SOAP. – Hepatitis B – SỔ TAY LÂM SÀNG

Kathy R. Reese and Cheryl A. Glass

Definition

A.The hepatitis B virus (HBV) causes inflammation of the liver. Acute HBV infection cannot be distinguished from other forms of acute viral hepatitis on the basis of clinical signs and symptoms or nonspecific laboratory findings. Acutely infected patients may be asymptomatic or symptomatic. The likelihood of developing symptoms of acute hepatitis is age dependent.

B.The presence of hepatitis B surface antigen (HBsAg) establishes the diagnosis of hepatitis B. Chronic HBV (CHB) versus acute infection is defined as the presence of HBsAg in serum for at least 6 months. Diagnostic criteria and clinical terms are available at the American Association for the Study of Liver Disease (AASLD) website located at www.aasld.org/publications/practice-guidelines-0.

C.The levels of serum alanine transaminase (ALT) and HBV DNA as well as liver fibrosis are important predictors of long-term outcome for decisions for antiviral treatment as well as treatment response.

D.Staging of liver disease severity using a liver biopsy or non-invasive tests such as elastography are important in guiding surveillance and assisting with treatment decisions.

E.Ten genotypes of HBV have been identified (A through J):

1.HBV genotypes A to H have been found in the United States, with genotypes A, B, and C being most prevalent.

F.Guidelines for monitoring patients who are CHB who are not currently on treatment as well as the management of CHB special populations are available on the AASLD website.

G.The Advisory Committee on Immunization Practices (ACIP) recommends that the following people receive hepatitis B vaccination:

1.All infants.

2.Unvaccinated children younger than 19 years.

3.People at risk for infection by sexual exposure:

a.Sex partners of HbsAg-positive persons.

b.Sexually active people who are not in a long-term, mutually monogamous relationship (e.g., persons with more than one sex partner during the previous 6 months).

c.People seeking evaluation or treatment for an sexually transmitted infection (STI).

d.Men who have sex with men (MSM).

4.People at risk for infection by percutaneous or mucosal exposure to blood:

a.Current or recent injection drug users.

b.Household contacts of people who are HbsAgpositive.

c.Residents and staff of facilities for developmentally disabled people.

d.Healthcare and public safety personnel with reasonably anticipated risk for exposure to blood or blood-contaminated body fluids.

e.Patients on hemodialysis, including peritoneal dialysis and home dialysis.

f.People with diabetes age 19 to 59 years; persons with diabetes age > 60 years at the discretion of the treating clinician.

5.International travelers to countries with high or intermediate levels of endemic HBV infection (HbsAg prevalence of >2%).

6.People with hepatitis C infection.

7.People with chronic liver disease (CLD; cirrhosis, fatty liver disease, alcoholic liver disease (ALD), autoimmune hepatitis and an ALT or AST level greater than twice the upper limit of normal).

8.HIV-infected persons.

9.People who are incarcerated.

10.All other people seeking protection from HBV infection.

Incidence

A.The majority of children and adults with CHB in the United States are immigrants, have immigrant parents, or became exposed through other close household contacts.

B.In 2016 the Centers for Disease Control and Prevention (CDC) noted the overall incidence of HBV was one case per 100,000. Since 2014, there has been an increase in the rate of new HBV infection, likely due to increasing injection drug use.

C.HBV is more severe among adults older than 60 years.

D.Approximately 95% of adults recover completely from HBV infection and do not become chronically infected.

E.Approximately 25% of those who become chronically infected during childhood and 15% of those who become chronically infected after childhood die prematurely from cirrhosis or liver cancer, and the majority remain asymptomatic until onset of cirrhosis or end-stage liver disease.

Pathogenesis

A.HBV is a hepadnavirus. HBV-related liver injury is largely caused by immune-mediated mechanisms mediated via cytotoxic T-lymphocyte lysis of infected hepatocytes. The virus is transmitted through perinatal, percutaneous, sexual exposure, and close person–person contact body fluids, such as wound exudates, semen, cervical secretions, and saliva that are HBsAg-positive. It is not transmitted by the fecal–oral route or by water. Blood and serum contain the highest concentration of virus; saliva contains the lowest.

