Liver lesions have a broad spectrum of pathologies ranging from benign liver lesions such as hemangiomas to malignant lesions such as primary hepatocellular carcinoma and metastasis. Imaging is a crucial step in diagnosing these conditions as liver enzymes can elevate in 8% of people in the U.S. A combination of medical history, serologic, and radiologic investigations can provide the diagnosis in most of these cases.[1] Liver lesions can be categorized into focal and diffuse liver lesions.

Focal liver lesions can subclassify into three main clinical categories.

1. Benign lesions that do not need treatment if they are asymptomatic, including hepatic hemangioma, focal nodular hyperplasia, and benign liver cysts
2. Benign lesions that require treatment, including hepatic adenoma, hepatic abscess, and adenomatosis
3. Malignant lesions, including hepatocellular carcinoma, cholangiocarcinoma, hepatic angiosarcoma, and liver metastases

Diffuse liver lesions can categorize into vascular, inflammatory diseases, and storage disease.

Benign liver lesions can be classified into 3 categories based on their origination:

Cholangiocellar: hepatic cyst, biliary cystadenoma, intraductal papillary neoplasm of the bile ducts, peribiliary cyst, intrahepatic bile adenoma,

Hepatocellular: focal nodular hyperplasia, hepatic adenoma

Mesenchymal: hemangioma, lipoma

Liver ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI) are the primary imaging modalities to diagnose liver lesions. Post intravenous (IV) contrast imaging has unique features in the liver because the liver has three distinct phases, which are the arterial phase, the portal venous phase, and the venous phase. The US can be a method of choice as a screening modality, and contrast-enhanced multidetector CT (MDCT) as a modality of choice in most hepatic imaging.

The most widely used anatomic classification of hepatic segments is Couinaud classification which describes eight functionally independent liver segments, based on vascularization, bile duct distribution, and lymphatic drainage. Each segment is a wedge-shaped with the apex directed towards the hepatic hilum. A single branch of the hepatic artery, portal vein, and bile duct enters through the apex into the hepatic segments. The hepatic vein runs between two adjacent segments and drains into the inferior vena cava (IVC). The middle hepatic vein, which runs from inferior vena cava to the gallbladder fossa, divides the liver into the right and left lobes. Right hepatic vein divides the right lobe into the anterior and posterior segments, and the falciform ligament divides the left lobe into medial and lateral segments. The portal vein divided each I horizontally into the superior and inferior segments. Segment I is the caudate lobe that has specific features, including the possibility of receiving dual blood supply from the right and left portal vein and draining directly into IVC. Segment II, III, and IV are left sections. Segments V, VI, VII, and VIII constitute the right hepatic section.

The hepatic blood supply is from the portal vein (about two-thirds), and the rest is from the hepatic artery; thus, maximum enhancement of the liver is attained during the portal venous phase, which is 60 to 120 seconds after the arterial phase enhancement. Tumors that get supply from the hepatic artery will enhance during the arterial phase, which was the principle in developing transarterial chemoembolization and chemoembolization. Arterial embolization and treatment targets tumors rather than normal hepatic cells.[2]

The hepatic veins enter the inferior vena cava and can be seen as echolucent tubes with thin walls. Portal triad which including the portal veins, hepatic arteries, and bile ducts surrounded by fibrofatty tissue, and can be seen as an echogenic foci throughout the liver. 

The portal vein forms from the junction of the superior mesenteric artery and splenic veins behind the neck of the pancreas. Inferior mesenteric vein, gastric, and cystic veins drain into the portal vein. It divides into the right hepatic vein and porta hepatis. Although the portal vein provides 75% of liver blood supply, it provides 50% of the oxygen supply of the liver. Portal hypertension or hepatic venous pressure gradient is defined as a portosystemic pressure gradient. Different pathologies can cause portal hypertension, including portal vein thrombosis, cirrhosis, viral hepatitis, Budd-Chiari syndrome, and congestive heart failure. US manifestations of portal hypertension are dilated portal vein (>13 mm), dilation of the splenic and superior mesenteric veins, presence of collateral vessels between the portal and systemic pathways, splenomegaly, ascites, and presence of biphasic or reversed flow (hepatofugal) in Doppler US which is diagnostic and pathognomonic for portal hypertension. Portal hypertension can be appreciated in CT and MRI with similar manifestations in the US and the presence of contrast in the paraumbilical vein, which is pathognomonic.

