Showing papers by "Do Young Kim published in 2014"

Controlled attenuation parameter (CAP) for detection of hepatic steatosis in patients with chronic liver diseases: a prospective study of a native Korean population

Abstract: Background Controlled attenuation parameter (CAP) is a non-invasive method of measuring hepatic steatosis using a process based on transient elastography. We investigated the diagnostic accuracy of CAP in detecting hepatic steatosis in patients with chronic liver disease (CLD). Methods A total of 135 patients with CLD who underwent liver biopsy and CAP were consecutively enrolled in this prospective study. The performance of CAP for detection of hepatic steatosis compared with liver biopsy was calculated using area under receiver operating characteristics curves (AUROC). Steatosis was categorized into S0 ( 66% of hepatocytes). Results Male gender predominated (n = 87, 64%) and the median age was 51 years. The aetiologies of CLD included non-alcoholic fatty liver disease (n = 56, 41.5%) and chronic viral hepatitis because of hepatitis B (n = 47, 34.8%) and C (n = 12, 8.9%). Steatosis repartition was: S0 31.1% (n = 42), S1 43.7% (n = 59), S2 18.5% (n = 25) and S3 6.7% (n = 9) respectively. In the multivariate analysis, steatosis grade and body mass index were independently associated with CAP (all P < 0.001), whereas fibrosis stage and activity grade were not. The AUROCs of CAP were 0.885 for ≥S1 (sensitivity 73.1%, specificity 95.2%), 0.894 for ≥S2 (sensitivity 82.4%, specificity 86.1%) and 0.800 for S3 (sensitivity 77.8%, specificity 84.1%). The optimal cut-off CAP values that maximized the Youden index were 250 dB/m (≥S1), 299 dB/m (≥S2), and 327 dB/m (=S3) respectively. Conclusions Our data showed that CAP had high diagnostic accuracy for detecting hepatic steatosis in patients with CLD and suggested that CAP is also applicable for Asian patients.

Surgical Resection After Down-Staging of Locally Advanced Hepatocellular Carcinoma by Localized Concurrent Chemoradiotherapy

Abstract: This study evaluated the down-staging efficacy and impact on resectability of concurrent chemoradiotherapy (CCRT) followed by hepatic arterial infusion chemotherapy (HAIC) in locally advanced hepatocellular carcinoma, and identified prognostic factors of disease-free survival (DFS) and overall survival (OS) after curative resection. DFS and OS were investigated using clinicopathologic variables. Functional residual liver volume (FRLV) was assessed before CCRT and again before surgery in patients with major hepatectomy. Tumor marker response was defined as elevated tumor marker levels at diagnosis but levels below cutoff values before surgery (α-fetoprotein < 20 ng/mL, protein induced by vitamin K absence or antagonist-II < 40 mAU/mL). Of 243 patients who received CCRT followed by HAIC between 2005 and 2011, 41 (16.9 %) underwent curative resection. Tumor down-staging was demonstrated in 32 (78 %) of the resected patients. FRLV significantly increased from 47.5 to 69.9 % before surgery in patients who underwent major hepatectomy. In addition, the OS of the curative resection group was significantly higher than the OS of the CCRT followed by HAIC alone group (49.6 vs. 9.8 % at 5-year survival; p < 0.001). By multivariate analysis, the poor prognostic factors for DFS after curative resection were tumor marker non-response and the presence of a satellite nodule; however, tumor marker non-response was the only independent poor prognostic factor of OS. CCRT followed by HAIC increased resectability by down-staging tumors and increasing FRLV. Curative resection may provide good long-term survival in tumor marker responders who undergo CCRT followed by HAIC.

