hepatitis%20c
HEPATITIS C

Hepatitis C can be transmitted through blood transfusions, organ transplants, percutaneous (especially IV drug use), sexual or perinatal route.

It has an incubation period of 14-180 days.

Goal of treatment is to prevent progression to chronic hepatitis C through antiviral treatment of acute hepatitis C. Also, it aims to prevent occurrence of liver-related complications through antiviral treatment of chronic hepatitis C.

Principles of Therapy

General Care

  • Supportive care
  • Consider hospitalization if there is vomiting, dehydration, signs of hepatic decompensation
    • Evaluate for advanced fibrosis or other conditions that may hasten liver fibrosis (eg HBV and HIV infections) to help guide treatment
      • Monitor for hepatocellular carcinoma with alpha-fetoprotein and liver ultrasound every 6 months
  • Screen for other sexually-transmitted diseases in cases of sexually acquired hepatitis or if otherwise appropriate

Goals of Treatment

  • Antiviral treatment for acute hepatitis C aims to prevent progression to chronic hepatitis C
  • Antiviral treatment of chronic hepatitis C aims to prevent occurrence of liver-related complications
    • HCV therapy reduces decompensation rate and hepatocellular carcinoma risk in patients with cirrhosis

Principles of Treatment

  • Treatment is indicated for both treatment-experienced and treatment-naive patients with compensated and decompensated liver disease
    • Interferon-free, Ribavirin-free, direct-acting antiviral-based regimens are the recommended treatment options 
      • NS3/4A (protease) inhibitors: Glecaprevir, Grazoprevir, Paritaprevir, Simeprevir, Voxilaprevir 
      • NS5A inhibitors: Daclatasvir, Elbasvir, Ledipasvir, Ombitasvir, Pibrentasvir, Velpatasvir 
      • NS5B polymerase inhibitor (nucleotide analogue): Sofosbuvir 
      • NS5B polymerase inhibitor (non-nucleoside analogue): Dasabuvir
  • Choice, course and duration of therapy are influenced by the HCV genotype which must be identified before starting treatment 
    • In areas where virological tests are unavailable or are costly, or if to simplify therapeutic regimen, pangenotypic therapy may be considered 
  • Treatment responses are usually characterized by HCV RNA testing
  • Eradication of infection is considered when there is sustained virologic response (SVR)
    • SVR is defined as the absence of HCV RNA in serum or plasma by a sensitive test at 12 weeks and 24 weeks after completing treatment
    • If HCV RNA assays are unavailable, undetectable HCV core antigen in serum or plasma 24 weeks after completing treatment can be an alternative endpoint of therapy
  • Rapid virologic response (RVR) is achieved when HCV RNA becomes undetectable (<50 IU/mL) in serum after 4 weeks of therapy
  • Early virologic response (EVR) is defined as 2-log drop or loss of HCV RNA 12 weeks into therapy
  • End of treatment response is defined as continued absence of detectable virus at end of treatment
  • Relapse is considered when HCV RNA becomes undetectable on treatment but is detected after discontinuation of therapy
  • Patients in whom HCV RNA levels remain stable while on treatment are considered non-responders while those whose HCV RNA levels decline but never become undetectable are referred to as partial responders

Individualize treatment based on the following:

  • Severity of liver disease
  • Previous therapy
  • Potential of serious side effects
  • Likelihood of treatment response
  • Presence of comorbid conditions

Spontaneous Resolution in Acute Infection

  • Chance of spontaneous resolution is greater in female patients and those with HCV genotype non-1 infection
  • Less likely to happen if infection lasts >12 weeks

