Cardiovascular risk in chronic hepatitis B patients treated with tenofovir disoproxil fumarate or tenofovir alafenamide

Background/Aims@#Tenofovir disoproxil fumarate (TDF) is known to have a lipid-lowering effect. This is in contrast to tenofovir alafenamide (TAF), which has a lipid-neutral effect. Therefore, concerns have been raised as to whether these differences affect long-term cardiovascular risk. Here, we aimed to evaluate the long-term risk of cardiovascular events in chronic hepatitis B (CHB) patients treated with TAF or TDF. @*Methods@#We retrospectively analyzed 4,124 treatment-naïve CHB patients treated with TDF (n=3,186) or TAF (n=938) between 2012 and 2022. The primary outcome was a composite endpoint of major adverse cardiovascular events (MACE), including myocardial infarction, ischemic stroke, and hospitalization for unstable angina or heart failure. Serial changes in lipid profiles between two treatments were also explored. @*Results@#The median age of the patients was 50.6 years, and 60.6% of the patients were male. At baseline, 486 (11.8%) and 637 (15.4%) of the patients had dyslipidemia and fatty liver, respectively. A total of 42 MACE occurred, with an annual incidence of 0.2%/100 person-years (PYs). At 1, 3, and 5 years, the cumulative risk of MACE was 0.4%, 0.8%, and 1.2% in patients treated with TDF, and 0.2%, 0.7%, and 0.7% in patients treated with TAF, respectively (p=0.538). No significant differences in the risk of MACE were observed between TDF and TAF. A multivariable analysis found that current smoker and a history of cardiovascular events were risk factors associated with an increased risk of MACE. @*Conclusions@#Patients treated with TAF had comparable risks of cardiovascular outcomes, defined as MACE, as patients treated with TDF.

Prediction of Hepatocellular Carcinoma Development in Korean Patients after Hepatitis C Cure with Direct-Acting Antivirals

Background/Aims@#With the wide application of direct-acting antivirals (DAAs) for hepatitis C virus infection, the number of patients achieving a sustained virologic response (SVR) will continue to increase. However, no consensus has been achieved on exempting SVR-achieving patients from hepatocellular carcinoma (HCC) surveillance. @*Methods@#Between 2013 and 2021, 873 Korean patients who achieved SVR following DAA treatment were analyzed. We evaluated the predictive performance of seven noninvasive scores (PAGE-B, modified PAGE-B, Toronto HCC risk index, fibrosis-4, aspartate aminotransferase-toplatelet ratio index, albumin-bilirubin, and age male albumin-bilirubin platelet [aMAP]) at baseline and after SVR. @*Results@#The mean age of the 873 patients (39.3% males) was 59.1 years, and 224 patients (25.7%) had cirrhosis. During 3,542 person-years of follow-up, 44 patients developed HCC, with an annual incidence of 1.24/100 person-years. Male sex (adjusted hazard ratio [AHR], 2.21), cirrhosis (AHR, 7.93), and older age (AHR, 1.05) were associated with a significantly higher HCC risk in multivariate analysis. The performance of all scores at the time of SVR were numerically better than those at baseline as determined by the integrated area under the curve. Timedependent area under the curves for predicting the 3-, 5-, and 7-year risk of HCC after SVR were higher in mPAGE-B (0.778, 0.746, and 0.812, respectively) and aMAP (0.776, 0.747, and 0.790, respectively) systems than others. No patients predicted as low-risk by the aMAP or mPAGE-B systems developed HCC. @*Conclusions@#aMAP and mPAGE-B scores demonstrated the highest predictive performance for de novo HCC in DAA-treated, SVR-achieving patients. Hence, these two systems may be used to identify low-risk patients that can be exempted from HCC surveillance.

Subclassification of advanced-stage hepatocellular carcinoma with macrovascular invasion: combined transarterial chemoembolization and radiotherapy as an alternative first-line treatment

