Sections

Hepatitis B

Presentation

History

Inquire into patients’ sexual history, occupational history, illicit drug use, and any contacts with known infection.

The spectrum of the symptomatology of hepatitis B disease varies from subclinical hepatitis to icteric hepatitis to fulminant, acute, and subacute hepatitis during the acute phase, and from an asymptomatic chronic infection state to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) during the chronic phase.

Papular acrodermatitis, also recognized as Gianotti-Crosti syndrome, has been associated with hepatitis B, most commonly in children with acute infection.^[40]

The following multisystem manifestations may occur in hepatitis B virus (HBV) infection:

Pleural effusion and hepatopulmonary and portopulmonary syndrome may occur in patients with cirrhosis
Diffuse intravascular coagulation may occur in patients with fulminant hepatitis
Myocarditis, pericarditis, and arrhythmia occur primarily in patients with fulminant hepatitis
Arthralgias and arthritic (serum sickness) subcutaneous nodules may also occur, but these are rare
Guillain-Barre syndrome, encephalitis, aseptic meningitis, and mononeuritis multiplex may occur in patients with acute hepatitis B
Pancreatitis may develop
Aplastic anemia is uncommon, and agranulocytosis is extremely uncommon

A variety of cutaneous manifestations have been recognized during the early course of viral hepatitis, including hives and a fleeting maculopapular rash. These various lesions are episodic, palpable, and, at times, pruritic. A discoloration of the skin can be identified after the resolution of the exanthem, particularly on the lower extremities. Women are more prone to developing cutaneous manifestations.

Acute phase

The incubation period is 1-6 months in the acute phase of hepatitis B infection. Anicteric hepatitis is the predominant form of expression for this disease. The majority of the patients are asymptomatic, but patients with anicteric hepatitis have a greater tendency to develop chronic hepatitis. Patients with symptomatology have the same symptoms as patients who develop icteric hepatitis.

Icteric hepatitis is associated with a prodromal period, during which a serum sickness –like syndrome can occur. The symptomatology is more constitutional and includes the following:

Anorexia
Nausea
Vomiting
Low-grade fever
Myalgia
Fatigability
Disordered gustatory acuity and smell sensations (aversion to food and cigarettes)
Right upper quadrant and epigastric pain (intermittent, mild to moderate)

Patients with fulminant and subfulminant hepatitis may present with the following:

Hepatic encephalopathy
Somnolence
Disturbances in sleep pattern
Mental confusion
Coma
Ascites
Gastrointestinal (GI) bleeding
Coagulopathy

Chronic phase

Patients with chronic hepatitis B disease can be immune tolerant or have an inactive chronic infection without any evidence of active disease. These patients are generally asymptomatic.

Patients with chronic active hepatitis, especially during the replicative state, may complain of symptomatology such as the following:

Symptoms similar to those of acute hepatitis
Fatigue
Anorexia
Nausea
Mild upper quadrant pain or discomfort

If progressive liver disease is present, the following symptomatology may be present:

Hepatic decompensation
Hepatic encephalopathy
Somnolence
Disturbances in sleep pattern
Mental confusion
Coma
Ascites
GI bleeding
Coagulopathy

Physical Examination

The physical examination findings in hepatitis B disease vary from minimal to impressive (in patients with hepatic decompensation), according to the stage of disease.

Patients with acute hepatitis usually do not have any clinical findings, but the physical examination can reveal the following:

Low-grade fever
Jaundice (10 days after appearance of constitutional symptomatology, lasting for 1-3 mo)
Hepatomegaly (mildly enlarged, soft liver)
Splenomegaly (5-15%)
Palmar erythema (rarely)
Spider nevi (rarely)

The physical examination of patients with chronic hepatitis B virus (HBV) infection can reveal stigmata of chronic liver disease such as the following:

Hepatomegaly
Splenomegaly
Muscle wasting
Palmar erythema
Spider angioma
Vasculitis (rarely)

Patients with cirrhosis may have the following findings:

Ascites
Jaundice
History of variceal bleeding
Peripheral edema
Gynecomastia
Testicular atrophy
Abdominal collateral veins (caput medusa)

