Persistently Rising Alpha-fetoprotein in the Diagnosis of Hepatocellular Carcinoma: A Review

Hepatocellular carcinoma (HCC), one of the most common malignant tumors worldwide, is known for its grim prognosis, with untreated life expectancy being only a matter of months after the diagnosis. The difficulty in making a diagnosis early is one of the main contributing factors to the poor prognosis. Alpha-fetoprotein (AFP) had long been used as a surveillance tool, but suboptimal specificity and sensitivity has prompted liver societies to abandon the recommendation for its universal use, even in combination with ultrasonography. Most studies have shown no obvious correlation between serum AFP level and HCC tumor size, stage, or survival post-diagnosis. However, some studies concluded that a gradual rise or persistent elevation in AFP were positive predictors for tumor development. Other studies reported a fall in AFP followed by a rise in patients with HCC as well as persistently rising AFP levels without development of HCC on follow up. Our calculation of the sensitivity and specificity of persistently rising AFP for HCC were both low, at 60% and 35.8%, respectively, indicating that the presence of persistently rising AFP per se did not offer diagnostic benefit. In addition, our calculated mean slopes of persistently rising AFP levels in HCC and non-HCC patients were numerically very different, but the difference was not statistically significant. We conclude that the published data do not support a role for rising AFP levels per se in the diagnosis of HCC.     

Controversies regarding and perspectives on clinical utility of biomarkers in hepatocellular carcinoma

The prevalence of hepatocellular carcinoma (HCC) worldwide parallels that of persistent infection with the hepatitis B virus (HBV) and/or hepatitis C virus (HCV). According to recommendations by the World Health Organization guidelines for HBV/HCV, alpha-fetoprotein (AFP) testing and abdominal ultrasound should be performed in routine surveillance of HCC every 6 mo for high-risk patients. These examinations have also been recommended worldwide by many other HCC guidelines over the past few decades. In recent years, however, the role of AFP in HCC surveillance and diagnosis has diminished due to advances in imaging modalities. AFP was excluded from the surveillance and/or diagnostic criteria in the HCC guidelines published by the American Association for the Study of Liver Diseases in 2010, the European Association for the Study of the Liver in 2012, and the National Comprehensive Cancer Network in 2014. Other biomarkers, including the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), des-γ-carboxyprothrombin, Dickkopf-1, midkine, and microRNA, are being studied in this regard. Furthermore, increasing attention has focused on the clinical utility of biomarkers as pre-treatment predictors for tumor recurrence and as post-treatment monitors. Serum and tissue-based biomarkers and genomics may aid in the diagnosis of HCC, determination of patient prognosis, and selection of appropriate treatment. However, further studies are needed to better characterize the accuracy and potential role of these approaches in clinical practice.     

Sensitivity of commonly available screening tests in detecting hepatocellular carcinoma in cirrhotic patients undergoing liver transplantation

OBJECTIVE: Recognition of hepatocellular carcinoma (HCC) is important in the management of patients awaiting liver transplantation. HCCs >5 cm in diameter are at high risk to recur after transplant. The goal of this study was to assess the sensitivity of the diagnostic tests employed in a pretransplant screening program. METHODS: The study is a retrospective analysis of charts of 106 consecutive adults transplanted over a 1-yr period. All patients had ultrasonography (US), computerized tomography (CT), and serum alpha fetoprotein (AFP) testing within 6 months of transplantation. Radiographic reports were subdivided into low-risk and high-risk groups, based upon level of suspicion for HCC. The results were compared to explant pathology. RESULTS: Pathological analysis of 106 explants revealed HCC in 19 patients. High-risk US exams had a positive predictive value (PPV) of 0.69 and a negative predictive value (NPV) of 0.91 in the diagnosis of HCC. High-risk CT exams had a PPV of 0.67 and an NPV of 0.90. When patients had either a high-risk US or a high-risk CT, there was a PPV of 0.59 and an NPV of 0.83. Of the 19 patients with HCC, three had high-risk US and low-risk CT; two had high-risk CT and low-risk US. Four patients, all with HCC <4 cm, had low-risk US, CT, and serum AFP. CONCLUSIONS: US, CT, and serum AFP, as single tests, are insensitive for detection of HCC in the cirrhotic liver. However, they are highly specific. Sensitivity and specificity for US are comparable to those for CT. Given its lower cost, US is preferable to CT for routine screening of HCC in patients with end-stage liver disease undergoing liver transplantation.     

