Hepatitis B Virus - Management Flashcards
List the risk factors that should be assess during history taking in chronic HBV infection patients
1) FHx HBV (vertical transmission) and liver disease
2) Hx blood transfusions before 1992 (HCV)
3) Hx needle stick injury (HCV, HIV)
4) Sexual Hx (partners, practices, protection, past Hx STI, pregnancy plan)
5) Alcohol use
List investigations to be order in chronic HBV infection patients
1) CBC for PLT (look for coagulopathy)
2) LFT for AST/ALT (assess active liver disease)
3) RFT for elevated Cr (look for hepatorenal syndrome)
4) PT for coagulopathy
5) HBeAg for replication and infectivity
6) HBV DNA for replication and infectivity
7) anti-HBeAg for inactive phase of chronic HBV infection
8) Fibroscan to assess liver stiffness as surrogate marker for degree of cirrhosis
9) OGD to screen for esophageal varices as 1/3 die during 1st esophageal variceal rupture
List investigations to screen for other causes of liver disease
1) HCV –> anti-HCV
2) HDV –> anti-HDV
3) HAV –> anti-HAV
4) HIV –> anti-HIV
5) Hemochromatosis –> elevated iron + total iron binding capacity (TIBC) = transferrin saturation >50%, ferritin >200ng/mL
6) Autoimmune hepatitis (both soluble liver antigen SLA)
1. Type 1: anti-smooth muscle, anti-actin, ANA, ANCA,
2. Type 2: antibody to liver/kidney microsomes ALKM-1
Outline the criteria and rationale for liver biopsy in chronic HBV hepatitis
1) HBsAg +ve >6m
2) HBV DNA >2000
3) AST/ALT >2x normal
Necessary as patients w/histologically active or advanced liver disease may benefit from treatment
Outline the advantages of Fibroscan
1) USG based elastography for assessment of mean hepatic tissue stiffness
2) quick, inexpensive, reproducible
3) painless, non-invasive
4) samples a large area of hepatic tissue
Outline the disadvantages of Fibroscan
1) Liver stiffness influenced by inflammation as well as fibrosis
2) Thus assessment of liver stiffness as surrogate marker for fibrosis may overestimate cirrhosis due to inflammatory contribution
Outline the mechanism of Fibroscan
Shear Wave Elastography (SWE)
1) Mechanically excite hepatic parenchyma to monitor for tissue response
2) Shear wave propagate faster in fibrotic tissue
Strain Elastography
1) Compress the liver
2) Fibrous tissue displaces less and strains less than normal tissue
List the major complications of HBV infection
Note that the presence of 1 complication can already be considered cirrhotic decompensation
1) Cirrhosis (2% annual incidence w/chronic HBV)
1. Portal HT
1, Portal hypertensive gastropathy
2. Esophageal variceal hemorrhage
3. Ascites
1, Hepatic hydrothorax
4. Spontaneous bacterial peritonitis
5. Hepatorenal syndrome
6. Hepatopulmonary syndrome
7. Hepatic encephalopathy
2) Hepatocellular carcinoma (5% annual ischemia in patients w/HBV related cirrhosis)
- incidence higher w/higher HBV DNA load >2000
- also higher w/HBeAg +ve or HBsAg +ve
3) Renal Diseases
1. Membranous GN
2. IgA nephropathy
List the triad in hepatopulmonary syndrome
1) Liver disease
2) Impaired oxygenation
3) Intrapulmonary vascular dilations (IPVDs)
Outline the principles of management in chronic HBV infection patients
1) Reduce progression of chronic liver disease
2) Reduce transmission to others
3) Prevent complications of chronic HBV infection such as cirrhosis and HCC
List the parameters to consider when deciding the management of chronic HBV infection patients
1) HBeAg status
2) ALT elevation from normal
3) HBV DNA for HBeAg -ve cases
State the management for
1) HBsAg +ve
2) HBeAg +ve
3) ALT >2x normal
In late immune clearance phase
1) Q1-3m FU for ALT, HBeAg