Histological subclassification of cirrhosis can predict recurrence after curative resection of hepatocellular carcinoma

Abstract: Background Recurrence of hepatocellular carcinoma (HCC) after curative resection continues to be a major cause of death. This prospective study is designed to investigate whether histological subclassification of cirrhosis using the Laennec system could predict recurrence in patients with hepatitis B virus (HBV)-related HCC after curative resection. Methods Patients with HBV-related HCC who underwent curative resection and showed Laennec stage 3 to 4 were enrolled and the cases with stage 4 were subclassified histologically into three groups (stages 4A, 4B and 4C) according to the Laennec system. Between February 2006 and August 2009, 92 patients were recruited. Results Stage 3, 4A, 4B and 4C were identified in 24 (26.1%), 15 (16.3%), 43 (46.7%) and 10 (10.9%) patients respectively. The cumulative incidence rates of recurrence at 1, 2 and 3 years were 24.2%, 40.5% and 55.1% respectively. On multivariate analysis, serum albumin [hazard ratio (HR), 0.528; 95% confidence interval (CI), 0.312–0.891; P = 0.017] and Edmondson–Steiner grade III–IV (HR, 3.456; 95% CI, 1.123–10.517; P = 0.031) were significantly correlated with early recurrence (<1 year), whereas stage 4C (HR, 5.426; 95% CI, 1.030–28.598; P = 0.046) was the only independent risk factor for late recurrence (≥1 year). Conclusions Histological subclassification of cirrhosis using the Laennec system is a significant predictor of late recurrence in patients with HBV-related HCC after curative resection.

Emerging therapies for hepatitis C.

Abstract: The combination of pegylated interferon (PEG-IFN) and ribavirin (RBV), the current therapy for hepatitis C virus (HCV) infection, has saved the lives of many HCV-infected patients. Direct-acting antivirals (DAAs) target several sites of HCV nonstructural proteins, resulting in the cessation of viral replication. The first NS3/4A protease inhibitors consisted of boceprevir and telaprevir, which have shown superior efficacy against genotype 1 HCV infection when combined with PEG-IFN/RBV compared with the standard therapy in both treatment-naive and -experienced patients. Simeprevir, faldaprevir, and asunaprevir are second-wave, first-generation NS3/4A inhibitors that have already been or will soon be approved. Second-generation protease inhibitors are in clinical trials. Daclatasvir is the first approved DAA belonging to the class of NS5A replication complex inhibitors. The potency of daclatasvir is very high, and this drug is an important and essential component of combination regimens for all genotypes. Sofosbuvir, the first approved NS5B polymerase inhibitor, is characterized by high potency and genetic barriers to resistance. Sofosbuvir combined with RBV achieved an interferon-free regimen in genotype 2 or 3 patients with a reduced treatment duration. It can also be used in combination with PEG-IFN/RBV in genotype 1 patients for 12 weeks. DAAs have provided new hope for curing HCV infections with a short treatment duration and acceptable adverse events.

Impact of spontaneous hepatocellular carcinoma rupture on recurrence pattern and long-term surgical outcomes after partial hepatectomy

Abstract: The clinical significance of spontaneous hepatocellular carcinoma (HCC) rupture association with recurrence pattern and long-term surgical outcomes remains under debate We investigated the impact of spontaneous HCC rupture on recurrence pattern and long-term surgical outcomes after partial hepatectomy From 2000 to 2012, 119 patients with diagnosed ruptured HCC were reviewed To compare outcomes between staged hepatectomy in spontaneously ruptured HCC and hepatectomy in non-ruptured HCC, we performed propensity score-matching to adjust for significant differences in patient characteristics Overall survival, disease-free survival, and recurrence pattern were compared between the matched groups Forty-four patients with newly diagnosed ruptured HCC and Child A class were initially treated with transcatheter arterial embolization for hemostasis Three patients underwent emergency laparotomy, 18 underwent staged hepatectomy, and 23 received transarterial chemoembolization (TACE) alone after transcatheter arterial embolization Among the 23 patients treated with TACE alone, 10 had resectable tumors The staged hepatectomy group shows significantly higher overall survival with TACE alone than the resectable tumor group (P < 0001) After propensity score-matching, overall survival, disease-free survival, and recurrence pattern were not significantly different between the ruptured HCC with staged hepatectomy group and the non-ruptured HCC with hepatectomy group Peritoneal recurrence rates were similar at 143 % versus 100 %, respectively (P = 0632) Patients with spontaneously ruptured HCC with staged hepatectomy show comparable long-term survival and recurrence pattern as patients with non-ruptured HCC having similar tumor characteristics and liver functional status Thus, spontaneous HCC rupture may not increase peritoneal recurrence and decrease long-term survival after partial hepatectomy

