Hepatitis B Management

Evaluation

The evaluation of patients suspected of hepatitis B begins with a history and physical examination. All chronic hepatitis B patients who are HBsAg positive should be tested for HBeAg, anti-HBe, HBV DNA, and ALT, and assessed for fibrosis stage non-invasively (FIB-4 or hepatic elastography) or by liver biopsy. HBeAg and anti-HBe are important in determining the phase of chronic HBV infection. HBV DNA serum level is used to diagnose, establish the phase of the infection, decide to treat, and monitor treatment. In HBeAg-positive chronic hepatitis B, HBV DNA level is >20,000 IU/mL while it is <20,000 IU/mL in HBeAg-negative chronic hepatitis B. Reflex HBV DNA testing may be considered in those testing positive on HBsAg as an additional strategy to promote linkage to care and treatment and to promote diagnosis. ALT and/or AST levels may be normal or elevated in chronic hepatitis B.  

CBC, PT, and serum albumin are also measured to determine disease severity. Diagnosis of hepatitis D in patients with chronic hepatitis B may be done using serological assay to detect total anti-HDV followed by a nucleic acid testing (NAT) to detect HDV RNA and active (viremic) infection in patients who are positive for anti-HDV. 

Serological testing for anti-HDV antibodies may be considered in patients with positive HBsAg especially in the following:

• Individuals born in HDV-endemic countries, regions and areas
• Individuals with advanced liver disease, receiving HBV treatment and with features suggestive of HDV infection (eg low HBV DNA with high ALT levels)
• Individuals with increased risk of HDV infection (eg hemodialysis recipients, people living with hepatitis C or HIV, people who inject drugs, sex workers, and MSM)

It is also essential to screen high-risk patients for HCC every 6-12 months using ultrasound and serum AFP. 

The initial assessment of patients with chronic hepatitis B includes the phase of infection, degree of fibrosis or cirrhosis, and presence of coinfection.

If the patient meets the criteria for chronic hepatitis B, a liver biopsy may be done to grade the stage of liver disease as chronic hepatitis B may evolve into cirrhosis and HCC. A liver biopsy is essential in determining disease activity in cases of inconclusive biochemical and HBV markers. Liver biopsy is indicated in patients with persistently elevated ALT but persistently low HBV DNA to exclude other causes of liver disease, and in patients who do not meet the criteria for treatment but at risk for developing histologically active or advanced liver disease (eg with normal or mildly elevated ALT levels [<2x the ULN], persistently elevated HBV viral load [>6 months], and >40 years of age or a family history of HCC) that would benefit from treatment. 

Regular monitoring is essential throughout the course of chronic HBV infection to detect phase transitions and determine when management needs to be adjusted, including when to start antiviral therapy. As HBV DNA and ALT levels fluctuate during the course of chronic hepatitis B, disease phase should be determined using HBV DNA and ALT measurements obtained on at least two occasions over a 6- to 12- month interval.

Principles of Therapy

Acute Hepatitis B

The main goal of treatment for acute hepatitis B is to prevent the risk of acute or subacute hepatic failure. Another relevant goal of treatment is to improve the quality of life by shortening the disease duration associated with symptoms as well as the risk of chronicity. Supportive care should be given as treatment with antivirals is generally not recommended. Consider hospitalization and expert referral if there is vomiting, dehydration or signs of hepatic decompensation. Consider treatment with nucleoside or nucleotide analogues in patients with severe acute hepatitis. 

Chronic Hepatitis B

Individuals positive for anti-HBc with or without HBsAg may require antiviral prophylaxis in the setting of immunosuppression. Baseline renal function tests should be performed before initiation of antiviral therapy and monitored periodically thereafter, with at least annual testing in patients receiving Tenofovir disoproxil fumarate. Switching from Tenofovir disoproxil fumarate to an alternative nucleos(t)ide analogue is recommended for patients who develop declining renal function. Surveillance for HCC every 6 months using ultrasound and serum AFP is recommended in HBsAg-positive individuals with cirrhosis regardless of age or other risk factors, those with a family history of HCC, and those >40 years of age with HBV DNA level >20,000 IU/mL and without family history of HCC or evidence of cirrhosis.

