[2] HCV is spread primarily by blood-to-blood contact associated with injection drug use, poorly sterilized medical equipment, needlestick injuries in healthcare, and transfusions.

[17] Symptoms and laboratory findings suggestive of liver disease should prompt further tests and can thus help establish a diagnosis of hepatitis C infection early on.

[26] Liver cirrhosis may lead to portal hypertension, ascites (accumulation of fluid in the abdomen), easy bruising or bleeding, varices (enlarged veins, especially in the stomach and esophagus), jaundice, and a syndrome of cognitive impairment known as hepatic encephalopathy.

[28] The most common problem due to hepatitis C but not involving the liver is mixed cryoglobulinemia (usually the type II form) – an inflammation of small and medium-sized blood vessels.

[53] Percutaneous contact with contaminated blood is responsible for most infections; however, the method of transmission is strongly dependent on both geographic region and economic status.

[15] Tattooing is associated with two- to threefold increased risk of hepatitis C.[56] This could be due to improperly sterilized equipment or contamination of the dyes used.

[63] A fomite (/ˈfoʊmaɪt/) or fomes (/ˈfoʊmiːz/) is any inanimate object that, when contaminated with or exposed to infectious agents (such as pathogenic bacteria, viruses or fungi), can transfer disease to a new host.

[66] HCV is not spread through casual contact, such as hugging, kissing, or sharing eating or cooking utensils,[66] nor is it transmitted through food or water.

[24] Limitations in the implementation and enforcement of stringent standard precautions in public and private medical and dental facilities are known to have been the primary cause of the spread of HCV in Egypt, the country that had the highest rate of infection in the world in 2012, and currently Egypt becomes the first country to achieve WHO validation on the path to elimination of hepatitis C.[70] For more, see HONOReform (Hepatitis Outbreaks National Organization for Reform).

[18] Chronic infections are typically asymptomatic during the first few decades,[18] and thus are most commonly discovered following the investigation of elevated liver enzyme levels or during a routine screening of high-risk individuals.

[16] A recombinant immunoblot assay is used to verify the immunoassay and the viral load is determined by an HCV RNA polymerase chain reaction.

[8] Previously, testing was recommended for those at high risk, including injection drug users, those who have received blood transfusions before 1992,[63] those who have been incarcerated, those on long-term hemodialysis,[63] and those with tattoos.

[108] Several alternative therapies are claimed by their proponents to be helpful for hepatitis C, including milk thistle, ginseng, and colloidal silver.

[4] Spontaneous resolution following acute infection appears more common in females and younger patients and may be influenced by certain genetic factors.

[4] Hepatitis C infection rates increased substantially in the 20th century due to a combination of intravenous drug abuse and the reuse of poorly sterilized medical equipment.

[117] It was believed that the high prevalence in Egypt was linked to a discontinued mass-treatment campaign for schistosomiasis, using improperly sterilized glass syringes.

Despite this discovery, international research efforts to identify the virus, initially called non-A, non-B hepatitis (NANBH), failed for the next decade.

In 1987, Michael Houghton, Qui-Lim Choo, and George Kuo at Chiron Corporation, collaborating with Daniel W. Bradley at the Centers for Disease Control and Prevention, used a novel molecular cloning approach to identify the unknown organism and develop a diagnostic test.

[130] In 1988, Alter confirmed the virus by verifying its presence in a panel of NANBH specimens, and Chiron announced its discovery at a Washington, D.C. press conference in May 1988.

Chiron's Japanese marketing subsidiary, Diagnostic Systems KK, introduced the term "Hepatitis C" in November 1988 in Tokyo news reports publicizing the testing of the emperor's blood.

In response, the pharmaceutical industry established a nationwide network of "Astro-Turf" patient advocacy groups to raise awareness (and fear) of the disease.

[139] This discovery enabled proper characterization of the viral particle and rapid research into the development of protease inhibitors replacing early interferon treatments.

These drugs are marketed as "cures;" however, because they were approved on the basis of surrogate markers and not clinical endpoints such as prolonging life or improving liver health, many experts question their value.

[140][141] After blood screening began, a notable hepatitis C prevalence was discovered in Egypt, which claimed six million individuals were infected by unsterile needles in a late 1970s mass chemotherapy campaign to eliminate schistosomiasis (snail fever).

[155] Factors associated with an increased rate of infection include membrane rupture of longer than 6 hours before delivery and procedures exposing the infant to maternal blood.

HCV infection is frequently found in children who have previously been presumed to have non-A, non-B hepatitis, and cryptogenic liver disease.

People with stable HIV who never received medication for HCV may be treated with a combination of peginterferon plus ribavirin with caution to the possible side effects.

Despite moderate success, research highlights the need for pre-clinical testing in mammalian systems such as mouse, particularly to develop vaccines in poorer communities.

While scientists have used human cell culture systems such as hepatocytes, questions have been raised about their accuracy in reflecting the body's response to infection.

This engineering process is known to create humanized mice and provide opportunities to study hepatitis C within the 3D architectural design of the liver and evaluate antiviral compounds.