Hepatomegaly and liver cirrhosis are two main pathologies that distort the liver anatomy. Cardiac disease, including congestive heart failure, restrictive cardiomyopathy, and right-sided valvular disease, can cause hepatomegaly and dilation of hepatic veins, which is called passive hepatic congestion. It is due to hepatic venous drainage impairment and stasis of blood in hepatic parenchyma. US manifestations of passive hepatic congestion are right hepatic lobe enlargement, inferior vena cava, and hepatic vein enlargement. Changes in hepatic vein and IVC velocity pattern can be appreciated in color Doppler US with loss of normal triphasic flow and flattening of the waveform in hepatic veins. Congestive right heart failure also can cause painless, diffuse wall thickening of the gallbladder. The most common etiologies of cirrhosis are alcohol, followed by viral hepatitis, cryptogenic infection, vascular pathologies, and metabolic disorders. The most common US changes in cirrhosis are nodularity appearance in the surface, heterogeneous echotexture, relative enlargement of caudate lobe in comparison to the right lobe, and atrophy of the medial segment of the left lobe. The presence of portal hypertension imaging changes increase the sensitivity and specificity of cirrhosis based on the US changes, but these usually happen in the advanced and late stage of cirrhosis.[1]

Plain films are rarely useful in assessing hepatic pathology except to evaluate for hepatomegaly when the liver shadow extends beyond the shadow of the right kidney.

CT of the liver can be done with different protocols, including unenhanced, single-phase, dual-phase, and triphasic contrast-enhanced. Each of these liver CT protocols is important in the evaluation of different liver pathologies. The single-phase contrast-enhanced CT is generally the modality of choice in the portal venous phase in CT that is typically 70 seconds after intravenous (IV) contrast injection, and the liver has the maximum enhancement. It can provide information mainly about diffuse liver pathologies, for instance, liver cirrhosis, and hypovascular metastatic liver disease. The dual-phase contrast-enhanced CT is the primary imaging modality conducted in the portal venous phase and the late arterial phase, which can be obtained approximately 35 seconds after IV injection and might be able to provide better information about hypervascular lesions.[3] This protocol can be helpful in hypervascular metastatic lesions like renal cell carcinoma, breast cancer, melanoma, and endocrine tumors, and also for preoperative evaluation for partial hepatic resection. It can provide information about liver anatomy and its vasculature to the surgeon. Triphasic contrast-enhanced CT is non-enhanced, arterial and portal venous phase or arterial, venous, and the delayed phase. Arterial phase enhancement begins approximately 20 to 25 seconds after IV contrast injection. Hypervascular pathologies, like most benign and malignant hepatic lesions, can be appreciated in this phase. Triphasic protocols usually use in patients with possible cirrhosis and hepatocellular carcinoma (HCC). HCC is a hypervascular lesion that enhances during the arterial phase, and it has a fast wash-out during the portal venous phase. Cholangiocarcinoma is one of the liver pathologies that can be appreciated better in triphasic CT, with non-enhanced, portal venous phase and delayed phase (10 to 15 minutes) by hyperenhancement on the delayed phase because of the presence of plenty amount of fibrous tissue.

Fatty liver disease is a common condition that can present with different patterns. Because of its important and serious consequences in a long time, detailed descriptions of fatty changes by radiologists are important. Six main important patterns of fatty liver infiltrations are diffuse, focal, geographic, subcapsular, multifocal, and perivascular. Fatty liver changes are hyperechoic lesions in comparison to the spleen and renal cortex. Hepatic steatosis, either diffuse or focal, is best evaluated on a non-contrast CT of the abdomen. In hepatic steatosis, the liver measures at least 10 Hounsfield Units (HU) less than spleen on a non-contrast study. On a contrast-enhanced CT scan, the liver and spleen have different rates of contrast uptake. In the portal venous phase, a hepatic attenuation of 25 HU less than the spleen is suggestive of steatosis. Fatty liver disease in MRI can be appreciated by the signal drop in gradient-echo T1-weighted out-of-phase images in comparison to in-phase.

