Cirrhosis differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Charmaine Patel, M.D. [2]}

Overview

Cirrhosis can present in a similar way to some other diseases. History, physical examination, and diagnostic testing can help to differentiate cirrhosis from other diseases such as malignancy, constrictive pericarditis, Budd-Chiari syndrome, portal vein thrombosis and splenic vein thrombosis.

Differentiating Cirrhosis from other Diseases

Differential diagnosis of cirrhosis on the basis of jaundice is as follows:

Classification of jaundice based on etiology Disease History and clinical manifestations Diagnosis Lab Findings Other blood tests Other diagnostic Family history Fever RUQ Pain Pruritis AST ALT ALK BLR Indirect BLR Direct Viral serology Jaundice Hepatocellular Jaundice Hemochromatosis + - -/+ - ↑ ↑ ↑/N ↑/N N - Ferritin ↑ Liver biopsy Wilson's disease + - -/+ - ↑ ↑ N ↑/N N - Serum cerulloplasmin ↑ Liver biopsy Viral hepatitis - -/+ - - ↑ ↑ N ↑/N N + Specific viral antibody for each type - Alcoholic hepatitis - -/+ -/+ - ↑↑ ↑ N ↑/N N - - - Drug induced hepatitis - -/+ - - ↑ ↑ N ↑/N N - - - Autoimmune hepatitis -/+ - - -/+ ↑ ↑ N ↑/N N - Anti-LKM antibody Liver biopsy Cirrhosis -/+ -/+ -/+ - ↑ ↑ ↑/N ↑/N ↑/N -/+ Low platate Small liver on ultrasond Cholestatic Jaundice Common bile duct stone -/+ - + + N N ↑ N ↑ - Dilated ducts on sono CT/ERCP Hepatitis A cholestatic type - -/+ + + N N ↑ N ↑ + HAV- AB Abdominal ultrasound EBV / CMV hepatitis - -/+ + + N N ↑ N ↑ + Positive serology Primary biliary cirrhosis -/+ - -/+ + N/↑ N/↑ ↑ N ↑ - AMA positive Liver biopsy Primary sclerosing cholangitis -/+ - -/+ + N/↑ N/↑ ↑ N ↑ - Beading on MRCP Liver biopsy Pancreatic carcinoma + - -/+ - N/↑ N/↑ ↑ N ↑ - Mass on ultrasond CT scan for diagnosis Isolated Jaundice Crigler-Najjar type 2 + - - - N N N ↑ ↑ - Genetic testing Gilbert + - - - N N N ↑ ↑ - Genetic testing Rotor syndrome + - - - N N N N ↑ - Genetic testing Liver biopsy Dubin-Johnson syndrome + - - - N N N N ↑ - Genetic testing Liver biopsy Hereditory spherocytosis + - -/+ - N N N ↑ N - Genetic testing Osmotic fragility G6PD deficiency + - - - N N N ↑ N - Genetic testing Thalassemia + - - - N N N ↑ N - Genetic testing Sickle cell disease + - - - N N N ↑ N - Genetic testing Paroxismal nocturnal hemoglobinoria - - - - N N N ↑ N - Flocytometery Immune hemolysis - -/+ - - N N N ↑ N - Autoantibodies Hematoma - -/+ - - N N N ↑ N - Anemia Truma or surgery in history