甲胎蛋白应答在肝细胞癌治疗中的预后价值

肝细胞癌（HCC）是最常见的肝脏恶性肿瘤。因其恶性程度高、预后差,准确评估患者的治疗效果及预后情况至关重要。尽管目前影像学是肝癌预后评估的标准方法,但其仍存在诸多局限性。甲胎蛋白是重要的肝癌肿瘤标志物,广泛的应用于肝癌的筛查、诊断及预后评价。总结了甲胎蛋白应答在评判肝癌患者预后的相关文献。整体上,甲胎蛋白应答在肝癌患者接受射频消融、肝动脉化疗栓塞、钇90放射性栓塞、索拉菲尼等分子靶向药物、全身化疗、肝动脉灌注化疗或同步放化疗等治疗后具有良好的预后价值。     

Surveillance for early diagnosis of hepatocellular carcinoma: How best to do it?

Surveillance for hepatocellular carcinoma(HCC)is considered a standard of care for patients with chronic liver disease who are at risk of developing this malignancy.Several studies have shown that surveillance can improve the prognosis of patients diagnosed with HCC through an increased likelihood of application of curative or effective treatments.Repetition of liver ultrasonography(US)every 6 mo is the recommended surveillance program to detect early HCCs,and a positive US has to entrain a well-defined recall policy based on contrast-enhanced,dynamic radiological imaging or biopsy for the diagnosis of HCC.Although HCC fulfills the accepted criteria regarding cost-effective cancer screening and surveillance,the implementation of surveillance in clinical practice is defective and this has a negative impact on the cost-effectiveness of the procedure.Education of both physicians and patients is of paramount importance in order to improve the surveillance application and its benefits in patients at risk of HCC.The promotion of specific educational programs for practitioners,clinicians and patients is instrumental in order to expand the correct use of surveillance in clinical practice and eventually improve HCC prognosis.     

Economic evaluation of a surveillance program of hepatocellular carcinoma (HCC) in India

Purpose Surveillance of patients of cirrhosis of liver is practiced for early detection of HCC. No data from any developing country on cost-effectiveness of such a program are available. Methods Economic evaluation of HCC surveillance was embedded in a prospective study undertaken to estimate the incidence of HCC in 194 cirrhotics. The protocol consisted of 6 monthly abdominal ultrasound (US) and serum alphafetoprotein (AFP) estimation, and yearly triple phase CT. Cost was estimated from the hospital and patient perspectives. Cost-effectiveness ratios for detecting a case of HCC were estimated. Modeling was done to estimate cost effectiveness with different combinations of diagnostic tests. Results Cost-effectiveness ratios of HCC surveillance program per HCC case detected were estimated as US$ 280 from the hospital perspective. From patient perspective, these were US$ 9,965 for outstation and US$ 2,808 for local patients. Cost-effectiveness ratio for direct medical cost per case of HCC detected by 6 monthly US and AFP, the EASL protocol, was estimated to be US$ 1,510 in the private sector. Conclusion The cost of HCC surveillance program is exorbitant for India (gross national income per capita US$ 620) and possibly other low/middle income countries.     

Risk factors and diagnostic biomarkers for nonalcoholic fatty liver disease-associated hepatocellular carcinoma: Current evidence and future perspectives

High rates of excessive calorie intake diets and sedentary lifestyles have led to a global increase in nonalcoholic fatty liver disease (NAFLD). As a result, this condition has recently become one of the leading causes of hepatocellular carcinoma (HCC). Furthermore, the incidence of NAFLD-associated HCC (NAFLD-HCC) is expected to increase in the near future. Advanced liver fibrosis is the most common risk factor for NAFLD-HCC. However, up to 50% of NAFLD-HCC cases develop without underlying liver cirrhosis. Epidemiological studies have revealed many other risk factors for this condition; including diabetes, other metabolic traits, obesity, old age, male sex, Hispanic ethnicity, mild alcohol intake, and elevated liver enzymes. Specific gene variants, such as single-nucleotide polymorphisms of patatin-like phospholipase domain 3, transmembrane 6 superfamily member 2, and membrane-bound O-acyl-transferase domain-containing 7, are also associated with an increased risk of HCC in patients with NAFLD. This clinical and genetic information should be interpreted together for accurate risk prediction. Alpha-fetoprotein (AFP) is the only biomarker currently recommended for HCC screening. However, it is not sufficiently sensitive in addressing this diagnostic challenge. The GALAD score can be calculated based on sex, age, lectin-bound AFP, AFP, and des-carboxyprothrombin and is reported to show better diagnostic performance for HCC. In addition, emerging studies on genetic and epigenetic biomarkers have also yielded promising diagnostic potential. However, further research is needed to establish an effective surveillance program for the early diagnosis of NAFLD-HCC.     

