21/2/24, 19:59 Pretreatment evaluation of chronic hepatitis B virus infection in the patient with HIV - UpToDate

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Pretreatment evaluation of chronic hepatitis B virus

infection in the patient with HIV
AUTHORS: Kenneth E Sherman, MD, PhD, Chloe L Thio, MD
SECTION EDITOR: David L Thomas, MD
DEPUTY EDITOR: Jennifer Mitty, MD, MPH

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Jan 2024.

This topic last updated: Aug 03, 2023.

INTRODUCTION

The era of potent antiretroviral therapy (ART) has led to declining rates of opportunistic
infections and a new focus on other leading causes of morbidity, such as end-stage liver
disease secondary to chronic hepatitis B virus (HBV) infection [1]. HIV treatment guidelines
generally recommend treatment of chronic HBV in all patients with HIV/HBV coinfection [2-
4]; ART should include agents with dual activity against HIV and HBV.

The pretreatment evaluation of chronic HBV in patients living with HIV will be reviewed here.
The epidemiology, clinical manifestations, diagnosis, treatment, and prevention of HBV
infection in patients with HIV are discussed separately. (See "Epidemiology, clinical
manifestations, and diagnosis of hepatitis B in patients living with HIV" and "Treatment of
chronic hepatitis B in patients with HIV" and "Prevention of hepatitis B virus infection in
adults with HIV".)

APPROACH TO EVALUATION

Most patients with HIV and chronic HBV will be treated for their HIV and HBV, regardless of
the stage of liver disease or their level of immunosuppression (ie, CD4 cell count). (See
"Treatment of chronic hepatitis B in patients with HIV", section on 'Rationale for treatment'.)

The pretreatment evaluation of such patients includes obtaining baseline markers of disease
activity (used to monitor the response to therapy), information to determine which antiviral

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agents to use for HBV treatment, and information to assess for other causes of liver injury
and complications of advanced liver disease (eg, varices, hepatocellular carcinoma).

Baseline assessments include:

● A detailed history and physical examination to assess for hepatotoxic medications and
evidence of advanced liver disease. (See 'Hepatotoxic medications' below and 'Stage of
liver disease' below.)

● Laboratory testing to evaluate markers of HBV activity, kidney function, liver function,
and coexisting causes of liver disease. (See 'Baseline markers of disease activity' below
and 'Information needed for drug selection' below and 'Evaluation for other causes of
liver disease' below and 'Screening and prevention' below.)

● Noninvasive assessment of liver disease. (See 'Stage of liver disease' below.)

● Ultrasound-based imaging to screen for evidence of hepatocellular carcinoma. (See

'Hepatocellular carcinoma screening' below.)

The following discussion will review the evaluation of HIV/HBV coinfected patients as it
pertains to HBV treatment. A detailed discussion on the initial evaluation of HIV infection is
found elsewhere. (See "Selecting an antiretroviral regimen for treatment-experienced
patients with HIV who are failing therapy" and "Initial evaluation of adults with HIV".)

BASELINE MARKERS OF DISEASE ACTIVITY

Certain baseline tests are obtained to assess the level of HBV activity, and are also used to
monitor response to therapy and/or guide future treatment decisions. These tests include
aminotransferase levels, HBV DNA level, hepatitis B e antigen (HBeAg), and hepatitis B e
antibody (anti-HBe). (See 'Aminotransferase levels' below and 'HBV DNA' below and 'Hepatitis
B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe)' below.)

Hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B
core antibody (anti-HBc) are typically obtained prior to the pretreatment evaluation as they
are needed to make the diagnosis of chronic or occult HBV. (See "Hepatitis B virus: Screening
and diagnosis in adults".)

Aminotransferase levels — The activity of HBV infection is inferred by elevations of

aminotransferase levels. Reductions in these levels are suggestive of a treatment response.
(See "Monitoring the patient with HIV and chronic hepatitis B virus infection", section on
'Abnormalities of aminotransferases'.)

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HBV DNA — HBV DNA is also used to monitor response to therapy. One treatment goal is to
achieve an undetectable HBV DNA. Patients who do not achieve an appropriate virologic
response may be non-adherent to their medications or may have developed drug-resistant
HBV. (See "Treatment of chronic hepatitis B in patients with HIV", section on 'Response to
therapy' and "Monitoring the patient with HIV and chronic hepatitis B virus infection".)

Hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe) — HBeAg is a marker

of HBV replication and infectivity. For individuals who are HBeAg positive, seroconversion
from HBeAg to anti-HBe is usually associated with declines in serum HBV DNA. A more
detailed review of serologic markers for HBV infection is found elsewhere. (See "Hepatitis B
virus: Screening and diagnosis in adults", section on 'Hepatitis B e antigen and antibody'.)

INFORMATION NEEDED FOR DRUG SELECTION

Most patients with HIV and HBV coinfection will be treated with an antiretroviral regimen
that includes a tenofovir-emtricitabine containing backbone; these agents are considered
first-line treatment for both infections. However, the ultimate choice depends upon the
patient’s prior treatment history for HIV and/or HBV, as well as their kidney function. The
presence of hepatitis D coinfection may also impact treatment. (See "Treatment of chronic
hepatitis B in patients with HIV", section on 'Approach to treatment'.)

Kidney function — We obtain a baseline serum creatinine and urinalysis prior to starting
treatment. The approach to treatment depends in part upon the estimated glomerular
filtration rate. (See "Treatment of chronic hepatitis B in patients with HIV", section on
'Approach to treatment'.)

Among those individuals receiving tenofovir, serum creatinine and urinalysis should be
monitored. (See "Patient monitoring during HIV antiretroviral therapy", section on 'ART-
associated toxicity'.)

Treatment history — A careful treatment history should be obtained to determine whether

or not the patient has received prior lamivudine (which may also be used to treat HIV
infection). Entecavir, one of the agents used to treat HBV, is less likely to suppress HBV DNA
in patients with lamivudine-resistant HBV.

HBV resistance testing in some patients — A baseline HBV resistance panel is sometimes
obtained in patients with prior exposure to lamivudine/emtricitabine since HBV resistance
has been reported in patients using these agents (especially if they were used as
monotherapy). Reasons for and against resistance testing are described below:

● Some experts assume that patients with prior lamivudine/emtricitabine treatment have
lamivudine-resistant virus and treat accordingly, without obtaining a baseline
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resistance panel.

● Other providers feel that a baseline resistance panel can help guide treatment
decisions, particularly in patients who have reduced kidney function or who are at risk
of developing renal insufficiency on treatment.

Hepatitis D antibody — Patients should be tested for antibody to hepatitis D virus (HDV),
which can only cause infection in patients with chronic HBV and may accelerate liver disease
progression. This virus requires HBsAg to complete replication in the hepatocyte. In some
cases, HDV infection is treated with interferon. The diagnosis and treatment of hepatitis D
virus infection are discussed elsewhere. (See "Treatment and prevention of hepatitis D virus
infection" and "Epidemiology, clinical manifestations and diagnosis of hepatitis D virus
infection".)

EVALUATION FOR OTHER CAUSES OF LIVER DISEASE

Patients with chronic HBV infection should be evaluated for concurrent causes of liver
disease. Many of these can be addressed, which may help prevent progression to end-stage
liver disease. More detailed discussions of the evaluation of abnormal liver function tests, as
well as hepatobiliary disease in individuals with HIV, are found elsewhere. (See "Approach to
the patient with abnormal liver biochemical and function tests" and "Evaluation of the
patient with HIV and hepatobiliary complaints".)

As examples, we assess all patients with HIV for the following:

Hepatitis C — All patients with chronic HBV should be evaluated for hepatitis C virus (HCV)
infection (eg, hepatitis C antibody). Approximately one-third of all patients with HIV have
serologic evidence of HCV exposure, and the vast majority of such patients have chronic
infection. (See "Screening and diagnosis of chronic hepatitis C virus infection".)

Hepatic steatosis — Patients with HIV may be at increased risk for hepatic steatosis
compared with those who do not have HIV, and this may be associated with abnormal
aminotransferase levels. Hepatic steatosis may be suggested on ultrasound, which is also
used to screen for hepatocellular carcinoma. It may also be suggested from transient
elastography if a controlled attenuation parameter score is also obtained. (See
'Hepatocellular carcinoma screening' below and "Management of nonalcoholic fatty liver
disease in adults".)

