Prophylactic Antibiotic Use in Transarterial Chemoembolization for Hepatocellular Carcinoma: an Open-label, Randomised, Prospective Study
Phase: PHASE3
Conditions: Antibiotic Prophylaxis
Sponsor: Nadeem Iqbal

Title: Prophylactic antibiotic use in transarterial chemoembolization for hepatocellular 
carcinoma: an open-label, randomised, prospective study 
Introduction: 
Liver cancer especially hepatocellular carcinoma (HCC) is among the top five most common 
carcinomas in the world [1]. The treatment options for HCC includes surgery, liver 
transplantation, and radiofrequency ablation (RFA) with good survival rates. However, most 
HCC patients have angioinvasion. Furthermore, multiple lesions cannot be treated with such 
treatment strategies [2]. Image-guided transarterial chemoembolization (TACE) is accepted 
worldwide as a standard of care treatment for patients with hepatocellular carcinoma (HCC) in 
intermediate stage and good performance status [3]. TACE procedures, performed by the 
interventional radiologists, are minimally invasive with excellent outcomes as part of the 
nonsurgical treatment of HCC [1, 4]. Post-procedure-infection is uncommon but can lead to 
liver abscess and prolonged hospital stay. [7, 8] The chances of post-procedure-infection are 
higher in patients taking anticancer drugs due to immunosupression. [5, 6]. Incidence of liver 
abscess after TACE is 0.1 – 4.5% but carries a mortality rate  of up to 50% [7, 8, 9]. 
TACE was linked to a risk of liver abscess. Prophylactic antibiotics pre-procedure lower this 
risk and ensuing surgical intervention [6]. Prophylactic antibiotics may not be required in 
TACE for HCC patients [10, 11, 12]. Moreover, old age, compromised hepatic function, 
hypoalbuminemia, portal vein cancer embolus, invasive procedures, using broad-spectrum 
antibiotics, and having diabetes mellitus are the independent risk factors for hospital-acquired 
infections (HAIs) after TACE in patients with primary liver cancer [1, 13]. 
According to the latest Cardiovascular and Interventional Radiological Society of Europe 
(CIRSE) standards of practice guidelines (2021), routine antibiotic prophylaxis is not 
recommended [14]. However, prophylactic antibiotics are recommended in cases where there 
is a high risk of developing a liver abscess. These include biliary obstruction or the presence 
of a bilioenteric anastomosis. The choice of agent is dependent on the suspected path ogens 
(upper gastrointestinal tract ﬂora) and consideration should be given to potential hepatotoxicity 
of each agent. In complex cases involving multiple organisms, antibiotic resistance, or 
allergies, consulting with a microbiologist may be beneficial [14]. 
 

To date, it is uncertain whether the use of antibiotics as prophylaxis before TACE is beneficial 
or not in the prevention of postoperative infection. 
Excessive antibiotic use is a global problem and carries risks of adverse drug reactions like 
allergy or anaphylaxis, increased cost, and contributes to the emergence antimicrobial 
resistance [15, 16]. Therefore, it is the need of the hour to explore the utility of prophylactic 
antibiotics in TACE. 
This study aims to determine the effectiveness of prophylactic antibiotic use for TACE and 
occurrence of postoperative liver abscess.  
Methods 
Inclusion Criteria: 
1. Age 18 - 65 years 
2. Diagnosis of primary liver cancer or hepatocellular carcinoma 
3. Patients receiving TACE in PKLI & RC 
 
Exclusion Criteria: 
1. Receiving two or more TACE during the same hospitalization 
2. Use of any antibiotics other than the prophylactic antibiotic in 48hours prior to TACE 
3. Known hypersensitivity to specified antibiotic used in the study 
4. Incomplete or missing laboratory investigations and data 
5. Taking Sorafenib before TACE 
6. TACE combined with ablation or immunetherapy 
7. Tumor size >10 cm 
8. Portal vein thrombosis 
9. Dilated biliary channels on CT scan / Billiary invasion by tumor  
 
Study Outcomes: 
1. Predominantly neutrophilic leukocytosis ( > 11 ×109/L) with fever ( > 38 °C) in upto 
48 hours post-TACE 
2. Occurrence of liver abscess as diagnosed by imaging within 30 days of the procedure 

3. Liver abscess requiring an intervention (e.g., percutaneous transhepatic abscess 
drainage (PTAD), percutaneous transhepatic abscess puncture or liver abscess 
incision) within 30 days of TACE 
 
Sampling Technique: 
In this study, consecutive sampling technique and randomization by lottery method will be 
applied. In lottery method the investigator will randomly draw numbers from the box to 
choose sample until the final sample size reaches. Two numbers will be assigned as ‘1’ for 
antibiotic group and ‘2’ for no antibiotic group. 
 
Current standard of care treatment at PKLI&RC (as per local guidelines) would be given to 
all patients receiving TACE for the intervention group or ‘antibiotic group’ (i.e., Inj. 
Ceftriaxone 1g, intravenous × stat). While no antibiotic would be given to the ‘no antibiotic 
group’. 
Statistical analysis:  
1. Data to be recorded on Excel sheet and subsequently exported to SPSS version 24 for 
further analysis. 
2. A univariate analysis will be employed for the comparison of variations in patients’ 
baseline characteristics between the preventive medication group and the 
nonpreventive medication group. The Student’s t-test will be employed to evaluate if 
the obtained data had a homogeneous variance and a normal distribution. For 
nonhomogeneous variance, the comparisons were made using a one-way analysis of 
variance (ANOVA). In order to compare categorical variables, Fisher’s exact test or 
Pearson’s 2 test was used as applicable. 
3. The univariate analysis included chi-square tests for categorical variables and t-tests 
for continuous variables. Significant variables (P < 0.01) in univariate analysis and 
covariates considered clinically influential were then analyzed by multivariate 
stepwise logistic regression (forward stepwise logistic regression) to identify 
significant variables. We applied univariate and multivariate logistic regression models 
to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for significant 

variables for finding potential risk factors in WBC＞11×109/L group or postoperative 
infection group.  
4. P value less than 0.05 was considered statistically significant. 
 
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