**3.8. Glasgow prognostic score in hepatocellular carcinoma**

and T lymphocytes, and higher ratio also correlates with lower overall survival. The combination of these findings suggests that neutrophils might facilitate tumour progression. They suppress adaptive immunity by death ligand expression [66]. Correlation between NLR and PD-L1 expression in the centre of tumour but not peritumoural tissues has been described [67]. High NLR was associated with CD163-positive tumour-associated macrophages [24]. High NLR was associated with higher peritumoural but not intratumoural CD163 and IL-17-

Platelet-to-lymphocyte ratio (PLR) is another frequently assessed estimate of SIR, although fewer publications have been devoted to PLR than to NLR. Nevertheless, prognostic role of PLR has been evaluated in different aspects of HCC patient treatment, including surgery [31,

In the largest Western series enrolling 370 HCC patients, treated by surgical resection, higher preoperative PLR was identified as an independent risk factor of worse overall survival and recurrence-free survival [31]. Other research groups have confirmed the association between PLR and prognosis. Higher preoperative PLR is an independent predictor of worse overall survival in HCC patients undergoing curative liver resection [69, 70] as was shown in two large Eastern cohorts comprising 778 [70] and 1804 [69] patients, respectively. The significant association with overall survival (p < 0.001) was retained in specific subgroups, e.g., patients having cirrhosis or being positive for HbsAg [70]. In some studies, the associations between PLR and prognosis were statistically significant but not independent. Thus, PLR was significantly associated with disease-free and overall survival in 332 HCC patients after hepatectomy [71]. The association between higher PLR and shorter recurrence-free survival in HCC patients undergoing curative liver resection was statistically significant but not independent [70]. Finally, no association has been found in some studies. Hence, in 113 HCC patients undergoing curative resection, PLR was not confirmed as a significant prognostic factor for

PLR has been analysed in the context of liver transplantation. Already in early studies, statistically significant association was found between pretransplantation PLR and cancer recurrence after liver transplantation. In 146 patients, the recurrence-free survival was 80.7 *versus*

In 122 Chinese patients undergoing transarterial chemoembolisation (TACE) for HBV-related HCC, high pre-treatment PLR (≥96.13) was an independent, statistically significant (p = 0.001)

In 414 patients affected by recurrent HCC and treated by thermal ablation, high pre-treatment PLR (≥87.87) was associated with higher risk of recurrence and worse recurrence-free survival. The 1- and 3-year recurrence rates in high *versus* low PLR groups were 56.0 and 79.5

Regarding sorafenib-treated cases, PLR has not shown prognostic value in patients receiving sorafenib for advanced HCC. Although the negative result could be attributed to the small

group size (16 patients), significant association with NLR was still confirmed [75].

69, 70], transplantation, sorafenib treatment, TACE and ablation techniques.

recurrence-free survival. NLR was found to be superior in this study [28].

91.6%; the difference was statistically significant as confirmed by p = 0.02 [72].

factor that predicted worse survival [73].

*versus* 39.9 and 54.8%; p < 0.05 [74].

expressing cells [68].

**3.7. Platelet-to-lymphocyte ratio in HCC patients**

56 Hepatocellular Carcinoma - Advances in Diagnosis and Treatment

The prognosis and treatment options of HCC patients depend not only on tumour progression but also on the extent of liver dysfunction. As a consequence, several staging systems have been proposed to predict prognosis for HCC, including Glasgow prognostic score (GPS), based on the levels of C-reactive protein and albumin (**Table 1**). GPS in HCC patients with hepatocellular carcinoma is an independent prognostic predictor after hepatic resection, with higher score indicating worse prognosis [80]. Thus, among 144 patients who underwent surgical resection for HCC, GPS 2 was associated with worse disease-free (HR = 2.527; 95% CI: 1.163–5.490; p = 0.019) and overall (HR = 8.012; 95% CI: 2.818–22.784; p < 0.001) survival, but GPS 1 with shorter overall (HR = 2.277; 95% CI: 1.029–5.039; p = 0.042) survival than seen in patients preoperatively presenting with GPS 0 [80]. The independent prognostic role of GPS for overall survival was confirmed by other research teams [81] and meta-analysis [82]. Modified GPS score and dynamics of GPS score have also shown prognostic value. Thus, elevated modified GPS was associated with overall survival (HR = 2.21; 95% CI: 1.73–2.82; p < 0.05) in a meta-analysis of 2047 HCC patients [83]. Dynamics of GPS (assessed in association with hepatitis B infection status) was an independent predictor of overall survival in 247 patients treated by liver resection [84]. In addition, GPS was related to blood transfusion requirement and postoperative pulmonary complications after liver resection for HCC [85]. In patients undergoing liver transplantation for HCC, elevated GPS, reaching 1 or 2, was


**Acknowledgements**

\*, Dzeina Mezale<sup>1</sup>

, Ilze Fridrihsone<sup>1</sup>

\*Address all correspondence to: ilze.strumfa@rsu.lv

2 Latvian Institute of Organic Synthesis, Riga, Latvia

1 Department of Pathology, Riga Stradins University, Riga, Latvia

3 Department of Surgery, Riga Stradins University, Riga, Latvia

**Author details**

Ilze Strumfa<sup>1</sup>

Dainis Balodis<sup>1</sup>

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**Table 1.** Glasgow prognostic score and its modifications [30].

significantly associated with poor overall (p = 0.018) and recurrence-free (p = 0.030) survival. Complex scoring system has been created on the basis of Milan criteria and GPS [86].

Regarding advanced HCC, GPS retained independent prognostic value for survival (HR= 1.410; 95% CI = 1.060–1.874; p = 0.018). In addition to the statistical significance of results, the biological survival differences by GPS were also remarkable, e.g., median survival was 480 days in patients presenting with GPS 0 and 154 days in those having GPS 1 or 2 [87]. GPS was an independent prognostic factor (HR = 5.483; 95% CI: 2.563–11.729; p < 0.001) for overall survival in patients undergoing sorafenib treatment: the median survival in those having GPS 0 *versus* elevated GPS 1 or 2 was 18.1 *versus* 5.2 months; p < 0.001 [88].

In HCC patients undergoing transarterial chemoembolisation, GPS was an independent prognostic factor for overall survival (HR = 1.697; 95% CI: 1.325–2.174; p < 0.001). It was also found to be superior to other inflammation scores as NLR, PLR or modified GPS. Based on these findings, the authors proposed a new complex score that included Child-Pugh stage, number of tumour nodules and proportion of affected liver, AFP, presence or absence of portal vein thrombosis and GPS. The new score was also a significant predictor of survival as the HR was 1.724; 95% CI: 1.347–2.285; p < 0.001 [89].
