Hepatitis C — Causes, Genotypes, RNA Testing & Direct-Acting Antiviral Cure Guide — Symptoms, Causes & Treatment | MyMedicPlus

Hepatitis C virus (HCV) infection is a bloodborne viral disease causing chronic hepatic inflammation in 55–85% of infected individuals. Of the 6 HCV genotypes (GT1-6, with multiple subtypes), GT1 predominates in Europe and North America (60%), GT3 in South Asia and parts of Europe (20%), and GT4-6 in Africa, the Middle East, and Asia. An estimated 58 million people live with chronic HCV globally, with 1.5 million new infections annually and 290,000 deaths per year from HCV-related cirrhosis and hepatocellular carcinoma (HCC). The advent of direct-acting antivirals (DAAs) since 2014 has transformed HCV from a chronic, difficult-to-treat disease to one that is curable in over 95% of patients with short 8–12-week oral regimens with minimal side effects. The WHO targets HCV elimination as a public health threat by 2030.

HCV is transmitted via percutaneous exposure to infected blood. Principal transmission routes: injecting drug use (sharing needles, syringes, or equipment — the dominant route of new HCV infection in high-income countries, accounting for 70–80% of new cases); blood transfusion or organ transplantation prior to universal HCV screening (1992 in most developed countries — major historical route); unsterile medical, dental, or tattooing equipment (major route in low-income countries); needlestick injuries in healthcare workers; vertical transmission (mother-to-child — approximately 5–6%, risk increased if mother is HIV co-infected); and sexual transmission (low risk in heterosexual couples — 0.07%/year; higher in HIV-positive MSM, particularly with high-risk sexual practices). HCV is not transmitted through casual contact, saliva, hugging, or sharing food/utensils.

Acute HCV infection (first 6 months): 70–80% are asymptomatic. Those with symptoms develop a self-limiting hepatitis: fatigue, nausea, anorexia, right upper quadrant discomfort, mild jaundice, and elevated ALT. Spontaneous viral clearance occurs in only 15–45% of acute cases. Chronic HCV infection: predominantly asymptomatic for decades. Symptoms develop with progressive liver fibrosis and cirrhosis. Fatigue is the most common chronic symptom (reported in 50–70%). As cirrhosis develops: ascites (abdominal distension from fluid accumulation), variceal bleeding (haematemesis or melaena — from portal hypertension), jaundice, peripheral oedema, hepatic encephalopathy (confusion, asterixis), and splenomegaly. Extrahepatic manifestations: cryoglobulinaemia (joint pain, purpura, peripheral neuropathy), membranoproliferative glomerulonephritis, porphyria cutanea tarda, lichen planus, and lymphoma (B-cell non-Hodgkin's).

HCV antibody test (anti-HCV IgG — ELISA): first-line screening test. Positive result confirms HCV exposure but does not distinguish active infection from past cleared infection. Window period: antibodies may be undetectable in the first 8–12 weeks post-exposure — RNA testing detects infection earlier. HCV RNA (PCR): confirms active viraemia and quantifies viral load (IU/mL); detectable from 1–2 weeks post-infection. HCV RNA is the definitive test for active infection — negative anti-HCV with positive HCV RNA suggests acute infection in the window period (or immunocompromised host unable to produce antibodies). HCV genotype testing: guides DAA regimen choice and duration in some settings. Liver assessment: liver function tests (ALT, AST, bilirubin, albumin, INR); FIB-4 score (non-invasive fibrosis marker using age, AST, ALT, platelet count) — FIB-4 above 3.25 suggests advanced fibrosis (F3–F4); liver stiffness measurement (FibroScan elastography — non-invasive quantification of liver fibrosis); liver biopsy (rarely required now — gold standard but invasive). Assessment for HCC: ultrasound + AFP every 6 months in all patients with cirrhosis.

