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Diffuse Disease

  • The hepatocyte is a parenchymal liver cell that performs all liver functions.
  • Diffuse hepatocellular disease affects hepatocytes and interferes with liver function.
  • Measurement: hepatic enzyme levels are elevated with cell necrosis.
  • Types of diffuse disease include Fatty liver infiltration, Hepatitis (acute and chronic), Cirrhosis (acute and chronic).

Fatty Infiltration (Fatty Liver)

  • Fatty liver or steatosis (pronunciation: stee·uh·tow·suhs) is an acquired, reversible disorder of metabolism, resulting in an accumulation of triglycerides within hepatocytes.
  • Fatty infiltration implies increased lipid accumulation in hepatocytes and is the result of major liver injury or systemic disorders leading to impaired or excessive fat metabolism.

Causes of Fatty Liver

  • Obesity
  • Excessive alcohol intake
  • Poorly controlled hyperlipidemia
  • Diabetes
  • Excess corticosteroids
  • Pregnancy
  • Total parenteral hyperalimentation
  • Severe hepatitis
  • Glycogen storage disease (genetic disorder)
  • Cystic fibrosis
  • Pharmaceutical factors

Focal Fatty Infiltration and Focal Fatty Sparing

  • There can be focal regions of normal liver within areas of fatty infiltration (focal fatty infiltration).
  • Focal fatty sparing commonly occurs next to the gallbladder, porta hepatis, caudate lobe, and liver margins.

Diffuse Disease: Hepatitis

  • Hepatitis is the general name for inflammatory and infectious disease of the liver.
  • Causes: viral, bacterial, fungal, or parasitic; may result from local infection (e.g., viral hepatitis), infection elsewhere in the body (e.g., infectious mononucleosis, amebiasis), or chemical/drug toxicity.
  • Inflammation range: mild inflammation impairs hepatocyte function; more severe inflammation and necrosis may obstruct blood and bile flow and impair liver cell function.
  • Lab findings: may cause elevation of ALT, AST, conjugated and unconjugated bilirubin.

Viral Hepatitis

  • Hepatitis A, B, and C are the most common hepatotropic viruses:
    • HAV: Hepatitis A virus
    • HBV: Hepatitis B virus
    • HCV: Hepatitis C virus

Hepatitis A (HAV)

  • Worldwide distribution; spread primarily by fecal contamination (virus lives in alimentary tract).
  • Endemic in developing countries; infection often occurs early in life.
  • Clinical course: acute infection with possible complete recovery or death from acute liver failure.

Hepatitis B (HBV)

  • HBV exists in the bloodstream; spread via transfusions of infected blood or plasma or contaminated needles; high risk to healthcare workers due to transmission routes.
  • Virus is also found in body fluids (saliva, semen) and may be spread by sexual contact.

Hepatitis C (HCV)

  • Diagnosed by presence of anti-HCV antibodies in blood ({ ext{anti-HCV}}).
  • Transmission: blood and body fluids; commonly via sharing needles or sexual contact.

Acute Viral Hepatitis—Epidemiology and Course

  • In the United States, approximately 60\% of acute viral hepatitis is type B, 20\% is type A, and 20\% is other types.
  • Initial symptoms: flulike illness and GI symptoms such as loss of appetite, nausea, vomiting, and fatigue.
  • Outcome: can be fatal with secondary acute hepatic necrosis or progress to chronic hepatitis and potentially portal hypertension, cirrhosis, and hepatocellular carcinoma (HCC).

Acute Hepatitis

  • Definition: clinical illness without complications; recovery usually within approximately 4\ \text{months}
  • Pathologic changes include:
    • Liver cell injury and swelling, hepatocyte degeneration potentially leading to necrosis.
    • Reticuloendothelial and lymphocytic response with Kupffer cell enlargement.
    • Regeneration of hepatocytes.

Acute Hepatitis: Ultrasound Features

  • Liver texture may be normal or portal vein borders may appear more prominent.
  • May show a "Starry Night" liver appearance (Van Gogh).
  • Parenchyma is slightly more echogenic than normal.
  • Attenuation may be present.
  • Hepatosplenomegaly may be present.
  • Gallbladder wall may be thickened.

Chronic Hepatitis

  • Defined as hepatic inflammation extending beyond 6\ \text{months}.
  • Causes: viral, metabolic, autoimmune, or drug-induced.
  • Chronic active hepatitis features more extensive changes than chronic persistent hepatitis:
    • Inflammation extends across the limiting plate, spreading perilobularly with piecemeal necrosis, often with fibrosis.
  • Symptoms may include nausea, anorexia, weight loss, tremors, jaundice, dark urine, fatigue, and varicosities.
  • Chronic persistent hepatitis: benign, self-limiting.
  • Chronic active hepatitis commonly progresses to cirrhosis and liver failure.