Background@#/Aim: The Barcelona Clinic Liver Cancer (BCLC) guidelines recommend systemic therapy as the only first-line treatment for patients with BCLC stage C hepatocellular carcinoma (HCC) despite its heterogeneity of disease extent. We aimed to identify patients who might benefit from combined transarterial chemoembolization (TACE) and radiation therapy (RT) by subclassifying BCLC stage C. @*Methods@#A total of 1,419 treatment-naïve BCLC stage C patients with macrovascular invasion (MVI) who were treated with combined TACE and RT (n=1,115) or systemic treatment (n=304) were analyzed. The primary outcome was overall survival (OS). Factors associated with OS were identified and assigned points by the Cox model. The patients were subclassified into three groups based on these points. @*Results@#The mean age was 55.4 years, and 87.8% were male. The median OS was 8.3 months. Multivariate analysis revealed a significant association of Child-Pugh B, infiltrative-type tumor or tumor size ≥10 cm, main or bilateral portal vein invasion, and extrahepatic metastasis with poor OS. The sub-classification was categorized into low (point ≤1), intermediate (point=2), and high (point ≥3) risks based on the sum of points (range, 0–4). The OS in the low, intermediate, and high-risk groups was 22.6, 8.2, and 3.8 months, respectively. In the low and intermediate-risk groups, patients treated with combined TACE and RT exhibited significantly longer OS (24.2 and 9.5 months, respectively) than those who received systemic treatment (6.4 and 5.1 months, respectively; P<0.0001). @*Conclusions@#Combined TACE and RT may be considered as a first-line treatment option for HCC patients with MVI when classified into low- and intermediate-risk groups.

The Concept of Health Systems Science and Educational Needs in the Korean Context / 의학교육논단

Physicians should be able to address health-related issues of patients and populations from a multidimensional perspective. Therefore, medical schools have a social responsibility to develop and implement curricula that enable trainees to acquire the competencies needed to improve all aspects of patient care and healthcare delivery. This study explored the concept of health systems science concept as the third pillar of medical education (the other two are basic science and clinical medicine) in the Korean context, as well as related educational needs. The theoretical foundation of health systems science is the biopsychosocial conceptual model, which emphasizes the biological, psychological, and social factors surrounding patients. We concluded that the three domains (core functional, foundational, linking) and 12 subcategories of health systems science proposed by the Association of American Medical Colleges could be applied to Korean medical education. Health systems science education must be emphasized to solve the various healthcare problems facing Korea today and to train physicians to provide medical services in line with society’s needs. Introducing a health systems science curriculum will be challenging in the Korean medical environment, which has traditionally emphasized basic science and clinical medical education. Health systems science education should begin in the basic medical education phase, where physicians’ professional identity is formed, and continue through graduate medical education. It is essential to understand related educational needs, develop curricular content, conduct faculty development programs, and provide financial resources for the development of an integrated curriculum.

Instructional Design for Systems Thinking Education in Health Systems Science / 의학교육논단

Systems thinking, a linking domain of health systems science (HSS), is an approach that investigates specific problems from a holistic perspective. It supports improving patients’ health, fulfilling their health needs, and anticipating issues that threaten patient safety within the healthcare system. It also helps solve problems through critical thinking and reflection. This study aimed to develop an curriculum on systems thinking, explore the effectiveness of the course, and investigate the applicability of HSS education at individual universities. In this study, the ADDIE (Analysis, Design, Development, Implementation, and Evaluation) model was utilized to design, develop, implement, and evaluate an elective course on systems thinking. In the design process, learning outcomes and goals were developed, and educational content, teaching-learning methods, and student evaluation methods were linked. In the development process, class materials and evaluation materials were prepared. In the implementation process, the course was implemented, and the evaluation process analyzed the results of learning performance and curriculum assessments. The evaluation found the following results. First, the students in the study realized the importance of systems thinking and experienced the need for systems thinking through non-medical and medical situations. Second, the students were very satisfied with the learning activities in the course (mean=4.84), and the results of the self-competence evaluation, conducted before and after the course, also showed a significant improvement. This study confirmed the effectiveness of the elective course, and its results can serve as a reference for developing an HSS curriculum .

Safety of direct oral anticoagulants compared to warfarin in cirrhotic patients with atrial fibrillation

