Hepatitis C virus

Associated infections

• Acute hepatitis C
• Chronic hepatitis C infection
• Cirrhosis and hepatic decompensation
• Hepatocellular carcinoma
• Extrahepatic manifestations including mixed cryoglobulinaemia

Transmission route

HCV is transmitted almost exclusively by direct percutaneous exposure to infected blood. The principal routes are the sharing of injecting equipment, transfusion of unscreened blood or blood products, and the reuse or inadequate sterilisation of medical and dental equipment, particularly syringes and needles. In high-income countries with universal donor screening, injecting drug use accounts for the large majority of new infections; historic transfusion-acquired infection remains a significant proportion of the prevalent chronic population. Unsafe therapeutic injection practice remains an important route internationally, and non-medical percutaneous exposures including tattooing, body piercing and cosmetic procedures performed with inadequately sterilised equipment have been implicated.

Perinatal and sexual transmission occur but are considerably less efficient than for hepatitis B virus. Mother-to-child transmission occurs in a small percentage of pregnancies to viraemic women and is more likely where HIV co-infection is present. Sexual transmission is uncommon in heterosexual monogamous relationships but occurs at appreciably higher rates among men who have sex with men, particularly in association with HIV infection and practices that involve mucosal trauma. The virus is not transmitted by casual contact, food, water or breast milk, and there is no evidence of transmission through shared washroom facilities, coughing or sneezing.

In procedural settings, patient-to-patient transmission has been documented and confirmed by phylogenetic analysis in a small number of gastrointestinal endoscopy incidents. Molecular sequencing has been decisive in these investigations, allowing near-identical viral sequences in a source patient and a subsequently infected patient to be distinguished from unrelated community infection. In every well-characterised incident the identified failures were breaches of established practice rather than inadequacies of the recommended process: omission of manual cleaning of the endoscope working channel before disinfection, failure to sterilise reusable biopsy forceps between patients, and unsafe handling of syringes or multi-dose vials during sedation. Large-scale infection control lapses at non-hospital procedural clinics have prompted patient notification exercises involving thousands of individuals, and these have generally found low absolute rates of transmission, which is consistent with the conclusion that where reprocessing is performed correctly the risk of HCV transmission by endoscopy is very low.

Relevance in endoscopy and reprocessing

HCV is the bloodborne virus most closely associated in the published literature with endoscopy-related patient-to-patient transmission, and the incidents concerned repay close reading because they define the specific practice failures that facilities need to guard against. The most frequently identified breach is the abbreviation or omission of manual cleaning of the endoscope working channel before high-level disinfection. Blood and mucus retained within a narrow channel shield residual virus from the disinfectant, so a channel that has not been brushed and flushed cannot be assumed to have been disinfected regardless of what the automated reprocessor cycle log shows. The second is the reuse of channel accessories that require sterilisation, in particular reusable biopsy forceps, which pass through the same lumen and enter tissue; where these were reprocessed by high-level disinfection rather than sterilisation, or reused without any intervening cycle, transmission followed. The third is injection practice during sedation: reuse of syringes, re-entry into a multi-dose vial with a used syringe, or use of a single-patient vial across multiple patients.

When the full reprocessing sequence is applied, the residual risk is very low. Leak testing detects channel damage that would otherwise prevent effective cleaning; point-of-use pre-cleaning prevents soil drying within channels; manual cleaning with correctly sized brushes and a validated detergent removes the organic burden; a validated high-level disinfection cycle with the correct connector set and verified minimum recommended concentration inactivates the virus; and thorough alcohol flushing, forced-air drying and hanging storage prevent both residual moisture and recontamination. Sterilisation, not high-level disinfection, applies to biopsy forceps, sphincterotomes and any accessory that breaches the mucosa. Documented competency of reprocessing staff, traceability linking each device and cycle to each patient, and routine audit of injection practice are the systems that make these steps reliable rather than aspirational.

Where a breach is suspected or confirmed, the response follows the reprocessing-failure pathway. The implicated device and accessories should be quarantined, the reprocessing and traceability records for the affected period retrieved, and the cohort of potentially exposed patients defined by working back to the last cycle known to be compliant. Infection prevention, the sterilising services manager, the proceduralist and executive should convene, and the state or territory public health unit should be engaged early, since it will advise on the threshold for notification and on the testing algorithm. Where a look-back is warranted, affected patients are contacted, offered baseline HCV RNA and antibody testing together with HBV and HIV serology, and offered repeat testing after the relevant window period, with counselling, written information and a clear referral route for anyone found positive. Because HCV is curable, identifying an infected patient through a look-back carries direct clinical benefit, and any transmission identified should be sequenced where possible so that the epidemiological link can be confirmed or excluded rather than assumed.