Factors Affecting the Accuracy of Controlled Attenuation Parameter (CAP) in Assessing Hepatic Steatosis in Patients with Chronic Liver Disease

Abstract: Background & Aims Controlled attenuation parameter (CAP) can measure hepatic steatosis. However, factors affecting its accuracy have not been described yet. This study investigated predictors of discordance between liver biopsy (LB) and CAP. Methods A total of 161 consecutive patients with chronic liver disease who underwent LB and CAP were enrolled prospectively. Histological steatosis was graded as S0 ( 66% of hepatocytes). Cutoff CAP values were calculated from our cohort (250, 301, and 325 dB/m for ≥S1, ≥S2, and S3). Discordance was defined as a discrepancy of at least two steatosis stages between LB and CAP. Results The median age (102 males and 59 females) was 49 years. Repartition of histological steatosis was as follows; S0 26.1% (n = 42), S1 49.7% (n = 80), S2 20.5% (n = 33), and S3 3.7% (n = 6). In multivariate linear regression analysis, CAP value was independently associated with steatosis grade along with body mass index (BMI) and interquartile range/median of CAP value (IQR/MCAP) (all P<0.05). Discordance was identified in 13 (8.1%) patients. In multivariate analysis, histological S3 (odd ratio [OR], 9.573; 95% confidence interval [CI], 1.207–75.931; P = 0.033) and CAP value (OR, 1.020; 95% CI, 1.006–1.034; P = 0.006) were significantly associated with discordance, when adjusting for BMI, IQR/MCAP, and necroinflammation, reflected by histological activity or ALT level. Conclusions Patients with high grade steatosis or high CAP values have a higher risk of discordance between LB and CAP. Further studies are needed to improve the accuracy of CAP interpretation, especially in patients with higher CAP values.

Non-invasive diagnosis of hepatitis B virus-related cirrhosis

Abstract: Chronic hepatitis B (CHB) infection is a major public health problem associated with significant morbidity and mortality worldwide Twenty-three percent of patients with CHB progress naturally to liver cirrhosis, which was earlier thought to be irreversible However, it is now known that cirrhosis can in fact be reversed by treatment with oral anti-nucleotide drugs Thus, early and accurate diagnosis of cirrhosis is important to allow an appropriate treatment strategy to be chosen and to predict the prognosis of patients with CHB Liver biopsy is the reference standard for assessment of liver fibrosis However, the method is invasive, and is associated with pain and complications that can be fatal In addition, intra- and inter-observer variability compromises the accuracy of liver biopsy data Only small tissue samples are obtained and fibrosis is heterogeneous in such samples This confounds the two types of observer variability mentioned above Such limitations have encouraged development of non-invasive methods for assessment of fibrosis These include measurements of serum biomarkers of fibrosis; and assessment of liver stiffness via transient elastography, acoustic radiation force impulse imaging, real-time elastography, or magnetic resonance elastography Although significant advances have been made, most work to date has addressed the diagnostic utility of these techniques in the context of cirrhosis caused by chronic hepatitis C infection In the present review, we examine the advantages afforded by use of non-invasive methods to diagnose cirrhosis in patients with CHB infections and the utility of such methods in clinical practice

Factors affecting the accuracy of controlled attenuation parameter (CAP) in assessing hepatic steatosis in patients with chronic liver disease.

Abstract: Background & Aims Controlled attenuation parameter (CAP) can measure hepatic steatosis. However, factors affecting its accuracy have not been described yet. This study investigated predictors of discordance between liver biopsy (LB) and CAP. Methods A total of 161 consecutive patients with chronic liver disease who underwent LB and CAP were enrolled prospectively. Histological steatosis was graded as S0 ( 66% of hepatocytes). Cutoff CAP values were calculated from our cohort (250, 301, and 325 dB/m for ≥S1, ≥S2, and S3). Discordance was defined as a discrepancy of at least two steatosis stages between LB and CAP. Results The median age (102 males and 59 females) was 49 years. Repartition of histological steatosis was as follows; S0 26.1% (n = 42), S1 49.7% (n = 80), S2 20.5% (n = 33), and S3 3.7% (n = 6). In multivariate linear regression analysis, CAP value was independently associated with steatosis grade along with body mass index (BMI) and interquartile range/median of CAP value (IQR/MCAP) (all P<0.05). Discordance was identified in 13 (8.1%) patients. In multivariate analysis, histological S3 (odd ratio [OR], 9.573; 95% confidence interval [CI], 1.207–75.931; P = 0.033) and CAP value (OR, 1.020; 95% CI, 1.006–1.034; P = 0.006) were significantly associated with discordance, when adjusting for BMI, IQR/MCAP, and necroinflammation, reflected by histological activity or ALT level. Conclusions Patients with high grade steatosis or high CAP values have a higher risk of discordance between LB and CAP. Further studies are needed to improve the accuracy of CAP interpretation, especially in patients with higher CAP values.

