Hepatitis C Virus
Venue: Annals of Internal Medicine

The advent of novel therapies has transformed the approach to patients with hepatitis C virus (HCV) infection. This virus is the most common blood borne pathogen in the United States and is estimated to infect over 3 million Americans, most of whom were born from 1945 through 1965 (1, 2) It is a leading cause of morbidity and mortality, primarily through development of liver fibrosis and cirrhosis; persons with chronic infection live an average of 2 decades less than healthy persons (3) Sustained virologic response (SVR)when HCV RNA is undectable at least 12 weeks after completion of antiviral therapyis considered evidence of cure. This results in a significant reduction of life threatening complications and overall mortality (4) but was achieved in fewer than half of treated patients when interferon based regimens were the standard of care (5) Over the past few years, more efficacious and tolerable regimens have become available. With current antiviral treatment, more than 90% of treated patients can be cured with all oral regimens containing as few as 1 daily pill for 8 to 24 weeks. This revolution in therapeutics has occurred since In the Clinic last reviewed hepatitis C (6) Transmission and Prevention What factors increase the risk for HCV infection? Most persons with HCV were exposed via a percutaneous exposure to infected blood. There are 2 primary methods of blood borne transmission: injection drug use and nosocomial exposure. Shared injection equipment, such as needles and syringes, contaminated with infected blood may result in exposure and transmission. The intensity and duration of exposure increase the probability of infection, explaining the high rates of HCV among persons who inject drugs (PWID) and those with hemophilia who received combined blood products from many donors before implementation of strict screening methods. A growing epidemic of prescription opioid abuse seems to be linked to injection drug use, particularly heroin, resulting in a rapid increase of HCV incidence in various areas of the United States (7) Such cosmetic procedures as tattooing and piercing are considered extremely low risk for HCV transmission as long as strict infection control measures are followed. Nosocomial exposure continues to be a significant source of HCV transmission in settings where infection control measures are not followed. In the United States, that includes exposure to blood products before 1992, when screening of donor blood was instituted. Higher rates of HCV infection are also found in patients receiving hemodialysis and in medical settings around the world that lack adequate infection control practices (8) Outbreaks have also been associated with narcotic diversion by HCV infected health care workers who contaminate equipment by first injecting themselves (9) HCV may be transmitted via sexual transmission, as HCV RNA is occasionally detected in the semen of viremic patients. However, studies of heterosexual couples with discordant serostatus have shown that such transmission is possible but extremely inefficient (10) HCV seems to be transmitted at a higher rate in men who have sex with men (MSM) particularly those who practice unprotected anal intercourse and have HIV (11) HCV may be transmitted from mother to child at a rate of approximately 4%5% (12) Breastfeeding is not associated with transmission and is considered safe (13) How can person to person transmission be prevented? Persons who inject drugs should be enabled to access harm reduction measures, such as opioid agonist therapy (14) and needle and syringe exchange. Together, these measures are more likely to be effective than either alone (15) Tattooing and piercing should be done with strict infection control protocols. Condoms are not recommended for long term heterosexual monogamous couples with discordant HCV serostatus. However, they are recommended for persons with multiple partners and for HIV positive MSM for prevention of HCV and other pathogens. Infections within households can be minimized by avoiding potential blood exposures via shared toothbrushes and razors; other activities, such as sharing utensils, do not result in transmission. Persons who are cured of HCV infection will not infect others. However, reinfection is possible after achievement of SVR, emphasizing the importance of prevention in persons at ongoing risk. No vaccine is currently available against HCV. How can risk be reduced in the health care setting? To minimize the risk for patient to patient transmission, blood banks should avoid paid donors and routinely screen donated products. Health care workers and volunteers should follow infection control practices that avoid reuse of contaminated equipment. Abolishing use of multidose vials should be considered. Postexposure prophylaxis for needlestick injuries to prevent transmission from a patient to a health care worker is not recommended by