Prof Amany Zekry

Description:Objective: Cure of hepatitis C virus (HCV) infection decreases liver- and all-cause mortality. However, the risk of early mortality after HCV cure remains. We examined factors associated with cause-specific mortality after direct-acting antiviral (DAA) therapy. Methods: DAA-treated adults (recruited 2016-2021) were followed up to September 2023. Medication, health-service use, and deaths were obtained from population databases. The primary outcome was all-cause and cause-specific mortality. Results: Among 3619 patients (average 52.0 years (SD = 10.5), 66.0% male, 33.6% with cirrhosis) followed for a median of 6.8 years (IQR 5.5-7.4), 423 (11.7%) died (40.6% due to liver disease, 13.2% self-harm/accidental poisoning and 12.3% respiratory disease/lung cancer). Cirrhosis (adjusted hazard ratio (adj-HR) = 14.51, 95% CI 6.87-30.64), FIB4 > 3.25 (adj-HR = 4.22, 95% CI 2.63-6.80), nonsustained virological response (SVR) (adj-HR = 3.94, 95% CI 2.64-5.88) and age ≥ 60 years (adj-HR = 1.88, 95% CI 1.32-2.69) increased liver-related mortality risk. Mortality was threefold higher in non-SVR (32.4% of 210 patients vs. 10.2% of 2894 with SVR, p < 0.001). Non-SVR increased risk of liver mortality (adj-HR = 4.30, 95% CI 2.90-6.37). Mental health medication use (adj-HR = 2.82, 95% CI 1.40-5.67), loss to clinical follow-up (adj-HR = 2.61, 95% CI 1.31-5.21) and injection drug use/opioid replacement therapy (adj-HR = 2.26, 95% CI 1.23-4.14) increased risk of self-harm/accidental poisoning-related mortality. Age ≥ 60 years and diabetes increased mortality risk from other extrahepatic cancer (adj-HR = 2.68, 95% CI 1.31-5.51 and adj-HR = 2.57, 95% CI 1.15-5.72) and cardiovascular disease (adj-HR = 2.71, 95% CI 1.06-4.19 and adj-HR = 2.28, 95% CI 1.03-5.05). Conclusions: Liver-related death drives mortality for cirrhotic patients. Curing HCV remains critical. Holistic HCV care, with attention to mental health illnesses in younger patients, metabolic comorbidities, and better cancer screening for older patients may reduce excess mortality.

Description:The complementary information found in different modalities of patient data can aid in more accurate modelling of a patient's disease state and a better understanding of the underlying biological processes of a disease. However, the analysis of multi-modal, multi-omics data presents many challenges. In this work, we compare the performance of a variety of ensemble machine learning (ML) algorithms that are capable of late integration of multi-class data from different modalities. The ensemble methods and their variations tested were (i) a voting ensemble, with hard and soft vote, (ii) a meta learner, and (iii) a multi-modal AdaBoost model using hard vote, soft vote, and meta learner to integrate the modalities on each boosting round, the PB-MVBoost model and a novel application of a mixture of expert's model. These were compared to simple concatenation. We examine these methods using data from an in-house study on hepatocellular carcinoma, plus validation datasets on studies from breast cancer and irritable bowel disease. We develop models that achieve an area under the receiver operating curve of up to 0.85 and find that two boosted methods, PB-MVBoost and AdaBoost with soft vote were the best performing models. We also examine the stability of features selected and the size of the clinical signature. Our work shows that integrating complementary omics and data modalities with effective ensemble ML models enhances accuracy in multi-class clinical outcome predictions and produces more stable predictive features than individual modalities or simple concatenation. We provide recommendations for the integration of multi-modal multi-class data.