2) Tx if persistent after 1-3m
3) Immediate Tx if jaundice OR decompensation
State the management for
1) HBsAg +ve
2) HBeAg +ve
3) ALT 1-2x normal
In early immune clearance phase
1) Q3m FU for ALT
2) Q6m FU for HBeAg
3) Liver biopsy if persistent >3m or >40y/o
4) Tx as needed
State the management for
1) HBsAg +ve
2) HBeAg +ve
3) ALT less than 1x normal
In immune tolerance phase
1) Q3-6m FU for ALT
2) Q6-12m FU for HBe Ag
State the management for
1) HBsAg +ve
2) HBeAg -ve
3) ALT >2x normal
4) HBV DNA >20 000
In reactivation phase
1) Tx if persistent >3m
State the management for
1) HBsAg +ve
2) HBeAg -ve
3) ALT 1-2x normal
4) HBV DNA >2000 - 20 000
In reactivation phase
1) Q3m FU for ALT and HBV DNA
2) Liver biopsy if persistent >3m
State the management for
1) HBsAg +ve
2) HBeAg -ve
3) ALT less than 1x normal
4) HBV DNA less than 2000
In inactive carrier phase
1) Q3m FU for ALT 3x normal
2) After ALT 3x normal, Q6m FU for ALT
State the treatment for
1) HBeAg +ve
2) HBV DNA >20 000
3) ALT less than 2x normal
In immune tolerance phase
1) Observe and treat only when ALT elevates
2) Liver biopsy if >40y/o, FHx HCC 3m
3) Tx indicated if
1. HBV DNA >2000
2. Biopsy shows moderate/severe inflammation + fibrosis
State the treatment for
1) HBeAg +ve
2) HBV DNA >20 000
3) ALT >2x normal
In immune clearance phase
1) Observe Q3-6m for spontaneous e-seroconversion
2) Immediate Tx if jaundice or decompensation
3) Biopsy before treatment if no e-seroconversion
4) Tx endpoint = e-seroconversion
5) Use IFNα/pegIFNα, LAM, ADV, ETV, TDF or LdT
State the treatment for
1) HBeAg -ve
2) HBV DNA >2000
3) ALT >2x normal
In reactivation phase or immune clearance phase
1) Tx w/IFNα/pegIFNα, LAM, ADV, ETV, TDF or LdT
2) Tx endpoint not defined
State the treatment for
1) HBeAg -ve
2) HBV DNA >2000
3) ALT 1-2x normal
In reactivation phase or immune clearance phase
1) Liver biopsy to assess liver pathology
2) Tx if moderate/severe inflammation + fibrosis
State the treatment for
1) HBeAg -ve
2) HBV DNA ≤2000
3) ALT normal
In inactive phase
1) Observe
2) Monitor for rise in HBV DNA >2000 >3m
3) Monitor for rise in ALT >2x normal >3m
State indications for initiating antiviral therapy in HBeAg+ve patients
1) HBV DNA >20 000 + ALT >2x normal
2) Compensated cirrhosis + HBV DNA >2000
3) Decompensated cirrhosis + detectable HBV DNA
4) Recurrent abortive immune clearance
5) >40y/o + HBeAg +ve + HBV DNA >2000
6) Icteric hepatitis flares
7) Advanced histologic findings
- moderate/severe inflammation
- bridging fibrosis/cirrhosis
Outline the outcomes of antiviral therapy in HBeAg +ve patients
1) HBV replication suppression
2) ALT normalization
3) Low chance of e-seroconversion
State indications for initiating antiviral therapy in HBeAg-ve patients
1) Immediately once HBeAg -ve w/HBV DNA >2000 and ALT >2x normal
2) Immediate as sustained remission is rare in the absence of antiviral treatment
3) FU closely to distinguish HBeAg negative chronic hepatitis versus inactive carrier state
List the antiviral options in chronic HBV hepatitis
1) Nucleoside analogues
1st gen: lamivudine
2nd gen: telbivudine
3rd gen: entecavir
2) Nucleotide analgoues
1st gen: adefovir
2nd gen: tenofovir
3) Interferons
Standard interferon
Pegylated interferon
Outline clinically significant points regarding lamivudine monotherapy for chronic HBV infection
1) PO 100mg/d (52w)
- dose reduction necessary w/CrCl continue until 12m post e-seroconversion to reduce relapse
- in HBeAg -ve –> unclear; some have sustained response but some become lamivudine resistant especially >1y as lamivudine resistant mutants are selected for
2) Prone to resistance especially by YMDD mutants
