In addition to the standard medical history, the initial history of patients with chronic hepatitis B should focus on risk factors for HBV, including family history of HBV or liver disease, history of alcohol use, any prior evaluation for cirrhosis or hepatocellular carcinoma (HCC), prior treatment of HBV, presence of advanced liver disease, history of extrahepatic manifestations of HBV, co-occurring viral infections, and other key noninfectious comorbidities.
Identifying Risk Factors for HBV
A key aspect of the initial evaluation of persons with chronic HBV is to identify risk factors for HBV acquisition. This information helps the clinician to better assess the duration of infection, determine the risk of advanced liver disease, and provide counseling regarding prevention of HBV transmission to others. Globally, the majority of chronic HBV infections are acquired before the age of 5 years, with perinatal transmission the most common mode of infection, especially in countries with high HBV endemicity (Table 1).[6,7] For persons from these endemic regions, it is important to ask about family history of chronic HBV, particularly in mother or siblings, as that may provide a clue to perinatal transmission. In the United States, injection drug use and sex with multiple partners are the most important risk factors for acquiring HBV.[8] Important elements of the initial history include prior or current injection drug use, history of multiple sex partners, prior exposure to blood or bodily fluids (including occupational exposure), and family history of HBV or liver disease.[5] At the initial intake, some individuals may be reluctant to disclose a history of remote injection drug use or multiple sex partners. Care should be taken to establish rapport and a safe environment for ongoing discussion of these activities, whether past or current.
History of Alcohol Use
Due to its deleterious effects on the liver, it is important to inquire about alcohol use among persons with chronic HBV. Less is known about the synergistic effects of alcohol use and chronic HBV when compared to the effects of alcohol use and chronic hepatitis C virus (HCV). Although there is no clear guidance on what quantity of alcohol may be safe in persons with chronic HBV infection, studies suggest heavy alcohol use in persons with HBV can increase the risk of HCC 1.3- to 8.4-fold, in comparison to individuals with chronic HBV who are not heavy drinkers.[9,10,11,12] Accordingly, persons with chronic HBV should be counseled to avoid alcohol and be directed to educational resources, such as those provided by the National Institute on Alcohol Abuse and Alcoholism (NIAAA).[13,14] In clinical practice, it can often be challenging to obtain an accurate history of alcohol consumption. A general approach would be to assess quantity of use over a specified period of time without using qualifiers such as “heavy” or “excessive” in the inquiry. Several well-validated screening tools, as outlined below, are available to help assess for alcohol use disorder.
- CAGE: The CAGE is a 4-question screening tool for alcohol use disorder that focuses on Cutting down, Annoyance by criticism, Guilty feeling, and Eye-openers (see CAGE screening tool) (Figure 1).[15]
- AUDIT: The AUDIT, or Alcohol Use Disorder Identification Test, is a 10-item questionnaire that can be used to screen for hazardous drinking.[16]
- AUDIT-C: A shorter 3-question version of the AUDIT, known as the AUDIT-C, has also been validated and performs similarly to the AUDIT for detecting heavy drinking and/or alcohol dependence (see AUDIT-C screening tool) (Figure 2).[17]
Prior Evaluation for Cirrhosis
Cirrhosis is a key predictor of liver-related complications such as HCC and is an indication for HCC screening. In addition, treatment of chronic HBV is indicated for all persons with cirrhosis.[13,18] As such, among persons who have previously been engaged in HBV care, it is important to understand if they have undergone a prior evaluation for cirrhosis and what that evaluation revealed. Although guidelines do not specify the best method to diagnose cirrhosis in persons with chronic HBV, a variety of modalities are currently used, including liver biopsy, hepatic ultrasound, transient elastography, laboratory markers, and clinical examination. Understanding the results and timing of prior fibrosis assessments can inform the need for antiviral therapy and help triage the need for additional fibrosis assessment. A more detailed discussion on evaluating for cirrhosis in persons with chronic HBV can be found in the module When to Initiate HBV Treatment.
