presentation of hepatitis

Overview of Acute Viral Hepatitis

• Symptoms and Signs |
• Diagnosis |
• Treatment |
• Prevention |
• Key Points |

Acute viral hepatitis is diffuse liver inflammation caused by specific hepatotropic viruses that have diverse modes of transmission and epidemiologies. Although acute viral hepatitis can be asymptomatic, a nonspecific viral prodrome is often followed by anorexia, nausea, and often fever or right upper quadrant pain. Jaundice can develop, typically as other symptoms begin to resolve. Most cases resolve spontaneously, but some progress to chronic hepatitis. Occasionally, acute viral hepatitis progresses to acute liver failure (indicating fulminant hepatitis). Diagnosis is by liver tests and serologic tests to identify the virus. Good hygiene and universal precautions can prevent acute viral hepatitis. Depending on the specific virus, preexposure and postexposure prophylaxis may be possible using vaccines or serum globulins. Treatment is usually supportive.

(See also Causes of Hepatitis and Neonatal Hepatitis B Virus Infection .)

Acute viral hepatitis is a common, worldwide disease that has different causes; each type shares clinical, biochemical, and morphologic features. The term acute viral hepatitis often refers to infection of the liver by one of the hepatitis viruses. Other viruses (eg, Epstein-Barr virus , yellow fever virus , cytomegalovirus ) can also cause acute viral hepatitis but less commonly.

Etiology of Acute Viral Hepatitis

At least 5 specific viruses appear to be responsible (see table Characteristics of Hepatitis Viruses ) for acute viral hepatitis:

Hepatitis A (HAV)

Hepatitis B (HBV)

Hepatitis C (HCV)

Hepatitis D (HDV)

Hepatitis E (HEV)

Other unidentified viruses probably also cause acute viral hepatitis.

Characteristics of Hepatitis Viruses

Symptoms and Signs of Acute Viral Hepatitis

Some manifestations of acute hepatitis are virus-specific (see discussions of individual hepatitis viruses) and some patients are asymptomatic, but in general, acute infection tends to develop in predictable phases:

Incubation period: The virus multiplies and spreads without causing symptoms (see table Characteristics of Hepatitis Viruses ).

Prodromal (pre-icteric) phase: Nonspecific symptoms occur; they include profound anorexia, malaise, nausea and vomiting, a newly developed distaste for cigarettes (in smokers), and often fever or right upper quadrant abdominal pain. Urticaria and arthralgias occasionally occur, especially in HBV infection.

Icteric phase: After 3 to 10 days, the urine darkens, followed by jaundice . Systemic symptoms often regress, and patients feel better despite worsening jaundice. The liver is usually enlarged and tender, but the edge of the liver remains soft and smooth. Mild splenomegaly occurs in 15 to 20% of patients. Jaundice usually peaks within 1 to 2 weeks.

Recovery phase: During this 2- to 4-week period, jaundice fades.

Appetite usually returns after the first week of symptoms. Acute viral hepatitis usually resolves spontaneously 4 to 8 weeks after symptom onset.

Anicteric hepatitis (hepatitis without jaundice) occurs more often than icteric hepatitis in patients with HCV infection and in children with HAV infection. It typically manifests as a minor flu-like illness.

Recrudescent hepatitis occurs in a few patients and is characterized by recurrent manifestations during the recovery phase.

Manifestations of cholestasis may develop during the icteric phase (called cholestatic hepatitis) but usually resolve. When they persist, they cause prolonged jaundice, elevated alkaline phosphatase, and pruritus, despite general regression of inflammation.

Diagnosis of Acute Viral Hepatitis

Liver tests (aspartate aminotransferase [AST] and alanine aminotransferase [ALT] elevated out of proportion to alkaline phosphatase, usually with hyperbilirubinemia)

Viral serologic testing

Prothrombin/international normalized ratio (PT/INR) measurement

Initial diagnosis of acute hepatitis

Acute hepatitis must first be differentiated from other disorders that cause similar symptoms. In the prodromal phase, hepatitis mimics various nonspecific viral illnesses and is difficult to diagnose. Anicteric patients suspected of having hepatitis based on risk factors are tested initially with liver tests, including aminotransferases, bilirubin, and alkaline phosphatase. Acute hepatitis often manifests in the icteric phase and so should be differentiated from other disorders causing jaundice (see figure Simplified Diagnostic Approach to Possible Acute Viral Hepatitis ).

Acute hepatitis can usually be differentiated from other causes of jaundice by

Its marked elevations of AST and ALT: Often ≥ 400 IU/L (6.68 microkat/L)

ALT is typically higher than AST, but absolute levels correlate poorly with clinical severity. Values increase early in the prodromal phase, peak before jaundice is maximal, and fall slowly during the recovery phase. Urinary bilirubin usually precedes jaundice. Hyperbilirubinemia in acute hepatitis varies in severity, and fractionation has no clinical value. Alkaline phosphatase is usually only moderately elevated; marked elevation suggests extrahepatic cholestasis and prompts imaging tests (eg, ultrasonography).

Liver biopsy is usually not needed unless the diagnosis is uncertain.

If laboratory results suggest acute hepatitis, particularly if ALT and AST are > 1000 IU/L (16.7 microkat/L), PT/INR is measured to assess liver function.

Manifestations of portosystemic encephalopathy combined with bleeding diathesis or prolongation of INR suggest acute liver failure , indicating fulminant hepatitis .

If acute hepatitis is suspected, efforts are next directed toward identifying its cause. A history of exposure may provide the only clue of drug-induced or toxic hepatitis. The history should also elicit risk factors for viral hepatitis.

Prodromal sore throat and diffuse adenopathy suggest infectious mononucleosis rather than viral hepatitis.

Simplified Diagnostic Approach to Possible Acute Viral Hepatitis

In patients with findings suggesting acute viral hepatitis, the following studies are done to screen for hepatitis viruses A, B, and C:

IgM antibody to HAV (IgM anti-HAV)

Hepatitis B surface antigen (HBsAg)

IgM antibody to hepatitis B core (IgM anti-HBc)

Antibody to HCV (anti-HCV)

Hepatitis C RNA (HCV-RNA) polymerase chain reaction

If any are positive, further serologic testing may be necessary to differentiate acute from past or chronic infection (see tables Hepatitis A Serology , Hepatitis B Serology , and Hepatitis C Serology ).

