Hepatitis C

Publication Date: February 1, 2017
Last Updated: March 14, 2022



Counseling of infected persons on avoiding transmission of HCV

  • The infected person should cover any bleeding wound or cuts and apply disinfectants immediately in order to keep the blood away from others.
  • An infected person should not donate blood or organs, although organs from HCV-positive patients may be used in those who are already HCV-positive.
  • Those who inject drugs should be counseled regarding the risk of transmission of HCV and advised to inject safely if they intend to continue.
  • Vomit and other bodily secretions from an HCV-infected patient should be disposed of with disinfectant—e.g., bleaching powder and glutaraldehyde solution.
  • The risk of sexual transmission of HCV is low. Spouses are not recommended to take barrier precautions as a risk reduction strategy. However, HCV infection in non-IDU men who have sex with men (MSM) has increasingly been reported in the literature, especially in HIV-positive patients.
  • Transmission of HCV is low through breast milk, so breast-feeding should not be stopped.
  • Household contacts and physical contact are not recognized risk factors for HCV transmission, so an HCV-infected person should not be barred from any activities of normal life.

Prevention in the community and health-care settings

  • All blood donors must be screened for hepatitis C antibodies and/or HCV RNA.
  • In health-care settings, adherence to universal precautions for infection control is essential. This should include the use of disposable or adequately sterilized materials for invasive procedures, and adequate cleansing and sterilization of instruments.
  • It is important to educate tattooists, barbers, foot/hand care workers, and practitioners of traditional or alternative therapies about ways of minimizing blood contamination. This involves sterilization techniques for procedures that involve skin penetration or breaks to mucosal surfaces.
  • As transmission of HCV via injecting drug use is an increasing trend, it is important to implement an education campaign about the harm of drug use, especially among school-age children. Harm reduction programs such as needle/syringe programs should also be implemented.
  • Those who have received surgical or dental treatment can be at risk of acquiring HCV infection and should be offered testing, especially in health-care systems in which transmission associated with surgical and dental treatment has been a major risk.
  • Individuals with a history of blood transfusion have a higher risk of HCV infection and should be offered testing.
  • Chronic hepatitis C patients should be vaccinated against hepatitis B after screening.
  • Use of injections is only preferable in approved health-care settings, and injections should be discouraged as much as possible, especially in settings in which medical supervision is not available. When mandatory, injections must be carried out in accordance with WHO recommendations on safe injecting practice.
  • An appropriate protocol for needlestick injury should be drawn up and followed in all hospitals (public and private), as recommended by the Centers for Disease Control and Prevention (CDC).
  • All skin lesions on the hands of health-care workers should be covered with waterproof dressing, and if possible double gloving with a blood indicator in the glove should be used.
  • Health-care workers should be vaccinated for HBV.

Treatment response predictors

Recommendations for preferred HCV treatment regimens are continuing to evolve, but they still depend on several factors that compromise a SVR in some cases:
  • HCV genotype
  • Prior HCV treatment history
  • Compensated versus decompensated liver disease
  • Drug–drug interactions
  • Chronic kidney disease
  • Solid organ transplant recipients
The following are predictive factors for a less favorable response to treatment with DAA combinations:
  • Previous treatment with DAAs
  • Liver cirrhosis (Child–Pugh B and C)
  • Poor treatment adherence

