History and exam
Key diagnostic factors
common
unsafe medical practices
The most common worldwide cause is unsafe injection practices during medical treatment.[32]
intravenous or intranasal drug use
Many infections are due to illicit injection drug use.[35]
history of transfusion or organ transplantation
Blood transfusion before 1992 or clotting factor transfusion before 1987 is a risk factor in the US.
Transfusion-associated cases occurred before blood donor screening. In Western countries, infection occurs in fewer than 1 per 2 million transfused units of blood.[38]
Organ transplant recipients are also at risk.
Other diagnostic factors
uncommon
constitutional symptoms
Chronic hepatitis C is usually asymptomatic, but some patients may have nonspecific symptoms such as fatigue, myalgia, or arthralgia.
jaundice
May indicate advanced liver disease. Less commonly seen in acute infection.
ascites
Indicates advanced liver disease.
signs of hepatic encephalopathy
Confusion, altered consciousness, or coma may suggest advanced liver disease.
extrahepatic manifestations
Occasionally patients may present with signs of extrahepatic manifestations (e.g., vasculitis, renal complications, skin manifestations such as porphyria cutanea tarda).
Risk factors
strong
unsafe medical practices
intravenous or intranasal drug use
Globally, approximately 830,000 new infections attributable to injection drug use occur each year; the US, China, Russia, and India account for approximately 60% of infections.[34] Many infections are due to illicit injection drug use; however, intranasal drug use may also result in infection.[35] The pooled incidence of hepatitis C virus in people who inject drugs was 12.1 per 100 person years between 1992 and 2021, and the risk of acquisition was higher in younger people and women compared to older people and men.[36] The pooled incidence was 13.9 per 100 person years before 2015 and 8.6 per 100 person years between 2015 and 2021.[34]
A combination of needle and syringe programs and opioid substitution therapy (e.g., methadone) reduced the acquisition of hepatitis C by 71% in intravenous drug users compared to minimal harm reduction.[37]
[ 
]
[Evidence C]
blood transfusion or organ transplant
Blood transfusion before 1992 or clotting factor transfusion before 1987 is a risk factor in the US. Similar time frames apply in other resource-rich countries (e.g., before September 1991 [blood transfusion] or 1986 [clotting factor] in the UK).
Transfusion-associated cases occurred before blood donor screening. Currently, in developed countries, infection occurs in fewer than 1 per 2 million transfused units of blood.[38]
Organ transplant recipients are also at risk.
heavy alcohol use
Increases risk for progression to cirrhosis, though not acquisition of or clearance of the virus.
interleukin (IL)-28B gene polymorphism
Favorable IL-28B variant (C/C) is associated with natural viral clearance; patients with the C/C genotype are 3 times more likely to spontaneously clear acute infection relative to patients with variants at the same loci (T/T and C/T).[39]
People with African ancestry are less likely to have the C/C genotype, and as a consequence appear to be least likely to spontaneously clear the virus.[40]
HIV
People with HIV infection are less likely to clear the hepatitis C virus and are more likely to have progression of liver disease (especially if low CD4 counts).[41]
HIV-positive men who have sex with men (MSM) are at substantially increased risk of infection. However, the incidence in HIV-negative MSM is low.[20][42]
weak
dialysis
Prevalence among patients on dialysis, particularly hemodialysis, is consistently higher than in healthy populations, suggesting that dialysis patients may be at higher risk of acquiring the infection.[45] The global prevalence of HCV infection in patients on dialysis has been estimated to be approximately 24%. Prevalence varies depending on geographic region and dialysis type.[46] While the full extent of transmission in dialysis units is unknown, outbreaks continue to occur.[47]
healthcare work
For healthcare workers who sustain percutaneous exposure to blood from an anti-HCV-positive patient, the average risk of transmission of hepatitis C virus is 1.8%, although rates as high as 6% to 10% have been reported.[48]
tattoos/body piercing
acupuncture
Users of acupuncture may have a higher risk of HCV transmission compared with controls.[51] However, studies are conflicting.
multiple sex partners
infected mother (for fetus)
The perinatal (vertical) transmission rate has been estimated to be 6%, and 75% of infants will go on to develop chronic infection and late complications.[28]
Transmission of infection from mothers to infants is increased if the mother is co-infected with HIV or has a high serum titer of hepatitis C virus (HCV) RNA.[54][55]
The risk of vertical transmission associated with amniocentesis and chorionic villus sampling is generally low.[56]
It should be noted that breast-feeding is generally considered safe; however, an infected mother should avoid nursing if she has cracked and/or bleeding nipples.
male sex
vitamin D deficiency
Low vitamin D levels have been associated with severe fibrosis, not achieving sustained virologic response, and advanced inflammation.[58]
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