Background/Aims@#The safety of direct oral anticoagulants (DOACs) compared with warfarin in patients with both nonvalvular atrial fibrillation (AF) and clinically confirmed liver cirrhosis (LC) has not been well studied. We compared the risk of a major bleeding event between DOAC and warfarin treatments in this patient population. @*Methods@#A total of 238 cirrhotic patients with AF were retrospectively analyzed. The major bleeding event risk was compared between DOAC- and warfarin-treated groups. The median follow-up duration was 5.6 years. @*Results@#Among the 238 study patients with LC and AF, 128 (53.8%) received DOACs and 110 (46.2%) received warfarin. The mean patient age was 68.8 years, and 78.2% were men. A major bleeding event occurred in 10 and 20 patients in the DOAC and warfarin groups, respectively, most commonly caused by gastrointestinal bleeding (70.0%). The cumulative risk of major bleeding did not differ between the groups by log-rank test (p = 0.12). This finding did not change when using 60 propensity score-matched pairs. A multivariable Cox regression model indicated that the concomitant use of antiplatelet agents (adjusted hazard ratio [aHR], 2.06; 95% confidence interval [CI], 1.00 to 4.30; p = 0.048) and presence of esophageal or gastric varices confirmed by endoscopic examination (aHR, 2.31; 95% CI, 1.03 to 5.17; p = 0.04) were associated with major bleeding in the entire cohort. @*Conclusions@#A major bleeding event risk is not increased by DOAC compared with warfarin treatment. Antiplatelet agent use and varices are independently associated with a higher risk of major bleeding during anticoagulation.

Removal of a Trigger Cord Stuck between Bands during Endoscopic Multiple-Band Ligation for Treating Esophageal Variceal Hemorrhage

Endoscopic variceal ligation is the preferred endoscopic treatment method for esophageal variceal bleeding. The incidence of complications such as chest pain, bleeding, stricture formation, and aspiration pneumonia is low. We report a case wherein a malfunctioning multiple-band ligator could have potentially caused damage to the esophageal varices and massive bleeding. The equipment was safely removed using scissors and forceps. To the best of our knowledge, this is the first published report detailing the management of a case of esophageal variceal bleeding.

Stereotactic body radiation therapy for small (≤5 cm) hepatocellular carcinoma not amenable to curative treatment: Results of a single-arm, phase II clinical trial

Background/Aims@#Stereotactic body radiation therapy (SBRT) is used as an alternative ablative treatment in patients with hepatocellular carcinoma (HCC) not suitable for curative treatments. The purpose of this prospective study was to evaluate the long-term efficacy of SBRT for small (≤5 cm) HCCs. @*Methods@#A phase II, single-arm clinical trial on SBRT for small HCCs was conducted at an academic tertiary care center. The planned SBRT dose was 45 Gy with a fraction size of 15-Gy over 3 consecutive days. The primary endpoint was 2-year local control rate. Radiologic responses were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) and the modified RECIST criteria. @*Results@#Between 2013 and 2016, 50 patients (53 lesions) were enrolled, with a median follow-up period of 47.8 months (range, 2.9–70.6). Patients’ age ranged from 41 to 74 years, and 80% were male. Median tumor size was 1.3 cm (range, 0.7–3.1). The 2- and 5-year local control rates were 100% and 97.1%, respectively. The 5-year overall survival rate was 77.6%. Six months after SBRT, radiologic responses were evident in 44 lesions (83%) according to the RECIST criteria and 49 (92.4%) according to the modified RECIST criteria. None of the patients showed grade ≥3 adverse events. @*Conclusions@#SBRT showed excellent results as an ablative treatment for patients with small HCCs while showing minimal toxicities. SBRT can be a good alternative for both curative and salvage intents in patients with HCCs that are unsuitable for curative treatments.

Comparison of surgical resection versus transarterial chemoembolization with additional radiation therapy in patients with hepatocellular carcinoma with portal vein invasion

BACKGROUND/AIMS: Portal vein invasion (PVI) is a poor prognostic factor in patients with hepatocellular carcinoma (HCC). We intended to compare the effects of surgical resection and transarterial chemoembolization (TACE) with additional radiation therapy (RT) in HCC patients with PVI. METHODS: The subjects comprised 43 patients who underwent surgical resection for HCC with PVI without previous treatment and another 43 patients who received TACE followed by RT (TACE+RT) as initial treatment who were matched for Child-Pugh class, tumor size, and extent of PVI. Disease progression and death after the treatment were examined, and progression-free survival (PFS) and overall survival (OS) were compared between groups. Predisposing factors affecting OS were analyzed using univariate and multivariate analyses in HCC patients with PVI. RESULTS: The subjects (Age [51, 24-74; median, range], Sex [81/13; male/female], Etiology [78/1/15; hepatitis B virus {HBV}/ hepatitis C virus {HCV}/non-HBV and non-HCV]) were followed for a median of 17 (2-68) months. There were no differences in clinical or tumor characteristics between the resection and TACE+RT groups. The cumulative PFS was not significantly different between groups. The median PFS was 5.6 and 4.0 months in the resection and TACE+RT groups, respectively. However, the cumulative OS was significantly longer in patients treated with resection than in those treated with TACE+RT (P=0.04). The median OS was 26.9 and 14.2 months in the resection and TACE+RT groups, respectively. Univariate and multivariate analyses revealed that surgical resection was an independent predictive factor for better survival outcome. CONCLUSIONS: Surgical resection might be an effective treatment in HCC patients with PVI.

