Transplant and non-transplant HCC patients at a single institution.

Background and Aim: Patients with hepatocellular carcinoma (HCC) are managed in various hospital departments, which complicates the assessment of the overall picture. In our large liver transplant institute, we evaluate all HCC patients in a weekly multi-disciplinary liver tumor board, and their data are prospectively collected in an institutional HCC database to evaluate HCC causes, tumor features, treatments, and survival. Materials and Methods: Baseline data for patients (n=1322) were prospectively recorded, including hepatitis status, routine clinical serum parameters, radiological assessment of maximum tumor diameter (MTD), tumor number, presence of macroscopic portal vein thrombosis (PVT), and serum alpha-fetoprotein (AFP) levels. Results: Cirrhosis was found in 81.1% of patients; 58.5% had hepatitis B virus (HBV), 14.9% hepatitis C virus (HCV), 8.9% cryptogenic cirrhosis, and less than 2% had alcoholism. MTD was <5 cm in 61.95% of patients, and 31.9% had PVT. The median overall survival was more than six-fold greater for the 444 liver transplant patients than for those without surgery. Transplanted patients had smaller tumors, whereas larger tumors (MTD >10 cm) were primarily in the no-surgery group. Parallel differences were found for AFP levels (highest in the no-surgery group). PVT was present in similar proportions (25.0% for transplant, 28.0% for no-surgery). The presence of cirrhosis was higher in the transplant group. MTD and levels of serum AFP, gamma-glutamyl transferase (GGT), and blood platelets were prognostic parameters for transplant. Furthermore, AFP and GGT levels were prognostic for transplanted PVT patients. Only albumin was prognostic in the no-surgery patients. Conclusion: Transplanted HCC patients have longer survival, smaller tumors, and more severe liver damage than no-surgery patients. Prognostic subsets were identified within the surgery and the PVT groups.

Discordance among aggressiveness characteristics of hepatocellular carcinoma: Portal vein thrombosis and multifocality, related to tumor size, but not to serum alpha-fetoprotein level.

Background and aims: Hepatocellular carcinoma (HCC) is characterized by several clinically important prognostic parameters, including portal vein thrombosis (PVT), tumor multifocality, and serum alpha-fetoprotein (AFP) levels, in addition to maximum tumor diameter (MTD). However, associations among these parameters have not been thoroughly examined. Thus, the study aimed to investigate the correlations among these HCC characteristics in a prospectively collected database. Methods: An 8080 HCC patient database derived from our weekly HCC council meeting was examined with respect to the correlations at baseline patient presentation between increases in MTD and changes in the percentage of patients with PVT, multifocality, or AFP levels. Results: The percentage of patients with PVT and with multifocality (tumor nodule numbers ≥3) significantly increased with enlarging MTD, regardless of the serum AFP level, showing the independence of PVT and multifocality on AFP. The percentage of patients with multifocality increased with enlarging MTD, in the presence or absence of PVT, showing the independence of multifocality from PVT. Therefore, discordance was found between different tumor parameters. Conclusions: A statistically significant association was found between PVT and MTD and between multifocality and MTD, all three of which are independent of AFP. PVT and multifocality appeared to be independent of each other. Although PVT and multifocality were independent of AFP, they were also augmented with high serum AFP levels. The results suggest the possibility of multiple pathways of tumor progression in the later stages of HCC development.

Liver Transplantation for Hepatocellular Carcinoma in Patients with Inherited Metabolic Liver Diseases: A Single-Center Analysis.

