Hepatomegaly

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Hepatomegaly Microchapters
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Overview
Causes
Differential Diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Iqra Qamar M.D.[2] Cafer Zorkun, M.D., Ph.D. [3]

Synonyms and keywords: Enlarged liver; liver enlargement

Overview

The liver is an organ present in vertebrates and some other animals. The adult human liver normally weighs between 1.4 - 1.6 kilograms (3.1 - 3.5 pounds), and it is a soft, pinkish-brown "boomerang shaped" organ. It is located on the right side of the upper abdomen below the diaphragm. The liver size increases with age and it ranges between 5 cm to 15 cm in adulthood. A normal liver is less than 16 cm in ultrasound evaluation. Hepatomegaly may be found in physical examination or during imaging studies. Imaging is more accurate in determining liver size. In some certain conditions normal liver may be palpated as enlarged liver including thin people, during deep inspiration, right pleural effusion, and when emphysema results in hyperinflation of the chest with diaphragmatic descent and downward displacement of the liver. Common pathologic causes that may result in hepatomegaly are hepatitis, storage disorders, impaired venous outflow, infiltrative disorders, and biliary obstruction.

Causes

Causes of hepatomegaly may be classified on the basis of etiology into hepatitis, storage disorders, impaired venous outflow, infiltrative and obstructive causes.

Etiology		Disease
Hepatitis	Infections	Acute and chronic viral hepatitis
		Bacterial liver abscess
		Parasitic infections
		Granulomatous hepatitis
	Ischemia	Ischemic hepatitis ("shock liver")
	Toxins	Alcoholic hepatitis
	Steatosis	Alcoholic fatty liver disease
		Nonalcoholic steatohepatitis
	Drugs/Medications	Drug induced liver injury (DILI)
	Immune mediated hepatitis	Autoimmune hepatitis
	Copper deposition	Wilson disease
Storage disorders	Glycogen	Glycogen storage disorders
		Diabetes mellitus
	Lipid	Gaucher disease
		Nonalcoholic steatohepatitis
	Protein	Alpha-1 antitrypsin deficiency
	Iron	Hemochromatosis
Impaired venous outflow	Cardiac	Right heart failure
		Constrictive pericarditis
	Hepatic vein	Hepatic vein thrombosis
		Inferior vena cava web
	Intrahepatic	Sinusoidal obstruction syndrome
		Peliosis hepatis
Infiltrative diseases	Benign primary liver tumors	Hemangiomas
		Adenomas
		Focal nodular hyperplasia
	Malignant primary liver tumors	Hepatocellular carcinoma
		Cholangiocarcinoma
		Fibrolamellar carcinoma
		Hemangioendothelioma
	Metastatic/disseminated tumors	Myeloma
		Lymphoma
		Leukemia
		Metastatic solid tumors
Biliary obstruction	Primary biliary cirrhosis
	Primary sclerosing cholangitis
	Biliary atresia
Other	Anatomic variations	Riedel's lobe
	Cystic liver disease	Polycystic liver disease
		Caroli's disease

Differential diagnosis

Patients with hepatomegaly need to be differentiated from other patients presenting with similar complaints such as abdominal pain.

Abbreviations: RUQ= Right upper quadrant of the abdomen, LUQ= Left upper quadrant, LLQ= Left lower quadrant, RLQ= Right lower quadrant, LFT= Liver function test, SIRS= Systemic inflammatory response syndrome, ERCP= Endoscopic retrograde cholangiopancreatography, IV= Intravenous, N= Normal, AMA= Anti mitochondrial antibodies, LDH= Lactate dehydrogenase, GI= Gastrointestinal, CXR= Chest X ray, IgA= Immunoglobulin A, IgG= Immunoglobulin G, IgM= Immunoglobulin M, CT= Computed tomography, PMN= Polymorphonuclear cells, ESR= Erythrocyte sedimentation rate, CRP= C-reactive protein, TS= Transferrin saturation, SF= Serum Ferritin, SMA= Superior mesenteric artery, SMV= Superior mesenteric vein, ECG= Electrocardiogram, US = Ultrasound

