Hepatitis C is a common cause of chronic hepatitis. It is often asymptomatic until manifestations of chronic liver disease occur. Diagnosis is confirmed by finding positive anti-HCV and positive HCV-RNA ≥ 6 months after initial infection. Treatment is with direct-acting antiviral medications; permanent elimination of detectable viral RNA is possible.
(See also Causes of Hepatitis, Overview of Chronic Hepatitis, and Acute Hepatitis C.)
Hepatitis lasting > 6 months is generally defined as chronic hepatitis, although this duration is arbitrary.
There are 6 major genotypes of hepatitis C virus (HCV), which vary in their response to treatment. Genotype 1 is more common than genotypes 2, 3, 4, 5, and 6; it accounts for approximately 70% of cases of chronic hepatitis C in the United States (1).
Acute hepatitis C becomes chronic in 65 to 85% of patients (2). The U.S. Centers for Disease Control and Prevention (CDC) estimate that in 2023 there were approximately 100,000 newly reported cases of chronic hepatitis C (3). Worldwide, 50 million people are estimated to have chronic hepatitis C (4).
Chronic hepatitis C progresses to cirrhosis in 15 to 30% of patients within 20 years (4). Hepatocellular carcinoma can result from HCV-induced cirrhosis but results only rarely from chronic infection without cirrhosis (unlike in chronic HBV infection).
Up to 16% of patients with alcohol-related liver disease harbor HCV (5). The reasons for this high association are unclear because concomitant alcohol and illicit drug use accounts for only a portion of cases. In these patients, HCV and alcohol act synergistically to worsen liver inflammation and fibrosis (6).
General references
1. Manos MM, Shvachko VA, Murphy RC, et al. Distribution of hepatitis C virus genotypes in a diverse US integrated health care population. J Med Virol. 2012;84(11):1744-1750. doi:10.1002/jmv.23399
2. Martinello M, Solomon SS, Terrault NA, et al. Hepatitis C. Lancet. 2023;402(10407):1085-1096. doi:10.1016/S0140-6736(23)01320-X
3. U.S. Centers for Disease Control and Prevention (CDC). 2023 Viral Hepatitis Surveillance Report. Published April 15, 2025. Accessed April 29, 2026.
4. World Health Organization (WHO). Hepatitis C. Published July 25, 2025. Accessed April 30, 2026.
5. Novo-Veleiro I, Calle Cde L, Domínguez-Quibén S, et al. Prevalence of hepatitis C virus infection in alcoholic patients: cohort study and systematic review. Alcohol Alcohol. 2013;48(5):564-569. doi:10.1093/alcalc/agt044
6. Novo-Veleiro I, Alvela-Suárez L, Chamorro AJ, et al. Alcoholic liver disease and hepatitis C virus infection. World J Gastroenterol. 2016;22(4):1411-1420. doi: 10.3748/wjg.v22.i4.1411
Symptoms and Signs of Chronic Hepatitis C
Many patients are asymptomatic and do not have jaundice, although some have malaise, anorexia, fatigue, and nonspecific upper abdominal discomfort. Often, the first findings are signs of cirrhosis (eg, splenomegaly, spider nevi, palmar erythema) or complications of cirrhosis (eg, portal hypertension, ascites, encephalopathy).
Chronic hepatitis C is occasionally associated with lichen planus, cutaneous vasculitis, glomerulonephritis, porphyria cutanea tarda, mixed cryoglobulinemia, and, perhaps, non-Hodgkin B-cell lymphoma. Symptoms of cryoglobulinemia include fatigue, myalgias, arthralgias, neuropathy, glomerulonephritis, and rashes (urticaria, purpura, leukocytoclastic vasculitis); asymptomatic cryoglobulinemia is more common.
Screening for Chronic Hepatitis C
One-time, routine screening is recommended for all people ≥ 18 years old, regardless of risk factors.
