Digestive system diseases

To the Editor:In October 2016, we achieved the eradication and control of hepatitis C virus (HCV) in a New South Wales correctional centre, which we believe to be a first of its kind in NSW. HCV prevalence in NSW prisons is 30–40 times higher than in the community, where prevalence is about 1%.1,2 Elevated risk of HCV infection is associated with the high proportion of prisoners who have injected drugs, the rate of injecting in prison, and restricted or limited access to bleach and needle and syringe programs.3 The Justice Health and Forensic Mental Health Network (the Network) is responsible for health care in the NSW forensic mental health and criminal justice systems. The availability of direct-acting antivirals on the Pharmaceutical Benefits Scheme in March 20164 created an opportunity for the Network to cure all patients with HCV infection in one prison. The Compulsory Drug Treatment Program (CDTP) is run at the Compulsory Drug Treatment Correctional Centre — a stand-alone prison with a stable sentenced inmate population, where patients with repeat drug-related charges participate in comprehensive drug treatment and rehabilitation. Patients at this correctional centre have longer sentences than those in other centres, which allowed for the full course of treatment. The Network, Corrective Services NSW and Hepatitis NSW formed a partnership to ensure that patients were able to access health centres, have their medication scripted and administered, could undertake monitoring and were supported through the Network’s established nurse-led model of care.5 All 58 patients in the CDTP were offered screening, and 54 patients with risk factors were screened; of these, 18 patients had chronic HCV infection. After further work-up, including liver elastography to measure fibrosis, all patients were concurrently commenced on treatment. Of the remaining four patients who were not screened, all had recent negative HCV pathology results. Three months after the treatment, 15 patients achieved sustained virological response equating to cure of their chronic HCV infection, and three patients were released before final assessment.6 Concurrent treatment commencement with the direct-acting antivirals was recognised as an innovative measure in reducing re-infection, in conjunction with the more common practices of harm minimisation education and use of the hospital-grade disinfectant for general cleaning purposes offered by Corrective Services NSW to all incarcerated people. Throughout the course of the project, two new patients were admitted, screened, and returned negative HCV pathology results. A proactive screening approach with patient consent was adopted to ensure that new cases were able to be identified and treated to maintain elimination. Maintaining a prison HCV-free may mean that patients have to take some responsibility with regard to sharing needles with new inmates. A peer education approach is being developed to increase patients’ ownership of a prison’s HCV-free status. The CDTP treatment model, combined with ongoing screening of new admissions, is an innovative approach for eliminating HCV, and is considered suitable for adoption in similar-sized prisons across Australia. The Network is currently rolling out this approach within NSW.

James Blogg · James Wood · Colette McGrath · Camilla Lobo

To the Editor: We read with interest Mendelson and colleagues’ article regarding the underutilisation of computed tomography colonography (CTC) for colorectal cancer detection in Australia.1 The authors state that “CTC is less accurate in the diagnosis of small or diminutive polyps … However, in the context of symptomatic patients, this is not relevant”.1 This overlooks the importance of detecting small adenomas as well as flat, right-sided colonic lesions such as sessile serrated polyps. It is well established that the early detection and treatment of these lesions reduces interval colorectal cancer.2 To state that these are “not relevant” in symptomatic patients is inaccurate. High definition white light with the aid of chromoendoscopy tools such as narrow band imaging in optical colonoscopy (OC) has significantly improved the ability of endoscopists to detect diminutive and subtle lesions. CTC has a markedly limited ability to detect small and flat lesions when compared with OC.3 The authors reference phase 2 data from the National Bowel Cancer Screening Program, stating that “the great majority of OCs (about nine in ten) were normal”. However, polyps were detected in 34.9% of participants.4 The authors appear to define normality as the absence of a cancer or advanced adenoma (one in ten colonoscopies). We argue that the detection of any adenoma is important and is not “normal”, as it highlights a cohort of patients at risk of colorectal cancer and requiring ongoing polyp surveillance. We also question the authors’ suggestion that a negative CTC obviates the need for OC in lower risk patients with positive faecal immunochemical test results. OC provides the opportunity to detect and treat a range of polypoid and non-polypoid colonic pathology and although a negative CTC may help exclude a cancer, it does not address the range of other potentially morbid or precancerous causes of occult faecal blood. Given these limitations, a cautious approach should be adopted if CTC is to be used as an alternative to OC in all lower risk patients.