Chronic Hepatitis: Ultrasound Findings

  • Liver parenchyma is coarse with decreased brightness of portal triads.
  • Attenuation is not as marked as in fatty infiltration.
  • The liver does not typically increase in size with chronic hepatitis.
  • Fibrosis may be evident, potentially producing soft posterior shadowing.

Diffuse Disease: Cirrhosis

  • Definition: chronic degenerative disease characterized by fibrous tissue covering lobes; parenchyma degenerates; lobules infiltrated with fat.
  • Essential feature: simultaneous parenchymal necrosis, regeneration, and diffuse fibrosis leading to disorganization of lobular architecture.

Causes of Cirrhosis

  • #1 cause is Hepatitis C
  • Alcoholic liver disease
  • NAFLD (non-alcoholic fatty liver disease)
  • NASH (non-alcoholic steatohepatitis)
  • Hepatitis B
  • Other causes:
    • Hemochromatosis (iron deposition)
    • Wilson disease (copper deposition)

Types of Cirrhosis

  • Micronodular (micro-nodular) cirrhosis: most commonly due to chronic alcohol abuse.
  • Macronodular (macro-nodular) cirrhosis: caused by chronic viral hepatitis or other infection.

Clinical Presentation

  • Acute cirrhosis: asymptomatic or may have nausea, flatulence, ascites, pale stools, weakness, abdominal pain, varicosities, spider angiomas; classic presentation includes hepatomegaly, jaundice, and ascites.
  • Chronic cirrhosis: nausea, anorexia, weight loss, jaundice, dark urine, fatigue, varicosities; may progress to liver failure and portal hypertension.

Cirrhosis: Ultrasound Progression

  • Early phase: hepatomegaly; increased echogenicity and coarse texture; possible vascular changes (loss of triphasic hepatic waveform, altered hepatic artery waveform).
  • Mid phase: coarse echotexture, nodular borders, lobe atrophy, ascites.
  • Late phase: coarse echotexture, hyperechoic, small in size, nodular borders, possible nodules (may be cancerous), ascites, portal hypertension.

Glycogen Storage Disease

  • Six categories based on clinical symptoms and enzymatic defects; most common is type I or von Gierke disease.
  • Inherited disease with abnormal storage and accumulation of glycogen in tissues, especially liver and kidneys; large amounts of glycogen deposited in liver and kidneys.

Imaging Notes

  • A patient with von Gierke disease may show hepatomegaly with increased echogenicity; sonography may reveal round, homogeneous adenomas; large adenomas may be inhomogeneous.
  • Hepatic adenomas can be associated with glycogen storage diseases.

Hemochromatosis

  • Rare disorder of iron metabolism with excess iron deposits throughout the body.
  • Can lead to cirrhosis and portal hypertension.
  • Sonographic findings:
    • Hepatomegaly
    • Cirrhotic changes
    • Increased echogenicity may be uniform across the hepatic parenchyma.

Hepatic Vascular Flow Abnormalities

  • There are various abnormalities in hepatic vascular flow; see imaging resources for examples (link provided in original materials).

Diffuse Abnormalities of the Liver Parenchyma

  • Biliary obstruction (proximal and distal)
  • Extrahepatic mass
  • Passive hepatic congestion

Biliary Obstruction: Proximal

  • Proximal obstruction to the cystic duct can be caused by:
    • Gallstones
    • Carcinoma of the common bile duct
    • Metastatic tumor invasion of the porta hepatis
  • Clinically: jaundice and pruritus; labs show elevation in direct bilirubin and alkaline phosphatase ({ ext{ALP}}).

Biliary Obstruction: Distal

  • Distal obstruction distal to the cystic duct may be caused by:
    • Stones in the common duct
    • Extrahepatic mass at the porta hepatis
    • Stricture of the common duct
  • Clinically: common duct stones cause RUQ pain, jaundice, pruritus; labs show increased direct bilirubin and ALP.

Extrahepatic Mass, Common Duct Stricture, and Passive Hepatic Congestion

  • Extrahepatic mass in porta hepatis can mimic biliary obstruction.
  • Common duct stricture: often occurs after cholecystectomy; lab profile shows direct bilirubin and ALP elevation.
  • Passive hepatic congestion: secondary to congestive heart failure; hepatomegaly; labs are normal to mildly elevated.

Focal Hepatic Disease

  • May be congenital or acquired; may be solitary or multiple.
  • Often asymptomatic; may not require treatment (about 5% of population; usually not until the 50s).
  • If seen in patients younger than 50 years, check kidneys for autosomal dominant polycystic kidney disease (ADPKD).
  • Simple hepatic cysts: well-demarcated, thin-walled, anechoic with posterior acoustic enhancement.

