Hepatitis B virus: Difference between revisions
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m (Text replacement - "Clinical Presentation" to "Clinical Manifestations") |
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==Background== |
==Background== |
||
===Microbiology=== |
===Microbiology=== |
||
+ | |||
− | * Reverse-transcription double-stranded DNA (RT-dsDNA) virus |
||
+ | *Reverse-transcription double-stranded DNA (RT-dsDNA) virus |
||
− | * Genotypes A through J vary in geographic distribution and clinical severity |
||
+ | *Genotypes A through J vary in geographic distribution and clinical severity |
||
{| class="wikitable" |
{| class="wikitable" |
||
− | ! |
+ | !Genotype!!B!!C!!A!!D!!E-J |
|- |
|- |
||
− | ! colspan=6 | |
+ | ! colspan="6" |Clinical characteristics |
|- |
|- |
||
− | | |
+ | |Modes of transmission |
− | | |
+ | |Perinatal/vertical |
− | | |
+ | |Perinatal/vertical |
− | | |
+ | |Horizontal |
− | | |
+ | |Horizontal |
− | | |
+ | |Horizontal |
|- |
|- |
||
− | | |
+ | |Tendency of chronicity |
− | | |
+ | |Lower |
− | | |
+ | |Higher |
− | | |
+ | |Higher |
− | | |
+ | |Lower |
− | | |
+ | |No data |
|- |
|- |
||
− | | |
+ | |HBeAg positivity |
− | | |
+ | |Lower |
− | | |
+ | |Higher |
− | | |
+ | |Higher |
− | | |
+ | |Lower |
− | | |
+ | |No data |
|- |
|- |
||
− | | |
+ | |HBeAg seroconversion |
− | | |
+ | |Earlier |
− | | |
+ | |Later |
− | | |
+ | |Earlier |
− | | |
+ | |Later |
− | | |
+ | |No data |
|- |
|- |
||
− | | |
+ | |HBsAg seroclearance |
− | | |
+ | |More |
− | | |
+ | |Less |
− | | |
+ | |More |
− | | |
+ | |Less |
− | | |
+ | |No data |
|- |
|- |
||
− | | |
+ | |Histological activity |
− | | |
+ | |Lower |
− | | |
+ | |Higher |
− | | |
+ | |Lower |
− | | |
+ | |Higher |
− | | |
+ | |No data |
|- |
|- |
||
− | ! colspan=6 | |
+ | ! colspan="6" |Clinical outcomes |
|- |
|- |
||
− | | |
+ | |Response to interferon-α |
− | | |
+ | |Higher |
− | | |
+ | |Lower |
− | | |
+ | |Higher |
− | | |
+ | |Lower |
− | | |
+ | |Lower in G |
|- |
|- |
||
− | | |
+ | |Response to NRTIs |
− | | colspan=4 | |
+ | | colspan="4" |No significant differences |
− | | |
+ | |No data |
|- |
|- |
||
− | ! colspan=6 | |
+ | ! colspan="6" |Viroloical characteristics |
|- |
|- |
||
− | | |
+ | |Viral load |
− | | |
+ | |Lower |
− | | |
+ | |Higher |
− | | colspan=3 | |
+ | | colspan="3" |No data |
|- |
|- |
||
− | | |
+ | |Frequency of PC A1896 mutation |
− | | |
+ | |Higher |
− | | |
+ | |Lower |
− | | |
+ | |Lower |
− | | |
+ | |Higher |
− | | |
+ | |No data |
|- |
|- |
||
− | | |
+ | |Frequency of basal core promoter T1762/A1764 mutation |
− | | |
+ | |Lower |
− | | |
+ | |Higher |
− | | |
+ | |Higher |
− | | |
+ | |Lower |
− | | |
+ | |No data |
|- |
|- |
||
− | | |
+ | |Frequency of preS deletion utation |
− | | |
+ | |Lower |
− | | |
+ | |Higher |
− | | colspan=3 | |
+ | | colspan="3" |No data |
|} |
|} |
||
+ | === Phases of Chronic Infection === |
||
− | == Clinical Manifestations == |
||
+ | |||
− | === Acute === |
||
+ | * '''Phase 1:''' HBeAg + chronic infection (previously immune tolerant) |
||
− | * 75% are asymptomatic |
||
+ | ** Viral replication including HBeAg without evidence of immune response |
||
− | * Symptoms range from self-resolving jaundice to fulminant liver failure in about 5% |
||
+ | * '''Phase 2:''' HBeAg + chronic hepatitis (previously immune active) |
||
+ | ** Elevated liver enzymes and HBV DNA |
||
+ | * '''Phase 3:''' HBeAg – chronic infection (previously inactive carrier) |
||
