The efficacy of treatment for hepatocellular carcinoma in elderly patients

Background@#/Aim: Despite the increasing proportion of elderly patients with hepatocellular carcinoma (HCC) over time, treatment efficacy in this population is not well established. @*Methods@#Data collected from the Korean Primary Liver Cancer Registry, a representative cohort of patients newly diagnosed with HCC in Korea between 2008 and 2017, were analyzed. Overall survival (OS) according to tumor stage and treatment modality was compared between elderly and non-elderly patients with HCC. @*Results@#Among 15,186 study patients, 5,829 (38.4%) were elderly. A larger proportion of elderly patients did not receive any treatment for HCC than non-elderly patients (25.2% vs. 16.7%). However, OS was significantly better in elderly patients who received treatment compared to those who did not (median, 38.6 vs. 22.3 months; P0.05). After IPTW, in intermediate-stage HCC, surgery (median, 66.0 vs. 90.3 months) and transarterial therapy (median, 36.5 vs. 37.2 months), and in advanced-stage HCC, transarterial (median, 25.3 vs. 26.3 months) and systemic therapy (median, 25.3 vs. 26.3 months) yielded comparable OS between the elderly and non-elderly HCC patients (all P>0.05). @*Conclusions@#Personalized treatments tailored to individual patients can improve the prognosis of elderly patients with HCC to a level comparable to that of non-elderly patients.

Loco-regional therapies competing with radiofrequency ablation in potential indications for hepatocellular carcinoma: a network meta-analysis

Background/Aims@#There is no clear consensus on the relative ranking of interventional and radiation techniques with indications similar to those of radiofrequency ablation (RFA) for the treatment of early hepatocellular carcinoma (HCC). We used a network meta-analysis to compare the efficacy of non-surgical treatments for early HCC. @*Methods@#We searched databases for randomized trials assessing the efficacy of loco-regional treatments for HCCs ≤5 cm with no extrahepatic spread or portal invasion. The primary outcome was the pooled hazard ratio (HR) for overall survival (OS), and secondary outcomes included overall and local progression-free survival (PFS). A frequentist network meta-analysis was performed, and the relative ranking of therapies was assessed with P-scores. @*Results@#Nineteen studies comparing 11 different strategies in 2,793 patients were included. Chemoembolization plus RFA improved OS better than RFA alone (HR 0.52, 95% confidence interval [CI] 0.33–0.82; P-score=0.951). Cryoablation, microwave ablation, laser ablation, and proton beam therapy had similar effects on OS compared with RFA. For overall PFS, but not local PFS, only chemoembolization plus RFA performed significantly better than RFA (HR 0.61, 95% CI 0.42–0.88; P-score=0.964). Injection of percutaneous ethanol or acetic acid was significantly less effective than RFA for all measured outcomes, while no differences in progression outcomes were identified for other therapies included in the network. @*Conclusions@#Our results suggest that chemoembolization combined with RFA is the best option for local treatment of early HCC. Cases with potential contraindications for RFA may benefit from a tailored approach using thermal or radiation modalities.

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.

Cervicocerebral atherosclerosis and its hepatic and coronary risk factors in patients with liver cirrhosis

Background/Aims@#We aimed to investigate the silent atherosclerotic burden of cervicocephalic vessels in cirrhotic patients compared with the general population, as well as the relevant risk factors including coronary parameters. @*Methods@#This study included 993 stroke-free patients with liver cirrhosis (LC) who underwent magnetic resonance angiography (MRA) of the head and neck as a pre-liver transplant assessment and 6,099 health checkup participants who underwent MRA examination. The two cohorts were matched for cerebrovascular risk factors, and the prevalence of atherosclerosis in major intracranial and extracranial arteries was compared in 755 matched pairs. Moreover, traditional, hepatic, and coronary variables related to cerebral atherosclerosis were assessed in cirrhotic patients. @*Results@#Overall, intracranial atherosclerosis was significantly less prevalent in the LC group than in the matched control group (2.3% vs. 5.4%, P=0.002), whereas the prevalence of extracranial atherosclerosis was similar (4.4% vs. 5.8%, P=0.242). These results were maintained in multivariate analyses of the pooled samples, with corresponding adjusted odds ratios [ORs] of LC of 0.56 and 0.77 (95% confidence intervals [CIs], 0.36–0.88 and 0.55–1.09). In the LC group, lower platelet count was inversely correlated with intracranial atherosclerosis (adjusted OR, 0.31; 95% CI, 0.13–0.76). Coronary artery calcium (CAC) score ≥100 was the only predictive factor for both intracranial and extracranial atherosclerosis (adjusted ORs, 4.06 and 5.43, respectively). @*Conclusions@#LC confers protection against intracranial atherosclerosis, and thrombocytopenia may be involved in this protective effect. High CAC score could serve as a potential surrogate for cervicocerebral vascular screening in asymptomatic cirrhotic patients.