In individuals who achieved HBsAg loss, continued HCC surveillance every 6 months is recommended for those with cirrhosis, those with a family history of HCC, men who cleared HBsAg after age 40 years, and women who cleared HBsAg after age 50 years.  

Periodic screening for HCC in high-risk carriers is likewise essential. HCC may have a long asymptomatic stage lasting for 2 years or longer. Carriers of HBV at high risk for developing HCC include Asian men >40 years, Asian women >50 years, patients with cirrhosis, with HBV genotype C, with HDV coinfection regardless of cirrhosis status, with HCV coinfection, persistent HBV DNA of >2,000 IU/mL, or those with a family history of HCC in a first-degree relative. For persons with HCV coinfection, HCV is treated and HCC surveillance is performed according to HBV monoinfection criteria.  

HCC surveillance is advised in non-cirrhotic persons with HIV coinfection for men ≥18 years old and for women ≥40 years old. For persons with multiple viral infections (eg HBV plus HDV/HCV and/or HIV), the surveillance recommendation should be that of the coinfection with the highest associated risk (eg if HBV-HDV-HCV, surveillance would follow that for HBV-HDV).  

A liver biopsy may be performed to assess the degree of liver damage, rule out other causes of liver disease, and help predict the prognosis. It is also recommended for chronic hepatitis B patients who are candidates for antiviral therapy.  

In patients without clinical evidence of cirrhosis, with persistently normal ALT, HBV DNA of <2,000 IU/mL, regardless of HBeAg status or age, treatment is not recommended.  

Treatment is recommended in adults and adolescents ≥12 years of age with chronic hepatitis B including pregnant and non-pregnant women of reproductive age with:

• Significant fibrosis based on APRI score >0.5 or transient elastography value of >7.0 kPa or evidence of cirrhosis which is based on clinical criteria or an APRI score of >1.0 or a transient elastography value of >12.5 kPa regardless of HBV DNA or ALT levels
• HBV DNA >2,000 IU/mL and an ALT level above ULN (30 U/L for males and 19 U/L for females), measured on at least two occasions for adolescents in a 6- to 12-month period
• HBeAg-positive without cirrhosis with HBV DNA ≥20,000 IU/mL and ALT levels ≥2x ULN
• HBeAg-negative without cirrhosis with HBV DNA ≥2,000 IU/mL and ALT level ≥2x ULN
• Persistently abnormal ALT levels which are defined as two ALT values above ULN at unspecified intervals during a 6- to 12-month period regardless of APRI score in the absence of access to HBV DNA assay
• Presence of coinfections (eg HIV, hepatitis D, or hepatitis C), family history of liver cancer or cirrhosis, immune suppression (eg long-term steroids, solid organ or stem cell transplant), comorbidities (eg diabetes or metabolic dysfunction-associated steatotic liver disease), extrahepatic manifestations (eg glomerulonephritis, vasculitis) regardless of APRI score or HBV DNA or ALT levels

A shared decision-making approach is used to consider risk factors (eg age, sex, stage of fibrosis, pill burden, cost, need for regular monitoring) and to discuss the risks and benefits of antiviral treatment in the following patients:

• HBsAg-positive, HBeAg-positive or negative with viremia not meeting disease-specific treatment indications and who are in high-risk scenarios for transmission to others
• Less than 40 years old in the immune-tolerant phase who are interested in starting treatment earlier
• HBsAg-positive, HBeAg-positive (not immune tolerant or immune active) or HBeAg-negative (not inactive or immune active) chronic HBV infection without cirrhosis and in the indeterminate phase
  • Monitor regularly those not on antiviral therapy and re-evaluate decision regarding treatment initiation at each follow-up visit if treatment has not been initiated

