Chemotherapy Treatment

Chemotherapy can produce several liver changes such as steatosis, steatohepatitis and sinusoidal obstruction syndrome (SOS), which can lead to the development of regenerative nodular lesions, mainly focal nodular hyperplasia like (FNH). This association is typical in patients who are treated for colorectal cancer with oxaliplatin and developed de novo FNH-like lesions (5,6). Oxaliplatin induces SOS, which leads to perfusion imbalance with increased arterial hepatic inflow, which is thought to be the cause of nodular regenerative hyperplasia (NRH) nodules, as well as FNH-like (6,7,8,9,10,11) (Figures 1,2,3). NRH is a rare condition characterized by the diffuse transformation of normal liver into small regenerative nodules with little or no fibrosis. The diagnosis of NRH is hystological. NRH usually becomes clinically evident years after the liver injury, on MRI the liver parenchyma can seem heterogeneous and signs of portal hypertension can be observed or on the other hand, regenerative nodules can clearly be seen on imaging. NRH nodules can be hypointense in early dynamic phases with progressive contrast enhancement in portal and delayed phases. In the hepatobiliary phase, NRH nodules are iso or hyperintense to the liver.

FNH-like nodules have similar imaging findings as classic FNH. 

Regenerative nodules and FNH-like lesions have also been described in patients receiving other chemotherapy agents, myeloproliferative disorders and in hematopoietic stem cell transplantation (Figure 4). (Table 1). 

Cardiac diseases

Hepatocellular lesions can also occur in long-standing heart failure or patients with chronic constrictive pericarditis due to low cardiac output and passive venous congestion (Figures 5,6,7).

Liver alterations have also been described in patients with a single functioning ventricle who have undergone the Fontan procedure, where an anastomosis between the cava vein or the right atrium and the pulmonary arteries is performed (4,12). Passive venous congestions and chronic hepatic ischemia from low cardiac output are mechanisms that lead to hepatic dysfunction with posteriorly fibrosis and cirrhosis. Patients with Fontan procedure and, especially, cirrhosis can develop hepatocellular carcinoma (HCC) in long-standing disease; therefore, these patients should be regularly screened. FNH-like lesions are frequent in patients with Fontan procedure and their diagnosis is difficult in the setting of cirrhosis where HCC has to be excluded. In patients with Fontan procedure benign FNH-like nodules can have washout in delayed phases. These nodules, usually, lack ancillary features favoring malignancy, such as signal hyperintensity on T2WI. In these cases, further evaluation with hepatobiliary agent may be helpful. Although less than 10% of HCC lesions can retain the hepatobiliary contrast agent, the presence of homogeneous contrast uptake in the hepatobiliary phase in a liver nodule in the setting of Fontan procedure, increases the probability that the nodule is benign (13) (Figure 8).

Congenital hepatic fibrosis

Vascular derangement in hepatic fibrosis leads to heterogeneous hepatic perfusion that contributes to the formation of regenerative nodules and other hepatocellular lesions like adenomatous hyperplasia. From a pathological point of view, the hypothesis for the development of regenerative nodules is supported by the presence of less portal vein branches and arteriovenous anastomosis (2). The most frequent lesions are FNH-like nodules, which have to be differentiated from HCC, especially in the setting of cirrhosis (Figure 9).

Rendu-Osler-Weber

Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome, is a genetic autosomal dominant disorder with dilatations of postcapillary venules that enlarge and merge with arterioles without the interposed capillary bed, forming arteriovenous communications. Liver involvement is associated with mutations in the ALK1 gene. As in other organs, microscopic telangiectasias and direct arteriovenous and portovenous shunts also occur in the liver parenchyma. The vascular lesions enlarge forming multiple intrahepatic shunts, including hepatic artery to portal vein (arterioportal), hepatic artery to hepatic vein (arteriosystemic), and portal vein to hepatic vein (portosystemic). The increase in hepatic flows leads to enlarged and tortuous hepatic arteries and portal veins (4,15). FNH-like nodules are the most common lesions in HTT, having a higher prevalence than in the general population (Figures 10,11).(Table 2). 

Budd-Chiari Syndrome (BCS)

This syndrome is characterized by hepatic outflow obstruction, thrombotic or not thrombotic, with hepatomegaly, ascites, and abdominal pain. Benign regenerative nodules have been also described. The hepatic congestion and venous obstructions lead to increased arterial flow and portal hypertension, causing parenchymal regenerative changes and cirrhosis. Increased survival of patients with BCS has increased the prevalence of regenerative nodules, especially FNH-like lesions (Figure 12). The differential diagnosis between regenerative nodule and HCC can be difficult, especially in the setting of cirrhosis, where stability in time, hepatobiliary contrast uptake, and serum alpha-fetoprotein (AFP) levels must be closely evaluated before any biopsy decision. The regenerative nodules in BCS have not been reported to have malignant potential (4,16). (Table 3).

Portal Cavernoma

Cavernous transformation of the portal vein occurs after portal vein thrombosis. The development of multiple collateral venous vessels aims to supply the portal inflow. However, it is not enough and the arterial hepatic inflow to the liver, finally, increases. Regenerative changes occur in the hepatic parenchyma with hypertrophy of the central segments and atrophy of the liver periphery (17). A single-center series demonstrated that FNH-like lesions are common in patients with portal cavernomatosis, with a prevalence of 21% (12 of 58 patients). Two imaging findings were common to all lesions, intense and homogenous enhancement in arterial dominant phase fading to isointensity later in venous and interstitial phases as well as an isointensity to the liver parenchyma on T2WI (Figure 13). All lesions in this study lacked a central scar, probably because of their small size (18). Postosystemic shunts for treatment of extrahepatic vein obstruction, especially in children, are associated with the development of FNH-like liver nodules (Figure 14). (Table 4). 

Alcoholic cirrhosis

Classic FNH occurs in normal liver parenchyma. FNH-like nodules are hyperplastic hepatocellular lesions similar to FNH that develop in cirrhotic liver, especially in alcoholic cirrhosis (Figure 15). FNH-like can have washout in delayed phases resembling HCC. Iso-hypointensity in T2 and homogenous contrast uptake in hepatobiliary phase favors a regenerative type nodule (19,20).