Classification of pain in the abdomen based on etiology			Disease	Clinical manifestations								Diagnosis		Comments
				Symptoms					Signs
				Abdominal Pain	Fever	Nausea or vomiting	Jaundice	Weight loss	Hypo- tension	Guarding	Rebound Tenderness	Lab Findings	Imaging
Abdominal causes	Inflammatory causes	Pancreato-biliary disorders	Acute suppurative cholangitis	RUQ	+	+	+	−	+	+	+	Abnormal LFT WBC >10,000	Ultrasound shows biliary dilatation/stents/tumor	Septic shock occurs with features of SIRS
			Acute cholangitis	RUQ	+	−	+	−	−	−	−	Abnormal LFT	Ultrasound shows biliary dilatation/stents/tumor	Biliary drainage (ERCP) + IV antibiotics
			Acute cholecystitis	RUQ	+	+	+	−	−	−	−	Hyperbilirubinemia Leukocytosis	Ultrasound shows: Gallstone Inflammation	Murphy’s sign
			Acute pancreatitis	Epigastric	+	+	±	+	±	−	−	Increased amylase / lipase	Ultrasound shows evidence of inflammation CT scan shows severity of pancreatitis	Pain radiation to back
			Chronic pancreatitis	Epigastric	−	±	±	+	−	−	−	Increased amylase / lipase Increased stool fat content Pancreatic function test	CT scan Calcification Pseudocyst Dilation of main pancreatic duct	Predisposes to pancreatic cancer
			Pancreatic carcinoma	Epigastric	−	+	+	+	−	−	−	↑ Alkaline phosphatase ↑ serum bilirubin ↑ gamma-glutamyl transpeptidase ↑ CA 19-9	MDCT with  PET/CT MRI	Skin manifestations may include: Bullous pemphigoid Cicatricial pemphigoid Migratory superficial thrombophlebitis (classic Trousseau's syndrome) Pancreatic panniculitis
			Disease	Abdominal Pain	Fever	Nausea or vomiting	Jaundice	Weight loss	Hypo- tension	Guarding	Rebound Tenderness	Lab Findings	Imaging	Comments
			Primary biliary cirrhosis	RUQ/Epigastric	−	−	+	−	−	−	−	Increased AMA level, abnormal LFTs	ERCP	Pruritis
			Primary sclerosing cholangitis	RUQ	+	−	+	−	−	−	−	Increased liver enzymes Increased IgM, IgG4 Anti-neutrophil cytoplasmic antibody (p-ANCA) Anti-nuclear antibody (ANA) Anti-smooth muscle antibody (Anti-Sm) Anti-endothelial antibody Anti-cardiolipin antibody	ERCP and MRCP shows Multiple segmental strictures Mural irregularities Biliary dilatation and diverticula Distortion of biliary tree	The risk of cholangiocarcinoma in patients with primary sclerosing cholangitis is 400 times higher than the risk in the general population.
			Cholelithiasis	RUQ/Epigastric	±	±	±	−	−	−	−	Leukocytosis	Ultrasound shows gallstone	Fatty food intolerance
		Gastric causes	Peptic ulcer disease	Diffuse	±	+	−	+	Positive if perforated	Positive if perforated	Positive if perforated	Ascitic fluid LDH > serum LDH Glucose < 50mg/dl Total protein > 1g/dl	Air under diaphragm in upright CXR	Upper GI endoscopy for diagnosis
			Disease	Abdominal Pain	Fever	Nausea or vomiting	Jaundice	Weight loss	Hypo- tension	Guarding	Rebound Tenderness	Lab Findings	Imaging	Comments
			Gastritis	Epigastric	±	+	−	Positive in chronic gastritis	−	−	−	H.pylori infection diagnostic tests	Endoscopy	H.pylori gastritis guideline recommendation
			Gastroesophageal reflux disease	Epigastric	−	±	−	−	−	−	−	N	Gastric emptying studies	Esophageal manometry Endoscopy for alarm signs
