Risk Factors for Hepatocellular Carcinoma in Patients with Cirrhosis

Recent research suggests an increase in the incidence of hepatocellular carcinoma (HCC) in the United States, which may be related to an upsurge in the sequelae of chronic liver disease from hepatitis C virus. In addition to factors related to the underlying etiology of liver disease, a number of host factors such as age, gender, and ethnic background may be associated with this increased risk. The aim of this study was to evaluate a number of potential risk factors for HCC in patients with cirrhosis. Patients with biopsy proven HCC were identified from our pathology and cancer registry databases. All those without histologic or clinical cirrhosis and non-HCC hepatic malignancies were excluded. Cirrhotic patients without HCC were also selected from the Cleveland Clinic unified transplant database and were designated controls. Extensive clinicodemographic data were obtained from the databases and chart reviews. When available, paraffin-embedded liver biopsy blocks were obtained for HFE gene analysis. Univariate comparisons were made with chi-square and Fisher's exact test and multivariate analysis was carried out with logistic regression. A total of 760 patients were included in this study, 244 documented cases of HCC and 516 cirrhotic controls without HCC. Patients' age (RR = 3.1 [2.6-3.8]; P < 0.0001), male gender (RR = 3.4 [2.3-5.1]; P < 0.0001), African-American ethnicity (RR = 3.1 [1.6-5.8]; P = 0.0005), and other non-Caucasian ethnicity (RR = 6.9 [3.2-14.4]; P < 0.0001) were independently associated with HCC. Restricting the analysis to HCV-related cirrhosis, the same risk factors remained independently associated with HCC: age (decade; RR = 2.3 [1.6-3.4]; P < 0.0001), male gender (RR = 2.9 [1.2-7.0]; P = 0.02), African-American ethnicity (RR = 3.1 [1.3-7.4]; P = 0.009), and other non-Caucasian ethnicity (RR = 15.8 [1.9-134]; P = 0.01). Iron studies did not reveal an increased risk for iron overload or HFE mutation. Male gender, advancing age, and non-Caucasian ethnic background are independently associated with HCC.     

Risk Factors for Hepatocellular Carcinoma in Turkey

The contribution of hepatitis B, hepatitis C, and excess alcohol intake to the development of hepatocellular carcinoma in Turkey was assessed. The study was conducted through a questionnaire sent to seven major medical referral centers in different regions of Turkey and is based on 207 patients seen in the period 1994–1997. Of the seven centers, two were located in West Turkey (54 patients), two were in Central Turkey (85 patients), and two were in south and southeast Turkey (68 patients). In 196 of the 207 patients (94.7%), there was a history of chronic liver disease, and in 180 patients (87%) liver cirrhosis was documented. Of the 207 patients, 116 (56%) had hepatitis B, 48 (23.2%) had hepatitis C, and 33 (15.9%) had a history of excess alcohol intake. Anti-delta testing was available in 69 of 116 patients with hepatitis B, and anti-HDV was positive in 13 of these patients (13/69, 18.8%). Of the 33 patients with a history of heavy alcohol intake, 18 had concomitant chronic viral hepatitis infection, and alcohol alone was the etiology of hepatocellular carcinoma in only 15 cases (7.2%). The distribution of etiologic factors was not homogenous in different geographical regions in Turkey. In central, south, and southeastern Turkey, the predominant etiology of hepatocellular carcinoma was hepatitis B, whereas in western Turkey the impact of hepatitis B, hepatitis C, and alcohol was similar. This study indicates that hepatitis B virus infection is the leading cause of hepatocellular carcinoma in Turkey, followed by hepatitis C infection and alcoholic liver disease.     

肝细胞癌患者中p53基因变化的相关因素分析

ｐ５３基因的变化已被认为是肿瘤病因学和分子发病机制的重要线索。为了阐明ＨＣＣ的主要致病因子及其在ＨＣＣ发病机制中的相对意义，本研究对ｐ５３基因变化较常见的中国南部地区的７０例ＨＣＣ患者采用Ｘ＾２检验等，分析一般资料、嗜肝病毒感染和病理资料与ｐ５３基因的ＬＯＨ则与嗜肝病毒感染和癌周组织中的肝硬化程度相关。以上结果提示，ＨＣＣ的主要致病因素是嗜肝病毒感染和高度流行区的某些其它因素，其中嗜肝病毒感染在Ｈ     

Development of Tivantinib as Treatment for Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a rapidly rising cause of liver-related death worldwide. Most patients are diagnosed at an advanced stage of disease, when systemic therapy is the only viable option for treatment. Significant strides have been made in the molecular understanding of HCC development and growth stimulation. The c-Met pathway has been found to be an important pathway in half of all patients with HCC. HCC tumors with high c-Met activation are associated with an aggressive phenotype and poor prognosis. Tivantinib is a MET receptor tyrosine kinase inhibitor with a broad spectrum of anti-tumor effects currently being studied for the treatment of HCC. Phase I and II data are available for tivantinib in the treatment of solid tumors, including HCC. There appears to be an adequate safety profile, with the main side-effect being neutropenia. In HCC patients with elevated c-Met activity, tivantinib results in an improved time to progression of 2.7 months, compared with 1.4 months in placebo-treated patients. Further studies are ongoing, but early data suggest that tivantinib is a therapy that deserves close attention in the coming years for patients with HCC.     