Long-term changes of liver stiffness values assessed using transient elastography in patients with chronic hepatitis B receiving entecavir.

Abstract: Background & Aims Liver stiffness (LS) measurement using transient elastography allows for accurate evaluation of liver fibrosis in patients with chronic liver disease. We aimed to investigate the influence of antiviral treatment using entecavir (ETV) on LS values in patients with chronic hepatitis B (CHB). Methods 121 patients with CHB who completed a 3-year ETV treatment were recruited. LS values were measured before starting ETV (baseline) and after the completion of the 3-year treatment. A significant decline in the LS value was defined as a ≥30% drop from the baseline. Results The median baseline LS value of the patients was 14.3 kPa. However, it decreased significantly to 7.3 kPa after 3-year ETV treatment (P < 0.001). A higher baseline LS value was the single independent predictor of a significant decline in LS value on multivariate analysis (P<0.001; hazard ratio [HR], 1.155; 95% confidence interval [CI], 1.073–1.243). Using an optimal cutoff baseline LS value of 11.5 kPa (area under receiver operating characteristic curve, 0.781; 95% CI, 0.698–0.863, P < 0.001; sensitivity 75.6%; specificity, 62.8%), patients with baseline LS values of ≥11.5 kPa had a greater probability of experiencing a significant decline in the LS value than those with baseline LS values of <11.5 kPa (P < 0.001; HR, 5.240; 95% CI, 2.340–11.732). Conclusions In patients with CHB, LS values were decreased significantly after a 3-year ETV treatment. A higher baseline LS value was the single independent predictor of a significant decline in the LS value.

Therapeutic benefit of radiotherapy in huge (≥10 cm) unresectable hepatocellular carcinoma.

Abstract: Background & aims Huge (≥10 cm) hepatocellular carcinomas (HCCs) show dismal prognosis and only a limited number of cases are eligible for curative resection. We studied the therapeutic benefit of radiotherapy (RT) in patients with huge unresectable HCCs. Methods Data from 283 patients with huge HCCs and preserved liver function who underwent non-surgical treatment from July 2001 to March 2012 were retrospectively reviewed. Patients were divided into 4 groups according to the initial treatment: Group A (N= 49), transarterial chemoembolization (TACE); Group B (N = 35), TACE + RT; Group C (N = 50), hepatic arterial infusion chemotherapy; and Group D (n = 149), concurrent chemoradiotherapy (CCRT). Results and conclusions The median follow-up period was 27.8 months (range, 12.9-121.9 months). The median overall survival (OS) was longer in Groups B (15.3 months) and D (12.8 months) than in Groups A (7.5 months) and C (8.2 months; Group B vs. A, Bonferroni corrected P [P(c)] = 0.04; Group B vs. C, P(c) = 0.02; Group D vs. A, P(c) = 0.01; Group D vs. C, Pc = 0.006). Groups B and D also showed superior progression-free survival (PFS) and intrahepatic control than Groups A and C. In multivariate analysis, tumour multiplicity, serum alpha-foetoprotein level (≥200 ng/ml) and initial treatment were independent prognostic factors for OS and PFS. Patients with huge unresectable HCCs treated with RT, either as CCRT or in combination with TACE, showed excellent intrahepatic control and prolonged survival. RT could be considered a promising treatment modality in these patients.

