TY - JOUR

T1 - Prognostic biomarkers in and selection of surgical patients with hepatocellular carcinoma

AU - Pommergaard, Hans Christian

N1 - Funding Information: This work was financially supported by the Harboe foundation, the Risom foundation and the Dagmar Marchall foundation, for which I am grateful.

PY - 2023/5

Y1 - 2023/5

N2 - Hepatocellular carcinoma (HCC) is the sixth most common cancer and the fourth leading cause of cancer deaths globally with increasing incidence. In most cases, HCC develops as a result of an underlying chronic liver disease. The stage at the time of diagnosis is closely correlated with prognosis with a 5-year survival of more than 70% for patients with early-stage HCC. These patients are generally suitable for curative treatment, such as resection, ablation or liver transplantation. In contrast, 5-year survival may be as low as 5% for patients in advanced stages of the disease. Due to organ shortage and the risk of mortality for patients on the waiting list for liver transplantation, survival in patients undergoing transplantation due to HCC should be comparable to those with benign indications. However, there is an ongoing debate concerning the best criteria for the selection of patients with HCC for transplantation, as the current criteria may rule out patients with a good prognosis. Liver resection may be performed in patients with HCC in non-cirrhotic livers and cirrhotic livers with preserved liver function. However, careful selection of patients is crucial due to high recurrence risk (>50%) and severe complications in >10% of liver resections for HCC. The aims of this thesis were to identify prognostic biomarkers in and improve the selection of patients undergoing transplantation and resection for HCC, respectively. Yet another aim was to improve upon the existing early detection of recurrence. The seven studies included in this thesis provided novel insights into prognostic biomarkers and selection of surgical patients with HCC. Firstly, the literature was reviewed regarding biomarkers to detect recurrence after transplantation for HCC. Next, two novel tumour-related prognostic biomarkers were identified and the applicability of circulating tumour DNA (ctDNA) was evaluated. Moreover, using data from the European Liver Transplant Registry (ELTR), vascular invasion and locoregional treatment were identified as important prognostic markers. Lastly, using propensity score calibration, prognostic differences between HCC in cirrhotic and non-cirrhotic livers were clarified. The studies included in this thesis add important knowledge towards better selection of patients for transplantation and resection of HCC, respectively. In future guidelines, alpha-fetoprotein, radiological markers of vascular invasion and response to locoregional treatment may be included in selection criteria for transplantation of patients with HCC. In addition, the novel biomarkers identified may add important prognostic information and improve the selection of patients. For resected patients, a proper balance between survival benefit and risk of recurrence and complications may be ensured. For transplanted patients, optimized selection means that the utility of donor organs is maximized by more accurately selecting patients with favourable tumour biologies.

AB - Hepatocellular carcinoma (HCC) is the sixth most common cancer and the fourth leading cause of cancer deaths globally with increasing incidence. In most cases, HCC develops as a result of an underlying chronic liver disease. The stage at the time of diagnosis is closely correlated with prognosis with a 5-year survival of more than 70% for patients with early-stage HCC. These patients are generally suitable for curative treatment, such as resection, ablation or liver transplantation. In contrast, 5-year survival may be as low as 5% for patients in advanced stages of the disease. Due to organ shortage and the risk of mortality for patients on the waiting list for liver transplantation, survival in patients undergoing transplantation due to HCC should be comparable to those with benign indications. However, there is an ongoing debate concerning the best criteria for the selection of patients with HCC for transplantation, as the current criteria may rule out patients with a good prognosis. Liver resection may be performed in patients with HCC in non-cirrhotic livers and cirrhotic livers with preserved liver function. However, careful selection of patients is crucial due to high recurrence risk (>50%) and severe complications in >10% of liver resections for HCC. The aims of this thesis were to identify prognostic biomarkers in and improve the selection of patients undergoing transplantation and resection for HCC, respectively. Yet another aim was to improve upon the existing early detection of recurrence. The seven studies included in this thesis provided novel insights into prognostic biomarkers and selection of surgical patients with HCC. Firstly, the literature was reviewed regarding biomarkers to detect recurrence after transplantation for HCC. Next, two novel tumour-related prognostic biomarkers were identified and the applicability of circulating tumour DNA (ctDNA) was evaluated. Moreover, using data from the European Liver Transplant Registry (ELTR), vascular invasion and locoregional treatment were identified as important prognostic markers. Lastly, using propensity score calibration, prognostic differences between HCC in cirrhotic and non-cirrhotic livers were clarified. The studies included in this thesis add important knowledge towards better selection of patients for transplantation and resection of HCC, respectively. In future guidelines, alpha-fetoprotein, radiological markers of vascular invasion and response to locoregional treatment may be included in selection criteria for transplantation of patients with HCC. In addition, the novel biomarkers identified may add important prognostic information and improve the selection of patients. For resected patients, a proper balance between survival benefit and risk of recurrence and complications may be ensured. For transplanted patients, optimized selection means that the utility of donor organs is maximized by more accurately selecting patients with favourable tumour biologies.

U2 - 10.1111/apm.13309

DO - 10.1111/apm.13309

M3 - Comment/debate

C2 - 37186326

AN - SCOPUS:85153769883

VL - 131

SP - 1

EP - 39

JO - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica

JF - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica

SN - 0903-4641

IS - S146

ER -