Development and Validation of a Metabolic-related Prognostic Model for Hepatocellular Carcinoma

Background and Aims: Growing evidence suggests that metabolic-related genes have a significant impact on the occurrence and development of hepatocellular carcin...     

Sorafenib in the Treatment of Advanced Hepatocellular Carcinoma

Management of advanced hepatocellular carcinoma (HCC) is still a challenge to physicians since these patients are not candidates for surgical or ablative therapy. The disease carries a very poor prognosis with an expected survival of 4–6 months. No chemotherapeutic agent has been proven to improve the clinical outcome in such patients. A multikinase inhibitor, sorafenib, previously tested and found effective in other solid tumors recently found to significantly improve survival in patients with advanced HCC. Sorafenib exerts its action through inhibition of several kinases involved in both tumour cell proliferation and angiogenesis. It was well tolerated at a dose of 400 mg twice daily and permanent discontinuation of the drug was rarely required.     

小肝细胞癌术后早期复发的危险因素分析

目的 探讨小肝细胞癌（sHCC）患者术后早期复发的危险因素。方法 收集2004至2006年上海东方肝胆外科医院手术切除肿瘤的sHCC患者75例。选取20项临床和病理学参数,以2年为早期复发的时限,应用COX风险比例模型进行单因素和多因素分析,筛选影响早期复发的独立危险因素。结果 本组75例sHCC患者经手术切除肿瘤后,1～5 a累积肿瘤复发率分别为10.7%、46.7%、76.0%、86.7%和92.0%;经COX风险比例模型分析,发现术前AFP＞400 μg/L（HR=2.477,95% CI=1.100～5.576,P=0.029）和肿瘤分布超过半肝（HR=5.801,95% CI=1.831～18.379,P=0.003）是sHCC患者术后早期复发的独立危险因素。结论 对于术前AFP＞400 μg/L和肿瘤分布超过半肝的sHCC患者,应加强术后随访,及早发现复发肿瘤并给予积极的治疗,以改善患者预后。     

Independent of Cirrhosis,Hepatocellular Carcinoma Risk Is Increased with Diabetes and Metabolic Syndrome

Background

Hepatocellular carcinoma is the most common primary liver malignancy, commonly a sequelae of hepatitis C infection, but can complicate cirrhosis of any cause. Whether metabolic syndrome and its components, type II diabetes, hypertension, and hyperlipidemia increase the risk of hepatocellular carcinoma independent of cirrhosis is unknown.

Independent Risk Factors for Hepatocellular Carcinoma Recurrence after Direct-Acting Antiviral Therapy in Patients with Chronic Hepatitis C

Background/AimsThis study was performed to evaluate the efficacy of direct-acting antivirals (DAAs) in Korean patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) and to investigate the risk factors associated with HCC recurrence.MethodsA total of 100 patients with HCV-related HCC, who were treated with DAAs between May 2015 and December 2016, were recruited from seven university hospitals in Korea. Claim data of 526 patients with HCC obtained from the Health Insurance Review and Assessment Service in South Korea were used for external validation of the results.ResultsAmong the 100 patients, 88% achieved a sustained virological response (SVR) 12 weeks after the end of DAA therapy (SVR12), and 37% experienced HCC recurrence after DAA therapy. Short last HCC treatment durability (<12 months) before DAA commencement was independently associated with HCC recurrence (hazard ratio [HR], 2.89; p=0.011). In the nationwide validation cohort, 20.3% of the patients experienced HCC recurrence. The last HCC treatment with a noncurative method, a short last HCC treatment durability (<12 months), and a longer total duration of HCC treatment (≥18 months) were independently related with HCC recurrence (HR 3.73, p<0.001; HR 3.34, p<0.001; and HR 1.74, p=0.006; respectively).ConclusionsDAA therapy showed an acceptable SVR12 rate in patients with HCV-related HCC. Short last HCC treatment durability (<12 months) was associated with HCC recurrence after DAA therapy. This finding suggests that the last HCC treatment durability is an important predictor of HCC recurrence after DAA therapy. (Gut Liver 2021;15-419)     

Hepatocellular carcinoma recurrence after liver transplantation: Risk factors,screening and clinical presentation