Hepatotoxic medications — Patients should be evaluated to determine whether or not they

are using hepatotoxic agents (eg, acetaminophen, alcohol). This is particularly important for
those with advanced liver disease. Such patients should be instructed to avoid these agents.

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(See "Cirrhosis in adults: Overview of complications, general management, and prognosis",

section on 'Avoidance of hepatotoxins'.)

SCREENING AND PREVENTION

In addition to evaluation for other causes of liver disease, patients coinfected with HIV and
HBV should be evaluated for the following:

● Cirrhosis
● Hepatocellular carcinoma
● Osteoporosis
● Immunity to hepatitis A virus

The results of this testing may prompt additional tests and/or treatments.

Stage of liver disease — Patients should be assessed for their stage of liver disease to
determine the need for further evaluation/management of portal hypertension. (See
"Cirrhosis in adults: Overview of complications, general management, and prognosis".)

A detailed discussion of how to assess patients for evidence of cirrhosis is found

elsewhere (see "Cirrhosis in adults: Etiologies, clinical manifestations, and diagnosis").
Briefly:

● History – Patients should be asked about easy bruisability, jaundice, dark urine, light
stools, history of gastrointestinal bleeding (eg, hematemesis or melena), signs
associated with hypogonadism (eg, impotence, infertility), and pruritus. In addition,
insomnia, altered sleep patterns, and recent automobile accidents may suggest the
presence of early hepatic encephalopathy. (See "Cirrhosis in adults: Etiologies, clinical
manifestations, and diagnosis", section on 'Symptoms'.)

● Physical examination – Patients should have a physical examination to determine if

there are any stigmata of advanced liver disease (eg, spider angiomata, splenomegaly,
palmar erythema, asterixis). Decompensated liver disease is likely if ascites and/or
encephalopathy are present. (See "Cirrhosis in adults: Etiologies, clinical manifestations,
and diagnosis", section on 'Physical examination'.)

● Laboratory testing – Patients should have laboratory testing that includes a complete
blood cell count, as well as measurements of albumin and the prothrombin time. A low
albumin and/or an elevated prothrombin time are suggestive of advanced liver disease
with hepatic decompensation. Leukopenia and thrombocytopenia may heighten
suspicion of portal hypertension. Although certain findings are suggestive of advanced
liver disease, they may also be a result of HIV infection. (See "Cirrhosis in adults:

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Etiologies, clinical manifestations, and diagnosis", section on 'Laboratory findings' and

"The natural history and clinical features of HIV infection in adults and adolescents",
section on 'AIDS and advanced HIV infection'.)

● Evaluation for fibrosis – Patients should also be assessed for fibrosis through the use
of a noninvasive method (eg, biomarkers, such as fibrosis marker panels; calculated
scores, such as AST to platelet ratio index; or ultrasound-based technology, such as liver
elastography). Some centers can provide magnetic resonance elastography (MRE),
which is highly accurate but relative expensive. Increasing data support the use of
noninvasive methods rather than liver biopsy to evaluate liver stage. As an example, a
meta-analysis of 2772 Asian patients with chronic HBV found that the sensitivity and
specificity of transient elastography for cirrhosis was 84.6 and 81.5 percent, respectively
[5]. (See "Noninvasive assessment of hepatic fibrosis: Overview of serologic tests and
imaging examinations".)

However, a biopsy can help determine the true degree of hepatic fibrosis when
laboratory evaluations suggest the presence of portal hypertension and noninvasive
markers indicate mild liver disease. (See "Histologic scoring systems for chronic liver
disease".)

Hepatocellular carcinoma screening — All patients with HIV and chronic HBV infection
should have a baseline ultrasound to screen for hepatocellular carcinoma (HCC). Patients
with obesity may require biphasic or triphasic computed tomography (CT) or enhanced
magnetic resonance imaging, since ultrasound may provide an inadequate survey of the liver
in such patients. Simple contrast CT is not recommended for HCC screening. A discussion on
how to monitor patients with HBV for HCC is found elsewhere. (See "Surveillance for
hepatocellular carcinoma in adults".)

