Melanoma, although only making up a small subset of cutaneous malignancies, accounts for a significant amount of morbidity and mortality. This is reportedly secondary to the high metastatic propensity of the tumour [6]. Liver metastasis secondary to malignant melanoma is relatively common, however, substantial replacement of liver by tumour resulting in impaired liver function is rare and limited to case reports [3, 7,8,9,10,11,12,13,14,15,16,17,18,19,20]. This case shares similarities with previously published cases, namely the rapid progression to liver failure and subsequent death,

Histologically, melanoma dissemination is characterized by leukemoid tumour infiltration of the liver sinusoids leading to obstruction, hepatocellular death, and liver failure [19]. Clinically, hepatic infiltration of MM is difficult to distinguish from other primary causes of hepatitis. Biochemical signs that increase suspicion of an underlying malignant aetiology include mild to moderately elevated serum aminotransferases, ALP and bilirubin levels, while an elevated lactate dehydrogenase (LDH) has been associated with tumour involvement previously [5]. LDH elevation has been previously identified as an ominous sign in the context of acute liver failure secondary to metastatic malignancy, as demonstrated in the presented case [8, 11, 17]. This is perceived to be secondary to extensive cellular ischaemia and necrosis, or related to release of LDH from the tumor cells themselves [8]. Imaging features are usually non-specific, however, hepatomegaly without defined nodular lesions is a usual manifestation of diffuse hepatic melanoma infiltration [20].

Previously, the pathophysiology of acute liver failure in the context of MM was postulated to be secondary to hepatic ischemia arising from sinusoidal infiltration and vessel invasion. This is supported in the case of the presented patient by the dramatic rise in serum aminotransferases and LDH, as well as the presence of pain [11]. It has also been hypothesised that simple replacement of the liver parenchyma by melanoma itself results in rapid liver failure [8].

Clinically, patients present with non-specific symptoms such as pain, fatigue, nausea and anorexia. The prognosis of the disease is exceedingly poor with life expectancy ranging from days to months based on previous case reports, while the diagnosis is commonly made posthumously due to severe coagulopathy precluding liver biopsy [20]. Treatment focuses on targeting the underling malignancy with a view to stabilise hepatic function to prevent further decompensation, however, given the degree of liver involvement in the presented case, it was deemed that despite immunotherapy, rapid progression of his underlying acute hepatic failure was the likely cause of death.

This case highlights an exceedingly uncommon cause of acute hepatic failure which initially presented with features suggestive of hepatitis. A potential diagnosis of immune checkpoint inhibitor hepatitis was flagged as a differential diagnosis, however, due to the coagulopathy, a biopsy was not pursued. MM is an extremely rare cause of acute liver failure with the literature limited to case reports. In such cases, the prognosis is poor, as demonstrated with the presented patient. Future research should aim to focus on the identification of early non-invasive biomarkers that could assist in aiding clinicians in the early diagnosis of hepatic metastasis in the case of metastatic melanoma. Early identification of hepatic disease in metastatic melanoma should prompt clinicians to implement or escalate therapy given the poor prognosis associated with progression to hepatic failure. In the case of rapid liver failure secondary to MM, the pathophysiology of the disease process is a relatively unknown entity given the lack of published literature pertaining to it. With earlier identification of metastatic disease, perhaps future studies could aim to focus on the tumor microenvironment in the liver to determine the processes that occur at a cellular level that drives progression to liver failure. In the case of abdominal pain with progressive liver function derangement and subsequent acute hepatic failure, metastatic malignancy, including but not limited to MM, should be considered as a potential diagnosis given its associated poor prognosis.