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.

Impact of the Liver Imaging Reporting and Data System on Research Studies of Diagnosing Hepatocellular Carcinoma Using MRI

Objective@#Since its introduction in 2011, the CT/MRI diagnostic Liver Imaging Reporting and Data System (LI-RADS) has been updated in 2014, 2017, and 2018. We evaluated the impact of CT/MRI diagnostic LI-RADS on liver MRI research methodology for the diagnosis of hepatocellular carcinoma (HCC). @*Materials and Methods@#The MEDLINE, EMBASE, and Cochrane databases were searched for original articles reporting the diagnostic performance of liver MRI for HCC between 2011 and 2019. The MRI techniques, image analysis methods, and diagnostic criteria for HCC used in each study were investigated. The studies were classified into three groups according to the year of publication (2011–2013, 2014–2016, and 2017–2019). We compared the percentage of studies adopting MRI techniques recommended by LI-RADS, image analysis methods in accordance with the lexicon defined in LI-RADS, and diagnostic criteria endorsed by LI-RADS. We compared the pooled sensitivity and specificity between studies that used the LI-RADS and those that did not. @*Results@#This systematic review included 179 studies. The percentages of studies using imaging techniques recommended by LI-RADS were 77.8% for 2011–2013, 85.7% for 2014–2016, and 84.2% for 2017–2019, with no significant difference (p = 0.951). After the introduction of LI-RADS, the percentages of studies following the LI-RADS lexicon were 0.0%, 18.4%, and 56.6% in the respective periods (p < 0.001), while the percentages of studies using the LI-RADS diagnostic imaging criteria were 0.0%, 22.9%, and 60.7%, respectively (p < 0.001). Studies that did not use the LI-RADS and those that used the LIRADS version 2018 showed no significant difference in sensitivity and specificity (86.3% vs. 77.7%, p = 0.102 and 91.4% vs. 89.9%, p = 0.770, respectively), with some difference in heterogeneity (I2 = 94.3% vs. 86.7% in sensitivity and I2 = 86.6% vs. 53.2% in specificity). @*Conclusion@#LI-RADS imparted significant changes in the image analysis methods and diagnostic criteria used in liver MRI research for the diagnosis of HCC.

The effects of immune checkpoint modulators on the clinical course of patients with resectable hepatocellular carcinoma

Background@#/Aim: Immune checkpoint proteins regulating T-cell mediated anti-tumor immunity have been reported to affect clinical outcomes in multiple malignancies. This study aimed to investigate the prognostic effect of histological expression of immune checkpoint proteins in patients with resected hepatocellular carcinoma (HCC). @*Methods@#A total of 221 patients with HCC who underwent curative resection were included. Expression of programmed-cell death ligand-1 (PD-L1) in tumor cells (tPD-L1) and tumor infiltrating mononuclear cells (TIMCs) (iPD-L1), programmed-cell death-1 in TIMCs (iPD-1), and cytotoxic T lymphocyte antigen-4 in TIMCs (iCTLA-4) were measured immunohistochemically. @*Results@#Histo-positivity for iCTLA-4, iPD-1, iPD-L1, and tPD-L1 was 32.1%, 42.5%, 35.3%, and 14.9%, respectively. Multivariate logistic analyses revealed that male sex and tumor >5 cm were variables related to iCTLA-4 positivity (odds ratio [OR], 0.46 and 1.94, respectively; P<0.05). Poor differentiation was related to PD-L1 expression in both tumor cells and TIMCs (OR, 2.88 and 3.46, respectively; P<0.05). Microvascular invasion was significantly associated only with iPD-L1 (OR, 2.24; P<0.05). In time-dependent outcome analyses, expression of immune checkpoint proteins in TIMCs (i.e., iCTLA-4, iPD-1, and iPD-L1) was significantly related to longer overall survival and non-cancer-related survival (all P<0.05), but not to time-to-recurrence or cancer-specific deaths. Concurrent activation of the PD-1:PD-L1 and CTLA-4 pathways predicted improved outcomes in terms of overall survival and non-cancer related survival (P=0.06 and P=0.03, respectively). @*Conclusions@#Immune checkpoint proteins upregulated in TIMCs in HCC tissues have individual and additive effects in prolonging the survival of patients, specifically in terms of survival not related to cancer recurrence.