Methionine Adenosyltransferase 1: A Proteomic Surrogate Marker of Early Hepatocellular Carcinoma in Cirrhotic Patients

BACKGROUND/AIMS: Because there is a lack of effective biomarkers, we aimed to discover proteomic candidate markers for hepatocellular carcinoma (HCC) in cirrhotic patients at the highest-risk of HCC, and to validate the markers. METHODS: We collected tumor tissue from 5 cirrhotics with HCC, and from 5 cirrhotics without HCC, who underwent liver resection or transplantation. These tissue samples were analyzed by 2-dimensional difference gel electrophoresis coupled with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and potential markers were validated at the transcriptional and translational levels. We also performed western blot assays using other blood samples from 10 cirrhotics with HCC and 10 without HCC. RESULTS: Among the 66 distinguishable spots on 2-D gel images, we identified 15 proteins overexpressed more than 1.5 fold in terms of volume ratio in the tumors. Ten of the over-expressed proteins were identified by MALDI-TOF MS; of those, only methionine adenosyltransferase 1 (MAT1), a protein specific for liver, and acyl-CoA dehydrogenase were significantly up-regulated in tumors in further immunoblotting analyses (Ps<0.05). There was no between-pair difference in MAT1 mRNA measured by real-time polymerase chain reaction (P=0.96). However, in western blots of serum samples, distinct MAT1 bands were observed in all 10 HCC patients, but in only 2 of the non-HCC patients. CONCLUSIONS: MAT1 is a potential marker for surveillance in cirrhotic patients with and without prior HCC.

Budd-Chiari syndrome with antiphospholipid syndrome and systemic lupus erythematosus in a patient with Klinefelter's syndrome / 영남의대학술지

Klinefelter's syndrome is the most common congenital abnormality that causes primary hypogonadism. It is associated with diseases that predominantly affect women, such as systemic lupus erythematosus (SLE), and it can sometimes cause veno-occlusive disease. We experienced a case of Budd-Chiari syndrome (BCS) in a 33-year-old man with Klinefelter's syndrome presented with hematemesis and edema in both lower extremities. The clinical and laboratory findings were compatible with SLE, antiphospholipid syndrome, and BCS. To the best of our knowledge, this is the first case report to describe a simultaneous presentation of these four clinical syndromes in a single patient.

Surgical Removal of Migrated Coil after Embolization of Jejunal Variceal Bleeding: A Case Report / 대한소화기학회지

Jejunal variceal bleeding is less common compared with esophagogastric varices in patients with portal hypertension. However, jejunal variceal bleeding can be fatal without treatment. Treatments include surgery, transjugular intrahepatic porto-systemic shunt (TIPS), endoscopic sclerotherapy, percutaneous coil embolization, and balloon-occluded retrograde transvenous obliteration (BRTO). Percutaneous coil embolization can be considered as an alternative treatment option for those where endoscopic sclerotherapy, surgery, TIPS or BRTO are not possible. Complications of percutaneous coil embolization have been reported, including coil migration. Herein, we report a case of migration of the coil into the jejunal lumen after percutaneous coil embolization for jejunal variceal bleeding. The migrated coil was successfully removed using surgery.

Budd-Chiari syndrome with antiphospholipid syndrome and systemic lupus erythematosus in a patient with Klinefelter's syndrome / 영남의대학술지

Klinefelter's syndrome is the most common congenital abnormality that causes primary hypogonadism. It is associated with diseases that predominantly affect women, such as systemic lupus erythematosus (SLE), and it can sometimes cause veno-occlusive disease. We experienced a case of Budd-Chiari syndrome (BCS) in a 33-year-old man with Klinefelter's syndrome presented with hematemesis and edema in both lower extremities. The clinical and laboratory findings were compatible with SLE, antiphospholipid syndrome, and BCS. To the best of our knowledge, this is the first case report to describe a simultaneous presentation of these four clinical syndromes in a single patient.

