Plasma hPG80 (Circulating Progastrin) as a Novel Prognostic Biomarker for Hepatocellular Carcinoma

Alpha-fetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC) prognosis. However, AFP is not useful in establishing a prognosis for patients with a tumor in the early stages. hPG80 (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers, including HCC. In this study, we evaluated the prognostic value of plasma hPG80 in patients with HCC, alone or in combination with AFP. A total of 168 HCC patients were tested prospectively for hPG80 and analyzed retrospectively. The prognostic impact of hPG80 and AFP levels on patient survival was assessed using Kaplan-Meier curves and log-rank tests. hPG80 was detected in 84% of HCC patients. There was no correlation between hPG80 and AFP levels in the training and validation cohorts. Both cohorts showed higher sensitivity of hPG80 compared to AFP, especially at early stages. Patients with high hPG80 (hPG80+) levels (optimal cutoff value 4.5 pM) had significantly lower median overall survival (OS) compared to patients with low hPG80 (hPG80−) levels (12.4 months versus not reached respectively, p < 0.0001). Further stratification by combining hPG80 and AFP levels (cutoff 100 ng/mL) improved prognosis in particular for those patients with low AFP level (hPG80−/AFP+ and hPG80−/AFP−, 13.4 months versus not reached respectively, p < 0.0001 and hPG80+/AFP+ and hPG80+/AFP−, 5.7 versus 26 months respectively, p < 0.0001). This was corroborated when analyses were performed using the BCLC staging especially at early stages. Our findings show that hPG80 could serve as a new prognostic biomarker in HCC. Used in combination with AFP, it improves the stratification of the patients in good and poor prognosis, especially for those patients with negative AFP and early-stage HCC.

Correlation of Hepatocellular Carcinoma with Different Levels of Alpha-Fetoprotein in Pakistani Population

Objective: To assess pathological, biochemical and clinical parameters in HCC patients with low, normal and high AFP levels. Methodology: This comparative analytical study was conducted in Liver and Gastric Clinic, Holy Family Hospital, Rawalpindi from June 2019-June 2020.Sample size was calculated as 225 by WHO sample size calculator . Non randomized convenient sampling was used. Patients were divided into three groups according to AFP values; <200 ng/ml, 200-400ng/ml and >400 ng/ml. Patients demographic details, medical history, clinical symptoms and signs, biochemical parameters and pathological findings on ultrasonography and CECT were assessed. Data was analyzed by SPSS version 21. Descriptive statistics were calculated for categorical variable. p Value less than 0.05 was considered significant. Results: Out of 256 patients, 161 (62.9%) were males and 95 (37.1%) were females.The mean age of patients was 60.5 years ± 10.5. 94.4% of patients with HCC had Hepatitis C. Anorexia, jaundice and abdominal distension, hepatomegaly and splenomegaly were more frequent in patients having high AFP level. Serum bilirubin, tumor size, number of lesions, BCLC staging and other pathological parameters associated with HCC worsens as AFP levels increase. Conclusion: Alpha-fetoprotein levels are significantly associated with clinical and pathological parameters of hepatocellular carcinoma thus can be used as a better diagnostic and prognostic tool.

Vascular Endothelial Growth Factor Levels Difference among Hepatocellular Cancer Patients Based on Barcelona Clinic Liver Cancer Staging

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. It depends on angiogenesis for growth and metastasis. Vascular endothelial growth factor (VEGF), a growth factor for angiogenesis, is hoped to be a biomarker for the diagnosis of HCC and its development. AIM: The objective of the study is to determine the difference of VEGF levels among HCC patients based on barcelona clinic liver cancer (BCLC) staging. METHODS: A cross-sectional study was conducted at Haji Adam Malik General Hospital Medan, Indonesia between January and December 2018. Patients aged 18 years or older with HCC were enrolled using consecutive sampling method. Patients with cholangiocarcinoma, hemangioma, and liver metastasis were excluded from the study. The diagnosis of HCC was confirmed by triphasic computed tomography-scanning. Circulating VEGF levels were determined from serum specimen using Quantikine Human VEGF-enzyme-linked immunosorbent assay. All patients were grouped based on BCLC staging. Kruskal Wallis-H test was applied at 95% confidence interval. p < 0.05 was considered significant. RESULTS: Of 60 patients, 47 (78.3%) were male. Mean age of patients was 61.4 (SD11.7) years. Hepatitis B was the most common etiology (70.0%) of HCC. Based on BCLC staging, 25 (41.7%) patients were in stage C. Median VEGF level was 951.25 pg/mL. There was a statistically significant difference in VEGF levels (p = 0.006) where patients in Stage C (1,009.6 pg/mL) and D (1,189.7 pg/mL) had higher VEGF levels compared to those in Stage A (578 pg/mL). CONCLUSION: There was a statistically significant difference of VEGF levels among HCC patients based on BCLC staging.

Nonalcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: Clinical Patterns, Outcomes, and Prognostic Factors for Overall Survival—A Retrospective Analysis of a Slovak Cohort

Objective: To compare NAFLD-related HCC and other etiology-related HCC and to describe predictive factors for survival in patients with NAFLD-related HCC independent of the BCLC staging system. Methods: We performed a multicenter longitudinal retrospective observational study of patients diagnosed with HCC during the period from 2010 through 2016. Results: 12.59% of patients had NAFLD-related HCC, and 21.91% had either NAFLD or cryptogenic etiology. NAFLD-related HCC patients were younger (p = 0.0007), with a higher proportion of women (p < 0.001) compared to other etiology-related HCC patients. The NAFLD group had a significantly lower proportion of patients with liver cirrhosis at the time of HCC diagnosis (p < 0.0001), and they were more frequently diagnosed with both diabetes and metabolic syndrome when compared to other etiology-related HCC (p < 0.0001). We did not find any difference in the overall survival or in the progression-free survival between NAFLD-related and other etiology-related HCC patients staged as BCLC B and BCLC C. NAFLD-related HCC patients with three or more liver lesions had a shorter overall survival when compared to patients with one or two liver lesions (p = 0.0097), while patients with baseline CRP values of ≥5 mg/L or with PLR ≥ 150 had worse overall survival (p = 0.012 and p = 0.0028, respectively). ALBI Grade 3 predicted worse overall survival compared to ALBI Grade 1 or 2 (p = 0.00021). In NAFLD-related HCC patients, PLR and ALBI remained significant predictors of overall survival even after adjusting for BCLC. Conclusion: NAFLD-related HCC patients have a similar prognosis when compared to other etiology-related HCC. In NAFLD-related HCC patients, ALBI and PLR are significant predictors of the overall survival independent of the BCLC staging system.

Ramucirumab for Patients with Intermediate-Stage Hepatocellular Carcinoma and Elevated Alpha-Fetoprotein: Pooled Results from Two Phase 3 Studies (REACH and REACH-2)

<b><i>Background:</i></b> Intermediate-stage hepatocellular carcinoma (HCC), as defined by Barcelona Clinic Liver Cancer (BCLC) stage B, is heterogeneous in terms of liver function and tumor burden. REACH and REACH-2 investigated ramucirumab in patients with HCC after prior sorafenib, with REACH-2 enrolling only patients with baseline α-fetoprotein (AFP) ≥400 ng/mL. An exploratory analysis of outcomes by BCLC stage was performed. <b><i>Methods:</i></b> A pooled meta-analysis of independent patient data (stratified by study) from REACH (AFP ≥ 400 ng/mL) and REACH-2 was performed. All patients had Child-Pugh A, Eastern Cooperative Oncology Group performance status 0–1, prior sorafenib treatment, and either HCC BCLC stage B (refractory/not amenable to locoregional therapy) or BCLC stage C. Patients were randomized to ramucirumab 8 mg/kg or placebo every 2 weeks. Median overall survival (OS) and progression-free survival were estimated by the Kaplan-Meier method. Treatment effects in BCLC stage B and C were evaluated by Cox proportional-hazards model; prognosis of BCLC staging for OS was evaluated by multivariate Cox proportional-hazards model. Tumor responses were evaluated according to Response Evaluation in Solid Tumors v1.1. Liver function was assessed with albumin-bilirubin score. <b><i>Results:</i></b> Baseline characteristics were generally balanced between treatment arms in each BCLC stage. BCLC staging trended as an independent prognostic factor for OS (B vs. C; hazard ratio [HR] 0.756 [95% CI 0.546–1.046]). Consistent treatment benefit was observed for ramucirumab versus placebo across BCLC stages. Median OS for ramucirumab versus placebo was 13.7 versus 8.2 months; HR (95%): 0.43 (0.23–0.83) and 7.7 versus 4.8 months; HR (95%): 0.72 (0.59–0.89) for BCLC stage B and C, respectively. Adverse events (AEs) were consistent with observations from both studies; hypertension was the most frequent grade ≥3 AE. Liver function was preserved throughout the study and similar between treatment arms in both BCLC stages. <b><i>Conclusions:</i></b> Ramucirumab provided a better survival benefit irrespective of BCLC stage and was well tolerated without compromising liver function during treatment.