Diagnostic performance of ultrasonography-guided core-needle biopsy according to MRI LI-RADS diagnostic categories

Purpose@#According to the American Association for the Study of Liver Diseases (AASLD) guidelines, biopsy is a diagnostic option for focal hepatic lesions depending on the Liver Imaging Reporting and Data System (LI-RADS) category. We evaluated the diagnostic performance of ultrasonography-guided core-needle biopsy (CNB) according to LI-RADS categories. @*Methods@#A total of 145 High-risk patients for hepatocellular carcinoma (HCC) who underwent magnetic resonance imaging (MRI) followed by CNB for a focal hepatic lesion preoperatively were retrospectively enrolled. Focal hepatic lesions on MRI were evaluated according to LI-RADS version 2018. Pathologic results were categorized into HCC, non-HCC malignancies, and benignity. The categorization was defined as correct when the CNB pathology and surgical pathology reports were identical. Nondiagnostic results were defined as inadequate CNB pathology findings for a specific diagnosis. The proportion of correct categorizations was calculated for each LI-RADS category, excluding nondiagnostic results. @*Results@#After excluding 16 nondiagnostic results, 131 lesions were analyzed (45 LR-5, 24 LR-4, 4 LR-3, and 58 LR-M). All LR-5 lesions were HCC, and CNB correctly categorized 97.8% (44/45) of LR-5 lesions. CNB correctly categorized all 24 LR-4 lesions, 16.7% (4/24) of which were non-HCC malignancies. All LR-M lesions were malignant, and 62.1% (36/58) were non-HCC malignancies. CNB correctly categorized 93.1% (54/58) of LR-M lesions, and 12.5% (3/24) of lesions with CNB results of HCC were confirmed as non-HCC malignancies. @*Conclusion@#In agreement with AASLD guidelines, CNB could be helpful for LR-4 lesions, but is unnecessary for LR-5 lesions. In LR-M lesions, CNB results of HCC did not exclude non-HCC malignancy.

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.

The quick sepsis-related organ failure score has limited value for predicting adverse outcomes in sepsis patients with liver cirrhosis

Background/Aims@#The quick Sepsis-related Organ Failure Assessment (qSOFA) is a newly developed risk stratification tool, which has been presented along with a new sepsis definition, to classify infected patients outside of the intensive care unit (ICU). We evaluated the clinical usefulness of qSOFA for predicting adverse outcomes in sepsis patients with liver cirrhosis. @*Methods@#We performed a retrospective cohort study to assess the utility of qSOFA in sepsis patients with liver cirrhosis for whom medical emergency teams (METs) were activated in general wards at an academic tertiary care hospital between March 2008 and December 2015. qSOFA, Systemic inflammatory response syndrome (SIRS), modified early warning score (MEWS), and sequential (sepsis- related) organ failure assessment (SOFA) scores were calculated according to data at MET activation. @*Results@#Of 188 patients, 69 (36.7%) had a qSOFA score of 0 or 1 point and 119 (63.3%) had ≥ 2 points. The areas under the receiver operating characteristic curve (AUROC) for ICU transfer on the SOFA (AUROC, 0.691; 95% confidence interval [CI], 0.615 to 0.767) or MEWS (AUROC, 0.663; 95% CI, 0.586 to 0.739) were significantly higher compared to those for qSOFA (AUROC, 0.589; 95% CI, 0.507 to 0.671) or SIRS (AUROC, 0.533; 95% CI, 0.451 to 0.616). @*Conclusions@#Our findings suggest that qSOFA score may have limited utility in predicting adverse outcomes in sepsis patients with liver cirrhosis at MET activation. Either MEWS or another screening tool is needed for detecting early sepsis in these patients.

Evaluation of Drug-Induced Liver Injury Developed During Hospitalization Using Electronic Health Record (EHR)-Based Algorithm

