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Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally. Early detection and treatment response monitoring of HCC are vital for improved outcomes. Traditional diagnostic methods rely on imaging, serum tumor markers, and invasive liver tissue biopsy. The advent of liquid biopsy has revolutionized cancer diagnostics and management. Liquid biopsy involves the detection and analysis of tumor-derived components, such as circulating tumor DNA, circulating tumor cells, and extracellular vesicles, in various body fluids. These components reflect tumor characteristics, genetic alterations, and functional changes, providing valuable information for HCC diagnosis and treatment response monitoring. Liquid biopsy offers several advantages, including its non-invasive nature, potential for repetitive sampling, and real-time monitoring of disease progression and treatment response. However, challenges remain, including the sensitivity of detection methods, and standardization. In this review, we discuss the methods, current status, and prospects of liquid biopsy for HCC, highlighting its potential as a valuable tool in HCC management.

Transarterial chemoembolization (TACE) is a widely used hepatocellular carcinoma (HCC) treatment. Some cases of supraumbilical skin rash after TACE in patients with HCC have been reported. To the best of the authors’ knowledge, there are no reports on atypical, generalized rashes caused by doxorubicin systemic absorption after TACE. This paper presents the case of a 64-year-old male with HCC who developed generalized macules and patches one day after a successful TACE procedure. A histology examination of a skin biopsy of a dark reddish patch on the knee revealed severe interface dermatitis. He was treated with a topical steroid, and all skin rashes improved within a week with no side effects. This report presents this rare case with a literature review on skin rash after TACE.

Purpose: To investigate the prognostic value of the neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in patients with hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT). Methods: The medical records of HCC patients treated with SBRT between 2008 and 2019 were reviewed retrospectively. The NLR and PLR were calculated from the serum complete blood count before and after SBRT, and the prognostic values of the NLR and PLR for the treatment outcomes were evaluated. Results: Thirty-nine patients with 49 HCC lesions were included. After a median follow-up of 26.8 months (range, 8.4-80.0 months), three-year local control, overall survival (OS), and progression-free survival (PFS) rate were 97.4%, 78.3%, and 35.2%, respectively. Both NLR and PLR increased significantly after SBRT and decreased slowly to the pre-SBRT value at 6 months. Univariable analysis showed that gross tumor volume (GTV) >14 cc, post-SBRT PLR >90, and PLR change >30 were associated with a poorer OS (p=0.002, p=0.011, and p=0.001, respectively), and the PLR change was significant in multivariable analysis (hazard ratio [HR], 10.09; 95% CI, 1.15-88.40; p=0.037). For PFS, GTV >14 cc, post-SBRT NLR >2.5 and post-SBRT PLR >90 were predictive of a poorer PFS in univariable analysis (p=0.011, p=0.004 and p=0.041, respectively) and only post-SBRT NLR >2.5 remained significant in multivariable analysis (HR, 2.44; 95% CI, 1.03-5.76; p=0.042, respectively). Conclusions: The NLR and PLR increased transiently after SBRT, and the post-SBRT NLR and PLR were associated with the clinical outcomes of HCC patients.

Detection of hepatocellular carcinoma (HCC) at an early stage enables patients to receive curative treatment with survival gains. Current international liver society guidelines recommend the enrollment of patients at high risk for HCC in surveillance programs. In Korea, surveillance for HCC advocated for patients with chronic hepatitis B, chronic hepatitis C, and liver cirrhosis. The established surveillance tool for HCC is liver ultrasonography plus serum alpha-fetoprotein measurement every 6 months. However, there would be obstacles to the improvement of efficacy and cost-effectiveness of the HCC surveillance test. Assessing who is at risk of developing HCC remains incompletely validated. Also, which surveillance tools to use according to patients’ characteristics are controversial. The present paper reviews the latest knowledge regarding the strategies and cost-effectiveness of HCC surveillance.

Hepatocellular carcinoma (HCC) has heterogeneous molecular and pathological features and biological behavior. Large-scale genetic studies of HCC were accumulated, and a pathological-molecular classification of HCC was proposed. Approximately 35% of HCCs can be classified into distinct histopathological subtypes according to their molecular characteristics. Among recently identified subtypes, macrotrabecular massive HCC, neutrophil-rich HCC, vessels encapsulating tumor clusters HCC, and progenitor phenotype HCC (HCC with CK19 expression) are associated with a poor prognosis, whereas the lymphocyte-rich HCC subtype is related to a better prognosis. This review provides up-to-date knowledge on the pathological diagnosis of HCC according to the updated World Health Organization Classification of Digestive System Tumors 5th ed.