Modern direct-acting antivirals (DAAs) are highly effective, well-tolerated, and achieve sustained virological response (SVR — undetectable HCV RNA 12 weeks post-treatment, equivalent to cure) in over 95% of patients regardless of genotype. Pan-genotypic DAA regimens: sofosbuvir/velpatasvir (Epclusa) — 12 weeks, all genotypes, can be used in compensated cirrhosis; glecaprevir/pibrentasvir (Maviret) — 8 weeks for non-cirrhotic patients (all genotypes), 12 weeks for compensated cirrhosis; ledipasvir/sofosbuvir (Harvoni) — 8–12 weeks for GT1, 4, 5, 6. Decompensated cirrhosis: sofosbuvir/velpatasvir/voxilaprevir (Vosevi) or sofosbuvir + ribavirin with hepatology specialist input. SVR12 results in: normalisation of liver inflammation, regression of liver fibrosis in 75% of patients with advanced fibrosis, significantly reduced risk of cirrhosis progression, decompensation, and HCC. HCC risk does not disappear after SVR in cirrhotics — ongoing 6-monthly ultrasound surveillance is required. Patients with active injecting drug use or on opioid substitution therapy (methadone, buprenorphine) should be treated without delay — DAAs are safe with these medications.

Chronic HCV infection causes progressive hepatic fibrosis and a range of serious complications if untreated. Cirrhosis develops in 15–20% of chronically infected patients after 20–30 years — a risk dramatically accelerated by heavy alcohol use, HIV coinfection, and metabolic liver disease. Once cirrhosis is established, annual HCC incidence is 1–3%, and 5-year risk of decompensation (variceal bleeding, ascites, hepatic encephalopathy) is 15–20%. Hepatocellular carcinoma (HCC) is a major complication — HCV is responsible for approximately 25% of global HCC cases; surveillance with 6-monthly ultrasound remains mandatory even after successful DAA cure in patients with cirrhosis, as HCC risk persists (though substantially reduced post-SVR). Life-threatening decompensation events from portal hypertension include variceal haemorrhage (oesophageal and gastric varices causing massive upper gastrointestinal bleeding — mortality per episode 15–25%), ascites, spontaneous bacterial peritonitis, hepatic encephalopathy (confusion to coma from ammonia accumulation), and hepatorenal syndrome (functional acute kidney failure). Extrahepatic manifestations of HCV are immune complex-mediated: mixed cryoglobulinaemia (causing cutaneous vasculitis with palpable purpura, peripheral neuropathy, arthralgia, and membranoproliferative glomerulonephritis), B-cell non-Hodgkin lymphoma (2-fold increased risk), lichen planus, and porphyria cutanea tarda. Successful DAA treatment achieving SVR significantly reduces — but does not eliminate — the long-term risk of cirrhosis complications and HCC, making ongoing surveillance in high-risk patients essential even after cure.

There is no vaccine for HCV. Prevention strategies focus on harm reduction: use of sterile needles and syringes for every injection — needle exchange programmes are highly effective; do not share any drug equipment (spoons, cotton, water, tourniquets); ensure tattooing and body piercing is done with sterile equipment in regulated settings; universal HCV blood product screening (virtually eliminates transfusion-transmitted HCV in countries with screening programmes); post-exposure prophylaxis (no effective PEP exists for HCV — management is observation with HCV RNA at 4–6 weeks and 12 weeks post-exposure); HCV testing for all people who inject drugs (annually or more frequently), blood transfusion recipients before 1992, and HIV-positive individuals (particularly MSM). Following SVR, patients can be reinfected — safe injecting practices should be maintained. Avoid alcohol in chronic HCV — accelerates liver fibrosis progression significantly.

Request HCV testing from your GP if: you have ever injected drugs (even once), received a blood transfusion or organ transplant before 1992, were born to an HCV-positive mother, or have unexplained elevated liver enzymes (ALT). All HIV-positive individuals should be tested for HCV. If diagnosed with HCV, seek prompt referral to a hepatologist or specialist with experience in DAA prescribing — treatment should not be delayed, as newer pan-genotypic regimens cure over 95% of patients regardless of genotype or prior treatment history. Seek urgent assessment for: haematemesis or melaena (varices), severe abdominal pain with ascites (spontaneous bacterial peritonitis), or sudden confusion in a person with known cirrhosis (hepatic encephalopathy) — these are life-threatening complications of advanced liver disease.