If serologically confirmed HBV infection is severe, anti-HDV is measured.

If the patient has recently traveled to an endemic area or is immunosuppressed, IgM antibody to HEV (IgM anti-HEV) should be measured if the test is available.

Biopsy is usually unnecessary but, if done, usually reveals similar histopathology regardless of the specific virus:

Patchy cell dropout

Acidophilic hepatocellular necrosis

Mononuclear inflammatory infiltrate

Histologic evidence of regeneration

Preservation of the reticulin framework

HBV infection can occasionally be diagnosed based on the presence of ground-glass hepatocytes (caused by HBsAg-packed cytoplasm) and using special immunologic stains for the viral components. However, these findings are unusual in acute HBV infection and are much more common in chronic HBV infection.

Treatment of Acute Viral Hepatitis

Supportive care

Treatment of acute hepatitis C, partly to prevent transmission to others

No treatments attenuate acute viral hepatitis. Alcohol should be avoided because it can increase liver damage. Restrictions on diet or activity, including commonly prescribed bed rest, have no scientific basis.

Patients with acute HCV infection should be treated with antiviral therapy upon initial diagnosis without awaiting spontaneous resolution in order to prevent transmission to others. Owing to the high efficacy and safety, the same regimens that are recommended for chronic HCV infection are recommended for acute infection ( 1 ).

Viral hepatitis should be reported to the local or state health department.

Treatment reference

1. American Association for the Study of Liver Diseases (AASLD) and Infection Diseases Society of America (IDSA) : HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. Management of Acute HCV Infection. Accessed May 7, 2024.

Prevention of Acute Viral Hepatitis

Because treatments have limited efficacy, prevention of viral hepatitis is very important.

General measures

Good personal hygiene helps prevent transmission, particularly fecal-oral transmission as occurs with HAV and HEV.

Blood and other body fluids (eg, saliva, semen) of patients with acute HBV and HCV infection and stool of patients with HAV infection are considered infectious. Barrier protection is recommended, but isolation of patients does little to prevent spread of HAV and is of no value in HBV or HCV infection.

Posttransfusion infection is minimized by avoiding unnecessary transfusions and by screening all donors for hepatitis B and C. Screening has decreased the incidence of posttransfusion hepatitis B and hepatitis C, which are now extremely rare in the United States.

Immunoprophylaxis

Immunoprophylaxis can involve active immunization using vaccines and passive immunization.

Vaccines for hepatitis A and hepatitis B are available in the United States.

Routine vaccination for hepatitis A and B is recommended in the United States for all children and for adults at high risk (see Adult Immunization Schedule ).

A vaccine for hepatitis E is not available in the United States but is available in China.

No product exists for immunoprophylaxis of HCV or HDV. However, prevention of HBV infection prevents HDV infection. The propensity of HCV for changing its genome hampers vaccine development.

Transmission is the fecal-oral route for hepatitis A and E parenterally or via blood for hepatitis B and C.

Hepatitis B and C, unlike hepatitis A, predispose to chronic hepatitis and liver cancer (if chronic).

Patients with acute viral hepatitis may be anicteric or even asymptomatic.

Do viral serologic testing (IgM anti-HAV, HBsAg, anti-HCV) if clinical findings are consistent with acute viral hepatitis and AST and ALT are elevated out of proportion to alkaline phosphatase.

Treat patients supportively. Treat acute hepatitis C to prevent transmission.

Routine vaccination for hepatitis A and B is recommended in the United States for all children and for adults at high risk.

Copyright © 2024 Merck & Co., Inc., Rahway, NJ, USA and its affiliates. All rights reserved.

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Hepatitis is an inflammation of the liver that is caused by a variety of infectious viruses  and noninfectious agents leading to a range of health problems, some of which can be fatal. There are five main strains of the hepatitis virus, referred to as types A, B, C, D and E. While they all cause liver disease, they differ in important ways including modes of transmission, severity of the illness, geographical distribution and prevention methods. In particular, types B and C lead to chronic disease in hundreds of millions of people and together are the most common cause of liver cirrhosis, liver cancer and viral hepatitis-related deaths. An estimated 354 million people worldwide live with hepatitis B or C, and for most, testing and treatment remain beyond reach.

Some types of hepatitis are preventable through vaccination. A WHO study found that an estimated 4.5 million premature deaths could be prevented in low- and middle-income countries by 2030 through vaccination, diagnostic tests, medicines and education campaigns. WHO’s global hepatitis strategy, endorsed by all WHO Member States, aims to reduce new hepatitis infections by 90% and deaths by 65% between 2016 and 2030.

Many people with hepatitis A, B, C, D or E exhibit only mild symptoms or no symptoms at all. Each form of the virus, however, can cause more severe symptoms. Symptoms of hepatitis A, B and C may include fever, malaise, loss of appetite, diarrhoea, nausea, abdominal discomfort, dark-coloured urine and jaundice (a yellowing of the skin and whites of the eyes). In some cases, the virus can also cause a chronic liver infection that can later develop into cirrhosis (a scarring of the liver) or liver cancer. These patients are at risk of death.

Hepatitis D (HDV) is only found in people already infected with hepatitis B (HBV); however, the dual infection of HBV and HDV can cause a more serious infection and poorer health outcomes, including accelerated progression to cirrhosis. Development of chronic hepatitis D is rare.

Hepatitis E (HEV) begins with mild fever, reduced appetite, nausea and vomiting lasting for a few days. Some persons may also have abdominal pain, itching (without skin lesions), skin rash or joint pain. They may also exhibit jaundice, with dark urine and pale stools, and a slightly enlarged, tender liver (hepatomegaly), or occasionally acute liver failure.

Safe and effective vaccines are available to prevent hepatitis B virus (HBV). This vaccine also prevents the development of hepatitis D virus (HDV) and given at birth strongly reduces transmission risk from mother to child. Chronic hepatitis B infection can be treated with antiviral agents. Treatment can slow the progression of cirrhosis, reduce incidence of liver cancer and improve long term survival. Only a proportion of people with chronic hepatitis B infection will require treatment. A vaccine also exists to prevent infections of hepatitis E (HEV), although it is not currently widely available. There are no specific treatments for HBV and HEV and hospitalization is not usually required. It is advised to avoid unnecessary medications due to the negative effect on liver function caused by these infections.

