ojgas Open Journal of Gastroenterology 2163-9450 2163-9469 Scientific Research Publishing 10.4236/ojgas.2024.1412046 ojgas-137942 Articles Medicine Healthcare Value of Inflammatory Scores in the Assessment of the Prognosis of Hepatocellular Carcinoma (HCC) during Hospitalization, in Internal Medicine Department of University Hospital Centre of Bouake Yapa Gnadou Stéphane Keny 1 2 Konan Nguessan Michel 3 4 Kouassi Lauret 1 2 Touré Kadidiata 1 2 Ouattara Tiépé Rokia 3 4 Koné Famoussa 1 2 Kouamé Kouamé Gilles 1 2 Acho Jean Kévin 1 2 Gboko Komenan Kouman Landry 1 2 Bouagnon Patrick Roland 1 2 Koffi Marie Sandrine 1 2 Traoré Danielle 1 2 Touré Lazare 1 2 Sako Kalifa 1 2 Ouattara Solange 1 2 Wognin Manzan Anastasie 1 2 Abbé Fiacre 3 4 Koffi Georges Stéphane 3 4 Ouattara Bourhaïma 1 2 aDepartment of Internal Medicine, Teaching Hospital of Bouake, Bouake, Cote d’Ivoire aMedical Sciences Training and Research Unit, Alassane Ouattara University, Bouake, Cote d’Ivoire aDepartment of Internal Medicine, Treichville Teaching Hospital, Abidjan, Cote d’Ivoire aMedical Sciences Training and Research Unit, Félix Houphouet Boigny University, Abidjan, Cote d’Ivoire 04 12 2024 14 12 447 457 25, October 2024 1, October 2024 1, December 2024 © Copyright 2014 by authors and Scientific Research Publishing Inc. 2014 This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/ Background and aim: Hepatocellular carcinoma (HCC) is one of the leading causes of death in Africa. Many inflammatory scores have been used to predict the prognosis of this disease in various situations. The aim of this study was to determine the influence of NLR, PLR and SII on the prognosis of advanced HCC in hospitalized patients. Materials and methods: It was a cross-sectional analytical study carried out in the Internal Medicine Department of Bouake University Hospital over a period of 3 years. Results: Out of 96 patients included in the study, we found a significant association between SII and CHILD score ≥ B. We also identified NLR as an independent predictor of hepatic encephalopathy. Conclusion: This study shows the relationship between inflammatory scores and hepatic insufficiency and the possibility of using NLR to predict in-hospital hepatic encephalopathy in patients suffering from advanced HCC. Inflammation Score Hepatocellular Carcinoma Prognosis West Africa 1. Introduction

Hepatocellular carcinoma (HCC) is a public health problem. According to the Global Cancer Observatory (Globocan), in 2022, HCC was the fourth most common cancer in Africa, behind breast, cervical and prostate cancer, with 7,3844 new cases and 70,315 deaths [1] . In sub-Saharan Africa, HCC occurs mainly in young men infected by viral hepatitis B, the major risk factor of this disease [2] , which is particularly transmitted during childhood and pregnancy. The current challenge for WHO member states is the reduction of hepatitis-related mortality of 65% and new infections of 90% by 2030, [3] , only achievable by vaccination against viral hepatitis B. However, low socio-economic status of patients could be a significant obstacle because of low health literacy of patients, and limited healthcare resources and access, including lack of insurance or ability to pay for care [4] . Beyond prevention, the assessment of the prognosis of HCC has evolved in recent years, probably because of a better understanding of the relationship between cancer and inflammation.

Inflammation is common in HCC and contributes to the poor prognosis of the disease [5] . It can precede development of malignancy or may be the consequence of oncogenic change that drives a tumor-promoting inflammatory milieu, stimulating angiogenesis, metastasis, subverts adaptive immunity and alters response to treatment. [6] . Thus, inflammation-based scores have been used as cost-effective biomarkers for diagnosis and assessment of prognosis of digestif [7] [8] and extra-digestive cancers [9] - [11] . In HCC, elevated neutrophil to lymphocyte ratio (NLR) [12] , platelet-to-lymphocyte ratio (PLR) [13] , Systemic Inflammation Index (SII) [14] , aspartate aminotransferase to lymphocyte ratio index (ALRI) [15] , or Prognostic nutritional index (PNI) [16] before treatment, have been correlated with a poor prognosis in patients after curative or palliative treatment, with a relative superiority of NLR over PLR, ALRI, and SII in Trans-arterial chimioembolisation (TACE) [17] . In sub-Saharan Africa, few studies focused on inflammatory scores in the assessment of HCC’s prognosis especially for in-hospital patients.