Hepatitis A screening — Patients should be evaluated for prior vaccination to hepatitis A

virus (HAV), or for evidence of previous HAV infection by measuring the total hepatitis A
antibody. Individuals without evidence of prior HAV vaccination or infection should be
vaccinated, since persons with chronic HBV infection are at increased risk for fulminant HAV.
(See "Hepatitis A virus infection: Treatment and prevention".)

Bone density screening — We obtain a baseline dual-energy x-ray absorptiometry (DXA)

scan in all patients with advanced liver disease (advanced liver disease and tenofovir can
both lead to bone loss) [6]. A discussion of bone density screening in patients with HIV is
found elsewhere. (See "Bone and calcium disorders in patients with HIV", section on 'Bone
mineral density screening'.)

SOCIETY GUIDELINE LINKS

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Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Opportunistic
infections in adults with HIV".)

SUMMARY AND RECOMMENDATIONS

● General approach – The pretreatment evaluation of patients with HIV and hepatitis B
virus (HBV) coinfection typically includes: a detailed history and physical examination to
assess for hepatotoxic medications and evidence of advanced liver disease; laboratory
testing to evaluate markers of HBV activity, kidney function, liver function, and
coexisting causes of liver disease; assessment of liver disease through noninvasive
testing; and ultrasound imaging to screen for evidence of hepatocellular carcinoma.
(See 'Approach to evaluation' above.)

● Determining HBV disease activity – Certain baseline tests are obtained to assess the
level of HBV activity, and are also used to monitor response to therapy and/or guide
future treatment decisions. These tests include aminotransferase levels, HBV DNA level,
hepatitis B e antigen (HBeAg), and hepatitis B e antibody (anti-HBe). For some patients,
HBV resistance testing should also be performed. (See 'Baseline markers of disease
activity' above.)

● Considerations for regimen selection – Most patients with HIV/HBV coinfection will be
treated with an antiretroviral regimen that includes a tenofovir-emtricitabine containing
backbone; these agents are considered first-line treatment for both infections.
However, the ultimate choice depends upon the patient’s prior treatment history for
HIV and/or HBV, as well as their kidney function. The presence of hepatitis D coinfection
may also impact treatment. (See 'Information needed for drug selection' above.)

● Evaluation for other causes of liver disease – Patients with chronic HBV infection
should be evaluated for other causes of liver disease. Many of these can be addressed,
which may help prevent the progression to end-stage liver disease. (See 'Evaluation for
other causes of liver disease' above.)

● Additional testing – Patients should be evaluated for cirrhosis, hepatocellular

carcinoma, osteoporosis, and immunity to hepatitis A virus. The results of this
evaluation may prompt the need for additional tests and/or treatments that can reduce
the risk of future complications. (See 'Screening and prevention' above.)

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REFERENCES
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1. Weber R, Sabin CA, Friis-Møller N, et al. Liver-related deaths in persons infected with the
human immunodeficiency virus: the D:A:D study. Arch Intern Med 2006; 166:1632.

2. Saag MS, Gandhi RT, Hoy JF, et al. Antiretroviral Drugs for Treatment and Prevention of
HIV Infection in Adults: 2020 Recommendations of the International Antiviral Society-
USA Panel. JAMA 2020; 324:1651.

3. European guidelines for treatment of HIV-infected adults. Available at: http://www.eacso

ciety.org/guidelines/eacs-guidelines/eacs-guidelines.html (Accessed on July 24, 2023).

4. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of a
ntiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and
Human Services. Available at Human Services. Available at: http://aidsinfo.nih.gov.bibliot
ecavirtual.udla.edu.ec/contentfiles/lvguidelines/AdultandAdolescentGL.pdf (Accessed on
July 24, 2023).

5. Chon YE, Choi EH, Song KJ, et al. Performance of transient elastography for the staging
of liver fibrosis in patients with chronic hepatitis B: a meta-analysis. PLoS One 2012;
7:e44930.

6. Nakchbandi IA. Osteoporosis and fractures in liver disease: relevance, pathogenesis and
therapeutic implications. World J Gastroenterol 2014; 20:9427.
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