Lucan · Conditions

Chronic hepatitis C

Australian guidance: ASHM Australian Consensus Hep C Treatment Guidance

1. Definition and epidemiology

Chronic hepatitis C is defined by detectable hepatitis C virus (HCV) RNA in plasma or whole blood in the absence of clinical features of acute hepatitis, typically persisting beyond six months from initial infection. Approximately 75 to 85 percent of people acutely infected fail to clear the virus spontaneously, developing chronic infection. In Australia, an estimated 117,000 people were living with chronic HCV as of the mid-2020s, with injecting drug use (current or ever) the dominant transmission route; blood transfusions before 1990 account for a significant historical burden.

2. Pathophysiology

HCV is a positive-sense, single-stranded RNA flavivirus with six major genotypes (1 to 6), though genotype-specific treatment distinctions have largely been rendered obsolete by pangenotypic direct-acting antivirals (DAAs). Following hepatocyte infection, viral replication triggers both innate and adaptive immune responses. The virus evades immune clearance through high-level replication and mutation, establishing chronic intrahepatic infection. Persistent viral replication drives a cycle of hepatocyte necrosis, Kupffer cell and stellate cell activation, and progressive periportal and bridging fibrosis (per Robbins Ch 18). The fibrogenic cascade is mediated by transforming growth factor-beta (TGF-beta), which stimulates hepatic stellate cell trans-differentiation to myofibroblasts. Over 15 to 25 years, unchecked fibrosis proceeds through METAVIR stages F0 to F4, culminating in regenerative nodule formation and established cirrhosis. Superimposed steatosis (seen in genotype 3 infection and concurrent metabolic disease) accelerates fibrotic progression. Alcohol is a key modifiable cofactor that markedly amplifies fibrogenesis at any stage.

3. Clinical presentation and diagnostic criteria

Most people with chronic HCV are asymptomatic for decades, which is why targeted testing of at-risk populations is essential. When present, symptoms include fatigue, right upper quadrant discomfort, and non-specific malaise. Advanced disease manifests with features of portal hypertension: spider naevi, palmar erythema, jaundice, encephalopathy, hepatomegaly, splenomegaly, ascites, and peripheral oedema. Extrahepatic manifestations include mixed cryoglobulinaemia, membranoproliferative glomerulonephritis, porphyria cutanea tarda, and lichen planus. Diagnostic criteria require positive HCV antibody (Ab) followed by confirmatory detectable HCV RNA on a reflex or separate PCR test. HCV Ab positivity alone indicates past exposure and does not distinguish active from cleared infection.

4. Investigations and AU-specific cutoffs

The ASHM-recommended initial test is HCV antibody with reflex HCV RNA (qualitative PCR if Ab is positive). Testing is indicated for all people with risk factors including injecting drug use, sharing of snorting equipment, blood transfusions before 1990 in Australia, unsterile tattooing or body piercing, unsterile medical or dental procedures in high-prevalence countries, time in prison, needlestick injury, mother-to-child transmission, men who have sex with men, people with HIV or hepatitis B virus (HBV) co-infection, and those born in high-prevalence regions (Africa, the Middle East, the Mediterranean, Eastern Europe, and South Asia). Clinical indicators for testing include abnormal liver function tests (LFTs), using AU-specific cutoffs: alanine aminotransferase (ALT) above 30 U/L in males or above 19 U/L in females, and jaundice.

Once HCV RNA is confirmed positive, pre-treatment assessment includes: LFTs (including aspartate aminotransferase, AST) and INR; full blood count (FBC); urea, electrolytes, and creatinine with estimated glomerular filtration rate (eGFR); and liver fibrosis staging. Fibrosis staging uses non-invasive methods: the APRI (AST to Platelet Ratio Index) score, with values below 1.0 making cirrhosis unlikely, and elastography (FibroScan), with values above 12.5 kPa consistent with cirrhosis. Viral coinfection screening includes HIV Ab/Ag, hepatitis A IgG (vaccinate if negative), and HBsAg, anti-HBc and anti-HBs (vaccinate if negative). Heavy alcohol use and fatty liver disease should also be assessed.

5. Management

Australian treatment guidance now recommends offering treatment to all people with detectable HCV RNA in plasma or whole blood who have a risk factor for HCV transmission, regardless of the duration of infection. Two first-line pangenotypic DAA regimens are PBS-listed. Prior to prescribing, drug-drug interactions must be checked at hep-druginteractions.org, and PBS Authority Script Line approval obtained (1800 020 613). Patients with cirrhosis (APRI at or above 1.0, or elastography above 12.5 kPa) or prior treatment failure must be discussed with or referred to a specialist before initiating therapy. HCV treatment is not recommended during pregnancy or lactation; contraception counselling is required pre-treatment. Alcohol minimisation and harm reduction strategies should be discussed at every clinical contact.

6. Pharmacology and AU PBS notes

First-line option 1: Sofosbuvir/velpatasvir (SOF/VEL; brand name Epclusa) 400/100 mg once daily as a single tablet. Duration is 12 weeks regardless of whether compensated cirrhosis is present.

First-line option 2: Glecaprevir/pibrentasvir (GLE/PIB; brand name Maviret) 100/40 mg per pill, three pills once daily. Duration is 8 weeks for patients without cirrhosis, and 8 weeks for those with compensated cirrhosis (Child-Pugh A); a 12-week course may be considered at prescriber discretion for compensated cirrhosis.

Both regimens are pangenotypic (effective across HCV genotypes 1 to 6). Side effects are generally minimal with DAA therapy. SOF/VEL requires dose caution with renal impairment (eGFR below 30 mL/min); GLE/PIB is renally safe but is contraindicated in decompensated cirrhosis (Child-Pugh B or C). Specialist referral is required for: prior DAA treatment failure, cirrhosis with APRI at or above 1.0 and no available elastography score, HCV/HIV or HCV/HBV coinfection, eGFR below 50 mL/min, complex drug interactions, complex co-morbidities, and paediatric patients. The online remote consultation form at reach-C.ashm.org.au provides specialist advice with turnaround under 24 hours.

7. Complications and monitoring

During treatment: Monitoring is generally not required routinely, but should be individualised. Dose interruptions are managed according to the duration of DAA therapy.

4 to 12 weeks post-treatment: HCV RNA PCR to confirm sustained virological response (SVR4; a negative result here is defined as cure). LFTs should also be checked at this visit.

Post-treatment follow-up based on clinical status: - No cirrhosis and normal LFTs (males ALT below 30 U/L, females ALT below 19 U/L): no clinical follow-up for HCV is required. - Ongoing risk factors: annual HCV RNA test; if re-infected, offer re-treatment and harm reduction strategies. - Abnormal LFTs post-treatment: evaluate for other causes of liver disease and refer to a specialist. - Cirrhosis confirmed: long-term specialist monitoring is mandatory, including 6-monthly abdominal ultrasound for hepatocellular carcinoma (HCC) surveillance, assessment for oesophageal varices, 2-yearly DEXA scans with serum vitamin D monitoring for osteoporosis, and elastography and platelet count to assess clinically significant portal hypertension.

Key complications of chronic HCV include cirrhosis (15 to 30 percent at 20 years), HCC (annual risk approximately 1 to 4 percent in those with established cirrhosis), hepatic decompensation (ascites, variceal haemorrhage, hepatic encephalopathy, hepatorenal syndrome), and extrahepatic manifestations including mixed cryoglobulinaemic vasculitis and membranoproliferative glomerulonephritis. Achieving SVR is associated with near-elimination of HCC risk in non-cirrhotic patients and meaningful risk reduction even in those with cirrhosis.

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.