+ | ** HBeAg clears and liver enzymes normalize, but ongoing low-level viral replication |
||
+ | * '''Phase 4:''' HBeAg – chronic hepatitis (previously HBeAg-negative chronic hepatitis) |
||
+ | ** Increasing viral load with fluctuating liver enzymes |
||
+ | * '''Phase 5:''' HBsAg negative |
||
+ | ** HBsAb positive or negative, other studies return to normal |
||
+ | |||
+ | ==Clinical Manifestations== |
||
+ | ===Acute=== |
||
+ | |||
+ | *75% are asymptomatic |
||
+ | *Symptoms range from self-resolving jaundice to fulminant liver failure in about 5% |
||
+ | |||
+ | ===Chronic=== |
||
+ | |||
+ | *Chronic hepatitis B begins as e antigen positive, usually with very high levels of HBV DNA and necroinflammation. |
||
+ | *Four types of chronic hepatitis B |
||
+ | **'''Immunotolerant''' hepatitis B: HBV DNA levels (>20,000 IU/ml), HBeAg positive, with normal ALT |
||
+ | ***Common after vertical transmission and can persist for years before progressing to another form |
||
+ | **'''HBeAg-positive immune-active''' chronic hepatitis B: HBsAg-positive, HBV DNA levels (>20,000 IU/ml), HBeAg positive, anti-HBe negative with elevated ALT |
||
+ | **'''HBeAg-negative immune-active''' chronic hepatitis B: HBsAg-positive, HBV DNA levels (<20,000 IU/ml), HBeAg negative, anti-HBe positive, with elevated ALT |
||
+ | ***Results from anti-HBe seroconversion when a mutation decreases HBeAg expression |
||
+ | **'''Inactive hepatitis B''' (healthy carrier): HBsAg for > 6 months without any evidence of necroinflammation and HBV DNA levels are < 2,000 IU/m |
||
+ | ***May still transmit it, but overall a better prognosis |
||
+ | *'''Hepatocellular carcinoma''' is a risk in chronic hepatitis B, but especially in certain populations including cirrhosis |
||
+ | *'''Polyarteritis nodosa''' |
||
+ | *'''Membranous nephropathy''' or '''membranoproliferative glomerulonephritis''' |
||
+ | *Sensorimotor neuropathy |
||
+ | *Sjogren syndrome |
||
+ | |||
+ | ==Investigations== |
||
+ | |||
+ | *[[Hepatitis B serology]] |
||
+ | |||
+ | ==Management== |
||
+ | ===Acute=== |
||
+ | |||
+ | *Supportive care |
||
+ | |||
+ | ===Chronic=== |
||
+ | |||
+ | *HBsAg present ≥6 months |
||
+ | *HBV-DNA is variable |
||
+ | *Can be HBeAg positive or negative, with generally higher HBV DNA levels in HBeAg-positive patients |
||
+ | *ALT can be normal or elevated |
||
+ | *Liver boipsy shows chronic hepatitis and variable necroinflammation or fibrosis |
||
+ | |||
+ | ====Immune-active==== |
||
+ | |||
+ | *HBsAg present ≥6 months and HBeAg either positive or negative |
||
+ | *Intermittently or persistently elevated ALT and AST |
||
+ | |||
+ | =====Indications for treatment===== |
||
+ | |||
+ | *ALT ≥2x ULN or evidence of significant histologic disease, AND |
||
+ | *Elevated HBV DNA |
||
+ | **> 2000 IU/mL if HBeAg negative |
||
+ | **> 20,000 IU/mL if HBeAg positive |
||
+ | |||
+ | ====Immune-tolerant==== |
||
+ | *HBsAg present for ≥6 months and HBeAg positive |
||
− | === Chronic === |
||
+ | *HBV DNA typically over 1 million |
||
+ | *Normal or minimally-elevated ALT and AST |
||
+ | *That is, high viral load but normal ALT |
||
+ | =====Indications for treatment===== |
||
− | * Chronic hepatitis B begins as e antigen positive, usually with very high levels of HBV DNA and necroinflammation. |
||
− | * Four types of chronic hepatitis B |
||
− | ** '''Immunotolerant''' hepatitis B: HBV DNA levels (>20,000 IU/ml), HBeAg positive, with normal ALT |
||
− | *** Common after vertical transmission and can persist for years before progressing to another form |