BACKGROUND/AIMS: Liver transplantation is an acceptable treatment for some selected hepatocellular carcinoma. We report our experience of 6 patients with liver transplantation for hepatocellular carcinoma with background inherited metabolic disease. MATERIALS AND METHODS: This is a single-center retrospective, descriptive study. Consecutive patients who underwent liver transplantation for hepatocellular carcinoma with background inherited metabolic disease were included in the study. The record of the patients was accessed, and the following data were extracted: sociodemographic variables, type of metabolic disease, date of liver transplantation, tumor characteristics, laboratory parameters, Model for End-Stage Liver Disease score, immediate- and long-term outcome after transplantation, disease-free survival, and overall survival. Data were analyzed using Statistical Package for the Social Sciences version 25.0. RESULTS: Six patients received liver transplantation for hepatocellular carcinoma with background inherited metabolic liver disease. The median age was 4.5 years. The median Model for End-Stage Liver Disease score was 29.30. The median maximum tumor diameter was 2.15 cm. Three patients had multiple tumor nodules. Half of the patients had microvascular invasion. Four of the patients had a moderately differentiated tumor. Progressive familial intrahepatic cholestasis type II is the commonest inherited metabolic disease seen in 3 patients. Median follow-up is 46.1 months. Half of the patients are currently more than 5 years post liver transplantation with no features of recurrence. The estimated survival rates at 1, 3, and 5 years are 100%, 83.3%, and 83.3%, respectively. CONCLUSION: Liver transplant for these categories of patients is associated with good disease-free and overall survival, even in the presence of some seemingly poor prognostic features.

Parameters Predicting Microvascular Invasion and Poor Differentiation in Hepatocellular Carcinoma Patients with Normal Alpha-fetoprotein Level Before Liver Transplantation.

BACKGROUND/AIMS: The aim of this study is to evaluate the parameters that might be associated with pathologically diagnosed microvascular invasion and poor differentiation, using complete blood count and routine clinical biochemistry test results, in hepatocellular carcinoma patients before liver transplantation. MATERIALS AND METHODS: The data of patients who underwent liver transplantation for hepatocellular carcinoma at our institute, between March 2006 and November 2021, was researched retrospectively. RESULTS: The incidence of microvascular invasion was 28.6%, poor differentiation rate was 9.3%, hepatocellular carcinoma recurrence rate after liver transplantation was 12.1%, and median time to recurrence was 13 months, in the patients with normal alpha-fetoprotein levels. After univariate and multivariate analysis, maximum tumor diameter >4.5 cm and the number of nodules (n > 5) were found to be independent risk factors for microvascular invasion, and number of nodules >4 and mean platelet volume ≤8.6 fL were found to be independent risk factors for poor differentiation. Serum alpha-fetoprotein levels were still within the normal range at the recurrence time, in 53% of the patients who had recurrence after liver transplantation, but surprisingly were elevated in 47% of the patients at time of hepatocellular carcinoma recurrence. CONCLUSIONS: In hepatocellular carcinoma patients with normal alpha-fetoprotein levels before liver transplantation, independent risk factors of the presence of microvascular invasion were maximum tumor diameter and number of nodules, and independent risk factors of poor differentiation were mean platelet volume and number of nodules. Furthermore, serum alpha-fetoprotein levels were still normal at time of recurrence in 53% of hepatocellular carcinoma patients whose alpha-fetoprotein levels were normal before liver transplantation but were elevated in 47% of the patients at recurrence time, despite having normal levels before liver transplantation.

Serum Inflammation Parameters and Survival in Hepatocellular Carcinoma Patients: Importance of Albumin and Gamma-Glutamyltranspeptidase.

INTRODUCTION: Many single and combination blood tests that reflect local or systemic inflammation have been shown to be useful prognosticators in patients with a variety of tumor types. To try to clarify, this issue in patients with nonsurgically treatable hepatocellular carcinoma, multiple serum parameters were evaluated for their relationship to survival. METHODS: A prospectively collected database was interrogated of 487 patients with known hepatocellular carcinoma and documented survival and having all the inflammation parameters of interest in this study, together with baseline tumor characteristics from CT scans. Serum parameters included NLR, PLR, CRP, ESR, albumin, and GGT. RESULTS: All the parameters had significant hazard ratios on Cox regression model. Combination double parameters with hazard ratios >2.0 were: ESR plus GGT, albumin plus GGT, albumin plus ESR. The triplet combination of albumin plus GGT plus ESR had a hazard ratio of 6.33. Using Harrell's concordance index (C-index), the highest inflammation-based 2-parameter prognostic score was for albumin plus GGT. When clinical characteristics of patients with high values for albumin plus low values for GGT were compared to low values for albumin plus high values for GGT (worse prognosis), statistically significant differences were found for tumor size, tumor focality, macroscopic portal vein invasion, and serum alpha-fetoprotein levels. Addition of ESR did not provide additional tumor information. CONCLUSION: The combination of serum albumin plus GGT levels was the most prognostically useful among the inflammation parameters that were tested, and reflected significant differences in tumor aggressiveness characteristics.