3) Cheap drug but subsequent rescue therapy may outweigh lower upfront cost
4) 70% lamivudine resistance in 5y
5) 50% lamivudine e-seroconversion in 5y
6) Only for cases with
1. Short anticipated treatment duration
2. Low pretreatment HBV DNA
7) Salvage/rescue Tx requires nucleotide analogues adefovir and tenofovir
8) Entecavir is NOT used as rescue Tx in lamivudine resistant cases as YMDD (rtM204V/I) mutation diminishes the barrier to entecavir resistance; 2nd barrier is rtL180M mutation found upstream to YMDD
Outline clinically significant points regarding entecavir monotherapy for chronic HBV infection
1) PO 0.5mg/d (52w)
- dose reduction necessary w/CrCl less than 50mL/min
- in HBeAg +ve –> continue until 12m post e-seroconversion to reduce relapse
- in HBeAg -ve –> continue until undetectable HBV DNA and HBsAg measured at 2 time points >6m
- in cirrhosis –> continue indefinitely
2) 1% entecavir resistance in 5y for nucleoside naive
3) 50% entecavir resistance in 5y for previous lamivudine
Outline clinically significant points regarding telbivudine monotherapy for chronic HBV infection
1) More potent antiviral than lamivudine and adefovir
2) Selects for same lamivudine resistant mutants
3) More expensive than lamivudine
4) Limited role as primary monotherapy
5) Risk of peripheral neuropathy and myopathy
Outline clinically significant points regarding adefovir monotherapy for chronic HBV infection
1) PO 10mg/d (48w)
- induces creatinine increase of ≥0.5 mg/dL 20% by 48w i.e. risk of nephrotoxicity
- in HBeAg +ve –> continue until 12m post e-seroconversion to reduce relapse
- in HBeAg -ve –> at lesast 4-5y to suppress HBV DNA
2) Similar effectiveness as lamivudine
3) Less effective than telbivudine, entecavir, tenofovir
4) 29% adefovir resistance in 5y
Outline clinically significant points regarding tenofovir monotherapy for chronic HBV infection
1) 300mg/d
- dose reduction necessary w/CrCl less than 50mL/min
- less nephrotoxicity compared to adefovir
- in HBeAg+ve in immune tolerance –> do not treat
- in HBeAg+ve in immune clearance –> treat till….?
2) More effective than lamivudine or adefovir
3) Similar effectiveness as telbivudine, entecavir, tenofovir
Look up rates of resistance in 1y and 5y for each drug
Look up rates of seroconversion in 1y and 5y for each
Lamivudine 70% in 5y Entecavir 1% in 5y for nucleoside naive Entecavir 50% in 5y for lamivudine resistant Adefovir 29% in 5y Tenofovir 0% in 5y
Outline clinically significant points regarding interferon monotherapy for chronic HBV infection
1) PEG-IFN2a 180mcg/w (48w)
- only treat if ALT ≥2x normal
- unresponsive –> use antivirals
- responsive –> transient –> use antivirals
- responsive –> sustained –> monitor HBeAg, HBV DNA, ALT
If standard IFNa use either regimen for 16-32w
- 5 million units (MU) daily
- 10 million units 3x a week
Advantages of interferon versus antivirals
1) Finite duration of treatment
2) Absence of selecting resistant mutants
3) More durable response
Disadvantages of interferon versus antivirals
1) Interferon side effects are troubling
2) Contraindicated in decompensated cases
Outline the single most important parameter to assess if antiviral treatment is indicated in HBV cases
elevated ALT
If there is no elevated ALT, interferon or antiviral therapy need not be administered
Outline the rationale for no treatment in HBeAg+ve patients with normal ALT
Antiviral treatment in this setting does not increase rates of e-seroconversion compared to no treatment
Only at ALT ≥2x normal will antivirals confer such benefit
Outline the indication for antiviral therapy in HBeAg-ve patients
