Gastroenterology · Viral Hepatitis
The facts most likely to be tested
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The HCV antibody (anti-HCV) test is the initial screening tool, but a positive result must be confirmed with HCV RNA PCR to distinguish active infection from resolved disease.
Chronic infection develops in approximately 75-85% of patients, making it a major cause of chronic liver disease; historically the leading indication for liver transplantation in the United States, though alcohol-associated and metabolic (MASH) liver disease now predominate in the DAA era.
Extrahepatic manifestations of Hepatitis C include mixed cryoglobulinemia, porphyria cutanea tarda, and lichen planus.
The current standard of care for treatment is direct-acting antivirals (DAAs), such as sofosbuvir/velpatasvir, which achieve a sustained virologic response (SVR) in over 95% of patients.
Patients with chronic Hepatitis C are at significantly increased risk for hepatocellular carcinoma (HCC), necessitating ultrasound surveillance every 6 months in patients with cirrhosis.
Transmission occurs primarily through parenteral exposure to infected blood, with intravenous drug use (IVDU) being the most significant risk factor.
The CDC recommends one-time universal screening for all adults aged 18 and older regardless of risk (except where HCV RNA prevalence is below 0.1%), plus screening in every pregnancy.
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A 52-year-old male presents to the clinic for a routine physical. He has a history of remote IV drug use in his 20s but denies current symptoms. Physical exam reveals palpable purpura on the lower extremities and arthralgias. Laboratory studies show elevated transaminases and a positive HCV antibody test. A follow-up HCV RNA PCR is positive.
Which of the following extrahepatic conditions is most likely associated with this patient's diagnosis?
Mixed cryoglobulinemia
The patient's presentation of purpura and arthralgias in the setting of chronic Hepatitis C is classic for mixed cryoglobulinemia, a systemic vasculitis associated with HCV.
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Etiology / Epidemiology
Primarily transmitted via IV drug use and blood transfusions (pre-1992). Birth-cohort (1945-1965) testing has been replaced by universal screening of all adults 18 and older.
Clinical Manifestations
Usually asymptomatic; chronic infection leads to cirrhosis and extrahepatic manifestations like cryoglobulinemia.
Diagnosis
Screen with HCV antibody; confirm active infection with HCV RNA PCR.
Treatment
Curative therapy with sofosbuvir/velpatasvir; screen for HBV before initiation.
Prognosis
75-85% progress to chronic infection; hepatocellular carcinoma risk is concentrated in those who develop cirrhosis.
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Epidemiology & Etiology
HCV is a single-stranded RNA virus of the family Flaviviridae (genus Hepacivirus) transmitted via parenteral exposure. IV drug use remains the most common current risk factor. Universal screening is recommended for all adults aged 18+ and all pregnant women during each pregnancy.
Pertinent Anatomy
The virus primarily targets hepatocytes. Chronic inflammation leads to portal fibrosis and eventual cirrhosis, altering hepatic blood flow and synthetic function.
Pathophysiology
HCV induces chronic inflammation, leading to a high rate of viral persistence (75-85%). Persistent immune-mediated damage causes progressive fibrosis, leading to bridging fibrosis and cirrhosis. The virus also triggers immune complex deposition, causing extrahepatic manifestations.
Clinical Manifestations
Most patients are asymptomatic until advanced disease. Look for palmar erythema, spider angiomata, and ascites in cirrhotic patients. Red flags include jaundice, encephalopathy, and variceal bleeding. Associated with mixed cryoglobulinemia (palpable purpura, arthralgias, glomerulonephritis) and porphyria cutanea tarda.
Diagnosis
Initial screening is HCV antibody (anti-HCV). A positive result must be confirmed with HCV RNA PCR to distinguish resolved infection from active viremia. Genotype testing is no longer required for most patients due to pan-genotypic regimens.
Treatment
Under the simplified algorithm, first-line options are glecaprevir/pibrentasvir for 8 weeks or sofosbuvir/velpatasvir for 12 weeks; genotype testing is not required. Black box warning: risk of HBV reactivation; check HBsAg, anti-HBs, and anti-HBc before starting. Treatment is curative, aiming for a sustained virologic response (SVR).
Prognosis
Patients with cirrhosis require ultrasound every 6 months for hepatocellular carcinoma surveillance, continued after cure; confirm cure with HCV RNA 12 weeks or more after therapy ends (SVR12). Chronic infection significantly increases the risk of end-stage liver disease and liver transplantation.
Differential Diagnosis
Hepatitis B: positive HBsAg and IgM anti-HBc
Alcoholic Hepatitis: AST:ALT ratio > 2:1
Autoimmune Hepatitis: positive ANA and anti-smooth muscle antibodies
Hemochromatosis: elevated ferritin and transferrin saturation
Wilson Disease: low ceruloplasmin and Kayser-Fleischer rings