One-time screening is recommended for people < 18 years old with the following characteristics (1):
Are currently using or have ever injected illicit drugs, even if only once or only in the distant past
Have used intranasal illicit drugs or glass crack pipes
Are adolescent men who have sex with men
Combine sex with illicit drug use to enhance the sexual encounter ("chem sex")
Are currently or have ever been treated with long-term hemodialysis
Have percutaneous or parenteral exposures in an unregulated setting
Have abnormal alanine aminotransferase (ALT) levels or unexplained chronic liver disease
Work in health care or public safety and were exposed to HCV-positive blood through a needlestick, other injury by a sharp object, or mucosal contact
Have HIV infection or are starting preexposure prophylaxis (PrEP) for HIV
Are infected with HBV
Have ever been incarcerated
Are children born to HCV-infected women
Solid organ transplant donors and recipients
Such testing is important because symptoms may not develop until the hepatitis C has extensively damaged the liver, years after the initial infection.
Screening reference
1. American Association for the Study of Liver Disease (AALD) and the Infectious Disease Society of America (IDSA). HCV Testing and Linkage to Care. Updated October 24, 2022. Accessed April 30, 2026.
Diagnosis of Chronic Hepatitis C
Serologic testing (anti-HCV) with reflex HCV-RNA polymerase chain reaction (PCR)
The diagnosis of chronic hepatitis C is suspected in patients with any of the following:
Suggestive symptoms and signs
Incidentally noted elevations in aminotransferase levels
Previously diagnosed acute hepatitis
Serologic testing for anti-HCV is performed initially, followed by confirmatory HCV-RNA PCR if positive. In immunocompromised patients or those who were exposed ≤ 6 months ago, HCV-RNA PCR should be sent initially as antibodies may be absent (1). Diagnosis of chronic hepatitis C is confirmed by positive anti-HCV and detectable HCV-RNA persisting ≥ 6 months after initial infection (see table ).
Hepatitis C Serology and Nucleic Acid Amplification Testing
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; PCR = polymerase chain reaction. | |||
Liver biopsy is rarely used in the evaluation of hepatitis C and has been supplanted by noninvasive imaging (eg, ultrasound elastography, magnetic resonance elastography) and serum markers of fibrosis, as well as scoring systems for fibrosis based on serologic markers.
HCV genotyping is not routinely required in treatment-naive patients because first-line therapies are effective in treating HCV across the range of genotypes ("pangenotypic") (2). However, genotype testing may be useful to guide treatment after treatment failure or when considering a genotype-specific treatment regimen.
Quantitative HCV-RNA testing is used primarily to evaluate treatment response during and after treatment, and to identify a sustained virologic response to treatment (3).
Other tests
Liver tests are needed if not previously performed; they include serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase.
Other tests should be performed to evaluate liver function; they include serum albumin, bilirubin, platelet count, and prothrombin time/international normalized ratio (PT/INR).
Patients should be tested for HIV and hepatitis B infection because transmission of these infections is similar.
If symptoms or signs of cryoglobulinemia develop during chronic hepatitis C, cryoglobulin levels and rheumatoid factor should be measured; high levels of rheumatoid factor and low levels of complement suggest cryoglobulinemia.
Noninvasive assessment of fibrosis (FIB-4 index or other blood-based tests, ultrasound, and elastography) is performed to evaluate degree of fibrosis after chronic hepatitis C is diagnosed (4, 5, 6).
Screening for complications
Patients with chronic HCV infection and advanced fibrosis or cirrhosis should be screened every 6 months for hepatocellular cancer with ultrasound and serum alpha-fetoprotein measurement (3, 7).
Diagnosis references
1. American Association for the Study of Liver Diseases (AASLD) and Infection Diseases Society of America (IDSA). HCV Testing and Linkage to Care. Updated October 24, 2022. Accessed May 14, 2026.
2. American Association for the Study of Liver Diseases (AASLD) and Infection Diseases Society of America (IDSA). Initial Treatment of Adults with HCV Infection. Updated October 24, 2022. Accessed May 14, 2026.