1) Persistent/intermittent ALT ≥2x normal
2) Biopsy shows moderate/severe inflammation
3) Biopsy shows bridging fibrosis/cirrhosis
List the preference of HBV antivirals in renal impairment
1) Entecavir
2) Tenofovir
3) Adefovir
State the dose for standard and pegylated interferon in HBV –> which HBV genotype is more susceptible to e and s-seroconversion w/interferon treatment
Standard: 5MU daily or 10MU 3x/week
- HBeAg+ve –> 16-32w
- HBeAg-ve –> 12-24m
PEG-IFN2a: 180mcg weekly for 48w
HBV genotype A more likelty to achieve e and s-seroconversion w/interferon therapy
State the dose for lamivudine in HBV
100mg daily
dose adjust for CrCl less than 50mL/min
State the dose for adefovir in HBV
10mg daily
dose adjust for CrCl less than 50mL/min
State the dose for entecavir in HBV
0.5mg daily for nucleoside naive
1mg daily for lamivudine resistance/decompensated liver
State the dose for telbivudine in HBV
600mg daily
State the dose for tenofovir in HBV
300mg daily
dose adjust for CrCl less than 50mL/min
Summarize the doses of interferons and antivirals in HBV
1) Standard IFN = 5MU daily OR 10MU 3x/week
- 16-32w for HBeAg+ve
- 12-24m for HBeAg-ve
2) PEG-IFN2a = 180mcg for 48w
3) Lamivudine = 100mg daily
4) Telbivudine = 600mg daily
5) Entecavir = 0.5mg daily in naive; 1mg daily in lamivudine resistant
6) Adefovir = 10mg daily
7) Tenofovir = 300mg daily
Outline the treatment endpoint of HBeAg+ve chronic hepatitis
1) e-seroconversion confirmed by 2 tests 2m apart
2) HBV DNA undetectable
3) Continue treatment at least 12m after e-seroconversion to reduce rate of relapse
Outline the treatment endpoint of HBeAg-ve chronic hepatitis
1) s-seroconversion confirmed by 2 test 2m apart
- only 5% lose HBs-Ag after 5y continued therapy
Outline the treatment endpoint of compensated cirrhosis
1) Prevent hepatic failure
2) Prevent HCC
3) Give lifelong treatment
Outline the treatment endpoint of decompensated cirrhosis
1) Lifelong treatment
Outline the treatment of acute HBV infection
1) Antivirals not routinely indicated as only 1% develop hepatic failure from HBV infection
2) Indications for antivirals in acute HBV hepatitis
1. Coagulopathy (INR>1.5)
2. Marked jaundice (bilirubin>10mg/dL)
3. Protracted course (>4w)
State the management for this patient.
25y/M Asian HBsAg +ve HBeAg +ve HBV DNA 140 million IU/mL ALT 100 (40 is normal)
1) HBeAg+ve and HBV DNA elevated indicative of replicative phase
2) Elevated ALT 2x normal alongside above findings suggest immune clearance phase of HBV infection
3) If no spontaneous e-seroconversion start antiviral therapy
4) 1st line: entecavir, tenofovir
State the management for this patient.
20y/F HBsAg +ve HBeAg -ve HBV DNA 250 000 IU/mL ALT 60 (normal 40) Biopsy: mild portal inflammation + no fibrosis
1) HBeAg -ve chronic hepatitis but uncommon for patients to be in this phase of chronic HBV infection at such a young age
2) Likely to have precore HBV variant
3) These variants have a low rate of sustained response to approved antiviral therapy
4) As the patient is young and only has mild histological changes observation is acceptable –> FU Q3-6m
5) Treat if ALT persistently elevated >3m
State the management for this patient.
22y/M HBsAg +ve HBeAg +ve anti-HBe -ve HBV DNA 14 million IU/mL ALT 20-30 (normal 40) Biopsy normal
1) In replicative immune tolerance phase
2) Treatment at this point unnecessary and would not be beneficial
3) No significant inflammation on liver biopsy
4) ALT normal (predicts low probability of e-seroconversion if treated w/antivirals) –> less than 5% after 1y treatment
State the management for this patient.