Hepatitis C (HCV) can cause both acute and chronic infection. Some people recover on their own, while others develop a life-threatening infection or further complications, including cirrhosis or cancer. There is no vaccine for hepatitis C. Antiviral medicines can cure more than 95% of persons with hepatitis C infection, thereby reducing the risk of death from cirrhosis and liver cancer, but access to diagnosis and treatment remains low.

Hepatitis A virus (HAV) is most common is low- and middle-income countries due to reduced access to clean and reliable water sources and the increased risk of contaminated food. A safe and effective vaccine is available to prevent hepatitis A. Most HAV infections are mild, with the majority of people recovering fully and developing immunity to further infection. However, these infections can also rarely be severe and life threatening due to the risk of liver failure.

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Hepatitis is a general term used to describe inflammation of the liver. Liver inflammation can be caused by several viruses (viral hepatitis), chemicals, drugs, alcohol, certain genetic disorders or by an overactive immune system that mistakenly attacks the liver, called autoimmune hepatitis. Depending on its course, hepatitis can be acute, which flares up suddenly and then goes away, or chronic, which is a long-term condition usually producing more subtle symptoms and progressive liver damage.

Types of Hepatitis

There are five viruses that cause the different forms of viral hepatitis: hepatitis A, B, C, D and E. Hepatitis A is mostly a food-borne illness and can be spread through contaminated water and unwashed food. It is the easiest to transmit, especially in children, but is also the least likely to damage the liver and is usually mild and is completely resolved within six months. Hepatitis B can be transmitted through exposure to contaminated blood, needles, syringes or bodily fluids and from mother to baby. It is a chronic disorder and in some cases may lead to long-term liver damage, liver cancer and cirrhosis of the liver after many years of carrying the virus. Hepatitis C is only transmitted through infected blood or from mother to newborn during childbirth. It too can lead to liver cancer and cirrhosis in the long term. Hepatitis D is only found in people who are also infected with hepatitis B. Hepatitis E is predominantly found in Africa, Asia and South America. Certain generally safe medications can be toxic to the liver and cause hepatitis (drug-induced hepatitis) when taken in excess or in very high doses. These include acetaminophen (Tylenol) and even vitamin A. Check with your pediatrician about appropriate dosing for your child.

Autoimmune hepatitis

Hepatitis A

• Hepatitis B
• Hepatitis C
• Hepatitis D

Hepatitis E

Neonatal hepatitis

Abdominal tenderness, especially in the upper right corner

Jaundice (yellowing of the skin and the white portion of the eyes)

Dark-colored urine

Lightly colored stools

Abdominal pain

Nausea with or without vomiting

Abdominal swelling due to fluid retention

The following are required to diagnose hepatitis:

Physical exam, which may or may not reveal a swollen, enlarged liver

Blood tests to check liver enzymes that are elevated when the liver is damaged or infected, as well as blood tests to check for the presence of any of the five viruses causing hepatitis

Ultrasound of the liver to detect any changes

Liver biopsy to confirm suspected inflammation when other tests are inconclusive and to determine the exact degree of liver damage

To prevent infection, children — or anyone who has not been previously vaccinated — should be vaccinated against hepatitis B and hepatitis A. There are no vaccines against hepatitis types C, D and E. There is no cure for hepatitis once it occurs. Treatment focuses on preventing further damage to the liver, reversing existing damage if possible and symptom relief. Most cases of acute hepatitis will resolve over time. In autoimmune hepatitis, certain medications may be used to help keep the overactive immune system in check and prevent further attacks on the liver.

When to Call for Help?

If your child develops symptoms suggestive of liver inflammation, as listed above, call your pediatrician.

• Alcoholic Hepatitis
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• Hepatitis A and E
• Hepatitis in Children
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Overview of Acute Viral Hepatitis

• Symptoms and Signs |
• Diagnosis |
• Treatment |
• Prevention |
• Key Points |

Acute viral hepatitis is diffuse liver inflammation caused by specific hepatotropic viruses that have diverse modes of transmission and epidemiologies. Although acute viral hepatitis can be asymptomatic, a nonspecific viral prodrome is often followed by anorexia, nausea, and often fever or right upper quadrant pain. Jaundice can develop, typically as other symptoms begin to resolve. Most cases resolve spontaneously, but some progress to chronic hepatitis. Occasionally, acute viral hepatitis progresses to acute liver failure (indicating fulminant hepatitis). Diagnosis is by liver tests and serologic tests to identify the virus. Good hygiene and universal precautions can prevent acute viral hepatitis. Depending on the specific virus, preexposure and postexposure prophylaxis may be possible using vaccines or serum globulins. Treatment is usually supportive.

(See also Causes of Hepatitis and Neonatal Hepatitis B Virus Infection .)

Acute viral hepatitis is a common, worldwide disease that has different causes; each type shares clinical, biochemical, and morphologic features. The term acute viral hepatitis often refers to infection of the liver by one of the hepatitis viruses. Other viruses (eg, Epstein-Barr virus , yellow fever virus , cytomegalovirus ) can also cause acute viral hepatitis but less commonly.

Etiology of Acute Viral Hepatitis

At least 5 specific viruses appear to be responsible (see table Characteristics of Hepatitis Viruses ) for acute viral hepatitis:

Hepatitis A (HAV)

Hepatitis B (HBV)

Hepatitis C (HCV)

Hepatitis D (HDV)

Hepatitis E (HEV)

Other unidentified viruses probably also cause acute viral hepatitis.

Characteristics of Hepatitis Viruses

Symptoms and Signs of Acute Viral Hepatitis

Some manifestations of acute hepatitis are virus-specific (see discussions of individual hepatitis viruses) and some patients are asymptomatic, but in general, acute infection tends to develop in predictable phases:

Incubation period: The virus multiplies and spreads without causing symptoms (see table Characteristics of Hepatitis Viruses ).

Prodromal (pre-icteric) phase: Nonspecific symptoms occur; they include profound anorexia, malaise, nausea and vomiting, a newly developed distaste for cigarettes (in smokers), and often fever or right upper quadrant abdominal pain. Urticaria and arthralgias occasionally occur, especially in HBV infection.

Icteric phase: After 3 to 10 days, the urine darkens, followed by jaundice . Systemic symptoms often regress, and patients feel better despite worsening jaundice. The liver is usually enlarged and tender, but the edge of the liver remains soft and smooth. Mild splenomegaly occurs in 15 to 20% of patients. Jaundice usually peaks within 1 to 2 weeks.