Understanding the Drawbacks of the Current Tumor Staging Systems: How to Improve?

Tumor stage definition is required for the description of the diagnosis and the development and use of treatment guidelines, as well as to enable clinical research (including clinical trials) and cancer surveillance [...].

EMT and Inflammation: Crossroads in HCC.

Hepatocellular carcinoma is one of the major causes of cancer-related deaths worldwide and is associated with several inflammatory mediators, since 90% of HCCs occur based on chronic hepatitis B or C, alcoholism or increasingly metabolic syndrome-associated inflammation. EMT is a physiological process, with coordinated changes in epithelial gene signatures and is regulated by multiple factors, including cytokines and growth factors such as TGFß, EGF, and FGF. Recent reports propose a strong association between EMT and inflammation, which is also correlated with tumor aggressiveness and poor outcomes. Cellular heterogeneity results collectively as an outcome of EMT, inflammation, and the tumor microenvironment, and it plays a fundamental role in the progression, complexity of cancer, and chemoresistance. In this review, we highlight recent developments concerning the association of EMT and inflammation in the context of HCC progression. Identifying potential EMT-related biomarkers and understanding EMT regulatory molecules will likely contribute to promising developments in clinical practice and will be a valuable tool for predicting metastasis in general and specifically in HCC.

Critical overview of resection for Bismuth-Corlette type IV perihilar cholangiocarcinoma.

BACKGROUND: Current standard treatment for perihilar cholangiocarcinoma (pCCA) is surgical resection. Bismuth-Corlette (BC) type IV pCCA is accepted as an unresectable disease. In the present study, the results of non-transplant surgical approaches in patients with BC type IV pCCA were examined. METHODS: Medical records of consecutive patients with BC type IV pCCA between 2010 and 2021 were retrospectively reviewed. Patients were subdivided according to operation type. Postoperative survival rates were compared. RESULTS: Hemihepatectomy with caudate lobe and extrahepatic bile duct (EHBD) resection was performed in 15 patients and only EHBD resection was performed in 10 patients. Ten of the cases were found to be unresectable at the stage of laparotomy. Median follow-up was 41.3 (24.8-57.9) months. Overall survival rate for all 35 patients was 56.4% at 1 year, 32.2% at 2 years, and 16.1% at 3 years. When survivals were compared according to operation type, 1, 2, and 3-year survivals were 80%, 57.1% and 42.9% for the hepatectomy group; 55.6%, 44.4% and 11.1% for the EHBD resection group; 75%, 0% and 0% in laparotomy-only group, respectively (p = 0.13). The best survival rates were obtained in patients with pCCA who underwent hepatectomy and were lymph node negative, 100% for 1 year, 66.7 for 2 years and 50% for 3 years. CONCLUSION: It is difficult to achieve high survival rates in BC type IV pCCA. However, these patients mostly benefit from resective treatments. Acceptable survival rates can be achieved, especially in the R0N0 patient group.

Comparison of patients with hepatitis B virus-associated hepatocellular carcinoma: Data from two hospitals from Turkey and China.