The primary goal of treatment in chronic hepatitis B treatment is to permanently suppress HBV or to eliminate it. It is necessary to achieve continued viral suppression to reduce or prevent hepatic disease and disease progression. The short-term goals are to sustain the suppression of HBV DNA, ALT normalization, to prevent decompensation, and to decrease hepatic necroinflammation and fibrosis during and after therapy. The long-term goals of therapy are to avoid hepatic decompensation, reduce or prevent progression to cirrhosis and/or HCC, and prolong survival. Achievement of functional cure, which is defined as sustained, undetectable circulating HBsAg (at least 24 weeks off therapy) and HBV DNA below the limit of quantification, is an optimal endpoint of treatment. An intermediate treatment endpoint is the confirmed loss of HBeAg and seroconversion to anti-HBe antibodies (for patients who are HBeAg-positive) in combination with HBV DNA <2,000 IU/mL.

Other goals of treatment include:

• Improvement of HBV-associated extrahepatic manifestations (eg cryoglobulinemia vasculitis, glomerulopathies, non-Hodgkin lymphoma, non-rheumatoid arthritis, panarteritis nodosa, rheumatoid arthritis, serum sickness-like syndrome)
• Prevention of HBV transmission including mother-to-child (vertical) transmission in pregnant women with high viremia and horizontal transmission (eg sexual, parenteral, nosocomial)
• Prevention of HBV reactivation in patients requiring chemotherapy or immunosuppression
• Improvement in patient reported outcomes and quality of life

Endpoints used to assess response include the following:

• Biochemical response: Normalization of serum ALT
• Virological response: HBV DNA of <104 copies/mL and sustained seroconversion from HBeAg to anti-HBe
• Histological response: Decrease in histology activity compared to pretreatment liver biopsy or a reduction of at least 1 point in fibrosis by Metavir staging
• Complete response: Fulfill criteria of biochemical and virological response and loss of HBsAg

Definition of treatment response in nucleos(t)ide analogue-adherent patients:

• Complete virological response: Undetectable HBV DNA measured with a sensitive assay (<20 IU/mL)
• Partial virological response: HBV DNA does not decline steadily and remains >2,000 IU/mL
• Virological non-response: decline <1 log10 at 6 months of nucleos(t)ide analogue treatment
• Virological resistance: HBV DNA increases to ≥1 log10 above nadir

Considerations Prior to Initiation of Treatment  

Prior to initiation of treatment, it is important to consider the age of the patient, the severity of the liver disease, the likelihood of response, potential adverse events, and complications (eg presence of bone or renal disease, HIV coinfection, pregnancy). HBeAg-positive patients with elevated ALT levels and compensated liver disease should be observed for 3 to 6 months for spontaneous seroconversion from HBeAg to anti-HBe prior to initiation of treatment. The choice of therapy will depend on the availability, cost of medication, prior treatment history, the necessary number of clinic visits, the expected duration of treatment, and patient or clinician preference.  

Other Considerations in Pharmacologic Therapy  

There is no evidence that combination therapy of two direct antiviral agents results in better viral suppression compared to a single agent. Antiviral therapy does not remove the risk of HCC, thus HCC surveillance must continue. In treating concurrent infections such as HCV, HDV, and HIV infection, it is important to identify the dominant virus as this will determine the therapeutic regimen. Concurrent hepatitis C infection may be treated with the same antiviral therapy for HCV monoinfection.  

Indefinite treatment with nucleos(t)ide analogues is recommended in all patients with cirrhosis (based on clinical evidence, APRI score, or transient elastography score) to prevent risk of reactivation which can cause an acute hepatitis flare. HBV reactivation may be induced by immunosuppressive agents (eg cancer chemotherapy, checkpoint inhibitors, bone marrow and stem cell treatment, anti-tumor necrosis factor, novel immunobiologics [eg tyrosine kinase inhibitors, chimeric antigen receptor T-cell treatment] and therapy for HCV).  