B.The incubation period is 45 to 160 days (2–5 months), with an average of 120 days. An infected person can infect others 4 to 6 weeks before symptoms appear and for an unpredictable time thereafter.

C.The production of antibodies against HBsAg confers protective immunity and can be detected in patients who have recovered from HBV or in those patients who have been vaccinated. The immunoglobulin M (IgM) subtype indicates an acute infection or reactivation. Immunoglobulin G (IgG) subtype indicates chronic infection.

Predisposing Factors

A.Higher prevalence populations born in regions of high or intermediate HBV prevalence of >2% including (the percentage is the area of the country) Africa, Asia, South Pacific, Middle East, Eastern and Western Europe, North America/Alaskan Eskimos, Mexico and Central America, Australia, and the Caribbean.

B.U.S.-born persons not vaccinated as an infant whose parents were born in regions with high HBV endemicity (>8%).

C.MSM.

D.Drug use, sharing needles.

E.Occupational exposure to blood or blood-contaminated body fluids.

F.Household, needle-sharing, and sexual contacts of HbsAg-positive persons.

G.Perinatal exposure, by vertical infection.

H.Receiving blood transfusions or blood products for hemophilia.

I.End-stage renal disease, including predialysis, hemodialysis, peritoneal dialysis.

J.Staffing or residing in institutions.

K.International travel.

L.Incarceration in long-term correction facilities.

M.Percutaneous contact with inanimate objects contaminated with HBV; virus can survive 1 week or longer.

Common Complaints

A.The following symptoms occur in the acute phase of HBV:

1.Anicteric hepatitis: Asymptomatic (majority of patients).

2.Icteric hepatitis: Associated with a prodromal period:

a.Anorexia.

b.Nausea and vomiting.

c.Low-grade fever.

d.Myalgia.

e.Fatigue.

f.Aversion to food and cigarettes.

g.Intermittent, mild to moderate right upper quadrant (RUQ) and epigastric pain.

h.Tea-colored urine.

i.Clay-colored bowel movements (BMs).

3.Hyperacute, acute, and subacute hepatitis symptoms:

a.Hepatic encephalopathy (HE).

b.Somnolence.

c.Disturbances in sleep pattern.

d.Mental confusion.

e.Coma.

B.The following symptoms occur in the chronic phase of HBV:

1.Asymptomatic: May be healthy carriers without any evidence of active disease.

2.During the replicative state, common symptoms are:

a.Fatigue.

b.Anorexia.

c.Nausea.

d.Mild upper quadrant pain or discomfort.

e.Hepatic decompensation.

Other Signs and Symptoms

A.Icteric phase (10 days after the appearance of constitutional symptoms and lasts for 1 to 3 months):

1.Jaundice of sclera and skin.

2.Tea-colored urine.

3.Clay-colored stools, often precede jaundice.

4.RUQ tenderness.

5.Hepatomegaly.

Subjective Data

A.Review onset, duration, course, and severity of symptoms. Ask the patient for specifics about urine and stool color.

B.Ask the patient about other family members and sexual contacts with similar symptoms.

C.Review family history of hepatocellular carcinoma (HCC).

D.Discuss the patient’s history of blood transfusions, tattoos, incarceration, intravenous (IV) drug use, and alcohol abuse.

E.Ask about high-risk sexual practices.

F.Review the patient’s occupational exposure.

G.Inquire about recent international travel.

H.Establish the patient’s usual weight; note amount of any weight lost and over what length of time.

I.Has the patient ever had a liver biopsy?

J.Review for a history of variceal bleeding.

K.Ask if the patient has ever been treated for any type of hepatitis?

1.How long ago was the patient treated?

2.Did the patient complete therapy? If not, why?

3.What was the patient’s response to therapy (i.e. nonresponder, relapser, etc.)?

Physical Examination

A.Check temperature, pulse, respirations, blood pressure (BP), height and weight to calculate body mass index (BMI).

B.Inspect:

1.Observe general appearance, muscle wasting, ascites, and peripheral edema.

2.Inspect the skin for tattoos and piercings, jaundice, palmar erythema, rash, spider nevi, spider angioma, and dehydration.

3.Inspect the eyes for yellow sclera.