24y/M who wants to be a surgeon HBsAg +ve HBeAg +ve anti-HBe -ve HBV DNA 80 million IU/mL ALT 45 (normal 40) Biopsy: macrovesicular fat, no portal fibrosis
1) Healthcare providers performing invasive exposure prone procedures require monitoring by an expert panel
2) HBV infected healthcare providers can only conduct exposure prone procedures if low (less than 10-20IU/mL) or undetectable HBV viral load is documented every 6m
3) If HBV DNA levels rise above 20IU/mL the provider must abstain from exposure-prone procedures until subsequent testing alongside changing drug therapy
4) Unlikely to respond to antiviral treatment at the moment and high HBV DNA load –> cannot allow this patient to do exposure prone procedures
State the management for this patient.
50y/M Asian HBsAg +ve HBeAg -ve ALT 75 (normal 40) Biopsy: moderate hepatitis w/bridging fibrosis
1) HBeAg -ve chronic hepatitis in immune clearance or reactivation phase
2) In view of moderate hepatitis w/bridging fibrosis and elevated ALT 1-2x normal antiviral therapy is indicated
3) Start entecavir or tenofovir
4) Prevents progression to cirrhosis, hepatic decompensation, and hepatocellular carcinoma
State the management for this patient.
75y/F HBsAg +ve HBeAg +ve HBV DNA 1600 IU/mL ALT 50 (normal 40) Hx ascites Hx esophageal varices Not for liver transplant
1) In view of old age and decompensated liver disease antiviral treatment is indicated
2) Entecavir better than tenofovir as less nephrotoxicity as these patients may be at risk for renal failure
State the management for this patient.
40y/M; pretreatment ALT 129 moderate inflammation
HBeAg +ve despite 1y lamivudine
HBV DNA undetectable now
1) Continuation of treatment
Advantage –> potential for e-seroconversion
Disadvantage –> breeding lamivudine resistant mutants
- YMDD mutants present in 15-30% at 1y; 70% at 4y
2) Switch to tenofovir or entecavir; tenofovir better
- tenofovir better as less prone to inducing nucleoside resistant HBV than entecavir
State the management for this patient.
56y/F
HBeAg +ve
Biopsy: early cirrhosis
Lamivudine suppressed HBV DNA to undetectable levels and normalized ALT
However, at 18m she developed flare in ALT w/increasing HBV DNA; remains HBeAg +ve
1) Likely developed breakthrough infection w/lamivudine resistant mutant –> confirm resistance
2) Check drug compliance
3) Switch to tenofovir NOT entecavir
State the management for this patient.
68y/M Hospitalized for low grade fever, abd pain, anorexia, jaundice HBsAg +ve anti-HBc +ve IgM HBV DNA 300 000IU/mL ALT 2000 (normal 40) Total bilirubin 8.0mg/dL INR 1.5 No other causes of liver disease Not known to be HBV carrier BIsexual
1) Bisexuality is a risk factor for HBV infection
2) Seems like a case of acute HBV
3) Can also be reactivation of chronic HBV as anti-HBc can persist for up to 2y or be present in exacerbations of chronic hepatitis B
4) Chronic exacerbation more likely if
1. Cirrhosis at diagnosis
2. FHx HBV
3. Hx liver disease
5) Acute HBV more likely if
1. Known recent exposure
2. No known Hx liver disease
6) Antivirals not routinely indicated for acute HBV unless
1. Coagulopathy develops (INR >1.5)
2. Marked jaundice (bilirubin >10mg/dL)
3. Protracted course (>4w from onset)
Outline indications for antiviral therapy in HBV
1) No cirrhosis + HBV DNA >20 000IU/mL + ALT >2x ULN
2) Compensated cirrhosis + HBV DNA >2000IU/mL regardless of ALT
3) Decompensated cirrhosis + w/detectable HBV DNA regardless of ALT
4) Prevention of HBV reactivation during chemotherapy or immunosuppression
Outline the role of interferon in chronic HBV ladies w/fertility wish
1) Nucleosides and nucleotides not recommended in pregnancy
2) For patients in immune clearance phase PEG-IFNα2a can be used to induce viral suppression
3) PEG-IFNα2a has advantage of finite 48w treatment
4) Given as weekly SC injection of 180mcg PEG-IFNα2a
5) Allows HBeAg +ve laides to achieve viral suppression and be drug free to become pregnant