Long-term, often indefinite nucleos(t)ide analogue therapy for chronic hepatitis B is recommended but discontinuation of therapy may be considered in the following:

• If HBeAg-positive at initiation of therapy: Achieved HBeAg seroconversion (HBeAg-negative and anti-HBe-positive for at least two consecutive measurements at least 6 months apart) for ≥1 year, with undetectable HBV DNA (two consecutive measurements at least 6 months apart) maintained for at least 2 years. HBsAg loss is achieved (with or without anti-HBs seroconversion) followed by at least one additional year of consolidation treatment
• If HBeAg-negative at initiation of therapy: Undetectable HBV DNA (two consecutive measurements at least 6 months apart) maintained for at least 2 years. An alternative approach for HBeAg-negative persons is to not withdraw nucleos(t)ide analogue therapy until HBsAg loss is achieved and confirmed
• Quantitative HBsAg level <100 IU/mL
• Individuals with persistently normal ALT levels and persistently undetectable HBV DNA levels for at least 2 years
• Individuals without history or clinical evidence of advanced fibrosis/cirrhosis, hepatic decompensation (eg hepatic encephalopathy, variceal bleed, ascites, hepatorenal syndrome), HCC or extrahepatic complications of HBV
• No coinfection with HIV or HDV
• Individuals who are suitable and willing for close follow-up and frequent monitoring after discontinuation and long term for reactivation

Retreatment is recommended in the following patients who discontinued nucleos(t)ide analogue therapy:  

• Reappearance of HBsAg or HBeAg after prior loss or seroconversion
• ALT ≥5x ULN regardless of HBV DNA level
• HBV DNA level ≥10,000 IU/mL (≥4 log10 IU/mL) regardless of ALT level
• Total bilirubin of >2.5 mg/dL
• Any symptoms of hepatic decompensation
• If treatment initiation criteria are met (HBV DNA ≥2,000 IU/mL and ALT ≥2x ULN)
• Extrahepatic complications of HBV
• Patient preference to restart therapy after appropriate counseling

Peginterferon alfa therapy predictors of response and early discontinuation criteria identify patients with a high likelihood of response and limit treatment duration:

• HBeAg-positive patients:
  • Genotype A or D week 12: No decline in HBsAg from baseline; week 24: HBsAg >20,000 IU/mL
  • Genotype B or C week 12 and 24: HBsAg >20,000 IU/mL
• HBeAg-negative patients:
  • Genotype D week 12: No decline in HBsAg and HBV DNA decline <2log10 from baseline

Suboptimal Response to Antiviral Therapy  

Suboptimal virologic response to nucleos(t)ide analogue therapy includes the following:

• Slow decline: Quantifiable HBV DNA after 96 weeks of therapy and <5-log decline from baseline
• Plateau: HBV DNA ≤1 log/mL decline in the past 6 months
• Breakthrough: HBV DNA increased ≥1 log or >100 IU/mL after achieving undetectability

In all cases of suboptimal response, the initial steps include evaluation and reinforcement of treatment adherence and confirmation if medications are taken correctly (eg with food [Tenofovir] or on empty stomach [Entecavir]), more frequent follow-up of HBV DNA levels to establish pattern, and consideration of resistance testing (particularly if the individual meets criteria for virologic breakthrough). Once adherence is confirmed, an antiviral change is considered if a plateau or virologic breakthrough is determined. In most cases, switching to an alternative antiviral is preferred (lower pill burden) but add-on therapy can also be considered. After the change of antivirals, HBV DNA is monitored every 3 months until undetectable, then every 6 months. For those with slow decline, monitoring for decline is continued without changing therapy.  

Relapse and Flare  

Biochemical relapse is defined as an increase in ALT levels >2x the ULN. Viral relapse is defined as HBV DNA >2,000 IU/mL, while hepatitis flare is defined as an increase in ALT levels >5x the ULN. Severe hepatitis flare is defined as ALT levels >1,000 U/L or ALT <1,000 U/L with a total bilirubin ≥3.5 mg/dL or an INR ≥1.5. Independent risk factors associated with increased risk of relapse include the presence of cirrhosis, older age, shorter nucleos(t)ide analogue treatment duration, and higher pretreatment HBV DNA levels.