The aim of this study was to determine the influence of NLR, LPR and SII on the prognosis of advanced HCC in hospitalized patients.

 2. Materials and Methods <xref ref-type="bibr" rid="scirp.137942-"></xref>2.1. Study Design

This was a cross-sectional analytical study carried out in the Internal Medicine Department of Bouake University Hospital over a period of 3 years, from 1 January 2020 to 31 December 2022.

 2.2. Patients

Inclusion criteria: patient aged 14 years old or more with advanced HCC. Advanced HCC was HCC at stage C or D of Barcelona Clinic Liver Classification. The diagnosis of HCC was done if one of the following conditions were fulfilled:

Exclusion criteria: patients with viral or bacterial infection, including ascites fluid infection, and patients treated with anti-inflammatory drugs were not included in the study. Also, incomplete records for the studied parameters were not included.

 2.3. Baseline Characteristics

We collected sociodemographic, clinical, biological and radiological characteristics of patients on a standardized survey form ( Appendix 1 ). Blood count, was used to calculate inflammatory scores by the following formulas:

The cut-off of NLR, PLR and SII were chosen according to their significance in systematic review and meta-analysis. We also considered the race and ethnicity of patients to choose these cut-off.

 2.4. Data Source

All the data of this study came from the medical records of the patients.

 2.5. Statistical Analysis

Statistical analysis was performed using Epi-info 7 software.

Data were processed and analyzed using epi info7 software. Word and Excel were used for graphical representations. Quantitative variables were expressed as median or mean with extremes, and qualitative variables were expressed as proportion. The Chi-square test was used to find a relationship between the categorical variables. When the expected number of participants was less than 5, the Fisher test was applied. The significance level was less than 5% for univariate analyses.

After descriptive analysis of our data, we performed univariate analysis and if association were found between variables, a multivariate analysis was performed. we firstly analyzed the influence of sociodemographic (age, sex) and morphological characteristics of HCC (number and size of nodules) on inflammatory scores. Then we assessed the influence of inflammatory scores (NLR, PLR, SII scores) on the following prognostic data such as liver function (hepatic encephalopathy, child score), death, length of stay, performans status and BCLC stage.

 2.6. Ethics Statement

The study was conducted in accordance with the ethical guidelines of the 1975 Declaration of Helsinki (6th revision, 2008). All data were anonymized during the study process and kept confidentially within the Internal Medecine Department

The study was conducted in accordance with the principles of the Declaration of Helsinki.

 3. Results

Out of 160 HCC patients, 96 patients met the criteria and were included in the study. Sixty-four patients were excluded from the study, including 47 for ascites infection and 17 patients for incomplete data. The mean age was 48.1 ± 15 years and the sex ratio was 3.7. The educational level was absent (31%), primary (46%), secondary (17%) and university (6%). HCC was classified as BCLC C in 55% of cases and BCLC D in 45%. The mean length of stay was 4.5 ± 4.8 days. The means of inflammatory scores were 4.02 ± 2.97 (NLR), 163.9 ± 133.8 (PLR) and 1004.6 ± 1068 (SII) as shown in Table 1 .

<xref ref-type="bibr" rid="scirp.137942-"></xref>Table 1. Mean of neutrophils, lymphocytes, platelets count and inflammation scores in the 96 patients.

Parameters

Means

Neutrophils (cells/mL)

5900 ± 3400 (9000; 21800)

Lymphocytes(cells/mL)

1800 ± 1100 (500; 8600)

Platelets (cells/mL)

235700 ± 132700 (19000; 565000)

NLR

4.02 ± 2.97 (0.01; 17.45)

PLR

163.9 ± 133.8 (12.8; 929.4)

SII

1004.6 ± 1068.8 (2.3; 8271.8)

PLR, was significantly associated with age (RR = 1.64; CI 95: 1.24; 2.17). There was no association between inflammatory scores and sex, size and number of hepatic nodules ( Table 2 ).

<xref ref-type="bibr" rid="scirp.137942-"></xref>Table 2. Influence of age, sex, number and size of nodules on inflammation scores.