There are various causes of hepatocellular carcinoma, including viral hepatitis, and treatment strategies are often established based on the radiology diagnosis, unlike other carcinomas. The liver imaging reporting and data system (LI-RADS) is a diagnostic system developed by the American College of Radiologists for clear communication and standardized reports of the liver imaging findings. It was recently included in the clinical guidance of the American Association for the Study of Liver Diseases. In addition, the radiologic findings of hepatocellular carcinoma (HCC) enable a prediction of the prognosis after treatment and a diagnosis of diseases because the use of gadoxetic acid MRI has become more common. Thus, the role of radiology for the diagnosis and treatment of HCC is expected to be developed further.

Biomarkers are key components of the clinical management of cancer patients because they have contributed to significant survival improvements in these patients. They allow the classification of patients based on common features and facilitate risk stratification, early detection, diagnosis, and prediction of the prognosis or treatment response. In hepatocellular carcinoma (HCC), there are few biomarkers incorporated in clinical practice. Despite this, this has been an extensive area of research in recent years, with increasing efforts to identify the biomarkers across the cancer care continuum from risk stratification to early detection to prognostication and treatment response. The heterogeneous nature of HCCs has restricted the performance of biomarkers. HCC biomarkers have limited roles in risk stratification, diagnosis, and treatment response. Currently, the main role of biomarkers is in the surveillance of HCC to detect it at an earlier stage and reduce mortality, which is the focus of this review.

Backgrounds/Aims: Post-hepatectomy liver failure (PHLF) is a major concern for patients with hepatocellular carcinoma (HCC) who have undergone liver resection. The albumin-bilirubin (ALBI) score is a novel model for assessing liver function. We aimed to investigate the effectiveness of the ALBI score as a predictor of PHLF in HCC patients who have undergone hepatectomy in South Korea. Methods: Between January 2014 and November 2018, HCC patients who underwent hepatectomy and indocyanine retention rate at 15 min (ICG-R15) test were enrolled in this study. Results: A total of 101 patients diagnosed with HCC underwent hepatectomy. Thirty-two patients (31.7%) experienced PHLF. The ALBI score (OR 2.83; 95% CI 1.22-6.55; p=0.015), ICG-R15 (OR 1.07; 95% CI 1.02-1.12; p=0.007) and ALBI grade (OR 2,86; 95% CI 1.08-7.58; p=0.035) were identified as independent predictors of PHLF by multivariable analysis. The area under the receiver operating characteristic curve of the ALBI score and ICG-R15 were 0.676 (95% CI 0.566-0.785) and 0.632 (95% CI 0.513-0.752), respectively. The optimal cutoff value of the ALBI score in predicting PHLF was -2.62, with a sensitivity of 75.0% and a specificity of 56.5%. Conclusions: The ALBI score is an effective predictor of PHLF in patients with HCC, and its predictive ability is comparable to that of ICG-R15.

Purpose The purpose of this study was to evaluate the usefulness of multiphasic CT and 18F-fluorodeoxyglucose (FDG) PET/CT for the differentiation of combined hepatocellular carcinomacholangiocarcinoma (cHCC-CCA) from hepatocellular carcinoma (HCC). Materials and Methods From January 2007 to April 2016, 93 patients with pathologically confirmed HCC (n = 84) or cHCC-CCA (n = 9) underwent CT and PET/CT imaging. Contrast enhancement patterns were divided into three types based on the attenuation of the surrounding liver parenchyma: type I (early arterial enhancement with delayed washout), type II (early arterial enhancement without delayed washout), and type III (early hypovascular, infiltrative appearance, or peripheral rim enhancement). Results cHCC-CCAs (89%) had a higher PET/CT positive rate than did HCCs (61%), but the PET/ CT positive rate did not differ significantly (p = 0.095). Among the 19 cases of the type II enhancement pattern, 3 (21%) of 14 HCCs and 4 (80%) of 5 cHCC-CCAs were PET/CT positive. cHCC-CCAs had a significantly higher PET/CT positive rate (p = 0.020) in the type II enhancement pattern. Conclusion The PET/CT positive rate of cHCC-CCA was significantly higher than that of HCC in lesions with a type II enhancement pattern. The 18F-FDG PET/CT can be useful for the differentiation of cHCCCCA from HCC in lesions with a type II enhancement pattern on multiphasic CT.

