Hepatitis

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Overview
Classification Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E Alcoholic Hepatitis Autoimmune Hepatitis
Differential Diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Seyedmahdi Pahlavani, M.D. [2], Usama Talib, BSc, MD [3]

Overview

Hepatitis refers to the inflammation of the liver. The etiologic agent could be infectious (almost always viral) or non-infectious. Hepatitis can be acute and self limiting or can be chronic and progress to cirrhosis or hepatocellular carcinoma (HCC). Most common causes of infectious hepatitis are viral in origin. These include hepatitis A, B, C, D and E . Non infectious causes of hepatitis include autoimmune, alcohol, drugs and toxins. Alcoholic hepatitis and and non alcoholic steatohepatitis (NASH) are the most common non-infectious types of hepatitis.

The common manifestation of acute hepatitis are fever, jaundice, fatigue, abdominal pain, and hepatomegaly. Diagnosis of hepatitis is based on the clinical manifestations and laboratory findings. In rare conditions liver biopsy is required for either the diagnosis or formulating a treatment plan.

Classification

Hepatitis may be classified depending on the duration of the disease into the following types:

• Acute hepatitis
• Chronic hepatitis

Hepatitis may also be classified on the basis of various causes into the following types:

• Infectious hepatitis
• Non-infectious hepatitis

Infectious Hepatitis

Infectious hepatitis can be classified according to the causative viral agent in to 7 major categories.

Viral Hepatitis                                                                                                                                                                                                                                                                                         Hepatitis A   Hepatitis B   Hepatitis C   Hepatitis D   Hepatitis E   Hepatitis F   Hepatitis G   Other                                                                                                                             • EBV hepatitis • CMV hepatitis • HSV hepatitis • Coxsackie B virus hepatitis

Non-Infectious Hepatitis

Non-infectious Hepatitis

Alcoholic hepatitis

Non-alcoholic steatohepatitis (NASH)

Alpha 1 antitrypsin deficiency

Autoimmune hepatitis

Obstructive hepatitis

Drug related hepatitis

Toxin related hepatitis

Ischemic hepatitis

•Gallstones •Tumors

•Isoniazid •NSAIDs •Beta-lactam antibiotics •Sulfa-containing drugs •HAART

Chemicals

Differential diagnosis

Hepatitis must be differentiated from other conditions that may cause fever, fatigue, nausea and vomiting, and elevated liver enzymes.

Disease		Clinical manifestations					Laboratory findings			Additional findings
		Symptoms			Signs		Transaminitis (elevated AST and ALT)	Viral markers	Autoimmune markers
		Nausea & vomiting	Abdominal pain	Arthralgia	Jaundice	Hepatomegaly
Acute viral hepatitis	Hepatitis A	+++	++	+	+++	+	+++	HAV Ab	---	Fecal-oral transmission Usually acute and self limit Fever usually present
	Hepatitis B	+++	++	++	+++	+	+++	HBs Ag, HBc Ab, HBe Ag	---	Percutaneous transmission most common May cause acute hepatic failure or may become chronic Fever usually present
	Hepatitis C	+++	++	++	+++	+	+++	HCV Ab	---	Percutaneous transmission is most common Higher rate of chronic progression Associated with extra hepatic manifestation such as cryoglobulinemia and membranoproliferative glomerulonephritis Fever usually present
	Hepatitis E	++	++	+/-	++	+	+++	HEV Ab	---	Fecal-oral transmission May cause fulminant disease in pregnancy Fever usually present
	CMV hepatitis	+/-	++	-	+	+	++	CMV-specific immunoglobulin (Ig)M antibody	--	Usually manifests as mononucleosis syndrome fever usually present
	EBV hepatitis	+/-	++	-	+/-	+	++	Heterophile antibody test, monospot test	--	Systemic manifestations as mononucleosis syndrome Fever usually present
Autoimmune hepatitis		-	+	+/-	++	+	+++	---	ANA, ASMA, anti SLA/LP, ANCA, ALKM-1 antibodies	Liver biopsy may be required for diagnosis
Alcoholic hepatitis		+/-	+	-	+	-	AST>ALT	---	---	History of alcohol intake
Drug induced hepatitis		+/-	+	-	+	+	++	---	---	May cause either cholestatic or hepatocellular injury

Diagnosis

Hepatitis A

• Acute HAV infection is diagnosed by the presence of IgM antibodies to HAV.
• Immunity against the virus can be detected by a positive total anti-HAV but can not differentiate a recent from a previous infection.
• Anti-HAV can also be detected after vaccination against the virus.

Hepatitis B

• HBsAg: seen in both acute and chronic infection
• IgM anti-HBc: indicates a recent HBV infection
• Anti-HBs: Present after resolution of infection and after vaccination.
• HBsAg+anti-HBc with negative IgM anti-HBc: Chronic HBV infection.
• Total anti-HBc only: could suggest acute, chronic, resolved infection or a false-positive result.

Hepatitis C

• Enzyme immunoassays (EIA) or enhanced Chemiluminescence Immunoassay (CIA) are used to test for HCV infection and when recommended, a supplemental antibody test.
• Nucleic Acid Amplification Test (NAAT) detects HCV RNA after a positive antibody test.
• HCV RNA is used to detect new infections in a previously infected individual.
• Previous infection does not confer immunity.

Treatment

Treatment of hepatitis A and hepatitis E is supportive as they are usually self-limited. Chronic hepatitis E is treated with the antiviral ribavirin.

Hepatitis B infection is treated with pegylated interferon alfa or nucleoside analogs (entecavir, tenofovir) based on the clinical picture including ALT and HBV DNA levels and presence or absence of cirrhosis.

Treatment is indicated in chronic Hepatitis C infection which is defined as the presence of detectable HCV RNA levels for 6 months. The selection of treatment regimen depends on viral genotype, presence or absence of cirrhosis and other patient factors. Some of the commonly used antiviral regimens include sofosbuvir-velpatasvir, glecaprevir-pibrentasvir and ledipasvir-sofosbuvir

Acute hepatitis D has no specific treatment. For chronic hepatitis D infection, treatment is indicated with PEG interferon alfa for patients with detectable HDV RNA, elevated ALT and evidence of active liver disease. Asymptomatic patients can be monitored for development of active disease.

Alcoholic hepatitis is generally treated with alcohol abstinence and supportive care in mild to moderate cases. Severe cases are treated with tapering courses of glucocorticoids.

Autoimmune hepatitis is treated with glucocorticoid mono therapy or combination of glucocorticoid with azathioprine. Treatment decision is based on symptom severity, laboratory and histologic findings.