Description:Background: Integration of palliative and supportive care in cancer treatment pathways is becoming standardised. While there has been significant qualitative research in oncology on palliative and supportive care integration into clinical care, there is little evidence that focusses on clinicians who manage hepatocellular carcinoma (HCC) and their perceptions on palliative and supportive care. Objective: To investigate the attitudes and perceptions regarding palliative and supportive care of healthcare professionals managing patients with HCC. Methods: Qualitative study involving semi-structured individual interviews transcribed verbatim and analysed thematically. Methods: A total of 25 healthcare professionals including hepatologists, gastroenterology trainees, hepatology clinical nurse consultants, social workers, and palliative care specialists providing care to patients with HCC recruited at 4 tertiary hospitals via purposive sampling. Results: The following themes emerged: (1) availability of palliative care services, (2) need for clear referral pathways and processes, (3) patients' limited understanding of palliative care, (4) recognition of benefits of palliative care, and (5) the lack of training in hepatology services for palliative care provision. Conclusions: Health professionals' perceptions of integration of palliative and supportive care in liver cancer care are hampered by multiple barriers. Opportunities to establish a more cohesive approach to care integration for patients with liver cancer have been identified. TRIAL REGISTRATION: ACTRN12623000010695 (date of registration 9/01/2023). What is already known about the topic? • Integration of palliative and supportive care for cancer can have profound benefits for patients' symptom burden and quality of life. • There is a lack of empirical studies examining the perspectives of health professionals who manage liver cancer on the integration of palliative and supportive care into the treatment pathways for patients. What this paper adds • This study identifies a number of barriers to the implementation of palliative and supportive care into liver cancer treatment algorithms. • The absence of sufficient evidence in clinical guidelines impairs the capacity of health professionals to improve the integration of palliative and supportive care for liver cancer patients. Implications for practice, theory, or policy. • As liver cancer prevalence increases, further effort is required to develop appropriate evidence-based clinical guidelines and referral pathways to support the integration of palliative and supportive care within existing liver cancer services.

Description:The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD)-previously described as nonalcoholic fatty liver disease-continues to rise globally. Despite this, therapeutic measures for MASLD remain limited. Recently, there has been a growing interest in the gut microbiome's role in the pathogenesis of MASLD. Understanding this relationship may allow for the administration of therapeutics that target the gut microbiome and/or its metabolic function to alleviate MASLD development or progression. This review will discuss the interplay between the gut microbiome's structure and function in relation to the development of MASLD, assess the diagnostic yield of gut microbiome-based signatures as a noninvasive tool to identify MASLD severity, and examine current and emerging therapies targeting the gut microbiome-liver axis.

Description:BackgroundHepatocellular carcinoma is a burdensome form of liver cancer with an increasing global prevalence. Emerging evidence has shown that early palliative care introduction at diagnosis of any life-limiting illness improves patient and carer outcomes. Despite this, patients with hepatocellular carcinoma usually receive palliative care late. These patients are important stakeholders in the provision of palliative care, but their perceived barriers regarding its delivery are poorly defined.AimThis pilot study aimed to identify the barriers perceived by patients to integrating palliative care into the hepatocellular carcinoma treatment algorithm.DesignPatients living with hepatocellular carcinoma undertook semi-structured interviews about their perceptions of palliative care. We compared these perceptions before and after providing a brief explanation of palliative care. Interview data was inductively coded in NVivo 12 (2018) and thematically analysed.ResultsTwenty-one patients were interviewed. 16 perceived palliative care to mean end-of-life therapy, and nine participants had no prior knowledge of palliative care. After hearing a definition of palliative care, 17 participants reported changed positive attitudes. Seven participants supported a name change, including four participants who continued to reject palliative care following the explanation due to the negative stigma associated with the term 'palliative care'.ConclusionThere is significant misperception about the purpose of palliative care among patients with hepatocellular carcinoma, constituting a barrier to early integration. This can be feasibly addressed with a two-folded educational and renaming initiative to dispel patient misconceptions regarding palliative care. Effective strategies to achieve this should be developed and tested with relevant stakeholders, particularly patients.