Aims: There are many studies on the incidence of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC), but very little is known about the HCC features in different populations. The study aimed to compare characteristics in two cohorts of patients with HBV-associated hepatocellular carcinoma, from Turkey and China. Methods: Data on patients with HBV-associated HCC diagnosed by imaging or liver biopsy were retrospectively collected from Shandong Provincial Hospital (n = 578) and Inonu University Hospital (n = 359) between January 2002 and December 2020, and the liver function and HCC characteristics were compared. Continuous variables were compared using Student's t-test or Mann-Whitney U test and categorical variables were compared using the χ2 test or Fisher's exact test. Results: The patients in the Turkish cohort had significantly worse Child-Pugh scores (Child-Pugh A: 38.3% vs. 87.9%; Child-Pugh B: 40.3% vs. 11.1%; Child-Pugh A: 24.1% vs. 1.0%; p < 0.001) and significantly higher levels of aspartate aminotransferase (66.5 vs. 36.0; p < 0.001), alanine aminotransferase (47.5 vs. 33.0; p < 0.001), total bilirubin (20.8 vs. 17.9; p < 0.001), and lower albumin levels (32.0 vs. 40.0; p < 0.001) than patients in Chinese cohort. The tumor characteristics showed the Barcelona Clinic Liver Cancer (BCLC) score (BCLC 1: 5.1% vs. 71.8%; BCLC 2: 48.7% vs. 24.4%; BCLC 3: 24.4% vs. 3.8%; BCLC 4: 21.8% vs. 0; all p < 0.001), maximum tumor diameter (5.0 vs. 3.5; p < 0.001), alpha-fetoprotein values (27.7 vs. 13.2; p < 0.001), and percentage of patients with portal vein tumor thrombus (33% vs. 6.1%; p < 0.001) were all significantly worse in the Turkish cohort compared with Chinese cohort. Conclusions: HBV-associated HCC from the Turkish cohort had worse liver function and more aggressive clinical characteristics than patients from the Chinese cohort.

The Effect of Pre-transplant Lipid Profile on Post-transplant Hepatocellular Carcinoma Recurrence: Retrospective Single-Center Analysis.

BACKGROUND: Plasma lipids have been shown to relate to tumor biology. We aimed to analyze the effect of pre-transplant plasma lipid profiles on post-transplant tumor recurrence in patients with hepatocellular carcinoma and to identify any possible relationship between the pre-transplant lipid profile with maximum tumor diameter, number of tumor nodules, tumor differentiation, portal vein invasion, or serum biomarker levels. METHODS: Patients with hepatocellular carcinoma who underwent liver transplants between 2006 and 2021 had data collected pro- spectively and were analyzed retrospectively. Patients who did not have lipid profile data before transplant and whose post-transplant follow-up period was <90 days were excluded. Patients who had pre-transplant plasma lipid data and whose post-transplant follow-up period was >90 days were included in this study (n = 254). RESULTS: Lower high-density lipoprotein cholesterol levels were found to be significantly associated with post-Tx recurrence (38 vs 29.5, P < .001) and were also significantly associated with macroscopic portal vein thrombosis (39 vs 30.4, P < .021). There was no significant association between plasma lipids and tumor differentiation. Higher high-density lipoprotein cholesterol levels were significantly asso- ciated with good overall and disease-free survivals (P = .024 and P = .001). CONCLUSION: Pre-transplant low plasma high-density lipoprotein cholesterol levels were significantly associated with portal vein throm- bosis and poor post-transplant overall and disease-free survivals.

Identification of 2 large size HCC phenotypes, with and without associated inflammation.

Background: Large HCCs can often be associated with low levels of cirrhosis. However, inflammation is also regarded as a driver of HCC growth. Objectives: To compare patients with large >5 cm HCCs having high versus low serum inflammation parameters. Materials and methods: A Turkish patient HCC dataset with known survivals was retrospectively analyzed after dichotomization according to several clinical inflammation markers. Results: Amongst several parameters examined, only AST levels were significantly associated with elevated AFP levels and increased percent PVT and tumor multifocality. The dichotomization of the cohort according to high or low AST levels resulted in 2 subcohorts with a 5-fold difference in median survival. The 2 AST-dichotomised cohorts comprised patients with similar large-size HCCs, but which were significantly different with respect to serum AFP levels, percent PVT, and percent tumor multifocality. Conclusions: Two large-sized HCC phenotypes were identified. One had more aggressive HCC characteristics, higher inflammatory indices, and worse survival. The other had the opposite. Despite inflammation being important for the growth of some large tumors, others of a similar size likely have different growth mechanisms.