||
− | ** '''HBeAg-positive immune-active''' chronic hepatitis B: HBsAg-positive, HBV DNA levels (>20,000 IU/ml), HBeAg positive, anti-HBe negative with elevated ALT |
||
− | ** '''HBeAg-negative immune-active''' chronic hepatitis B: HBsAg-positive, HBV DNA levels (<20,000 IU/ml), HBeAg negative, anti-HBe positive, with elevated ALT |
||
− | *** Results from anti-HBe seroconversion when a mutation decreases HBeAg expression |
||
− | ** '''Inactive hepatitis B''' (healthy carrier): HBsAg for > 6 months without any evidence of necroinflammation and HBV DNA levels are < 2,000 IU/m |
||
− | *** May still transmit it, but overall a better prognosis |
||
− | * '''Hepatocellular carcinoma''' is a risk in chronic hepatitis B, but especially in certain populations including cirrhosis |
||
− | * '''Polyarteritis nodosa''' |
||
− | * '''Membranous nephropathy''' or '''membranoproliferative glomerulonephritis''' |
||
− | * Sensorimotor neuropathy |
||
− | * Sjogren syndrome |
||
+ | *Adults >40 years, AND |
||
− | == Investigations == |
||
+ | *ALT rises above 2x ULN (i.e. becomes immune-active), OR |
||
− | * [[Hepatitis B serology]] |
||
+ | *Liver biopsy showing significant necroinflammation or fibrosis |
||
+ | =====Surveillance===== |
||
− | == Management == |
||
− | === Acute === |
||
− | * Supportive care |
||
+ | *Monitor at 3 to 6 month intervals, more frequently as ALT levels rise, consider treatment if >2x ULN/ |
||
− | === Chronic === |
||
− | * HBsAg present ≥6 months |
||
− | * HBV-DNA is variable |
||
− | * Can be HBeAg positive or negative, with generally higher HBV DNA levels in HBeAg-positive patients |
||
− | * ALT can be normal or elevated |
||
− | * Liver boipsy shows chronic hepatitis and variable necroinflammation or fibrosis |
||
− | ==== |
+ | ====Treatment Regimens==== |
− | * HBsAg present ≥6 months and HBeAg either positive or negative |
||
− | * Intermittently or persistently elevated ALT and AST |
||
+ | *One of pegylated-interferon (48 weeks), tenofovir (until 12 months post-HBeAg conversion), or entecavir (until 12 months post-HBeAg conversion) |
||
− | ===== Indications for treatment ===== |
||
+ | **Peg-IFN contraindicated in autoimmune disorders, uncontrolled psychiatric disease, cyptopenia, severe cardiac disease, uncontrolled seizures, and decompensated cirrhosis |
||
− | * ALT ≥2x ULN or evidence of significant histologic disease, AND |
||
+ | **Peg-IFN preferred in lamivudine resistance |
||
− | * Elevated HBV DNA |
||
+ | **Tenofovir is safe in pregnancy |
||
− | ** > 2000 IU/mL if HBeAg negative |
||
+ | *Duration depends on what stage is being treated |
||
− | ** > 20,000 IU/mL if HBeAg positive |
||
+ | **HBeAg positive and HBV DNA >20,000 and ALT >2 ULN |
||
+ | ***Peg-IFN for 48 weeks |
||
+ | ***Tenofovir or entecavir for at least 12 months after HBeAg seroconversion (Ag to Ab) |
||
+ | **HBeAg negative and HBV DNA > 2000 and ALT >2x ULN (or biopsy shows necroinflammation or fibrosis, or non-invasive testing shows fibrosis) |
||
+ | ***Peg-IGN for 1 year |
||
+ | ***Tenofovir or entecavir for many years, possibly indefinitely |
||
+ | *Continue HCC surveillance regardless of treatment |
||
− | ==== |
+ | ====Inactive chronic hepatitis B==== |
− | * HBsAg present for ≥6 months and HBeAg positive |
||
− | * HBV DNA typically over 1 million |
||
− | * Normal or minimally-elevated ALT and AST |
||
− | * That is, high viral load but normal ALT |
||
+ | *Defined by HBeAg-negative, anti-HBeAb-positive, normal ALT, and HBV DNA <2000 IU/mL |