Clinical features and outcomes of patients with hepatocellular carcinoma complicated with bile duct invasion

BACKGROUND/AIMS: Little is known about the treatment or outcomes of hepatocellular carcinoma (HCC) complicated with bile duct invasion. METHODS: A total of 247 consecutive HCC patients with bile duct invasion at initial diagnosis were retrospectively included. RESULTS: The majority of patients had Barcelona Clinic Liver Cancer (BCLC) stage C HCC (66.8%). Portal vein tumor thrombosis was present in 166 (67.2%) patients. Median survival was 4.1 months. Various modalities of treatment were initially employed including surgical resection (10.9%), repeated transarterial chemoembolization (TACE) (42.5%), and conservative management (42.9%). Among the patients with obstructive jaundice (n=88), successful biliary drainage was associated with better overall survival rate. Among the patients with BCLC stage C, overall survival differed depending on the initial treatment for HCC; surgical resection, TACE, systemic chemotherapy, and conservative management showed overall survival rates of 11.5, 6.0 ,2.4, and 1.6 months, respectively. After adjusting for confounders, surgical resection and repeated TACE were significant prognostic factors for HCC patients with bile duct invasion (hazard ratios 0.47 and 0.39, Ps <0.001, respectively). CONCLUSIONS: The survival of HCC patients with bile duct invasion at initial diagnosis is generally poor. However, aggressive treatments for HCC such as resection or biliary drainage may be beneficial therapeutic options for patients with preserved liver function.

Vitiligo Lesions Stopped Spreading after Oral Cyclosporine in a Vitiligo Patient Who Shows Systemic Steroid Resistance / 대한피부과학회지

No abstract available.

No association between the IL28B SNP and response to peginterferon plus ribavirin combination treatment in Korean chronic hepatitis C patients

BACKGROUND/AIMS: There are few available data regarding the association between the single nucleotide polymorphisms (SNPs) of the gene encoding interleukin 28B (IL28B) and a sustained virologic response (SVR) to peginterferon (PEG-IFN) plus ribavirin (RBV) therapy in Korean chronic hepatitis C patients. METHODS: This was a retrospective cohort study of 156 patients with chronic hepatitis C virus (HCV) infection who received combination treatment of PEG-IFN plus RBV. Blood samples from these patients were analyzed to identify the IL28B SNPs at rs12979860, rs12980275, rs8099917, and rs8103142. Association analyses were performed to evaluate the relationships between each IL28B SNP and SVRs. RESULTS: Seventy six patients with HCV genotype 1 and 80 with genotype non-1 were enrolled. The frequencies of rs12979860 CC and CT genotypes were 90.4% and 9.6%, respectively; those of rs12980275 AA and AG genotypes were 87.2% and 12.8%, respectively; those of rs8099917 TT and TG genotypes were 92.3% and 7.7%, respectively; and those of rs8103142 TT and CT genotypes were 90.4% and 9.6%, respectively. Among the patients with HCV genotype 1, the SVR rates were 69.7% and 80.0% for rs12979860 CC and CT, respectively (P=0.71). Among the HCV genotype non-1 patients, SVR rates were 88.0% and 100% for rs12979860 CC and CT (P=1.00), respectively. CONCLUSIONS: Genotypes of the IL28B SNP that are known to be favorable were present in most of the Korean patients with chronic hepatitis C in this study. Moreover, the IL28B SNP did not influence the SVR rate in either the HCV genotype 1 or non-1 patients. Therefore, IL28B SNP analysis might be not useful for the initial assessment, prediction of treatment outcomes, or treatment decision-making of Korean chronic hepatitis C patients.

A Case of Primaquine-Induced Acute Liver Failure / 대한내과학회지

Primaquine was approved for treatment of malaria in 1952 by the United States Food and Drug Administration (FDA). It has remained the only FDA-licensed drug capable of clearing the intra-hepatic schizonts and hypnozoites of Plasmodium vivax. It is associated with serious hazards and side effects, such as hemolytic anemia and methemoglobinemia. However, there is no report of primaquine causing liver injury in Korea. We describe a case of acute liver failure following primaquine overdose in a 19-year-old man.

