Hepatitis%20c Treatment

• Treatment is indicated for both treatment-naive and treatment-experienced patients with compensated and decompensated cirrhosis
  • Treatment-naive patients are those who have never been treated for HCV infection; treatment-experienced patients are those who are previously treated with Interferon or Peginterferon with or without Ribavirin, or Sofosbuvir plus Ribavirin with or without Peginterferon 
  • Interferon-free, Ribavirin-free, direct-acting antiviral (DAA)-based regimens are the recommended treatment options
    • NS3/4A (protease) inhibitors: Asunaprevir, 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
  • Boceprevir, a NS3/4A protease inhibitor, may be used in addition to standard therapy if with partial or no response to standard therapy
• Treatment is generally not recommended in patients with short life expectancy that cannot be resolved with HCV therapy, liver transplantation or another directed therapy 
• Choice, course and duration of therapy are influenced by the HCV genotype as well as the severity of liver disease which must both be identified before starting treatment
  • Patients with confirmed hepatitis C should be treated with DAA without awaiting spontaneous resolution
  • HCV genotyping should be considered in patients with cirrhosis
  • In areas where virological tests are unavailable or are costly, or if to simplify therapeutic regimen, pangenotypic therapy may be considered 
• Assess risk for a drug-drug interaction before starting HCV therapy or other medications during therapy in patients receiving DAAs and monitor for side effects during treatment 
  • Patients initiating DAA therapy should also be assessed for HBV or HIV coinfection and for the presence of resistance-associated substitutions (RASs) 
• 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 least 12 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
• 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
• Reinfection happens when HCV RNA or HCV core antigen reappears after an SVR in patients who have risk factors for infection, and that the infection is caused by a different genotype or a related strain of the same genotype from the prior infection
• Virological responses in patients with HCV infection treated with Interferon-based therapy can be defined as follows: 
  • 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
  • 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 or drug-drug interactions with concomitant medications
• Likelihood of treatment response
• Presence of comorbid conditions
  • In patients with HIV/HCV coinfection, antiretroviral therapy (ART) is suggested to be initiated first before DAA; however, if the patient is ineligible for ART, DAA can be initiated if there are no contraindications
  • In patients with hemoglobinopathies, the European Association for the Study of Liver (EASL) guidelines recommend DAA for HCV infection
  • Patients with HCV-associated cryoglobulinemia should be treated with DAA
  • Patients with renal impairment (eGFR <30 mL/min/m²) or those on hemodialysis, Sofosbuvir-free treatment regimen is preferred

Spontaneous Resolution in Acute Infection

• Patients with acute hepatitis C should be treated according to the simplified approach without awaiting spontaneous resolution
  • Patient education focusing in the reduction of viral transmission should be done
• 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

Goals of Treatment

• Antiviral treatment for acute hepatitis C aims to prevent progression to chronic hepatitis
• 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
• Prevent transmission of HCV 

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 
  • DAA 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: 
  • Sofosbuvir/Velpatasvir for 12 weeks (all genotypes)
  • Glecaprevir/Pibrentasvir for 8 weeks (all genotypes)
  • Sofosbuvir/Ledipasvir for 8-12 weeks (genotypes 1, 4, 5 and 6)
  • Grazoprevir/Elbasvir for 12 weeks (genotypes 1b and 4)
• 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

Simplified Pangenotypic HCV Treatment for Treatment-Naive Adults without Cirrhosis

• Recommended regimens:
  • Glecaprevir/Pibrentasvir for 8 weeks
  • Sofosbuvir/Velpatasvir for 12 weeks
• Patients with any of the following characteristics are ineligible for the simplified treatment:
  • Previous hepatitis C treatment
  • Cirrhosis
  • HIV/HBV coinfection
  • Current pregnancy
  • Known or suspected HCC
  • Prior liver transplantation
   

Simplified Pangenotypic HCV Treatment for Treatment-Naive Adults with Compensated Cirrhosis

• Recommended regimens:
  • Glecaprevir/Pibrentasvir for 8 weeks (all genotypes)
  • Sofosbuvir/Velpatasvir for 12 weeks (all genotypes except genotype 3)
• Patients with any of the following characteristics are ineligible for the simplified treatment:
  • Current or prior episode of decompensated cirrhosis
  • Previous hepatitis C treatment
  • End-stage renal disease (eGFR <30 mL/min/m²)
  • HIV/HBV coinfection
  • Current pregnancy
  • Known or suspected HCC
  • Prior liver transplantation
   

• Identify the HCV genotype and genotype 1 subtype (eg 1a or 1b) before initiating treatment to determine the choice and duration of therapy
• Genotype and subtype should be determined in areas or setting where subtypes of HCV are resistant to NS5A inhibitors, eg subtypes 1l, 3b, 3g, 4r, 6u, 6v

Retreatment for Patients with Failure of Prior Therapy

• Sofosbuvir-based treatment failure without cirrhosis or with compensated cirrhosis:
  • Sofosbuvir/Velpatasvir/Voxilaprevir x 12 weeks
  • Glecaprevir/Pibrentasvir x 16 weeks
    • Not recommended for genotype 3 with SOF/NS5A inhibitor experience
• Glecaprevir/Pibrentasvir treatment failure without cirrhosis or with compensated cirrhosis:
  • Glecaprevir/Pibrentasvir plus Sofosbuvir and weight-based Ribavirin x 16 weeks
  • Sofosbuvir/Velpatasvir/Voxilaprevir x 12 weeks
• Sofosbuvir/Velpatasvir/Voxilaprevir or Sofosbuvir plus Glecaprevir/Pibrentasvir treatment failure without cirrhosis or with compensated cirrhosis:
  • Glecaprevir/Pibrentasvir plus Sofosbuvir and weight-based Ribavirin x 16 weeks
    • Treatment duration can be extended to 24 weeks extremely difficult cases (eg genotype 3 with cirrhosis)
  • Sofosbuvir/Velpatasvir/Voxilaprevir plus weight-based Ribavirin x 24 weeks

Decompensated Cirrhosis

• Patients with genotypes 1-6 with decompensated cirrhosis and those with compensated cirrhosis with prior decompensation episodes should receive Sofosbuvir/Velpatasvir with weight-based Ribavirin for 12 weeks 
  • Ribavirin can be initiated at 600 mg/day with subsequent dose adjustments based on patient's tolerance 
  • If patient has contraindications to or is intolerant of Ribavirin, Sofosbuvir/Velpatasvir alone can be given for 24 weeks 
• Sofosbuvir/Velpatasvir with weight-based Ribavirin for 24 weeks can be given as retreatment for patients with genotypes 1-6 with decompensated cirrhosis who failed treatment with a DAA (protease inhibitor and/or NS5A inhibitor)-containing regimen 
• Treatment regimens that include an HCV protease inhibitor, eg Glecaprevir, Grazoprevir or Voxilaprevir, should not be given

HCV Genotype 1, 4, 5 or 6

• With decompensated cirrhosis who are Ribavirin eligible
  • Ledipasvir/Sofosbuvir with low initial dose of Ribavirin (may be increased as tolerated) x 12 weeks
• With decompensated cirrhosis who are Ribavirin ineligible
  • 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

HCV Genotype 2 or 3

• With decompensated cirrhosis who are Ribavirin ineligible
  • Sofosbuvir/Daclastavir or Sofosbuvir/Velpatasvir  x 24 weeks

• 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