hepatitis a to e… · hepatitis a oseen most commonly in developing countries but not exclusively...

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Hepatitis A to EAASLD Transplant Hepatology Board Review Course 2020

Janice Jou, MD MHSAssociate Professor

Oregon Health and Science University VA Portland Healthcare System

o Hepatitis A and Hepatitis Eo Hepatitis Co Hepatitis B and Hepatitis D

© 2020 AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASES WWW.AASLD.ORG 2

Outline

Hepatitis A• Acute infection, fecal oral

transmission• Previously declining incidence by

95% between 1995-2011• However, now increasing in 2016-

2018 by 294%• ~15,000 cases reported• Primary risks: persons who report

drug use or homelessness• MSM• Contaminated food

© 2020 AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASES WWW.AASLD.ORG 3MMWR, May 10, 2019, 68(18): 413-415

o Typical Presentation: jaundice, malaise, hepatomegaly, hepatitis with AST/ALT >1000• Symptoms typically resolve within 2 months• Jaundice peaks within the first few weeks

o Fulminant Hepatitis A• Rare cause of acute liver failure (ALF), <1% of reported cases• If ALF occurs, prognosis is poor• US ALF Study group (n=29)

• 55% spontaneously recovered• 31% liver transplant, 14% died


Hepatitis A

Taylor RM et al. Hepatology 2006, 44(6):1397-99

o Other clinical presentations• Cholestatic

• Itching, ↑↑↑ Bilirubin, prolonged course• Supportive care

• Prolonged • Relapsing

• IgM still detectable when liver tests increase after initial downtrend


Hepatitis A

o Seen most commonly in developing countries but not exclusively

o 4 genotypes• Genotypes 1 and 2 Fecal oral• Genotypes 3 and 4 Zoonotic transmission from animal reservoirs

o Commonly causes acute hepatitis with very high AST/ALTo Can present with neurologic symptoms: Guillain-Barre, Bell’s

palsy, acute meningoencephalitis


Hepatitis E

Davern TJ et al. Gastroenterology, 141:1665-1672

Hepatitis Eo HEV reported to be misdiagnosed as DILIo High mortality rates for patients with chronic liver disease/cirrhosis

• Pork consumption• Acute liver failure

o Pregnant women• Genotypes 1 and 2• Mortality 20-25% in third trimester


Davern TJ et al. Gastroenterology, 141:1665-1672

o Difficult to diagnoseo Accuracy of antibody and RNA

tests variableo Symptoms typically present 4

weeks after post infectiono HEV RNA undetectable about

3 weeks after symptom onset o Virus shed in stool for 5 weeks

after symptom onset


Hepatitis E

Kamar N et al. Lancet 2012


Kamar N et al. Clin Micro Rev 2014, 27(1):116-128

o Patients with detectable HEV RNA after 6 monthso Occurs predominantly with genotype 3 (zoonotic

transmission)o Populations: HIV, immunocompromised patients

(including liver disease, post transplant)o Treatment:

• Reduce immunosuppression in transplant patients• Ribavirin: 12 week course, Dose 600-1000

• Leads to viral clearance in a few weeks© 2020 AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASES

WWW.AASLD.ORG 10

Chronic Hepatitis E

Kamar N et al. Clin Micro Rev 2014, 27(1):116-128



Outline

o March 2020: USPSTF recommends screening for hepatitis C virus (HCV) infection in adults aged 18 to 79 years Grade B

o Acute HCV- treatment recommended once viremia identified

o Recommend reviewing www.hcvguidelines.org• Last update 2019


Hepatitis C

http://www.hcvguidelines.org/


www.hcvguidelines.org

© 2020 AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASES WWW.AASLD.ORG 14www.hcvguidelines.org



HCV Treatment Experienced

o https://www.hcvguidelines.org/sites/default/files/slides/HCVGuidance_400_Treatment-Experienced_12-2019.pptx


o Decompensated cirrhosis• MELD>20 may not benefit from treatment and may benefit more

from LT • Concern for further decompensation with use of protease inhibitor

containing regimens- do not use o HCC/HCV

• SVR 91% cirrhosis without HCC vs. 74% cirrhosis with HCC• Treat HCC first, then treat HCV

o Renal impairment/Renal Transplant• No specific dose adjustments• Sofosbuvir: renal clearance


HCV Treatment: Other Special Populations



© 2020 AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASES WWW.AASLD.ORG 17Cotter TG et al. Liver Transplantation 25(4):598-609

HCV pos and HCV neg recipient outcomes equivalent in DAA Era

© 2020 AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASES WWW.AASLD.ORG 18www.hcvguidelines.org


Organ Transplantation From HCV ViremicDonors to HCV Negative Recipients

o Shortened courses of HCV treatment should not be considered in liver transplant of HCV+ donor to HCV- recipient



© 2020 AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASES WWW.AASLD.ORG

20www.hcvguidelines.org

*Many prefer SOF/VEL due to favorable drug-drug interaction profile



Fibrosing Cholestatic Hepatitis o Rare, first described in HBVo Mainly seen in HCV post solid

organ transplanto Histology: ductular proliferation

(A), canalicular cholestasis (C), hepatocyte swelling (D), and sinusoidal/pericellular fibrosis (C)

o Elevated Alk Phos, TBilio Rapidly progressive, associated

with graft failure and deatho DAA therapy has been reported to

reverse process in some cases© 2020 AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASES

WWW.AASLD.ORG 21Verna EC et al. Liver Transplantation 19:78-88



Outline

© 2020 AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASES WWW.AASLD.ORG 23Hepatology, Volume: 67, Issue: 4, Pages: 1560-1599, First published: 05 February 2018, DOI: (10.1002/hep.29800)

HBV: Who to treat, HBeAg pos


HBV: Who to treat, HBeAg neg

Hepatology, Volume: 67, Issue: 4, Pages: 1560-1599, First published: 05 February 2018, DOI: (10.1002/hep.29800)

Treatment of HBVo Preferred regimens in HBV

• Entecavir, TDF, and TAFo Treatment of HBV in cirrhosis

• Treatment of HBV indicated in all patients with cirrhosis regardless of ALT or HBV DNA

• Lactic acidosis rare but serious side effect of NA/s• Need to closely monitor patients with decompensated cirrhosis


Terrault N et al. AASLD Guidance for HBV, 2018

Acute HBVo Benefit of treating acute HBV with NA’s unclearo Risks of treatment are low, thus antiviral treatment

recommended in severe acute HBV (bilirubin >3 mg/dL or direct bilirubin >1.5 mg/dL, INR>1.5, encephalopathy, or ascites

o Entecavir, TDF, or TAF preferred• Treatment should be continued until HBsAg clearance is confirmed or

indefinitely in those who undergo liver transplantation• Peg-IFN is contraindicated



HBV/HIV Co-Infectiono All patients with HBV/HIV coinfection should initiate ARVT,

regardless of CD4 count. • Regimen should be TDF or TAF plus lamivudine or emtricitabine.

o Patients who are already receiving effective ARVT that does not include a drug with antiviral activity against HBV should have treatment changed to include TDF or TAF with emtricitabine or lamivudine. Alternatively, entecavir is reasonable if patients are receiving a fully suppressive ARVT.

o If ARVT regimens are changed, care should be taken to ensure that a drug active against HBV is part of the regimen




RISK OF HBV REACTIVATION HBsAg +, HBcAb +

HBsAg neg, HBcAb +

Anti-CD 20 (rituximab, ofatumumab, Obinutuzumab) VERY HIGH (>20% risk)

MODERATE(1-10%)

Hematopoietic stem cell transplantation VERY HIGH MODERATEHigh dose corticosteroids (>20mg for 4 weeks) HIGH (11-20% risk) Low

Other Cytokine Inhibitors (e.g. anti-CD52) HIGH Low

Combination Cytotoxic Chemo withoutcorticosteroids (cyclophosphamide, adriamycin, vincristine)

MODERATE(1-10% risk)

Very low risk

Anti-TNF inhibitors MODERATE Very low riskAnti-rejection therapy for solid organ transplant MODERATE Very low riskMethotrexate, Azathioprine, 6-MP Low (<1% risk) Very low risk

Modified from Di Bisceglie AM et al. Hepatology 2014

HBV reactivation

HBV reactivationo Very high risk, high risk, and moderate risk of HBV

reactivation should start prophylaxis• Entecavir, TDF, or TAF preferred • Start as soon as possible before or at the latest simultaneously with

immunosuppressive therapy. • Continue prophylaxis during immunosuppressive therapy and at least

6 months after • Monitor at least 12 months after for patients receiving anti-CD20 therapies

o Low/Very low risk of HBV reactivation can be monitored• Check HBV-DNA levels q1-3 months while on treatment• Monitor for up to 12 months after cessation of immunosuppressive

therapy© 2020 AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASES

WWW.AASLD.ORG 29Terrault N et al. AASLD Guidance for HBV, 2018


Monitor ALT at baseline, end of treatment, and at

follow up

Modified from Lieber SR and Fried MW. Clin Liv Dis 2017Terrault N et al. AASLD Guidance for HBV, 2018

HBV Reactivation with HCV DAA Treatment

Check HBV DNA q4-8 weeks on treatment and 3

months post treatment if

otherwise does not meet AASLD

criteria for treatment

HBV in Liver Transplant Recipientso HBsAg pos recipients

• Reinfection rates now <10% with NA’s• HBsAg-positive receiving LT should receive NA’s lifelong

• Effectively prevents recurrent HBV disease• NA’s should be used with or without HBIG• Entecavir, TDF, and TAF preferred• HBIG monotherapy should not be used

• Combination antiviral therapy and HBIG reserved for groups at highest risk of progression: HDV or HIV coinfected patients

o Anti-HBc–positive donor graft• Long term NA recommended for prevention of viral reactivation• Entecavir, TDF, and TAF preferred



Hepatitis D


o In Western countries, under recognized• Risk factors for HDV à screen for HDV• <5% of chronic HBV

o HDV can replicate independently but uses HBV envelope protein to infect cells (assembly, secretion)

o HDV IgM/IgG, HDV RNAo Co-infection biphasic rise in liver tests

(initial rise followed by another rise several weeks later)

o Superinfection- acute hepatitis that can progress to liver failure Terrault N et al. AASLD Guidance for HBV, 2018

Chronic HDVo HBV viral loads low/suppressed in patients with HDVo Treatment:

• First, treat HBV • Peg-IFN-α for 12 months recommended in AASLD guidelines, but not

particularly well tolerated or effective

o HDV Post LT• Goal is to prevent HBV from recurring• HDV can recur by itself without HBV post LT, not particularly harmful

to graft


Roche B et al. Sem Liver Dis 2012Terrault N et al. AASLD Guidance for HBV, 2018

o Thank you and good luck!


hepatitis a to e… · hepatitis a oseen most commonly in developing countries but not exclusively...

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