Hepatocellular carcinoma in patients with chronic hepatitis C and cirrhosis in Denmark: A nationwide cohort study

Cirrhosis in patients with chronic hepatitis C increases the risk of hepatocellular carcinoma (HCC ), and surveillance with ultrasound (US ) and alpha‐fetoprotein (AFP ) is recommended. This study aimed to estimate changes in the HCC incidence rate (IR ) over time, HCC stage and prognosis, and AFP and US performed in patients with hepatitis C and cirrhosis. Eligible patients were identified in the Danish Database for Hepatitis B and C, and data from national health registries and patient charts were obtained. Tumour stage was based on Barcelona‐Clinic Liver Cancer stage, TNM classification and size and number of lesions combined into stages 0‐3. We included 1075 patients with hepatitis C and cirrhosis, free of HCC and liver transplant at baseline. During 4988 person years (PY ), 115 HCC cases were diagnosed. The HCC incidence rate increased from 0.8/100 PY [CI 95% 0.4‐1.5] in 2002‐2003 to 2.9/100 PY [2.4‐3.4] in 2012‐2013. One‐year cumulative incidence of at least one AFP or US was 53% among all patients. The positive predictive value of an AFP  ≥ 20 ng mL^?1 was 17%. Twenty‐three (21%) patients were diagnosed with early‐stage HCC (stage 0/1) and 84 (79%) with late stage. Median survival after HCC for early‐stage HCC disease was 30.1 months and 7.4 months for advanced HCC (stage 2/3). The incidence rate of HCC increased over time among patients with hepatitis C and cirrhosis in Denmark. Application of AFP and US was suboptimal, and most patients were diagnosed with advanced HCC with a poor prognosis.     

New sonographic techniques for the diagnosis and treatment of hepatocellular carcinoma

Ultrasound (US) contrast agents such as Levovist and Sonazoid are now commercially available in Japan. Innovative contrast agents and ultrasound technologies have dramatically changed both diagnostic and treatment strategies for hepatocellular carcinoma (HCC). Contrast-enhanced US is extremely useful in the differential diagnosis of hepatic tumors as well as in evaluation of post-treatment response of HCC after lipiodol transarterial chemoembolization and radio frequency ablation. Harmonic US sensitively detects residual cancer cells in HCC patients after treatment, to facilitate accurate guidance for needle insertion for US monitoring; no other imaging modalities, including computed tomography (CT) or magnetic resonance imaging (MRI), have such capability. In 2005, the breakthrough technology of pure arterial phase imaging, which depicts only intranodular arterial accumulated maximum intensity projection images, was developed from advanced raw data storing and accumulation technologies. This technique can clearly identify whether blood supplyin the tumor is of arterial or portal origin, to facilitate the non-invasive characterization of nodular lesions associated with liver cirrhosis. Again, CT or MRI do not have such capabilities. This innovative technique can help differentiate premalignant lesions from overt HCC. Concurrent real-time imaging of multi-detector CT and US, known as real-time virtual sonography, has recently become available. This technique greatly facilitates the treatment guidance for HCC. These newly introduced sonographic techniques are dramatically changing the diagnostic and therapeutic strategies for HCC, which are expected to improve the prognosis of HCC patients.     

The 2008 Okuda lecture: Management of hepatocellular carcinoma: From surveillance to molecular targeted therapy

Hepatocellular carcinoma (HCC) is responsible for approximately 600 000–700 000 deaths worldwide. It is highly prevalent in the Asia‐Pacific region and Africa, and is increasing in Western countries. Alpha fetoprotein (AFP) alone is insufficient for HCC screening. A combination with other tumor markers, such as PIVKA‐II and AFP‐L3, and periodical ultrasound surveillance is necessary. Sensitivity of AFP in depicting HCC is highest, followed by PIVKA‐II and AFP‐L3, but the order of the specificity is inverse, AFP‐L3, PIVKA‐II, and AFP. Sonazoid‐enhanced ultrasound (US) is extremely useful to characterize hepatic tumors equal to or more than multidetector row computed tomography (MDCT). Sonazoid‐enhanced US with defect re‐perfusion imaging is a breakthrough technique in the treatment of HCC. Defect re‐perfusion imaging will markedly change the therapeutic strategy for liver cancer. Gd‐EOB‐DTPA‐magnetic resonance imaging is a newly developed imaging technique in the detection and diagnosis of HCC. It is the most sensitive tool in the differentiation of early HCC from dysplastic nodules. Regarding the treatment strategy, there has been no established systemic chemotherapy for advanced HCC, except for Sorafenib. Empirically, intrahepatic arterial infusion chemotherapy using implanted reservoir port is known to be effective in response rate and overall survival for advanced HCC with vascular invasion. Sorafenib in combination with transcatheter arterial chemoembolization or adjuvant use after ablation or resection will significantly prolong the life expectancy if ongoing clinical trials provide positive results. In conclusion, it is expected that readers will gain deeper insight into the latest progress and updated diagnosis and treatment of HCC described in this review.     

