAC.

Cryptococcosis is a life threatening, opportunistic fungal disease in human immunodeficiency virus-infected individual. Lymph node involvement as a presenting feature in Cryptococcosis is not a common manifestation. A prompt diagnosis is of utmost importance in this disseminated form of cryptococcosis. There are very few reports, however, of cryptococcal lymphadenitis as a presenting feature. We report here a case of cryptococcal lymphadenitis that was diagnosed by fine-needle aspiration cytology of the involved cervical lymph node.

Alder-Reilly Anomaly in Hurler's Syndrome in a Neonate: A Rare Case Report.

A 22-days-old male newborn baby presented with persistence of neonatal jaundice since birth. On clinical examination he had coarse facial features, a prominent forehead, enlarged tongue, icterus, hepatosplenomegaly, skeletal deformities and bilateral inguinal hernia. On investigation the peripheral smear revealed Alder-Reilly anomaly in the neutrophils suggesting mucopolysaccharidosis. Mucopolysaccharide excretion spot test of the urine was positive; and an assay for glycosaminoglycans in the urine was also high, which confirmed the clinical diagnosis of Hurler's syndrome. We present this rare case to highlight the association of Alder-Reilly anomaly and bilateral inguinal hernia in Hurler's syndrome even in neonates.

Profile of patients with incidentally detected nonalcoholic fatty liver disease (IDNAFLD) in coastal eastern India.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) has emerged as the commonest hepatic problem in both developed and developing countries. This study was conducted to delineate the clinical profile of incidentally detected NAFLD patients. METHODS: A retrospective analysis of clinical, biochemical and histological parameters was performed for 632 patients in whom fatty liver was diagnosed by ultrasonography during 2006-2010. Every patient's clinical presentation, history, liver function tests, blood sugar, lipid profile, ultrasonogram, histology and other relevant investigations were analyzed. Patients referred for transaminitis or overt chronic liver disease were excluded. RESULTS: Out of 632 consecutive NAFLD patients, 484 (76.6%) were males and 148 (23.4%) were females. Mean age of our patients was 42.44 +/- 10.18 years. Their mean body mass index (BMI) was 26.14 +/- 3.38 kg/m2. Obesity (BMI > 25), diabetes mellitus, hypertension, hyperlipidemia, metabolic syndrome and insulin resistance were present in 61.7%, 15.2%, 19.8%, 62.0%, 40.0%, and 54.4% patients, respectively. SGOT and SGPT were elevated in 38.29% and 55.1% patients, respectively. The common primary diseases for which these patients sought consultation were non-ulcer dyspepsia (NUD) (54.5%) and irritable bowel syndrome (IBS) (29.4%). Of the 64 patients who underwent liver biopsy, one-fourth had definite NASH while one-third patients had fibrosis. CONCLUSION: In India, incidentally detected NAFLD (IDNAFLD) patients are predominantly middle aged males, most of whom are not lean. Most of these patients seek consultation for functional bowel disease.

Extraovarian primary peritoneal papillary serous carcinoma.

OBJECTIVE: To identify an unusual histologic entity, extraovarian primary peritoneal carcinoma (EOPPC) along with a review of the recent literature. METHODS: A thorough clinical examination along with detail laboratory parameters was studied in a 56-year-old female who presented with ascites and an elevated serum CA-125. Multiple microscopic sections were studied from the surgical specimen received comprising of total hysterectomy, bilateral salpingo-oophorectomy and omentectomy. RESULTS: A diagnosis of EOPPC was made after a thorough study. CONCLUSION: A correct diagnosis and timely management of this unusual histologic entity can result in long-term disease-free survival of the patient.

Cytodiagnosis of granular cell tumor: a case report.

A young male aged 28 years presented with a subcutaneous nodule in the left arm. Fine needle aspiration diagnosis was benign granular cell tumor which was confirmed by histopathology. Since it is an uncommon tumor, of controversial histogenesis, it is being reported here.

Endovascular papillary angioendothelioma in an elderly female.

Endovascular papillary angioendothelioma (EPA) is a rare vascular tumor of low grade malignancy, encountered primarily in children. However some cases have also been reported in adults. A sixty year old female with EPA is described here. She presented with a swelling in the neck. Total surgical excision was performed. Histomorphology revealed anastomosing lymphatic channels showing intraluminal papillary fronds with hyaline vascular cores and hobnailing of endothelial cells. A diagnosis of EPA was made based on this picture. This tumor is recurrent and nodal metastasis has been reported in some cases.