Updated AASLD hepatitis B guidance of 2018

This AASLD 2018 Hepatitis B Guidance is an update on AASLD 2016 Practice Guidelines for Treatment of Chronic Hepatitis B1 and previous hepatitis B virus (HBV) guidelines from 2009. The 2018 updated guidance on chronic hepatitis B (CHB) includes (1) updates on treatment since the 2016 HBV guidelines (notably the use of tenofovir alafenamide) and guidance on (2) screening, counseling, and prevention; (3) specialized virological and serological tests; (4) monitoring of untreated patients; and (5) treatment of hepatitis B in special populations, including persons with viral coinfections, acute hepatitis B, recipients of immunosuppressive therapy, and transplant recipients.The Guidelines have been published in Hepatology.

Guidance Statements on Screening for Hepatitis B Infection

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


2. Screening is recommended in all persons born in countries with a HBsAg seroprevalence of ≥2%, U.S.‐born persons not vaccinated as infants whose parents were born in regions with high HBV endemicity (≥8%), pregnant women, persons needing immunosuppressive therapy, and the at‐risk groups listed in Table.


3. Anti‐HBs–negative screened persons should be vaccinated.


4. Screening for anti‐HBc to determine prior exposure is not routinely recommended but is an important test in patients who have HIV infection, who are about to undergo HCV or anticancer and other immunosuppressive therapies or renal dialysis, and in donated blood (or, if feasible, organs)

Guidance Statements on Counseling of Persons Who Are HBsAg Positive

1. HBsAg‐positive persons should be counseled regarding prevention of transmission of HBV to others (Table 5).


2. For HCWs and students who are HBsAg positive:
   
   
   
   1. They should not be excluded from training or practice because they have hepatitis B.
   
   
   2. Only HBsAg‐positive HCWs and students whose job requires performance of exposure‐prone procedures are recommended to seek counseling and advice from an expert review panel at their institution. They should not perform exposure‐prone procedures if their serum HBV‐DNA level exceeds 1,000 IU/mL but may resume these procedures if their HBV‐DNA level is reduced and maintained below 1,000 IU/mL.
   
   
   
   


3. Other than practicing universal precautions, no special arrangements are indicated for HBV‐infected children in community settings, such as daycare centers, schools, sports clubs, and camps, unless they are prone to biting.


4. Abstinence or only limited use of alcohol is recommended in HBV‐infected persons.


5. Optimization of body weight and treatment of metabolic complications, including control of diabetes and dyslipidemia, are recommended to prevent the concurrent development of metabolic syndrome and fatty liver.

Guidance Statements on Counseling of Persons Who Are HBsAg Negative and anti‐HBc Positive (With or Without anti‐HBs)

1. Screening for anti‐HBc is not routinely recommended except in patients who have HIV infection or who are about to undergo HCV therapy or immunosuppressive treatment.


2. Persons who are anti‐HBc positive without HBsAg are not at risk of transmission of HBV, either sexually or to close personal contacts.


3. Persons who are positive only for anti‐HBc and who are from an area with low endemicity with no risk factors for HBV should be given the full series of hepatitis B vaccine.


4. Persons who are positive only for anti‐HBc and have risk factors for hepatitis B (Table3) are not recommended for vaccination unless they are HIV positive or immunocompromised.

Guidance Statements on Counseling of Women in Pregnancy

1. HBV vaccination is safe in pregnancy, and pregnant women who are not immune to or infected with HBV should receive this vaccine series.


2. Women identified as HBsAg positive during pregnancy should be linked to care for additional testing (ALT, HBV DNA, or imaging for HCC surveillance if indicated) and determination of need for antiviral therapy.


3. Women who meet standard indications for HBV therapy should be treated. Women without standard indications but who have HBV DNA >200,000 IU/mL in the second trimester should consider treatment to prevent mother‐to‐child transmission.1


4. HBV‐infected pregnant women who are not on antiviral therapy, as well as those who stop antiviral at or early after delivery, should be monitored closely for up to 6 months after delivery for hepatitis flares and seroconversion. Long‐term follow‐up should be continued to assess need for future therapy.


5. The potential risk of mother‐to‐child transmission of HBV with amniocentesis should be included in the risk of harms versus benefits discussion in HBsAg‐positive mothers with high‐level viremia.


6. HBV‐infected pregnant women with cirrhosis should be managed in high‐risk obstetrical practices and treated with TDF to prevent decompensation.


7. Sexual partners of women identified as HBV‐infected during pregnancy should be assessed for HBV infection or immunity and receive HBV vaccine if appropriate.


