Epidemiology of hepatitis B related hepatocellular carcinoma in South Australia: Strategies for improved outcomes based on optimizing treatment uptake, screening program and percutaneous interventions

Author: Mohamed Chinnaratha

Chinnaratha, Mohamed, 2017 Epidemiology of hepatitis B related hepatocellular carcinoma in South Australia: Strategies for improved outcomes based on optimizing treatment uptake, screening program and percutaneous interventions, Flinders University, School of Medicine

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Background & aims: The aims of this thesis were to investigate five clinically relevant questions concerning chronic hepatitis B (CHB) - related hepatocellular carcinoma (HCC); (1) what is the epidemiology of CHB- related HCC in South Australia (SA)? (2) What are the estimated clinical benefits of increasing treatment uptake in CHB? (3) Is there a survival benefit within a dedicated HCC screening program in high risk groups? (4) What are the local recurrence rates and disease free survival rates following percutaneous ablation therapies in HCC? and (5) what type of thermal ablation therapy provides superior outcomes?

Methods: For aim 1, subjects notified with CHB between 1996 and 2010 in SA were probabilistically linked with cancer and death registry records to calculate the survival, crude and age-standardized incidence rates. Using a Markov mathematic model for aim 2, the cost-effectiveness of increasing treatment uptake in CHB was assessed. The current level of treatment uptake (2.9%) was compared with recommended targets of 10% and 15% to calculate the incremental cost per quality-adjusted life years (QALYs) gained. Aim 3 was assessed by comparing the overall survival (OS), tumour stage at diagnosis and the proportion of patients having curative therapy between those diagnosed within and outside of a dedicated HCC screening program. Aim 4 was investigated with a multicentre retrospective cohort study investigating local recurrence rates following percutaneous ablation. For aim 5, a meta-analysis was performed to assess differences in local tumour progression rates (LTP) post radiofrequency (RFA) and microwave ablation (MWA).

Results: The overall crude and age-standardized CHB- related HCC incidence was 111.3/100,000 and 189.1/100,000 person-years respectively, and rates for men were significantly higher than for women. CHB- related HCC incidence increased in a linear fashion during the study period with an annual percentage change of 20.8%. Median OS was 12.5 months, with a trend towards longer survival between 2006 and 2010 (21.8 months).

Increasing HBV treatment uptake to 15% was associated with the highest mean QALY gained (8.20) compared to 10% (7.99) and 2.9% (7.68) uptake rates. The corresponding mean cost/person over 10 years was AU$60,133 v AU$61,964 and AU$64,597 respectively. Higher treatment uptake was cost-effective with at least 2 years of increased uptake rates.

HCC diagnosed within a dedicated screening program had a better median OS compared to those diagnosed outside the program [26.8 v 11.5 months, p=0.01]. Subjects within the program had an earlier stage HCC and a significantly greater proportion were treated with curative intent. Propensity score adjustment using baseline clinical characteristics estimated a 58% real reduction in HCC mortality for patients diagnosed within the program.

With respect to outcomes following percutaneous thermal ablation, the local recurrence rate was 23.4%. Overall mean (±SD) local recurrence-free survival was 46.9 (±3.6) months and this was marginally higher in nodules ≤2cm. Poorly differentiated HCC and pre-treatment AFP >50 kIU/L were independent predictors of local recurrence.

Meta-analysis comparing RFA and MWA suggested that both techniques were equally safe and effective; MWA was more effective in preventing local recurrence when treating larger tumours. Other outcomes including completion ablation rates and adverse events were similar between the groups.

Conclusions: CHB- related HCC has been progressively increasing in SA over the past two decades. Increasing treatment uptake rates in CHB improves the survival by reducing the number of expected clinical events. Dedicated, centralised HCC screening programs provide improved HCC outcomes relative to an unscreened HCC population. There is a relatively high local recurrence rate following percutaneous ablation therapy for HCC and both MWA and RFA provide similar clinical outcomes.

Keywords: Hepatitis B, hepatocellular carcinoma, South Australia

Subject: Medicine thesis

Thesis type: Doctor of Philosophy
Completed: 2017
School: School of Medicine
Supervisor: Assoc Prof Alan J Wigg