Inhibition of tumour angiogenesis and growth by small hairpin HIF-1α and IL-8 in hepatocellular carcinoma

Abstract: Background & Aims Hypoxia-inducible factor-1α (HIF-1α), a key transcription factor in the cellular response to hypoxia, and interleukin 8 (IL-8), a key mediator of angiogenesis, are important in cancerous tumour growth. In this study, we evaluated the effects of HIF-1α and IL-8 knockdown on angiogenesis and tumour growth in hepatocellular carcinoma (HCC). Methods Hepatocellular carcinoma cell lines were infected with adenoviruses expressing small-hairpin RNA (shRNA) specific for HIF-1α or IL-8, cultured under hypoxic conditions (1% O2), and examined for their levels of HIF-1α, IL-8, and angiogenesis factors using immunoblot. The effects of adenovirus-mediated shRNA-induced HIF-1α and IL-8 knockdown on tumour growth and angiogenesis were also investigated in a subcutaneous Hep3B-tumour mouse model. Results Hypoxia-inducible factor-1α knockdown directly repressed tumour growth, whereas IL-8 knockdown indirectly repressed tumour growth. Combined knockdown of HIF-1α and IL-8 increased survival rates of mice. HIF-1α and IL-8 knockdown also decreased microvessel density and tumour volume in vivo. Similarly, HIF-1α and IL-8 knockdown inhibited the angiogenic effects of HCC cell-conditioned media on tube formation and invasion by endothelial cells in vitro. Conclusion These findings indicate that shRNA-induced HIF-1α and IL-8 knockdown inhibit angiogenesis and tumour growth in HCC. Further development of HIF-1α and IL-8 shRNA technologies could lead to effective therapies for HCC.

Liver stiffness value-based risk estimation of late recurrence after curative resection of hepatocellular carcinoma: development and validation of a predictive model.

Abstract: Background Preoperative liver stiffness (LS) measurement using transient elastography (TE) is useful for predicting late recurrence after curative resection of hepatocellular carcinoma (HCC). We developed and validated a novel LS value-based predictive model for late recurrence of HCC. Methods Patients who were due to undergo curative resection of HCC between August 2006 and January 2010 were prospectively enrolled and TE was performed prior to operations by study protocol. The predictive model of late recurrence was constructed based on a multiple logistic regression model. Discrimination and calibration were used to validate the model. Results Among a total of 139 patients who were finally analyzed, late recurrence occurred in 44 patients, with a median follow-up of 24.5 months (range, 12.4–68.1). We developed a predictive model for late recurrence of HCC using LS value, activity grade II-III, presence of multiple tumors, and indocyanine green retention rate at 15 min (ICG R15), which showed fairly good discrimination capability with an area under the receiver operating characteristic curve (AUROC) of 0.724 (95% confidence intervals [CIs], 0.632–0.816). In the validation, using a bootstrap method to assess discrimination, the AUROC remained largely unchanged between iterations, with an average AUROC of 0.722 (95% CIs, 0.718–0.724). When we plotted a calibration chart for predicted and observed risk of late recurrence, the predicted risk of late recurrence correlated well with observed risk, with a correlation coefficient of 0.873 (P<0.001). Conclusion A simple LS value-based predictive model could estimate the risk of late recurrence in patients who underwent curative resection of HCC.

Clinical outcomes and prognostic factors of patients with advanced hepatocellular carcinoma treated with sorafenib as first-line therapy: a Korean multicenter study.

Abstract: Background and Aim Sorafenib is recommended as a standard treatment for advanced hepatocellular carcinoma (HCC). The efficacy and safety of sorafenib as a first-line therapy in Korean patients with advanced HCC were investigated. Methods From 2007 to 2012, 86 patients with advanced HCC (Barcelona Clinic Liver Cancer stage C) treated with sorafenib as a first-line therapy were enrolled from five tertiary hospitals. Predictors of overall survival (OS) and progression-free survival (PFS) were analyzed. Results The median age was 59.5 years, and 71 (82.6%) were males; 57 (66.3%) patients were in Child–Pugh class A. The median OS and PFS were 5.0 (range 4.0–5.9) and 3.2 (range 2.6–3.7) months, respectively. Regarding OS, Child–Pugh class A (6.0 vs 2.8 months), tumor diameter < 5 cm (6.0 vs 4.3 months), baseline α-fetoprotein < 200 ng/mL (5.8 vs 4.1 months), and the advent of hand-foot-skin reaction of ≥ grade 2 (5.9 vs 4.0 months) were independent favorable predictors (all P < 0.05). Similarly, regarding PFS, Child–Pugh class A (4.3 vs 2.1 months), tumor diameter < 5 cm (3.9 vs 2.8 months), baseline α-fetoprotein < 200 ng/mL (5.6 vs 2.8 months), and the advent of hand-foot-skin reaction of ≥ grade 2 (4.5 vs 2.6 months) were independent favorable predictors (all P < 0.05). All toxicities during sorafenib treatment were manageable. Conclusions Because the efficacy of sorafenib seems marginal in Korean patients with treatment-naive HCC, how to select candidates with favorable outcomes should be further investigated.