||
− | ===== Indications for treatment ===== |
||
+ | *Monitor ALT q3mo for 1 year, then q6-12mo |
||
− | * Adults >40 years, AND |
||
− | * ALT rises |
+ | *If ALT rises, check HBV-DNA and HBsAg for activity |
− | * Liver biopsy showing significant necroinflammation or fibrosis |
||
− | ==== |
+ | ====HCC screening==== |
− | * Monitor at 3 to 6 month intervals, more frequently as ALT levels rise, consider treatment if >2x ULN/ |
||
+ | *Screen if HBsAg-positive with cirrhosis, or HBsAg-positive at higher risk (Asian men >40yrs, black men >40yrs, Asian women >50yrs, family history, HDV coinfection) |
||
− | ==== Treatment Regimens ==== |
||
+ | *First-line is ultrasound every 6 months |
||
− | * One of pegylated-interferon (48 weeks), tenofovir (until 12 months post-HBeAg conversion), or entecavir (until 12 months post-HBeAg conversion) |
||
+ | *Second-line is AFP levels every 6 months |
||
− | ** Peg-IFN contraindicated in autoimmune disorders, uncontrolled psychiatric disease, cyptopenia, severe cardiac disease, uncontrolled seizures, and decompensated cirrhosis |
||
− | ** Peg-IFN preferred in lamivudine resistance |
||
− | ** Tenofovir is safe in pregnancy |
||
− | * Duration depends on what stage is being treated |
||
− | ** HBeAg positive and HBV DNA >20,000 and ALT >2 ULN |
||
− | *** Peg-IFN for 48 weeks |
||
− | *** Tenofovir or entecavir for at least 12 months after HBeAg seroconversion (Ag to Ab) |
||
− | ** HBeAg negative and HBV DNA > 2000 and ALT >2x ULN (or biopsy shows necroinflammation or fibrosis, or non-invasive testing shows fibrosis) |
||
− | *** Peg-IGN for 1 year |
||
− | *** Tenofovir or entecavir for many years, possibly indefinitely |
||
− | * Continue HCC surveillance regardless of treatment |
||
+ | ===Prophylaxis in Immunosuppression=== |
||
− | ==== Inactive chronic hepatitis B ==== |
||
− | * Defined by HBeAg-negative, anti-HBeAb-positive, normal ALT, and HBV DNA <2000 IU/mL |
||
− | * Monitor ALT q3mo for 1 year, then q6-12mo |
||
− | * If ALT rises, check HBV-DNA and HBsAg for activity |
||
+ | *Risk stratify based on type of immune suppression and serologic status |
||
− | ==== HCC screening ==== |
||
+ | **'''High-risk''' (>10%): |
||
− | * Screen if HBsAg-positive with cirrhosis, or HBsAg-positive at higher risk (Asian men >40yrs, black men >40yrs, Asian women >50yrs, family history, HDV coinfection) |
||
+ | ***HBsAg positive, or HBsAg negative but HBcAb positive, plus B-cell depletion such as rituximab and ofatumumab |
||
− | * First-line is ultrasound every 6 months |
||
+ | ***HBsAg positive, plus anthracyclines (doxorubicin, epirubicin), prednisone >10-20 mg/day for ≥4 weeks |
||
− | * Second-line is AFP levels every 6 months |
||
+ | **'''Moderate-risk''' (1-10%) |
||
+ | ***HBsAg positive, or HBsAg negative but HBcAb positive, plus TNF-α inhibitors (etanercept, adalimumab, certolizumab, certolizumab, infliximab), other cytokine or integrin inhibitors (abatacept, ustekinumab, natalizumab, vedolizumab), and tyrosine kinase inhibitors (imatinib, nilotinib, ibrutinib) |
||
+ | ***HBsAg positive: prednisone <10 mg/day for ≥4 weeks |
||
+ | ***HBsAg negative but HBcAb positive: prednisone >10-20 mg/day for ≥4 weeks, antracycline derivatives (doxorubicin and epirubicin) |
||
+ | **'''Low-risk''' (<1%) |
||
+ | ***HBsAg positive, or HBsAg negative but HBcAb positive, plus traditional immunosuppressants (azathioprine, 6-MP, methotrexate) |
||
+ | ***HBsAg negative or HBcAb positive, plus prednisone <10 mg/day for ≥4 weeks |