Simon Hew · Zaid SM Ardalan

In reply

Richard M Mendelson · Tom R Sutherland · Andrew F Little

To the Editor: After reading the recent article by van Driel and colleagues,1 we want to report on hepatitis C treatment outcomes in a Sydney general practice. New direct-acting antiviral (DAA) therapy for the treatment of chronic hepatitis C became widely available in Australia on 1 March 2016 via the Pharmaceutical Benefits Scheme, and general practitioners are able to prescribe it in consultation with a specialist. We describe here the treatment outcomes from the first 60 days of DAA prescribing in a single general practice clinic. We searched the clinic database to extract demographic and clinical data for all patients prescribed DAA from 1 March to 30 April 2016. We found that 47 patients had been prescribed DAA agents by a GP, five had received DAA therapy via an early access program, 41 had genotype 1 hepatitis C virus (HCV), six patients had genotype 3 HCV, and 11 patients had co-infection with HIV. All treated patients had an assessment of liver fibrosis performed with a FibroScan. Most patients had early liver disease, with three having cirrhosis. On 1 May 2017, we assessed the outcome data: 33 patients were treated with ledipasvir and sofosbuvir (all had genotype 1 HCV), nine were treated with daclatasvir and sofosbuvir (three had genotype 1 HCV, and six had genotype 3 HCV), and five patients were treated with paritaprevir + ritonavir + ombitasvir + dasabuvir (all had genotype 1 HCV). Forty-six patients had started treatment, with sustained virological response (SVR16; ie, undetectable virus 16 weeks after the end of treatment) results available for 45 patients. One patient had treatment failure, one had not started treatment and one patient was waiting on SVR results. On-treatment SVR (cure) rate was 96%. A steadily increasing percentage of patients in Australia are receiving hepatitis C treatment prescribed by their GPs, with 19% of prescriptions provided in this setting in September 2016.2 GPs are well placed to provide care for patients living with chronic hepatitis C, with reassuringly high cure rates.

David Baker · Marilyn McMurchie · Vanessa Farr

To the Editor: The demand for human leukocyte antigen (HLA) typing in the diagnostic work-up of coeliac disease (CD) in Australia has driven a 14-fold rise in testing since 2003 (Medicare Benefits Schedule data, item 71151). Although HLA typing offers limited specificity for CD, its clinical utility results from its exceptional negative predictive value (> 99%) when the specific HLA susceptibility genotypes are not detected.1 Unlike traditional tests for CD, HLA typing results are informative even when the patient is following a gluten free diet. While the accuracy of HLA typing in CD has not been reported, HLA test results are assumed by clinicians to be definitive. Our findings challenge this view. Discrepancies between several patients’ clinical diagnosis of CD and their negative HLA-DQ2 and -DQ8 typing results in AJD’s practice led to repeat HLA testing with another laboratory. The subsequent reporting of a genotype consistent with CD prompted a clinical audit (2013–2016). Of 211 patients with HLA typing results, nine had been coperformed by two separate laboratories (laboratories 1 and 2), either deliberately or inadvertently. Of these nine patients, six returned conflicting results. An additional DNA sample from all six patients was sent for HLA genotyping by a reference laboratory, where genetic susceptibility for CD was confirmed in five patients (Box). Laboratories 1 and 2 differed in the detection of risk alleles and in the interpretation of or reporting of the results in all six cases. Laboratory 2 identified an at-risk allele in only two of the six patients, and of the four patients with a reported negative genotype, two were subsequently confirmed to have definite CD. These preliminary findings raise serious concerns about CD HLA testing errors that adversely affect patient care. Although identified in Queensland, these laboratories routinely outsource their HLA typing to laboratories in New South Wales and Victoria, indicating that several Australian states are involved. We are particularly concerned about laboratories new to HLA testing or laboratories that are not participating in stringent quality assessment programs as the sourced reference laboratory does. Therefore, we suggest that an assessment of the performance and quality control measures of all laboratories offering HLA typing is urgently needed. Consistent adoption of evidence-based guidelines that describe optimal HLA testing and reporting1 should form part of the solution. Box – Human leukocyte antigen (HLA) typing results from three laboratories† Patient Laboratory 1 Laboratory 2 Reference laboratory Confirmed CD “Consistent with DQ2 phenotype; susceptible for CD” Genotype not supplied; “Not susceptible for CD” HLA-DQ2.2/2.5; susceptible to CD Incorrect Confirmed CD “Consistent with DQ2 phenotype; susceptible for CD” Genotype not supplied; “Not susceptible for CD” HLA-DQ2.2; susceptible to CD Incorrect CD excluded “Consistent with DQ2 phenotype; susceptible for CD” Genotype not supplied; “Not susceptible for CD” HLA-DQ2.2; susceptible to CD Incorrect CD not excluded; on GFD “Consistent with DQ8 phenotype; susceptible for CD” Genotype not supplied; “Not susceptible for CD” No susceptibility to CD detected Incorrect Normal CD serology “DQ2 and DQ8 not identified; no genotype susceptibility for CD” “DQA1*0505 has been detected; small percentage susceptible to CD” DQA1*05 (HLA-DQ7); low risk susceptibility to CD Incorrect CD excluded “DQ2 and DQ8 not identified; no genotype susceptibility for CD” “DQA1*0505 has been detected; small percentage susceptible to CD” DQA1*05 (HLA-DQ7); low risk susceptibility to CD Incorrect CD = coeliac disease. GFD = gluten free diet. ND = not detected. † The reference laboratory was in the Victorian Transplantation and Immunogenetics Service in Melbourne. In addition to the incorrect typing results, laboratory 2 failed to report the specific alleles detected and laboratory 1 failed to distinguish between HLA-DQ2.5 and DQ2.2.