4.Inspect the mucous membranes and nail beds for clubbing and cyanosis.

5.Evaluate for the presence of gynecomastia and small testes.

C.Auscultate:

1.Auscultate lung fields and the heart.

2.Auscultate all quadrants of the abdomen. Evaluate for an abdominal bruit.

D.Percuss abdomen.

E.Palpate:

1.Palpate all quadrants of the abdomen for masses, liver enlargement or tenderness, characteristics of cirrhosis, and hepatosplenomegaly.

2.Palpate the lymph nodes for lymphadenopathy.

3.Palpate for testicular atrophy.

Diagnostic Tests

A.Diagnostic test for HBV antigens and antibodies (see Tables 14.16 and 14.17).

B.Complete blood count (CBC) with platelets.

C.Complete liver panel:

1.AST/ALT.

2.Total bilirubin.

3.Prothrombin time (PT)/international normalized ratio (INR).

4.Albumin.

D.Alkaline phosphatase (ALP).

E.Other viral infection markers.

F.Alpha-fetoprotein (AFP; rule out other causes of liver disease).

G.Gamma-glutamyl transpeptidase (GGT).

H.Serum iron levels (screen for hemochromatosis).

I.Thyroid profile.

J.Blood glucose/A1C.

TABLE 14.16 Diagnostic Tests for Hepatitis B Antigens and Antibodies

Factors to Be Tested	HBV Antigen or Antibody	Indication
HBsAg	HBsAg	Detects acutely or chronically infected; antigen used in hepatitis B vaccine
Anti-HBs	Antibody to HBsAg	Identifies resolved HBV infections; determines immunity after immunization
HBeAg	HBeAg	Identifies at risk of transmitting HBV
Anti-HBe	Antibody to HBeAg	Identifies lower risk of transmitting HBV
Anti-HBc	Antibody to HBcAg; IgM (HBcAg)	Identifies acute, resolved, or chronic HBV infection; anti-HBc not present after immunization.
IgM anti HBc	IgM antibody to HBcAg	Identifies acute or recent HBV infections (includes HBsAg-negative during the window phase of infection)

HBcAg; hepatitis B core antigen; HBeAg, hepatitis B e-antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; IgM, immunoglobulin M.

K.After HBV confirmation:

1.HBV genotype.

2.HBV DNA viral load.

L.Serum fibrosis panel:

1.Aspartate platelet ratio index (APRI)—AST-to-platelet ratio index used for estimating hepatic fibrosis. Online calculator can be found at: www.hepatitisc.uw.edu/page/clinical-calculators/apri

2.Fibrosis-4 (FIB-4) is an index for estimating hepatic fibrosis based on a calculation derived from AST, ALT, platelet concentrations, and age. Online calculator can be found at www.hepatitisc.uw.edu/page/clinical-calculators/fib-4.

3.FibroTest (FibroSure)—commercial biomarker test that uses the results of six blood markers to estimate hepatic fibrosis.

M.Imaging:

1.Ultrasonography: FibroScan—transient shear wave elastography measures liver stiffness as a surrogate for fibrosis.

2.CT or MRI to help exclude biliary obstruction.

N.Liver biopsy to assess the severity of disease.

O.Pregnancy testing before antiviral therapy.

P.Before oral antiviral therapy is introduced, all patients should be screened for HIV.

Q.Hepatitis C virus (HCV) and HIV testing to rule out coinfection.

Differential Diagnoses

A.Hepatitis B.

B.Exclusion of other types of hepatitis (A, C, D, E, viral, or autoimmune hepatitis).

C.Infectious mononucleosis.

D.Hepatotoxic drug ingestion, for example, chloramphenicol, acetaminophen, or methyldopa.

E.Metastic cancer to the liver.

F.Alcoholic cirrhosis.

G.Hemochromatosis.

H.Wilson’s disease.

Plan

A.General interventions:

1.Before any form of HBV therapy is started, and optimally at the first presentation, the patient needs to be provided with information about the natural history of chronic hepatitis B infection and the fact that most infections remain entirely without symptoms even in those with severe disease, so there is a need for regular lifelong monitoring.

