Cirrhosis differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sudarshana Datta, MD [2]

Overview

Cirrhosis may present in a similar way to some other diseases. History, physical examination, and diagnostic testing may 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: ^[1]

Classification of jaundice based on etiology		Disease	History and clinical manifestations				Diagnosis
			History and clinical manifestations				Lab Findings						Other blood tests	Other diagnostic
			Family history	Fever	RUQ Pain	Pruritis	AST	ALT	ALK	BLR Indirect	BLR Direct	Viral serology	Other blood tests	Other diagnostic
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

Differential diagnosis of cirrhosis based on altered hepatic function:

Condition	Differentiating signs and symptoms	Differentiating Tests
Cirrhosis	Abdominal pain and bloating Menstrual irregularities Symptoms of hypogonadism: Impotence Infertility Testicular atrophy Loss of libido Easy bruisability Decompensated cirrhosis may present with Jaundice Increase in abdominal girth due to ascites Pruritus Signs of upper gastrointestinal bleeding: Hematemesis Hematochezia Melena Symptoms due to hepatic encephalopathy: Altered mental status Confusion Sleep disturbances	Ultrasound findings in cirrhosis are as follows:^[2]^[3]^[4]^[5]^[6]^[7]^[8]^[9] Changes in liver contour: shrunken, irregular appearance Non homogeneous appearance of the hepatic tissue Increased surface nodularity Increase in echogenecity from focal fatty infiltration Atrophy of the right lobe and hypertrophy of the caudate or left lobe Splenomegaly Ascites Varices Hepatic or portal vein thrombosis
Constrictive pericarditis	Increased jugular venous pressure atrial fibrillation tachycardia Quiet heart sounds with a third heart sound (ventricular knock)	EKG will show: tachycardia Atrial fibrillation Low-voltage QRS complexes T wave abnormalities Doppler ultrasound shows ventricular filling abnormalities
Budd-Chiari Syndrome	Abdominal pain Diarrhea Ascites	Doppler ultrasound and CT of the abdomen shows absence of the hepatic vein filling Abdominal CT will show a rapid clearing of the caudate lobe of the liver
Splenic vein thrombosis	Signs and symptoms of: Upper abdominal pain radiating to the back Vomiting Poor bowel sounds Fever Shock Cullen's sign Grey-Turner's sign	Ultrasound of the abdomen and CT will show evidence of a splenic vein thrombosis Normal hepatic venous pressure gradient is present
Portal vein thrombosis	Symptoms depend on the underlying cause: If pancreatitis is present, the patient may develop: Upper abdominal pain radiating to the back Vomiting Poor bowel sounds fever shock Cullen's sign Grey-Turner's sign If the cause is ascending cholangitis, symptoms include: Fever rigors Right upper quadrant pain Dark urine Pale stools If abdominal sepsis is the cause, symptoms include: fever abdominal pain Signs of peritonitis	Doppler ultrasound and abdominal CT show a portal vein filling defect, and absence of flow in the portal vein. MR or direct angiography show a normal hepatic venous pressure gradient.
Schistosomiasis	Patients may have a history of travel to endemic areas Constitutional symptoms such as Malaise rigors anorexia weight loss vomiting Diarrhea headache Muscular aches weakness abdominal pain urticaria fever lymphadenopathy	MR or direct angiography shows a normal hepatic venous pressure gradient
Sarcoidosis	Dry cough with dyspnea Anterior or posterior uveitis dry eyes glaucoma Skin findings may include: Maculopapular lesions on the face, back, arms and legs erythema nodosum on the legs	Chest x ray may show: hilar lymphadenopathy Upper lobe fibrosis Diffuse reticulonodular shadowing Liver biopsy shows non-necrotizing, non-caseating granulomas
Inferior vena cava obstruction	Signs and symptoms of renal cell carcinoma: Hematuria flank pain Flank or abdominal mass Weight loss hypertension	Ultrasound of the abdomen shows evidence of inferior vena cava obstruction
Nodular regenerative hyperplasia	None	Liver biopsy shows small regenerative nodules with little or no fibrosis on reticulin staining
Idiopathic portal hypertension (hepatoportal sclerosis)	None	Liver biopsy shows 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 (indicative of ascites due to portal hypertension)
Exudate - SAAG < 1.1 g/dL (indicative of ascites due to other etiologies)