Recovery phase: During this 2- to 4-week period, jaundice fades.

Appetite usually returns after the first week of symptoms. Acute viral hepatitis usually resolves spontaneously 4 to 8 weeks after symptom onset.

Anicteric hepatitis (hepatitis without jaundice) occurs more often than icteric hepatitis in patients with HCV infection and in children with HAV infection. It typically manifests as a minor flu-like illness.

Recrudescent hepatitis occurs in a few patients and is characterized by recurrent manifestations during the recovery phase.

Manifestations of cholestasis may develop during the icteric phase (called cholestatic hepatitis) but usually resolve. When they persist, they cause prolonged jaundice, elevated alkaline phosphatase, and pruritus, despite general regression of inflammation.

Diagnosis of Acute Viral Hepatitis

Liver tests (aspartate aminotransferase [AST] and alanine aminotransferase [ALT] elevated out of proportion to alkaline phosphatase, usually with hyperbilirubinemia)

Viral serologic testing

Prothrombin/international normalized ratio (PT/INR) measurement

Initial diagnosis of acute hepatitis

Acute hepatitis must first be differentiated from other disorders that cause similar symptoms. In the prodromal phase, hepatitis mimics various nonspecific viral illnesses and is difficult to diagnose. Anicteric patients suspected of having hepatitis based on risk factors are tested initially with liver tests, including aminotransferases, bilirubin, and alkaline phosphatase. Acute hepatitis often manifests in the icteric phase and so should be differentiated from other disorders causing jaundice (see figure Simplified Diagnostic Approach to Possible Acute Viral Hepatitis ).

Acute hepatitis can usually be differentiated from other causes of jaundice by

Its marked elevations of AST and ALT: Often ≥ 400 IU/L (6.68 microkat/L)

ALT is typically higher than AST, but absolute levels correlate poorly with clinical severity. Values increase early in the prodromal phase, peak before jaundice is maximal, and fall slowly during the recovery phase. Urinary bilirubin usually precedes jaundice. Hyperbilirubinemia in acute hepatitis varies in severity, and fractionation has no clinical value. Alkaline phosphatase is usually only moderately elevated; marked elevation suggests extrahepatic cholestasis and prompts imaging tests (eg, ultrasonography).

Liver biopsy is usually not needed unless the diagnosis is uncertain.

If laboratory results suggest acute hepatitis, particularly if ALT and AST are > 1000 IU/L (16.7 microkat/L), PT/INR is measured to assess liver function.

Manifestations of portosystemic encephalopathy combined with bleeding diathesis or prolongation of INR suggest acute liver failure , indicating fulminant hepatitis .

If acute hepatitis is suspected, efforts are next directed toward identifying its cause. A history of exposure may provide the only clue of drug-induced or toxic hepatitis. The history should also elicit risk factors for viral hepatitis.

Prodromal sore throat and diffuse adenopathy suggest infectious mononucleosis rather than viral hepatitis.

Simplified Diagnostic Approach to Possible Acute Viral Hepatitis

In patients with findings suggesting acute viral hepatitis, the following studies are done to screen for hepatitis viruses A, B, and C:

IgM antibody to HAV (IgM anti-HAV)

Hepatitis B surface antigen (HBsAg)

IgM antibody to hepatitis B core (IgM anti-HBc)

Antibody to HCV (anti-HCV)

Hepatitis C RNA (HCV-RNA) polymerase chain reaction

If any are positive, further serologic testing may be necessary to differentiate acute from past or chronic infection (see tables Hepatitis A Serology , Hepatitis B Serology , and Hepatitis C Serology ).

If serologically confirmed HBV infection is severe, anti-HDV is measured.

If the patient has recently traveled to an endemic area or is immunosuppressed, IgM antibody to HEV (IgM anti-HEV) should be measured if the test is available.

Biopsy is usually unnecessary but, if done, usually reveals similar histopathology regardless of the specific virus:

Patchy cell dropout

Acidophilic hepatocellular necrosis

Mononuclear inflammatory infiltrate

Histologic evidence of regeneration

Preservation of the reticulin framework

HBV infection can occasionally be diagnosed based on the presence of ground-glass hepatocytes (caused by HBsAg-packed cytoplasm) and using special immunologic stains for the viral components. However, these findings are unusual in acute HBV infection and are much more common in chronic HBV infection.

Treatment of Acute Viral Hepatitis

Supportive care

Treatment of acute hepatitis C, partly to prevent transmission to others

No treatments attenuate acute viral hepatitis. Alcohol should be avoided because it can increase liver damage. Restrictions on diet or activity, including commonly prescribed bed rest, have no scientific basis.

Patients with acute HCV infection should be treated with antiviral therapy upon initial diagnosis without awaiting spontaneous resolution in order to prevent transmission to others. Owing to the high efficacy and safety, the same regimens that are recommended for chronic HCV infection are recommended for acute infection ( 1 ).

Viral hepatitis should be reported to the local or state health department.

Treatment reference

1. American Association for the Study of Liver Diseases (AASLD) and Infection Diseases Society of America (IDSA) : HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. Management of Acute HCV Infection. Accessed May 7, 2024.

Prevention of Acute Viral Hepatitis

Because treatments have limited efficacy, prevention of viral hepatitis is very important.

General measures

Good personal hygiene helps prevent transmission, particularly fecal-oral transmission as occurs with HAV and HEV.

Blood and other body fluids (eg, saliva, semen) of patients with acute HBV and HCV infection and stool of patients with HAV infection are considered infectious. Barrier protection is recommended, but isolation of patients does little to prevent spread of HAV and is of no value in HBV or HCV infection.

Posttransfusion infection is minimized by avoiding unnecessary transfusions and by screening all donors for hepatitis B and C. Screening has decreased the incidence of posttransfusion hepatitis B and hepatitis C, which are now extremely rare in the United States.

Immunoprophylaxis

Immunoprophylaxis can involve active immunization using vaccines and passive immunization.

Vaccines for hepatitis A and hepatitis B are available in the United States.

Routine vaccination for hepatitis A and B is recommended in the United States for all children and for adults at high risk (see Adult Immunization Schedule ).

A vaccine for hepatitis E is not available in the United States but is available in China.

No product exists for immunoprophylaxis of HCV or HDV. However, prevention of HBV infection prevents HDV infection. The propensity of HCV for changing its genome hampers vaccine development.