			Gastric outlet obstruction	Epigastric	−	±	−	+	−	−	−	Complete blood count Basic metabolic panel	Abdominal x-ray- air fluid level Barium upper GI studies- narrowed pylorus	Succussion splash
			Gastroparesis	Epigastric	−	+	−	+	±	−	−	Hemoglobin Fasting plasma glucose Serum total protein, albumin, thyrotropin (TSH), and an antinuclear antibody (ANA) titer HbA1c	Scintigraphic gastric emptying	Succussion splash Single photon emission computed tomography (SPECT) Full thickness gastric and small intestinal biopsy
			Gastrointestinal perforation	Diffuse	+	-	±	−	+	+	±	WBC> 10,000	Air under diaphragm in upright CXR	Hamman's sign
			Dumping syndrome	Lower and then diffuse	−	+	−	+	+	−	−	Glucose challenge test Hydrogen breath test	Upper GI series Gastric emptying study	Postgastrectomy
		Intestinal causes	Disease	Abdominal Pain	Fever	Nausea or vomiting	Jaundice	Weight loss	Hypo- tension	Guarding	Rebound Tenderness	Lab Findings	Imaging	Comments
			Acute appendicitis	Starts in epigastrium, migrates to RLQ	+	+	−	−	Positive in perforated appendicitis	+	+	Leukocytosis	Ct scan Ultrasound	Positive Rovsing sign Positive Obturator sign Positive Iliopsoas sign
			Acute diverticulitis	LLQ	+	+	−	−	Positive in perforated diverticulitis	+	+	Leukocytosis	CT scan Ultrasound	History of constipation
			Inflammatory bowel disease	Diffuse	±	−	±	+	−	−	−	Anti-neutrophil cytoplasmic antibody (P-ANCA) in Ulcerative colitis Anti saccharomyces cerevisiae antibodies (ASCA) in Crohn's disease	String sign on abdominal x-ray in Crohn's disease	Extra intestinal findings: Uveitis Arthritis
			Irritable bowel syndrome	Diffuse	−	−	−	+	−	−	−	Normal	Normal	Symptomatic treatment High dietary fiber Osmotic laxatives Antispasmodic drugs
			Whipple's disease	Diffuse	±	−	±	+	±	−	−	Thrombocytopenia Hypoalbuminemia Small intestinal biopsy for Tropheryma whipplei	Endoscopy is used to confirm diagnosis. Images used to find complications Chest and joint x-ray CT MRI Echocardiography	Extra intestinal findings: Uveitis Endocarditis Encephalitis Dementia Hepatosplenomegaly Arthritis Ascites
			Disease	Abdominal Pain	Fever	Nausea or vomiting	Jaundice	Weight loss	Hypo- tension	Guarding	Rebound Tenderness	Lab Findings	Imaging	Comments
			Toxic megacolon	Diffuse	+	−	−	−	+	±	+	Anemia Leukocytosis especially in patients with Clostridium difficile infection Hypoalbuminemia Metabolic alkalosis associated with a poor prognosis Metabolic acidosis secondary to ischemic colitis	CT and Ultrasound shows: Loss of colonic haustration Hypoechoic and thickened bowel walls with irregular internal margins in the sigmoid and descending colon Prominent dilation of the transverse colon (>6 cm) Insignificant dilation of ileal bowel loops (diameter >18 mm) with increased intraluminal gas and fluid
			Tropical sprue	Diffuse	+	−	−	+	−	−	−	Fat soluble vitamin deficiency Hypoalbuminemia Fecal stool test	Barium studies: Dilation and edema of mucosal folds	Steatorrhea- 10-40 g/day (Normal=5 g/day)
			Celiac disease	Diffuse	−	−	−	+	−	−	−	IgA endomysial antibody IgA tissue transglutaminase antibody Anti-gliadin antibody Small bowel biopsy	US: Bull’s eye or target pattern Pseudokidney sign	Gluten allergy