Performance of protein induced by vitamin K absence or antagonist-II assessed by chemiluminescence enzyme immunoassay for hepatocellular carcinoma detection: a meta-analysis

Objectives: In the setting of surveillance for hepatocellular carcinoma (HCC) detection, the use of serum biomarkers in addition to ultrasonography (US) is still a matter of debate. Hence, we performed a meta-analysis to evaluate the diagnostic accuracy of protein induced by vitamin K absence or antagonist-II (PIVKA-II) and alpha-fetoprotein (AFP) alone or in combination for HCC detection in patients at risk of tumor development.

Materials and methods: We performed a systematic search in PubMed and Scopus database for original articles published in English from 2011 to 2017, investigating the accuracy of PIVKA-II alone or in combination with AFP (reported as area under the curve [AUC]) for HCC detection among patients at risk of tumor development. Furthermore, we focused on studies in which serum PIVKA-II was assessed by highly sensitive chemiluminescence immunoassay (CLEIA).

Results: A total of 11 studies (873 patients with HCC and 1244 patients with advanced liver disease/cirrhosis) were included in the meta-analysis. The weighted summary AUC (sAUC) of PIVKA-II and AFP for the discrimination between patients with HCC and those without was 0.791 (0.746–0.837) and 0.767 (0.732–0.803), respectively. The combination of PIVKA-II?+?AFP results in a sAUC of 0.859 (0.837–0.882). The performance for HCC detection of PIVKA-II?+?AFP was significantly superior to each biomarker used alone (ΔsAUC?=?0.068, p?=?.032 and ΔsAUC?=?0.092, p?Conclusion: In clinical practice, the use of PIVKA-II?+?AFP in addition to US examination may improve the effectiveness of surveillance among patients at risk for HCC development.     

Application of surveillance programs for hepatocellular carcinoma in the Asia–Pacific Region

Hepatocellular carcinoma (HCC) is a potential target for cancer surveillance (or screening) as it occurs in well-defined, at-risk populations and curative therapy is possible only for small tumors. Surveillance has been recommended by regional liver societies and is practiced widely, but its benefits are not clearly established. Hepatic ultrasonography with or without alpha fetoprotein (AFP) performed every 6 months is the preferred program. Surveillance of HCC has been well shown to detect small tumors for curative treatment, which may be translated to improved patient survival. However, most studies are limited by lead-time bias, length bias for early diagnosis of small HCC, different tumor growth rates and poor compliance with surveillance. Cost-effectiveness of surveillance programs depends on the rate of small HCC detected 'accidentally' (routine imaging) in a comparator group, annual incidence of HCC with various etiologies, patient age and the availability of liver transplantation. The incremental cost-effectiveness for 6-monthly AFP and ultrasound has been estimated from approximately $US26 000–74 000/quality adjusted life years (QALY). All cirrhotic patients are therefore recommended for HCC surveillance unless the disease is too advanced for any curative treatment. As chronic hepatitis B can develop into HCC without going through liver cirrhosis, high-risk non-cirrhotic chronic hepatitis B patients are also recommended for HCC surveillance. In conclusion, HCC surveillance could be effective at reducing disease-specific mortality with acceptable cost-effectiveness among selected patient groups, provided it is a well-organized program.     