||
+ | *Concern especially with chronic steroids and rituximab |
||
+ | *Can have the following effects |
||
+ | **Asymptomatic HBV DNA and ALT |
||
+ | **Hepatic failure |
||
+ | **Death |
||
+ | *If ≥7.5mg/d should be screened |
||
+ | **HBsAg +/- HBcAb if they're adding a second agent (rituximab, TNF-alpha inhibitors, or other) |
||
+ | **Refer to Hepatology or Infectious Diseases |
||
+ | *Prophylaxis with lamivudine until 6 months after chemotherapy |
||
+ | ==Further Reading== |
||
− | === Prophylaxis in Immunosuppression === |
||
− | * Risk stratify based on type of immune suppression and serologic status |
||
− | ** '''High-risk''' (>10%): |
||
− | *** HBsAg positive, or HBsAg negative but HBcAb positive, plus B-cell depletion such as rituximab and ofatumumab |
||
− | *** HBsAg positive, plus anthracyclines (doxorubicin, epirubicin), prednisone >10-20 mg/day for ≥4 weeks |
||
− | ** '''Moderate-risk''' (1-10%) |
||
− | *** HBsAg positive, or HBsAg negative but HBcAb positive, plus TNF-α inhibitors (etanercept, adalimumab, certolizumab, certolizumab, infliximab), other cytokine or integrin inhibitors (abatacept, ustekinumab, natalizumab, vedolizumab), and tyrosine kinase inhibitors (imatinib, nilotinib, ibrutinib) |
||
− | *** HBsAg positive: prednisone <10 mg/day for ≥4 weeks |
||
− | *** HBsAg negative but HBcAb positive: prednisone >10-20 mg/day for ≥4 weeks, antracycline derivatives (doxorubicin and epirubicin) |
||
− | ** '''Low-risk''' (<1%) |
||
− | *** HBsAg positive, or HBsAg negative but HBcAb positive, plus traditional immunosuppressants (azathioprine, 6-MP, methotrexate) |
||
− | *** HBsAg negative or HBcAb positive, plus prednisone <10 mg/day for ≥4 weeks |
||
− | * Concern especially with chronic steroids and rituximab |
||
− | * Can have the following effects |
||
− | ** Asymptomatic HBV DNA and ALT |
||
− | ** Hepatic failure |
||
− | ** Death |
||
− | * If ≥7.5mg/d should be screened |
||
− | ** HBsAg +/- HBcAb if they're adding a second agent (rituximab, TNF-alpha inhibitors, or other) |
||
− | ** Refer to Hepatology or Infectious Diseases |
||
− | * Prophylaxis with lamivudine until 6 months after chemotherapy |
||
+ | *[https://doi.org/10.1002/hep.29800 Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance] |
||
− | == Further Reading == |
||
+ | *Hepatitis B virus genotypes: Global distribution and clinical importance. ''World J Gastroenterol''. 2014;20(18):5427–5434. doi: [https://doi.org/10.3748/wjg.v20.i18.5427 10.3748/wjg.v20.i18.5427] |
||
− | * [https://doi.org/10.1002/hep.29800 Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance] |
||
− | * Hepatitis B virus genotypes: Global distribution and clinical importance. ''World J Gastroenterol''. 2014;20(18):5427–5434. doi: [https://doi.org/10.3748/wjg.v20.i18.5427 10.3748/wjg.v20.i18.5427] |
||
[[Category:Hepadnaviridae]] |
[[Category:Hepadnaviridae]] |
Revision as of 13:55, 31 July 2020
Background
Microbiology
- Reverse-transcription double-stranded DNA (RT-dsDNA) virus
- Genotypes A through J vary in geographic distribution and clinical severity
Genotype | B | C | A | D | E-J |
---|---|---|---|---|---|
Clinical characteristics | |||||
Modes of transmission | Perinatal/vertical | Perinatal/vertical | Horizontal | Horizontal | Horizontal |
Tendency of chronicity | Lower | Higher | Higher | Lower | No data |
HBeAg positivity | Lower | Higher | Higher | Lower | No data |
HBeAg seroconversion | Earlier | Later | Earlier | Later | No data |