Transarterial chemoembolization (TACE) is a common treatment for unresectable hepatocellular carcinoma (HCC). The most common complications after TACE are non-specific symptoms called post-embolization syndrome, such as abdominal pain or fever. Rare complications, such as liver failure, liver abscess, sepsis, pulmonary embolism, cholecystitis, can also occur. On the other hand, gallbladder perforation is quite rare. This paper reports a case of gallbladder perforation following TACE. A 76-year-old male with a single 9-cm-sized HCC underwent TACE. Five days after TACE, he developed persistent right upper quadrant pain and ileus. An abdomen CT scan confirmed gallbladder perforation with bile in the right paracolic gutter and pelvic cavity. Percutaneous transhepatic gallbladder drainage was performed with the intravenous administration of antibiotics. After 1 month, the patient underwent right hemihepatectomy and cholecystectomy. Physicians should consider the possibility of gallbladder perforation, which is a rare complication after TACE, when unexplained abdominal pain persists.

Background/Aims: A switch to systemic therapy, such as sorafenib, should be considered for hepatocellular carcinoma (HCC) patients refractory to transarterial chemoembolization (TACE). On the other hand, treatment changes are difficult if the liver function worsens to Child-Pugh B or C. Therefore, predicting the risk factors for non-responsiveness to TACE and deteriorating liver function may be helpful. Methods: Newly diagnosed Child-Pugh A HCC patients who underwent TACE from January 2012 to June 2018 were included. After 1 year, this study evaluated whether there was a treatment response to TACE and whether the Child-Pugh class had worsened. Results: Among 121 patients, 65 were refractory and 56 responded to TACE. In multivariable logistic regression analysis, the tumor size, tumor number, and albumin at the time of the diagnosis of HCC were significant prognostic factors for the treatment response to TACE. Among 65 patients who presented TACE-refractoriness, 27 showed liver function deterioration from Child-Pugh class A to class B or C after TACE. In multivariable logistic regression analysis, bilirubin at the diagnosis of HCC was a significant prognostic factor for liver function deterioration. A predictive algorithm based on the regression equations revealed a sensitivity, specificity, positive predictive value, and negative predictive value of 74.1%, 74.5%, 45.5%, and 90.9%, respectively, for TACE-refractoriness and liver function deterioration. Conclusions: The prognostic model incorporating the tumor size, tumor number, albumin, and bilirubin at the diagnosis of HCC may help identify patients who show a poor response to TACE and aggravation of liver function after TACE, who may benefit from early switching into systemic therapy before liver function aggravation.

Multiple studies have shown that oral antiviral therapies reduced the incidence of hepatocellular carcinoma (HCC) and improved the survival of patients with chronic hepatitis B when compared with that of untreated patients. In particular, entecavir and tenofovir share the qualities of high efficacy in reducing the HBV DNA levels, and they have excellent tolerability and safety. These drugs modified the natural history of liver fibrosis, improve liver function, decrease the incidence of HCC, decrease the need for liver transplantation, and improve survival. Many studies have suggested that long-term antiviral therapy reduces the risk of HCC and liver cirrhosis in patients with chronic hepatitis. The mechanism of these drugs in reducing the risk of HCC is not clear. This article reviews the mechanisms of carcinogenic HBV by conducting a review of the literature on the efficacy of therapy for reducing the risk of HCC. A few recent articles have suggested that tenofovir offers advantages over entecavir in terms of HCC prevention, but these articles have the inherent limitations of observational data. No other head-to-head randomized trials exist. Further randomized studies would help provide stronger evidence of the association between the type of antiviral agent and the HCC outcomes. Only achieving complete viral eradication from the liver will truly decrease the mortality and incidence of HCC.