Curative resection of hepatocellular carcinoma with intrabile duct tumor growth mimicking hilar bile duct carcinoma

A 62-year-old Japanese male was admitted with obstructive jaundice and underwent percutaneous transhepatic cholangiodrainage (PTCD). An initial diagnosis was made of hilar bile duct carcinoma, based on demonstrated irregular stenosis of the hilar hepatic bile ducts without obvious tumor within the liver and negative alpha-fetoprotein (AFP). Enhanced computed tomography (CT) showed an irregular low density area around the hepatic hilum and the umbilical portion of the portal vein, suggesting carcinomatous invasion with blood flow disturbances. In contrast, intraoperative ultrasonography (US) raised the suspicion of an ill-defined lesion in Couinaud's segment 2 (segment 2) and intrabile duct tumor formation. A radical extended left and caudate lobectomy of the liver was successfully performed, with additional resection of extrahepatic bile duct and enbloc resection of regional lymph nodes. Unexpectedly, histological analysis of the resected specimen showed the final diagnosis to be hepatocellular carcinoma (HCC) of segment 2 with intrabile duct tumor growth. This case demonstrates that HCC with intrabile duct tumor growth toward the heptic hilum can mimic hilar bile duct carcinoma, when the tumor itself is equivocal on preoperative imaging and AFP is negative. In such cases, intraoperative US and guided biopsy may be of value for definitive diagnosis and selection of the optimal procedure.     

Surveillance for hepatocellular carcinoma in patients with chronic viral hepatitis in the United States of America

BACKGROUND: Measurement of serum alpha-fetoprotein (AFP) and abdominal ultrasound (US) examination are used for the early detection of hepatocellular carcinoma (HCC) in chronic liver disease patients. However, the accuracy and usefulness of these tests in a clinical setting in the United States of America have not been clarified. METHODS: We conducted a 7-year prospective surveillance study by using both AFP and US to detect HCC in 602 patients with chronic viral hepatitis. Our main goal was to determine the optimal test for detection of early HCC. We also assessed the clinical outcome of HCC patients identified during this time period. RESULTS: Thirty-one cases of HCC were detected. Serum AFP levels were elevated in 74% of HCC patients, but was also high in 10% of patients who did not develop HCC. The positive predictive value for AFP to detect HCC was only 12% or less for all AFP cut-off values, and the maximum joint sensitivity and specificity as determined by receiver operator characteristic analysis was approximately 65 and 90%, respectively. Abdominal US identified all 31 cases of HCC. The positive predictive value for US examinations to detect HCC was 78%, while the sensitivity and specificity was 100 and 98%, respectively. After detection of HCC, 24 (77%) patients died within a mean of 16.7 +/- 19.4 months. CONCLUSIONS: Our study indicates that US examination was more accurate in detecting HCC. Because of its poor predictive value and low sensitivity, serum AFP should not be used as the only test for screening and surveillance for HCC.     

Hepatocellular carcinoma surveillance:An evidence-based approach

Hepatocellular carcinoma(HCC) makes up 75%-85% of all primary liver cancers and is the fourth most common cause of cancer related death worldwide. Chronic liver disease is the most significant risk factor for HCC with 80%-90% of new cases occurring in the background of cirrhosis. Studies have shown that early diagnosis of HCC through surveillance programs improve prognosis and availability of curative therapies. All patients with cirrhosis and high-risk hepatitis B patients are at risk for HCC and should undergo surveillance. The recommended surveillance modality is abdominal ultrasound(US) given that it is cost effective and noninvasive with good sensitivity. However, US is limited in obese patients and those with non-alcoholic fatty liver disease(NAFLD). With the current obesity epidemic and rise in the prevalence of NAFLD, abdominal computed tomography or magnetic resonance imaging may be indicated as the primary screening modality in these patients. The addition of alpha-fetoprotein to a surveillance regimen is thought to improve the sensitivity of HCC detection.Further investigation of serum biomarkers is needed. Semiannual screening is the suggested surveillance interval. Surveillance for HCC is underutilized and low adherence disproportionately affects certain demographics such as nonCaucasian race and low socioeconomic status.     

