Kausik Das1, Abhijit Chowdhury2. 1. Department of Hepatology, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, 244 A.J.C. Bose Road, Kolkata, 700020, India. kausikdasmail@gmail.com. 2. Department of Hepatology, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, 244 A.J.C. Bose Road, Kolkata, 700020, India. achowdhury2002@yahoo.co.in.
Abstract
INTRODUCTION: Non-alcoholic fatty liver (NAFL) in the absence of overweight and/or obesity, defined by the anthropometric parameter, body mass index (BMI), has been designated as 'lean NASH.' While maintaining a close pathophysiological link with metabolic syndrome (MS) and insulin resistance (IR), the presence of subtle alterations in measures of total body and regional adiposity not exceeding the designed cut-offs, are hallmarks of 'lean NASH.' MATERIAL AND METHODS: Available literature related to non-alcoholic steatohepatitis (NASH) in lean or non-obese individuals and its pathogenesis in general published in English language journals till the time of manuscript preparation were reviewed and critically analysed. ANALYSIS: Being a closely related but variant phenotype of NASH, its features metabolically resemble the well-characterized entity 'metabolically obese normal weight (MONW)' individuals. Apart from total body adiposity, distribution of fat in different body compartments has assumed greater pathophysiologic relevance in characterizing 'lean NASH'. Detection of NASH in stringently defined non-obese individuals, by both BMI and waist circumference indices, indicates existence of a subset of NASH in which fat compartmentalization at ectopic sites is not picked up by the anthropometric yardsticks used. Volume [Quantity] and biological behavior of the visceral and deep subcutaneous adipose tissues contribute to this variant of NASH in non-obese subjects. Genetic predisposition to IR and MS along with the environmental influences like childhood nutritional status, dietary composition and gut microbiome possibly play pathogenetic role. CONCLUSION: The most important concern is in the principles of nomenclature within syndromes where clinical dissimilarities exist despite biological similarities. Till a uniformly acceptable pathophysiological and/or etiology-based classification emerges, the term "lean NASH" would continue to provide us an opportunity to ponder over and refine this subset of fatty liver in non-obese people and potentially significant liver disease.
INTRODUCTION:Non-alcoholic fatty liver (NAFL) in the absence of overweight and/or obesity, defined by the anthropometric parameter, body mass index (BMI), has been designated as 'lean NASH.' While maintaining a close pathophysiological link with metabolic syndrome (MS) and insulin resistance (IR), the presence of subtle alterations in measures of total body and regional adiposity not exceeding the designed cut-offs, are hallmarks of 'lean NASH.' MATERIAL AND METHODS: Available literature related to non-alcoholic steatohepatitis (NASH) in lean or non-obese individuals and its pathogenesis in general published in English language journals till the time of manuscript preparation were reviewed and critically analysed. ANALYSIS: Being a closely related but variant phenotype of NASH, its features metabolically resemble the well-characterized entity 'metabolically obese normal weight (MONW)' individuals. Apart from total body adiposity, distribution of fat in different body compartments has assumed greater pathophysiologic relevance in characterizing 'lean NASH'. Detection of NASH in stringently defined non-obese individuals, by both BMI and waist circumference indices, indicates existence of a subset of NASH in which fat compartmentalization at ectopic sites is not picked up by the anthropometric yardsticks used. Volume [Quantity] and biological behavior of the visceral and deep subcutaneous adipose tissues contribute to this variant of NASH in non-obese subjects. Genetic predisposition to IR and MS along with the environmental influences like childhood nutritional status, dietary composition and gut microbiome possibly play pathogenetic role. CONCLUSION: The most important concern is in the principles of nomenclature within syndromes where clinical dissimilarities exist despite biological similarities. Till a uniformly acceptable pathophysiological and/or etiology-based classification emerges, the term "lean NASH" would continue to provide us an opportunity to ponder over and refine this subset of fatty liver in non-obesepeople and potentially significant liver disease.