Transmission is the fecal-oral route for hepatitis A and E parenterally or via blood for hepatitis B and C.

Hepatitis B and C, unlike hepatitis A, predispose to chronic hepatitis and liver cancer (if chronic).

Patients with acute viral hepatitis may be anicteric or even asymptomatic.

Do viral serologic testing (IgM anti-HAV, HBsAg, anti-HCV) if clinical findings are consistent with acute viral hepatitis and AST and ALT are elevated out of proportion to alkaline phosphatase.

Treat patients supportively. Treat acute hepatitis C to prevent transmission.

Routine vaccination for hepatitis A and B is recommended in the United States for all children and for adults at high risk.

Copyright © 2024 Merck & Co., Inc., Rahway, NJ, USA and its affiliates. All rights reserved.

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Clinical Signs and Symptoms of Hepatitis A

• Most people who get hepatitis A have a mild, short-term illness.
• Adults are more likely than children to have symptomatic HAV infection.
• Clinicians should conduct serologic testing on patients if they have signs or symptoms consistent with HAV infection.
• CDC does not recommend routine hepatitis A screening.

Disease presentation

Older children and adults with HAV infection will typically experience symptoms.

Most (70%) of infections in children younger than age 6 are not accompanied by symptoms. When symptoms are present, young children typically do not have jaundice; most (>70%) older children and adults with HAV infection have jaundice. 1 2

Among symptomatic patients, 10%–15% might experience prolonged or relapsing symptoms up to 6 months after they become infected. 1 3 4 5 6

Incubation period

The average incubation period for HAV is 28 days (range: 15–50 days). 3 4 5

Virus survival

Depending on the environmental conditions, the virus can live outside the body for months. 6

For the public‎

Common symptoms.

Hepatitis A symptoms, which usually last less than 2 months, occur abruptly, and can include:

• Abdominal pain, nausea, and/or vomiting
• Dark urine or clay-colored stools
• Loss of appetite

For detailed guidance on clinical care and treatment for hepatitis A, keep reading .

Clinical assessment

Clinicians should conduct serologic testing on patients if they have signs or symptoms consistent with HAV infection and/or if they think they may have been infected with HAV. CDC does not recommend routine hepatitis A screening.

• Wasley A, Fiore A, Bell BP. Hepatitis A in the era of vaccination . Epidemiol Rev 2006;28:101–11. Epub 2006 Jun 14. Review.
• Schiff ER. Atypical clinical manifestations of hepatitis A . Vaccine 1992;10 Suppl 1:S18.
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Hepatitis A

Learn more about hepatitis A, a liver disease caused by the hepatitis A virus (HAV). Find HAV information for the public and health professionals.

For Everyone

Health care providers.

Hepatitis B Clinical Presentation

• Author: Nikolaos T Pyrsopoulos, MD, PhD, MBA, FACP, AGAF, FAASLD, FRCP(Edin); Chief Editor: BS Anand, MD  more...
• Sections Hepatitis B
• Practice Essentials
• Pathophysiology
• Epidemiology
• Patient Education
• Physical Examination
• Approach Considerations
• Diagnostic Tests
• Radiologic Studies
• Liver Biopsy and Histologic Features
• Pharmacologic Management
• Surgical Intervention
• Hepatitis B and Pregnancy
• Vaccination
• Long-Term Monitoring
• 2016 and 2018 AASLD Guidelines
• 2017 and 2018 EASL Recommendations
• 2015 and 2020 WHO Guidelines Summary
• Medication Summary
• Interferons
• Antihepadnaviral, Reverse Transcriptase inhibitors
• Vaccines, Inactivated, Viral
• Questions & Answers
• Media Gallery

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:

Low-grade fever

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

Disturbances in sleep pattern

Mental confusion

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

Mild upper quadrant pain or discomfort

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

Hepatic decompensation

GI bleeding

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:

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:

History of variceal bleeding

Peripheral edema

Gynecomastia

Testicular atrophy

Abdominal collateral veins (caput medusa)

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• 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).

Contributor Information and Disclosures

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.

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.

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.

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.

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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Hepatitis b.

Nishant Tripathi ; Omar Y. Mousa .

Affiliations

Last Update: July 9, 2023 .

• Continuing Education Activity

Hepatitis B infection is a serious global healthcare problem. Often transmitted via body fluids like blood, semen, and vaginal secretions, the hepatitis B virus can cause liver injury. After infection with the hepatitis B virus, the majority of adults are able to clear the infection. Patients can present with acute symptomatic disease or have an asymptomatic disease that is identified during screening for the hepatitis B virus. This article focuses on identifying who is at risk of hepatitis B, and clinical evaluation and management of patients with hepatitis B by an interdisciplinary team. It also focuses on preventive measures.

• Describe the epidemiology of hepatitis B.
• Outline the common blood tests for the diagnosis of hepatitis B infection.
• Review the complications of hepatitis B infection.
• Explain the importance of collaboration and communication amongst the interdisciplinary teams to enhance the delivery of care for patients affected by hepatitis B.
• Introduction

Hepatitis B viral infection is a serious global healthcare problem. It is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV). It is often transmitted via body fluids like blood, semen, and vaginal secretions. The majority (more than 95%) of immunocompetent adults infected with HBV can clear the infection spontaneously. Patients can present with acute symptomatic disease or have an asymptomatic infection that is identified during screening for HBV. The clinical manifestations of HBV infection vary in both acute and chronic diseases. During the acute infection, patients can have subclinical or anicteric hepatitis, icteric hepatitis, or less commonly fulminant hepatitis. In chronic infection, patients can have an asymptomatic carrier state, chronic hepatitis, cirrhosis, and hepatocellular carcinoma.

Initial symptoms are nonspecific and may include anorexia, nausea, vomiting, abdominal pain, and jaundice. In cases of severe liver damage, patients can develop jaundice, hepatic encephalopathy, ascites, gastrointestinal bleeding secondary to esophageal varices, coagulopathy, or infections. Diagnosis is based on serologic blood tests in patients with suspected signs and symptoms and associated risk factors for viral hepatitis. This will be discussed in more detail below.

Transmission of hepatitis B involves the transfer of the virus from infected people to non-immune people in various ways. Major modes of transmission for hepatitis B are as follows:

1. Horizontal transmission: It involves the transmission of hepatitis B through sexual contact or mucosal surface contact. Unprotected sex and injection drug use are major modes of transmission in low to intermediate prevalence areas. [1]  

2. Vertical transmission: Vertical transmission involves the maternal-to-newborn perinatal transmission of the virus. [2]  It is the predominant mode of transmission in high-prevalence areas. 

