Hepatitis C is caused by an RNA virus that is often parenterally transmitted. It sometimes causes typical symptoms of viral hepatitis, including anorexia, malaise, and jaundice but may be asymptomatic. Fulminant hepatitis and death rarely occur. Chronic hepatitis develops in about 75% and can lead to cirrhosis and rarely hepatocellular carcinoma. Diagnosis is by serologic testing. Treatment is with antiviral medications. No vaccine is available.
(See also Causes of Hepatitis, Overview of Acute Hepatitis, and Chronic Hepatitis C.)
In the United States, 5023 cases of acute hepatitis C infection were reported in 2021 (1). However, because many cases are not recognized or not reported, the Centers for Disease Control and Prevention (CDC) estimates that the actual number of new infections was 69,800 in 2021 (1). The number of acute hepatitis C cases has been rising in the United States since 2013.
Hepatitis C virus (HCV) is a single-stranded RNA flavivirus that causes acute viral hepatitis and is a common cause of chronic viral hepatitis. Six major HCV subtypes exist with varying amino acid sequences (genotypes); these subtypes vary geographically and in virulence and response to therapy. HCV can also alter its amino acid pattern over time in an infected person, producing quasispecies.
HCV infection sometimes occurs simultaneously with specific systemic disorders, including the following:
Essential mixed cryoglobulinemia
Porphyria cutanea tarda (about 60 to 80% of porphyria patients have HCV infection, but only a few patients infected with HCV develop porphyria)
The mechanisms are uncertain.
Up to 20% of patients with alcohol-related liver disease harbor HCV. The reasons for this high association are unclear because concomitant alcohol and drug use accounts for only a portion of cases. In these patients, HCV and alcohol act synergistically to worsen liver inflammation and fibrosis.
Transmission of hepatitis C
Infection is most commonly transmitted through blood, primarily when parenteral drug users share needles, but also through sharing vessels for intranasal drug use, or tattoos or body piercing with nonsterile equipment.
Sexual transmission and vertical transmission of hepatitis C from mother to infant are relatively rare.
Transmission of hepatitis C through blood transfusion has become very rare since the advent of screening tests for donated blood.
Some sporadic cases occur in patients without apparent risk factors.
HCV prevalence varies with geography and other risk factors.
General reference
1. Centers for Disease Control and Prevention: Viral Hepatitis Surveillance — United States. Accessed June 17, 2024.
Symptoms and Signs of Acute Hepatitis C
Hepatitis C may be asymptomatic during the acute infection. Its severity often fluctuates, sometimes with recrudescent hepatitis and roller-coaster aminotransferase levels for many years or even decades. Fulminant hepatitis is extremely rare.
HCV has the highest rate of chronicity (about 75%). The resultant chronic hepatitis C is usually asymptomatic or benign but progresses to cirrhosis in 20 to 30% of patients; cirrhosis often takes decades to appear. Hepatocellular carcinoma can result from HCV-induced cirrhosis but results only rarely from chronic infection without cirrhosis (unlike in hepatitis B).
Diagnosis of Acute Hepatitis C
Serologic testing
HCV RNA measurement
In the initial diagnosis of acute hepatitis, viral hepatitis should be differentiated from other disorders causing jaundice (see figure Simplified Diagnostic Approach to Possible Acute Viral Hepatitis).
If acute viral hepatitis is suspected, the following tests are done to screen for hepatitis viruses A, B, and C:
IgM antibody to hepatitis A virus (IgM anti-HAV)
Hepatitis B surface antigen (HBsAg)
IgM antibody to hepatitis B core (IgM anti-HBc)
Antibody to HCV (anti-HCV) and HCV RNA
If the anti-HCV test is positive, HCV RNA is measured to distinguish active from past hepatitis C infection (see table Hepatitis C Serology).
In hepatitis C, serum anti-HCV represents chronic, past, or acute infection; the antibody is not protective. When cases are unclear or when suspicion for hepatitis C is high, HCV RNA is measured. Anti-HCV usually appears within 2 weeks of acute infection but is sometimes delayed; however, HCV RNA is positive sooner.
Hepatitis C Serology
Marker | Acute HCV Infection | Chronic HCV Infection | Prior HCV Infection* |
|---|---|---|---|
Anti-HCV | + | + | + |
HCV RNA | + | + | − |
* Patients have had HCV infection and spontaneously recovered or been successfully treated. | |||
Anti-HCV = antibody to HCV; HCV = hepatitis C virus. | |||
Other tests
Liver tests are needed if not previously done; they include serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase.
Other tests should be done to evaluate liver function and disease severity; they include serum albumin, bilirubin, platelet count, and prothrombin time/international normalized ratio (PT/INR).
Treatment of Acute Hepatitis C
Antiviral therapy
There are a number of highly effective direct-acting antivirals (DAAs) for hepatitis C that may decrease the likelihood of developing chronic infection. DAAs also help prevent transmission to others. Current recommendations are to start treatment after the initial diagnosis of acute HCV, without waiting for spontaneous resolution.
Viral hepatitis should be reported to the local or state health department.
Treatment reference
1. American Association for the Study of Liver Diseases (AASLD)–Infectious Diseases Society of America (IDSA): HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C: Management of Acute HCV Infection. Accessed May 8, 2024.
Prevention of Acute Hepatitis C
Patients should be advised to avoid high-risk behavior (eg, sharing needles to inject drugs, getting tattoos and body piercings).
Blood and other body fluids (eg, saliva, semen) are considered infectious. Risk of infection after a single needlestick exposure is about 1.8% (1). Barrier protection is recommended, but isolation of patients is of no value in preventing acute hepatitis C.
Risk of transmission from HCV-infected medical personnel appears to be low, and there are no CDC recommendations to restrict health care workers with hepatitis C infection from working.
Posttransfusion infection is minimized by avoiding unnecessary transfusions and screening all donors for hepatitis B and C. Screening has decreased the incidence of posttransfusion hepatitis B and hepatitis C, which are now extremely rare in the United States.
No product exists for immunoprophylaxis of HCV. The propensity of HCV for changing its genome hampers vaccine development.
Preexposure or postexposure prophylaxis with antiviral therapy is not recommended.
Prevention reference
1. Centers for Disease Control and Prevention: Updated U.S. public health service guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for postexposure prophylaxis. MMWR Recommen Rep 50(RR11):1-42, 2001. PMID: 11442229
Key Points
Hepatitis C is usually transmitted by parenteral contact with contaminated blood; transmission from mucosal contact with other body fluids and perinatal transmission from infected mothers are rare.
About 75% of patients with acute hepatitis C develop chronic hepatitis C, which leads to cirrhosis in 20 to 30%; some patients with cirrhosis develop hepatocellular carcinoma.
Diagnose by testing for antibody to HCV and HCV RNA.
Treat with antivirals after initial diagnosis of hepatitis C, without waiting for spontaneous resolution.
There is no vaccine for hepatitis C.
More Information
The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
Bhattacharya D, Aronsohn A, Price J, et al: Hepatitis C Guidance 2023 Update: American Association for the Study of Liver Diseases– Infectious Diseases Society of America Recommendations for testing, managing, and treating hepatitis C virus infection. Clin Infectious Dis 2023. https://doi.org/10.1093/cid/ciad319