B. See Section III: Patient Teaching Guide Jaundice and Hepatitis.

1.Instruct the patient to avoid sexual activity until he or she is free of HBsAg.

2.Recommend abstinence or minimal alcohol consumption. More than seven drinks of alcohol per week for women and more than 14 drinks per week for men are associated with an increase of cirrhosis and HCC.

3.Any blood spills should be cleaned using 1:10 dilution of bleach to water for disinfecting the area. Gloves should be worn when cleaning up any blood spills.

4.There are no dietary restrictions with acute and chronic hepatitis (without cirrhosis).

5.Diets for decompensated cirrhosis, portal hypertension, or encephalopathy are prescribed:

a.Low-sodium diet (1.5 g/d).

b.High-protein diet (white-meat protein, e.g., pork, turkey, and fish).

c.Fluid restriction of 1.5 L/d in the presence of hyponatremia.

C.Pharmaceutical therapy: The goal of treatment is to prevent progression to cirrhosis, hepatic failure, and hepatocellular cancer:

1.Primary prevention includes vaccination. Vaccination is up to 95% effective. Immunizations schedules are located on the CDC website www.cdc.gov/hepatitis/hbv/hbvfaq.htm.

a.There are three single-antigen hepatitis B vaccines (ENGERIX-B, RECOMBIVAX BH, and HEPLISAV-B). There are two combination vaccines:

b.PEDIARIX: Combined hepatitis B; diphtheria, tetanus, acellular pertussis (DTaP); and inactivated poliovirus (IPV) vaccine. Cannot be administered before age 6 weeks or after age 7 years.

c.TWINRIX®: Combined hepatitis A and hepatitis B vaccine. Recommended for persons age ≥18 years who are at increased risk for both hepatitis A virus (HAV) and HBV infections.

2.If serum HBV DNA exceeds 1,000 international unit (IU)/mL antiviral therapy is recommended. See Table 14.18 for current HBV therapy:

a.All patients need to be screened for HIV prior to antiviral therapy.

b.Females need to have a pregnancy test prior to therapy.

c.All antivirals require close monitoring due to side-effect profiles.

d.Dose adjustment is required in the presence of renal impairment, dialysis, and is used with caution in patients with a history of pancreatitis.

3.Orthotopic liver transplantation (OLT) is the treatment of choice for patients with fulminant hepatic failure who do not recover and for patients with end-stage liver disease.

4.Immunize against hepatitis A for individuals with CHB if not already immune.

Follow-Up

A.Laboratory monitoring:

1.Screening should be performed using both HBsAg and anti-HBs.

2.Screening for anti-HBc to determine prior exposure is not routinely recommended:

a.Test in patients who have HIV infection.

b.Test persons about to initiate HCV or anticancer and other immunosuppressive therapy or renal analysis and in donated blood.

3.Monitor liver function (ALT) every 3 to 6 months for active disease.

4.Monitor HBeAg every 3 to 6 months dependent on ALT levels.

5.Monitor CBC and creatinine every month (1–2 days prior to treatment).

6.Monitor HBV DNA viral load every 3 to 6 months when the patient is on treatment in the reactivation phase.

B.Laboratory, physical examination, and psychosocial evaluation are required for antiviral therapy:

1.Monitor for mental dysfunction related to interferon (IFN), including depression, psychosis, aggressive behavior, hallucinations, violent behavior, suicidal ideation, suicide attempt, and homicidal ideation (rare), even without previous history of psychiatric illness.

C.Risk of exposure to HBsAg ceases when antigen disappears from the bloodstream, usually within 6 to 8 weeks of infection.

D.HBV reactivation is the abrupt reappearance or rise in HBV DNA in a patient with previously inactive or resolved hepatitis B. It is often accompanied by a flare in disease activity with elevation of liver enzymes with or without symptoms, and can be severe, resulting in death:

1.Patients at highest risk for HBV reactivation:

a.Patients undergoing cancer chemotherapy.

b.Patients taking immunosuppressive therapy including:

i.Black box warning for Rituximab and other drugs that target B lymphocytes.

ii.High-dose steroids.

iii.Anti-tumor necrosis factor (TNF) agents.

c.Patients with HIV who have discontinued HBV active antiviral drugs.

d.Patients undergoing solid organ or bone marrow transplantation.

e.Patients coinfected with hepatitis C.