NLR

PLR

SII

Age > 65

7 (33.3%)

3 (14.3%)

5 (23.8%)

1.11 (0.7; 1.5)

1.64 (1.24; 2.17)

1.3 (0.99; 1.85)

0.057

0.005

0.09

male

32 (43.84%)

30 (76.9%)

32 (43.8%)

gender

1.39 (1.03; 1.87)

1.06 (0.5; 2.21)

1.31 (0.95; 1.80)

0.05

0.86

0.12

Multiples nodules

26 (41.9%)

25 (40.3%)

25 (40.3%)

1.16 (0.85; 1.59)

0.98 (0.69; 1.39)

1.03 (0.74; 1.44)

0.35

0.93

0.84

Nodule size > 3 cm

10 (66.7%)

19 (47.5%)

15 (37.5%)

1.32 (0.90; 1.93)

0.78 (0.45; 1.36)

1.12 (0.59; 2.11)

0.07

0.44

0.69

Mortality was 18.7%. No association was found between inflammation scores and death in patients hospitalized for more than 5 days. In univariate analysis, NLR and SII were respectively identified as risk factors for hepatic encephalopathy (RR = 1.49; CI 95: 1.1; 2.01) and CHILD ≥ B score (RR = 3.93; CI 95: 1.24; 12.4). In multivariate analysis, NLR alone was identified as an independent predictor of hepatic encephalopathy ( Table 3 ).

<xref ref-type="bibr" rid="scirp.137942-"></xref>Table 3. Association between inflammation scores and prognostic factors in advanced HCC.

Death

Length of stay ≥5j

Encephalo-pathy

Child score ≥ B

PS ≥ 3

BCLCD

NLR (n)

≥4 (37)

9 (24.3%)

26 (70.3%)

16 (43.2%)

32 (86.5%)

19 (51.3%)

18 (48.6%)

RR*

1.1 (0.90; 1.38)

0.91 (0.47; 1.74)

1.49 (1.1; 2.01)

2 (0.80; 5.1)

1.1 (0.74; 1.67)

1.15 (0.79; 1.68)

p

0.26

0.78

0.002

0.11

0.59

0.44

aOR*

3.90 (1.37; 11.15)

p

0.01

PLR (n)

≥164 (39)

9 (23.1%)

31 (79.5%)

12 (30.8%)

33 (84.6%)

18 (46.1%)

17 (43.6%)

RR

1.09 (0.89; 1.34)

1.93 (0.74; 5.02)

1.11 (0.86; 1.43)

1.71 (0.72; 4.1)

0.94 (0.64; 1.39)

0.99 (0.69; 1.42)

p

0.36

0.17

3.90

0.20

0.77

0.97

SII (n)

≥1004 (39)

8 (21.1%)

31 (81.6%)

14 (36.8%)

35 (92.1%)

19 (50%)

18 (47.4%)

RR

1.04 (0.85; 1.28)

1.87 (0.87; 3.9)

1.28 (0.97; 1.68)

3.93 (1.24; 12.4)

1.06 (0.71; 1.6)

1.11 (0.76; 1.61)

p

0.63

0.08

0.05

0.007

0.74

0.56

aOR

3.78 (0.96; 14.85)

p

0.05

RR: risk ratio (univariate analysis); aOR: Adjusted Odds Ratio (multivariate analysis); p value; *PS = Performans status.

 4. Discussion 4.1. Epidemiological Characteristics

Over 96 patients included in our study, 45% were at end-stage of HCC. Our results were similar to those of Pkossou (40.3%) [18] , but significantly lower than those of Pantong in Nigeria (61.43%) [19] , certainly due to the large number of HIV-infected patients in his study. In fact, HIV infection is associated with a faster clinical presentation and shorter survival [19] . HCC occurred predominantly in young men (48.1 years) and more than 70% of patients had a low level of education. Our results were comparable to those of Diallo in Senegal (47 years) [20] , and Bekolo in Cameroon who reported a mean age of 51.8 years in a sample of more than 900 patients [21] . Both authors observed male predominance. Another author noted a low level of education [22] .