Diffuse fatty liver is the most common form of liver steatosis. The severity of involvement can be described in the US as mild, moderate, severe, and measure quantitively in MRI, as the most accurate non-invasive method. Diffuse steatosis with hepatomegaly and increased caudate-to right lobe ratio increase the possibility of non-alcoholic steatohepatitis (NASH). Focal hepatic steatosis can have similar imaging features as some benign and malignant liver lesions, in which MRI can be helpful to differentiate. Areas in the liver that are more susceptible for focal hepatic steatosis are peri vesicular and subcapsular adjacent to the hepatic hilum or falciform ligament, which are the same areas for focal hepatic sparing in the diffuse fatty infiltration as a result of altered intrahepatic blood flow with aberrant venous system and no portal inflow. Geographic fatty liver disease can be secondary to some parenchymal disease like cholangitis, or involvement of the right liver lobe can be related to the feeding of this part of the liver by the superior mesenteric vein, which has lipogenic materials from gastrointestinal tracts. Subcapsular fat deposition can be seen in insulin-dependent diabetes patients due to the accumulation of fat in the subcapsular region secondary to higher insulin concentration. Multifocal fat deposition can resemble metastasis, abscesses, lymphoma, sarcoidosis, and hemangiomatosis in the US and CT, but MRI can differentiate the presence of fat with the signal drop in out of phase images. Fat deposition around the portal vein and/or hepatic vein can have similar US and CT imaging characteristic features as Budd-Chiari syndrome, periportal edema, and MRI can differentiate fat deposition from other pathologies.

Non-contrast CT can be useful for the evaluation and detection of iron and calcium deposition in the liver. Amyloidosis and Wilson disease mainly have nonspecific liver imaging features. Amyloidosis, abnormal deposition of amyloid fibrils, can have a nonspecific liver imaging manifestation like diffuse hepatomegaly, or diffuse or focal areas of hypo attenuation, heterogeneous appearance, or periportal involvement.[4] Wilson disease is an autosomal recessive disorder that causes accumulation of copper in different organs such as basal ganglia, cornea, and liver. The CT manifestation of Wilson disease in the liver can be nodular areas of hyper attenuation as a result of fatty infiltration and copper accumulation in the liver.[5]

The presence of gas in the portal vein can have various etiologies, and it should be differentiated from pneumobilia, which is peripheral in portal venous gas in comparison to the pneumobilia, which is central. It will manifest as echogenic foci in the portal vein lumen in the US, and foci of low density in the liver, portal vein and its branches in CT. Pneumobillia is the presence of gas in the biliary tree, which is more central. Portal venous gas can be because of umbilical vein catheterization, necrotizing enterocolitis, postoperative finding in corrective bowel surgery in children, and can be related to ischemic bowel, inflammatory bowel disease, after upper and lower endoscopic procedure, intra-abdominal sepsis in adults. Pneumobillia can be seen in the setting of recent biliary instrumentation, incompetent sphincter of Oddi, biliary-enteric surgical anastomosis, spontaneous biliary-enteric fistula.

The hepatic abscess is one of the cystic liver lesions, usually from an infectious process in the gastrointestinal system that carried the infection to the liver via the portal venous system, and Escherichia coli is the most common microorganism. The imaging characteristic of a hepatic abscess is a double target sign, which is a central area of low attenuation, surrounded by two layers of rings. The inner layer can appear as a high attenuation rim, with early and persistent delayed contrast enhancement, and the outer layer enhances only in the delayed phase. Hepatic abscess in T2-weighted MRI is diagnosable with an irregular wall with late enhancement and central area of hyperintensity.[6] Candidiasis fungemia is another infection process that can occur in immunocompromised patients as a result of disseminated candidiasis. Liver and spleen involvement is visible in CT as multiple small hypoattenuating lesions, which may have ring-enhancing and can look like microabscesses. Although MRI has better sensitivity and specificity, CT has been using more frequently because it is less expensive and more accessible.[7]

Magnetic resonance (MR) imaging has some advantages and disadvantages in comparison to the US and CT. Lack of ionizing radiation, higher cross-sectional resolution, presence of extracellular and hepatocyte-specific contrast agents, and the ability to give better and more accurate information about the diffuse liver lesion and characterization of focal liver lesions make the MR the best imaging modality in liver imaging. But it costs more, takes longer time to take the images, and needs patient cooperation such as breath-holding to have better and fewer motion artifacts.