A James M Daveson · Michael Varney · Kate E Jackson · Jason A Tye-Din

To the Editor:Hepatitis E virus (HEV) genotype 3, the most common genotype in high income countries, is transmitted by ingestion of high risk food — including pork, deer and shellfish — and by blood transfusion. Rural residence, travel to hyperendemic areas (eg, southern Europe) and animal exposure are other risk factors.1 Both de novo and reactivated HEV infection can lead to chronic infection in up to 60% of immunocompromised patients, particularly in solid organ transplant (SOT) recipients.1,2 Moreover, 10% of patients who are chronically infected develop cirrhosis.1 In a 2013 study, the seroprevalence of HEV in Australian blood donors was 5.99%.3 Autochthonous transmission in Australia, including one patient who was a liver transplant recipient, is well documented.4,5 However, the seroprevalence and rate of chronic HEV infection in SOT recipients in Australia are unknown. We carried out a study to investigate this in an Australian tertiary hospital. In phase 1 of our study, we recruited renal transplant recipients attending routine outpatient follow-up in 2014–15; phase 2 was limited to seropositive participants from phase 1. The study was approved by the Northern Sydney Local Health District Human Research Ethics Committee (LNR/14/HAWKE/300). Seventy-four patients consented to participate in phase 1, and post-transplant stored serum was tested for HEV IgG. Six participants were HEV IgG positive. One seropositive participant died of invasive fungal infection before phase 2. The remaining five participants who were seropositive consented to phase 2, of whom one was HEV IgM positive. We tested plasma for HEV RNA and no phase 2 participants had evidence of ongoing chronic infection. While our study had limitations and we did not identify any participant with chronic infection, it is important to note that Australian SOT recipients are exposed to HEV and are at risk of chronic infection. Effective therapy for chronic HEV is available; therefore, we recommend that SOT recipients who have abnormal liver function tests should be tested for HEV RNA in blood to maximise early diagnosis. In addition, with respect to risk mitigation, previous Australian research supports a link between local pork consumption and HEV infection,4 and French guidelines suggest that SOT recipients should avoid consuming food containing pork liver.6 We believe that similar advice should be given to SOT recipients in Australia. Moreover, consideration should be given to screening donated blood in Australia for HEV RNA, as done in France and the United Kingdom, with experts calling for such screening across the European Union.7,8 The Australian Red Cross Blood Service has undertaken a large scale screening study of donated plasma for HEV RNA to estimate the local risk of HEV transmission by blood transfusion, with results currently pending.9

James P Newcombe · Stella McGinn · Bruce Wong · Archie Darbar · George Kotsiou