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Hepatitis C and the Hep C Virus: Symptoms, Causes, Diagnosis, Transmission, Treatment, Complications

Hepatitis_C
Source: cadenaser.com

    Definition

    Hepatitis C is an Infection with Hepatitis virus Typ c. It leads to inflammation of the liver and leads in his end-stage to liver cirrhosis. HCV makes 20 % of all acute hepatitis in the USA and 40% of chronic hepatitis.
    Spontaneous resolution may occurs in 20-50% of cases.

    Transmission


    • Inject illicit drugs
    • Sexual transmission, especially M2M
    • Blood transfer
    • Meternal fetal transmission
    • Tattooing, sharing razors, acupuncture

    Clinical manifestation

    General nonspecific symptoms:

    • Arthralgias
    • Myalgias
    • Pruritus
    • Sensory neuropathy
    • Symptoms of liver cirrhosis:
           -   Hepatic encephalopathy
           -   Ascites/ Ankle edema
           -   Hematemesis/Melena
    Signs on clinical examination are in general the signs of advanced liver disease:
    • Icterus
    • Spider nevi
    • Palmar erythema
    • Fetor hepaticus
    • Finger clubbing
    •  Petechia
    • Ascites/ caput medusa
    • Gynecomastia/ small tests
    • Signs of pruritus and scratching on skin

    Diagnosis

    To confirm the infection:

    • HCV antibody, when positive HCV RNA (PCR)
    • HCV antibody negative but clinical suspect HCV RNA or follow up controlling HCV antibodies every 2 months for 6 months.
    • HCV genotyping:
         o   1 (a,b,c); most spread worldwide 40-80%, associated with severe disease and high rate an HCC
         o   2 (a,b,c): besser response to medication
         o   3 (a,b)-4-5-6
    HCV antibodies
    HCV RNA (PCR)
    Meaning:
    +
    +
    Active disease
    +
    -
    No active disease
    - but suspect
    Do PCR RNA
    Repeat HCV Antibodies

    Other tests to do in general:

    • Liver transaminase, Bilirubin
    • Liver synthesis tests: albumin, quick, CHE
    • Kidney tests
    • CBC
    • Thyroid function
    • Screening for coinfection with HIV and Hepatitis B
    • Screening for cryoglobulinemia: to be found in 50 % of cases
    • Liver biopsy: to assess the liver fibrosis
    • ultrasound of the liver

    Treatment

    Good to know:
    Hepatitis C has become a curable disease with the use of antiviral agents (>95%)

    There are two goals of the therapy: two goals
    1-     To achieve sustained eradication of HCV (SVR), which is defined as the persistent absence of HCV RNA in serum 12 weeks after completing antiviral treatment.
    2-     To prevent progression to cirrhosis, hepatocellular carcinoma (HCC), and decompensated liver disease requiring liver transplantation.

    Old therapies:
    • Interferon 1, Interferon 2a, Interferon 2b, PEG-Interferon 2a/2b
    • Interferon+ Ribavirin 30-40% sustained virologic response (SVR)
    • PEG-Interferon 2a + Ribavirin: standard dose for 48 months Gynotyp 1/ low dose Ribavirin for 24 months Genotype 2 or 3: 40-55%  SVR
    • SE: hematologic depression, Depression
    • Interferon is NO longer recommended

    Neu therapies:

    • Direct antiviral agents (DAAs): target specifically various sites of viral replication: just for Patients over 18 years old.
    • NS3/4 targeting protease inhibitors
                  ·        Grazoprevir
                  ·        Glecaprevir

    • NS5B targeting polymerase inhibitors
                  ·        Nucleotide: Sofosbuvir
                  ·        Non-nucleotide: Dasabuvir

    • NS5A targeting agents
                 ·        Elbasvir
                 ·        Velpatasvir

    Considerations for the therapy:

    • Before initiating the therapy HCV Genotype and resistance-associated substitutions (RASs) should be defined.
    • Monitoring for spontaneous clearance for a minimum of 6 months before initiating treatment.

    Some recommended regimes in naïve patients:
    The daily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg) (Zepatier) for 12 weeks: 94-97% SVR:

    • With RASs: treat 16 weeks + Ribavirin
    • Without RASs: treat 12 weeks without Ribavirin
    • Contraindication: Liver cirrhosis CHILD B and C
    The daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (Epclusa) (100 mg) for 12 weeks: 98-99% SVR:

    • Can be given regardless liver cirrhosis
    One of the recommended regimes in decompensated liver cirrhosis:
    The daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) with a low initial ribavirin dose (600 mg, increase as tolerated)/ or weight-based Ribavirin for 12 weeks

    Complications

    Hepatic complication:
    • Liver cirrhosis
    • Hepatocellular carcinoma HCC

    Extrahepatic complications:
    • Cryoglobulinemia
    • Membranoproliferative glomerulonephritis
    • Idiopathic thrombocytopenic purpura
    • Raynaud syndrome
    • Sjögren syndrome
    • Porphyria cutanea tarda
    • Necrotizing cutaneous vasculitis

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