What are the potential complications of hepatitis C infection?

Complications of Hepatitis C

Hepatic Complications

Hepatitis C virus infection leads to progressive liver disease with cirrhosis developing in 5-20% of chronically infected patients over 20-25 years, followed by hepatocellular carcinoma at a rate of 1-2% annually in cirrhotic patients, and end-stage liver disease occurring in approximately 30% of cirrhotic patients over 10 years. 1, 2

Progression to Cirrhosis

• Chronic infection develops in 55-85% of acutely infected individuals, with the majority progressing silently without symptoms until advanced disease manifests 1, 3
• The median time from infection to cirrhosis is approximately 30 years, though this varies substantially based on individual risk factors 1
• Once compensated cirrhosis develops, 5-year survival exceeds 90%, but drops precipitously to 50% after decompensation 1, 4

Hepatocellular Carcinoma Risk

• The annual incidence of HCC in cirrhotic patients ranges from 1-4% per year, making it a primary cause of HCV-related mortality 4, 5
• Even after achieving sustained virological response (SVR), cirrhotic patients face an 8-year cumulative HCC incidence of 8.7%, compared to only 1.8% in patients with bridging fibrosis 5
• Lifelong HCC surveillance with ultrasound every 6 months remains mandatory for all cirrhotic patients even after viral cure 2, 5
• Age significantly impacts HCC risk post-SVR: patients under 45 years have 2.6% 8-year HCC incidence versus 12.2% in those over 60 years 5

End-Stage Liver Disease

• Patients with HCV-related cirrhosis face approximately 30% risk of hepatic decompensation over 10 years 1, 2
• Decompensation events include ascites, variceal bleeding, hepatic encephalopathy, and hepatorenal syndrome 1
• Portal hypertension portends greater likelihood of developing future hepatic complications in untreated patients 1

Extrahepatic Manifestations

HCV causes numerous immunologically-mediated extrahepatic complications affecting multiple organ systems, with mixed cryoglobulinemia being the most clinically significant. 1, 4

Cryoglobulinemia and Vasculitis

• Mixed cryoglobulinemia represents the chief extrahepatic manifestation, causing systemic vasculitis with skin manifestations and internal organ damage 1, 4
• Symptomatic cryoglobulinemia constitutes an indication for priority antiviral treatment 1, 3
• Membranoproliferative glomerulonephritis occurs as an immune-mediated renal complication 4

Metabolic and Cardiovascular Complications

• Clear causal relationships exist between chronic HCV and insulin resistance, type 2 diabetes mellitus, and cardiovascular diseases 3
• HCV functions as an independent risk factor for cardiovascular manifestations including carotid atherosclerosis, heart failure, and excess cardiovascular mortality 4
• Diabetes mellitus independently predicts more severe liver disease and serves as a risk factor for HCC development post-SVR 4, 5

Other Extrahepatic Conditions

• Porphyria cutanea tarda occurs as a recognized dermatologic complication 4
• Malignant lymphomas show increased incidence in chronic HCV infection 6

Factors Accelerating Disease Progression

Alcohol Consumption

• Daily alcohol intake ≥50 grams increases fibrosis progression risk by 30% and dramatically accelerates cirrhosis development 1, 4
• Even moderate alcohol consumption (>10 grams/day) may enhance disease progression 4
• The combination of obesity and ≥15 alcoholic drinks weekly yields an adjusted relative rate of liver-related death of 18.9, compared to 3.16 in lean individuals 4
• There is no known safe level of alcohol use for patients with chronic hepatitis C 1

Demographic and Metabolic Factors

• Age >40 years at time of infection and male sex independently predict more severe liver disease and faster fibrosis progression 1, 4, 3
• Obesity and substantial hepatic steatosis accelerate disease trajectory 1, 4
• Diabetes mellitus independently predicts more severe disease and increases HCC risk 4, 5

Coinfections

• HIV coinfection accelerates progression to cirrhosis and is associated with 14-fold higher liver-related mortality 2, 3
• HBV coinfection worsens prognosis and requires additional monitoring during HCV treatment due to HBV reactivation risk 1

Critical Clinical Pitfalls

Normal ALT Does Not Exclude Progressive Disease

• Significant fibrosis may be present despite repeatedly normal ALT levels, with 14-24% of persons with persistently normal ALT having more-than-portal fibrosis on biopsy 4, 3
• Assessment of liver disease severity is essential prior to treatment regardless of ALT patterns 1

Persistent Risk After Viral Cure

• Even after achieving SVR, patients with established cirrhosis remain at substantial risk for HCC and require continued surveillance 2, 3, 5
• The inflammatory damage and fibrotic changes are not always fully reversible even with viral eradication 3
• Patients with cirrhosis who achieve SVR show an annual risk of approximately 1% for HCC and 2% for clinical disease progression 5

Treatment Prioritization

• Patients with advanced fibrosis (F3-F4) require priority treatment due to highest risk of complications 2
• Lower platelet counts at baseline independently predict HCC development even after SVR 5
• Treatment should ideally occur before cirrhosis develops to prevent the need for lifelong HCC surveillance 5