Polycystic Liver Disease

  • Inherited in an autosomal dominant pattern; affects about 1 in 500 individuals.
  • 50%–74% of patients with polycystic renal disease have hepatic cysts; 60% have associated polycystic renal disease.
  • Features: small (<2–3 cm), multiple cysts throughout the hepatic parenchyma; they may enlarge and cause biliary obstruction at the porta hepatis.

Focal Inflammatory Disease of the Liver

  • Hepatic abscesses occur most often as complications of biliary tract disease, surgery, or trauma.
  • Three basic types: intrahepatic, subhepatic, subphrenic.
  • Clinically: fever, elevated white cell count, RUQ pain.
  • Sonographic focus: solitary or multiple liver lesions; abnormal fluid collections in Morison's pouch, subdiaphragmatic, or subphrenic spaces.

Pyogenic (Bacterial) Abscess

  • Pyogenic abscesses account for approx. 80\% of hepatic abscesses.
  • Routes for infection:
    • Biliary tract disease (most common)
    • Portal vein or hepatic artery
    • Direct extension from contiguous infection
    • Trauma (rarely)
  • Sources include cholangitis; portal pyemia from appendicitis/diverticulitis/inflammatory disease; direct spread from another organ; infarction after embolization or from sickle cell anemia.

Amebic Abscess

  • Necrotic material collection in a liver cavity caused by Entamoeba histolytica.
  • Parasite reaches liver via portal vein; common in immigrants or travelers.
  • Amebiasis acquired by ingesting cysts in contaminated water/food; typically starts in colon and cecum; organism may migrate to liver.
  • Clinical: GI symptoms possible; abdominal pain, diarrhea, leukocytosis, low fever.
  • Gross pathology: cavitary lesion filled with yellow necrotic material (no pus).

Sonographic Findings for Amebic Abscess

  • Abnormal liver function tests, upper abdominal pain, malaise.
  • Diffuse fibrosis with echogenic bands along the long axis of the intrahepatic portal vein; portal hypertension and portal vein obstruction can be present.
  • Other differential: schistosomiasis (worm entry via skin, migrates to liver; portal hypertension).

Echinococcal Cyst (Hydatid Disease)

  • Infectious cystic disease of the liver, common in sheep-herding regions.
  • Causative organism: Echinococcus (tapeworm); humans are intermediate hosts; dogs are definitive hosts.
  • Life cycle: eggs shed in canine feces; humans ingest eggs; larvae reach liver via portal circulation.
  • Imaging features: daughter cysts; inner cyst layers; "water-lily sign" with floating membranes in the cyst.
  • Imaging example: complex mass with fluid and debris components; water-lily sign can be seen.

Fungal Abscess (Candidiasis)

  • Candida infection in immunocompromised hosts (chemo, transplant, HIV).
  • Sonographic appearance options: wheel within a wheel, bull's-eye, uniformly hypoechoic focus, echogenic focus.

Pneumocystis Carinii

  • Common organism causing opportunistic infection in AIDS; also in transplant patients or those on chemotherapy.
  • Sonographic patterns range from diffuse tiny non-shadowing echogenic foci to extensive replacement of liver parenchyma with echogenic calcified clumps.

Chronic Granulomatous Disease

  • Congenital defect in phagocytes; increased susceptibility to severe infections; more common in boys, but may occur in girls.
  • Sonographic findings: poorly marginated hypoechoic mass with posterior enhancement; calcification may be present with posterior shadowing; aspiration needed to classify.

Benign Hepatic Tumors

Cavernous Hemangioma

  • Benign, congenital tumor of large vascular spaces; most common benign liver tumor; more common in women.
  • Often asymptomatic; rare cases may bleed causing RUQ pain.
  • Ultrasound: irregular and echogenic due to vascular component.

Liver Cell Adenoma

  • Mass found more commonly in women; linked to oral contraceptive use.
  • Symptoms: RUQ pain, risk of rupture with bleeding into the tumor.
  • Incidence increased in patients with type I glycogen storage disease or von Gierke disease.
  • Surgical resection recommended due to risk of malignant transformation.

Liver Lipoma

  • Rare benign lesion; ultrasound artifact considerations (speed artifact) may appear on imaging.

Focal Nodular Hyperplasia (FNH)

  • Second most common benign liver mass after hemangioma; occurs mainly in women < 40 years.
  • Thought to arise from developmental hyperplasia related to a congenital vascular anomaly.
  • Often asymptomatic; lesions are more common in the right lobe; many are subcapsular or pedunculated.
  • Classic feature: central fibrous scar; composed of normal hepatocytes, Kupffer cells, bile duct elements, and fibrous tissue.
  • Multiple nodules can be separated by bands of fibrous tissue.
  • There can be increased bleeding within tumors.