Can the Limits of Liver Transplantation Be Expanded in Perihilar Cholangiocarcinoma?

The most common location of cholangiocarcinomas is the perihilar region with a frequency of 50-70%. Current standard treatment for perihilar cholangiocarcinomas (pCCA) is surgical resection. In cases where resection treatment is possible, the 5-year survival rate is 8-40%. However, using a very strict patient selection, neoadjuvant radiochemotherapy (NRCT), staging laparotomy, and liver transplantation (LT), called "the Mayo protocol," 5-year survivals of up to 70% in pCCA were reported. This treatment protocol clearly requires an intensive workforce and a harmonious multidisciplinary approach. Reoperation and retransplantation rates are high, which is a reflection of the NRCT. Multicenter studies, systemic reviews, and meta-analysis results, comparing both resection and LT in pCCA treatment and evaluating only LT results, pointed to LT with strict patient selection and full compliance with the treatment. The results of centers experienced in LT are better in treating pCCA. According to Mayo clinical data, histopathological diagnosis could not be obtained in half of the patients with pCCA before NRCT was given. This situation can be explained by the necrosis of the tumor due to the effect of NRCT and the fact that the tumor cannot be detected in the explant liver. This situation raises the following questions: did all patients actually have pCCA? Were these good results due to some patients not having pCCA? The 5-year survival rate was worse in patients with a pathological diagnosis than those without a pathological diagnosis. However, interestingly, recurrence rates were statistically similar in both groups. There was no difference in survival between LT and resection in the R0N0 subgroup in de novo pCCA. There are still many issues that need to be addressed and corrected in pCCA, which is one of the most problematic indications for LT. Significant success has been achieved with NRCT, staging laparotomy, and LT in selected patients with pCCA developing on the basis of PSC or early-stage unresectable de novo pCCA. It can be expected that new NRCT modalities will provide better survival by expanding the indications for LT in pCCA.

Microscopic Portal Vein Invasion in Relation to Tumor Focality and Dimension in Patients with Hepatocellular Carcinoma.

BACKGROUND: Microscopic portal vein invasion (microPVI) and tumor multifocality are hepatocellular carcinoma (HCC) prognosis factors. To investigate whether microPVI and multifocality are directly related to each other. METHODS: We retrospectively analyzed the relationships between microPVI, multifocality, and maximum tumor diameter (MTD) in prospectively collected transplanted HCC patients. RESULTS: HCCs with 1, 2, or ≥ 3 foci had more microPVI in larger than in smaller HCCs, with microPVI being present in 52.24% of single large foci. Conversely, microPVI patients had similar percentages of single and multifocal lesions. A linear regression model of MTD, showed microPVI best associated with MTD, with 2.49 as coefficient, whereas multifocality had a 0.83 coefficient. A logistic regression model of microPVI showed significant association with tumor multifocality, especially for small HCCs. Trends for microPVI and multifocality in relation to MTD revealed that both increased with MTD but more significantly for microPVI. Survival was similar in patients with small HCCs, with or without microPVI, but was significantly worse in microPVI patients with larger HCCs. No patient survival differences were found in relation to focality. CONCLUSIONS: MTD had stronger associations with microPVI than with multifocality. microPVI was associated with worse survival in patients with large HCCs, but survival was not impacted by number of tumor foci. microPVI and multifocality appear weakly related, having different behavior in relation to MTD and survival.

Incidental Hepatocellular Carcinoma after Liver Transplantation: Clinicopathologic Features and Prognosis.