			Infective colitis	Diffuse	+	±	−	−	Positive in fulminant colitis	±	±	Stool culture and studies Shiga toxin in bloody diarrhea PCR	CT scan Bowel wall thickening Edema
			Disease	Abdominal Pain	Fever	Nausea or vomiting	Jaundice	Weight loss	Hypo- tension	Guarding	Rebound Tenderness	Lab Findings	Imaging	Comments
			Colon carcinoma	Diffuse/ RLQ/LLQ	−	−	−	+	±	−	−	CBC Carcinoembryonic antigen (CEA)	Colonoscopy Flexible sigmoidoscopy Barium enema CT colonography	PILLCAM 2: A colon capsule for CRC screening may be used in patients with an incomplete colonoscopy who lacks obstruction
		Hepatic causes	Viral hepatitis	RUQ	+	+	+	+	Positive in fulminant hepatitis	Positive in acute	+	Abnormal LFTs Viral serology	US	Hep A and E have fecal-oral route of transmission Hep B and C transmits via blood transfusion and sexual contact.
			Liver abscess	RUQ	+	+	+	+	+	+	±	CBC Blood cultures Abnormal liver function tests	US CT
			Hepatocellular carcinoma/Metastasis	RUQ	+	−	+	+	−	−	−	High levels of AFP in serum Abnormal liver function tests	US CT Liver biopsy	Other symptoms: Splenomegaly Variceal bleeding Ascites Spider nevi Asterixis
			Disease	Abdominal Pain	Fever	Nausea or vomiting	Jaundice	Weight loss	Hypo- tension	Guarding	Rebound Tenderness	Lab Findings	Imaging	Comments
			Budd-Chiari syndrome	RUQ	±	−	±	−	−	−	−	Elevated serum aspartate aminotransferase and alanine aminotransferase levels may be more than five times the upper limit of the normal range. Elevated serum alkaline phosphatase and bilirubin levels, decreased serum albumin level.	Findings on CT scan suggestive of Budd-Chiari syndrome include: Early enhancement of the caudate lobe and central liver around the inferior vena cava Delayed enhancement of the peripheral liver with accompanying central low density (flip-flop appearance) Peripheral zones of the liver show reversed portal venous blood flow In the chronic phase, there is caudate lobe enlargement and atrophy of the peripheral liver in affected areas	Ascitic fluid examination shows: Total protein more than 2.5 g per deciliter White blood cells are usually less than 500/μL.
			Hemochromatosis	RUQ	−	−	−	−	−	−	−	>60% TS >240 μg/L SF Raised LFT Hyperglycemia	Ultrasound shows evidence of cirrhosis	Extra intestinal findings: Hyperpigmentation Diabetes mellitus Arthralgia Impotence in males Cardiomyopathy Atherosclerosis Hypopituitarism Hypothyroidism Extrahepatic cancer Prone to specific infections
			Cirrhosis	RUQ	−	−	+	+	+	−	−	Hypoalbuminemia Prolonged PT Abnormal LFTs Hyponatremia Thrombocytopenia	US Nodular, shrunken liver Ascites	Stigmata of liver disease Cruveilhier- Baumgarten murmur
			Disease	Abdominal Pain	Fever	Nausea or vomiting	Jaundice	Weight loss	Hypo- tension	Guarding	Rebound Tenderness	Lab Findings	Imaging	Comments
		Peritoneal causes	Spontaneous bacterial peritonitis	Diffuse	+	−	Positive in cirrhotic patients	−	±	+	+	Ascitic fluid PMN>250 cells/mm³ Culture: Positive for single organism	Ultrasound for evaluation of liver cirrhosis