Sexual contact includes unprotected intercourse (vaginal, oral, or anal) and mucosal contact involves any contact involving an infected patient’s saliva, vaginal secretion, semen, and blood.

Prevalence areas are based on the percentage of the population with hepatitis B surface antigen (HBsAg) positivity with greater than or equal to 8% representing high prevalence areas, 2-7% representing low to intermediate prevalence areas, and less than 2% representing low prevalence areas. [3]

• Epidemiology

HBV infection has the potential for progression to a chronic state and thus presents as a global public health threat for its associated morbidity and mortality. While hepatitis B vaccines are available, limited access to healthcare and lack of proper health education contributes to the increasing global prevalence of hepatitis B. Lower incidence of hepatitis B in the United States compared to Asia and Africa is due to better access to healthcare and better use of vaccinations and other preventive measures. 

 U.S. Statistics 

• Around 60,000 new cases of HBV infection annually [4]
• 2 million or more people with chronic hepatitis B infection [4]
• Prevalence is higher in black, Hispanic, and Asian populations compared to whites [5]  
• Prevalence is lower in people less than 12 years of age born in the U.S. 
• Accounts for 5% to 10% of chronic end-stage liver disease, and 10% to 15% of cases of hepatocellular cancer
• Causes 5000 deaths annually 

Worldwide Statistics

• 350-400 million of the world population has chronic hepatitis B. [6]
• The following population is known to have a higher prevalence: Asian Pacific Islanders, Alaskan Eskimos, and Australian aborigines. [6]
• The following geographic regions have higher prevalence: the Indian sub-continent, sub-Saharan Africa, and central Asia.
• The prevalence of hepatitis B is reduced after the initiation of the hepatitis B vaccination program.
• 10 genotypes (A-J) of hepatitis B have been identified. [7]

High-risk groups for HBV infection include intravenous drug users, infants born to infected mothers, males who have sexual intercourse with other males, hemodialysis patients (and workers), healthcare workers, household contacts of known patients with chronic HBV. A majority of the global HBV disease burden is primarily through vertical transmission.

• Pathophysiology

Hepatitis B virus is transmitted via percutaneous inoculation or through mucosal exposure with infectious bodily fluids. Oral-fecal transmission is possible but considerably rare. The incubation period of HBV infection is typically between 30 and 180 days, and while recovery is common in immunocompetent patients, a small percentage can progress to a chronic state, serologically defined as the presence of HBsAg for greater than six months. HBsAg is transmitted via blood contact or body secretions, and the risk of acquiring hepatitis B is considerably higher in individuals with close contact with HBsAg-positive patients.

The pathogenesis of liver disease in HBV infection is mainly immune-mediated, and in some circumstances, HBV can cause direct cytotoxic injury to the liver. HBsAg and other nucleocapsid proteins that are present on cell membranes promote T cells-induced cellular lysis of HBV-infected cells. Cytotoxic T cell response to HBV-infected hepatocytes is relatively ineffective; a significant majority of HBV DNA is cleared from the hepatic system prior to maximal T cell infiltration, suggesting that the immune response is likely more robust in the early stages of infection. The immune response may not be the sole etiology behind hepatic injury in hepatitis B patients. Hepatitis B-associated injury is also seen in post-liver transplant patients with hepatitis B that are on immunosuppressant therapy. The histological pattern that follows from this infection is termed fibrosing cholestatic hepatitis and is thought to be associated with an overwhelming exposure to HBsAg. This lends credence to the idea that hepatitis B may possess pathogenicity regardless of the immune system’s response. [8]

• Histopathology

Acute Hepatitis B Infection: Histologic findings include "lobular disarray, ballooning degeneration, multiple apoptotic bodies, Kupffer cell activation, and lymphocyte-predominant lobular and portal inflammation. [9]

Chronic Hepatitis B Infection:  Lymphocyte-predominant portal inflammation with interface hepatitis and spotty lobular inflammation. [9]

• History and Physical

Patients infected with HBV could be asymptomatic initially and, depending on the particular genotype, might not be symptomatic throughout the infected state. In these particular cases, careful history taking is important to establish a diagnosis. However, when symptomatic from acute HBV infection, patients can present with serum sickness-like syndrome manifested as fever, skin rash, arthralgia, and arthritis. This syndrome usually subsides with the onset of jaundice. Patients may also have fatigue, abdominal pain, nausea, and anorexia.

History taking should emphasize the social history, including sexual practices (e.g., unprotected, same-sex, etc.), illicit drug use, profession (e.g., healthcare worker, sex worker), and living arrangements (i.e., within the same household as a patient with HBV infection). Patients in high-risk groups (i.e., healthcare workers, IV substance abuse patients, etc.) or those from highly endemic areas may warrant testing. Those with certain mental illnesses like bipolar disorder, schizophrenia, or manic disorder are at an increased risk for contracting HBV infection during manic states within which one may participate in risky sexual behaviors, including unprotected sex.

Physical examination should also assess for stigmata of chronic liver disease, including jaundice, ascites, hepatomegaly, splenomegaly, palmar erythema, Dupuytren contractures, spider nevi, gynecomastia, caput medusa, and hepatic encephalopathy which suggests portal hypertension and cirrhosis.

Extrahepatic manifestations include polyarteritis nodosa and glomerular disease (membranous nephropathy and, less often, membranoproliferative glomerulonephritis). Aplastic anemia has also been described.

Diagnosis of Hepatitis B is based on proper history taking, physical examination, laboratory works, and imaging. 

Initial symptoms are nonspecific and can include anorexia, nausea, vomiting, abdominal pain, dark urine, clay-colored stool, and jaundice. In cases of severe liver damage, advanced findings specific to liver damage are common and can include hepatic encephalopathy, confusion, coma, ascites, gastrointestinal bleeding, coagulopathy, or infections. In cases of chronic hepatitis B, patients can have a chronic inactive infection, or they can develop findings of acute hepatitis known as chronic active hepatitis. 

