Page 42 - GTM-1-2

Global Translational Medicine Cirrhosis and hepatocellular carcinoma

1. Introduction data and clinical characteristics of the tumors; and (iv)
pathologically confirmed for HCC and liver cirrhosis.
Hepatocellular carcinoma (HCC) is a primary liver Meanwhile, the exclusion criteria were: (i) liver disease
cancer with an estimated 906,000 newly diagnosed cases due to co-infection with hepatitis C virus or other
and 830,000 deaths yearly, and is ranked the top six most hepatitis, genetic and autoimmune disorders, primary
common cancers and the third leading cause of cancer biliary cirrhosis, and sclerosing cholangitis; (ii) had prior
[1]
death worldwide in 2020 . Liver fibrosis is strongly treatment for HCC or have had anti-HBV treatment
associated with HCC, while 90% of HCC cases arising in within 6 months before prior to HCC diagnosis; (iii)
cirrhotic livers . For hepatitis B and C virus infection, having other malignant tumors; and (iv) being pregnant.
[2]
the presence of fibrosis and cirrhosis has been identified In the first cohort, the METAVIR scoring system was used
as risk factors for HCC; and the cancer risk is positively to evaluate the hepatic fibrosis stage, and the severity of
correlated with the fibrosis severity [3,4] . HCC development liver cirrhosis was histologically staged as 4A, 4B, and 4C
has also been shown to be linked to alcoholic cirrhosis, using the Laennec staging system, according to the size of
nonalcoholic steatohepatitis, and hemochromatosis, with regenerated nodules and the width of fibrous septa.
a yearly HCC incidence of 1.7% and 2.6% in alcoholic
cirrhosis and non-alcoholic steatohepatitis cirrhosis, To further validate the association of the severity of
[5]
respectively . It has been reported that cirrhosis, as a liver cirrhosis with the tumor size, we included another
late-stage form of fibrosis, contributes to an over 30‐fold independent cohort, in which the study subjects were
increase in HCC risk . Approximately 80% of hepatitis B recruited from four university hospitals (The Fifth Medical
[6]
and C patients presented with HCC are already cirrhotic , Center of Chinese PLA General Hospital, Beijing; The
[7]
and liver cirrhosis occurs in about 80% of HCC patients, Third Affiliated Hospital of Sun Yat-sen University,
indicating that liver cirrhosis is the major risk factor for the Guangzhou; Peking University Shenzhen Hospital,
[8]
development of HCC . Shenzhen; The Third Hospital of Hebei Medical University,
Shijiazhuang) in China from 2010 to 2018. The subjects
Recently, there has been emerging opinions suggesting in this cohort were recruited using the above-mentioned
that regenerative nodules (RNs) and fibrosis either exert inclusion and exclusion criteria. In this cohort, HCC were
physical forces to spatially restrict malignant hepatocytes or histopathologically and/or clinically diagnosed, while
activate immunosurveillance to suppress the development cirrhosis was diagnosed by a combination of clinical,
[9]
of HCC and “premalignant mutations” found in the RNs laboratory, and imaging approaches. This study was
were independent of carcinogenesis associated with HCC approved by the ethics committee of Peking University
development. As RNs are surrounded by fibrotic septa, Health Science Center (IRB00001052-19081) and
the fibrosis is postulated to act as a mechanical ‘‘fence’’ to conducted according to the 1964 Helsinki declaration and
constrain the transformation or spatially limit the spread its later amendments or comparable ethical standards.
of cancer cells . Apparently, such a novel view on the
[10]
cirrhosis as a liver-protective response to various injuries, 2.2. Statistical analysis
rather than a risk factor for HCC , has challenged the Statistical analysis was performed by SPSS 24.0 software
[9]
conventional view.
(IBM SPSS Statistics, New York, USA). Continuous
Few studies have been carried out to clarify the variables are expressed as mean ± standard deviation or
controversies on the role of cirrhosis in HCC development. median and interquartile range, and qualitative variables
Herein, this study aimed to investigate the potential are expressed as number and percentage (%). The t-test,
association of cirrhosis with hepatitis B virus (HBV)- Mann-Whitney U test, one-way analysis of variance, or
related HCC in two independent cohorts. Chi-square test were used to evaluate the differences
between groups, as appropriate. Factors that are possibly
2. Materials and methods associated with the tumor size were analyzed using logistic

2.1. Study subjects regression analysis. A forward selection method was
used in the multivariate analysis. P < 0.05 is considered
Two retrospective cohorts were used in this study. The first statistically significant.
cohort consisted of adult patients with HCC undergoing
curative resection in the Fifth Medical Center of Chinese 3. Results
PLA General Hospital (Beijing, China) between 2015
and 2017. The inclusion criteria were: (i) Age ≥18 years; 3.1. Patient characteristics
(ii) positive for hepatitis B surface antigen for at least A total number of 1431 patients diagnosed with HCC were
6 months; (iii) having complete information on laboratory included in this study, with 334 and 1087 patients from the

Volume 1 Issue 2 (2022) 2 https://doi.org/10.36922/gtm.v1i2.94