	Renal causes		Pyelonephritis	Unilateral	+	+	−	−	+	−	−	Urinalysis Urine culture Blood culture	CT MRI	CVA tenderness
			Renal colic	Flank pain	−	+	−	−	−	−	−	Hematuria	Ultrasound CT scan	Colicky abdominal pain Dysuria
	Hollow Viscous Obstruction		Small bowel obstruction	Diffuse	+	+	−	+	+	+	±	Leukocytosis with left shift indicates complications	Abdominal X ray Dilated loops of bowel with air fluid levels Gasless abdomen	"Target sign"– , indicative of intussusception Venous cut-off sign" – suggests thrombosis
			Volvulus	Diffuse	-	+	−	−	Positive in perforated cases	+	+	Leukocytosis	CT scan and abdominal X ray U shaped sigmoid colon	"Whirl sign"
			Biliary colic	RUQ	−	+	+	−	−	−	−	↑ bilirubin and alkaline phosphatase	Ultrasound
			Disease	Abdominal Pain	Fever	Nausea or vomiting	Jaundice	Weight loss	Hypo- tension	Guarding	Rebound Tenderness	Lab Findings	Imaging	Comments
	Vascular Disorders	Ischemic causes	Mesenteric ischemia	Periumbilical	Positive if bowel becomes gangrenous	+	−	+	Positive if bowel becomes gangrenous	Positive if bowel becomes gangrenous	−	Leukocytosis and lactic acidosis Amylase levels D-dimer	CT angiography SMA or SMV thrombosis	Also known as abdominal angina that worsens with eating
			Acute ischemic colitis	Diffuse	+	+	−	+	+	+	+	Leukocytosis	Abdominal x-ray Distension and pneumatosis CT scan Double halo appearance, thumbprinting Thickening of bowel	May lead to shock
		Hemorrhagic causes	Ruptured abdominal aortic aneurysm	Diffuse	±	+	−	+	+	−	−	Fibrinogen D-dimer	Focused Assessment with Sonography in Trauma (FAST)	Unstable hemodynamics
			Intra-abdominal or retroperitoneal hemorrhage	Diffuse	±	±	−	−	+	−	−	↓ Hb ↓ Hct	CT scan	History of trauma
			Disease	Abdominal Pain	Fever	Nausea or vomiting	Jaundice	Weight loss	Hypo- tension	Guarding	Rebound Tenderness	Lab Findings	Imaging	Comments
	Gynaecological Causes	Tubal causes	Torsion of the cyst/ovary	RLQ / LLQ	−	+	−	−	−	±	±	↑ ESR ↑ CRP	Ultrasound	Sudden onset & severe pain
			Acute salpingitis	RLQ / LLQ	+	−	−	−	−	±	±	Leukocytosis	Pelvic ultrasound	Vaginal discharge
			Cyst rupture	RLQ / LLQ	−	+	−	−	+	±	±	↑ ESR ↑ CRP	Ultrasound
		Pregnancy	Ruptured ectopic pregnancy	RLQ / LLQ	−	+	−	−	+	+	+	Positive pregnancy test	Ultrasound	History of Missed period Vaginal bleeding
Extra-abdominal causes	Pulmonary disorders	Pleural empyema		RUQ/Epigastric	+	−	−	+	−	−	−	Thoracentesis	Chest X-ray Pleural opacity Localization of effusion	Physical examination Crackles Egophony Increased tactile fremitus
		Pulmonary embolism		RUQ/LUQ	±	−	−	−	±	−	−	ABGs D-dimer	CXR V/Q scan Spiral CT pulmonary angiogram	Dyspnea Tachycardia Pleuretic chest pain
		Pneumonia		RUQ/LUQ	+	+	−	−	+	−	−	ABGs Leukocytosis Pancytopenia	CXR CT chest Bronchoscopy	Shortness of breath Cough
	Cardiovascular disorders	Myocardial Infarction		Epigastric	±	+	−	−	Positive in cardiogenic shock	−	−	Cardiac enzymes	ECG Echocardiogram Wall motion abnormality Wall rupture Septal rupture	Chest pain, tightness, diaphoresis Complications: Arrythmias Mitral regurgitation Ventricular wall rupture Septal rupture

References

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