Hepatitis C

Overview

Hepatitis C is an inflammation of the liver caused by the hepatitis C virus (HCV). HCV is an RNA virus in the Flaviviridae family. HCV infection may result in acute hepatitis, but may also be asymptomatic. A significant proportion of patients develop chronic hepatitis which can result in chronic liver diseases such as cirrhosis and liver cancer. Patients with chronic hepatitis C are infectious, and HCV is most efficiently transmitted by direct percutaneous exposure to infected blood or intravenous drug use. Treatment using direct-acting antivirals (DAAs) is effective but costly.

There is no vaccine for hepatitis C, but it can be treated with antiviral medications.

Disease epidemiology

Globally, it is estimated that approximately 290,000 people died from hepatitis C, mostly from cirrhosis and hepatocellular carcinoma in 2019. The highest burden of disease is in the Eastern Mediterranean Region and European Region, followed by South-East Asia Region and the Western Pacific Region.

The prevalence of HCV in Singapore is estimated to be around 0.1% of the general population, and 2% among persons with HIV infection, mostly among injecting drug users (IDUs). There were 18 cases of acute hepatitis C reported in 2020.

Pathogen(s)

Hepatitis C virus (HCV).

Transmission

Parenteral spread accounts for the majority of cases through shared needles/syringes in IDUs, transfusion of blood or blood products in the pre-1990s, renal dialysis, needle-stick injury or sharing a razor with an infected individual.

Sexual transmission occurs at a low rate – generally less than 1% per year of relationship, or about 2% of spouses in long term relationships – but these rates increase if the index patient is also infected with HIV. There has been a steadily rising incidence of acute HCV in MSM in some parts of the world, which is largely linked to HIV coinfection, presence of other STIs including syphilis and LGV, traumatic anal sex and use of recreational drugs.

Vertical (mother to infant) spread also occurs at a low rate, at about 5% or less. However, higher rates, up to 40%, are seen if the woman is both HIV- and HCV-positive. In all groups, transmission risk correlates with the presence of detectable HCVRNA in the mother’s blood.

Incubation period:  4 to 20 weeks.

Infectious period: 1 week or more before symptoms develop in the acute stage; lifelong in chronic infection.

Clinical features

Persons newly infected with HCV typically are either asymptomatic or have a mild clinical illness. Cases of acute icteric hepatitis is uncommon.

Complications:

• Acute fulminant hepatitis is rare (less than 1% of all hepatitis C infections) but is more common after hepatitis A superinfection of chronic hepatitis C carriers.

• Approximately 50% to 85% of infected patients become chronic carriers, a state which is normally asymptomatic but may cause nonspecific ill health. Type 1 genotype is more likely to clear spontaneously but leads to more severe chronic infection. Once established, the chronic carrier state rarely resolves spontaneously (0.02% per year). Symptoms and/or signs are worse if there is a high alcohol intake or other liver disease. Significant liver disease can be present in the 35% of carriers who have normal serum ALT levels.

• Mortality in acute hepatitis is very low (less than 1%) but up to 30% of chronic carriers will progress to severe liver disease after 14 to 30 years of infection, with an increased risk of liver cancer (approximately 14% of all patients and up to 33% of those with cirrhosis). HIV coinfection also worsens the prognosis although this may be ameliorated to some degree by ART.

Risk factors

Risk factors include:

• Unprotected sex with a person who has HCV or is co-infected with HCV and HIV.

• Having multiple sex partners;Inconsistent condom use if the relationship is not monogamous.

• History or current presence of other STIs.

Men who have sex with men (MSM) and intravenous drug users (IVDU) are considered at risk groups for HCV acquisition.

Diagnosis

• Screening ELISA, confirmatory test e.g. recombinant immuno-blot assay (RIBA), third generation immunoassay or HCV-PCR for RNA. In HIV-infected patients with a low CD4 count (less than 200 cells/mm³) the EIA may be negative and an HCV-PCR may be needed for diagnosis.