3. American Association for the Study of Liver Diseases (AASLD) and Infection Diseases Society of America (IDSA). Monitoring Patients Who Are Starting HCV Treatment, Are on Treatment, or Have Completed Therapy. Updated December 19, 2023. Accessed May 20, 2026.
4. Castera L, Rinella ME, Tsochatzis EA. Noninvasive Assessment of Liver Fibrosis. N Engl J Med. 2025;393(17):1715-1729. doi:10.1056/NEJMra2403308
5. Sterling RK, Patel K, Duarte-Rojo A, et al. AASLD Practice Guideline on blood-based noninvasive liver disease assessment of hepatic fibrosis and steatosis. Hepatology. 2025;81(1):321-357. doi:10.1097/HEP.0000000000000845
6. Huttman M, Parigi TL, Zoncapè M, et al. Liver fibrosis stage based on the four factors (FIB-4) score or Forns index in adults with chronic hepatitis C. Cochrane Database Syst Rev. 2024;8(8):CD011929. Published 2024 Aug 13. doi:10.1002/14651858.CD011929.pub2
7. Singal AG, Llovet JM, Yarchoan M, et al. AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology. 2023;78(6):1922-1965. doi:10.1097/HEP.0000000000000466
Treatment of Chronic Hepatitis C
Direct-acting antivirals
Overview of HCV treatment
(See also the American Association for the Study of Liver Disease [AASLD]–Infectious Disease Society of America [IDSA] practice guidelines Recommendations for Testing, Managing, and Treating Hepatitis C and When and in Whom To Initiate HCV Therapy.)
For chronic hepatitis C, treatment is recommended for all patients, except those with a short life expectancy due to comorbid conditions that cannot be remediated by HCV therapy, liver transplantation, or another directed therapy.
The goal of treatment is permanent elimination of HCV-RNA (ie, sustained virologic response), which is associated with permanent normalization of aminotransferase levels and cessation of histologic progression. Treatment results are more favorable in patients with less fibrosis than in patients with cirrhosis (1, 2).
All patients are treated with direct-acting antivirals (DAAs) that affect specific HCV targets, such as proteases or polymerase. HCVGuidelines.org is the source for current guidelines, which are updated frequently. DAAs are not used as single medications but are used in specific combinations to maximize efficacy. Treatment for most patients is with pangenotypic regimens that are effective against all genotypes. First-line pangenotypic regimens include sofosbuvir/velpatasvir and glecaprevir/pibrentasvir (3).
Decompensated cirrhosis due to hepatitis C is a relatively common indication for liver transplantation in the United States (4). HCV recurs almost universally in the graft (5). With DAA use, the sustained virologic response rate in patients who have had a liver transplant exceeds 95% (6). Because response rates are so high, transplantation of HCV-positive organs is performed, particularly among recipients who are also HCV-positive, thus expanding the pool of potential donors. If the recipient and donor are HCV-positive, treatment can be postponed until after transplantation, and an unnecessary pretransplantation course of treatment can be avoided.
Regimens of sofosbuvir/velpatasvir, elbasvir/grazoprevir, or glecaprevir/pibrentasvir are now considered to have a good safety profile and are effective in patients with end-stage kidney disease, including dialysis patients (7).
Treatment of hepatitis C in patients with decompensated cirrhosis should be performed in consultation with hepatologists, ideally in a liver transplantation center (8). HCV regimens that include protease inhibitors (those medications with the ending of -previr) should not be used in patients with decompensated cirrhosis because levels of protease inhibitors are increased in patients with hepatic dysfunction.
Hepatitis B reactivation resulting in liver failure and death has been reported during or after HCV treatment with DAAs (9). Therefore, all patients with hepatitis C being treated with DAAs should be checked for evidence of chronic or prior hepatitis B; tests should include all of the following:
Hepatitis B surface antigen (HBsAg)
Hepatitis B surface antibody (anti-HBs)
IgG antibody to hepatitis B core (IgG anti-HBc)
Patients with chronic hepatitis B or evidence of prior hepatitis B should be monitored for reactivation during and after HCV treatment (although risk of reactivation is low with prior hepatitis B and a negative HBsAg), and HBV antiviral therapy should be considered during the course of HCV treatment.