Background: The prognostic impact and clinicopathologic features of incidental hepatocellular carcinoma (iHCC) detected in explanted livers of patients undergoing liver transplantation (LT) has been a controversial issue in previous studies when compared with patients who are diagnosed with hepatocellular carcinoma (pdHCC) before LT. We aimed to review and compare these patient groups in a high-volume LT center. Methods: The present study involves a retrospective analysis of 406 HCC patients who received LT between January 2002 and April 2022. Among these patients, demographic data, histopathologic features and prognosis for iHCC and pdHCC were evaluated. Results: In our series, 406 patients' final diagnosis was HCC after they had received LT, nevertheless 54 patients in this HCC group were diagnosed incidentally after the pathological evaluation of the explanted livers. The etiology of the underlying liver disease between pdHCC (n = 352) and iHCC (n = 54) groups had some differences in our study population. Most of the patients in the pdHCC group had moderately differentiated tumors (45.7%). On the other hand, most of the patients in the iHCC group had well differentiated tumors (79.6%). There were 158 (44%) patients who met the Milan criteria in the pdHCC group while there were 48 (92%) patients in the iHCC group (p < 0.001). IHCC patients had statistically better 1, 3, 5 and 10 years disease-free and overall survival rates when compared with pdHCC patients. There was only 1 (1.8%) patient who had tumor recurrence in the iHCC group while 76 (21%) patients had tumor recurrence in the pdHCC group (p = 0.001). There is no disease free and overall survival difference when iHCC patients are compared with pdHCC patients who met the Milan criteria. Conclusion: It is the first study to show that iHCC patients may differ from pdHCC patients in terms of etiological features. IHCC tumors show better histopathologic features than pdHCC with low recurrence rate and iHCC patients have better survival rates than pdHCC patients.

A simple 2-parameter blood test alert for the presence of small hepatocellular carcinomas.

OBJECTIVES: The majority of HCCs present at an advanced stage in which potentially curative therapies cannot be used. Surveillance ultrasound has been found to increase the numbers of patients diagnosed with small tumors, but it is often not used. We aimed to try to identify widely-available and cheap potential serum markers for use in patients at risk for HCC. MATERIAL AND METHODS: A comparison was made of the complete blood count and liver function tests in a group of patients (n=114) with proven small HCCs (≤ 2 cm) and patients without HCC (n=506), all of whom were treated by liver transplantation in our Liver Transplantation Institute. RESULTS: Significant differences were found for blood levels of WBC, lymphocytes, total bilirubin and transaminases. Several 2-parameter combinations were assessed, but only the combination of total bilirubin and lymphocytes was found to be significantly different between patients with small HCCs and no HCC. Multivariate regression analysis showed significance only for total bilirubin levels and lymphocyte counts. The results were confirmed using a separate small cohort of non-transplant patients. CONCLUSION: The combination of elevated levels of total bilirubin and lymphocyte counts holds promise for identification of patients with chronic liver disease who are at risk for HCC.

A Combination of Blood Lymphocytes and AST Levels Distinguishes Patients with Small Hepatocellular Carcinomas from Non-cancer Patients.

PURPOSE: HCC patients typically present at an advanced tumor stage, in which surgical therapies cannot be used. Screening ultrasound exams can increase the numbers of patients diagnosed with small tumors, but are often not used in patients at risk for HCC. We evaluated clinically available and cheap potential blood tests as biomarkers for screening patients at risk for HCC. METHODS: A comparison was made of commonly used blood count and liver function parameters in a group of patients (n = 101) with small HCCs (≤ 3 cm) or without HCC (n = 275), who presented for liver transplantation in our institute. RESULTS: Significant differences were found for blood lymphocytes and AST levels. This 2-parameter combination was found to be significantly different between patients with small HCCs versus no HCC. Using the combination of lymphocytes and AST levels to dichotomize the HCC patients, only blood levels of alpha-fetoprotein among the tumor characteristics were found to be significantly different among the 2 HCC groups, as well as levels of blood total bilirubin, ALKP, and PLR ratio. The results were confirmed using a separate smaller cohort of non-transplanted small size HCC patients. CONCLUSION: The combination of elevated blood levels of lymphocyte counts and AST levels holds promise for screening of patients with chronic liver disease who are at risk for HCC.