Pretreatment assessment

The following should be assessed before DAA treatment is started:
  • Taking a detailed history and physical examination is essential, including the patient’s history of any other liver diseases and medical conditions that can adversely affect liver status, such as hepatitis B infection, alcoholism, autoimmunity, metabolic liver diseases, or hepatotoxic drugs. These should be inquired into and appropriate measures should be taken to reduce the risks.
  • Other evaluations should be considered (cardiopulmonary and psychiatric evaluation) and the risk of nonadherence should be assessed. Appropriate measures should be taken to reduce these risks.
  • Assessment for current/prior medications and adherence to previous treatments. Significant potential drug–drug interactions should also be assessed.
  • The extent of hepatic fibrosis should be checked using noninvasive measures:
    — Studies have demonstrated that FibroScan is a sensitive alternative to liver biopsy. The amount of fibrosis can be quantified very easily and reliably in more than 95% of the patients [45]. A correct interpretation of transient elastography must have an interquartile range/median values of < 30% and serum ALT < 5 × upper limit of normal. There should be no ongoing excessive alcohol intake, and the patient’s BMI should be taken into account. If the BMI is over 30 kg/m2, using extralarge (XL) probes may be considered.
    — In resource-limited regions and in places where FibroScan is not readily available, scores such as the fibrosis 4 index (FIB4), AST to platelet ratio index (APRI), and acoustic radiation force impulse (ARFI) can be used. An APRI score ≥ 2 can be used to predict the presence of cirrhosis. At its cut-off point, the ARFI score has a sensitivity of 48% but a specificity of 94% for predicting cirrhosis. It can also be used to predict the presence of significant fibrosis (stages 2–4). Using a cut-off value of 1.5, the sensitivity is 37% and the specificity is 95% for significant fibrosis [46,47].
    — Liver biopsy can only be considered when there is possibility of additional etiology.
  • Serum quantitation of HCV-RNA using a sensitive real-time PCR-based assay with a lower limit of detection of ≤ 15 IU/mL.
  • HCV genotyping.
  • In patients with suspected or known cirrhosis, the Child–Turcotte–Pugh score and Model for End-Stage Liver Disease (MELD) score should be calculated.
Recommendations for pretreatment monitoring
  1. A complete blood count(CBC), liver function tests (LFTs), serum albumin, INR, glomerular filtration rate (GFR), and a thyroid-stimulating hormone (TSH) test (if an IFN regimen is planned) should be performed within 12 weeks of the start of therapy.
  2. Quantitative PCR and genotyping anytime should be done before the start of therapy.
  3. Women of childbearing age must undergo urinary pregnancy testing before the start of therapy. Currently, all new oral therapy regimens, with or without ribavirin, are contraindicated for use during pregnancy or during breastfeeding due to a lack of sufficient safety information in humans, and adequate measures of contraception are still routinely recommended for female patients of childbearing age [48].
  4. With ribavirin-containing regimens, the patient’s age and cardiovascular comorbidity due to secondary anemia should be taken into account.

On-treatment assessment

Recommendations for patients receiving HCV treatment during their therapy:
  1. Compliance should be encouraged either at clinical visits or by phone. Any adverse events should be inquired about, and advice regarding drug–drug interactions should be given. The University of Liverpool provides a “HEP Drug Interaction Checker” (http://www.hep-druginteractions.org) [49].
  2. CBC, serum creatinine, GFR, and LFT assessments should be performed after 4 weeks of treatment. CBCs can be done more often in patients receiving ribavirin, if clinically indicated.
  3. TSH tests should be done at 12 weeks for those patients receiving interferon.
  4. Quantitative PCR assessment should be performed at the end of treatment and then 12 weeks afterward.

When to stop the treatment because of side effects

  • If there is a 10-fold or greater increase in ALT after 4 weeks of therapy.
  • If there is a less than 10-fold increase in ALT with one of the following:
    — Symptoms developing (nausea, vomiting, weakness)
    — Jaundice
    —Increases in bilirubin, alkaline phosphatase (ALP), or INR
  • If there is a less than 10-fold increase in ALT and the patient is asymptomatic, ALT assessment should be repeated at 6 weeks; if it is persistently high, one can consider stopping therapy.

Post-treatment assessment

For patients who fail to respond to treatment
  1. LFTs, CBC, INR every 6–12 months to assess disease progression (F4 patients).
  2. HCC surveillance for patients with advanced fibrosis (metavir F3/F4) using ultrasonography every 6 months.
  3. Endoscopic surveillance for varices in cirrhotic patients.
  4. Re-treatment evaluation once an effective alternative treatment is available. Pretreatment mutation testing is needed to select the best regimen at present. Currently, the guidelines recommend NS5A resistance evaluation in patients in whom DAAs fail, especially before considering elbasvir/grazoprevir for genotype 1a patients.
For patients who achieve an SVR
  1. For patients with F0–F2 fibrosis, the same recommendations apply as if they were never infected with HCV.
  2. For patients with F3–F4 fibrosis, twice-yearly ultrasound monitoring is recommended for HCC surveillance.
  3. Baseline endoscopic surveillance for cirrhotic patients, and if varices are found they should be treated and followed up in the standard way.
  4. If LFTs are persistently abnormal despite an SVR, other causes of liver disease should be assessed.