References

↑ Fargo MV, Grogan SP, Saguil A (2017). "Evaluation of Jaundice in Adults". Am Fam Physician. 95 (3): 164–168. PMID 28145671.
↑ Udell JA, Wang CS, Tinmouth J, FitzGerald JM, Ayas NT, Simel DL, Schulzer M, Mak E, Yoshida EM (2012). "Does this patient with liver disease have cirrhosis?". JAMA. 307 (8): 832–42. doi:10.1001/jama.2012.186. PMID 22357834.
↑ Becker CD, Scheidegger J, Marincek B (1986). "Hepatic vein occlusion: morphologic features on computed tomography and ultrasonography". Gastrointest Radiol. 11 (4): 305–11. PMID 3533689.
↑ Di Lelio A, Cestari C, Lomazzi A, Beretta L (1989). "Cirrhosis: diagnosis with sonographic study of the liver surface". Radiology. 172 (2): 389–92. doi:10.1148/radiology.172.2.2526349. PMID 2526349.
↑ Sanford NL, Walsh P, Matis C, Baddeley H, Powell LW (1985). "Is ultrasonography useful in the assessment of diffuse parenchymal liver disease?". Gastroenterology. 89 (1): 186–91. PMID 3891495.
↑ Giorgio A, Amoroso P, Lettieri G, Fico P, de Stefano G, Finelli L, Scala V, Tarantino L, Pierri P, Pesce G (1986). "Cirrhosis: value of caudate to right lobe ratio in diagnosis with US". Radiology. 161 (2): 443–5. doi:10.1148/radiology.161.2.3532188. PMID 3532188.
↑ Simonovský V (1999). "The diagnosis of cirrhosis by high resolution ultrasound of the liver surface". Br J Radiol. 72 (853): 29–34. doi:10.1259/bjr.72.853.10341686. PMID 10341686.
↑ Trinchet JC, Chaffaut C, Bourcier V, Degos F, Henrion J, Fontaine H, Roulot D, Mallat A, Hillaire S, Cales P, Ollivier I, Vinel JP, Mathurin P, Bronowicki JP, Vilgrain V, N'Kontchou G, Beaugrand M, Chevret S (2011). "Ultrasonographic surveillance of hepatocellular carcinoma in cirrhosis: a randomized trial comparing 3- and 6-month periodicities". Hepatology. 54 (6): 1987–97. doi:10.1002/hep.24545. PMID 22144108.
↑ "EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma". J. Hepatol. 56 (4): 908–43. 2012. doi:10.1016/j.jhep.2011.12.001. PMID 22424438.

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[pmid28145671-1] Fargo MV, Grogan SP, Saguil A (2017). "Evaluation of Jaundice in Adults". Am Fam Physician. 95 (3): 164–168. PMID 28145671.

[pmid22357834-2] Udell JA, Wang CS, Tinmouth J, FitzGerald JM, Ayas NT, Simel DL, Schulzer M, Mak E, Yoshida EM (2012). "Does this patient with liver disease have cirrhosis?". JAMA. 307 (8): 832–42. doi:10.1001/jama.2012.186. PMID 22357834.

[pmid3533689-3] Becker CD, Scheidegger J, Marincek B (1986). "Hepatic vein occlusion: morphologic features on computed tomography and ultrasonography". Gastrointest Radiol. 11 (4): 305–11. PMID 3533689.

[pmid2526349-4] Di Lelio A, Cestari C, Lomazzi A, Beretta L (1989). "Cirrhosis: diagnosis with sonographic study of the liver surface". Radiology. 172 (2): 389–92. doi:10.1148/radiology.172.2.2526349. PMID 2526349.

[pmid3891495-5] Sanford NL, Walsh P, Matis C, Baddeley H, Powell LW (1985). "Is ultrasonography useful in the assessment of diffuse parenchymal liver disease?". Gastroenterology. 89 (1): 186–91. PMID 3891495.

[pmid3532188-6] Giorgio A, Amoroso P, Lettieri G, Fico P, de Stefano G, Finelli L, Scala V, Tarantino L, Pierri P, Pesce G (1986). "Cirrhosis: value of caudate to right lobe ratio in diagnosis with US". Radiology. 161 (2): 443–5. doi:10.1148/radiology.161.2.3532188. PMID 3532188.

[pmid10341686-7] Simonovský V (1999). "The diagnosis of cirrhosis by high resolution ultrasound of the liver surface". Br J Radiol. 72 (853): 29–34. doi:10.1259/bjr.72.853.10341686. PMID 10341686.

[pmid22144108-8] Trinchet JC, Chaffaut C, Bourcier V, Degos F, Henrion J, Fontaine H, Roulot D, Mallat A, Hillaire S, Cales P, Ollivier I, Vinel JP, Mathurin P, Bronowicki JP, Vilgrain V, N'Kontchou G, Beaugrand M, Chevret S (2011). "Ultrasonographic surveillance of hepatocellular carcinoma in cirrhosis: a randomized trial comparing 3- and 6-month periodicities". Hepatology. 54 (6): 1987–97. doi:10.1002/hep.24545. PMID 22144108.

[pmid22424438-9] "EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma". J. Hepatol. 56 (4): 908–43. 2012. doi:10.1016/j.jhep.2011.12.001. PMID 22424438.

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Cirrhosis differential diagnosis

Overview

Differentiating Cirrhosis from other Diseases

Differentiating Cirrhosis from other Diseases Based on Ascitic Fluid

References

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