Hepatitis C virus (HCV)

Hepatitis C virus (HCV)

Hepatitis C virus (HCV) is a small enveloped RNA virus and a member of the family Flaviviridae. HCV comprises six genotypes and hundreds of subtypes with variable geographical distribution and bears significance in determining the rate of liver disease progression, development of HCC and specific therapeutic responses.

Clinical presentation

Initial and extrahepatic manifestations

Initial symptoms of HCV are often extrahepatic, most commonly involving the joints, muscle, and skin.

• Arthralgias

• Paresthesias

• Myalgias

• Pruritus

• Sicca syndrome

• Sensory neuropathy

Manifestations of advanced or decompensated liver disease

Symptoms characteristic of complications from advanced or decompensated liver disease are related to synthetic dysfunction and portal hypertension, such as:

• Mental status changes (hepatic encephalopathy)

• Ankle edema and abdominal distention (ascites)

• Hematemesis or melena (variceal bleeding)

Signs in patients with decompensated liver disease

Hand signs

• Palmar erythema

• Dupuytren contracture

• Asterixis

• Leukonychia

• Clubbing

Head signs

• Icteric sclera

• Temporal muscle wasting

• Enlarged parotid gland

• Cyanosis

Other signs

• Fetor hepaticus

• Gynecomastia

• Small testes

Abdominal signs

• Paraumbilical hernia

• Ascites

• Caput medusae

• Hepatosplenomegaly

• Abdominal bruit

• Ankle edema

• Scant body hair

Skin signs

• Spider nevi

• Petechiae

• Excoriations due to pruritus

Other common extrahepatic manifestations

• Cryoglobulinemia

• Membranoproliferative glomerulonephritis

• Idiopathic thrombocytopenic purpura

• Lichen planus

• Keratoconjunctivitis sicca

• Raynaud syndrome

• Sjögren syndrome

• Porphyria cutanea tarda

• Necrotizing cutaneous vasculitis

Investigations

General baseline studies

General baseline studies in patients with suspected HCV include:

• FBP

• LFT

• RFT

• TSH

• T3

• Screening tests for coinfection with HIV or HBV

• Screening for alcohol abuse, drug abuse, or depression

• Pregnancy testing

Tests for detecting HCV infection

• Hepatitis C antibody testing

• Qualitative and quantitative assays for HCV RNA PCR

• HCV genotyping

• Serologic testing (essential mixed cryoglobulinemia is a common finding)

Treatment

Use pangenotypic drugs which are efficacious, safe and cost-effective.

Who to treat

• Confirmed cases of Hepatitis C irrespective of clinical stage of the liver disease

• Patients with HCC who are eligible for liver transplant if feasible

• Liver transplant patients if MELD score is < 18 (pre transplant) or >18 (post-transplant)

Who not to treat

• HCC patients who are not eligible for liver transplant

• Patient with limited life expectancy due to ESLD (by MELD score or Child-Pugh), or non-hepatic related comorbidities

Pharmacological treatment

All individuals diagnosed with HCV infection who are ≥ 12 years old are eligible for treatment. In children (<12 years old), the treatment should be deferred until they reach that age.

Regimen for genotypes 1, 4, 5 and 6

• Ledipasvir (PO) 90 mg 24 hourly for 12–24 weeks

AND

• Sofosbuvir (PO) 400 mg 24 hourly for 12–24 weeks

AND

• Ribavirin (PO) given in two divided doses:

  • <75 kg body weight = 1 g/day

  • 75 kg body weight = 1.2 g/day

Duration:

• 12 weeks in treatment-naive patients

OR

• 24 weeks in treatment-experienced patients

Alternative regimen

• Sofosbuvir (PO) 400 mg daily

AND

• Ledipasvir (PO) 90 mg daily

AND

• Ribavirin if a patient has been previously exposed to other antivirals

When to stop medications

• Ribavirin regimen should be stopped if patients’ HB drops to <8.5 g/dL during follow up schedules.

• If there is adverse drug reaction.

• When there are ALT flares or massively increased ALT (>10 × ULN).

• If there is evidence of drug-to-drug interactions, consider switching with medication with a less interacting potential.

Clinical monitoring and follow up

• Assess treatment adherence, tolerance and toxicity at 4 weeks after treatment initiation.

Treatment toxicity

• Stop Ribavirin if HB drops to <8.5 g/dL.

• Stop all DAAs if ALT >10 × ULN and other causes have been ruled out.

• Stop Sofosbuvir if eGFR drops to <30 mL/min/1.73 m².