Validation of a Modified Child-Turcotte-Pugh Classification System Utilizing Insulin-Like Growth Factor-1 for Patients with Hepatocellular Carcinoma in an HBV Endemic Area

Lee, Dong Hoon; Lee, Jeong Hoon; Jung, Yong Jin; Gim, Jungsoo; Kim, Won; Kim, Byeong Gwan; Lee, Kook Lae; Cho, Yuri; Yoo, Jeong‐Ju; Lee, Minjong; Cho, Young Youn; Cho, Eun Ju; Yu, Su Jong; Kim, Yoon Jun; Yoon, Jung Hwan

doi:10.1371/journal.pone.0170394

Cited by 12 publications

(12 citation statements)

References 34 publications

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“…It was shown that serum IGF1 levels predict prognosis in cases of HCC. Lower plasma IGF1 levels were significantly correlated with advanced clinical parameters, shorter time to progression and poor overall survival [ 140 , 141 , 145 , 146 , 147 , 148 , 149 ], even in patients that underwent transarterial chemoembolization (TACE) [ 148 , 149 , 150 , 151 , 152 ] or other types of curative treatment, such as surgical resection or percutaneous ethanol injection [ 150 ]. Longitudinal observation of HCC cases (median follow-up period of 41.8 months) proved that IGF1 level was an independent predictor of poorer survival [ 151 ].…”

Section: Evidence From Epidemiologic and Clinicopathological Studimentioning

confidence: 99%

Insulin-Like Growth Factor (IGF) System in Liver Diseases

Adamek

Kasprzak

2018

IJMS

216

149

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Hepatocyte differentiation, proliferation, and apoptosis are affected by growth factors produced in liver. Insulin-like growth factor 1 and 2 (IGF1 and IGF2) act in response to growth hormone (GH). Other IGF family components include at least six binding proteins (IGFBP1 to 6), manifested by both IGFs develop due to interaction through the type 1 receptor (IGF1R). The data based on animal models and/or in vitro studies suggest the role of IGF system components in cellular aspects of hepatocarcinogenesis (cell cycle progression, uncontrolled proliferation, cell survival, migration, inhibition of apoptosis, protein synthesis and cell growth), and show that systemic IGF1 administration can reduce fibrosis and ameliorate general liver function. In epidemiologic and clinicopathological studies on chronic liver disease (CLD), lowered serum levels, decreased tissue expression of IGF1, elevated production of IGF1R and variable IGF2 expression has been noted, from the start of preneoplastic alterations up to the developed hepatocellular carcinoma (HCC) stage. These changes result in well-known clinical symptoms of IGF1 deficiency. This review summarized the current data of the complex role of IGF system components in the most common CLD (nonalcoholic fatty liver disease, cirrhosis, and hepatocellular carcinoma). Better recognition and understanding of this system can contribute to discovery of new and improved versions of current preventive and therapeutic actions in CLD.

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Section: Evidence From Epidemiologic and Clinicopathological Studimentioning

confidence: 99%

Insulin-Like Growth Factor (IGF) System in Liver Diseases

Adamek

Kasprzak

2018

IJMS

216

149

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“…The second study was done with 393 Korean patients with HCC, and the vast majority (78.9%) of patients in the study were hepatitis B virus-positive. 34 Although there was a trend towards a better prediction of survival by the IGF-CTP classification system compared to the original CTP system, the difference (14%) between the two classification systems was not statistically significant. However, the Korean study included 71.5% of early-intermediate stage HCC patients, defined as BCLC stages 0-B, who are classic candidates for surgery, transplant, ablation, and local therapy procedures, which may have affected their survival independently, Table 6 .…”

Section: Discussionmentioning

confidence: 80%

<p>Prognostic Significance of Serum Insulin-Like Growth Factor-1 in Hepatocellular Cancer Patients: A Validation Study</p>

