Overview
Hepatitis C
1. Clinical Overview
Summary
Hepatitis C is a blood-borne viral infection caused by the Hepatitis C Virus (HCV), a positive-sense single-stranded RNA virus of the Flaviviridae family. It is a major cause of chronic liver disease worldwide. Transmission occurs via blood-to-blood contact (Injecting drug use, Blood transfusions pre-screening, Needlestick injuries, Vertical transmission, Rarely sexual). Acute HCV is usually asymptomatic and often undiagnosed; approximately 75-85% progress to chronic infection (Defined as HCV RNA detectable ≥6 months). Chronic HCV can lead to cirrhosis (~20-30% over 20-30 years), hepatocellular carcinoma (HCC), and liver failure. The introduction of Direct-Acting Antivirals (DAAs) has revolutionised treatment – Cure rates (Sustained Virological Response, SVR) now exceed 95% with 8-12 week oral regimens. HCV is curable and elimination is a global health goal. [1,2,3]
Clinical Pearls
"The Silent Killer": Acute HCV is usually asymptomatic. Many patients are diagnosed only when they develop cirrhosis or HCC decades later.
"95%+ Cure Rate with DAAs": Modern DAA regimens cure almost all patients. Treatment is well-tolerated and usually takes 8-12 weeks.
"Transmission = Blood-to-Blood": Primarily IVDU, Historically blood transfusion (Pre-1992), Needlestick, Vertical, Rarely sexual.
"No Vaccine for HCV": Unlike Hepatitis A and B, There is NO vaccine for Hepatitis C.
2. Epidemiology
Demographics
| Factor | Notes |
|---|---|
| Global Prevalence | ~58 million chronically infected worldwide (WHO). |
| UK Prevalence | ~210,000 chronically infected. Significant reduction with treatment scale-up. |
| At-Risk Groups | People Who Inject Drugs (PWID), Received blood transfusion pre-1992, Born in endemic countries, HIV co-infection. |
Transmission Routes
| Route | Notes |
|---|---|
| Injecting Drug Use (IVDU) | Most common in developed countries (~90% of new infections in UK). Sharing needles, Syringes, Paraphernalia. |
| Blood Transfusion / Blood Products | Major route before screening (Pre-1992 UK). Now rare in screened countries. |
| Healthcare-Associated | Needlestick injuries. Unsafe injection practices in some countries. |
| Vertical (Mother-to-Child) | ~5% if mother HCV RNA positive. Higher if HIV co-infection. |
| Sexual Transmission | Low risk in heterosexual monogamous relationships. Higher in MSM (Especially with HIV). |
| Tattoos / Piercings | If unsterile equipment. |
| Other | Sharing razors, Toothbrushes (Rare). |
HCV Genotypes
| Genotype | Global Distribution | Notes |
|---|---|---|
| 1 | Most common globally (~46%). | Historically harder to treat. DAAs highly effective. |
| 2 | Common. | Generally easier to treat. |
| 3 | Common in South Asia, IVDU. | Higher cirrhosis/HCC risk. Some DAA regimens less effective. |
| 4 | Middle East, Africa. | |
| 5, 6 | Less common. |
3. Natural History
Acute HCV
| Feature | Notes |
|---|---|
| Incubation | 2-26 weeks (Average 6-7 weeks). |
| Symptomatic | Only ~15-25%. Jaundice, Fatigue, Nausea, RUQ pain. |
| Spontaneous Clearance | ~15-25% clear virus within 6 months. More common if symptomatic acute infection, Young, Female. |
| Progression to Chronic | ~75-85% develop chronic infection. |
Chronic HCV
| Feature | Notes |
|---|---|
| Definition | HCV RNA detectable ≥6 months. |
| Symptoms | Often asymptomatic for years. Fatigue common. |
| Cirrhosis | ~20-30% develop cirrhosis over 20-30 years. |
| Hepatocellular Carcinoma (HCC) | ~1-4% per year in those with cirrhosis. |
| Factors Accelerating Progression | Alcohol, Obesity, HIV co-infection, HBV co-infection, Older age at infection, Male sex. |
Extrahepatic Manifestations
| Manifestation | Notes |
|---|---|
| Mixed Cryoglobulinaemia | Vasculitis, Rash (Palpable purpura), Glomerulonephritis, Peripheral neuropathy. |
| Glomerulonephritis | Membranoproliferative GN. |
| Porphyria Cutanea Tarda | Skin fragility, Blistering. |
| Lymphoproliferative Disorders | B-cell Non-Hodgkin Lymphoma. |
| Type 2 Diabetes | Increased risk. |
| Fatigue | Common, Even without cirrhosis. |
4. Clinical Presentation
Acute HCV
| Symptom | Notes |
|---|---|
| Asymptomatic | Majority (~75-85%). |
| Jaundice | ~20-30% of symptomatic cases. |
| Fatigue, Malaise | Non-specific. |
| Nausea, Vomiting | |
| RUQ Discomfort | |
| Dark Urine, Pale Stools | If jaundice. |
Chronic HCV
| Symptom | Notes |
|---|---|
