Hepatitis B, Chronic

Symptoms of chronic hepatitis B vary depending on the degree of underlying liver damage.

Many patients, particularly children, are asymptomatic. However, malaise, anorexia, and fatigue are common, sometimes with low-grade fever and nonspecific upper abdominal discomfort. Jaundice is usually absent.

Often, the first findings are

Extrahepatic manifestations may include polyarteritis nodosa Polyarteritis Nodosa (PAN) Polyarteritis nodosa is a systemic necrotizing vasculitis that typically affects medium-sized muscular arteries and occasionally affects small muscular arteries, resulting in secondary tissue... read more and glomerular disease Overview of Glomerular Disorders The hallmark of glomerular disorders is proteinuria, which is often in the nephrotic range (≥ 3 g/day). Glomerular disorders are classified based on urine changes as those that manifest predominantly... read more .

The diagnosis Diagnosis Chronic hepatitis is hepatitis that lasts > 6 months. Common causes include hepatitis B and C viruses, nonalcoholic steatohepatitis (NASH), alcohol-related liver disease, and autoimmune liver... read more of chronic hepatitis B is suspected in patients with any of the following:

Diagnosis is confirmed by finding positive hepatitis B surface antigen (HBsAg) and IgG antibody to hepatitis B core (IgG anti-HBc) and negative IgM anti-HBc (see table Hepatitis B Serology Hepatitis B Serology* ) and by measuring hepatitis B virus DNA (quantitative HBV-DNA).

If chronic hepatitis B is confirmed, testing for hepatitis B e antigen (HBeAg) and antibody to hepatitis B e antigen (anti-HBe) is usually done to help determine the prognosis and to guide antiviral therapy. If serologically confirmed HBV infection is severe or if patients belong to a known at-risk population (eg, those with HIV infection, injection drug users, men who have sex with men, or immigrants from areas of high endemicity, and possibly those who are HBsAg-positive with low HBV DNA but high ALT levels), antibody to hepatitis D virus (anti-HDV) is measured.

Quantitative HBV-DNA tests (viral load) are also used before and during treatment to assess response.

Noninvasive assessment of fibrosis is done to evaluate degree of fibrosis after chronic hepatitis B is diagnosed.

Biopsy is occasionally done to evaluate the extent of liver damage and to exclude other causes of liver disease. Liver biopsy is most useful in cases that do not meet clear-cut guidelines for treatment (see also the American Association for the Study of Liver Disease's practice guideline Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance).

(See also the American Association for the Study of Liver Disease (AASLD) guidelines Hepatitis B Guidance 2018 Update.)

Antiviral treatment is indicated for patients with chronic hepatitis B and one or more of the following:

The goal is to eliminate HBV-DNA (1 Treatment reference Hepatitis B is a common cause of chronic hepatitis. Patients may be asymptomatic or have nonspecific manifestations such as fatigue and malaise. Diagnosis is by serologic testing. Without treatment... read more ). Treatment can occasionally cause loss of hepatitis B e antigen (HBeAg), or, even more rarely, loss of hepatitis B surface antigen (HBsAg). However, the majority of patients treated for chronic hepatitis B must be treated indefinitely. These drugs cannot cure the disease.

Stopping treatment prematurely can lead to relapse, which may be severe. However, treatment may be stopped if one of the following occurs:

Multiple antiviral drugs are active against hepatitis B, but only four are currently recommended: entecavir, tenofovir disoproxil fumarate, tenofovir alafenamide, and pegylated interferon-alfa (peginterferon alfa): Adefovir, interferon alfa, lamivudine, and telbivudine have been used but are no longer recommended as first-line treatment because of increased risk of adverse effects and development of drug resistance.

First-line treatment is usually with one of the following:

Oral antiviral drugs have few adverse effects and can be given to patients with decompensated liver disease. Lactic acidosis is a potential side effect, and lactic acid levels should be checked if there is clinical concern. Combination therapy has not proved superior to monotherapy. Patients should be tested for HIV before treatment is initiated.

If HBsAg becomes undetectable and HBeAg seroconversion occurs in patients with HBeAg-positive chronic HBV infection, these patients may be able to stop antiviral drugs. Patients with HBeAg-negative chronic HBV infection almost always need to take antiviral drugs indefinitely to maintain viral suppression; they have already developed antibodies to HBeAg, and thus the only specific criterion for stopping HBV treatment would be HBsAg that becomes undetectable.

Entecavir has a high antiviral potency, and resistance to it is uncommon; it is considered a first-line treatment for HBV infection. Entecavir is effective against adefovir-resistant strains. Dosage is 0.5 mg orally once a day; however, patients who have previously taken a nucleoside analog should take 1 mg orally once a day. Dose reduction is required in patients with renal insufficiency. Serious adverse effects appear to be uncommon, although safety in pregnancy has not been established.

Tenofovir has replaced adefovir (an older nucleotide analog) as a first-line treatment. Tenofovir is the most potent oral antiviral for hepatitis B; resistance to it is minimal. It has few adverse effects. There are two forms of tenofovir:

Dosage for TDF is 300 mg orally once a day; dosing frequency may need to be reduced if creatinine clearance is reduced. Potential side effects include nephropathy, Fanconi syndrome, and osteomalacia. If patients are at risk of renal impairment, creatinine clearance, serum phosphate, and urine glucose and protein should be checked at least annually. Bone density studies at baseline and during treatment should be considered if patients have a history of fracture or risk factors for osteopenia.

Dosage for TAF is 25 mg orally once a day; no dose adjustments are necessary if creatinine clearance is reduced. TDF and TAF are similar in efficacy, but TAF is safer in patients when renal toxicity or bone density is a concern. Serum creatinine and phosphorus, creatinine clearance, and urine glucose and protein should be checked before initiating and during therapy.

Pegylated interferon alfa can be used instead of interferon alfa. Dosage for pegylated interferon alfa is usually 180 mcg by injection once a week for 48 weeks. Adverse effects are similar to those of interferon alfa but may be less severe. More than 40% of patients treated with pegylated interferon alfa report fatigue, fever, myalgia, and headache. Other potential side effects include mood disturbances, cytopenia, and autoimmune disorders.

Contraindications to pegylated interferon alfa include the following:

The following tests should be used to monitor patients treated with pegylated interferon alfa:

Nonpreferred antiviral therapies (adefovir, lamivudine, telbivudine, interferon alfa) may be considered if the above drugs are unavailable.

Adefovir is a nucleotide analog. Dosage is 10 mg orally once a day. It is not a preferred first-line treatment because renal failure and lactic acidosis are risks.

Lamivudine (a nucleoside analog) is no longer considered first-line treatment for HBV infection because risk of resistance is higher and efficacy is lower than those of newer antiviral drugs. Dosage is 100 mg orally once a day; it has few adverse effects.

Telbivudine is a nucleoside analog that has greater efficacy and potency than lamivudine but also has a high rate of resistance; it is not considered first-line treatment. Dosage is 600 mg orally once a day.

Interferon alfa can be used but is no longer considered first-line treatment and has generally been replaced by pegylated interferon alfa.

Liver transplantation Liver Transplantation Liver transplantation is the 2nd most common type of solid organ transplantation. (See also Overview of Transplantation.) Indications for liver transplantation include Cirrhosis (70% of transplantations... read more should be considered for end-stage liver disease caused by HBV. In patients with HBV infection, the long-term use of first-line oral antivirals and peri-transplantation use of hepatitis B immune globulin (HBIG) has improved outcomes after liver transplantation. Survival is equal to or better than that after transplantation for other indications, and recurrences of hepatitis B are minimized.

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