Interpreting a detection

HCV is not a rinse-water surveillance target and is absent from every water quality parameter set applied under AS/NZS 5369. Final rinse water monitoring in endoscopy and CSD exists to detect organisms capable of colonising the water system and depositing on a reprocessed device at the final wetted step, principally Pseudomonas aeruginosa and other Gram-negative water organisms, non-tuberculous mycobacteria and Legionella species, with total viable count, conductivity and endotoxin used as indicators of system condition and treatment performance. A virus that replicates only in human hepatocytes cannot be recovered from, and is never sought in, that matrix.

A report of HCV RNA on a water or rinse-water sample should therefore be treated as a probable artefact rather than as evidence of a contaminated water system. Two mechanisms account for almost all such results. Specimen carryover occurs where a water sample is handled, extracted or amplified alongside clinical plasma or serum samples, some of which carry very high viral loads; small volumes of aerosol or droplet transfer during pipetting are sufficient to generate a low-level signal. Amplicon contamination occurs where previously amplified product contaminates reagents, pipettes, racks or bench surfaces and is carried into subsequent runs. Both are recognised failure modes in molecular laboratories and both are far more probable than a genuine finding, given that the virus has no mechanism by which it could reach or persist in a treated water loop.

The result should be resolved through the laboratory. Begin by confirming sample identity and matrix: check the chain of custody, the sampling point identifier, the collection date and time, the container type and the labelling, and confirm that the material tested was water rather than a misrouted clinical specimen. Next, establish whether the assay was validated for environmental matrices; HCV RNA assays are validated on plasma or serum, and their performance on a low-biomass, low-protein water matrix, including the behaviour of the extraction chemistry and any internal control, is undefined. Review the run controls, particularly the extraction blank and no-template control, and check whether the sample was positioned adjacent to a high-titre clinical specimen. Then resample the same point using fresh, unopened consumables and a separate sampling kit, and where feasible split the resample between two laboratories. Finally, escalate to laboratory quality management, which owns contamination control, run design and specimen segregation, rather than to the water safety group. The water safety group should be notified for awareness but should not initiate flushing, chemical disinfection, filter replacement or system shutdown, and the result should not be logged as a water quality exceedance or trended against the facility's rinse-water data. Any genuine clinical concern about HCV transmission is pursued independently through the reprocessing-failure and exposure pathway, using reprocessing records, traceability data, injection practice audit and patient testing, not through water quality management.

Antimicrobial resistance

Resistance-associated substitutions in the NS3/4A protease, NS5A and NS5B regions can reduce the activity of individual direct-acting antivirals and may contribute to treatment failure or influence the choice of retreatment regimen. Because the viral polymerase lacks proofreading capability, variants carrying such substitutions are generated continuously and may be present as minority populations before any treatment is given. Their clinical significance differs markedly between drug classes. Substitutions affecting NS5A inhibitors are the most consistently important, since they can confer substantial reductions in susceptibility and, unlike other classes, tend to persist for long periods after therapy is withdrawn. Substitutions affecting the NS3/4A protease generally impose a fitness cost and decline over time, and resistance to the nucleotide polymerase inhibitor class is uncommon.

In practice, current pangenotypic combination regimens have a sufficiently high barrier to resistance that baseline resistance testing is not required for most treatment-naive patients, and cure rates remain high in the presence of common baseline substitutions. Resistance testing has a defined role in the assessment of patients who have failed a previous direct-acting antiviral regimen, where the pattern of substitutions informs the selection of a retreatment combination and the decision whether to extend duration or add ribavirin. As with hepatitis B, apparent treatment failure should prompt assessment of adherence, drug interactions and possible reinfection before resistance is assumed, since reinfection after cure is common where exposure continues and is distinguishable from relapse by sequencing.

Antiviral resistance in HCV is a consideration for clinical management only. It has no relationship to the performance of cleaning, high-level disinfection or sterilisation processes used in reprocessing reusable medical devices. Resistance substitutions alter the binding of small-molecule inhibitors to viral enzymes and confer no tolerance of detergents, oxidising or alkylating disinfectants, or moist heat, and the lipid envelope that makes HCV readily inactivated by these agents is unaffected. No variation to reprocessing practice, cycle parameters or device handling is warranted for a patient with a resistant strain, and no reprocessing decision should be made on the basis of a resistance report.