HBsAg seroclearance | More | Less | More | Less | No data |
Histological activity | Lower | Higher | Lower | Higher | No data |
Clinical outcomes | |||||
Response to interferon-α | Higher | Lower | Higher | Lower | Lower in G |
Response to NRTIs | No significant differences | No data | |||
Viroloical characteristics | |||||
Viral load | Lower | Higher | No data | ||
Frequency of PC A1896 mutation | Higher | Lower | Lower | Higher | No data |
Frequency of basal core promoter T1762/A1764 mutation | Lower | Higher | Higher | Lower | No data |
Frequency of preS deletion utation | Lower | Higher | No data |
Phases of Chronic Infection
- Phase 1: HBeAg + chronic infection (previously immune tolerant)
- Viral replication including HBeAg without evidence of immune response
- Phase 2: HBeAg + chronic hepatitis (previously immune active)
- Elevated liver enzymes and HBV DNA
- Phase 3: HBeAg – chronic infection (previously inactive carrier)
- HBeAg clears and liver enzymes normalize, but ongoing low-level viral replication
- Phase 4: HBeAg – chronic hepatitis (previously HBeAg-negative chronic hepatitis)
- Increasing viral load with fluctuating liver enzymes
- Phase 5: HBsAg negative
- HBsAb positive or negative, other studies return to normal
Clinical Manifestations
Acute
- 75% are asymptomatic
- Symptoms range from self-resolving jaundice to fulminant liver failure in about 5%
Chronic
- Chronic hepatitis B begins as e antigen positive, usually with very high levels of HBV DNA and necroinflammation.
- Four types of chronic hepatitis B
- Immunotolerant hepatitis B: HBV DNA levels (>20,000 IU/ml), HBeAg positive, with normal ALT
- Common after vertical transmission and can persist for years before progressing to another form
- HBeAg-positive immune-active chronic hepatitis B: HBsAg-positive, HBV DNA levels (>20,000 IU/ml), HBeAg positive, anti-HBe negative with elevated ALT
- HBeAg-negative immune-active chronic hepatitis B: HBsAg-positive, HBV DNA levels (<20,000 IU/ml), HBeAg negative, anti-HBe positive, with elevated ALT
- Results from anti-HBe seroconversion when a mutation decreases HBeAg expression
- Inactive hepatitis B (healthy carrier): HBsAg for > 6 months without any evidence of necroinflammation and HBV DNA levels are < 2,000 IU/m
- May still transmit it, but overall a better prognosis
- Immunotolerant hepatitis B: HBV DNA levels (>20,000 IU/ml), HBeAg positive, with normal ALT
- Hepatocellular carcinoma is a risk in chronic hepatitis B, but especially in certain populations including cirrhosis
- Polyarteritis nodosa
- Membranous nephropathy or membranoproliferative glomerulonephritis
- Sensorimotor neuropathy
- Sjogren syndrome
Investigations
Management
Acute
- Supportive care
Chronic
- HBsAg present ≥6 months
- HBV-DNA is variable
- Can be HBeAg positive or negative, with generally higher HBV DNA levels in HBeAg-positive patients
- ALT can be normal or elevated
- Liver boipsy shows chronic hepatitis and variable necroinflammation or fibrosis
Immune-active
- HBsAg present ≥6 months and HBeAg either positive or negative
- Intermittently or persistently elevated ALT and AST
Indications for treatment
- ALT ≥2x ULN or evidence of significant histologic disease, AND
- Elevated HBV DNA
- > 2000 IU/mL if HBeAg negative
- > 20,000 IU/mL if HBeAg positive
Immune-tolerant
- HBsAg present for ≥6 months and HBeAg positive
- HBV DNA typically over 1 million
- Normal or minimally-elevated ALT and AST
- That is, high viral load but normal ALT
Indications for treatment
- Adults >40 years, AND
