Diagnosis and management of chronic hepatitis B: A patient‐friendly summary of the 2018 American Association for the Study of Liver Diseases practice guidance

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This article will summarize practice guidance/guidelines put forth by the American Association for the Study of Liver Diseases (AASLD) in an easy‐to‐read format for patients and their caregivers. The difference between guidance and guidelines is that guidelines are supported by very strong evidence, such as large randomized trials, whereas guidance statements are supported by smaller studies and expert opinion. This summary will hopefully help patients better understand their condition, but it should not replace expert medical care. The full document is available online at: https://doi.org/10.1002/hep.29800 ¹

CHRONIC HEPATITIS B

Chronic hepatitis B (CHB) is a lifelong infection due to the hepatitis B virus (HBV), a virus that infects the liver. Acute hepatitis B infections refer to infections of less than 6 months, and CHB refers to infections lasting more than 6 months. Most patients with CHB do not have symptoms. CHB can lead to serious liver problems, including cirrhosis, end‐stage liver disease, and liver cancer.

HBV is spread through infected body fluids (blood, semen) from an infected to an uninfected individual. It is not spread through casual contact, hugging, or coughing. Worldwide, perinatal (mother to child at birth) transmission is a common way of spreading CHB, especially in countries where CHB is endemic (high prevalence rates).

Screening, diagnosis, and prevention

Guidance Statements:

• Screening should be performed using both hepatitis B surface antigen (HBsAg) and antibody to hepatitis B surface antigen (anti‐HBs).

• Anti‐HBs‐negative screened persons should be vaccinated.

• HBsAg‐positive persons should be counseled regarding prevention of transmission of HBV to others.

• HBV vaccines have an excellent safety record and are given as a three‐dose series at 0, 1, and 6 months. A four‐dose and two‐dose series are also available.

• Sexual and household contacts of HBV‐infected persons who are negative for HBsAg and anti‐ HBs should receive HBV vaccination.

Patient Summary:

Patients with risk factors (Figure 1) should be screened for CHB by a blood test that measures HBsAg and hepatitis B surface antibody (anti‐HBs). Those without CHB (both the HBsAg and anti‐HBs are negative) should receive vaccination to prevent against future CHB infection. Those with CHB (HBsAg is positive) can protect others by taking certain measures. See Table 1 for a checklist for patients who have been diagnosed with CHB.

FIGURE 1.

Global prevalence and risk factors for CHB. *Those with end‐stage kidney disease, with diabetes mellitus, and at risk for occupational exposure to blood/blood‐contaminated body fluids should discuss screening for hepatitis B with their doctor. Adapted with permission from Lancet 2015; 386‐1546‐55

TABLE 1.

Hepatitis B: checklist if you have been diagnosed with hepatitis B

Get vaccinated against hepatitis A if not already immune.

✓ Hepatitis A can be spread through contaminated food or drink. Protecting yourself from hepatitis A is important, especially if you already have a chronic liver condition.

Have your household members and sexual contacts get screened for hepatitis B and vaccinated if not already immune.

✓ Remember both hepatitis A and hepatitis B are vaccine preventable for those not already infected!

Do not share toothbrush, razors, injection equipment, or glucose testing equipment. Cover any open wounds.

Clean blood spills with bleach solution.

Do not donate blood, organs, or sperm.

Use barrier protection during sexual intercourse.

Do not drink alcohol.

Establish regular care with a doctor familiar with how to care for patients with hepatitis B. This will likely include blood tests at least every 6‐12 months, even if you never have any symptoms.

See a doctor if you become pregnant.

Key Point: CHB is vaccine preventable in those without CHB. Patients with certain risk factors should be screened.

Phases of CHB infection

Guidance Statement:

• Given that CHB is a dynamic disease, persons who are not receiving treatment should be checked regularly to determine whether an indication for treatment has developed.

Patient Summary:

Once diagnosed with CHB, your doctor will order additional blood work, including hepatitis B envelope antigen (HBeAg), hepatitis B envelope antibody, alanine transaminase (ALT), and HBV DNA (viral load), to help determine what phase of liver disease you might be in and if treatment is needed. The phases of liver disease are not fixed. Occasionally blood tests are needed more frequently to better understand the virus activity in your body. Some key phases of CHB include immune‐tolerant (the immune system is not reacting to the viral infection), immune‐active (the immune system is reacting to the virus and causing liver inflammation), and inactive CHB (the virus is dormant in the liver cells). Table 2 summarizes the blood tests that characterize these key phases but does not include all phases involved in HBV management.

