Mitochondrial hepatopathy: Respiratory chain disorders- ‘breathing in and out of the liver’

Abstract

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.