Differential Diagnoses

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Media Gallery

Hepatitis B. Under higher-power magnification, ground-glass cells may be visible in chronic hepatitis B virus (HBV) infection. Ground-glass cells are present in 50% to 75% of livers with chronic HBV infection. Immunohistochemical staining is positive for hepatitis B surface antigen (HBsAg.)
Hepatitis B. Liver biopsy with hematoxylin stain showing stage 4 fibrosis (ie, cirrhosis) in a patient with hepatitis B.
Hepatitis B. Hepatitis B virus (HBV) is a hepadnavirus, highly resistant to extremes of temperature and humidity, that invades the hepatocytes. The viral genome is a partially double-stranded, circular DNA linked to a DNA polymerase that is surrounded by an icosahedral nucleocapsid and then by a lipid envelope. Embedded within these layers are numerous antigens that are important in disease identification and progression. Within the nucleocapsid are the hepatitis B core antigen (HBcAg) and precore hepatitis B e antigen (HBeAg), and on the envelope is the hepatitis B surface antigen (HBsAg). Transmission electron micrograph (TEM) from Graham Colm and Wikipedia, licensed under the Creative Commons Attribution 3.0 Unported license.
Hepatitis B. Serologic course of hepatitis B virus (HBV) infection. The flat bars show the duration of seropositivity in self-limited acute HBV infection. The pointed bars show that HBV DNA and e antigen (HBeAg) can become undetectable during chronic infection. Only immunoglobulin G (IgG) antibodies to the HBV core antigen (anti-HBc) are predictably detectable after resolution of acute hepatitis or during chronic infection. Antibody to hepatitis B surface antigen (anti-HBs) is generally detectable after resolution of acute HBV infection but may disappear with time. It is only rarely found in patients with chronic infection and does not indicate that immunologic recovery will occur or that the patient has a better prognosis. ALT = alanine transaminase. (Adapted from Liaw YF, Chu CM. Hepatitis B virus infection. Lancet. 2009;373(9663):582-92.)
Hepatitis B. Radiologic studies may be useful in all stages of hepatitis B infection. Ultrasonography, computed tomography (CT) scanning, or magnetic resonance imaging (MRI) may exclude biliary obstruction in acute infection. In chronic disease, ultrasonograms may show nonspecific increased echogenicity of the liver parenchyma. In patients with long-standing disease, CT imaging may be used to detect cirrhosis or hepatocellular carcinoma (as shown).
Hepatitis B. Long-standing cirrhosis leads to progressive replacement of liver parenchyma with fibrotic tissue. Over time, the liver contracts and develops a lobulated contour. These changes are readily apparent on cross-sectional imaging. This contrast-enhanced computed tomography (CT) scan demonstrates extensive cirrhosis, as well as malignant hepatocellular lesions (arrow).
Hepatitis B. Liver biopsy with hematoxylin stain showing stage 4 fibrosis (ie, cirrhosis) in a patient with hepatitis B.

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Author

Nikolaos T Pyrsopoulos, MD, PhD, MBA, FACP, AGAF, FAASLD, FRCP(Edin) Professor and Chief, Division of Gastroenterology and Hepatology, Professor of Physiology, Pharmacology, and Neuroscience, Medical Director of Liver Transplantation, Rutgers New Jersey Medical School

Nikolaos T Pyrsopoulos, MD, PhD, MBA, FACP, AGAF, FAASLD, FRCP(Edin) is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Liver Foundation, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Transplantation, International Liver Transplantation Society, Transplantation Society

Disclosure: Received research grant from: GRIFOLS. BAYER, DURECT, INTERCEPT, BEIGENE, BMS.

Coauthor(s)

Ranya Selim, MD Gastroenterologist/Transplant Hepatologist

Ranya Selim, MD is a member of the following medical societies: American College of Gastroenterology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Acknowledgements

George Y Wu, MD, PhD Professor, Department of Medicine, Director, Hepatology Section, Herman Lopata Chair in Hepatitis Research, University of Connecticut School of Medicine

George Y Wu, MD, PhD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, American Medical Association, American Society for Clinical Investigation, and Association of American Physicians

Disclosure: Springer Consulting fee Consulting; Gilead Consulting fee Review panel membership; Gilead Honoraria Speaking and teaching; Bristol-Myers Squibb Honoraria Speaking and teaching; Springer Royalty Review panel membership

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