Medical Archive

Introduction

Classification of chronic hepatitis

Classfication by cause

TYPE OFHEPATITIS	DIAGNOSTIC TEST(s)	AUTOANTIBODIES	THERAPY
Chronichepatitis B	HBsAg, IgG anti-HBc,HBeAg, HBV DNA	Uncommon	IFN-?, PEG IFN-? Oral agents:First-line: entecavir, tenofovir Second-line: lamivudine, adefovir,telbivudine
Chronichepatitis C	Anti-HCV, HCV RNA	Anti-LKM1a	PEG IFN-? plus ribavirinb Direct-acting oral agents: sofosbuvir, ledipasvir,velpatasvir ritonavir-boosted paritaprevir, ombitasvir, dasabavir elbasvir,grazoprevir daclatasvir, simeprevir
Chronichepatitis D	Anti-HDV, HDV RNA,HBsAg, IgG anti-HBc	Anti-LKM3	IFN-?, PEG IFN-?c
Autoimmunehepatitis	ANA d(homogeneous),anti- LKM1 (?)Hyperglobulinemia	ANA, anti-LKM1anti-SLAe	Prednisone, azathioprine
Drug-associated	?	Uncommon	Withdraw drug
Cryptogenic	All negative	None	Prednisone (?), azathioprine (?)

Classification by grade

Classification by stage

Chronic viral hepatitis

• https://www.kasl.org/guideline/guideline_Intro.html

Chronic hepatitis B

??? ??? ???? ?? ??. ??? ??? 90%?? ???
??? ?? IgM anti-HBc (-)

Treatment

• ?? ??
  • Entecavir, tenofovir, PEG-IFN ? ??
• LMV?? ? ?? ???
  • LMV? ??? ? HBV?? ???, YMDD variant? ??x
  • LMV+ADF(adefovir) ?? ?? ??.
• ??? ??????
  • Indication
    • HBV ?? ????? ???? ?? ??
    • ????? ?? ?????? ?? ??
    • ?? HBV DNA? ?? (>200,000 IU/mL) ??
• ????/????
  • ???? risk ???? ??? entecavir
• ???
  • ?? 24-28???? tenofovir DF? ??.

Chronic hepatitis C

??? 8?

Q) ? IgG? ?? ??? ??? ????
Envelope proteins have variations in their antigenic structure (>6 genotypes, multiple subtypes)
Due to RNA-dep. RNA polymerase that has no proofreading 3?->5? exonuclease activity.

Needlestick exposure
??????, ?????? ??? ??x

Diagnosis

Because HCV may spontaneously clear in up to half of affected patients, the diagnosis of chronic infection is a 2-step process that requires both a positive serologic test and a confirmatory molecular test.

• Serologic test (Anti-HCV antibody EIA)
  • False-positive: laboratory error
  • False-negative: chronic HCV in immunocompromised patients.
• Molecular test (HCV RNA PCR)
  • ?? ?? ?? ? HCV-RNA ????? 3?? ? ???? ??
  • False-negative: ??? 15%?? ????.
• Q. What if HCV antibody is positive, but there is no HCV RNA?
  • A1: Resolved infection
    • A minority (15%-40%) are able to spontaneously clear HCV infection
    • The presence of multiple positive immunoassays make resolved infection far more likely.
  • A2: False-positive HCV antibody test

Treatment

Type 1	? Bx ? fibrosis ??? ??	48? ??
Type 2/3	? Bx? optional, ribavirin ??	24? ??

• PegINF + Ribavirin? ??. 
  • ???? ?? ???? ??.
  • ?? ??? ?? ????? ???? ???.
• Direct acting antivirals (DAA)
  • ??? 2?? ??? DAA??, 12-24???? 90%? SVR ??.
  • ???? ??? ???? ?? ??
  • 3?? ? sofosbuvir? ?? ?? ??. +/- Ribavirin (palivizumab preferred in childhood)

Drug	Mechanism	Adverse effects
Ledipasvir	Viral phosphoprotein (NS5A) inhibitor; NS5A plays important role in replication.
Simeprevir	HCV protease (NS3/4A); prevents viral replication.	Photosensitivity reactions, rash.
Sofosbuvir	Inhibits HCV RNA-dependent RNA polymerase (NS5B) acting as a chain terminator.	Fatigue, headache, nausea.
Ribavirin	Inhibits synthesis of guanine nucleotides by inhibiting IMP dehydrogenase.	Hemolytic anemia, severe teratogen.

Sustained virologic response (SVR)? ?? ??
?? ?? ??, 6?? ? RNA ??? ?? ??

Chronic hepatitis D (delta hepatitis)

Autoimmune hepatitis

Definition

Immunopathogenesis

• Portal inflammation with lobular damage resulting in bridging necrosis
• False-positive EIA test for HCV
  • In the setting of hypergammaglobulinemia
  • Should always be confirmed with recombinant immunoblot assay (RIBA) for HCV.
• May also present with elevated p-ANCA
• Type 1
  • Classic type, m/c.
  • Associated with ANA, anti-smooth muscle antibodies (SMA)
• Type 2
  • More common in women of Western European descent
  • Associated with autoantibodies to circulating liver-kidney microsomes (anti-LKM1)

Clinical features

• Asymptomatic (25%)
  • Identified by abnormal LFTs
• Symptomatic
  • Fatigue, anorexia, nausea, jaundice
  • Can progress to fulminant liver failure &/or cirrhosis
• Often associated with other autoimmune disorders (eg, vitiligo, autoimmune thyroiditis, celiac disease)

Diagnostic criteria

• Hepatocellular pattern (?AST/ALT)
• Hypergammaglobulinemia >1.5 URL
• Elevated gamma gap (difference between total protein and albumin)
• Elevated autoantibodies
  • ANA (nonspecific)
  • Anti-smooth muscle (SMA)
  • Anti-liver/kidney microsomal type 1 (anti-LKM1)
• Biopsy (essential)
  • Portal & periportal lymphoplasmacytic infiltration.

Differential diagnosis

Treatment

Prednisone +/- azathioprine
??? ??? x, ??? ???? ??.