Objective: Abnormal liver tests have been associated with worse clinical outcomes in patients infected with COVID-19. This retrospective observational study from Singapore aims to elucidate simple clinical predictors of abnormal alanine aminotransferase (ALT) in COVID-19 infections. Design: 717 patients hospitalised with COVID-19 at the National Centre for Infectious Diseases (NCID), Singapore, from 23 January–15 April 2020 were screened, of which 163 patients with baseline normal alanine transferase (ALT) and at least two subsequent ALTs performed were included in the final analysis. Information on baseline demographics, clinical characteristics and biochemical laboratory tests were collected. Results: 30.7% of patients developed abnormal ALT. They were more likely to be older (60 vs. 55, p = 0.022) and have comorbidities of hyperlipidaemia and hypertension. The multivariate logistic regression showed that R-factor ≥1 on admission (adjusted odds ratio (aOR) 3.13, 95% Confidence Interval (CI) 1.41–6.95) and hypoxia (aOR 3.54, 95% CI 1.29–9.69) were independent risk factors for developing abnormal ALT. The patients who developed abnormal ALT also ran a more severe course of illness with a greater proportion needing supplementary oxygen (58% vs. 18.6%, p < 0.0005), admission to the Intensive Care Unit (ICU)/High Dependency Unit (HDU) (32% vs. 11.5%, p = 0.003) and intubation (20% vs. 2.7%, p < 0.0005). There was no difference in death rate between the two groups. Conclusions: Liver injury is associated with poor clinical outcomes in patients with COVID-19. R-factor ≥1 on admission and hypoxia are independent simple clinical predictors for developing abnormal ALT in COVID-19.

Background: Chronic liver diseases including non-alcoholic fatty liver disease (NAFLD) are associated with COVID-19 progression. With no signs of the pandemic abating, thousands worldwide are at risk of a severe disease course. Objective: We aimed to describe the epidemiological features, clinical course, treatment and outcomes of our patients with COVID-19 and chronic liver disease.Methods: A retrospective descriptive study of COVID-19 patients with chronic liver disease admitted to the National Centre for Infectious Diseases in Singapore between 29th February and 2nd May 2020 was performed. Results: 16 patients had chronic liver disease – 9 had NAFLD. In the NAFLD group, peak ALT was higher (median: 84 U/L vs 38 U/L; P = 0.042) and more patients had hyperlipidaemia (88.9% vs 28.6%; p=0.035), but median Body Mass Index (BMI) was not significantly higher (24.3 kg/m2 vs 24.2 kg/m2). NAFLD patients had a poorer clinical course: more required anti-viral medications (66.7% vs 0%; p=0.011), and time to negative swab was longer (24 days vs 13 days; p=0.008). 3 patients had liver cirrhosis (all non-NAFLD). 1 decompensated but none required intensive care unit admission or died.Conclusion: Our results show that in COVID-19 patients with chronic liver disease, those with NAFLD experience a more severe clinical course. In Asians, NAFLD can have poorer prognostic implications, despite them having only mildly raised BMI. We advocate that patients with NAFLD and liver cirrhosis should be closely monitored for COVID-19 disease progression.

Soft tissue sarcoma (STS) is currently treated by surgery and adjuvant or neoadjuvant radiotherapy. About 20 - 30% of patients develop local recurrence and 50% will eventually die of their disease. Adjuvant cytotoxic therapies improve disease free survival but overall survival is minimally effected. New treatments are required. As with many cancers there is an imbalance between cell growth and cell death and this also the case with STS. Cell growth signals such as those from the insulin-like growth factor receptor (IGF-1R) increases resistance to radiotherapy. We proved that IGF-1R family members are highly expressed in sarcoma tissue samples, particularly IGF-1R 80% positive, which is also significantly associated with histologic grade. This study investigates whether inhibiting IGF-1R can improve the sensitivity of radiotherapy in liposarcomas. Expression of IGF-1R and/or activated IGF-1R in 3 liposarcoma cell lines was detected by western blot and immunoprecipitation respectively. Crystal violet staining and/or clonogenic assays were used to assess anti-proliferative effects of irradiation and IGF-1R inhibitor (tyrphostin AG1024) or IGF-1R downstream pathway inhibitors (LY294002 and SB202190). Irradiation was performed using Therapax DXT300 Orthovoltage Radiation System. We found that the IGF-1R inhibitor can enhance radiotherapy, particularly in the 2 radio-insensitive sarcoma cell lines (combination index &lt;1 = synergism, CI &lt;0.1 for 449B; CI 0.1-0.3 for 778). The drug reduction index (DRI) at IC50 measures how much the dose of x-ray may be reduced when drug and x-ray were combined at the IC50 effect level compared with the dose of x-ray alone. The DRI for 449B and 778 was 3 and 5 fold for x-ray reduction respectively. In addition, we found that radiation can induce activation of IGF-1R in the sarcoma cell line detected with peak time at 4 hours. Using the IGF-1R inhibitor pre-treatment achieved more inhibitory effect than concurrent inhibitor plus X-ray or X-ray alone group. The greatest enhancement of radiosensitivity was observed with pre-treatment of AG1024 followed by combination therapy, resulting in an 80% decrease in cell survival fraction at the highest dose combination. We also used PI3K and p38 pathway inhibitors singly or together compared with the IGF-1R inhibitor in the presence or absence of X-ray or IGF-1 and discovered that both pathways are involved in radioresistance and the inhibition is at least partially IGF-1R dependent. Targeting the IGF-1R to radiosensitize liposarcomas is a novel treatment strategy that can potentially improve the prognosis of some patients with low radiosensitive liposarcoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5540.

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