Pharmacotherapy

Acute Hepatitis C

  • Treatment may be delayed for 8-12 weeks as there is a 20-50% chance of spontaneous resolution 
  • Consider pharmacotherapy to prevent progression to chronic hepatitis C, or to minimize transmission or loss to follow-up 
    • Direct-acting antiviral therapy was shown to be cost effective and improved clinical outcomes in comparison to delaying treatment until the chronic phase 
    • Measure HCV RNA prior to starting therapy and SVR at 12 and 24 weeks after therapy 
  • Pending further data that will establish the start time of the ideal treatment regimen and its duration, acute hepatitis C patients may be treated with the following antiviral regimens for 8 weeks: 
    • Sofosbuvir/Velpatasvir (all genotypes)
    • Glecaprevir/Pibrentasvir (all genotypes)
    • Sofosbuvir/Ledipasvir (genotypes 1, 4, 5 and 6)
    • Grazoprevir/Elbasvir (genotypes 1b and 4)
    • Ritonavir-boosted Ombitasvir, Paritaprevir, and Dasabuvir (genotype 1b)
  • Interferon (high-dose) or Peginterferon may also be used
    • Treat HCV genotype 1 for 24 weeks, genotype 2 , 3, or 4 for 12 weeks
    • Patients unresponsive to monotherapy should be given Peginterferon/Ribavirin or a protease inhibitor-based triple therapy

Chronic Hepatitis C

  • In limited-resource settings, Peginterferon/Ribavirin combination therapy may be considered in HCV genotypes 1, 4, or 6 treatment-naive patients with favorable IL28B genotypes and low viral load and in HCV genotypes 2 or 3 treatment-naive patients
    • For treatment-experienced patients, Peginterferon/Ribavirin can only be given in those who relapse with favorable IL28B genotype and without cirrhosis
  • Sofosbuvir with Peginterferon/Ribavirin for 12 weeks can be utilized as an alternative regimen in patients with genotypes 1, 3, 5 and 6

Pangenotypic Therapy

  • Having a high treatment efficacy across all 6 major genotypes, pangenotypic therapy is a simplified treatment regimen for chronic hepatitis C in treatment-naive and treatment-experienced patients without cirrhosis and with compensated cirrhosis
  • Reduces the need for genotyping to guide treatment decisions in limited-resource settings 
  • Makes treatment readily accessible at reduced cost
  • Prior to initiation of treatment, check for possible drug-drug interactions, and determine the presence of HCV replication (HCV RNA or HCV core antigen testing) and presence of fibrosis or cirrhosis (APRI or FIB-4 non-invasive testing) to see if patient would need post-treatment follow-up (eg surveillance for hepatocellular carcinoma) 
  • Pangenotypic regimens currently available include the following:
Regimen Treatment Experience Duration (weeks)
Glecaprevir/Pibrentasvir* Treatment naive or Peginterferon/Ribavirin (PEG/RBV) experienced without cirrhosis 8
Treatment naive or PEG/RBV experienced with cirrhosis, and non-NS5A (including NS3) or Sofosbuvir failures regardless of cirrhosis 12
Sofosbuvir/Daclatasvir** HCV/HIV coinfection when antiretroviral regimen cannot be made to accommodate recommended regimens 12
Sofosbuvir/Velpatasvir Treatment naive, or PEG/RBV ± NS3 protease inhibitor experienced, or non-NS5A experienced regardless of cirrhosis 12
GT1b, non-NS5A direct-acting antiviral experienced regardless of cirrhosis 12
Sofosbuvir/Velpatasvir/Voxilaprevir NS5A failures (including NS3 protease inhibitor) regardless of cirrhosis 12
GT1a, non-NS5A failures (including NS3 protease inhibitors) regardless of cirrhosis 12
PEG/RBV experienced with cirrhosis, or direct-acting antiviral failure (including NS5A inhibitors) regardless of cirrhosis 12
* Glecaprevir/Pibrentasvir x 16 weeks can be given to HCV genotype 3 patients with prior Interferon and/or Ribavirin therapy.
** Sofosbuvir/Daclatasvir x 12 weeks for compensated cirrhosis may be considered in areas where the genotype is known and prevalence of genotype 3 is <5%.
Modified from:
  • AASLD-IDSA HCV Guidance Panel. Hepatitis C guidance 2018 update: AASLD-IDSA recommendations for testing, managing, and treating hepatitis C virus infection. Clin Infect Dis. 2018 Oct 30;67(10):1477-1492.
  • European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2018. J Hepatol. 2018 Aug;69(2):461-511.
  • Genotype-specific Therapy