The diagnosis of hepatitis B relies on the appropriate history/physical and evaluation of serum or viral biomarkers. Viral serology of hepatitis B is usually detectable 1-12 weeks after initial infection with the primary viral marker being hepatitis B surface antigen (HBsAg). The presence of HBsAg rarely persists beyond 6 months after infection and typically precedes detectable quantities of the corresponding antibody to surface antigen (Anti-HBsAg). The period of time between the disappearance of HBsAg and the appearance of Anti-HBsAg is termed “the window period” or “serological gap.” During the window period, other viral serology could also be undetectable. HBsAg is the first virological marker to be detected thanks to its exposure on the viral surface and is indicative of an acute infection. Immune-mediated destruction of the nucleocapsid allows exposure of core antigen (HBcAg) or e antigen (HBeAg) with subsequent antibody development. Liver enzymes are typically elevated within the latter part of the replicative phase on infection thanks to active inflammatory processes, otherwise, liver transaminases could also be within their reference ranges. Hence, liver transaminases should not be a sole guide to diagnosing suspected hepatitis B infection.

The presence of antibodies to HBsAg indicates immunized status while the presence of antibodies to HBeAg refers to a possible chronic infection state. Seroconversion refers to the transition between an acute, immune-active phase to an inactive carrier state and is marked by the spontaneous development of antibodies to HBeAg. Earlier seroconversion has been related to more favorable outcomes while later seroconversion, in conjunction with recurrent bouts of reactivation and remission, is more liable to complications like liver cirrhosis, thus resulting in poorer outcomes. [10] The persistence of serum HBsAg for a duration of 6 months or greater delineates acute hepatitis B infection from chronic hepatitis B infection. Following groups of people should be screened for hepatitis B: [3]

• Persons born in high or intermediate endemic areas (HBsAg prevalence of greater than or equal to 2%). African countries, countries from North, Southeast, and East Asia. All countries from Australia and South Pacific (except for Australia and New Zealand). All countries from the Middle East (except for Israel and Cyprus). All countries from Eastern Europe (except for Hungary), Western Europe (Spain, Malta, and the indigenous population of Greenland), North America (Alaskan natives and indigenous populations of Northern Canada), Mexico, Guatemala, and Honduras. South America (Ecuador, Guyana, Suriname, Venezuela, and Amazonian areas). Caribbean (Antigua, Barbuda, Dominica, Grenada, Haiti, Jamaica, Saint Kitts and Nevis, Saint Lucia, and Turks and Caicos Islands).
• The unvaccinated U.S. citizens whose parents were born in high prevalence areas.
• History of illicit intravenous drug use.
• Men who have sex with men.
• Persons on immunosuppressive therapy.
• Persons with elevated ALT or AST of unknown origin.
• Blood, plasma, organ, tissues, or semen donors.
• Persons with end-stage renal disease.
• All pregnant women and infants born to HBsAg-positive mothers.
• Persons with chronic liver disease and HIV.
• Close contacts of HBsAg-positive persons, such as household, sexual, or needle-sharing.
• Persons with more than one sexual partner in the last six months.
• Persons requesting evaluation or treatment for sexually transmitted infections.
• Health care workers or public safety workers who are at risk for occupational exposure to blood or blood-contaminated body fluids.
• Residents and staff at facilities for developmentally disabled persons.
• Travelers to countries with an intermediate or high prevalence of Hepatitis B virus infection.
• Correctional facilities inmates.
• 19-59-year-old persons with diabetes who have not been vaccinated for Hepatitis B.
• Persons who are the source of blood or body fluid exposures that might require post-exposure prophylaxis.

Interpretation of Serologic Markers

Following serologic markers are often tested: Hepatitis B surface antigen (HBsAg), antibody to Hepatitis B surface antigen (anti-HBs), Hepatitis B core Ab (Anti-HBc) IgM, Hepatitis B core Ab (Anti-HBc) IgG, Hepatitis B e antigen (HBeAg), and Hepatitis B e antibody (anti-HBe). [10]

HBsAg: Acute infection (less than 6 months) or chronic infection (more than 6 months).

Anti-HBs: Recovery from acute infection or immunity from vaccination.

HBeAg: Mostly associated with high viral load.

Anti-HBe: Low replicative phase.

Anti-HBc IgM: Acute infection, an only marker present in the window period, can be present during exacerbation of chronic infection.

Anti-HBc IgG: Exposure to infection, chronic infection (if present along with HBsAg), recovery from acute infection (if present with anti-HBs), if isolated presence, may represent occult infection.

Other markers are: Hepatitis B viral DNA is for detection of viral load. Hepatitis B genotype provides input about disease progression and response to interferons. [11]

• Treatment / Management

Preventive measures constitute a major component of the management of hepatitis B. As of 2019, hepatitis B vaccines available in the United States are categorized into either single-antigen hepatitis B vaccines or combination vaccines.

Acute hepatitis B infection is self cleared in 95% of healthy adults. Management is supportive in a majority of patients. Patients with severe acute disease (2 of the 3: bilirubin more than 10 mg/dl, INR more than 1.6 and hepatic encephalopathy) and protracted acute severe disease (total bilirubin more than 3 mg/dl or direct bilirubin more than 1.5 mg/dl, INR more than 1.5, hepatic encephalopathy, or ascites) need antiviral treatment.

Management of chronic hepatitis B should include identification of HIV, hepatitis C, and hepatitis D coinfection, hepatitis B virus replication status, and severity of the disease. [10]  The severity of the disease is based on clinical assessment, blood counts, liver enzymes, and liver histology. [10]  While non-invasive tests are useful (blood test, imaging to measure liver stiffness) for chronic hepatitis B with normal alanine transferase, for patients with elevated or fluctuating alanine transferase, liver biopsy is necessary to identify if they need antiviral treatment. [10]

