Pocket Medicine: The Massachusetts General Hospital Handbook of Internal Medicine (46 page)

• Prevention: vaccinate all infants & children and at-risk adults (3 doses 0, 1 & 6–12 mo) • Postexposure (risk infxn ~30%) ppx: HBIG → vaccine (if unvac or known nonresponder)

Hepatitis C
(ssRNA; ~10% of acute viral hepatitis in U.S.;
NEJM
2011;364:2429)
• Transmission: blood (IVDU, transfusion) >> sexual; 20–30% w/o clear precipitant • Incubation: 1–5 mo; mean 6–7 wk

• Natural hx

acute infxn: 80% subclinical; 10–20% sx hepatitis w/ jaundice; fulminant hepatitis very rare; prob of spont clearance a/w
IL28B
& HLA class II genotypes (
Annals
2013;158:235)

chronic: up to 85% → chronic hepatitis, 20–30% of whom develop cirrhosis (after ~20 y) ↑ risk of cirrhosis in men, EtOH, HIV; HCC in 2–5% of cirrhotics/y

• Extrahepatic syndromes: cryoglobulinemia, porphyria cutanea tarda (blistering rash in sun-exposed areas), MPGN, MGUS, IPF, NHL and DM

• Serologic, virologic, & genetic tests

anti-HCV (ELISA):
in 6 wk, does
not
= recovery or immunity; can be
after recovery

HCV RNA:
w/in 2 wk, marker of active infection

HCV RIBA: used to confirm
anti-HCV ELISA in Pts w/ undetectable HCV RNA

HCV genotype (1–6): guides duration & predicts response to Rx

• Dx:
acute
hepatitis =
HCV RNA, ± anti-HCV;
resolved
=
HCV RNA, ± anti-HCV;
chronic
=
HCV RNA,
anti-HCV

• Treatment indications (
Hep
2009;49:1335 & 2011;54:1433;
NEJM
2013;368:1907)

Acute: if no spont. clearance at 8–12 wk, consider PEG-IFNɑ-2a/b ± RBV × 12–24 wk

Chronic: RNA
, plus bx w/ either chronic hepatitis & fibrosis stage >1 or compensated liver disease (in genotype 2 or 3, may proceed to Rx w/o bx b/c high response rate)

•
Triple therapy
(genotype 1):
PEG-IFN ɑ-2a/b, RBV, & protease inhibitor
(PI), either boceprevir (BOC) or telaprevir (TVR) (
NEJM
2011;364:1195 & 2405). Rx 24–48 wk; SVR rate 30–80% based on variables such as advanced fibrosis,
IL28B
genotype, prior response to IFN and rapid virologic resp ( RNA at wk 4 [TVR] or wk 8 [BOC]) (
Gastro
2012;142:1314) •
Dual therapy
(genotypes 2 & 3): PEG-IFNɑ-2a/b + RBV; Rx 24 wk; SVR rate ~80%

• Goal is
sustained virologic response
(SVR) =  viremia 24 wk after completion of Rx • IFN-free regimens incl. replic. complex, polymerase, & microRNA-122 inhibs. & other direct acting antivirals under study (
NEJM
2012;366:216; 2013;368:34, 45, 1685, 1867 & 1878) • Risks of Rx: flu-like sx, psych sx (if depressed can give SSRI), thyroid dysfxn, marrow suppression (can give EPO & G-CSF), hemolysis (RBV), sexual dysfxn; PIs w/ sig drug-drug interactions, worsen anemia, & TVR a/w rash/pruritus in 6%, DRESS/SJS in <1%

• Contraindic.: decompensated cirrhosis, preg, severe psych illness, active substance abuse, severe cardiac/pulm disease, uncontrolled DM, seizure d/o, autoimmune disease • CDC rec screening for HCV in anyone born 1945–1965 (
Annals
2012;156:263) • Vaccinate all chronic HCV patients against HBV and HAV if not immune

• Postexposure (needlestick risk ~3%) ppx: none; if HCV RNA →
, consider Rx w/in 3 mo
Hepatitis D
(RNA)
• Transmission: blood or sexual; endemic in Africa & E. Europe

• Pathogenesis: requires HBV to cause either simultaneous or superimposed infection

• Natural hx: in HBV ↑ severity of infxn and ↑ progression to cirrhosis and HCC in chronic carriers; clears w/ HBV

• Serologic/virologic tests: anti-HDV; follow HDV RNA during Rx (high relapse rate)

Hepatitis E
(ssRNA;
NEJM
2012;367:1237;
Lancet
2012;379:2477)
• In endemic areas most common cause of acute viral hepatitis