The Korean clinical practice guidelines for the management of hepatocellular carcinoma (HCC) was originally enacted in 2004 by the Korean Liver Cancer Association (KLCA)-National Cancer Center (NCC) Korea in order to provide medical practitioners with specific medical information regarding HCC to help them facilitate their understanding of the disease and treatment of the patients. KLCA-NCC Korea practice guidelines for the management of HCC have been revised entirely two times in 2009, and 2014. Although several major international liver association have established and revised clinical practice guidelines, since the medical environment in each country is somewhat different depending on race, region, institution, and economic conditions, it is necessary to revise the Korean guidelines to that reflect our medical environments and own research results. In this review, major change and its background will be summarized about 2018 updated clinical practice guidelines for the management of HCC.

Transcatheter arterial chemoembolization (TACE) improves the survival rate in patients with hepatocellular carcinoma (HCC). Despite the low probability, iatrogenic hepatic arterial dissections during interventional procedure are rarely created by the technical difficulties. Direct trauma from the guidewire, the tip of the catheter, or the jet of contrast injection can contribute to iatrogenic hepatic arterial dissections. We report one case of a female who had HCC necrosis caused by iatrogenic hepatic arterial dissection during TACE. Ischemia resulting from iatrogenic hepatic arterial dissection during TACE was smilar to the result of transarterial embolization for HCC on our case. To our knowledge, none of the similar cases was reported in previously published literatures.

Since the approval of sorafenib for patients with advanced hepatocellular carcinoma (HCC) in 2007, many drugs have failed in the first and second-line setting. Fortunately, during the recent 2 years, between 2017 and 2018, four drugs (regorafenib, lenvatinib, cabozantinib, and ramucirumab) were found to be effective and tolerable for patients with HCC as the first- or second-line therapy. Regorafenib, a multi-kinase inhibitor, has a similar structure to sorafenib, and was shown to improve the survival of patients who progressed after sorafenib treatment compared to the placebo control. According to the phase III trial of regorafenib, it became the first approved systemic therapy for patients with progression after sorafenib. Lenvatinib is also a tyrosine kinase inhibitor (TKI), and in a phase III trial comparing sorafenib and lenvatinib, the primary end-point of non-inferior survival was met. Based on the trial results, lenvatinb has become another systemic therapy for treatment-naïve patients with advanced HCC. Cabozantinib is a dual inhibitor of Mesenchymal-Epithelial Transition factor/Vascular Endothelial Growth Factor Receptor2, and was shown to prolong the overall survival in patients who progressed after sorafenib compared to the placebo. Ramucirumab is a monoclonal antibody to inhibit a single target of VEGFR2. First, this drug failed to improve the survival of patients who progressed after sorafenib failure. On the other hand, it was effective in patients with baseline AFP ≥400 ng/mL, In a subsequent clinical trial that enrolled only patients with AFP ≥400 ng/mL, ramucirumab was also found to improve the overall survival compared to placebo. Thus, ramucirumab became the first biomarker-driven systemic treatment. Another category of drugs that are attracting considerable interest are immune checkpoint inhibitors, such as anti-programmed cell death protein (PD) 1 or anti-PD-ligand 1. This review provides a synopsis of new systemic therapies, including TKI, monoclonal antibody, and immune-oncology drugs.

Purpose: To evaluate the usefulness of cone beam computed tomography (CT)- based parenchymal blood volume (PBV) mapping for the detection of marginal recurrence or residual hepatocellular carcinoma, after transcatheter arterial chemoembolization (TACE), and to compare it with multiphase dynamic CT (MDCT). Materials and Methods: From March 2015 to October 2016, 26 patients with 49 iodized nodules who underwent TACE and a pre-interventional MDCT scan were enrolled in our study. We evaluated the diagnostic efficacies of PBV mapping using cone beam CT and MDCT in the detection of marginal recurrences or viable tumors. Results: The sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of PBV mapping and MDCT were 100%, 96.7%, 94.7%, and 100%, and 77.9%, 93.5%, 87.5%, and 87.8%, respectively. The overall sensitivity for identifying local marginal recurrence was higher for PBV mapping than for MDCT (p < 0.005). The performances of PBV mapping and MDCT in the diagnosis of local marginal recurrence were significantly different (p = 0.037, McNemar test). Conclusion: Compared with MDCT, PBV mapping can significantly increase the detection of marginal recurrence or residual tumor after TACE because it is free of beam-hardening artifact. PBV mapping should be considered as a feasible modalityrelated tool for patients who have undergone chemoembolization.