Hepatitis D

The aim of treatment is to eradicate or to achieve long-term suppression of both HDV and HBV. Supportive care should be given, and hospitalization and expert referral are considered if there is vomiting, dehydration, or signs of hepatic decompensation. It is essential to screen the patient for other sexually transmitted diseases (STDs) in cases of sexually acquired hepatitis or if otherwise appropriate. Consideration of an expert referral is also important. Screening for HCC every 6 months with ultrasound is recommended in patients with chronic HDV and advanced fibrosis or cirrhosis is also recommended. HCC surveillance is the same as those with HBV alone in individuals with prior HDV infection (anti-HDV positive, HDV RNA negative).

Pharmacological therapy

Severe Acute Hepatitis B

Severe acute hepatitis B is characterized by coagulopathy, persistent jaundice for >4 weeks, or signs of acute hepatic failure. More than 95% of immunocompetent individuals with symptomatic acute hepatitis B would recover spontaneously without antiviral therapy. Antiviral therapy is given only to patients with acute liver failure or with a protracted severe course (ie total bilirubin >3 mg/dL, international normalized ratio of >1.5, presence of ascites or encephalopathy).

Entecavir, Tenofovir alafenamide or Tenofovir disoproxil fumarate may be used in these patients, while Peginterferon is contraindicated. Observational data have shown that early nucleos(t)ide analogue treatment can reduce rates of chronicity if treatment is initiated within 8 weeks of acute hepatitis B. Continue treatment until HBsAg is cleared, or at least 12 months after anti-HBe seroconversion without HBsAg loss, or indefinitely if to undergo liver transplantation.

Chronic Hepatitis B

Therapeutic options recommended for the treatment of chronic HBV infection include nucleos(t)ide analogues or immunomodulators (Peginterferon alfa and standard Interferon). Nucleoside analogues include Clevudine, Entecavir, Lamivudine, and Telbivudine. Nucleotide analogues include Adefovir, Tenofovir alafenamide and Tenofovir disoproxil fumarate. Nucleos(t)ide analogues are categorized by their HBV resistance profiles into low-barrier nucleos(t)ide analogues (eg Adefovir dipivoxil, Lamivudine, Telbivudine) and high-barrier nucleos(t)ide analogues (eg Entecavir, Tenofovir alafenamide, Tenofovir disoproxil fumarate). Long-term administration of a potent nucleos(t)ide analogue with a high barrier to resistance is the treatment of choice regardless of the severity of liver disease in patients with chronic hepatitis B. 

Preferred Agents

Entecavir

Entecavir is considered a first-line agent for the treatment of chronic HBV infection. Recommended for the treatment of patients with chronic HBV infection with established osteoporosis and/or impaired renal function, and as an alternative for children ≥2 years old and adolescents with chronic HBV infection. It is approved for the treatment of chronic HBV infection in adults with evidence of active viral replication and either evidence of persistent elevations in ALT or AST or histologically active disease. It is recommended in HBsAg-positive patients with decompensated cirrhosis or acute-on-chronic liver failure irrespective of HBV DNA levels. Its use is based on histologic, virologic, biochemical, and serologic responses in nucleoside-treatment-naive and Lamivudine-resistant adult patients with HBeAg-positive or HBeAg-negative chronic HBV infection with compensated liver disease. 

It appears to be superior to Lamivudine based on histologic improvement, reduction in viral load, and ALT normalization. It must be noted that Entecavir is avoided if with prior Lamivudine exposure. It is also effective in the treatment of patients with Adefovir and Tenofovir resistance. If a pregnant patient is receiving Entecavir or other antivirals, switch to Tenofovir alafenamide or Tenofovir disoproxil fumarate. 