Authors: Margareta Jernås; Jenny Palming; Kajsa Sjöholm; Eva Jennische; Per-Arne Svensson; Britt G Gabrielsson; Max Levin; Anders Sjögren; Mats Rudemo; Theodore C Lystig; Björn Carlsson; Lena M S Carlsson; Malin Lönn Journal: FASEB J Date: 2006-06-05 Impact factor: 5.191
Authors: Stephen S Lim; Theo Vos; Abraham D Flaxman; Goodarz Danaei; Kenji Shibuya; Heather Adair-Rohani; Markus Amann; H Ross Anderson; Kathryn G Andrews; Martin Aryee; Charles Atkinson; Loraine J Bacchus; Adil N Bahalim; Kalpana Balakrishnan; John Balmes; Suzanne Barker-Collo; Amanda Baxter; Michelle L Bell; Jed D Blore; Fiona Blyth; Carissa Bonner; Guilherme Borges; Rupert Bourne; Michel Boussinesq; Michael Brauer; Peter Brooks; Nigel G Bruce; Bert Brunekreef; Claire Bryan-Hancock; Chiara Bucello; Rachelle Buchbinder; Fiona Bull; Richard T Burnett; Tim E Byers; Bianca Calabria; Jonathan Carapetis; Emily Carnahan; Zoe Chafe; Fiona Charlson; Honglei Chen; Jian Shen Chen; Andrew Tai-Ann Cheng; Jennifer Christine Child; Aaron Cohen; K Ellicott Colson; Benjamin C Cowie; Sarah Darby; Susan Darling; Adrian Davis; Louisa Degenhardt; Frank Dentener; Don C Des Jarlais; Karen Devries; Mukesh Dherani; Eric L Ding; E Ray Dorsey; Tim Driscoll; Karen Edmond; Suad Eltahir Ali; Rebecca E Engell; Patricia J Erwin; Saman Fahimi; Gail Falder; Farshad Farzadfar; Alize Ferrari; Mariel M Finucane; Seth Flaxman; Francis Gerry R Fowkes; Greg Freedman; Michael K Freeman; Emmanuela Gakidou; Santu Ghosh; Edward Giovannucci; Gerhard Gmel; Kathryn Graham; Rebecca Grainger; Bridget Grant; David Gunnell; Hialy R Gutierrez; Wayne Hall; Hans W Hoek; Anthony Hogan; H Dean Hosgood; Damian Hoy; Howard Hu; Bryan J Hubbell; Sally J Hutchings; Sydney E Ibeanusi; Gemma L Jacklyn; Rashmi Jasrasaria; Jost B Jonas; Haidong Kan; John A Kanis; Nicholas Kassebaum; Norito Kawakami; Young-Ho Khang; Shahab Khatibzadeh; Jon-Paul Khoo; Cindy Kok; Francine Laden; Ratilal Lalloo; Qing Lan; Tim Lathlean; Janet L Leasher; James Leigh; Yang Li; John Kent Lin; Steven E Lipshultz; Stephanie London; Rafael Lozano; Yuan Lu; Joelle Mak; Reza Malekzadeh; Leslie Mallinger; Wagner Marcenes; Lyn March; Robin Marks; Randall Martin; Paul McGale; John McGrath; Sumi Mehta; George A Mensah; Tony R Merriman; Renata Micha; Catherine Michaud; Vinod Mishra; Khayriyyah Mohd Hanafiah; Ali A Mokdad; Lidia Morawska; Dariush Mozaffarian; Tasha Murphy; Mohsen Naghavi; Bruce Neal; Paul K Nelson; Joan Miquel Nolla; Rosana Norman; Casey Olives; Saad B Omer; Jessica Orchard; Richard Osborne; Bart Ostro; Andrew Page; Kiran D Pandey; Charles D H Parry; Erin Passmore; Jayadeep Patra; Neil Pearce; Pamela M Pelizzari; Max Petzold; Michael R Phillips; Dan Pope; C Arden Pope; John Powles; Mayuree Rao; Homie Razavi; Eva A Rehfuess; Jürgen T Rehm; Beate Ritz; Frederick P Rivara; Thomas Roberts; Carolyn Robinson; Jose A Rodriguez-Portales; Isabelle Romieu; Robin Room; Lisa C Rosenfeld; Ananya Roy; Lesley Rushton; Joshua A Salomon; Uchechukwu Sampson; Lidia Sanchez-Riera; Ella Sanman; Amir Sapkota; Soraya Seedat; Peilin Shi; Kevin Shield; Rupak Shivakoti; Gitanjali M Singh; David A Sleet; Emma Smith; Kirk R Smith; Nicolas J C Stapelberg; Kyle Steenland; Heidi Stöckl; Lars Jacob Stovner; Kurt Straif; Lahn Straney; George D Thurston; Jimmy H Tran; Rita Van Dingenen; Aaron van Donkelaar; J Lennert Veerman; Lakshmi Vijayakumar; Robert Weintraub; Myrna M Weissman; Richard A White; Harvey Whiteford; Steven T Wiersma; James D Wilkinson; Hywel C Williams; Warwick Williams; Nicholas Wilson; Anthony D Woolf; Paul Yip; Jan M Zielinski; Alan D Lopez; Christopher J L Murray; Majid Ezzati; Mohammad A AlMazroa; Ziad A Memish Journal: Lancet Date: 2012-12-15 Impact factor: 79.321
Authors: Manisha Chandalia; Ping Lin; Thanalakshmi Seenivasan; Edward H Livingston; Peter G Snell; Scott M Grundy; Nicola Abate Journal: PLoS One Date: 2007-08-29 Impact factor: 3.240
Authors: Alexandra Feldman; Sebastian K Eder; Thomas K Felder; Lyudmyla Kedenko; Bernhard Paulweber; Andreas Stadlmayr; Ursula Huber-Schönauer; David Niederseer; Felix Stickel; Simon Auer; Elisabeth Haschke-Becher; Wolfgang Patsch; Christian Datz; Elmar Aigner Journal: Am J Gastroenterol Date: 2016-08-16 Impact factor: 10.864
Authors: Kathryn D Tuttle; Katherine A Waugh; Paula Araya; Ross Minter; David J Orlicky; Michael Ludwig; Zdenek Andrysik; Matthew A Burchill; Beth A J Tamburini; Colin Sempeck; Keith Smith; Ross Granrath; Dayna Tracy; Jessica Baxter; Joaquin M Espinosa; Kelly D Sullivan Journal: Cell Rep Date: 2020-11-17 Impact factor: 9.423
Authors: Jeong-Ju Yoo; Won Kim; Moon Young Kim; Dae Won Jun; Sang Gyune Kim; Jong-Eun Yeon; Jin Woo Lee; Yong Kyun Cho; Sang Hoon Park; Joo Hyun Sohn Journal: Clin Mol Hepatol Date: 2018-08-08