Hepatitis C is caused by the hepatitis C virus. The hepatitis C virus is an R.N.A. virus. A flavivirus. Hepatitis C was previously known as non-A, non-B hepatitis. The hepatitis C virus was discovered in patients who received a transfusion and later developed hepatitis and were negative for hepatitis B and hepatitis A. The hepatitis C virus replicates in hepatocytes and some other cells, such as mononuclear cells. The hepatitis C virus has a high mutation rate that can affect treatment outcomes and treatment choices. Infection with more than one genotype of hepatitis C virus is possible. The hepatitis C virus is susceptible to disinfection/ cleaning supplies. Reinfection with hepatitis C virus following successful treatment or spontaneous clearance of infection is possible, although the rate of reinfection is lower than the rate of primary infection.

Worldwide there are an estimated 70 million people are living with hepatitis C. It is estimated that up to 3% of the world's population is infected with the hepatitis C virus (a similar rate in the United States). The n-hanes survey and evaluation estimates a 3% prevalence of hepatitis C infection in the United States. However, the actual prevalence may be higher as n-hanes does not include incarcerated persons, other institutionalized individuals, or homeless people in their sampling. It's estimated that there are up to 50 thousand cases of acute hepatitis C annually in the United States. In the U.S., about 2.5 million people are living with Hepatitis C. The prevalence of Hepatitis C among I.V. drug users in the U.S. is high, around 50%. I.V. Drug use is the most common mode of transmission of Hepatitis C Virus in the United States. Intravenous drug use is the most common highest risk factor for the hepatitis C virus. Efforts to reduce the transmission of H.I.V., such as education regarding safety needle use and needle exchange programs, have also helped decrease the incidence of hepatitis C. Although, the opioid crisis has led to an increased incidence of hepatitis C and H.I.V. in the United States and worldwide. Other at-risk populations/ risk factors for Hepatitis C are patients receiving dialysis, patients who previously received a transfusion, or previously received clotting factors. In the United States, transfusion and receiving clotting factors for hemophilia are no longer a threat for developing Hepatitis C infection due to donor screening for H.C.V. and the use of auto-clave/ pasteurization for clotting factor blood products. Worldwide hepatocellular carcinoma is the second leading cause of cancer death. 

Following exposure to the hepatitis C virus, most people will experience no infection at all. Most hepatitis C exposures do not lead to infection. Others will develop an acute hepatitis C infection that may be symptomatic or asymptomatic. There is more clearance of acute hepatitis C infection if the patient is symptomatic. People with acute and asymptomatic infections have a higher chance of developing chronic hepatitis C. Up to 30 percent of acute infections will be cleared by the immune system and not result in chronic hepatitis C infection. Therefore, most acute infections will result in chronic hepatitis C infection. Over half of the time, acute hepatitis C infection results in chronic hepatitis C infection. Patients with H.I.V. have a greater chance of developing chronic hepatitis C. Chronic hepatitis C can lead to liver cirrhosis and liver cancer, hepatocellular carcinoma. Hepatitis C is a significant cause of cirrhosis, liver failure, and hepatocellular carcinoma. Although, most people with chronic hepatitis C will not experience clinically symptomatic disease. Still chronic hepatitis C is the most common cause of liver transplants in the U.S.. 

Sexual transmission is possible for hepatitis C, more commonly with men who have sex with men. Additionally, sexual transmission occurs more often if someone has H.I.V./ AIDS. Infants of mothers with Hepatitis C are at risk of Hepatitis C infection resulting from vertical transmission. The vertical transmission rate from mother to baby is 6%, 11% if the mother is coinfected with H.I.V.. Breastfeeding does not spread the Hepatitis C virus to the infant. Although breastfeeding is not recommended if there is bleeding or cracking of the nipple. Healthcare workers have the occupational risk of hepatitis C transmission if a needle stick occurs. For hepatitis C, there is up to a 3% rate of seroconversion post needlestick exposure. Outbreaks of hepatitis C can happen in healthcare settings when the standard infection control procedures are not regularly followed. Some low-income countries may still reuse needles in medical facilities. Snorting, nasal inhalation, of cocaine can also transmit the hepatitis C virus. Crack cocaine smoking may also transmit the hepatitis C virus. Skin tattooing may also transmit the hepatitis C virus if tattooing is not done with proper infection control. Transmission from tattooing mainly occurs in incarcerated persons. Incarcerated persons have up to 30% prevalence of hepatitis C in the United States.
 
Many people with chronic hepatitis C infection will never be clinically symptomatic, and they may remain asymptomatic throughout their life. Initial signs and symptoms of hepatitis C infection are non-specific, fatigue, nausea and vomiting, abdominal pain, and possibly jaundice. Chronic hepatitis C infection can cause liver fibrosis which can lead to liver cirrhosis. There are higher rates of liver fibrosis seen with hepatitis C if the patient has fatty liver, non-alcoholic steatohepatitis. More liver fibrosis is seen with the hepatitis C virus genotype three. Hepatitis B and H.I.V. coinfection may make hepatitis C infection worse. H.I.V. makes hepatitis C worse, even successfully treated H.I.V. Measurements of fibrosis can be done by liver biopsy. Estimates of liver fibrosis can also be done with a laboratory test; a ratio test called the A.S.T. to platelet ratio index. Other laboratory estimates of liver fibrosis exist as well. Hepatic elastography ultrasound also measures for liver fibrosis and cirrhosis. Liver cirrhosis and fibrosis are associated with portal hypertension, which may cause ascites, hepato-renal syndrome, and ascites associated with spontaneous bacterial peritonitis. Liver failure may lead to hepatic encephalopathy. Fibrosis and cirrhosis may cause hepatocellular carcinoma. If the patient drinks alcohol, then there is a greater risk of hepatocellular carcinoma. More fibrosis tends to lead to more hepatocellular carcinoma. Patients infected with H.I.V., those who have non-alcoholic steatohepatitis, and people with diabetes are also at increased risk for hepatocellular carcinoma. Hepatocellular carcinoma is associated with an increased risk of non-Hodgkin's lymphoma. Treatment for hepatitis C decreases the risk of hepatocellular carcinoma.

