Medical Journal of Australia最新文献

To the Editor: We read with interest the excellent review by Hui and colleagues¹ on hepatocellular carcinoma (HCC) surveillance in Australia. HCC is increasing in incidence in Australia, and is often diagnosed late, when curative options are limited and mortality rates are high.¹ Surveillance is recommended in high risk individuals but uptake is suboptimal; a centralised surveillance program may provide an improved model of care delivery.¹ However, screening programs may only be successful in those with a diagnosis of a condition that increases their risk of HCC.

Improved case-finding strategies are recommended;¹ however, an important group not discussed in this article is pregnant people. This is a unique population who is universally tested for hepatitis B in Australia,² and who is often interacting with the health care system for the first time at a young age, without other comorbid conditions. In those at high risk of progression to HCC, such as women from sub-Saharan Africa aged over 20 years, antenatal diagnosis provides an opportunity for education. Linkage to specialist care during pregnancy also enables the development of an HCC surveillance plan to maximise the opportunities for early diagnosis of complications.

There is evidence to suggest that, in Australia, people who are diagnosed during pregnancy with a medical condition that is associated with long term complications, such as gestational diabetes³ and hypertensive disorders in pregnancy,⁴ often do not engage in recommended follow-up care in the postpartum period. Postpartum retention in care in those with hepatitis B in Australia is poorly documented, but appears similar to other antenatally diagnosed conditions, with existing data estimating that less than half engage with hepatitis B care during the first year postpartum.⁵ In addition to the barriers to accessing surveillance outlined by Hui and colleagues,¹ engagement in care during the postpartum period may be hampered by the need to juggle family and child care responsibilities, return to the workforce, and access to child care to allow attendance at appointments.

We recommend integrating existing antenatal screening and diagnosis into strategies to identify those at high risk who may benefit from HCC surveillance, and optimising postpartum pathways of care to support these individuals.

No relevant disclosures.

To the Editor: Hui and colleagues must be commended for underscoring that a program with centralisation should be a cornerstone for hepatocellular carcinoma (HCC) surveillance.¹ Indeed, with funding for quality assurance, it allows for monitoring of uptake to guarantee effectiveness and equitability. However, their narrative review deserved robust comments.

Firstly, the prerequisite for screening is a positive benefit to harm ratio and the highlighting of a positive randomised trial of patients from China should not have masked its major flaws and that another trial was negative.^{2, 3} Similarly, stating that “observational studies are inherently limited, given the potential for lead-time and length-time biases to overestimate survival benefit”¹ is a euphemism.

Further, the diagnosis of small nodules (< 2 cm) in a cirrhotic liver with fibrous septa and regenerative nodules is a complex issue requiring multiple investigations and, frequently, a biopsy.

Secondly, the analysis of the poor uptake of screening is wise⁴ but it should not have ignored that there is no consensus among national recommendations: neither for imaging techniques and the serum biomarkers, nor for their combination and frequency. Rather than including a table comparing recommendations for group surveillance among national recommendations (Box 2 in Hui et al¹), the authors should have included a table summarising the profusion of screening methods; having so many methods suggests that none are adequate.

Lastly, Hui and colleagues should not have ignored the warnings from the US National Cancer Institute summarising the evidence for benefits and harms of HCC screening: “Based on fair evidence, screening of persons at elevated risk does not result in a decrease in mortality from hepatocellular cancer” and “Good evidence for uncommon but serious harms”.⁵ At least Hui and colleagues should have recalled that the Gastroenterological Society of Australia must be commended as none of its four recommendations related to surveillance of HCC are graded A1.⁶

The recommendation for screening for HCC by some professional organisations, despite lack of evidence for a positive benefit to harm ratio on relevant clinical outcomes from randomised trials, is an exception in medicine. Exceptions in medicine rarely benefit patients.

No relevant disclosures.

In reply: On behalf of my co-authors, I thank Braillon for their interest in our article.¹ As highlighted by Braillon,² we accept there are some methodological limitations in the 2004 trial that investigated hepatocellular carcinoma (HCC) surveillance in Chinese hepatitis B patients with or without cirrhosis.³ Braillon also refers to an additional negative trial for HCC surveillance. We assume this is in reference to the study by Chen and colleagues, which found surveillance resulted in earlier HCC diagnosis but without a reduction in overall mortality.⁴ However, this trial was based on α-fetoprotein-only screening in Chinese hepatitis B patients between 1989 and 1995. These results cannot be generalised to modern clinical practice, given the considerable paradigm shift in surveillance, diagnosis and treatment over the past three decades.

In the absence of additional randomised trials, Braillon has shown that there remains some debate about the overall value of HCC surveillance. Further randomised trials are, however, unlikely to be practical or ethically feasible, given surveillance is a well established standard of care worldwide. A systematic review of contemporary observational data has found that HCC surveillance in cirrhotic patients results in early detection and improved survival due to curative treatment receipt, although the incidence and magnitude of surveillance-related harm is less well studied.⁵

Given HCC surveillance is an established standard of care in high risk patients, we feel there is merit in a centralised surveillance program. Beyond improving access and uptake, centralisation will provide high quality prospective data that can assess the real-world benefit and harms of surveillance in Australia.

HCC is an emerging and costly public health problem in many Western countries that remains under-recognised. An important tenet of public health is the prioritisation of preventive care. In the case of HCC, we argue that an increased focus on its primary and secondary prevention presents the greatest opportunity for improving outcomes for this devastating disease.

No relevant disclosures.