TABLE 2.

Key phases of CHB

Phase	e Antigen	e Antibody	ALT	HBV DNA	Treatment indicated? a
Immune tolerant b	Positive	Negative	Normal or minimally elevated	Usually high (>1 million IU/mL)	Usually not unless there is fibrosis or patients are older (>40 years)
Immune active c	Can be positive or negative	Can be positive or negative	Elevated	>20,000 IU/mL (eAg+) >2000 IU/mL (eAg−)	Usually
Inactive d	Negative	Positive	Normal	<2000 IU/ml	Usually not

Note: This table lists key phases in CHB but is not a comprehensive list. Please note that these phases are not fixed and given the dynamic nature of CHB, patients can transition from one to the other. Sometimes more frequent blood tests are necessary to understand HBV in your body.

^a Staging of liver disease is often necessary to help guide treatment decisions.

^b Immune tolerant indicates the immune system is not reacting to the viral infection.

^c Immune active indicates the immune system is reacting to the virus and causing liver inflammation.

^d Inactive indicates the virus is dormant in the liver cells.

Staging of your liver disease by assessing fibrosis or stiffness is often necessary to help guide treatment decisions. Most of the time, this can be done noninvasively with elastography or blood tests, but sometimes a liver biopsy may be helpful if there are additional causes of liver disease suspected.

Key Point: Blood work and staging (even if you have no symptoms) are important to help determine what phase of CHB you are currently in and can help determine whether treatment is necessary.

Treatment

2016 HBV Treatment Guidelines:

• The American Association for the Study of Liver Diseases (AASLD) recommends antiviral therapy for adults with immune‐active CHB (HBeAg negative or HBeAg positive) to decrease the risk of liver‐related complications.

• The AASLD recommends pegylated interferon, entecavir, tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF) as preferred initial therapy for adults with immune‐active CHB.

• The AASLD suggests indefinite antiviral therapy for HBeAg‐positive adults with cirrhosis with CHB who seroconvert to anti‐HBe on nucleos(t)ide analogue therapy, based on concerns for potential clinical decompensation and death, unless there is a strong competing rationale for treatment discontinuation.

• The AASLD suggests indefinite antiviral therapy for adults with HBeAg‐negative immune‐active CHB unless there is a compelling rationale for treatment discontinuation.

Patient Summary:

Treatment of CHB depends on your liver enzymes (ALT), as well as the level of your virus activity (HBV DNA, HBeAg, hepatitis B envelope antibody) (Figure 2). When the ALT is elevated, there is often inflammation in the liver that can lead to scarring. The goal of treatment is to reduce liver‐related complications, including liver disease progression to cirrhosis and liver cancer.

FIGURE 2.

Treatment algorithm for HBV. *Normal ALT level for women: 25 U/L. Normal ALT level for men: 35 U/L.

There are two recommended oral (pill) treatment options: tenofovir (either TDF or TAF) and entecavir. Oral therapy controls the virus, but the virus often reactivates if therapy is stopped. Another option is pegylated interferon, which is an injection therapy given for 48 weeks. This treatment is usually not given to people with cirrhosis. Although some people might be able to stop pill therapy, patients with cirrhosis should remain on treatment indefinitely to prevent any additional liver damage. Patients without cirrhosis should discuss treatment duration with their doctor. CHB treatment is often lifelong even in people without any liver damage. Table 3 summarizes key treatment points in special patient populations.

TABLE 3.

Special populations and key points regarding their management of hepatitis B

Special patient populations	Key points
Coinfection with HCV	All patients with CHB should be screened for HCV. Patients diagnosed with HCV should receive treatment. Those not on HBV treatment should be monitored for an HBV flare during HCV treatment.
Coinfection with HDV	Patients with the following risk factors should be tested for HDV: HIV, men who have sex with men, those who inject drugs, and immigrants from areas with high rates of HDV.
Coinfection with HIV	Antiviral medications should be started right away because medications can target both viruses.
Patients who receive immunosuppression	If you have cancer or an inflammatory/autoimmune condition and are on immunosuppressants, please talk to your doctor to determine whether you need medications for CHB.
Acute hepatitis B infection	>95% of adults with acute HBV will recover spontaneously. Those with severe illness and liver failure should receive treatment.
Children with CHB (age 2 to <18 years)	eAg‐positive children with elevated ALT level and measurable HBV DNA level should receive treatment. Children with persistently normal ALT level, regardless of HBV DNA level, do not require treatment.