8. Breastfeeding is not prohibited.

Guidance Statements for Prevention of Transmission of Hepatitis B From Individuals With Chronic HBV Infection

1. HBV vaccines have an excellent safety record and are given as a 3‐dose series at 0, 1, and 6 months (with or without hepatitis A vaccine). An alternate 4‐dose schedule given at 0, 7, and 21 to 30 days followed by a dose at 12 months can be used for the combination hepatitis A and B vaccine (Twinrix) for adults. Recently, a 2‐dose series given at 0 and 1 months has been approved for adults (HEPLISAV‐B).


2. Sexual and household contacts of HBV‐infected persons who are negative for HBsAg and anti‐HBs should receive HBV vaccination.


3. Newborns of HBV‐infected mothers should receive HBIG and HBV vaccine at delivery and complete the recommended vaccination series. Infants of HBsAg‐positive mothers should undergo postvaccination testing at 9‐15 months of age.


4. HCWs, sexual partners of persons with chronic HBV infection, chronic hemodialysis patients, and immunocompromised persons (including those with HIV) should be tested for their response to the vaccination 1‐2 months after the last dose of vaccine.


5. For nonresponders to the initial vaccine series, a repeat 3‐dose vaccination series is recommended, with a double dose used for immunocompromised patients, including those with cirrhosis.91


6. Follow‐up testing of vaccine responders is recommended annually for chronic hemodialysis patients.


7. Booster doses or revaccination are not recommended except if anti-HBs remains <10 mIU/mL after initial vaccination of infants born to HBsAg-positive mothers, in HCWs, hemodialysis patients and other individuals who are immunocompromised.

Guidance Statements for Monitoring Patients With Chronic HBV Infection Who Are Not Currently on Treatment

1. Given that CHB is a dynamic disease, persons who are not receiving treatment should be assessed regularly to determine whether an indication for treatment has developed.


2. HBeAg‐positive patients with persistently normal ALT should be tested for ALT at 3‐ to 6‐month intervals. If ALT levels increase above ULN, ALT along with HBV DNA should be tested more frequently. HBeAg status should be checked every 6‐12 months.


3. Patients who are HBeAg positive with HBV‐DNA levels >20,000 IU/mL and ALT levels less than 2 times the ULN (<50 U/L for females, <70 U/L for males) should undergo testing to evaluate histological disease severity, especially those >40 years old and who were infected at a young age (i.e., long duration of infection).
   
   
   
   • Liver biopsy offers the only means of assessing both fibrosis and inflammation. If the biopsy specimen shows moderate or severe inflammation (A2 or A3) or significant fibrosis (≥F2), treatment is recommended.
   
   
   • Alternative methods to assess fibrosis are elastography (preferred) and liver fibrosis biomarkers (e.g., FIB‐4 or FibroTest). If these noninvasive tests indicate significant fibrosis (≥F2), treatment is recommended.
   
   
   
   


4. Patients who are HBeAg negative with HBV‐DNA levels >2,000 IU/mL and elevated ALT levels less than 2 times the ULN should undergo testing to evaluate disease severity, especially those who are >40 years old and who were infected at a young age (i.e., long duration of infection).
   
   
   
   • Liver biopsy offers the only means of assessing both fibrosis and inflammation. If the biopsy specimen shows moderate or severe inflammation (A2 or A3) or significant fibrosis (≥F2), treatment is recommended.
   
   
   • Alternative methods to assess fibrosis are elastography (preferred) and liver fibrosis markers (e.g., FIB‐4 or FibroTest). If these noninvasive tests indicate significant fibrosis (≥F2), treatment is recommended.
   
   
   
   


5. Patients who are HBeAg negative with normal ALT (≤25 U/L women, ≤35 U/L men) and HBV DNA <2,000 IU/mL should be tested for ALT and HBV DNA every 3 months during the first year to confirm they have inactive CHB. Thereafter, their ALT and HBV‐DNA levels should be tested at 6‐ to 12‐month intervals. If costs are a concern, ALT monitoring alone can be used. When ALT levels increase above the normal limit, ALT along with HBV DNA should be tested more frequently (every 3‐6 months).


6. In persons with HBV DNA <2,000 IU/mL but elevated ALT levels, other causes of liver disease should be investigated, including, but not limited to, HCV or HDV, drug toxicity, nonalcoholic fatty liver, alcohol, or autoimmune liver disease.


7. Persons with inactive CHB should be evaluated for loss of HBsAg annually.


8. In persons who achieve sustained HBsAg seroclearance, routine ALT and HBV‐DNA monitoring are no longer required. HCC surveillance should continue if the person has cirrhosis, a first‐degree family member with HCC, or a long duration of infection (>40 years for males and >50 years for females who have been infected with HBV from a young age).