PURPOSE: The incidence of drug-induced liver injury (DILI) has been increasing; however, few algorithms are available to identify DILI in electronic health records (EHRs). We aimed to identify and evaluate DILI with an appropriate screening algorithm.METHODS: We collected data from 3 university hospitals between June 2015 and May 2016 using our newly developed algorithm for identifying DILI. Among patients with alanine transferase (ALT) ≤ 120 IU/L and total bilirubin (TB) ≤ 2.4 mg/dL in blood test results within 48 hours of admission, those who either had 1) ALT > 120 IU/L and TB > 2.4 mg/dL or 2) ALT > 200 IU/L at least once during hospitalization were identified. After excluding patients with liver disease-related diagnosis at discharge, medical records were retrospectively reviewed to evaluate epidemiological characteristics of DILI.RESULTS: The total number of inpatients was 256,598, of whom 1,100 (0.43%) were selected by the algorithm as suspected DILI. Subsequently, 365 cases (0.14% of total inpatients, 95% confidence interval, 0.13–0.16) were identified as DILI, yielding a positive predictive value of 33.1%. Antibiotics (n = 214, 47.2%) were the major class of causative drug followed by chemotherapeutic agents (n = 87, 19.2%). The most common causative drug was piperacillin-tazobactam (n = 38, 8.4%); the incidence of DILI by individual agent was highest for methotrexate (19.4 cases/1,000 patients administered the drug). Common reasons for excluding suspected DILI cases were ischemic hepatitis and postoperative liver dysfunction.CONCLUSIONS: Using our EHR-based algorithm, we identified that approximately 0.14% of patients developed DILI during hospitalization. Further studies are needed to modify criteria for more accurate identification of DILI.

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.

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.

Fibroblast growth factor receptor isotype expression and its association with overall survival in patients with hepatocellular carcinoma

BACKGROUND/AIMS: Fibroblast growth factor signaling is involved in hepatocarcinogenesis. The aim of this study was to determine the fibroblast growth factor receptor (FGFR) isotype expression in hepatocellular carcinoma (HCC) and neighboring nonneoplastic liver tissue, and elucidate its prognostic implications. METHODS: Immunohistochemical staining of FGFR1, -2, -3, and -4 was performed in the HCCs and paired neighboring nonneoplastic liver tissue of 870 HCC patients who underwent hepatic resection. Of these, clinical data for 153 patients who underwent curative resection as a primary therapy were reviewed, and the relationship between FGFR isotype expression and overall survival was evaluated (development set). This association was also validated in 73 independent samples (validation set) by Western blot analysis. RESULTS: FGFR1, -2, -3, and -4 were expressed in 5.3%, 11.1%, 3.8%, and 52.7% of HCCs, respectively. Among the development set of 153 patients, FGFR2 positivity in HCC was associated with a significantly shorter overall survival (5-year survival rate, 35.3% vs. 61.8%; P=0.02). FGFR2 expression in HCC was an independent predictor of a poor postsurgical prognosis (hazard ratio, 2.10; P=0.02) in the development set. However, the corresponding findings were not statistically significant in the validation set. CONCLUSIONS: FGFR2 expression in HCC could be a prognostic indicator of postsurgical survival.

A case of primary hepatic actinomycosis: an enigmatic inflammatory lesion of the liver

Primary hepatic actinomycosis is one of the chronic abscess-forming infections of the liver. Accurate diagnosis is frequently delayed due to its indolent course and nonspecific clinical and radiological manifestations. We report a case of a 57-year-old man presenting with asymptomatic multiple hepatic masses on follow-up abdominal computed tomography performed 1 year after stomach cancer surgery. Although a percutaneous liver biopsy procedure was conducted twice in order to obtain confirmative pathology, only a nonspecific organizing abscess with plasma cell infiltration was revealed, without identification of any organism in the tissue cultures. Ultimately, actinomycosis was diagnosed following the detection of sulfur granules on open surgical biopsied tissue. This case suggests that primary hepatic actinomycosis should be considered as one of the possible causes for enigmatic inflammatory lesions of the liver.

Focal type of peliosis hepatis

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.

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.

A Case of Metastatic Hepatocellular Carcinoma of the Orbit / 영남의대학술지

Orbital metastasis from hepatocellular carcinoma is very rare, with only 14 biopsy-proven cases from hepa tocellular carcinoma cases reported in English literature and three cases reported in Korea. Common symptoms of orbital metastasis are proptosis, visual loss, ocular pain and oculomotor dysfunction. For its precise diagnosis, we can perform fine needle aspiration biopsy, orbit CT or MRI, and ultrasonography. Radiotherapy is the mainstay in the treatment of orbital metastasis. In addition, chemotherapy, hormonal therapy and surgical intervention can play a role in the treatment of orbital metastasis according to the primary cancer and symptoms. However, the prognosis of orbital metastasis is poor. We report herein a rare case of a patient with orbital metastasis from hepatocellular carcinoma, which was treated with various modalities that included resection, and who had good clinical and radiological responses to radiation therapy and sorafenib (Nexavar, Bayer HealthCare).