Condition	Differentiating Signs and Symptoms	Differentiating Tests
Constrictive pericarditis	Increased jugular venous pressure, atrial fibrillation, and tachycardia. Quiet heart sounds with a third heart sound (ventricular knock) present.	EKG will show tachycardia, atrial fibrillation, low-voltage QRS complexes and T wave abnormalities. Doppler ultrasound will show ventricular filling abnormalities.
Budd-Chiari Syndrome	Abdominal pain, diarrhea, and worsening ascites.	Doppler ultrasound and CT of the abdomen will show absence of the hepatic vein filling. Abdominal CT will show a rapid clearing of the caudate lobe of the liver.
Splenic vein thrombosis	Similar signs and symptoms of acute pancreatitis with upper abdominal pain radiating to the back, vomiting, poor bowel sounds, fever and shock. Cullen's sign and Grey-Turner's sign may be present.	An ultrasound of the abdomen and CT will show evidence of a splenic vein thrombosis. Normal hepatic venous pressure gradient is present.
Portal vein thrombosis	Will depend on the underlying cause. If pancreatitis is present, upper abdominal pain radiating to the back, vomiting, poor bowel sounds, fever and shock. Cullen's sign and Grey-Turner's sign may be present. If the cause is ascending cholangitis, fever, rigors, right upper quadrant pain, dark urine, and pale stools may be seen. If abdominal sepsis is the cause, fever, abdominal pain and other signs of peritonitis will be seen.	Doppler ultrasound and abdominal CT will show a portal vein filling defect, and absence of flow in the portal vein. MR or direct angiography will show a normal hepatic venous pressure gradient.
Schistosomiasis	History of travel to endemic areas. Constitutional symptoms such as malaise, rigors, anorexia, weight loss, vomiting, diarrhea, headache, muscular aches, weakness and abdominal pain. Also urticaria, fever and lymphadenopathy may be seen.	MR or direct angiography will show a normal hepatic venous pressure gradient.
Sarcoidosis	Dry cough with dyspnea. Anterior or posterior uveitis, dry eyes and glaucoma. Skin findings may include maculopapular lesions on the face, back, arms and legs, and erythema nodosum on the legs.	Chest x ray may show hilar lymphadenopathy, upper lobe fibrosis, and diffuse reticulonodular shadowing. Liver biopsy will show non-necrotizing, non-caseating granulomas.
Inferior vena cava obstruction	Signs and symptoms of renal cell carcinoma, with hematuria, flank pain, flank or abdominal mass, weight loss and hypertension.	Ultrasound of the abdomen will show evidence of inferior vena cava obstruction.
Nodular regenerative hyperplasia	None	Liver biopsy will show small regenerative nodules with little or no fibrosis on reticulin staining.
Idiopathic portal hypertension (hepatoportal sclerosis)	None	Liver biopsy will show no evidence of cirrhosis.
Vitamin A intoxication, arsenic, and vinyl chloride toxicity	None	History generally reveals exposure.

Differentiating Cirrhosis from other Diseases Based on Ascitic Fluid

Ascites may be caused by portal hypertension due to cirrhosis of liver or due to other causes such as malignancy.Ascitic fluid analysis should be done to broadly categorize the cause of ascites.

Ascites is broadly classified as two types based on the serum-ascites albumin gradient (SAAG):

• Transudate - SAAG > 1.1 g/dL (indicates the ascites is due to portal hypertension).
• Exudate - SAAG < 1.1 g/dL (indicates the ascites is due to non-portal hypertension etiology).

Less common differentials

Cirrhosis should also be differentiated from other causes of hyperprolactinemia that may present as galactorrhea, amenorrhea, (in females) and infertility (in both males and females) including:

• Physiological:
  • Normal pregnancy
• Pathological:
  • Pituitary tumors (other than prolactinoma):
    • Somatotroph adenoma: Acromegaly
    • Corticotroph adenoma: Cushing's syndrome
  • Suprasellar tumors (tumors present in the region of the pituitary stalk)
  • Hypothyroidism
  • Chronic renal failure
  • Liver disease
    • Cirrhosis (with or without encephalopathy)
    • Viral hepatitis (with encephalopathy)
  • Seizure disorder
• Medication-induced:
  • Antipsychotic medications:
    • Haloperidol
    • Risperidone
  • Antiemetic medications:
    • Metoclopramide
    • Domperidone
  • Antihypertensive medications:
    • Methyldopa
    • Verapamil