Hepatic Malignancies

Hepatocellular Carcinoma (HCC)

  • The most common primary malignant neoplasm of the liver.
  • More often a metastatic site than a primary tumor; liver metastases are common from other cancers (lung is a common source of metastasis to liver).
  • Pathogenesis linked to cirrhosis (about 80\% of patients with preexisting cirrhosis develop HCC), chronic HBV infection, and dietary hepatocarcinogens.
  • Demographics: more common in men.
  • Clinical presentation: prior history of cirrhosis or hepatitis B/C, palpable mass, hepatomegaly, appetite disturbance, fever.
  • Presentation patterns: solitary massive tumor; multiple nodules; diffuse infiltrative masses.
  • Pathology: focal lesion; invasive lesion with necrosis and hemorrhage; poorly defined lesion.
  • Invasion patterns: invasion of hepatic veins causing Budd-Chiari syndrome; portal venous system invasion or thrombosis; tends to invade portal venous radicles.
  • Example imaging: HCC in a cirrhotic liver with portal vein thrombosis and Budd-Chiari syndrome.

Metastatic Disease

  • Most common form of neoplastic involvement of the liver.
  • Primary sites: colon, breast, lung; others include pancreas, stomach, esophagus, etc.
  • Prognosis: short survival after detection for HCC and certain other primaries (pancreas, stomach, esophagus); longer survival for head and neck cancer and colon cancer.
  • Spread mechanisms: tumor erodes vessel walls to spread via lymphatics or bloodstream to portal vein or hepatic artery.
  • Sonographic appearance: multiple well-defined iso-, hyper-, or hypoechoic lesions; may appear with necrosis in centers.

Other Primary and Pediatric Hepatic Neoplasms

Hepatoblastoma

  • Most common malignant liver tumor in infants and children; usually occurs before age 2.
  • Presentation: enlarged, asymptomatic abdominal mass.
  • Associated conditions: Beckwith-Wiedemann syndrome, familial adenomatous polyposis; elevated AFP.
  • Metastasis: to lungs; portal vein invasion.

Infantile Hepatic Hemangiomas (Infantile Hemangioendotheliomas)

  • Benign vascular tumor in neonates; rapid growth in first months of life.
  • Sonographic findings: hepatomegaly with possible masses; color Doppler shows high vascularity.
  • Clinical course: may cause congestive heart failure; often spontaneously regress by 12–18 months of age.

Lymphoma

  • Malignant neoplasm of lymphocytes; includes Hodgkin and non-Hodgkin lymphoma.
  • Hepatomegaly with normal or diffusely altered parenchymal echoes.
  • May present with focal hypoechoic masses.
  • Systemic symptoms: enlarged non-tender lymph nodes, fever, fatigue, night sweats, weight loss; bone pain or abdominal mass may occur.
  • Splenomegaly or retroperitoneal nodes can support diagnosis.

Elastography

  • Measures tissue stiffness.
  • Malignant lesions tend to be stiffer than benign lesions.
  • Overall parenchyma stiffness increases with fibrosis or cirrhosis.
  • Useful to identify patients with no or minimal fibrosis (where ultrasound alone may miss subtle disease) and to stage significant fibrosis or cirrhosis.

Liver Biopsy with Ultrasound Guidance

  • Ultrasound is used to guide liver biopsy for diagnostic sampling.
  • Provides histologic confirmation of diffuse or focal liver disease.

Hepatic Trauma

  • The liver is the third most commonly injured abdominal organ after the spleen and kidney.
  • Laceration occurs in about 3\% of trauma patients and is often associated with other injuries.
  • Management decisions depend on laceration size, amount of hemoperitoneum, and the patient’s clinical status.
  • The right lobe is affected more often than the left.
  • Injury spectrum ranges from small lacerations to large lacerations with hematomas, subcapsular hematomas, or capsular disruption.

Notes:

  • Throughout the material, ultrasound findings often correlate with stage and etiology (e.g., fatty infiltration versus cirrhosis). Recognize echotexture changes (coarse vs. fine), nodularity (micro- vs macro-nodular), and signs of portal hypertension (ascites, portosystemic collaterals).
  • Laboratory trends (ALT, AST, bilirubin, ALP) are used in conjunction with imaging to differentiate disease stages.
  • Some sections reference historical or clinical associations (e.g., von Gierke disease with hepatic adenomas) that can guide differential diagnoses.
  • Practical implications include the role of elastography in fibrosis assessment and the use of ultrasound-guided biopsy for definitive tissue diagnosis.