Prior Screening for Hepatocellular Carcinoma (HCC)
Given the oncogenic properties of HBV and the elevated risk for developing HCC among people with chronic HBV, it is also important to obtain information on prior screening for hepatocellular carcinoma, typically in the form of an abdominal ultrasound. Multiphase imaging studies, such as computed tomography (CT) and magnetic resonance imaging (MRI), are also used in some circumstances.[13,19]
Prior or Current Antiviral Therapy for HBV
When evaluating persons with chronic HBV, clinicians should inquire about prior or current antiviral therapy for HBV, including the type of treatment, duration of therapy, response to therapy, level of adherence, treatment-related adverse effects, and reasons for stopping therapy (if discontinued). For persons with HIV and chronic HBV coinfection, this would entail a detailed overview of past antiretroviral therapy because the nucleos(t)ide analogues emtricitabine, lamivudine, tenofovir alafenamide, or tenofovir DF are also active against HBV. This information can help guide recommendations for future treatment and predict the presence of resistance, particularly for lamivudine and adefovir—two drugs that are no longer recommended as first-line therapy due to their low barrier to resistance.[20,21]
Presence of Advanced Liver Disease
The management of persons with advanced liver disease can be complex. As discussed above, it is important to understand what, if any, prior testing the patient has undergone for cirrhosis, and it is similarly important to assess for signs and symptoms of decompensated cirrhosis including current or past ascites, hepatic encephalopathy, jaundice, scleral icterus, and gastrointestinal bleeding. If advanced liver disease is suspected, the clinician can calculate the Child-Turcotte-Pugh (CTP) stage to help estimate the severity of cirrhosis (see CTP Calculator). Persons with chronic HBV who are classified as CTP stage B or C have decompensated cirrhosis and should be urgently referred to a liver specialist.
Presence of Extrahepatic Manifestations
Hepatitis B can be associated with a variety of extrahepatic manifestations, most of which are immune mediated.[22] The most clinically significant extrahepatic manifestations include polyarteritis nodosa, glomerular disease (commonly membranous nephropathy or membranoproliferative glomerulonephritis), and a serum sickness-like reaction that can occur during acute HBV infection.[23,24,25]
Key Viral Comorbidities
During the initial evaluation of persons with chronic hepatitis B, it is important to evaluate for other viral infections, such as human immunodeficiency virus (HIV), HCV, hepatitis A virus (HAV), and possibly hepatitis D virus (HDV).
- HIV: Identifying persons with HIV and HBV coinfection is of particular importance, as coinfection has been shown to accelerate progressions of liver disease and increase liver associated mortality.[26] In addition, there is considerable overlap in the oral antivirals used to treat HBV and HIV, and therefore understanding the individual’s HIV status is critical to selecting an appropriate antiviral regimen for HBV (Table 2).[20,27]
- HCV: Coinfection with HCV can accelerate progression of liver disease in persons with chronic HBV.[28] Evaluation for HCV and HAV is especially important since there is highly effective and well tolerated treatment for HCV and persons undergoing treatment for HCV have risk of HBV reactivation.
- HAV: Acute hepatitis A can result in a more severe clinical course, including fulminant liver failure, in patients with chronic HBV.[29] Screening for HAV is important since there is a highly effective vaccine to prevent HAV infection.
- Hepatitis D Virus (HDV): HDV is a unique satellite virus that requires HBsAg to replicate and can therefore only occur in the presence of chronic HBV infection.[30] Coinfection with HDV can accelerate the progression of liver disease and increase the risk of developing HCC.[13] The American Association for the Study of the Liver (AASLD) guidelines recommend screening for HDV in key populations at highest risk, including those from regions of high HDV endemicity (Figure 3), persons with a history of injection drug use, men who have sex with men (MSM), individuals coinfected with HCV or HIV, persons with multiple sex partners or any history of sexually transmitted diseases, and those with persistently elevated liver enzymes despite low or undetectable HBV DNA levels.[13,31]
Noninfectious Comorbidities
When evaluating persons with chronic HBV infection, the clinician should inquire about any secondary causes of liver disease, such as nonalcoholic fatty liver disease (NAFLD), alcoholic hepatitis, alpha-1 antitrypsin deficiency, hemochromatosis, or autoimmune hepatitis.[32,33,34,35,36,37,38] A past or current history of obesity is important to obtain since obesity is strongly associated with the development of NAFLD.[39]