Angiomyolipoma (AML) is a rare benign mesenchymal tumor in the liver, which is composed of blood vessels, smooth muscle, and adipose cells. The proportion of each component varies, making a diagnosis difficult. This paper reports a case of AML in the liver without adipose tissue, mimicking a hepatocellular carcinoma (HCC), which was diagnosed by a surgical tissue biopsy. A 65-year-old woman was admitted for an evaluation of a hepatic mass that had been detected by ultrasonography. The serologic markers of viral hepatitis B and C were negative. The liver function tests and alpha fetoprotein level were within the normal limits. Magnetic resonance imaging revealed a 1.9 cm sized mass in segment 6 of the liver with early arterial enhancement and washout on the delayed phase accompanied by a rim-like enhancement, which is similar to the imaging findings of HCC. A frozen section examination during surgery indicated a hepatocellular neoplasm and suggested the possibility of HCC. On the other hand, the final pathologic diagnosis was epithelioid myoid type of AML with no adipose tissue component. The tumor cells were positive for human melanocyte B-45 and negative for cytokeratin and hepatocyte paraffin 1. This paper reports a very rare case of AML without adipose tissue in the liver mimicking HCC that was diagnosed by a surgical tissue biopsy.

Radiofrequency ablation (RFA) is a minimally invasive procedure that has been considered as a relatively safe treatment for patients with small hepatocellular carcinoma (HCC). However, RFA has been shown to be associated with complications including mechanical and thermal damage. A 74-year-old man with hepatitis C virus-associated HCC was admitted to our hospital. Abdominal computed tomography revealed two lobulated-HCC in segments 4 and 5. He had no medical history of hypertension and cardiac disease. During RFA, blood pressure was elevated to 200/140 mmHg. There was no evidence of pulmonary embolism, aortic dissection, or ischemic heart disease. Laboratory findings for catecholamine surge were all within normal limits. After continuous intravenous nitroglycerin and oral beta-blocker treatment, patient’s blood pressure gradually decreased and back within the normal range. Hypertensive crisis after RFA treatment for HCC is rare. Most reported cases of hypertensive crisis during RFA were related to adrenal gland injury with a release of catecholamine. In our case, the site of HCC was not close to the adrenal gland, and there was no evidence of catecholamine surge. Herein, we report a very rare case of hypertensive crisis without a surge in adrenal hormones after RFA treatment for HCC.

Hemothorax resulting from ruptured hepatocellular carcinoma (HCC) is extremely rare and is generally caused by ruptured intrathoracic metastatic lesions. However, we report a rare case of hemothorax resulting from intrathoracic rupture of primary HCC.

Transarterial chemoembolization (TACE) is a common treatment modality to locally manage hepatocellular carcinoma. Liver abscess and bile duct injury are common complications of TACE. However, hepatobronchial fistula is a rare complication. Herein, we report a case of lung abscess due to hepatobronchial fistula after TACE. A 67-year-old man, who had underwent TACE 6 months ago, presented cough and bile-colored sputum. He was diagnosed with lung abscess and hepatobronchial fistula. We performed endoscopic retrograde cholangiopancreatography; however, there was no improvement in his symptoms. Thereafter, partial hepatectomy and repair of fistula were successively conducted.

Multiple studies have shown that oral antiviral therapies reduced the incidence of hepatocellular carcinoma (HCC) and improved the survival of patients with chronic hepatitis B when compared with that of untreated patients. In particular, entecavir and tenofovir share the qualities of high efficacy in reducing the HBV DNA levels, and they have excellent tolerability and safety. These drugs modified the natural history of liver fibrosis, improve liver function, decrease the incidence of HCC, decrease the need for liver transplantation, and improve survival. Many studies have suggested that long-term antiviral therapy reduces the risk of HCC and liver cirrhosis in patients with chronic hepatitis. The mechanism of these drugs in reducing the risk of HCC is not clear. This article reviews the mechanisms of carcinogenic HBV by conducting a review of the literature on the efficacy of therapy for reducing the risk of HCC. A few recent articles have suggested that tenofovir offers advantages over entecavir in terms of HCC prevention, but these articles have the inherent limitations of observational data. No other head-to-head randomized trials exist. Further randomized studies would help provide stronger evidence of the association between the type of antiviral agent and the HCC outcomes. Only achieving complete viral eradication from the liver will truly decrease the mortality and incidence of HCC.