| Asymptomatic | Many years. Incidental finding on blood tests. |
| Fatigue | Most common symptom. |
| Cirrhosis Features | Jaundice, Ascites, Variceal bleeding, Encephalopathy (Late). |
| Extrahepatic Features | Rash, Arthralgia, Renal impairment (Cryoglobulinaemia). |
Examination Findings (Chronic/Cirrhosis)
| Finding | Notes |
|---|---|
| Hepatomegaly | Early. |
| Splenomegaly | Portal hypertension. |
| Stigmata of Cirrhosis | Spider naevi, Palmar erythema, Gynaecomastia, Ascites, Caput medusae. |
| Jaundice | Decompensated. |
| Track Marks | If IVDU. |
5. Investigations
Diagnosis
| Test | Interpretation |
|---|---|
| HCV Antibody (Anti-HCV) | Screening test. Positive = Exposure (Past or current). Does NOT distinguish past cleared vs current infection. |
| HCV RNA (PCR) | Confirms Active Infection. Detectable = Current infection. Undetectable = Cleared (Spontaneously or treated). |
Interpretation of Results
| Anti-HCV | HCV RNA | Interpretation |
|---|---|---|
| Negative | Negative | No infection / Very early acute (Window period). |
| Positive | Positive | Active HCV Infection (Acute or Chronic). |
| Positive | Negative | Past cleared infection (Spontaneous or Treated). OR False positive antibody. |
Genotype
| Test | Notes |
|---|---|
| HCV Genotype | Determines treatment regimen. Less critical with pangenotypic DAAs but still performed. |
Liver Disease Assessment
| Test | Notes |
|---|---|
| Liver Function Tests | ALT often elevated (May be normal). |
| FibroScan (Transient Elastography) | Non-invasive assessment of liver fibrosis. |
| FIB-4 / APRI Score | Non-invasive fibrosis scores. |
| Liver Biopsy | Rarely needed now. If fibrosis assessment uncertain. |
| USS Liver | Baseline. Surveillance for HCC if cirrhotic. |
Other Investigations
| Test | Notes |
|---|---|
| HBV Serology | Co-infection. Risk of HBV reactivation with DAA treatment. |
| HIV Test | Co-infection common in PWID. |
| Cryoglobulins | If vasculitis features. |
6. Management
Management Algorithm
SUSPECTED HCV EXPOSURE / RISK FACTORS
(IVDU, Blood transfusion pre-1992, Born in endemic country)
↓
SCREENING
- Anti-HCV Antibody
┌────────────────┴────────────────┐
NEGATIVE POSITIVE
↓ ↓
No HCV infection HCV RNA (PCR)
(Consider repeat if ↓
recent exposure) ┌──────┴──────┐
POSITIVE NEGATIVE
↓ ↓
ACTIVE HCV PAST CLEARED
INFECTION INFECTION
↓
CONFIRM CHRONIC HCV
(HCV RNA positive ≥6 months)
↓
ASSESS LIVER DISEASE
- LFTs
- FibroScan / FIB-4 / APRI
- USS Liver
- HBV / HIV co-infection
- Genotype
↓
TREATMENT (ALL PATIENTS WITH CHRONIC HCV)
┌──────────────────────────────────────────────────────────┐
│ **DIRECT-ACTING ANTIVIRALS (DAAs)** │
│ │
│ PANGENOTYPIC REGIMENS (First-Line, Any Genotype): │
│ - **Sofosbuvir/Velpatasvir (Epclusa)** – 12 weeks │
│ - **Glecaprevir/Pibrentasvir (Maviret)** – 8-12 weeks │
│ │
│ Other Regimens (Genotype-Specific): │
│ - Sofosbuvir/Ledipasvir (Harvoni) – Genotype 1, 4, 5, 6 │
│ - Elbasvir/Grazoprevir (Zepatier) – Genotype 1, 4 │
│ │
│ Treatment Duration: Usually 8-12 weeks │
│ Oral, Well-tolerated, Minimal side effects │
│ │
│ SVR (Cure) >95% │
└──────────────────────────────────────────────────────────┘
↓
SVR12 (Sustained Virological Response at 12 weeks)
- HCV RNA undetectable 12 weeks after treatment end
- = CURE
↓
POST-SVR FOLLOW-UP
┌──────────────────────────────────────────────────────────┐
│ NO CIRRHOSIS: │
│ - Discharge from hepatology │
│ - Lifestyle advice │
│ - Re-test if re-exposure risk │
│ │
│ CIRRHOSIS (Even if Cured): │
│ - **6-monthly HCC Surveillance (USS ± AFP)** │
│ - Variceal surveillance (OGD) │
│ - Ongoing cirrhosis management │
└──────────────────────────────────────────────────────────┘
DAA Classes
| Class | Target | Examples |
|---|---|---|
| NS5B Polymerase Inhibitors | Viral replication | Sofosbuvir |
| NS5A Inhibitors | Viral replication/assembly | Velpatasvir, Ledipasvir, Pibrentasvir |
| NS3/4A Protease Inhibitors | Viral protein processing | Glecaprevir, Grazoprevir |
Special Populations
| Population | Considerations |
|---|---|
| Cirrhosis | May need longer treatment (12 weeks). Consider ribavirin. HCC surveillance post-SVR. |
| Decompensated Cirrhosis | Avoid protease inhibitors. May need liver transplant assessment. |
| HBV Co-infection | Risk of HBV reactivation – Monitor/Treat HBV. |
| HIV Co-infection | Check drug-drug interactions. DAAs highly effective. |