原发性肝细胞癌血清中miR-888-5p的表达及临床意义

背景miR-888-5p高表达于原发性肝细胞癌(hepatocellular carcinoma,HCC)组织及HCC细胞系,可促进肿瘤细胞侵袭及转移,与疾病分期及预后不良相关.然而HCC患者血清中miR-888-5p的表达水平尚未被检测,血清miR-888-5p对于HCC诊断及预后判断相关价值尚未被评估.目的检测HCC患者血清中miR-888-5p表达水平,探究其对HCC的诊断价值及与临床特征之间的关系.方法收集68例HCC患者、46例慢性乙型病毒性肝炎(chronic hepatitis B,CHB)患者、43例肝硬化(liver cirrhosis,LC)患者及40例同期健康体检者,实时荧光定量聚合酶链反应(quantitative real-time polymerase chain reaction,qRT-PCR)法检测血清中miR-888-5p表达量,受试者工作特征(receiver operating characteristic,ROC)曲线评估其诊断HCC的价值,并分析与HCC临床特征之间的关系.结果HCC患者血清中miR-888-5p表达量较CHB、LC及健康者显著上调(P<0.05).ROC曲线提示,联合检测ROC曲线下面积(area under curve,AUC)为0.907,敏感性91.18%,特异性72.50%)对HCC诊断价值优于分别检测血清miR-888-5p(AUC=0.737,敏感性79.41%,特异性62.50%)及甲胎蛋白(alpha-fetoprotein,AFP)(AUC=0.819,敏感性73.53%,特异性97.50%),且对AFP阴性HCC也具有较高的诊断价值:AUC=0.793,敏感性90.90%,特异性62.50%.此外,miR-888-5p表达水平与HCC肺转移相关(P=0.01).结论血清miR-888-5p对HCC及AFP阴性HCC具有较高诊断价值,与AFP联合检测诊断价值更高.miR-888-5p表达水平与HCC肺转移相关,有望成为HCC早期诊断及评估预后的新型血清学分子标志物.     

Liver Imaging Reporting and Data System criteria for the diagnosis of hepatocellular carcinoma in clinical practice: A pictorial minireview

Hepatocellular carcinoma (HCC) is the sixth most common cancer. The main risk factors associated with HCC development include hepatitis B virus, hepatitis C virus, alcohol consumption, aflatoxin B1, and nonalcoholic fatty liver disease. However, hepatocarcinogenesis is a complex multistep process. Various factors lead to hepatocyte malignant transformation and HCC development. Diagnosis and surveillance of HCC can be made with the use of liver ultrasound (US) every 6 mo. However, the sensitivity of this imaging method to detect HCC in a cirrhotic liver is limited, due to the abnormal liver parenchyma. Computed tomography (CT) and magnetic resonance imaging (MRI) are considered to be most useful tools for at-risk patients or patients with inadequate US. Liver biopsy is still used for diagnosis and prognosis of HCC in specific nodules that cannot be definitely characterized as HCC by imaging. Recently the American College of Radiology designed the Liver Imaging Reporting and Data System (LI-RADS), which is a comprehensive system for standardized interpretation of CT and MRI liver examinations that was first proposed in 2011. In 2018, it was integrated into the American Association for the Study of Liver Diseases guidance statement for HCC. LI-RADS is designed to ensure high sensitivity, precise categorization, and high positive predictive value for the diagnosis of HCC and is applied to “high-risk populations” according to specific criteria. Most importantly LI-RADS criteria achieved international collaboration and consensus among liver experts around the world on the best practices for caring for patients with or at risk for HCC.     

鳞状细胞癌抗原与原发性肝癌相关性研究进展

<正>原发性肝癌(hepatocellular carcinoma,HCC)是世界上最常见的恶性肿瘤之一[1]。目前HCC的临床诊断主要依赖于影像学证据、血清学指标及肝组织的病理学和细胞学检查。其中影像学方法无法准确判断占位的良、恶性,而肝脏穿刺病理学检查是有创检查,一般医院尚难开展,甲胎蛋白(α-fetoprotein,AFP)是目前常用的HCC标记物,但其敏感性及特异性均不高。近年来,鳞状细胞癌抗原(squa-     

Hepatocellular carcinoma in non-cirrhotic liver: A comprehensive review

Hepatocellular carcinoma(HCC) is the most common type of primary liver cancer, which in turns accounts for the sixth most common cancer worldwide.Despite being the 6 th most common cancer it is the second leading cause of cancer related deaths. HCC typically arises in the background of cirrhosis, however,about 20% of cases can develop in a non-cirrhotic liver. This particular subgroup of HCC generally presents at an advanced stage as surveillance is not performed in a non-cirrhotic liver. HCC in non-cirrhotic patients is clinically silent in its early stages because of lack of symptoms and surveillance imaging; and higher hepatic reserve in this population. Interestingly, F3 fibrosis in non-alcoholic fatty liver disease, hepatitis B virus and hepatitis C virus infections are associated with high risk of developing HCC. Even though considerable progress has been made in the management of this entity, there is a dire need for implementation of surveillance strategies in the patient population at risk, to decrease the disease burden at presentation and improve the prognosis of these patients. This comprehensive review details the epidemiology, risk factors, clinical features,diagnosis and management of HCC in non-cirrhotic patients and provides future directions for research.