The highest prognostic impact of LDH among International Prognostic Indices (IPIs): an explorative study of five IPI factors among patients with DLBCL in the era of rituximab

Abstract: Although the International Prognostic Index (IPI) is considered as the current standard prognostication system for diffuse large B-cell lymphoma (DLBCL), prognostic heterogeneity is suggested to exist among the patients within the same IPI risk group. Hence, we investigated the pattern of distribution and prognostic impact of five IPI factors within the same IPI score. We retrospectively reviewed the medical records of 387 patients newly diagnosed as pathologically proven DLBCL between February 2002 and February 2010. We classified patients to IPI risk scores and categorized them according to the combinations of IPI. Then, we explored the frequency of five IPI factors and analyzed the correlation between these subgroups and efficacy outcomes: complete response (CR), event-free survival (EFS), and overall survival (OS). Survival estimates by IPI score in this cohort corresponded to the classic IPI. Elevated serum level of lactate dehydrogenase (LDH) was the most prevalently distributed factor throughout the scores, and patients with elevated serum level of LDH tended to have lower CR, inferior EFS, and/or OS irrespective of IPI scores. Particularly, among the subgroups of IPI score of 2, elevated serum level of LDH was significantly associated with inferior CR (73.1 vs 95.2 %), 3-year EFS (57 vs 87 %), and 3-year OS (58 vs 82 %). In addition, the higher serum level of LDH, particularly above 2,000 IU/L, was significantly correlated with the inferior survival outcomes (3-year EFS 78.0 vs 58.5 vs 45.5 vs 20.0 %, 3-year OS 86.0 vs 66.2 vs 58.2 vs 40.0 %). In conclusion, among five factors of IPI, elevated serum level of LDH seems to be the most frequently distributed and, more importantly, the most relevant IPI factor with the highest prognostic impact. These findings still warrant further validation in larger cohorts.

Clinical usefulness of double biomarkers AFP and PIVKA‐II for subdividing prognostic groups in locally advanced hepatocellular carcinoma

Abstract: Background & Aims In this study, we investigated the clinical usefulness of AFP and PIVKA-II in subdividing prognostic groups in patients with locally advanced HCC treated locally. Methods Patients who had undergone local treatment for locally advanced HCC between 2001 and 2006 were enrolled. Response to treatment was defined as a reduction in AFP or PIVKA-II by more than 50% from baseline levels at 1 month after the treatment completion. Patients were divided according to their AFP and PIVKA-II response: A↓P↓ [AFP response (+) and PIVKA-II response (+)]; A↓P↑ [AFP response (+) and PIVKA-II response (−)]; A↑P↓ [AFP response (−) and PIVKA-II response (+)]; A↑P↑ [AFP response (−) and PIVKA-II response (−)]. Clinical characteristics and prognosis were compared between groups. Results Patients were subdivided into four groups by the change in the level of the biomarkers AFP and PIVKA-II, and the survival outcomes of each group were distinct. Among patients with an AFP response, further subdivision by PIVKA-II response revealed that those in the A↓P↓ group had a longer median progression-free survival (PFS) and overall survival (OS) compared with those in the A↓P↑ group (PFS: 16.2 vs. 5.1 months, P = 0.009; OS: 26.3 vs. 7.3 months, P = 0.017). Combination of AFP and PIVKA-II response showed a predictive power for PFS and OS comparable to radiological criteria and better than AFP response alone. Conclusions In patients with locally advanced HCC, the use of a combination of two biomarkers, AFP and PIVKA-II, appears useful in predicting treatment outcomes through the subdivision of prognostic groups.