| Renal Impairment | Avoid sofosbuvir in severe CKD (eGFR less than 30). Glecaprevir/Pibrentasvir safe. |
| Pregnancy | DAAs not recommended. Treat before conception. |
7. Complications
| Complication | Notes |
|---|---|
| Cirrhosis | ~20-30% over 20-30 years. |
| Hepatocellular Carcinoma (HCC) | 1-4% per year once cirrhotic. Surveillance essential. |
| Liver Failure | End-stage. Transplant indication. |
| Cryoglobulinaemia | Vasculitis, GN, Neuropathy. Treatment of HCV improves. |
| Extrahepatic Manifestations | As above. |
8. Prognosis and Outcomes
| Factor | Notes |
|---|---|
| SVR (Cure) | Achieved in >95% with DAAs. |
| Post-SVR Without Cirrhosis | Excellent prognosis. Liver inflammation resolves. Low risk of progression. |
| Post-SVR With Cirrhosis | Reduced risk of decompensation and HCC, But risk remains. 6-monthly HCC surveillance mandatory. |
| Untreated Chronic HCV | Progressive liver disease. Cirrhosis, HCC, Liver failure. |
9. Prevention
| Measure | Notes |
|---|---|
| No Vaccine | Unlike HAV/HBV, No HCV vaccine available. |
| Harm Reduction | Needle exchange programmes. Opioid substitution therapy. Reduce transmission in PWID. |
| Blood Screening | All donated blood screened (Since 1991 UK). |
| Universal Precautions | Healthcare settings. |
| Treatment as Prevention | Treating PWID reduces community transmission. |
| Screening Programmes | Case-finding in high-risk groups. |
10. Evidence and Guidelines
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| HCV Management | NICE NG204 (2022) | Treat all with chronic HCV. Pangenotypic DAAs first-line. SVR12 confirms cure. |
| HCV Treatment | EASL (2020) | Similar. Simplified treatment algorithms. |
| HCV Elimination | WHO | Goal: Eliminate HCV as a public health threat by 2030. |
Key Points
- Treat All: All patients with chronic HCV should be offered treatment (Regardless of fibrosis stage).
- Pangenotypic DAAs: Sofosbuvir/Velpatasvir and Glecaprevir/Pibrentasvir are first-line for most patients.
- HCC Surveillance: Continues indefinitely in those with cirrhosis, Even after cure.
11. Patient and Layperson Explanation
What is Hepatitis C?
Hepatitis C is a virus that infects the liver. It is spread through blood-to-blood contact, Most commonly through sharing needles. Before blood donations were tested (Before 1991 in the UK), It could also be spread through blood transfusions.
What are the symptoms?
Most people have no symptoms when first infected. Over many years, The virus can damage the liver, Leading to:
- Tiredness.
- Liver scarring (Cirrhosis).
- Liver failure or Liver cancer (If untreated).
Many people don't know they have it until they are tested.
Can Hepatitis C be cured?
Yes! Hepatitis C is now curable with tablet treatment (Direct-Acting Antivirals). Treatment takes 8-12 weeks and cures more than 95% of people.
Who should be tested?
- Anyone who has ever injected drugs.
- Anyone who received a blood transfusion before 1991.
- People from countries where Hepatitis C is common.
- Healthcare workers with needlestick injuries.
Is there a vaccine?
There is NO vaccine for Hepatitis C (Unlike Hepatitis A and B). Prevention relies on not sharing needles and safe blood supplies.
12. References
Primary Sources
- National Institute for Health and Care Excellence. Hepatitis C (NG204). 2022.
- European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C. J Hepatol. 2020;73(5):1170-1218. PMID: 32956768.
- World Health Organization. Global hepatitis report, 2017. Geneva: WHO, 2017.
13. Examination Focus
Common Exam Questions
- Transmission: "What is the most common mode of HCV transmission in the UK?"
- Answer: Injecting Drug Use (IVDU).
- Progression to Chronic: "What percentage of acute HCV infections become chronic?"
- Answer: 75-85%.
- Cure Marker: "What defines cure (SVR) in HCV?"
- Answer: Undetectable HCV RNA 12 weeks after treatment completion (SVR12).
- Extrahepatic Manifestation: "What is the most common extrahepatic manifestation of HCV?"
- Answer: Mixed Cryoglobulinaemia.
Viva Points
- No Vaccine: Unlike HAV and HBV.
- Antibody Positive, RNA Negative = Cleared: Past infection (Spontaneous or treated). Antibody remains positive for life.
- HCC Surveillance Post-SVR: If cirrhotic, 6-monthly USS ± AFP continues indefinitely even after cure.
- Pangenotypic DAAs: First-line (Sofosbuvir/Velpatasvir or Glecaprevir/Pibrentasvir).
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.