Side‐effect profiles of TDF, TAF, and entecavir are similar; however, TAF or entecavir should be used in patients at risk for kidney dysfunction or bone disease. Only TDF should be used in pregnant women. Entecavir should be taken on an empty stomach, whereas TAF/TDF can be taken with or without food.

Key Point: Treating CHB depends on your virus activity and liver enzyme activity (ALT level). For patients without cirrhosis on HBV treatment: Do not stop treatment without first consulting with your doctor.

Health maintenance with CHB

Guidance Statement:

• Abstinence or only limited use of alcohol is recommended in HBV‐infected persons.

• Optimization of body weight and treatment of metabolic complications, including control of diabetes and dyslipidemia, are recommended to prevent concurrent development of metabolic syndrome and fatty liver.

• All HBsAg‐positive patients with cirrhosis should be screened (for hepatocellular carcinoma [HCC]) with ultrasound examination with alpha‐fetoprotein (AFP) every 6 months.

• HBsAg‐positive adults at high risk for HCC (including Asian or Black men >40 years of age and Asian women >50 years of age), persons with a first‐degree family member with a history of HCC, or persons with hepatitis D virus (HDV) should be screened with ultrasound examination with AFP every 6 months.

Patient Summary:

Patients with CHB can implement lifestyle modifications to improve their liver health. Although there is no specific diet for hepatitis B, it is important to limit or abstain from alcohol and to maintain a normal body mass index to prevent any additional liver damage from alcohol or fatty liver disease. Smoking tobacco also increases the risk for liver cancer.

Living with CHB involves routine screening of liver cancer (HCC) with a liver ultrasound with a blood test called AFP. Certain populations with CHB are at higher risk for development of liver cancer, including those with underlying liver disease, Asian or Black men older than 40 years, Asian women older than 50 years, those with a family history of liver cancer, and those with HDV infection. Having more than one liver problem (such as alcohol use, fatty liver) can further increase the risk for liver damage, including cirrhosis and liver cancer.

Key point: There are many things you can do to prevent CHB complications, including abstaining from alcohol, maintaining a healthy body weight, and getting ultrasounds to screen for liver cancer.

CHB and pregnancy

Guidance Statement:

• Women who meet standard indications for HBV therapy should be treated. Women without standard indications but who have HBV DNA levels >200,000 IU/mL in the second trimester should consider treatment to prevent mother‐to‐child transmission.

• HBV‐infected pregnant women who are not on antiviral therapy, as well as those who stop antiviral therapy at or early after delivery, should be monitored closely for up to 6 months after delivery for hepatitis flare and seroconversion (when the antigen goes away and the immune system begins to make antibodies against the virus).

• Breastfeeding is not prohibited.

• Newborns of HBV‐infected mothers should receive hepatitis B immune globulin and HBV vaccine at delivery and complete the recommended vaccination series. Infants of HBsAg‐positive mothers should undergo postvaccination testing at 9 to 15 months of age.

Patient Summary:

Pregnant women with CHB can transmit CHB to their baby. Regardless of pregnancy, patients meeting standard indications for treatment should be treated. Those not meeting standard indications should be treated in the third trimester if their HBV DNA level is >200,000 IU/mL (usually checked at weeks 26‐28) ² to reduce transmission risk. Infants of all women with CHB should receive hepatitis B immune globulin and HBV vaccination less than 12 hours after delivery. There are insufficient data to support C‐section to decrease mother‐to‐child transmission. All women with CHB should be monitored for a postpartum HBV flare.

Key Point: Pregnant women with CHB should consult with their liver doctor on monitoring HBV during pregnancy and whether treatment is necessary. If they need to be on medications, TDF is recommended. It is also safe to breastfeed even if the mother has hepatitis B.

CONFLICT OF INTEREST

C.H. has received consulting fees from Gilead, Inc.

Lee F, Ho C. Diagnosis and management of chronic hepatitis B: A patient‐friendly summary of the 2018 American Association for the Study of Liver Diseases practice guidance. Clinical Liver Disease. 2022;20:141–145. 10.1002/cld.1240