expert consensus, due to low risk for infection after a single exposure, high efficacy of antivirals if infected, and excess cost (16) Clinical Bottom Line: Transmission and Prevention HCV is most efficiently transmitted by exposure to infected blood. Persons who inject drugs are at highest risk but preventive measures may be effective. Sexual transmission is relatively inefficient; condoms are recommended in the setting of HIV or multiple sexual partners. Nosocomial transmission in health care settings may be prevented by adequate infection control practices. As more persons achieve cure of HCV infection via antiviral therapies, preventing HCV reinfection will be important for those with ongoing risk factors. Screening Should clinicians screen for HCV infection? Screening for HCV infection is warranted because both the acute and chronic phases are mostly asymptomatic. HCV infection is also relatively common in certain populations. There is a long latent periodusually decadesbefore liver disease manifests. Initial HCV serologic testing is relatively inexpensive. Moreover, infected patients can receive counseling to reduce or eliminate alcohol use and to prevent or detect other infections, such as HIV, and can obtain curative treatments that reduce morbidity and mortality and prevent transmission of HCV to others. Models show that screening at risk populations is a cost effective use of health care dollars (17) For these and other reasons, screening for HCV infection in certain populations is recommended by multiple professional societies and the U.S. Preventive Services Task Force (16, 18) What populations should be screened? Persons with a history of risk exposure should be screened at least once. Persons at ongoing risk, particularly PWID and HIV positive MSM, should be screened yearly (19) Because risk factorbased screening has not been entirely successful for various reasons, certain populations, irrespective of known risk factors, should be screened. In particular, the baby boomer generation, born from 1945 through 1965, contains 75% of patients of the HCV population, with U.S. prevalence estimated at 2.6% based on NHANES (the National Health and Nutrition Examination Survey) (1) Persons born in this cohort have the greatest risk for liver related complications due to becoming infected decades ago, including from intravenous drug use even if brief, receipt of blood products before 1992, and exposure to contaminated needles (e.g. tattoos or medical procedures) before the implementation of universal precautions. At least half of individuals with HCV are unaware of their status (1) Preliminary screening projects have found HCV prevalence in this birth cohort as high as 7%11% (20, 21) The higher prevalence may be explained in part by the demographics of the studied populations, as they included underserved populations far less likely to participate in NHANES (2) Persons in this birth cohort should be tested once. Other populations are screened regardless of risk factors, such as persons donating blood or organs. Due to high prevalence rates in settings as jails and prisons, screening should be strongly considered (22) Universal screening of adults outside the 19451965 birth cohort who do not have specific risk factors is not currently recommended.  Screening Screening for HCV is essential due to the long latent period before serious symptoms manifest, availability of therapies that interrupt the natural history, and the associated public and personal health burden. In addition to traditional risk factorbased screening, all persons born from 19451965 should be offered 1 time screening regardless of risk factors.  What is the natural history of HCV infection? The incubation period after exposure to HCV is typically several weeks. HCV RNA usually appears in the blood weeks before either increases in alanine aminotransferase (ALT) levels or development of anti HCV antibodies. This phase is asymptomatic in most individuals; a few will develop flu like symptoms, myalgia, or dark urine. Jaundice is relatively rare, and fulminant disease is extremely rare. Given this largely asymptomatic natural history, the vast majority of patients with acute infection do not present to medical care (23) After acute infection, the virus clears spontaneously in approximately 15%45% of individuals. Clearance is defined as repeated undetected HCV RNA measurements. Spontaneous viral clearance is more common among those who are infected at younger ages, women, and persons with certain genetic polymorphisms (such as the single nucleotide polymorphism rs12979860, near the interferon lambda 4 gene) (24, 25) Spontaneous clearance typically occurs within 612 months; later clearance without treatment has been described but is very rare (25) Patients who spontaneously clear HCV infection are not infectious and do not have an increased risk for HCV related liver disease. Chronic infection is usually asymptomatic but may result in extrah