    • Identify the HCV genotype and genotype 1 subtype (eg 1a or 1b) before initiating treatment to determine the choice and duration of therapy
    Genotype Regimen Treatment Experience Duration (weeks)
    1 Elbasvir/Grazoprevir Treatment naive or PEG/RBV experienced regardless of cirrhosis 12
    Ledipasvir/Sofosbuvir Treatment naive regardless of cirrhosis 12
    PEG/RBV (± NS3 protease inhibitor) experienced without cirrhosis 12
    Ombitasvir/Paritaprevir/Ritonavir plus Dasabuvir with weight-based Ribavirin Treatment naive or PEG/RBV experienced regardless of cirrhosis 12
    Simeprevir plus Sofosbuvir Treatment naive or PEG/RBV experienced without cirrhosis 12
    3 Daclatasvir plus Sofosbuvir with or without weight-based Ribavirin Treatment naive with compensated cirrhosis 24
    Sofosbuvir plus Elbasvir/Grazoprevir PEG/RBV experienced with compensated cirrhosis 12
    4 Elbasvir/Grazoprevir Treatment naive or PEG/RBV experienced with previous relapse, regardless of cirrhosis 12
    Ledipasvir/Sofosbuvir Treatment naive regardless of cirrhosis or PEG/RBV experienced without cirrhosis 12
    Ombitasvir/Paritaprevir/Ritonavir with weight-based Ribavirin Treatment naive or PEG/RBV experienced regardless of cirrhosis 12
    5 or 6 Ledipasvir/Sofosbuvir Treatment naive or PEG/RBV experienced regardless of cirrhosis 12
    Modified from:
  • AASLD-IDSA HCV Guidance Panel. Hepatitis C guidance 2018 update: AASLD-IDSA recommendations for testing, managing, and treating hepatitis C virus infection. Clin Infect Dis. 2018 Oct 30;67(10):1477-1492.
  • European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2018. J Hepatol. 2018 Aug;69(2):461-511.
  • Decompensated Cirrhosis

    HCV genotype 1 or 4

    • With decompensated cirrhosis who are Ribavirin ineligible
      • Daclatasvir plus Sofosbuvir x 24 weeks

    HCV genotype 1, 4, 5 or 6

    • With decompensated cirrhosis who are Ribavirin eligible
      • Sofosbuvir/Velpatasvir with weight-based Ribavirin x 12 weeks
      • Ledipasvir/Sofosbuvir with low initial dose of Ribavirin (may be increased as tolerated) x 12 weeks
    • With decompensated cirrhosis who are Ribavirin ineligible
      • Sofosbuvir/Velpatasvir x 24 weeks
      • Ledipasvir/Sofosbuvir x 24 weeks
    • With decompensated cirrhosis and in whom previous Sofosbuvir- or NS5A-based treatment has failed
      • Ledipasvir/Sofosbuvir with low initial dose of Ribavirin (may be increased as tolerated) x 24 weeks
      • Sofosbuvir/Velpatasvir with weight-based Ribavirin x 24 weeks

    HCV genotype 2 or 3

    • With decompensated cirrhosis who are Ribavirin ineligible
      • Sofosbuvir/Velpatasvir x 24 weeks
      • Daclatasvir plus Sofosbuvir x 24 weeks
    • With decompensated cirrhosis and in whom previous Sofosbuvir- or NS5A-based treatment has failed
      • Sofosbuvir/Velpatasvir with weight-based Ribavirin x 24 weeks

    Liver Transplantation

    • Indicated in patients with end-stage liver disease (cirrhosis), hepatocellular carcinoma, and acute liver failure (ie caused by viruses, drugs and toxic agents)
      • Considered in patients with expected survival of ≤1 year without transplantation or if quality of life is unsatisfactory due to the liver disease
    • Patients with HCV infection can be treated prior to or after transplant on a case-by-case basis 
      • If with hepatitis C recurrence posttransplant, treatment with antivirals is done and is started early in patients with significant graft damage
    • HCV replication is not a contraindication for liver transplantation, though antiviral therapy should be given after transplant
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