FDA-approved medications for chronic hepatitis B include interferons (peginterferon alfa-2a, interferon alfa-2b), nucleoside analogs (entecavir, lamivudine, telbivudine), and nucleotide analogs (adefovir, tenofovir). Entecavir and tenofovir are preferred for acute HBV infection if treatment is warranted, due to their relatively higher barrier to resistance. Entecavir combination drugs have been developed. However, a 2018 meta-analysis based on 24 studies involved with entecavir polytherapy vs entecavir monotherapy determined that entecavir combination drugs were no more effective than entecavir monotherapy. [12]  Vertical transmission of hepatitis B remains a significant cause of the global HBV burden. In a 2015 prospective, multicenter trial, administration of tenofovir in HBsAg-positive and/or HBeAg-positive mothers demonstrated a benefit in reducing ALT levels in mothers and decreasing infant HBsAg levels at 6 months postpartum. [13]  Major drawbacks for this study, however, include a relatively small sample size (n=118) and the lack of a placebo-based control group.  Oral nucleos(t)ide therapy has been shown to suppress viral replication and thus decrease the viral burden. Lamivudine was the first effective agent to successfully used to suppress viral counts but was associated with high drug resistance. [14]  A 2014 clinical trial comparing entecavir vs lamivudine in chronic B hepatitis reported better virological response in the entecavir group compared to the lamivudine group. [15]  The 2013 GAHB trial was a placebo-controlled, double-blind study that compared lamivudine with a placebo. HBsAg clearance was achieved in a majority of patients with lamivudine therapy but the overall strength of the study was weakened by low recruitment numbers (n = 35). [16] For patients in the immune-tolerant phase of hepatitis B infection, a stage marked by normal liver transaminases and HBV DNA, antiviral medications were not recommended. A randomized controlled study showed suboptimal control of viral burden, likely secondary to high circulating levels of HBV DNA. [17]  Regarding monotherapy versus combined therapy, there have been several limited studies addressing this issue. In the 2018 POTENT study, there was no demonstrated difference between monotherapy versus sequential therapy although there was insufficient data for statistical significance for HBsAg seroconversion. [18]

The counseling of patients on the prevention of transmission is extremely valuable. Lifestyle modifications include reducing intake of agents with potential for liver damage such as alcohol, hepatotoxic medications, herbal medications, and herbal supplements. 

The goals of antiviral therapy are: [10]

• Suppression of hepatitis B virus replication
• Reduction of liver inflammation
• Prevention of progression to liver cirrhosis and hepatocellular carcinoma

Appropriate treatment response is indicated by the following findings: [10]

• Blood tests: normalization of ALT
• Undetectable hepatitis B viral DNA
• Loss of HBsAg and HBeAg with seroconversion to anti-HBs and anti-HBe
• Reduced inflammation on liver biopsy with no worsening of fibrosis

Surgical intervention for hepatitis B is only indicated for fulminant liver disease requiring transplantation.

• Differential Diagnosis

The differential diagnosis for hepatitis B infection is broad due to the presence of non-specific symptoms such as fatigue, abdominal pain, nausea, and vomiting. Other etiologies of hepatitis (i.e., hepatitis A, hepatitis C, hepatitis E, alcoholic hepatitis, and autoimmune hepatitis) should be considered in conjunction with appropriate history taking and pertinent laboratory investigation.

Iron overload (hemochromatosis) can be associated with abdominal tenderness and abnormal liver transaminase levels. Pertinent findings that favor a diagnosis of hemochromatosis compared to hepatitis B include diffuse skin discoloration (bronze diabetes) and impaired glucose tolerance.

Wilson disease is a disease of excessive copper accumulation. It is associated with psychiatric disturbances due to copper accumulation in the basal ganglia. Kayser-Fleischer rings are pathognomonic for Wilson disease but are not completely sensitive (requires an expert ophthalmologist to confirm this finding). Laboratory evaluation that favors a diagnosis of Wilson disease includes low serum ceruloplasmin levels and elevated urinary copper, and if abnormal, requires further evaluation by a hepatologist.

• Alcoholic hepatitis
• Autoimmune hepatitis
• Drug-induced liver injury
• Hemochromatosis
• Hepatitis A
• Hepatitis C
• Hepatitis D
• Hepatitis E
• Hepatocellular carcinoma
• Human immunodeficiency virus
• Wilson disease

Acute HBV infection can be treated symptomatically and in immunocompetent patients, can spontaneously resolve. Those that progress to the chronic state, however, are at increased risk for the development of hepatocellular carcinoma, cirrhosis, or fulminant liver failure. The likelihood of risk is dependent on the particular genotype, and the method of transmission as vertical transmission has a higher risk of long-term complications compared to horizontal transmission cases.

• Complications

Unlike hepatitis A and hepatitis E, in which there is no chronic state, HBV infection has the potential for the development of a chronic state. Chronic hepatitis B predisposes a patient to the development of portal hypertension, cirrhosis, and its complications or hepatocellular carcinoma (HCC). As such, patients with HBV infection should be monitored closely, and a referral to a specialist is highly recommended.Fulminant liver failure from HBV infection requires an emergent liver transplant evaluation at a liver transplant center.

• Consultations

Hepatitis B management ideally involves interprofessional collaboration. Primary care, gastroenterology, hepatology, infectious disease, liver transplant, and palliative care services are among the different services involved.

• Deterrence and Patient Education

Patient education remains one of the most important components in preventative measures regarding HBV infection.

Education should be provided to expecting parents (particularly those from highly endemic regions) about the importance of vaccination and to clarify erroneous beliefs about vaccinations.Patient education should also include counseling about the avoidance of risky behaviors that predispose an individual to be infected, including promiscuous sexual activity or intravenous drug abuse. They should also be advised not to share items such as shaving razors, toothbrushes, or hair combs due to possible transmission via mucosal contact or through microtrauma to protective barriers.

• Pearls and Other Issues

Hepatitis D (a member of the delta virus family) has been long associated with HBV infections and cannot exert pathological influence without the presence of HBV infection. Two forms of infection exist; coinfection (acquired at the same time) and superinfection (hepatitis D infection in a patient with chronic hepatitis B infection). Superinfection tends to be more severe than coinfection. Due to the preexisting hepatitis B infection, anti-HBcAg IgM is undetectable in superinfection states but can be noted in coinfection.

• Enhancing Healthcare Team Outcomes

As hepatitis B infection is highly transmissible via accidental needlesticks, healthcare providers involved in taking care of a patient with HBV should exercise caution and practice proper preventative measures such as vaccination. Patient education should also include counseling about HBV transmission. The interprofessional team's role is crucial in ensuring the best patient outcomes.

The vaccination rate is low in many developing countries, and the majority of patients are undiagnosed. Educational programs and improved awareness among the general public and healthcare providers are necessary to improve the identification of the patients, reduce transmission of the disease, and reduce the complications of hepatitis B infection.

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Disclosure: Nishant Tripathi declares no relevant financial relationships with ineligible companies.

Disclosure: Omar Mousa declares no relevant financial relationships with ineligible companies.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

• Cite this Page Tripathi N, Mousa OY. Hepatitis B. [Updated 2023 Jul 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

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