Disease	Clinical Findings	Laboratory findings	Management
Somatotroph adenoma: Acromegaly	Clinical features of acromegaly are due to high level of human growth hormone (hGH): Soft tissue swelling of the hands and feet Brow and lower jaw protrusion Enlarged hands Enlarged feet Arthritis and carpal tunnel syndrome Increase in teeth spacing Macroglossia (enlarged tongue) Heart failure Kidney failure Compression of the optic chiasm leading to loss of vision in the outer visual fields (typically bitemporal hemianopia) Headache Diabetes mellitus Hypertension Cardiomegaly	Elevated insulin-like growth factor-1 (IGF-1) levels Elevated growth hormone levels	Medical management: Octreotide Bromocriptine Surgical management: Endonasal transsphenoidal surgery Radiation therapy
Corticotroph adenoma: Cushing's syndrome	Clinical features of Cushing's syndrome are due to increased levels of cortisol: Rapid weight gain, particularly of the trunk and face with sparing of the limbs (central obesity) Proximal muscle weakness A round face often referred to as a "moon face" Excess sweating Headache The excess cortisol may also affect other endocrine systems and cause, for example: Insomnia Reduced libido Impotence Amenorrhea Infertility Patients frequently suffer various psychological disturbances, ranging from euphoria to psychosis. Depression and anxiety are also common.	Dexamethasone suppression test 24 hour urinary measurement of cortisol	Medical management: Pasireotide Cabergoline Ketoconazole Metyrapone Mitotane Mifepristone Surgical management: Transsphenoidal pituitary resection
Hypothyroidism	Clinical features of hypothyroidism are due to deficiency of thyroxine: Fatigue Cold intolerance Decreased sweating Hypothermia Coarse skin Weight gain Hoarseness Goiter Fullness in the throat and neck Depression Emotional lability Attention deficit	Elevated TSH Low T4 Low T3 Elevated anti-thyroid antibodies(anti-TPO)	Levothyroxine
Chronic renal failure	There are no pathognomonic symptoms associated with chronic renal failure. Common non-specific symptoms of chronic renal failure include: Malaise Nausea Unintentional weight loss Pruritus Lower extremity edema Sleep disorders	Urinalysis: Albuminuria Hematuria Pyuria Red cell or white cell casts and crystals Fluid and electrolyte disturbances: Hyponatremia Hyperkalemia Hyperphosphatemia Hyperchloremia Metabolic acidosis Hypocalcemia Endocrine and metabolic disturbances: Hyperuricemia Hypertriglyceridemia Decreased HDL levels Vitamin D deficiency Increased Parathyroid hormone levels Hematologic abnormalities: Normocytic normochromic anemia Lymphocytopenia Leukopenia Thrombocytopenia	Medical management: Blood pressure management Control of blood glucose Protein restriction Management of anemia Management of electrolyte disturbance Dialysis Surgical management Kidney transplant
Liver disease: Cirrhosis	The clinical features of liver cirrhosis are very nonspecific. These include: Right upper quadrant abdominal pain Fever Fatigue and weakness Loss of appetite Diarrhea Nausea and vomiting Weight loss Abdominal pain and bloating when fluid accumulates in the abdomen Itching Menstrual irregularities	Elevated aminotransferases (AST & ALT) Elevated alkaline phosphatase (ALP) Elevated gamma-glutamyl transpeptidase Elevated bilirubin Low albumin Elevated prothrombin time Elevated globulin Hyponatremia Anemia Leukopenia and neutropenia Thrombocytopenia	Medical management: Treatment is usually directed towards the treatment of complications like ascites, esophageal varices, hepatic encephalopathy, hepatorenal syndrome, and spontaneous bacterial peritonitis. Some chronic constitutional symptoms that should be treated include: Pruritis: Cholestyramine is the drug of choice Hypogonadism: Topical testosterone preparations Osteoporosis: Calcium and vitamin D Pain management: NSAIDS, celecoxib, opioids Nutrition: Adequate caloric and protein intake, and multivitamin supplementation Surgical management: Liver transplantation
Seizure disorder	The clinical features of seizure disorder may include: Change in alertness, orientation and time perception Mood changes, such as unexplainable fear, panic, joy, or laughter Changes in sensation of the skin, usually spreading over the arm, leg, or trunk Vision changes, including seeing flashing lights Rarely, hallucinations (seeing things that aren't there) Falling, loss of muscle control, occurs very suddenly Muscle twitching that may spread up or down an arm or leg Muscle tension or tightening that causes twisting of the body, head, arms, or legs Shaking of the entire body Tasting a bitter or metallic flavor	Electroencephalogram	Medical management: Antiepileptic medications
Medication-induced	Clinical features of hyperprolactinemia after a specific period of regular medication ingestion	Discontinuation of the medication for 3 days and remeasurement of prolactin levels	Change to alternate medication