Guidance Statements for Treatment of Patients with HBV and HCV Coinfection

1. All HBsAg‐positive patients should be tested for HCV infection using the anti‐HCV test.


2. HCV treatment is indicated for patients with HCV viremia.


3. HBV treatment is determined by HBV‐DNA and ALT levels as per the AASLD HBV guidelines for monoinfected patients.1


4. HBsAg‐positive patients are at risk of HBV‐DNA and ALT flares with HCV DAA therapy, and monitoring of HBV DNA levels every 4‐8 weeks during treatment and for 3 months posttreatment is indicated in those who do not meet treatment criteria for monoinfected patients per the AASLD HBV guidelines.1


5. HBsAg‐negative, anti‐HBc–positive patients with HCV are at very low risk of reactivation with HCV‐DAA therapy. ALT levels should be monitored at baseline, at the end of treatment, and during follow‐up, with HBV‐DNA and HBsAg testing reserved for those whose ALT levels increase or fail to normalize during treatment or posttreatment.

TREATMENT OF PERSONS WITH IMMUNE‐ACTIVE DISEASE

• The AASLD recommends antiviral therapy for adults with immune‐active CHB (HBeAg negative or HBeAg positive) to decrease the risk of liver‐related complications


• The AASLD recommends peg‐IFN, entecavir, or tenofovir (TDF) as preferred initial therapy for adults with immune‐active CHB

TREATMENT OF IMMUNE‐TOLERANT ADULTS WITH CHRONIC HEPATITIS B

• The AASLD recommends against antiviral therapy for adults with immune‐tolerant CHB


• The AASLD suggests that ALT levels be tested at least every 6 months for adults with immune tolerant CHB to monitor for potential transition to immune‐active or immune‐inactive CHB


• The AASLD suggests antiviral therapy in the select group of adults >40 years of age with normal ALT and elevated HBV DNA (1,000,000 IU/mL) and liver biopsy specimen showing significant necroinflammation or fibrosis

TREATMENT OF HBeAg‐POSITIVE, IMMUNE‐ACTIVE PERSONS WITH CHRONIC HEPATITIS WHO SEROCONVERT TO ANTI‐HBe ON NA THERAPY

• The AASLD suggests that HBeAg‐positive adults without cirrhosis but with CHB who seroconvert to anti‐HBe on therapy discontinue NAs after a period of treatment consolidation


• The AASLD suggests indefinite antiviral therapy for HBeAg‐positive adults with cirrhosis with CHB who seroconvert to anti‐HBe on NA therapy, based on concerns for potential clinical decompensation and death, unless there is a strong competing rationale for treatment discontinuation

DURATION OF TREATMENT IN PERSONS WITH HBeAg‐NEGATIVE, IMMUNE‐ACTIVE CHB

• The AASLD suggests indefinite antiviral therapy for adults with HBeAg‐negative, immune‐active CHB unless there is a compelling rationale for treatment discontinuation

RENAL AND BONE DISEASE IN PERSONS ON NA THERAPY

• The AASLD suggests no preference between entecavir or tenofovir (TDF) regarding potential long‐term risks of renal and bone complications

• The AASLD suggests that persons with persistent low‐level viremia (<2,000 IU/mL) on entecavir or tenofovir monotherapy continue monotherapy, regardless of ALT


• The AASLD suggests 1 of 2 strategies in persons with virological breakthrough on entecavir or tenofovir monotherapy: either switch to another antiviral monotherapy with a high barrier to resistance or add a second antiviral drug that lacks cross‐resistance

MANAGEMENT OF ADULTS WITH CIRRHOSIS AND LOW‐LEVEL VIREMIA

• The AASLD suggests that adults with compensated cirrhosis and low‐level viremia (<2,000 IU/mL) be treated with antiviral therapy to reduce the risk of decompensation, regardless of ALT level.


• The AASLD recommends that HBsAg‐positive adults with decompensated cirrhosis be treated with antiviral therapy indefinitely regardless of HBV DNA level, HBeAg status, or ALT level to decrease risk of worsening liver‐related complications

Management of Chronic Hepatitis B in Pregnancy

• The AASLD suggests antiviral therapy to reduce the risk of perinatal transmission of HBV in HBsAg‐positive pregnant women with an HBV‐DNA level >200,000 IU/mL


• The AASLD recommends against the use of antiviral therapy to reduce the risk of perinatal transmission of HBV in HBsAg‐positive pregnant women with an HBV‐DNA level ≤200,000 IU/mL

Treatment of CHB in Children

• The AASLD suggests antiviral therapy in HBeAg‐positive children (ages 2 to <18 years) with both elevated ALT and measurable HBV‐DNA levels, with the goal of achieving sustained HBeAg seroconversion


• The AASLD recommends against the use of antiviral therapy in HBeAg‐positive children (ages 2 to <18 years) with persistently normal ALT, regardless of HBV‐DNA level.

For further reference log on to : https://doi.org/10.1002/hep.29800