Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Nov 27, 2021; 13(11): 1707-1726
Published online Nov 27, 2021. doi: 10.4254/wjh.v13.i11.1707
Mitochondrial hepatopathy: Respiratory chain disorders- ‘breathing in and out of the liver’
Amrit Gopan, Moinak Sen Sarma
Amrit Gopan, Department of Gastroenterology, Seth G.S Medical College and K.E.M Hospital, Mumbai 400012, India
Moinak Sen Sarma, Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
Author contributions: Gopan A conducted literature review, wrote the initial draft, and designed figures and tables; Sarma MS conceptualized the study, framed the design of the paper, and did critical revisions in structuring the final manuscript; Both authors have read and approved the final document.
Conflict-of-interest statement: Gopan A and Sarma MS declare no conflict of interest related to this publication.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Moinak Sen Sarma, DM, Associate Professor, Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Rae Bareilly Road, Lucknow 226014, India.
Received: May 24, 2021
Peer-review started: May 24, 2021
First decision: June 15, 2021
Revised: June 30, 2021
Accepted: August 18, 2021
Article in press: August 18, 2021
Published online: November 27, 2021

Mitochondria, the powerhouse of a cell, are closely linked to the pathophysiology of various common as well as not so uncommon disorders of the liver and beyond. Evolution supports a prokaryotic descent, and, unsurprisingly, the organelle is worthy of being labeled an organism in itself. Since highly metabolically active organs require a continuous feed of energy, any dysfunction in the structure and function of mitochondria can have variable impact, with the worse end of the spectrum producing catastrophic consequences with a multisystem predisposition. Though categorized a hepatopathy, mitochondrial respiratory chain defects are not limited to the liver in time and space. The liver involvement is also variable in clinical presentation as well as in age of onset, from acute liver failure, cholestasis, or chronic liver disease. Other organs like eye, muscle, central and peripheral nervous system, gastrointestinal tract, hematological, endocrine, and renal systems are also variably involved. Diagnosis hinges on recognition of subtle clinical clues, screening metabolic investigations, evaluation of the extra-hepatic involvement, and role of genetics and tissue diagnosis. Treatment is aimed at both circumventing the acute metabolic crisis and long-term management including nutritional rehabilitation. This review lists and discusses the burden of mitochondrial respiratory chain defects, including various settings when to suspect, their evolution with time, including certain specific disorders, their tiered evaluation with diagnostic algorithms, management dilemmas, role of liver transplantation, and the future research tools.

Keywords: Mitochondrial hepatopathy, Respiratory chain defects, Maternal inheritance, Neonatal liver failure, DNA depletion syndrome, Pearson syndrome

Core Tip: Liver disease with multi-system involvement should arouse the suspicion for mitochondrial respiratory chain hepatopathies. These disorders are predominantly autosomal recessive with some having a maternal inheritance. Presence of lactic acidosis without hypoglycemia is an important clue. A tiered evaluation yields the most data, with the final step being a genetic and enzyme analysis from tissue of interest. Treatment is largely supportive with blood transfusions, correction of acidosis and shock, providing cofactors and salvage therapies, with liver transplantation in a select group. A periodic follow-up is mandatory for monitoring evolution of disease including “migration” to other systems.