Although Fulvestrant is a steroidal antiestrogen and it can be associated with liver enzyme elevations, there is no cases of ALF described in literature. In case described liver biopsy excluded this hypothesis. Although liver metastasizing is a common phenomenon, ALF from the spread of the tumor is rare and can be a diagnostic challenge. Clinical, laboratory and radiologic findings are often nonspecific and inconclusive, as it were the case with our patient [
1]. According to the largest review of ALF, only 32 cases induced by diffuse metastatic breast cancer have been reported between 1950 and 2014 [
6]. The average age described is 47.9 ± 9.9 years such as in the case reported [
6]. Most of reported cases have occurred in patients with a previous history of known and treated breast cancer. Ductal carcinoma, like in the present case, is the most frequent one [
6]. Our patient had non-specific prodromal symptoms, such malaise and nausea 2 weeks prior to the onset of liver failure, as it has been described [
4]. Typically, liver metastases are asymptomatic with a focal/target pattern of parenchymal infiltration on ultrasonography and contrast-CT [
2]. However, in ALF, as in case reported, imaging may be not specific, without any focal abnormality of the liver parenchyma. In contrast, in such cases tumor cells invade diffusely liver sinusoids, without involving the parenchyma. Thus, liver surface is smooth, with a preserved shape and with no nodularity, despite an important degree of tumor infiltration. Hence, due to diffuse nature of spread typical findings are not seen on radiologic imaging [
2] and the majority of the cases of ALF induced by metastatic infiltration are diagnosed after death [
2,
7]. In a recent review of literature only 25% of cases were diagnosed premortem [
6]. However, a significant trend for increased
premortem diagnosis has been noticed [
6]. Several mechanisms have been proposed to explain the molecular mechanism of massive liver infiltration and hepatocellular injury that occur in such cases. First, loss of cellular adhesion molecules expression as E-cadherin and CD44 can be involved in this process. The first one, being a cell-to-cell and cell-to-extracellular-matrix adhesion protein, when absent allows cell detachment from the primary tumor and single-cell infiltration. On the other hand, CD44 is responsible for endothelium adhesion and its absence may reflect an inability of the metastatic cells to invade beyond the sinusoidal endothelium preventing the formation of a mass in the parenchyma (intrasinusoidal pattern) [
5,
8,
9]. Also, invasion of hepatic vessels by tumor cells may result in ischemia with neoplastic cells exerting a pressure effect on hepatocytes competing for nutrients and oxygen, finally leading to liver cell necrosis [
2]. Hepatic metastases, including from breast cancer, can also mimic cirrhosis [
7,
9]. This “pseudocirrhosis” or carcinomatous cirrhosis is the result of a desmoplastic response of the liver. Due to the infiltrating tumor and the associated inflammation, stellate cells are activated and produce collagen, causing an extensive fibrosis that results in the atrophy of hepatocytes [
5‐
9].
Most cases of ALF from neoplastic invasion have an extremely poor prognosis, with death occurring from 3 days to 6 months after presentation [
2]. The mortality rate of breast carcinoma with diffuse hepatic infiltration is 3 days to 2 months after presentation in 90% of the cases. [
2].
Premortem diagnosis is important because it affects therapy. Hepatic transplantation is contraindicated for this etiology and chemotherapy is limited by severally abnormal liver function and multiorganic failure [
5]. Nonetheless, there are a few clinical cases of patients with metastatic disease unrecognized prior to transplantation that underwent liver transplantation and adjuvant chemotherapy with success [
3]. There are also two cases of short-term reversal of ALF from metastatic breast cancer after chemotherapy with longer survival (9 months) [
5,
10].
In conclusion, we report a case of a rare cause of ALF induced by metastatic breast cancer. Although rare, physicians must have a high index of suspicion to consider this etiology when approaching a case of ALF, as diffuse intrasinusoidal hepatic metastases of breast cancer can infiltrate the liver with imaging studies remaining normal. There may be a role for liver transplantation in strict selected patients.