- ALT rises above 2x ULN (i.e. becomes immune-active), OR
- Liver biopsy showing significant necroinflammation or fibrosis
Surveillance
- Monitor at 3 to 6 month intervals, more frequently as ALT levels rise, consider treatment if >2x ULN/
Treatment Regimens
- One of pegylated-interferon (48 weeks), tenofovir (until 12 months post-HBeAg conversion), or entecavir (until 12 months post-HBeAg conversion)
- Peg-IFN contraindicated in autoimmune disorders, uncontrolled psychiatric disease, cyptopenia, severe cardiac disease, uncontrolled seizures, and decompensated cirrhosis
- Peg-IFN preferred in lamivudine resistance
- Tenofovir is safe in pregnancy
- Duration depends on what stage is being treated
- HBeAg positive and HBV DNA >20,000 and ALT >2 ULN
- Peg-IFN for 48 weeks
- Tenofovir or entecavir for at least 12 months after HBeAg seroconversion (Ag to Ab)
- HBeAg negative and HBV DNA > 2000 and ALT >2x ULN (or biopsy shows necroinflammation or fibrosis, or non-invasive testing shows fibrosis)
- Peg-IGN for 1 year
- Tenofovir or entecavir for many years, possibly indefinitely
- HBeAg positive and HBV DNA >20,000 and ALT >2 ULN
- Continue HCC surveillance regardless of treatment
Inactive chronic hepatitis B
- Defined by HBeAg-negative, anti-HBeAb-positive, normal ALT, and HBV DNA <2000 IU/mL
- Monitor ALT q3mo for 1 year, then q6-12mo
- If ALT rises, check HBV-DNA and HBsAg for activity
HCC screening
- Screen if HBsAg-positive with cirrhosis, or HBsAg-positive at higher risk (Asian men >40yrs, black men >40yrs, Asian women >50yrs, family history, HDV coinfection)
- First-line is ultrasound every 6 months
- Second-line is AFP levels every 6 months
Prophylaxis in Immunosuppression
- Risk stratify based on type of immune suppression and serologic status
- High-risk (>10%):
- HBsAg positive, or HBsAg negative but HBcAb positive, plus B-cell depletion such as rituximab and ofatumumab
- HBsAg positive, plus anthracyclines (doxorubicin, epirubicin), prednisone >10-20 mg/day for ≥4 weeks
- Moderate-risk (1-10%)
- HBsAg positive, or HBsAg negative but HBcAb positive, plus TNF-α inhibitors (etanercept, adalimumab, certolizumab, certolizumab, infliximab), other cytokine or integrin inhibitors (abatacept, ustekinumab, natalizumab, vedolizumab), and tyrosine kinase inhibitors (imatinib, nilotinib, ibrutinib)
- HBsAg positive: prednisone <10 mg/day for ≥4 weeks
- HBsAg negative but HBcAb positive: prednisone >10-20 mg/day for ≥4 weeks, antracycline derivatives (doxorubicin and epirubicin)
- Low-risk (<1%)
- HBsAg positive, or HBsAg negative but HBcAb positive, plus traditional immunosuppressants (azathioprine, 6-MP, methotrexate)
- HBsAg negative or HBcAb positive, plus prednisone <10 mg/day for ≥4 weeks
- High-risk (>10%):
- Concern especially with chronic steroids and rituximab
- Can have the following effects
- Asymptomatic HBV DNA and ALT
- Hepatic failure
- Death
- If ≥7.5mg/d should be screened
- HBsAg +/- HBcAb if they're adding a second agent (rituximab, TNF-alpha inhibitors, or other)
- Refer to Hepatology or Infectious Diseases
- Prophylaxis with lamivudine until 6 months after chemotherapy
Further Reading
- Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance
- Hepatitis B virus genotypes: Global distribution and clinical importance. World J Gastroenterol. 2014;20(18):5427–5434. doi: 10.3748/wjg.v20.i18.5427
References
- ^ Mustafa Sunbul. Hepatitis B virus genotypes: Global distribution and clinical importance. World Journal of Gastroenterology. 2014;20(18):5427. doi:10.3748/wjg.v20.i18.5427.