Skin-penetrating methotrexate alleviates imiquimod-induced psoriasiform dermatitis via decreasing IL-17-producing gamma delta T cells.

Abstract: Accumulating evidence has shown that the Toll-like receptor 7 agonist imiquimod (IMQ) induces psoriasiform skin inflammation in mice and that this inflammation is dependent on the IL-23/IL-17 axis. Moreover, it has been demonstrated that the main source of IL-17 is not Th17 but is dermal gamma delta (γδ) T cells in mouse psoriasiform skin. Recent advances in the understanding of immunopathogenesis of psoriasis led to an alteration in the treatment paradigm to the use of highly efficacious biologics. However, their high cost impedes the extensive use of these agents. Thus, inexpensive and safe medications are still considered valuable. In this study, we introduce the therapeutic efficacy of a newly formulated methotrexate (MTX), a chemical conjugate of MTX with cell permeable peptide, for the treatment of psoriasis. Topically applied skin-penetrating (SP)-MTX reduced the psoriasiform skin phenomenon, epidermal thickness and infiltrating immune cells into the dermis. IL-17A-producing dermal γδ T cells in the cellular infiltrate that contribute IL-23/IL-17 axis were well abrogated by SP-MTX. Furthermore, SP-MTX had no toxic effects on liver, kidney or myeloid cells, unlike systemic administration of MTX. In conclusion, topically applied SP-MTX ameliorated psoriasiform skin inflammation in mice with the criteria of clinical phenomenon, histopathology and immunology, without inducing systemic toxic effects.

Prognosis of hepatocellular carcinoma patients with extrahepatic metastasis and the controllability of intrahepatic lesions

Abstract: Although advanced hepatocellular carcinoma (HCC) with extrahepatic metastasis is recommended to be treated by a systemic chemotherapeutic agent without local treatment targeting the liver, studies reported that causes of death in these patients were mostly from progression of intrahepatic lesions. Thus, this study investigated prognosis and factors predicting survival in these patients so as to evaluate the role of local treatments against intrahepatic lesions when the patients already had extrahepatic metastasis. This retrospective study evaluated medical records of 277 patients with HCC and extrahepatic metastasis. The median survival was 5.9 months, and 257 patients died during the follow up. Factors affecting survival of HCC patients with extrahepatic metastasis were poor response to treatment of hepatic lesions (HR 2.207; 95 % CI; p < 0.001), applying local treatment specifically targeting intrahepatic lesions (HR 0.591; 95 % CI 0.436–0.803; p = 0.001), intrahepatic tumor size larger than 3 cm (HR 2.065; 95 % CI 1.444–2.954; p < 0.001), and ECOG performance status 2 or higher (HR 1.543; 95 % CI 1.057–2.253; p = 0.025). The patients with either complete or partial response to the therapy had 1- and 2-year survival rate of 48.8 and 12.1 % whereas patient with either stable or progressive disease had 1-year survival rate of 11.4 %. These results suggest that even in the HCC patients with extrahepatic metastasis, effective local treatment may still be beneficial for the survival especially in patients with acceptable performance status.

Use of the delta neutrophil index as a prognostic factor of mortality in patients with spontaneous bacterial peritonitis: implications of a simple and useful marker.

Abstract: Background Spontaneous bacterial peritonitis (SBP) is a common and life-threatening infection in patients with advanced cirrhosis. The prognostic value of a novel marker, the delta neutrophil index (DNI), was investigated relative to mortality in patients with SBP. Materials & Methods Seventy-five patients with SBP were studied from April 2010 to May 2012. DNI at initial diagnosis of SBP was determined and compared with 30-day mortality rates. Results Of the patients, 87.7% were men, and the median age of all patients was 59.0 yrs. The area under the receiver-operating characteristic (ROC) curve of DNI for 30-day mortality was 0.701 (95% confidence interval [CI], 0.553–0.849; p = 0.009), which was higher than that of C-reactive protein (0.640, 95% CI, 0.494–0.786; p = 0.076) or the model for end-stage liver disease score (0.592, 95% CI, 0.436–0.748; p = 0.235). From the ROC curve, with the sum of sensitivity and specificity, the cutoff value of DNI was determined to be 5.7%. In the high-DNI group (DNI ≥5.7%), septic shock and 30-day mortality were more prevalent compared with the low-DNI group (84.2% vs. 48.2%, p = 0.007; 57.9% vs. 14.3%, p<0.001, respectively). Patients with an elevated DNI had a higher risk of 30-day mortality compared with those with a low DNI (4.225, 95% CI, 1.631–10.949; p = 0.003). Conclusion A higher DNI at the time of SBP diagnosis is an independent predictor of 30-day mortality in patients with SBP.