Consultation/Referral

A.Patients with persistently elevated serum transaminase concentrations (exceeding twice the upper limits of normal), as well as those with elevated serum alpha-fetoprotein concentrations or abnormal ultrasounds, should be referred to a gastroenterologist for further management.

B.Patients who are coinfected with HBV or HIV or have end-stage renal disease should be referred to and managed by a hepatologist, infectious disease provider, or gastroenterologist for treatment.

C.Patients with decompensated cirrhosis should be referred for consideration of liver transplantation.

D.HBV-infected pregnant women with cirrhosis should be managed by a high-risk OB practice and should be treated with tenofovir disoproxil fumarate (TDF) to prevent decompensation.

Individual Considerations

A.Pregnancy:

1.Women should receive HBsAg testing during each pregnancy:

a.Those who are HBsAg-positive should have HBV DNA testing.

b.Prenatal HBsAg testing of all pregnant women is recommended to identify newborns who require immediate postexposure prophylaxis.

c.Extra care is necessary to evaluate the mother to ensure that the infant receives hepatitis B immune globulin (HBIG) and HBV vaccine within 12 hours of birth (see Table 14.19).

2.Pregnancy and lactation are not a contraindication to vaccination. No adverse effect on developing fetus has been observed when pregnant women are vaccinated against HBV.

3.Antiviral therapy in the third trimester is recommended for pregnant women with serum HBV DNA > 200,000 IU/mL:

a.TDF is the preferred therapy for prevention of mother-to-child transmission.

b.Antiviral therapy given for prevention of mother-to-child transmission is recommended to be discontinued at the time of delivery or up to 4 weeks postpartum:

i.Pregnant women who stop antiviral therapy at or early after delivery should be monitored for up to 6 months after delivery for hepatitis flares and seroconversion.

ii.Long-term follow-up should be continued to assess the need for future antiviral therapy.

c.Antiviral drug labels do not recommend breastfeeding while on therapy; however clinical studies support the safety of these drugs during breastfeeding.

B.Adults:

1.Most HBV infections are acquired in adolescence or adulthood, largely as a result of IV drug use, sexual contact, or occupational or household exposure. HBV infection is associated with other sexually transmitted diseases, including syphilis.

2.Patients who have received a blood transfusion should refrain from blood donation for 6 months, the incubation period for HBV. Blood should never be donated if the patient is a hepatitis B carrier or was infected with hepatitis C.

C.Geriatrics:

1.Vaccination against HBV is recommended in elderly individuals at risk for infection, including all nursing home residents.

2.HBV is more severe among adults older than 60 years:

a.There is substantial decrease in liver mass, in the number of hepatocytes, and in the portal blood flow, which results in alteration of metabolism. There are significant reductions in up to 30% to 40% in parenchymal volume, liver blood flow, and perfusion

b.The elderly have a higher rate of mortality than younger patients, reflecting in part a higher prevalence of comorbid conditions such as diminished immune response, metabolic derangement, nutritional deficiencies, and greater cumulative exposure to environmental hepatotoxins.

c.Those who do develop the disease have a greater tendency to deteriorate into chronic liver failure or HCC:

i.The risk of cirrhosis in highly linked to the HBV DNA level.

3.Liver transplant programs may have relative contraindication inclusion criteria for liver transplant for ages more than 65 to 70 years.

Resources

American Association for the Study of Liver Diseases: www.aasld.org.

American Liver Foundation: www.liverfoundation.org.

Centers for Disease Control and Prevention: www.cdc.gov/hepatitis.

Hepatitis and HIV: www.hivandhepatitis.com.

Hepatitis B Foundation: www.hepb.org.

Hepatitis Foundation International: www.hepfi.org.

Immunization Action Coalition: www.immunize.org.

National Institute of Diabetes and Digestive and Kidney Diseases: www2.niddk.nih.gov.

United Network for Organ Sharing: www.unos.org.

CDC Interpretation of Hepatitis B Serologic Test Results https://www.cdc.gov/hepatitis/hbv/pdfs/serologicchartv8.pdf