Hepatitis C — Symptoms, Causes & Treatment | MyMedicPlus

Hepatitis C is a liver infection caused by the hepatitis C virus (HCV), an RNA virus transmitted primarily through blood-to-blood contact. Approximately 58 million people have chronic hepatitis C globally, with 1.5 million new infections per year. Unlike hepatitis B, no vaccine exists for HCV. The pivotal development in hepatitis C treatment is the availability of direct-acting antivirals (DAAs) — oral medications that cure hepatitis C in over 95% of patients with 8–12 weeks of treatment, representing one of the greatest therapeutic advances in modern medicine. The hepatitis C virus has 6 major genotypes (genotypes 1–6) with significant geographic variation — genotype 1 predominates in North America and Europe; genotype 3 is common in South and Southeast Asia and is associated with more rapid fibrosis progression. Unlike HIV, HCV has no vaccine, making treatment the primary strategy for disease control and prevention. With effective treatment and cure of all infected individuals, WHO has set ambitious global targets to eliminate HCV as a public health threat by 2030 — a goal achievable with current DAA therapies.

HCV is primarily transmitted through sharing needles and injecting drug equipment — accounting for the majority of new infections in high-income countries. Healthcare-associated transmission occurs through unscreened blood transfusions (pre-1992 blood supply in most countries), contaminated medical equipment, and needle-stick injuries in healthcare workers. Sexual transmission occurs at low rates, elevated in men who have sex with men (MSM) with concurrent HIV or STIs. Mother-to-child transmission occurs in approximately 5% of births to HCV-infected mothers. Unlike HBV, casual contact does not transmit HCV. Blood transfusion-acquired HCV (pre-1992 screening era) affects a large cohort of patients aged 50–70 who were transfused before routine HCV testing was implemented — many are unaware of their infection. Tattoo and body piercing with non-sterile equipment transmit HCV in some settings. In regions with poor infection control, reuse of medical syringes and inadequate sterilisation of medical equipment causes substantial HCV transmission in healthcare settings.

Acute HCV infection is asymptomatic in 70–80% of cases — most people are unaware of infection for years or decades. Symptomatic acute infection causes fatigue, nausea, abdominal pain, and jaundice. Spontaneous viral clearance occurs in only 15–25% of acutely infected people; the remainder develop chronic infection. Chronic HCV progresses silently — many patients are diagnosed only when routine blood tests show elevated liver enzymes or when complications of advanced liver disease develop. Extrahepatic manifestations include mixed cryoglobulinemia (vasculitis, purpura, renal disease), lymphoma, thyroid disease, and type 2 diabetes. Mixed cryoglobulinemia from HCV immune complexes causes purpuric skin rash (palpable purpura from small vessel vasculitis), arthralgias, peripheral neuropathy, and membranoproliferative glomerulonephritis — all extrahepatic manifestations that may resolve with HCV cure. B-cell non-Hodgkin lymphoma risk is 2–3 times higher in HCV-infected individuals due to chronic lymphocyte stimulation. Type 2 diabetes and insulin resistance are independently linked to HCV infection through mechanisms including lipid metabolism disruption and hepatic insulin signalling impairment.

Initial screening uses the HCV antibody test (anti-HCV) — a positive result indicates exposure and needs confirmation. Reactive antibody tests are confirmed by HCV RNA (PCR) testing — detectable as early as 1–2 weeks after exposure. A positive HCV RNA confirms current active infection. HCV genotype (1–6) historically guided treatment choice and duration but is less critical with pangenotypic DAA regimens. FibroScan (transient elastography) and liver biopsy assess fibrosis stage (F0–F4 Metavir scale). WHO recommends universal HCV testing for people who inject drugs, those born between 1945–1965 (baby boomer generation), and those with prior blood transfusions before 1992. HCV RNA quantification using real-time PCR measures viral load in international units per millilitre (IU/mL) — useful for monitoring early treatment response (week 4 viral load) and confirming cure at 12 weeks post-treatment (sustained virological response, SVR12). HCV genotype testing using sequencing or line probe assay remains useful in settings using genotype-specific regimens, although pangenotypic DAAs have reduced its clinical urgency in high-income countries.

Modern DAA regimens cure over 95% of patients with 8–12 weeks of once-daily oral tablets. Pangenotypic regimens effective for all HCV genotypes include: sofosbuvir/velpatasvir (Epclusa, 12 weeks), glecaprevir/pibrentasvir (Mavyret, 8 weeks for treatment-naive patients without cirrhosis), and sofosbuvir/ledipasvir (Harvoni, genotype 1). Cure is defined as sustained virological response (SVR) — undetectable HCV RNA at 12 weeks after treatment completion. All patients with chronic HCV should be offered treatment. Drug interactions must be checked as DAAs interact with multiple common medications. Simplified treatment pathways allow primary care and community delivery of DAA therapy. Sofosbuvir (NS5B nucleotide inhibitor) has a very high barrier to resistance due to its mechanism of action and remains the backbone of most DAA regimens. Glecaprevir/pibrentasvir (Mavyret) achieves SVR in 8 weeks in treatment-naive non-cirrhotic patients across all genotypes and is approved for use in renal impairment — unlike sofosbuvir-based regimens which should be used cautiously in eGFR below 30. Treatment monitoring: LFTs, HCV RNA at weeks 4 and 12 post-treatment. Drug interactions with amiodarone (severe bradycardia with sofosbuvir), rifampicin, anticonvulsants, and some antiretrovirals must be checked using dedicated interaction tools (Liverpool HCV drug interactions website).

Without treatment, 20–30% of chronically infected patients develop cirrhosis within 20–30 years. Of those with cirrhosis, 1–4% per year develop hepatocellular carcinoma (HCC) and 3–6% decompensate (ascites, variceal bleeding, hepatic encephalopathy). HCV-related cirrhosis was the most common indication for liver transplantation before DAA availability. Importantly, even patients with established cirrhosis who achieve SVR have dramatically reduced risks of cancer and decompensation. HCC surveillance continues in those with cirrhosis even after HCV cure, as cancer risk persists (though substantially reduced) due to established cirrhotic architecture.

No vaccine exists for hepatitis C. Prevention relies on harm reduction: sterile needle programs for people who inject drugs (provide clean needles and syringes), opiate substitution therapy, and HCV testing and treatment as prevention. Never share needles, syringes, drug equipment, razors, or toothbrushes. Use standard precautions for blood exposure in healthcare settings. Achieve SVR through complete DAA treatment to eliminate infection and prevent liver disease progression. Annual HCV RNA testing is recommended for people who inject drugs due to reinfection risk after cure. Safe and affordable DAA access in low- and middle-income countries is critical for WHO's 2030 HCV elimination targets.

Get tested for hepatitis C if you have ever injected drugs (even once), had a blood transfusion or blood products before 1992, been born to a hepatitis C-positive mother, or had unprotected sex with a hepatitis C-positive person. Testing is a simple blood test — anti-HCV antibody confirmed by HCV RNA PCR. Seek emergency care for signs of decompensated liver disease: jaundice with confusion (hepatic encephalopathy), haematemesis (variceal bleeding), or severe abdominal distension (ascites). See a hepatologist promptly for: confirmed HCV infection — all chronic HCV patients should receive curative DAA treatment. See a doctor if you are HCV-positive and pregnant — vertical transmission risk and antiviral treatment decisions require specialist guidance. Hepatitis C is now curable with 8-12 weeks of oral treatment achieving over 95% cure rate.