Successful treatment for hepatitis C exists. Current effective treatments for Hepatitis C are called direct-acting antivirals, D.A.A..  In 2013 direct-acting antiviral combination therapy became available. Direct-acting antiviral therapy for the hepatitis C virus is an oral administration treatment lasting 8 to 12 weeks. The treatment options are complicated, and guidelines change with time. Some of the available directly acting antiviral medications are glecaprevir, sofosbuvir, sobuvir, ledipasvir. Treatment for hepatitis C often cures, resulting in R.N.A. from the hepatitis C virus to become undetectable. Pan genotypic direct-acting antivirals are available. Treatment combinations are based on the hepatitis C virus genotype. Before initiation of treatment for hepatitis C by a primary care provider, consulting with a specialist is recommended. Treatment options for hepatitis C depend on the severity of illness, if cirrhosis is present or not, if the patient is coinfected with H.I.V. or other infections such as latent hepatitis b infection, and if there is hepatitis C virus genomic resistance. Around 25% of patients with latent hepatitis B coinfection will experience reactivation of the hepatitis B virus when treated with D.A.A. treatments. The F.D.A. has issued a black box warning for D.A.A. treatments due to their association with the reactivation of the hepatitis B virus. Patients with hepatitis C and those undergoing treatment for hepatitis C should be encouraged to avoid alcohol, alcohol is a hepatotoxin, to avoid tylenol, and encourage weight loss for patients with non-alcoholic steatohepatitis. Patients undergoing hepatitis C treatment with D.A.A medications should also avoid some supplements, including but not limited to iron supplementation and St. John's wort, an herbal medication used for depression. Hepatitis C treatment can cure in just 8-12 weeks of oral therapy. Current therapies for hepatitis C with Direct Acting Antivirals have over a 90% cure rate. Reinfection with the hepatitis C virus following successful treatment for hepatitis C is possible. Primary care providers can treat patients with hepatitis C if they have a backup from a specialist. The project echo program for hepatitis C treatment has helped primary care providers treat hepatitis C with specialist support. Pregnant people are not recommended to receive hepatitis C treatment due to a lack of safety data. Therapy for the hepatitis C virus is recommended before a patient plans on becoming pregnant. Ribavirin treatment is contraindicated in pregnancy. Ribavirin is a category X medication due to concerns of teratogenesis. Breast-feeding is not recommended while receiving hepatitis C treatment. Children less than three or not recommended to receive hepatitis C treatment due to lack of safety data. Vaccination with hepatitis A and hepatitis B vaccines are recommended for those receiving treatment for hepatitis C and patients infected with hepatitis C not receiving treatment. Referral to a liver transplant specialist is recommended if the patient's INR is above 1.5 or if there are signs of liver decompensation.

The U.S.P.S.T.F. recommends all adults aged 18-79 be screened at least once during usual medical care for the Hepatitis C virus, a grade B recommendation. All pregnant people should be screened for hepatitis c during the first pre-natal visit of every pregnancy. Hepatitis C testing should be performed annually in men who have sex with men. And screened at least annually for H.I.V. screening. Additional patients that should be screened for hepatitis C are patients with persistently elevated A.L.T., those on hemodialysis, patients who received clotting factors before 1987, patients with H.I.V., children of infected HCV mothers, patients who were exposed to hepatitis C through sex or needle stick, patients who received transfusion or transplant before 1992 when hepatitis C screening of donor blood with third-generation hepatitis C antibodies was not available, patients who use intravenous drugs, patients with a history of intravenous drug use, even if only one time, men who have sex with men, patients with a history of incarceration, and patients with unexplained liver disease. The screening algorithm starts with hepatitis C antibody screening followed by nucleic acid testing, qualitative or PCR, as a confirmatory test for those with positive hepatitis C screening antibodies. There is no vaccine for the hepatitis C virus.

References:

Pregnancy and breastfeeding - HCV Guidelines (hepcguidelines.org.au)

Dienstag JL. Chronic Hepatitis. In: Jameson J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 20e. McGraw Hill; 2018.

Clinical Guidance for Treatment of Hepatitis C (idsociety.org)

DeMaria, Jr. A. Hepatitis C. In: Boulton ML, Wallace RB. eds. Maxcy-Rosenau-Last Public Health & Preventive Medicine, 16e. McGraw Hill; 2022. 

Recommendation: Hepatitis C Virus Infection in Adolescents and Adults: Screening | United States Preventive Services Taskforce (uspreventiveservicestaskforce.org)