Laçin

Yalçın

Karakaş

et al. 2020

JHC

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Background The Child–Turcotte–Pugh score (CTP) is the most commonly used tool to assess hepatic reserve and predict survival in hepatocellular cancer (HCC). The CTP stratification accuracy has been questioned and attempts have been made to improve the objectivity of the system. Serum insulin-like growth factor-1 (IGF-1)-CTP has been proposed to improve CTP prognostic accuracy. We aimed to validate the IGF-CTP score in our patient population. Patients and Methods A total of 84 diagnosed HCC patients were enrolled prospectively. IGF-CTP scores in addition to CTP scores were calculated. C-index was used to compare the prognostic significance of the two scoring systems and overall survival (OS). Results Cirrhosis was present in 48 (57.1%) patients, 35 (41.7%) patients were non-cirrhotic, 36 (42.8%) patients were hepatitis B (HBV) positive, and 8 (9.5%) patients were hepatitis C (HCV) positive. Serum IGF-1 levels were significantly lower in cirrhotic compared with non-cirrhotic patients (p=0.04). There was a significant difference in OS rates of patients with serum IGF-1 level <50 ng/mL and patients with serum IGF-1 levels ≥50 ng/mL (p=0.02); the OS rates were 6.5 and 14.8 months, respectively (p=0.02). The median OS of all patients was 7.38 months (95% CI: 5.89–13.79). The estimated C-index for CTP and IGF-CTP scores was 0.605 (95% CI: 0.538, 0.672) and 0.599 (95% CI: 0.543, 0.655), respectively. The U statistics indicated that the C-indices between two scoring systems are not statistically different (P= 0.91). Conclusion This study evaluated IGF-1 levels and the IGF-CTP classification in a predominantly HBV (+) cohort of HCC patients with 41.7% non-cirrhotic. Although the prognostic value was similar, among patients with CTP-A, class those reclassified as IGF-CTP B had shorter OS than those with IGF-CTP score A. Thus, further validations of IGF-CTP score in similar populations may add additional value as a stratification tool to predict HCC outcome.

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“…The IGF-CTP classification was developed and validated in two US cohorts where most patients had viral hepatitis as the underlying liver disease for HCC [ 14 , 17 ]. In the Egyptian validation study, all patients had viral-induced HCC [ 26 ], as was also the case in the Korean cohort, especially HBV (78.9%) [ 27 ] (Table 5 ). In contrast, our cohort had alcohol-induced liver disease as the most frequent underlying cause of HCC in 44.4% and viral hepatitis in only 24.6% of cases.…”

Section: Discussionmentioning

confidence: 84%

“…In a cohort with 393 Korean patients with HCC, mostly with underlying chronic viral hepatitis B, the IGF-CTP classification system showed no statistically significant improvement of stratification but demonstrated a trend towards better prediction of survival. In that analysis, only 14% of patients showed a difference between IGF-CTP class and CTP class [ 27 ]. In our cohort, 35.6% of patients were reclassified when using IGF-CTP.…”

Section: Discussionmentioning

confidence: 99%

“…Another difference between the present cohort and recent studies is the proportion of cirrhosis in the study population. In the US cohorts, liver cirrhosis was present in 62.6 and 63.6% of patients [ 14 , 17 ], whereas 48.9% of patients showed cirrhosis in the Korean study [ 27 ]. Only the Egyptian cohort had a similar proportion of cirrhosis as in our study, with 87% of patients in comparison to our study’s rate of 80.1% [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

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Validation of insulin-like growth factor-1 as a prognostic parameter in patients with hepatocellular carcinoma in a European cohort

et al. 2018

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BackgroundIn hepatocellular carcinoma (HCC), the third leading cause of cancer-related mortality worldwide, the Child-Turcotte-Pugh score (CTP) is one of the most established tools to assess hepatic reserve and determine survival. Serum levels of insulin-like growth factor-1 (IGF-1) are decreased in patients with chronic liver disease or HCC. A modified score combining circulating IGF-1 with the CTP score (IGF-CTP) was recently proposed.MethodsIGF-CTP scoring was evaluated in 216 patients diagnosed with HCC between 2007 and 2017 to assess the predictive value of serum IGF-1 levels for patient risk stratification and overall survival (OS).ResultsLiver cirrhosis was identified in 80.1% of the study cohort, and alcohol-induced liver disease was the most frequent underlying cause of HCC (44.4%). Serum IGF-1 levels were significantly lower in patients with HCC in cirrhosis compared with non-cirrhotic HCC (p < 0.01). A lower serum level of IGF-1 was associated with more advanced stages of liver cirrhosis (p < 0.05) and cancer stages (p < 0.001). Median OS in the cohort was 11.4 months (range 0.5–118.2 months). OS was significantly higher (10.9 vs. 7.9 months; p < 0.05) in patients with a serum IGF-1 level above the median of 43.4 ng/mL. Patient reassignment using IGF-CTP scoring reclassified 35.6% of patients. Through reassignment, stratification regarding OS was comparable to CTP.ConclusionsThis study is the first to investigate IGF-1 and the IGF-CTP classification in a European cohort of HCC patients. Serum IGF-1 correlates with OS in patients with HCC. However, the IGF-CTP classification was not superior compared to CTP score regarding OS.

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Validation of a Modified Child-Turcotte-Pugh Classification System Utilizing Insulin-Like Growth Factor-1 for Patients with Hepatocellular Carcinoma in an HBV Endemic Area

Cited by 12 publications

References 34 publications

Insulin-Like Growth Factor (IGF) System in Liver Diseases

Insulin-Like Growth Factor (IGF) System in Liver Diseases

<p>Prognostic Significance of Serum Insulin-Like Growth Factor-1 in Hepatocellular Cancer Patients: A Validation Study</p>

Validation of insulin-like growth factor-1 as a prognostic parameter in patients with hepatocellular carcinoma in a European cohort

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