Hepatitis B Before and After Hepatocellular Carcinoma.

Hepatitis B virus (HBV) is the one of most common causes of the hepatocellular carcinoma (HCC), especially in eastern world. The aim of this review is to try to understand the relationship between HBV and HCC and to reveal the role of prevention and treatment of HBV infection in reducing the incidence of HCC. Strategies to prevent HCC due to HBV can be classified into three categories. These are primary, secondary, and tertiary preventions. Hepatitis B vaccine is now in the most vital position in preventing HBV-associated HCC. In patients with chronic hepatitis B infection, suppressing viral load with potent antivirals such as tenofovir disoproxil fumarate (TDF) and entecavir (ETV) prevents the development of HCC and improves prognosis by reducing recurrence after HCC treatments. There is currently no clear consensus on which of these drugs should be preferred. Although data on tenofovir alafenamide (TAF) are scarce, available data with TDF suggest that TAF therapy will also be a strong actor for HCC.

Relationships Between Indices of Tumor Aggressiveness in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) aggressiveness factors include serum levels of alpha-fetoprotein (AFP), maximum tumor diameter (MTD), tumor multifocality, and presence of portal vein thrombosis (PVT). AIMS: The interdependence of these factors has not been closely studied. METHODS: A large HCC database was examined for the presence of patients with PVT and multifocality and was analyzed retrospectively for the relationship of these 2 parameters to each other and to MTD and survival. RESULTS: Multifocality was found to increase with increase in MTD in the whole cohort and especially in patients with PVT. PVT also increased with increasing MTD. Neither increases in multifocality nor in PVT depended on elevated serum AFP levels, although they each increased with higher AFP levels. PVT increased in monofocal tumors as MTD increased but increased further in multifocal tumors. CONCLUSIONS: Multifocality and PVT appear to be separate processes, each increasing with increase in MTD and AFP levels. The data support the hypothesis that in hepatocarcinogenesis, various factors cause increase in MTD, that in turn causes increased multifocality and PVT, which are non-co-dependent. However, both multifocality and PVT mechanisms involve both HCC cell growth and invasiveness, multifocality in liver parenchyma, and PVT in the portal vein.

CRP is a superior and prognostically significant inflammation biomarker for hepatocellular cancer patients treated by liver transplantation.

BACKGROUND: Inflammation and its markers are considered prognostically important for many cancers, including Hepatocellular Carcinoma (HCC). However, it is not really clear which markers are the best. AIMS: To assess in a cohort of prospectively-evaluated HCC patients who were treated with liver transplant and whose survival was known, multiple commonly used inflammatory markers in relation to survival and to both clinical and tumor aggressiveness parameters. RESULTS: Amongst 330 transplanted HCC patients, CRP was found to be the only significant inflammatory marker for survival, on multivariate Cox regression analysis. NLR, PLR, GGT, AST, ALT and the Glasgow inflammation score were also found to be significant, but on univariate analysis only. CRP was significant in patients with both small (< 5 cm) and large HCCs and in patients with elevated or low Alpha-Fetoprotein (AFP) levels. Comparison of HCC patients with high (>2.5 mg/ dL) compared low serum CRP levels showed significant differences for blood levels of NLR, LMR, Hb, total bilirubin and liver transaminases, as well as Maximum Tumor Diameter (MTD) and percent of patients with Portal Vein Thrombosis (PVT). CONCLUSIONS: Elevated serum CRP levels were associated with significantly increased MTD and percent of patients with PVT and significantly worse overall survival in HCC patients who were treated by liver transplantation.