Hepatitis

Characteristics
1. Hepatotropic (systemic infx primarily affect liver), RNA (Hep A & C) or DNA (Hep B) virus
2. Acute illness: Nausea, Anorexia, Fever, Malaise, Abd pain, jaundice or elevated liver enzymes
3. HBV and HCV can produce chronic infection

HAV HBV HCV

Main transmission Fecal-oral Blood, Sexual Blood
Perinatal transmission No Yes Yes
Most common RF Direct contact Born of infected mother Injection drug use
Chronic infection No Yes Yes
Course of infection Acute, then resolved Acute, then sometimes chronic Acute, then usually chronic
Treatment of Chronic infection N/A Yes, not curative Yes, curative
Protective immunity Yes Yes No
Vaccine available Yes Yes Yes

Hep A
1. Acute viral that replicated in liver, excreted in bile, shed in the stool; Incubation period of 28 days
2. Patient group affected is household or close personal contact to person. Fecal-oral, person to person, ingestion of contaminated food or
water
3. Recent HAV outbreaks in persons who use drugs, homeless among men who have sex with men
4. Symptoms
a. Children < 6 yo: asymptomatic
b. Jaundice, fever, fatigue, loss of appetite, diarrhea, joint pain; last < 2 months
5. Diagnosis
a. Either IgM anti-HAV in serum or HAV RNA in serum or stool
6. Treatment – Supportive care
7. Prevention
a. Vaccination – safe in pregnancy (single and combo products)
b. If exposed, post-exposure prophylaxis should be given within 2 weeks
Hep B
1. Virus enters the liver through bloodstream and replicates in the liver
2. Incubation period of 90 days to onset of jaundice and 60 days to onset of abnormal ALTs
3. Symptoms
a. New infected or < 5 yo: asymptomatic
b. Acute symptoms same as Hep A, but no diarrhea 4. Diagnosis

HBsAg Marker of presence of ongoing infection

Anti-HBs Marker of immunity
Total anti-HBc Marker of Exposure
IgM anti-HBc Marker of acute or recently acquired HVC infection
HBeAg Marker of high infectivity in acute or chronic HBV infection
Anti-HBe Marker of loss of viral replication and lower levels of virus
5. Management
a. Acute – supportive care
b. Chronic: therapy goals are sustained suppression, remission of liver disease, prevent cirrhosis, hepatic failure and HCC
c. Phases
i. Patients with…
i HbeAg- (e-) and/or cirrhosis: indefinite therapy
ii HbeAg+ (e+): treatment for at least 12 months OR until HBsAg loss
e+ Immune-tolerant e- Inactive (carrier)
Normal ALT, Elevated HBV DNA Monitor Normal ALT, Low or undetectable Monitor
HBV DNA
e+ Immune-active Treat if ALT > 2xULN, HBV e- Immune reactivation Treat indefinitely if ALT > 2xULN,
Elevated ALT, Elevated HBV DNA DNA > 20,000 IU/mL Elevated ALT, Elevated HBV DNA HBV DNA > 2,000
IU/mL
Otherwise, Monitor
Otherwise, Monitor
e+ Cirrhosis Treat indefinitely if HBV DNA e- Cirrhosis Treat indefinitely if
Elevated ALT, Elevated HBV > 2,000 IU/mL Elevated ALT, Elevated HBV DNA, HBV DNA > 2,000 IU/mL
DNA, Low albumin/plts Low albumin/plts
Otherwise, Monitor Otherwise, Monitor
 Hepatitis
d. First line = Nucleoside analogs
Peg-IFN-2a 180 ug SC weekly for 48 weeks Flu-like symptoms, fatigue, cytopenia, anorexia
Entecavir 0.5-1 mg PO QD Lactic acidosis
Tenofovir Disoproxil Fumarate 300 mg PO QD Nephropathy, Fanconi syndrome, Lactic acidosis
Tenofovir Alafenamide 25 mg PO QD Lactic acidosis
i. Monitoring: immune tolerant ALT Q3-6 months, eAg Q6-12 months or e- inactive patients ALT Q6-12 months
ii. HIV coinfection: three-drug regimen initiated to decrease resistant (Truvada, Descovy)
6. Prevention
a. Vaccination, single and combo products
Hep C
1. Differentiated into 7 genotypes (1-7) and then subtypes [1a, 1b most common in US, followed by 2 and 3]
2. Average times from exposure to symptom onset is 4-12 weeks
3. Symptoms
a. 2/3 of patients are asymptomatic for acute infection, 50% will develop chronic infection
b. Chronic infection: fatigue, depression, nausea, poor appetite, extrahepatic symptoms
4. Diagnosis
a. HCV RNA detectable 1-2 weeks after exposure
5. Management
a. Goal: HCV RNA undetectable 12 weeks after cessation or treatment, prevent complications and death b. Drug classes:
i. NS3/4a protease inhibitors (“-previr”)
1. Potent 3A4 inhibitors, low barrier to resistance
ii. NS5B polymerase inhibitors (“-buvir”)
1. higher barrier of resistance
iii. NS5A replication complex inhibitors (“-asvir”)
1. low barrier of resistance, but very potent

NS3/4a protease inhibitors Grazoprevir (GRZ)
Glecaprevir (GLE)
Voxilaprevir (VOX)
NS5B polymerase Sofosbuvir (SOF)
inhibitors
NS5A replication complex Ledipasvir (LDV)
inhibitors Elbasvir (ELB)
Velpatasvir (VEL)
Pibrentasvir (PIB)
ALT elevations (D/C >5xULN); CI Child-Pugh class B or C
HA, Fatigue; Not recommended in Child-Pugh class B, CI in class C
HA, GI issues, Fatigue; Not recommended in Child-Pugh class B or C
HA, Fatigue; DI with Amiodarone (bradycardia); No hepatic dosing adjustment
HA, Fatigue; pH dependent, No hepatic dosing adjustment
Check for NS5A mutation prior use
Check for NS5A mutation prior use
HA, Fatigue; Not recommended in Child-Pugh class B, CI in class C

AASLD/IDSA Recommended and Alternative Treatment Recommendations (as of 10/24/22)

HCV GT ELB/GRZ PIB/GLE* VEL/SOF/VOX* LDV/SOF VEL/SOF
Without cirrhosis

1a A P P P
1b P P P P
2 P P
3 P P
With compensated cirrhosis

1a A P P P
1b P P P P
2 P P
3 P Y93H + P Y93H +
Adult Dosing

50 mg/100 mg PO Q 120 mg/300 mg PO QD 100 mg/400 mg/100 90 mg/400 mg PO QD 100 mg/400 mg PO QD

x 12 weeks x 8 weeks mg PO QD x 12 weeks x 8-12 weeks x 12 weeks
* Must take with food, P – Preferred, A – Alternative
6. Prevention
a. Counsel infected patients how to avoid transmission/reinfection, post-exposure prophylaxis for HC personnel
References:
1. Nelson NP, Weng MK, Hofmeister MG, et al. Prevention of hepatitis A virus infection in the United States: recommendations of the Advisory Committee on
Immunization Practices, 2020. MMWR Recomm Rep 2020;69(No. RR-5):1-38.
2. Terrault, NA, Lok, AS.F., McMahon, BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance.
Hepatology 67(4):p1560-1599, April 2018. doi.10.1002/hep.29800
3. AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Accessed April 09, 2023.