Role of Biobran (Arabinoxylan Rice Bran) on Patients with Advanced Stage Hepatocellular Carcinoma

INTRODUCTION

Hepatocellular carcinoma (HCC) has taken fifth position among all cancers and being recognized as the third ranked common of all cancer-related deaths globally.¹ Being the fifth most common cancer in men and the eighth commonest in women, it is cleared that, malignancy of liver has proven its life-threatening impact.² The incidence of HCC in Bangladesh is the 8th among all cancers. Hepatocellular carcinoma ranks the third among all cancer-related deaths in Bangladesh.^3–5 However, in Bangladesh, most patients are diagnosed with advanced HCC due to the lack of the effective surveillance and monitoring system for HCC. The principal objective of the study is by using arabinoxylan rice bran (biobran), identifying the surviving time and enriching the living standard in terminal stage carcinoma of liver patients by using arabinoxylan rice bran (biobran).

The segment of rice which is found after taking away the husk and edible endosperm is called rice bran. Polysaccharides which have cell walls, having the rice seed endosperm. Carrying different kinds of bioactive components with chemo-preventive activity, rice bran includes γ-oryzanol, caffeic acid, ferulic acid, coumaric acid, tricin, phytic acid; the vitamin E isoforms α-tocopherol, γ-tocopherol, and various tocotrienols; phytosterols, for example, β-sitosterol, capesterol, stigmasterol, and carotenoids like α-carotene, β-carotene, lycopene, and lutein; micronutrients such as calcium, magnesium, and nine B vitamins; and essential amino acids such as histidine, tryptophan, arginine, and cysteine. The process of beneficial alteration of giving rise to rice bran with bacterial or fungal agents can enhance the biocompatibility by improving the efficacy of the antioxidant activities. The hemicellulose improves the extract with a huge number of carbohydrate-hydrolyzing enzymes accelerate the production of bio-brain from the shiitake mushroom.^6,7

The only three footsteps of generating process of MGN-3/biobran are: (1) polysaccharides, removal whereas the source is from rice bran; (2) production from origin of multiple shiitake-derived carbohydrate-hydrolyzing enzymes used to alter the extracted polysaccharides; and (3) half of the reaction of hydrolysis in rice bran hemicellulose polysaccharides by the carbohydrate-hydrolyzing enzymes obtained from shiitake mushrooms. Last but not the lease, altering the elements with high heat and pressure and final outcome is, achieving a powder form.⁶

It was previously found that, through their capability in increasing apoptosis, the effect in non-carcinogenic of the rice bran-derived bioactive elements is arbitrated, reduce cell proliferation, and significantly change the enhancement of cell cycle in cancerous cells (Figs 1 and 2).⁷

The best supportive treatment measures in the mean of cancer patients are known as best support care (BSC). The European Organization for Research and Treatment of Cancer (EORTC) defines BSC as, “supportive treatment interventions in case of patients having carcinoma encompass the multi-professional approach to the individual all-encompassing physical, psychosocial, cultural needs and spiritual and should have the existence at all times of the illness for patients of all ages and regardless of the current treatment intention of the interventions directed against the illness.” Approaching for the enhancing of the standard of life of patients through the management of pain as well as other physical, psychosocial, and spiritual problems.

MATERIALS AND METHODS

A study which was observational in type, was run by the Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka from September 2019 to December 2020. A sample size of 52 terminal stage of HCC patients was included [26 patients for biobran with BSC (biobran group) and 26 patients for BSC only)] clinical and biochemical parameters were evaluated at the level of standard, day-30, day-60, and day-90. Primary end point was durability at 3 months or death. Secondary end point was the improvement of quality of life assessed by the Eastern Cooperative Oncology Group (ECOG) performance status and improvement of liver function assessed by Child-Turcotte-Pugh (CTP) score.

The follow-up procedure was strictly maintained for all of the patients for at least 3 months or up to death. Adverse events were closely monitored. The death of admitted patients was recorded physically and those who died outside were recorded over the telephone.

Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, prothrombin time (INR), serum albumin, serum creatinine, serum electrolyte, complete blood count (CBC), alpha-fetoprotein (AFP), and hepatitis B surface antigen (HBsAg) were checked for all patients. Also, antigens with hepatitis B (HBeAg), anti-HBe, and anti-HBc were measured, if required. Using real-time PCR and anti HCV was checked and if positive, HCV RNA estimation was done. HBV DNA estimation was done for abdominal ultrasound, and CT scan/MRI and upper GI endoscopy were also accomplished as and when necessary. Fine needle aspiration for cytology was done where CT scan/MRI finding was inconclusive.

The information was gathered by the statistical package SPSS (version 20.0 IBM Corp: Armonk NY, USA). Variables in quantitative type distributing were published as mean ± standard deviation (SD) and those not normally distributed were expressed as median values (range). The Chi-square (χ²) test and Fisher’s exact test were used for comparing qualitative variables and the student’s t-test and paired t-test for comparing quantitative continuous variables when appropriate. Survival was evaluated with the Kaplan–Meier method. The p-values < 0.05 was top of the notch.

Overall fitness of a patient was often assessed by a performance status scale named ECOG. The ultimate feedback for the performance status of patients is found worse in almost all malignancies.

RESULTS

DISCUSSION

Regarding baseline ECOG performance status of the patients, the current study found that the majority of the terminal stage HCC patients presented with PS 3, 65% in the biobran group and 58% in the BSC group. However, no vital existence of (p > 0.05) variety is observed between the groups.

After 30 days of treatment, the majority of (67%) patients of the biobran group had shown improvement of performance status; but in the BSC group, there was no improvement in performance status among patients. This difference was statistically significant (<0.05). This observation is consistent with the observation of Takahara and Sano;^8,9 they found that the administration of biobran improves the quality of life in cancer bearing patients, including HCC patients.

In the present study, no significant improvement of Child–Pugh score was detected between the two groups after giving the treatment. In this study, it was observed that biobran administration had no survival benefit at 30, 60, and 90 days follow-up. Similarly, earlier study carried out by another study¹⁰ which illustrated no change in survival time by using various BRMs in HCC patients. In terminal stage (BCLC-D) HCC patients, the middle durability time is 3 months guided by the European Association for the study of liver (2018). In this study, the middle durable time for all the respondents, biobran group patients, and BSC group patients were 23, 24, and 19 days, respectively, for lower median survival time.⁸ They found in their study the median survival time was 1 month for terminal stage HCC patients. In the current study, it is observed that AFP level ≥ 200 ng/mL was associated with worse survival (p-value 0.047). Similar observation had been made by a previous established study⁸where AFP ≥ 400 ng/mL was associated with worse survival. The present study didn’t observe any adverse effects of biobran. Other studies also showed that none of the patients was developed any negative reaction produced by biobran.^8,11 The overall fitness of a patient was often assessed by the ECOG performance status scale. The patient’s outcome with three or four performance status is worse near to close to all carcinomas.

CONCLUSION

It can be concluded that biobran may have some transient effect on improving quality of life in terminal stage HCC patients, which was observed by improvement of ECOG Performance Status. However, this was not sustained. The sample size is so small that further validation is essential. However, it does not seem that biobran improves survival or regresses HCC progression. The effect of ECOG performance improvement by biobran may be applied on a case-by-case basis.

ORCID

Faysal Ahmed https://orcid.org/0009-0003-3147-5797

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