The liver MRI protocol consists of multiple sequences before and post-contrast. Post-contrast phases are including arterial phase, portal venous phase, equilibrium phase, hepatobiliary delayed phase, and later delayed phase. Hepatobiliary specific contrast agents that are used in liver MRI are mangafodipir trisodium (Mn-DPDP), gadobenate dimeglumine (Gd-BOPTA), and gadoxetic acid (Gd-EOB-DTPA). These contrast agents have specific characteristics such as specific receptors and transporters for uptake, different excretion percentage via biliary and renal, method of administration, and side effects. These hepatocyte-specific contrasts can help to identify and characterize the small liver lesion better, especially well-differentiated HCC. It can be used in distinguishing FNH from hepatic adenoma. Hepatic adenoma is visible in the hepatobiliary phase as a hypointense lesion versus FNH that is iso or hyperintense, evaluating hepatic metastases, HCC surveillance, and post-liver transplant evaluation. It can also differentiate tumors with hepatocellular from the nonhepatocellular origin.[8] Contrast agents that get secreted into bile can be used to differentiate hepatocellular adenoma (HCA) by early heterogeneous enhancement in T1-weighted fat-suppressed arterial phase MRI and then contrast washout in the portal venous phase. Because HCA does not have any bile ducts, uptake of biliary specific contrast is minimal in the delayed phase.[9]

The most sensitive imaging technique to assess the presence and degree of hepatic steatosis is in and out gradient recalled echo (GRE) MRI. However, the gold standard method to evaluate the presence of inflammatory and early fibrotic changes is a liver biopsy.[9] MR elastography is a newer technique introduced originally as US elastography, which can measure liver stiffness and degree of fibrosis. MR elastography does not have the possible bias of sampling that is present in liver biopsy, and it has better sensitivity and specificity in comparison to US elastography, that has limitations in obese patient and the presence of ascites. Iron overload and accumulation in hepatic cells and hepatic Kupffer cells, in hemochromatosis and hemosiderosis, respectively. The liver is the primary organ of deposition and can present as hepatomegaly as a first sign. It can be seen hypointense in comparison to paraspinal muscle signal in T1 and T2 Weighted and GRE T2 weighting MRI.

Hepatic hemangioma is the most common benign liver lesion that can be categorized into typical and atypical. A typical hepatic hemangioma can be appreciated in non-contrast CT as a hypo-attenuating lesion most of the time, in arterial phase contrast-enhanced CT as an area with nodular enhancement in the periphery, in portal venous phase and delayed phase with continuous enhancement of the periphery with filling of the central part with contrast. Hemangioma is hypointense in T1 imaging and hyperintense in T2 imaging. Gadolinium-enhanced contrast T1 imaging often shows nodular enhancement of the periphery with a progressive enhancement of the central part and retaining of the contrast in delayed imaging. Hepatobiliary contrast T1 imaging is non-specific and may not be helpful. Two main categories for atypical hemangioma are giant hepatic hemangioma and flash filling hepatic hemangioma. Giant hemangiomas are remarkably large but non-neoplastic vascular lesions that have similar radiologic manifestations as typical hepatic hemangioma. Flash filling hepatic hemangiomas/venous malformations have a smaller size (mostly less than 2 cm) and have a hyperechoic appearance in the US. They are hypo- or iso-dense in noncontract imaging and have flash, fast, and homogenous enhancement in the arterial phase with retaining of the contrast in the late phase. Flash filling hemangioma has similar imaging manifestation in CEUS and gadolinium-enhanced contrast MRI with quick, homogenous enhancement and no wash out in the late phase.