Role of 15-hydroxyprostaglandin dehydrogenase down-regulation on the prognosis of hepatocellular carcinoma

BACKGROUND/AIMS: The role of prostaglandin E2 (PGE2) in the modulation of cell growth is well established in colorectal cancer. The aim of this study was to elucidate the significance of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) down-regulation on the prognosis of hepatocellular carcinoma (HCC) patients. METHODS: The expression of 15-PGDH in HCC cell lines and resected HCC tissues was investigated, and the correlation between 15-PGDH expression and HCC cell-line proliferation and patient survival was explored. RESULTS: The interleukin-1-beta-induced suppression of 15-PGDH did not change the proliferation of PLC and Huh-7 cells in the MTS [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The induction of 15-PGDH by transfection in HepG2 cells without baseline 15-PGDH expression was suppressed at day 2 of proliferation compared with empty-vector transfection, but there was no difference at day 3. Among the 153 patients who received curative HCC resection between 2003 and 2004 at our institution, 15-PGDH expression was observed in resected HCC tissues in 56 (36.6%), but the 5-year survival rate did not differ from that of the remaining 97 non-15-PGDH-expressing patients (57.1% vs 59.8%; P=0.93). Among 50 patients who exhibited baseline 15-PGDH expression in adjacent nontumor liver tissues, 28 (56%) exhibited a reduction in 15-PGDH expression score in HCC tissues, and there was a trend toward fewer long-term survivors compared with the remaining 22 with the same or increment in their 15-PGDH expression score in HCC tissues. CONCLUSIONS: The prognostic significance of 15-PGDH down-regulation in HCC was not established in this study. However, maintenance of 15-PGDH expression could be a potential therapeutic target for a subgroup of HCC patients with baseline 15-PGDH expression in adjacent nontumor liver tissue.

Could HBx Protein Expression Affect Signal Pathway Inhibition by Gefitinib or Selumetinib, a MEK Inhibitor, in Hepatocellular Carcinoma Cell Lines?

Hepatitis B virus X (HBx) protein has been known to play an important role in development of hepatocellular carcinoma (HCC). The aim of this study is to find out whether HBx protein expression affects antiproliferative effect of an epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitor and a MEK inhibitor in HepG2 and Huh-7 cell lines. We established HepG2 and Huh-7 cells transfected stably with HBx gene. HBx protein expression increased pERK and pAkt expression as well as beta-catenin activity in both cells. Gefitinib (EGFR-TK inhibitor) inhibited pERK and pAkt expression and beta-catenin activity in both cells. Selumetinib (MEK inhibitor) reduced pERK level and beta-catenin activity but pAkt expression was rather elevated by selumetinib in these cells. Reduction of pERK levels was much stronger with selumetinib than gefitinib in both cells. The antiproliferative efficacy of selumetinib was more potent than that of gefitinib. However, the antiproliferative effect of gefitinib, as well as selumetinib, was not different between cell lines with or without HBx expression. Signal pathway activation by HBx might not be strong enough to attenuate the antiproliferative effect of EGFR-TK inhibitor. Future experiments are needed to understand the role of HBx protein expression in HCC treatment using molecular targeting agent.

Prognostic value of serum osteopontin in hepatocellular carcinoma patients treated with transarterial chemoembolization / 대한간학회지

BACKGROUND/AIMS: Osteopontin (OPN) is overexpressed in hepatocellular carcinoma (HCC) with postoperative recurrence or extrahepatic metastasis. However, its prognostic value in patients treated with transarterial chemoembolization (TACE) is unclear. We investigated the utility of serum OPN levels and changes therein as prognostic markers in HCC patients who have received TACE. METHODS: Forty-six patients with HCC were enrolled. Serum OPN levels were measured before and 4 weeks after TACE. Serum biochemistry and computed tomography (CT) scans were analyzed. We evaluated baseline serum OPN levels and subsequent changes therein in relation to tumor responses and cumulative survival rates following TACE. A decreasing pattern was defined as a decrease after TACE of more than 10% relative to baseline levels. A "responder" was defined as a patient who exhibited a tumor necrosis rate of higher than 50% on the follow-up CT scan. RESULTS: Higher initial serum OPN levels were associated with a large tumor, portal vein invasion, and an advanced tumor stage. Patients who had lower initial serum OPN levels and those who exhibited decreasing patterns after TACE tended to have more favorable tumor responses (P=0.043 and 0.055, respectively) and exhibited better cumulative survival rates (P=0.036 and 0.030, respectively). However, the initial serum OPN level and subsequent changes in serum OPN levels were not independent predictors for survival on multivariate analysis. CONCLUSIONS: Serum OPN levels were significantly higher in patients with advanced HCC. In addition, HCC patients with low pretreatment serum OPN levels and those for whom serum OPN declined following TACE exhibited better tumor responses and survived for longer.