 4.2. Inflammatory Scores and Neutrophil, Lymphocyte and Platelet Count

In our study, the means of inflammatory scores were 4.02 ± 2.97 (NLR), 163.9 ± 133.8 (PLR) and 1004.6 ± 1068 (SII), and were superior to the cut-off of NLR, PLR and SII required to predict cancer prognosis in the literature. In the study of Zhang [8] , RNL was 2.1, RPL and SII were respectively 139.5 and 438.7. This study was about gastric cancer and was not carried out in Africa. But, another study was done in Ivory coast and showed lower inflammatory scores (NLR > 2.5 and PLR > 92) [23] . In this study, patients at intermediate stage of HCC were also included. Moreover, lymphocyte count was higher (1881 vs 1800), while platelet (168000 vs 235000) and neutrophil count (4153 vs 5900) were lower. Thus, the lower lymphocyte count versus higher platelet and neutrophil count of our patients matched with their advanced stage of HCC and performans status (PS ≥ 3), although no statistical association was found between inflammatory scores, PS and BCLC D. In fact, B cells limits the growth of hepatic tumors and T cells prevents the initial steps carcinogenesis [24] , whereas neutrophils have been shown to be a poor prognostic factor by promoting the development of HCC through p53 and STAT3 signaling pathways [25] and platelets facilitate the tumor cells invasion [26] .

 4.3. Inflammatory Scores and Sociodemographic and Morphological Characteristics

In our study, PLR was significantly higher in elderly patients. In the elderly, especially in the case of pathological aging, there is a dysregulation of the immune system which may be responsible for chronic inflammation [27] . No association was found between inflammatory scores and number or tumor size. However, this association was described for the number and size of tumors. In fact, in a study carried out over 1000 patients, NLR was only associated with tumor size ≥ 2 cm, while PLR was significantly associated with tumor size ≥ 2 cm with a strong association with tumor size > 3 cm [28] . In addition, a recent meta-analysis suggested a significant association between increased SII, multiple tumor numbers (OR = 1.42, 95% CI = 1.09 - 1.85, p = 0.009) and maximum tumor diameter > 5 cm (OR = 3.06, 95% CI = 1.76 - 5.30, p < 0.001), without association with sex.

 4.4. Inflammatory Scores and Liver Function

In our study, an increased SII was associated with altered liver function (CHILD score ≥B), and NLR was identified as independent predictor of hepatic encephalopathy. The relationship between inflammation and liver function is well known. Indeed, inflammation was associated with both the presence and severity of hepatic encephalopathy [29] . Moreover, NLR at discharge was identified as a significant predictor of 30-, 90- and 180-day readmissions in patients with hepatic encephalopathy [30] .

 4.5. Inflammatory Scores and in-Hospital Survival

No association was found between inflammatory scores and death. In several studies, inflammation score were significantly associated with poor prognosis, during the follow-up after curative or palliative treatment [31] [32] .

 5. Limitation of the Study

Our study was cross-sectional and based on medical records. It is possible that there may be information bias, particularly concerning the use of anti-inflammatory treatments, which is frequent in our patients. Nevertheless, all patients with infections were excluded from the study.

 6. Conclusion

This study demonstrates the influence of age on inflammatory score. It also shows the relationship between inflammatory scores and hepatic insufficiency and the possibility to use NLR to predict in-hospital hepatic encephalopathy on patients suffering from advanced HCC. A prospective study may give more information about these findings.

 Financial Support

The authors received no fees for this study.

 <xref ref-type="bibr" rid="scirp.137942-"></xref> Appendix 1: Standardized Survey Form

File number.............................. Year.................................

Entry date........................ Date of discharge..........................................

Epidemiological data

Age................. Sex.................... Religion..................................

Level of education................. Profession.............................

Prognostic data

Neutrophiles……………………………………………………………………

Lymphocytes……………………………………………………………………

Platelet…………………………………………………………………………..

Performance status score (WHO): 01/2/3/4

Edemato-ascitic decompensation/yes/no/

Abundance of ascites: absent or low/medium/high

Prothrombin rate....................... Total bilirubin ............

conjugated bilirubin........................ Glasgow score......................... Asterixis.................. Jaundice.. /yes/no/ Hepatic encephalopathy: Absent grade I grade II grade IIIa grade IIIb

Child Pugh score: A/B/C; BCLC: A/B/C/D/

Ascites fluid infection/yes/no/. Digestive hemorrhage/yes/no/.

Liver size............Number of nodule ...............Nodule size..............

Portal vein thrombosis/yes/no/

Extrahepatic metastasis: peritoneal/pulmonary/bone/Other........Death: Yes/no

Lengh of stay……………………………………………………………………………….
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