Entecavir inhibits HBV polymerase activities such as base priming, reverse transcription of the negative strand from the pregenomic messenger RNA, and synthesis of the positive strand of HBV DNA.

Studies in rodents exposed to high doses (ie 3-40x that given to humans) of Entecavir showed an increased incidence of lung adenomas, brain gliomas, and HCC.

Tenofovir alafenamide

Tenofovir alafenamide is used as a first-line agent for the treatment of immune-active chronic HBV infection in adults with compensated liver disease. It is recommended for the treatment of patients with chronic HBV infection with established osteoporosis and/or impaired renal function (eGFR >15 mL/min), and as an alternative for children ≥6 years old weighing at least 25 kg with chronic HBV infection. It is recommended in HBsAg-positive patients with decompensated cirrhosis or acute-on-chronic liver failure irrespective of HBV DNA levels. It is approved for use in patients with HIV in combination with Emtricitabine with or without other HIV drugs. It may be given at 28 weeks of gestation to prevent mother-to-child transmission in pregnant women with HBV DNA levels (viral load) >200,000 IU/mL at any point during the pregnancy, regardless of HBsAg status. Treatment is initiated immediately if the patient presents after 28 weeks of gestation. It may be discontinued at delivery when used solely to prevent perinatal HBV transmission and may be initiated or continued during breastfeeding in women who require ongoing HBV treatment. It may be considered as an alternative agent in patients with treatment failure due to suspected or confirmed resistance to Adefovir, Entecavir, Lamivudine, and Telbivudine. It is equally effective as Tenofovir disoproxil fumarate but uses a lower dose, thus it has fewer systemic adverse effects. Clinical trials with follow-up at 2 years reported no resistance to Tenofovir alafenamide therapy. 

Tenofovir alafenamide is a phosphonamidite prodrug of Tenofovir that inhibits HBV replication through incorporation into the viral DNA by HBV reverse transcriptase resulting in DNA chain termination. Its potential significant side effect includes lactic acidosis; hence, it is essential to perform HIV testing prior to initiating therapy and to monitor lactic acid levels.


Tenofovir disoproxil fumarate  

Tenofovir disoproxil fumarate is used as a first-line agent for the treatment of chronic HBV infection, as an alternative agent in patients with treatment failure due to suspected or confirmed resistance to Adefovir, Entecavir, Lamivudine, and Telbivudine, and as an alternative for adolescents ≥12 years old with chronic HBV infection. It is recommended in HBsAg-positive patients with decompensated cirrhosis or acute-on-chronic liver failure irrespective of HBV DNA levels. It may be given at 28 weeks of gestation to prevent mother-to-child transmission in pregnant women with HBV DNA levels (viral load) >200,000 IU/mL at any point during the pregnancy, regardless of HBsAg status. Treatment is initiated immediately if the patient presents after 28 weeks of gestation. It may be discontinued at delivery when used solely to prevent perinatal HBV transmission, and may be initiated or continued during breastfeeding in women who require ongoing HBV treatment. It must be noted that Tenofovir disoproxil fumarate has a more extensive safety record in pregnancy than Tenofovir alafenamide. Tenofovir disoproxil is also recommended to be used in combination with Lamivudine or Emtricitabine as an alternative agent regimen for the treatment of chronic HBV infection if monotherapy with Tenofovir disoproxil fumarate is not available. It is an effective antiviral agent for hepatitis B (chronic HBeAg positive or HBeAg negative) that so far has no resistance detected.  

Tenofovir disoproxil fumarate is a prodrug of Tenofovir and it inhibits HBV polymerase resulting in the inhibition of viral replication. Its potential significant side effects include lactic acidosis, nephropathy, Fanconi syndrome, and osteomalacia. It is essential to perform HIV testing prior to initiating therapy and to monitor renal function at baseline, within the first 4 weeks of treatment, after 3 months of treatment, and every 3-6 months thereafter; bone density at baseline and during treatment; and lactic acid levels if with clinical concern.

