17-Beta-Hydroxysteroid Dehydrogenase 13 Loss of Function Does Not Confer Protection to Nonalcoholic Fatty Liver Disease in Indian Population.

Background: A splice variant in HSD17B13 gene is demonstrated to protect against nonalcoholic fatty liver disease (NAFLD), and mitigate the effect of Patatin-like phospholipase domain-containing 3 (PNPLA3-I148M). It is being explored as a putative drug target and in polygenic risk scores. Based on whole exome sequencing (WES) in our cohort of biopsy proven NAFLD and limited data on the variant in our ethnicity, we sought to explore its role. Methods: This is a cross-sectional study that recruited 1,020 individuals with ultrasound/biopsy-confirmed NAFLD and matched controls. Liver enzymes and lipid profiles were estimated (Beckman coulter LX750/DXH800); WES was performed in NAFLD patients and controls (Illumina; HiSeqX); HSD17B13-A-INS/I148M-PNPLA3 variants were genotyped (sequencing/qR T-PCR); HSD17B13 protein expression was estimated (immunohistochemistry); the Student's t-test/Mann-Whitney U/Chi-square test and odds ratio (95% confidence interval) were used. Results: There was no significant difference (Odds ratio = 0.76; 95% CI -0.57 to 1.03; P = 0.76) in the frequency of the rs72613567-A-INS between controls and patients (17.8% vs. 14.4%). No difference in the ALT (Alanine transaminase; 72.24 ± 65.13 vs. 73.70 ± 60.06; P = 0.51) and AST levels (Aspartate aminotransferase; 60.72 ± 55.59 vs. 61.63 ± 60.33; P = 0.91) between HSD17B13-wild and variant carriers were noted. Significantly elevated liver enzymes were seen in PNPLA3-148-variant/HSD17B13-wild compared with PNPLA3-148-variant/HSD17B13-variant (90.44 ± 59.0 vs. 112.32 ± 61.78; P = 0.02). No difference in steatosis (P = 0.51) between HSD17B13-wild and variant carriers was noted. No other variants in the intron-exon boundaries were identified. Although, protein expression differences were noted between wild and variant carriers, no difference in the extent of steatosis was seen. Conclusion: Our study reports lack of association of the splice variant with reduced risk of NAFLD, and mitigating the effect of PNPLA3 variant. Ethnicity-based validation must be carried out before including it in assessing protection against NAFLD.

Hemophagocytic Lymphohistiocytosis Masquerading as Acute Liver Failure: A Single Center Experience.

BACKGROUND/AIM: Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening disorder of extreme inflammation and unregulated immune response which require prompt recognition and early introduction of definitive therapy. HLH can present with wide range of hepatic dysfunction ranging from mild elevation of transaminases to liver failure. This study is carried out to describe the clinical and laboratory presentation of HLH. METHODS: Patients who were diagnosed with HLH between January 2013 and December 2015 were retrospectively included in this study. RESULTS: Six patients were diagnosed as secondary HLH with median age of 28.5 years at diagnosis. All patients were presented with history of deep jaundice and high grade fever with pancytopenia and splenomegaly. Underlying diagnosis was viral infections in 4 and probable viral infection in remaining two. Bone marrow hemophagocytosis was present in 3 cases. Three patients were treated with corticosteroids only and one each with corticosteroids with cyclosporine or intravenous immunoglobulin (IVIG) and HLH treatment protocol. One patient died due to acute respiratory distress syndrome (ARDS); another patient died in follow-up due to respiratory failure due to pneumonia. CONCLUSIONS: HLH is rare and potentially life-threatening cause of prolonged fever, jaundice and pancytopenia. Early diagnosis and initiation of specific therapy can improve clinical outcome.

Feasibility and efficiency of a new 22G core needle: a prospective comparison study.

