Mitochondrial DNA depletion consisting the systemic reduction of mtDNA copy number in cells may have a heterogenous genetic basis, resulting from pathogenic change in nuclear genes involved in mtDNA synthesis. The mode of inheritance is autosomal recessive. Severe hepatocerebral disease, represents one of many different clinical forms of so called mitochondrial depletion syndrome (MDS). We present liver histopahology of 13 children, who eventually died in the course of hepatocerebral MDS confirmed molecularly, harbouring mutations of DGUOK, MPV17, and POLG genes. Material comprising 8 autopsy and 5 liver biopsy specimens showed quite reproducible pattern of parenchymal damage which we consider potentially helpful in differential diagnosis and planning of the diagnostic investigation in families of children who died due to early onset acute liver failure and encephalopathy.