Hepatitis B_Management

Hepatitis B_Management 2

Nonpharmacological

Patient Education

Acute Hepatitis B

Partner notification for at-risk contacts is essential. Contact tracing should include any sexual contact (penetrative vaginal or anal or oral/anal) or needle-sharing partners within 2 weeks before the onset of jaundice until the patient becomes negative for HBsAg. All non-immune sexual and household contacts must be vaccinated.

Provide the patients with a detailed explanation of their condition and emphasize the disease’s long-term implications (eg long-term medical therapy, continuous monitoring) for their and their partners’ health. Shared decision making is promoted in order to support patients in choosing the best treatment option for them. Provide clear and accurate written information for easier understanding. Advise the patients to avoid unprotected sexual intercourse and emphasize condom use. Screen patients for other STDs in cases of sexually acquired hepatitis or if otherwise appropriate. 

Chronic Hepatitis B

Partner notification is essential. Trace contacts as far back as any episode of jaundice or to the time when the infection is thought to have been acquired. All non-immune sexual and household contacts must be vaccinated.

Provide the patients with a detailed explanation of their condition and emphasize the disease’s long-term implications (eg long-term medical therapy, continuous monitoring) for their and their partners’ health. Shared decision making is promoted in order to support patients in choosing the best treatment option for them. Provide clear and accurate written information for easier understanding. Advise patients to observe abstinence or limited use of alcohol to prevent further liver injury.

Counseling regarding the prevention of transmission of HBV is also important. To prevent sexual transmission, protected sexual intercourse like condom use is done. To prevent perinatal transmission, post-delivery, infants of HBV-infected mothers should receive hepatitis B immune globulin (HBIg) within 12 hours and hepatitis D vaccine within 24 hours of birth. Counseling to prevent inadvertent transmission via environmental contamination from a blood spill is also done.

Hepatitis D

Partner notification for at-risk contacts is essential. Provide the patient with a detailed explanation of his condition and emphasize the disease's long-term implications (eg long-term medical therapy, continuous monitoring) for their and their partner’s health. Provide clear and accurate written information for easier understanding. Advise patients to avoid unprotected sexual intercourse. 

Hepatitis B_Management 3

Surgery

Liver Transplantation

Liver transplantation is indicated in patients with end-stage liver disease (cirrhosis), HCC, and acute liver failure (ie caused by viruses, drugs, and toxic agents). It is considered in patients with expected survival of ≤1 year without transplantation or if the quality of life is unsatisfactory due to liver disease. Patients with HBV infection should be evaluated for liver transplantation despite antiviral therapy as the development of liver failure cannot be predicted.

The combination therapy with HBIg and nucleos(t)ide analogues helps prevent HBV recurrence in these patients undergoing liver transplantation. Recipient patients without anti-HBs should receive prophylaxis for HBV recurrence if transplanted liver is anti-HBc positive. HDV replication is not a contraindication for liver transplantation. 

Prevention

Prevention and Post-exposure Prophylaxis of Hepatitis B

¹Vaccination of household contacts (especially children and adolescents) of persons with acute hepatitis B virus infection is also encouraged. Consider postvaccination testing (anti-HBs) for sexual partners of persons with chronic hepatitis B virus infection. Those found to be antibody negative should receive a second, complete, vaccination series.
²Skin and wound sites exposed to blood or body fluids with HBV infection should be washed with soap and water immediately following contact; exposed mucous membranes should be flushed with water.

Revaccination is recommended for infants born to HBsAg-positive mothers, healthcare practitioners, hemodialysis patients, and immunocompromised individuals when anti-HBs is <10 mIU/mL. Postvaccination serologic testing is recommended only for infants born to HBsAg-positive mothers, healthcare practitioners, hemodialysis patients, immunocompromised individuals (eg HIV-positive patients, stem-cell transplant recipients, cancer patients receiving chemotherapy), and sexual partners of HBsAg-positive individuals.

Hepatitis B_Follow up