Utility of Inflammatory Markers in Predicting Hepatocellular Carcinoma Survival after Liver Transplantation

Abstract

Inflammatory markers have been studied in cancers and chronic states of inflammation. They are thought to correlate with tumor pathology through disruption of normal homeostasis. Markers such as neutrophil to lymphocyte ratio (NLR) among others have shown promise as prognostic tools in various cancers. In this study, we evaluate complete blood count based inflammatory markers in hepatocellular carcinoma (HCC) to predict overall and recurrence-free survival of patients after liver transplant. Between 2001 and 2017, all HCC indicated liver transplants were retrospectively reviewed. Inclusion criteria included presence of complete blood cell counts with differential within three months prior to transplantation. Exclusion criteria included retransplantation and inadequate posttransplant followup. A total of 160 patients with HCC were included in the study. Of those, 74.4% had hepatitis C virus as the underlying cause of HCC. Calculated Model for End stage Liver Disease (MELD) scores were statistically worse in patients with elevated NLR (≥5), derived NLR (≥3), and low lymphocyte to monocyte ratio (LMR) (<3.45), whereas elevated platelet to lymphocyte ratio (PLR) (≥150) did not correlate with MELD. Of the tumor characteristics, low LMR was associated with tumor presence and microvascular invasion on explant. Though overall survival trended towards better outcomes with low NLR and dNLR and high LMR, these did not reach statistical significance. High LMR also trended towards better recurrence-free survival without statistical significance. Low PLR was associated with statistically significant overall and recurrence-free survival. In conclusion, while prior studies in HCC have identified NLR as surrogate for tumor burden and survival, in this study we highlight that PLR is a good surrogate of mortality and recurrence-free survival in HCC transplant patients. Further, future study of PLR, NLR, and LMR in larger HCC populations before and after interventions may help clarify their clinical utility as a simple and noninvasive clinical tool as prognostic markers.

Postoperative Trends and Prognostic Values of Inflammatory and Nutritional Biomarkers after Liver Transplantation for Hepatocellular Carcinoma

“…The removal of the chronically inflamed cirrhotic liver and the regaining of normal liver function, with recovery from the complications of liver failure and portal hypertension, contrast with a high surgical invasiveness, potentially severe surgical complications, and immunosuppressant toxicity [ 13 , 14 ]. However, the data assessing the post-transplant outcome in terms of inflammatory state are very limited [ 1 , 15 ], while data on the post-transplant metabolic recovery are extremely heterogeneous, variably reporting a significant increase in the prevalence of metabolic syndrome and an incomplete recovery from pre-LT sarcopenia [ 16 , 17 , 18 ].…”

<p>Inflammation-Based Prognostic Scores in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma After Liver Transplantation</p>

“…Recent studies have shown that predictors of HCC recurrence post LT have emerged, including AFP, microvascular invasion, platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), neutrophil to lymphocyte ratio (NLR) and systemic Immune-Inflammation Index (SII). [4][5][6] There is increasing evidence that correlates preoperative immunological statuses with not only postoperative complications but also long-term outcomes of patients with certain tumors, which is associated with poorer cancer-specific survival in patients with malignant tumors. [7][8][9] In addition, a growing number of studies have shown that circulating immune inflammatory cells such as platelets, neutrophils and lymphocytes play an important role in promoting the proliferation, invasion and migration of cancer cells by changing the tumor microenvironment.…”

Serum levels of inflammatory markers CRP, ESR and albumin in relation to survival for patients with hepatocellular carcinoma

“…Inflammation, both local (CRP) and systemic (ESR) has recently emerged as an important reflection of HCC aggressiveness and prognosticator. Various other clinical approaches have been taken to its measurement, including peripheral blood neutrophil to lymphocyte (NLR) and platelet to lymphocyte (PLR) ratios 21,33‐49 . These novel markers of disease activity are especially needed for that 50% of HCC patients who do not have elevated AFP levels 30,46,50 .…”

“…Various other clinical approaches have been taken to its measurement, including peripheral blood neutrophil to lymphocyte (NLR) and platelet to lymphocyte (PLR) ratios. 21,[33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49] These novel markers of disease activity are especially needed for that 50% of HCC patients who do not have elevated AFP levels. 30,46,50 However, a central unanswered question is why elevated values of these inflammation markers predict poor survival.…”