Liver transplantation is the best treatment option for cirrhotic patients with earlystage hepatocellular carcinoma, but it faces the problem of scarcity of donors and the risk of tumor recurrence, which affects between 15% and 20% of the cases,despite the use of restrictive criteria. The risk of recurrence depends on a number of factors, related to the tumor, the patient, and the treatment, which are discussed in this review. Some of these factors are already well established, such as the histopathological characteristics of the tumor, Alpha-fetoprotein(AFP)levels, and waiting time. Other factors related to the biological behavior of the tumor and treatment should be recognized because they can be used in the refinement of the selection criteria of transplant candidates and in an attempt to reduce recurrence. This review also discusses the clinical presentation of recurrence and its prognosis, contributing to the identification of a subgroup of patients who may have better survival, if they are timely identified and treated.Development of recurrence after the first year, with AFP levels ≤ 100 ng/mL, and single site capable of locoregional therapy are associated with better survival after recurrence.     

Biomarker-based MicroRNA Therapeutic Strategies for Hepatocellular Carcinoma

Recently, microRNAs (miRNAs) have emerged as key factors involved in a series of biological processes, ranging from embryogenesis to programmed cell death. Its link to aberrant expression profiles has rendered it a potentially attractive tool for the diagnosis, prognosis, or treatment of various diseases. Accumulating evidence has indicated that miRNAs act as tumor suppressors in hepatocyte malignant transformation by regulating development, differentiation, proliferation, and tumorigenesis. Here, we summarize recent progress in the development of novel biomarker-based miRNA therapeutic strategies for hepatocellular carcinoma (HCC).     

Hepatocellular carcinoma： Epidemiology, risk factors and pathogenesis

Hepatocellular carcinoma （HCC） is the commonest primary malignant cancer of the liver in the world. Given that the burden of chronic liver disease is expected to rise owing to increasing rates of alcoholism, hepatitis B and C prevalence and obesity-related fatty liver disease, it is expected that the incidence of HCC will also increase in the foreseeable future. This article summarizes the international epidemiology, the risk factors and the pathogenesis of HCC, including the roles of viral hepatitis, toxins, such as alcohol and aflatoxin, and insulin resistance.     

Development and Validation of an RNA Binding Protein-associated Prognostic Model for Hepatocellular Carcinoma

Background and AimsThe survival rate of patients with hepatocellular carcinoma is variable. The abnormal expression of RNA-binding proteins (RBPs) is closely related to the occurrence and development of malignant tumors. The primary aim of this study was to identify RBPs related to the prognosis of liver cancer and to construct a prognostic model of liver cancer.MethodsWe downloaded the hepatocellular carcinoma gene sequencing data from The Cancer Genome Atlas (cancergenome.nih.gov/) database, constructed a protein-protein interaction network, and used Cytoscape to realize the visualization. From among 325 abnormally expressed genes for RBPs, 9 (XPO5, enhancer of zeste 2 polycomb repressive complex 2 subunit [EZH2], CSTF2, BRCA1, RRP12, MRPL54, EIF2AK4, PPARGC1A, and SEPSECS) were selected for construction of the prognostic model. Then, we further verified the results through the Gene Expression Omnibus (www.ncbi.nlm.nih.gov/geo/) database and in vitro experiments.ResultsA prognostic model was constructed, which determined that the survival time of patients in the high-risk group was significantly shorter than that of the low-risk group (p<0.01). Univariate and multivariate Cox regression analysis suggested that the risk score was an independent prognostic factor (p<0.01). We also constructed a nomogram based on the risk score, survival time, and survival status. At the same time, we verified the high expression and cancer-promoting effects of EZH2 in tumors.ConclusionsSurvival, receiver operating characteristic curve and independent prognostic analyses demonstrated that we constructed a good prognostic model, which might be useful for estimating the survival of patients with hepatocellular carcinoma.     

Causes of Death in Patients with Unresectable Hepatocellular Carcinoma

Most patients with hepatocellular carcinoma (HCC) also have cirrhosis, an independent cause of death. We considered an alternative definition of tumor-related death in patients with HCC and attempted to validate our definition. Two hundred thirty-seven HCC patients were diagnosed, followed, and died over a 12-year period and were evaluated every 2 months, including their last 6 months of life. We defined death by cancer if there was, in the last 6 months of life, a CT scan increase of >25% in the sum of tumor index lesions’ cross-sectional areas or new onset of, or increase in, either vascular invasion or metastatic disease (Group 1). Patients with stable cancer were considered to have died from any other cause (Group 2). We found that 135 (57%) patients died from cancer progression (Group 1), whereas 102 (43%) patients did not (Group 2). There was a statistically significant difference between Group 1 and Group 2 patients in percentage with bilobar disease (P = 0.03), more than one tumor (P = 0.01), an increase in AFP (P = 0.04), vascular invasion (P = 0.001), and the presence of metastases (P = 0.01). We conclude that 57% of patients with unresectable HCC died as a direct result of cancer progression, but 43% did not. The latter died from complications of their cirrhosis, including sepsis, GI bleeds, and renal failure.