Hepatitis C--practice essentials

Practice Essentials

Hepatitis C is
an infection caused by the hepatitis C virus (HCV) that attacks the liver and
leads to inflammation. The World Health Organization (WHO) estimates that about
3% of the world’s population has been infected with HCV and that there are more
than 170 million chronic carriers who are at risk of developing liver cirrhosis
and/or liver cancer.

Essential update: CDC advises follow-up HCV RNA test
after initial positive test result for HCV antibody

The CDC now
recommends that all patients who test positive for hepatitis C virus (HCV)
antibodies receive a follow-up HCV RNA test.^{[1, 2]} The existing
CDC guidelines for laboratory testing and reporting of antibody to HCV do not
distinguish between past infection that has resolved and current infection that
requires care and evaluation for treatment. The lack of this complete testing
regimen helps explain why up to 3 in 4 individuals who are infected with HCV do
not know it—and, thus, do not receive the curative antiviral therapy they need.

The new
recommendation is supported by a study of HCV infections reported to the CDC by
2 cities and 6 states between 2005 and 2011, which found that of 217,755
persons with newly reported HCV infections, 107,209 (49.2%) were HCV antibody –
positive only, and 110,546 (50.8%) were reported with a positive HCV RNA result
that confirmed current HCV infection.

Signs and symptoms

Initial
symptoms of hepatitis C are often extrahepatic, most commonly involving the
joints, muscle, and skin. Examples include the following:

• Arthralgias


• Paresthesias


• Myalgias


• Pruritus


• Sicca
  syndrome


• Sensory
  neuropathy

Symptoms
characteristic of complications from advanced or decompensated liver disease
are related to synthetic dysfunction and portal
hypertension, such as the following:

• Mental
  status changes (hepatic
  encephalopathy)


• Ankle
  edema and abdominal distention (ascites)


• Hematemesis
  or melena (variceal bleeding)

Physical
findings usually are not abnormal until portal hypertension or decompensated
liver disease develops. Signs in patients with decompensated liver disease
include the following:

• Hand
  signs: Palmar erythema, Dupuytren contracture, asterixis, leukonychia, clubbing


• Head
  signs: Icteric sclera, temporal muscle wasting, enlarged parotid gland,
  cyanosis


• Fetor
  hepaticus


• Gynecomastia,
  small testes


• Abdominal
  signs: Paraumbilical hernia, ascites, caput medusae, hepatosplenomegaly,
  abdominal bruit


• Ankle
  edema


• Scant body
  hair


• Skin
  signs: Spider nevi, petechiae, excoriations due to pruritus

Other common
extrahepatic manifestations include the following:

• Cryoglobulinemia:
  Membranoproliferative glomerulonephritis


• Idiopathic
  thrombocytopenic purpura


• Lichen
  planus^[3]


• Keratoconjunctivitis
  sicca


• Raynaud
  syndrome


• Sjögren
  syndrome


• Porphyria
  cutanea tarda


• Necrotizing
  cutaneous vasculitis


• Non-Hodgkin
  lymphoma

See Clinical
Presentation for more detail.

Diagnosis

General
baseline studies in patients with suspected hepatitis C include the following:

• Complete
  blood cell count with differential


• Liver
  function tests, including alanine aminotransferase level


• Thyroid
  function studies


• Screening
  tests for coinfection with HIV or hepatitis B
  virus (HBV)


• Screening
  for alcohol abuse, drug abuse, or depression

Tests for
detecting hepatitis C virus (HCV) infection include the following:

• Hepatitis
  C antibody testing: Enzyme immunoassays (EIAs), rapid diagnostic tests
  (RDTs), and point-of-care tests (POCTs)


• Recombinant
  immunoblot assay


• Qualitative
  and quantitative assays for HCV RNA (based on polymerase chain reaction
  [PCR] or transmission-mediated amplification [TMA])


• HCV
  genotyping


• Serologic
  testing (essential mixed cryoglobulinemia is a common finding)

Liver biopsy
is not mandatory before treatment but may be helpful. Some restrict it to the
following situations:

• The
  diagnosis is uncertain


• Other
  coinfections or disease may be present


• The
  patient has normal liver enzyme levels and no extrahepatic manifestations


• The
  patient is immunocompromised

See Workup
for more detail.

Management

Treatment of
acute hepatitis C includes the following:

• 6 months
  of standard interferon (IFN) therapy is commonly successful


• Initiation
  of therapy is typically 2-4 months after onset of illness

The 2 goals of
treatment of chronic hepatitis C are as follows :

• To achieve
  sustained eradication of HCV (ie, sustained virologic response)


• To prevent
  progression to cirrhosis, hepatocellular carcinoma (HCC), and
  decompensated liver disease necessitating liver transplantation

Treatment of
chronic hepatitis C includes the following:

• Monotherapy
  (initial studies; not current standard of care)


• Combination
  therapy: IFN with ribavirin, IFN with the addition of a polyethylene
  glycol molecule (pegylated IFN; PEG-IFN), PEG-IFN with ribavirin


• Protease
  inhibitors (eg, boceprevir and telaprevir) as third component of
  combination therapy

Recommendations
for nonresponse or relapse^[4] include the
following:

• No SVR
  after a full course of PEG-IFN plus ribavirin: Do not re-treat, even with
  a different PEG-IFN


• No
  response to antiviral therapy, advanced fibrosis: Screen for
  hepatocellular carcinoma (HCC) and varices, and evaluate for liver
  transplantation if appropriate


• Mild
  fibrosis: Monitor without treatment

See Treatment
and Medication for more detail.

Medication Summary

Combination therapy with
pegylated interferon alfa (PEG-IFN alfa) and the nucleoside analogue ribavirin
is the current standard of care in patients infected with hepatitis C virus
(HCV). Patients with HCV genotype 1 have a much less favorable response to
therapy and are treated for 12 months, compared with patients infected with
genotypes 2 and 3, in whom a 6-month course of therapy is sufficient.

If viremia is present after 6
months, additional therapy has a negligible incremental benefit, and treatment
should be stopped in all patients regardless of the viral genotype. With HIV
coinfection, all patients with a response to therapy at the end of 6 months
should receive an additional 6 months of combination therapy regardless of the
genotype. Patients with acute HCV infection should be treated for 6 months.

The addition of protease
inhibitors to the combination of PEG-IFN alfa and ribavirin is becoming the new
standard of care for the treatment of chronic HCV infection. Regimens that
include a protease inhibitor significantly improve sustained virologic response
rates in patients with genotype 1 HCV infection, albeit with higher rates of
discontinuation because of adverse events.