Hepatitis C differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Yazan Daaboul, Serge Korjian

Overview

Hepatitis C must be differentiated from other diseases that cause hepatic injury and abnormal liver function tests such as other viral hepatitides (Hepatitis A, Hepatitis B, and Hepatitis E) and non-viral etiologies such as alcoholic liver disease, non-alcoholic steatohepatitis, drug-induced liver injury, autoimmune hepatitis, hepatocellular carcinoma, liver abscess, pancreatitis, and bowel obstruction.

Differential Diagnosis

The differential diagnosis of hepatitis C includes other etiologies of viral hepatitis and non-viral etiologies:

Viral Hepatitis Differential Diagnosis

• Viral Hepatitis A
• Viral Hepatitis B
• Viral Hepatitis D
• Viral Hepatitis E

Non-Viral Hepatitis Differential Diagnosis

• Autoimmune hepatitis
• Alcoholic liver disease
• Non-alcoholic steatohepatitis (NASH)
• Drug-induced liver injury (DILI)
• Liver abscess
• Hepatocellular carcinoma
• Cholelithiasis
• Cholecystitis
• Cholangitis
• Chronic biliary disease
• Trauma
• Abdominal aneurysm
• Gastritis
• Gastroenteritis
• Peptic ulcer disease
• Bowel obstruction
• Pancreatitis
• Pancreatic cancer
• Malignant lymphoma
• Hereditary metabolic disorders (Wilson disease, alpha-1 antitrypsin deficiency)

Differential diagnosis of jaundice as one pf symptoms of hepatitic C are:

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 Liver infiltration: Hemochromatosis, amyloidosis + - -/+ - ↑ ↑ ↑/N ↑/N N - Ferritin ↑ in hemochromatosis 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 Nonalcoholic steatohepatitis -/+ - - - ↑ ↑ N ↑/N N - High lipids liver biopsy Ischemic hepatopathy -/+ - -/+ - ↑ ↑ N ↑/N N - Cardiovascular risk factors Clinical setting 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 ↑ - Pos. autoantibodies Beading on MRCP, Liver biopsy Sickle cell disease + - - +/- N/↑ N/↑ ↑ N ↑ - Genetic testing Pancreatic carcinoma + - -/+ -/+ N/↑ N/↑ ↑ N ↑ - - CT scan for diagnosis AIDS cholangiopathy - - -/+ -/+ N/↑ N/↑ ↑ N ↑ - Pos. HIV Sono or ERCP for diagnosis Parasites induces cholestasis - - -/+ -/+ N/↑ N/↑ ↑ N ↑ - Ab or parasite serology Sono or ERCP for diagnosis Intrahepatic cholestasis of pregnancy -/+ - -/+ + ↑ ↑ ↑ N ↑ - Low PLT, Neg viral serology Diagnosed clinically 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 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 if happened in hepatitis C based on altered hepatic function are:

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: 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 Abdominal MRI may also be helpful in the diagnosis of portal hypertension. Findings on MRI suggestive of cirrhosis with portal hypertension include: Cirrhotic liver, as shrinkage and atrophy in liver Re-canalized umbilical vein--pathognomonic Dilated portal vein and/or splanchnic veins Esophageal varices Collaterals in any abdominal organ Splenomegaly Ascites Transient elastography and the Acoustic Radiation Force Impulse (ARFI) technique are well-established methods for the staging of fibrosis in various liver diseases:   The FibroScan (transient elastography) uses elastic waves to determine liver stiffness which theoretically may be converted into a liver score. The FibroScan produces an ultrasound image of the liver (from 20-80mm) along with a pressure reading (in kPa). Transient elastography is much faster than a biopsy (usually lasts 2.5-5 minutes) and is completely painless. Findings on transient elastography may show reasonable correlation with the severity of cirrhosis: Increasing scarring of the liver is associated with increasing "stiffness" of the tissue.
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