Interferon-free all-oral treatment regimens for CHC since 2014

  • In December 2013 and January 2014, second-generation DAAs were approved by the FDA for treatment of chronic hepatitis genotype 1, which is the most prevalent genotype and one that is considered to be difficult to treat. The first of these was sofosbuvir (SOF), which is an NS5B polymerase inhibitor. The first trial using SOF/RBV was the ELECTRON study. This reported SVRs in 84% of 25 treatment-naïve patients after 24 weeks of therapy (SVR 24). In a subsequent study of a regimen consisting of sofosbuvir and RBV for 24 weeks in 60 treatment-naïve patients with genotype 1 with poor prognostic factors such as African-American ethnicity, ccIL28B, and viral load more than 800,000 IU/mL, the SVR 24 rates were 68%.
  • In the ELECTRON study, SOF/RBV was administered in genotype 2 and 3 patients without cirrhosis, and 100% achieved SVR 24. In the FISSION trial, with SOF/RBV administered for 12 weeks in 499 treatment-naïve patients, the SVR 12 rates were 97% for patients with HCV genotype 2. In genotype 3 patients, the SVR 12 rates were only 56%. Similarly, in the POSITRON trial the SVR 24 rates after 24 weeks of treatment were 61% for genotype 3 and 93% for genotype 2. Similar results were achieved in the FUSSION trial, with poor SVR rates of 62% for patients infected with genotype 3.
  • Since then, a number of drugs in separate or fixed-dose combinations have been approved by the FDA, including daclatasvir, 3D Regimen, paritaprevir + dasabuvir/ombitasvir + ritonavir (Viekira pak).
  • One of the most recent FDA-approved pan-genotype combinations, available under the trade name Epclusa, contains sofosbuvir + velpatasvir. In a phase 3 trial, Feld et al. administered this combination for 12 weeks and reported an SVR 12 of 99% in patients with genotypes 1, 2, 4, 5, and 6. The ASTRAL-3 trial reported an SVR 12 of 95% in genotype 3 patients treated with sofosbuvir + velpatasvir for 12 weeks. In another trial, Curry et al. used this combination in decompensated patients, with SVRs of 83% in patients who used the combination for 12 weeks, 86% in those who used it for 24 weeks, and 94% in patients who used the combination along with ribavirin for 12 weeks.
  • Zepatier is another pan-genotypic DAA-based combination approved in 2016. The combination contains 100 mg of grazoprevir and 50 mg of elbasvir. A combination of Zepatier with sofosbuvir was investigated in the C-SWIFT study, with an efficacy of more than 90% when given for 8 weeks in patients with genotype 1 and 12 weeks in those with genotype 3.

Treatment of special populations

As the new DAAs have better efficacy and safety, the argument for early treatment has become relatively weaker. The new recommendations are therefore as follows.
  • Regular laboratory monitoring with HCV RNA is recommended at least for 6 months in order to assess spontaneous clearance.
  • Counseling is required for patients with acute HCV infection to ensure avoidance hepatotoxic drugs (e.g., acetaminophen) and alcohol. The patients should also take precautionary measures to reduce the risk of transmitting the disease to others.
  • Early treatment can only be considered in special circumstances—e.g., in individuals who are at risk of transmitting the disease to others (such as intravenous drug abusers, or surgeons), patients who are already suffering from advanced liver disease for some other reason, and those in whom the chances of being lost to follow-up are greater. Even in these patients, one should at least wait for 12–16 weeks before starting therapy.
  • If indicated, treatment for acute HCV infection can be administered using DAAs with the same regimens as for chronic disease.
  • Prophylactic therapy is not recommended in needlestick injuries, as the infectivity rate is very low.

Recommendation Grading



Hepatitis C

Authoring Organization

Publication Month/Year

February 1, 2017

Last Updated Month/Year

January 17, 2024

Document Type


External Publication Status


Country of Publication


Inclusion Criteria

Female, Male, Adult, Older adult

Health Care Settings

Ambulatory, Long term care, Outpatient

Intended Users

Social worker, epidemiology infection prevention, nurse, nurse practitioner, physician, physician assistant


Counseling, Assessment and screening, Diagnosis, Prevention, Management

Diseases/Conditions (MeSH)

D006526 - Hepatitis C


hepatitis C, HCV, acute infection, chronic infection