Inspecting Management Strategies of Hepatocellular Carcinoma in a Tertiary Centre in Western Rajasthan

BACKGROUND Hepatocellular carcinoma (HCC) is a lethal malignancy which mostly develops in patients with cirrhosis. It is usually diagnosed late in the course of the illness and the median survival following diagnosis ranges between 6 - 20 months. India lacks data on management strategies and their efficacy. In the absence of data on treatment protocols and its adequacy; we evaluated our own centre data for a period of 1 year to get the estimate of incidence, aetiology, treatment adequacy and response to treatment. Barcelona Clinic Liver Cancer (BCLC) prognostic staging classification comprising five stages is used for prognostication, which is based on the extent of the primary lesion, performance status, vascular invasion and extrahepatic spread. Surgical therapies including resection and transplantation are feasible in early stages (BCLC stage 0 and stage A). Trans arterial chemoembolisation is recommended in intermediate stage (BCLC stage B) while systemic therapies are recommended in advanced stage (BCLC stage C). Best supportive care is recommended in terminal stage (BCLC stage D). This study has included BCLC staging for staging classification and patients were assessed for adequacy of management. METHODS This study was done as a retrospective hospital based observational study. All HCC patients presenting to Mahatma Gandhi Hospital attached to Dr. Sampurnanand Medical College, Jodhpur, Western Rajasthan from January to December 2014 were included. HCC was diagnosed based on European Association for the study of the Liver–European Organisation for Research and Treatment of Cancer (EASL–EORTC) clinical practice guidelines 2011. Patients were classified according to Barcelona Clinic Liver Cancer staging and management given was recorded. RESULTS Thirty-two patients who were diagnosed with HCC between January to December 2014 were included in the study. In three fourths of the patients (24) HCC was diagnosed based on typical findings on dynamic imaging studies (triple phase contrast enhanced CT-computed tomography abdomen and / or MRI- magnetic resonance imaging abdomen). Liver biopsy was needed in one fourth of the patients. Majority of the patients (87.5 %) had cirrhosis of the liver at the time of diagnosis of HCC. Some of these patients [5 (17.8 %)] were known cirrhotic patients. CONCLUSIONS Hepatitis B was the most common aetiology of HCC as mentioned previously in other studies, which is vaccine preventable. HCC is rarely diagnosed at an early stage in developing countries. Various treatment modalities are available which depend on the stage, local expertise and affordability. If the surveillance recommendations are strictly adhered,HCC can be diagnosed at an early stage. Affordability and compliance will remain issues in HCC management in our country increasing the socio-economic burden on the society. KEY WORDS Hepatocellular Carcinoma (HCC), BCLC Staging, Survival

Adherence to the modified Barcelona Clinic Liver Cancer guidelines: Results from a high-volume liver surgery center in East Asias

Background and aims The Barcelona Clinic Liver Cancer (BCLC) staging system is the most widely applied staging system for hepatocellular carcinoma (HCC) and is recommended for treatment allocation and prognostic prediction. The BCLC guidelines were modified in 2018 to indicate that Child-Pugh A without any ascites is essential for all stages except stage D. This study sought to provide a description of patients with HCC treated at a high-volume liver surgery center in Taiwan where referral is not needed and all treatment modalities are available and reimbursed by the National Health Insurance program. As such, certain variables that could modulate treatment decisions in clinical practice, including financial constraints, the availability of treatment procedures, and the expertise of the hospital, could be excluded. The study further sought to evaluate the adherence to the modified BCLC guidelines. Methods This was a retrospective study with prospectively collected data. 1801 consecutive patients with de novo HCC were enrolled through our institution from 2011–2017. Results There were 302 patients with stage 0, 783 with stage A, 242 with stage B, 358 with stage C, and 116 with stage D HCC. Treatment adhering to the modified BCLC guidelines recommendations was provided to 259 (85.8%) stage 0 patients, 606 (77.4%) stage A patients, 120 (49.6%) stage B patients, 93 (26.0%) stage C patients, and 83 (71.6%) stage D patients. Conclusions We reported treatment adhering to the modified BCLC guidelines at a high-volume liver surgery center in Taiwan. We found that non-adherence to the modified BCLC staging system was common in treating stage B and C patients.