• HCV-RNA will be positive after 2 weeks. HCV serology is usually positive (90%) 3 months after exposure but can take as long as 9 months.

• Chronic infection is confirmed if HCV-RNA assay is positive 6 months after the first positive test. All patients being considered for therapy should have a viral RNA test to confirm viraemia and genotype assay.

Treatment and management

All HCV-positive patients should be referred to a liver specialist for consideration of treatment. Patients with hepatitis C should be vaccinated against hepatitis A and B, given the high rate of fulminant hepatitis in co-infection hepatitis A and C and the worse prognosis of hepatitis B and C co-infection.

Acute hepatitis C infection is defined as the first six months of HCV infection following HCV exposure. However, most acute HCV infection goes undetected because the majority are asymptomatic.

With the advent and efficacy of direct acting antiviral (DAA) regimens for chronic HCV infection, there is less urgency to treat acute HCV infection. The Infectious Disease Society of America (IDSA) recommends waiting six months to evaluate for spontaneous clearance of HCV before considering initiating DAA.

In the following situations, treatment during acute phase may be preferable:

• Patients as risk of complications of HCV such as those with severe disease or have other comorbid liver disease.

• Patients who pose a high risk of transmission to others.

Pregnancy and breastfeeding considerations:

• Routine testing for HCV infection is not recommended for all pregnant women. Pregnant women with a known risk factor for HCV infection should be offered counselling and testing.

• There is at present no known way of reducing the risk of vertical transmission. Women should be informed of the potential risk of transmission in pregnancy.

• Breastfeeding: There is no firm evidence of additional risk of transmission except, perhaps in women who are symptomatic with a high viral load.

Refer to the Department of Sexually Transmitted Infections Control (DSC)'s website for more information on HCV.

Precaution, prevention, and control

Hepatitis C screening should be considered in all IDUs, especially if equipment has been shared, and in people sustaining a needle-stick injury if the donor HCV status is:

• Positive or unknown

• Sexual partners of HCV positive individuals

• MSM

• All HIV-positive patients

• Female sex workers

• Tattoo recipients

• Alcoholics

• Ex-prisoners

Routine periodic HCV testing is also recommended for persons with ongoing risk factors (e.g., injecting drug use or hemodialysis).

There is currently no available vaccine or immunoglobulin preparation that will prevent transmission.

Prevention of hepatitis C:

• Using condoms consistently and correctly when engaging in sexual activity.

• Limit the number of sex partners.

• Avoid sharing needles or any equipment used for injecting drugs, piercing, or tattooing.

• Safe and appropriate use of healthcare injections.

• Safe handling and disposal of needles and medical waste.

Management of sexual contacts:

Partner notification should be performed. Contact tracing to include any sexual contact (penetrative vaginal or anal sex) or needle sharing partners during the period in which the index case is thought to have been infectious. The infectious period is from two weeks before the onset of jaundice in acute infection, or trace back to the likely time of infection (e.g. blood transfusion, first needle sharing) although this may be impractical for periods longer than two or three years. Consider testing children born to infectious women. Sexual transmission should be discussed. It seems likely that if condoms are used consistently, then sexual transmission will be avoided.

Notification

Acute hepatitis C is a notifiable disease.

Who should notify:

• Medical practitioners

• Laboratories

When to notify:

• On clinical suspicion or laboratory confirmation

How to notify:

• Please refer to the Infectious Disease Notifications for more information.

Notification timeline:

• Within 72 hours from time of diagnosis

Resources

Refer to the Resources page for the communicable disease surveillance in Singapore.

Refer to DSC’s website for more information about HCV.

References

• Centers for Disease Control and Prevention. STI treatment guidelines: Hepatitis C virus (HCV) infections. 2021.

• Department of Sexually Transmitted Infections Control (DSC). STI management guidelines 7^th edition. 2021.

• World Health Organization. Hepatitis C. 2023.