BACKGROUND AND STUDY AIMS: Histological examination of core tissue samples may have advantages over cytology in endoscopic ultrasound (EUS)-guided sampling. We aimed to evaluate the feasibility and efficiency of a new 22G core biopsy needle. PATIENTS AND METHODS: Consecutive patients with a pancreatic mass lesion or peri-intestinal lymphadenopathy sequentially underwent fine needle biopsy with both a newly developed 22G core needle (the FNB needle) and a standard 22G fine needle aspiration (FNA) needle, in randomized order. RESULTS: In 144 patients, mean age 48 years (± standard deviation [SD] 14; range 18 - 82), with 145 lesions (mean lesion size 39 ± 15 mm, range 15 - 99), EUS-guided sampling was technically feasible with both needles in all patients. Mean number of passes to obtain sufficient tissue was 1.2 ± 0.5 with the core needle vs. 2.5 ± 0.9 with the standard needle (P < 0.001). FNB specimens were adequate for evaluation in 125 (86.2 %) vs. 127 (87.6 %) with FNA (P = 0.72). Among 139 patients available for follow-up, FNB provided a correct diagnosis in 110 (79.1 %) and FNA in 112 (80.6 %) (P = 0.73). Sensitivity, specificity, positive and negative predictive values, and accuracy for diagnosis of malignancy were 90 %, 100 %, 100 %, 93 %, 96 % for FNB and 77 %, 100 %, 100 %, 85 %, 92 % for FNA, respectively (P > 0.05). CONCLUSION: FNB with the new 22G core needle was technically feasible, efficient and comparable to FNA with a standard needle. The core needle required fewer passes to provide an adequate sample, offering potentially shorter procedure time.

The diagnostic accuracy and strength of agreement between endoscopic ultrasound and histopathology in the staging of ampullary tumors.

AIM: Ampullary tumors are rare. Reports on ampullary tumor staging are heterogeneous and combine both periampullary and ampullary tumors. This study assessed the performance of endoscopic ultrasound (EUS) in the local staging of ampullary tumors only. METHODS: Data were collected retrospectively. We included patients with an ampullary tumor who underwent EUS and surgical resection. Tumor (T) and nodal (N) TNM staging for EUS and histopathological (HP) staging were compared. RESULTS: From 2009 to 2010, a total of 79 patients with ampullary tumors were identified. Of these, 26 had both EUS and Whipple's surgery and were included (28 did not undergo resection, 13 had palliative surgery only and 12 had resection without EUS). For T staging by HP, there were 2 (7.7 %) T1, 11 (42.3 %) T2, 12 (46.2 %) T3 and 1 (3.8 %) T4 tumors. The accuracy of EUS T staging was 73.1 % with a Kappa value of 0.564 (p < 0.0001). The sensitivity, specificity, positive predictive value (PPV), negative predictive values (NPV) of EUS, respectively were 50.0 %, 91.7 %, 33.3 % and 95.7 % for T1 tumors; 81.8 %, 80.0 %, 75.0 % and 85.7 % for T2; 75.0 %, 92.9 %, 90.0 % and 81.3 % for T3 tumors. For N staging by HP, 17 (65.4 %) were N0 and 9 (34.6 %) N1. The N staging diagnostic accuracy was 80.8 % with a Kappa value of 0.586 (p = 0.003). The sensitivity, specificity, PPV, NPV for N0 disease were 82.4 %, 77.8 %, 87.5 % and 70.0 %, respectively while for N1 they were 77.8 %, 82.4 %, 70.0 % and 87.5 %, respectively. CONCLUSIONS: EUS had a moderate strength of agreement with histopathology for both T and N staging, and a high diagnostic accuracy for nodal staging.

Indian task force for celiac disease: current status.

There are limited data on celiac disease (CD) from India. The limited knowledge about CD in India might be attributed to several factors. The first meeting of the Indian Task Force for Celiac Disease was held in the Asian Institute of Gastroenterology, Hyderabad, India in December 2008. The objectives of the meeting were to focus research on prevalence of CD in the wheat-eating Northern vs the rice-eating Southern Indian population, low-budget serological assays to study the underprivileged population, to involve other medical subspecialties in CD, to suggest proper legislation regarding wheat food labeling, and to organize affordable food substitutes for patients with celiac disease.