Treatment references
1. Itokawa N, Atsukawa M, Tsubota A, et al. Efficacy of direct-acting antiviral treatment in patients with compensated liver cirrhosis: A multicenter study. Hepatol Res. 2019;49(2):125-135. doi:10.1111/hepr.13256
2. Miotto N, Mendes LC, Zanaga LP, et al. All-oral direct antiviral treatment for hepatitis C chronic infection in a real-life cohort: The role of cirrhosis and comorbidities in treatment response. PLoS One. 2018;13(7):e0199941. Published 2018 Jul 10. doi:10.1371/journal.pone.0199941
3. American Association for the Study of Liver Diseases (AASLD) and Infection Diseases Society of America (IDSA). Initial Treatment of Adults with HCV Infection. Updated October 24, 2022. Accessed May 14, 2026.
4. Kwong AJ, Kim WR, Lake JR, et al. OPTN/SRTR 2023 Annual Data Report: Liver. Am J Transplant. 2025;25(2S1):S193-S287. doi:10.1016/j.ajt.2025.01.022
5. Dhanasekaran R, Firpi RJ. Challenges of recurrent hepatitis C in the liver transplant patient. World J Gastroenterol. 2014;20(13):3391-3400. doi:10.3748/wjg.v20.i13.3391
6. Brzdęk M, Zarębska-Michaluk D, Tronina O, et al. Treatment with Direct-Acting Antivirals in Patients with HCV Infection After Liver Transplantation. J Clin Med. 2026;15(1):346. Published 2026 Jan 2. doi:10.3390/jcm15010346
7. American Association for the Study of Liver Diseases (AASLD) and Infection Diseases Society of America (IDSA). Patients with Renal Impairment. Updated October 24, 2022. Accessed May 14, 2026.
8. American Association for the Study of Liver Diseases (AASLD) and Infection Diseases Society of America (IDSA). Patients with Decompensated Cirrhosis. Updated October 24, 2022. Accessed May 14, 2026.
9. American Association for the Study of Liver Diseases (AASLD) and Infection FDiseases Society of America (IDSA). HCV Testing and Linkage to Care. Updated October 24, 2022. Accessed May 14, 2026.
Prognosis for Chronic Hepatitis C
Prognosis depends on whether patients have a sustained virologic response (SVR) (ie, no detectable HCV-RNA at 12 weeks after completion of treatment).
Patients who have an SVR have a > 99% chance of remaining HCV-RNA–negative and are typically considered cured (1). Nearly 95% of patients with an SVR have improved histologic findings, including fibrosis and histologic activity index; in addition, risk of progression to cirrhosis, hepatic failure, and liver-related death is reduced. In patients who have cirrhosis and portal hypertension and who were treated with interferon-based regimens, an SVR has been shown to reduce portal pressures and significantly reduce risk of hepatic decompensation, liver-related death, all-cause mortality, and hepatocellular carcinoma (2).
Prognosis references
1. Lynch EN, Russo FP. Outcomes and follow-up after hepatitis C eradication with direct-acting antivirals. J Clin Med. 2023;12(6):2195. doi: 10.3390/jcm12062195
2. van der Meer AJ, Veldt BJ, Feld JJ, et al. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA. 2012;308(24):2584-2593. doi:10.1001/jama.2012.144878
Key Points
Chronic hepatitis C infection develops in 65 to 85% of patients with acute infection and leads to cirrhosis in 15 to 30%; some patients with cirrhosis develop hepatocellular carcinoma.
Diagnosis is confirmed by positive anti-HCV and positive HCV-RNA.
Pangenotypic direct-acting antiviral regimens can permanently eliminate HCV-RNA in > 95% of patients.
Patients with decompensated cirrhosis should be treated by hepatologists, and regimens containing protease inhibitors should not be used.
Drug Information for the Topic