Focal nodular hyperplasia (FNH) is the second most common benign liver mass, after hemangioma, with a hepatocellular origin, which has a central scar with fat and fibrous tissue contents and an increased density of hepatocytes in about 80% of FNH. MRI has better sensitivity and specificity in diagnosing FNH in comparison to CT and ultrasound. FNH is consist of hepatocytes, bile ducts, and Kupffer cells in an abnormal alignment, US imaging in FNH is very subtle changes in the liver contour or change in parenchymal echogenicity. FNH is iso- or hypointense in nonenhanced T1 imaging and has a homogenous enhancement in the arterial phase. FNH can be appreciated in multiphasic MRI with hyperintense and delayed enhancement in T2 weighted images due to retaining of contrast in hepatocytes because of the presence of a central scar.[10]

Hepatic adenomas are rare and benign liver tumors with the hepatocellular origin, most commonly related to long term oral contraceptive use. Other factors that can precipitate hepatic adenomas are anabolic steroids, glycogen storage diseases, obesity, metabolic syndrome. Although hepatic adenomas are benign liver tumors, they have a potential risk of bleeding and malignant degeneration. Surgical resection is the recommended treatment for hepatic adenomas. In patients which resection is not feasible or not preferable, modifying the risk factors, if there is any, observe with imaging and alpha-fetoprotein levels, or hepatic arterial embolization is the other approaches to hepatic adenoma.

A hepatic cyst is a common hepatic lesion with cholangiocellular origin. Benign hepatic cyst(s) can be found in 5% of the general population. Its size can vary from microscopic to 20 cm. The US can characterize hepatic cyst as anechoic lesions with thin walls and the presence of posterior acoustic enhancement, which confirms the fluid content of the cyst, and very thin septa in some of the cyst. In the CT, it can be appreciated as an area of low internal attenuation with a thin wall and the possible presence of thin septa. Cysts can be appreciated in the MRI as an area of homogenous low signal in T1-weighted imaging and homogenous high internal signal on T2 weighted imaging and absence of enhancement with contrast.

Hepatocellular carcinoma (HCC) is the most common primary liver tumor. Cirrhosis and chronic hepatitis are the major risk factors for the development of HCC. Alpha-fetoprotein becomes elevated in two-thirds of HCC. Elevated alpha-fetoprotein in the presence of cirrhosis is suggestive of HCC and can be seen in 90% of patients with HCC. HCC can have different appearances in the US from focal hypoechoic, hyperechoic, and heterogeneous lesions. Most HCCs are hypervascular in color Doppler. In contrast-enhanced US, HCC can be appreciated with enhancement in the arterial phase and wash out in the portal venous phase. MRI and CT have a sensitivity of 81% and 68% in detecting HCC, respectively. In CT, the enhancement pattern is similar to the contrast-enhanced US. Because of the possible arterioportal shunt in HCC, focal fatty changes might be seen as focal fat deposition in the normal liver or focal fat sparing around the HCC in the diffuse hepatic steatosis. HCC is the consequence of regenerative nodules progression to dysplastic nodules, and high-grade dysplastic nodules to low grade HCC. Regenerative and dysplastic nodules are feeding by the portal vein; thus, they are indistinguishable from each other on imaging, although dysplastic nodules are premalignant, and regenerative nodules are not. Most regenerative and dysplastic nodules are hypo-intense in T2- weighted images and have variable intensity in T1- weighted images. Regenerative nodules and low-grade dysplastic nodules are isointense in contrast-enhanced MRI.[11] Hepatocellular carcinoma (HCC) receives blood from the hepatic artery, in comparison to healthy hepatic tissue that gets supply from the portal vein. Because of this characteristic, HCC can be appreciated in multiphasic, contrast-enhanced MRI by increasing contrast enhancement in the arterial phase and contrast washout in the portal phase with peripheral rim enhancement. HCC appears slightly hyperintense T2-weighted unenhanced MRI. Both hepatic artery and portal vein are feeding cholangiocarcinoma, so there is an increasing contrast enhancement in both arterial and venous phases.[9][11]

Fibrolamellar carcinoma is a subtype of HCC, but it has a better prognosis, younger patient’s age at the time of diagnosis, and no alpha-fetoprotein elevation. Fibrolamellar HCC in imaging is usually large at the time of diagnosis and does not have a capsule. Fibrolamellar carcinoma appears on T1- and T2-weighted MRI as a large, heterogeneous mass with central hypointensity due to central fibrotic scar.[12]

Metastatic liver lesions are usually hypointense on T1-weighted imaging and hyperintense on T2-weighted images. Most metastatic liver tumors are hypovascular, and portal venous phase is the best time frame to be visualized. Some metastatic tumors, including renal cell carcinoma, melanoma, and sarcoma, are hypervascular. These liver metastases can be appreciated best in the arterial phase.[13]