Use of the Delta Neutrophil Index as a Prognostic Factor of Mortality in Patients with Spontaneous Bacterial Peritonitis: Implications of a Simple and Useful Marker

Abstract: Background Spontaneous bacterial peritonitis (SBP) is a common and life-threatening infection in patients with advanced cirrhosis. The prognostic value of a novel marker, the delta neutrophil index (DNI), was investigated relative to mortality in patients with SBP. Materials & Methods Seventy-five patients with SBP were studied from April 2010 to May 2012. DNI at initial diagnosis of SBP was determined and compared with 30-day mortality rates. Results Of the patients, 87.7% were men, and the median age of all patients was 59.0 yrs. The area under the receiver-operating characteristic (ROC) curve of DNI for 30-day mortality was 0.701 (95% confidence interval [CI], 0.553–0.849; p = 0.009), which was higher than that of C-reactive protein (0.640, 95% CI, 0.494–0.786; p = 0.076) or the model for end-stage liver disease score (0.592, 95% CI, 0.436–0.748; p = 0.235). From the ROC curve, with the sum of sensitivity and specificity, the cutoff value of DNI was determined to be 5.7%. In the high-DNI group (DNI ≥5.7%), septic shock and 30-day mortality were more prevalent compared with the low-DNI group (84.2% vs. 48.2%, p = 0.007; 57.9% vs. 14.3%, p<0.001, respectively). Patients with an elevated DNI had a higher risk of 30-day mortality compared with those with a low DNI (4.225, 95% CI, 1.631–10.949; p = 0.003). Conclusion A higher DNI at the time of SBP diagnosis is an independent predictor of 30-day mortality in patients with SBP.

Risk assessment of liver-related events using transient elastography in patients with chronic hepatitis B receiving entecavir.

Abstract: Goals:We investigated whether liver stiffness (LS) values can predict liver-related events (LREs) development in patients with chronic hepatitis B (CHB).Background:LS values using transient elastography provides accurate assessment of liver fibrosis in patients with chronic liver disease.Methods:Bet

Clinical outcomes of transjugular intrahepatic portosystemic shunt for portal hypertension: Korean multicenter real-practice data

Abstract: BACKGROUND/AIMS This retrospective study assessed the clinical outcome of a transjugular intrahepatic portosystemic shunt (TIPS) procedure for managing portal hypertension in Koreans with liver cirrhosis. METHODS Between January 2003 and July 2013, 230 patients received a TIPS in 13 university-based hospitals. RESULTS Of the 229 (99.6%) patients who successfully underwent TIPS placement, 142 received a TIPS for variceal bleeding, 84 for refractory ascites, and 3 for other indications. The follow-up period was 24.9 ± 30.2 months (mean ± SD), 74.7% of the stents were covered, and the primary patency rate at the 1-year follow-up was 78.7%. Hemorrhage occurred in 30 (21.1%) patients during follow-up; of these, 28 (93.3%) cases of rebleeding were associated with stent dysfunction. Fifty-four (23.6%) patients developed new hepatic encephalopathy, and most of these patients were successfully managed conservatively. The cumulative survival rates at 1, 6, 12, and 24 months were 87.5%, 75.0%, 66.8%, and 57.5%, respectively. A high Model for End-Stage Liver Disease (MELD) score was significantly associated with the risk of death within the first month after receiving a TIPS (P=0.018). Old age (P<0.001), indication for a TIPS (ascites vs. bleeding, P=0.005), low serum albumin (P<0.001), and high MELD score (P=0.006) were associated with overall mortality. CONCLUSIONS A high MELD score was found to be significantly associated with early and overall mortality rate in TIPS patients. Determining the appropriate indication is warranted to improve survival in these patients.

Effective Biliary Drainage and Proper Treatment Improve Outcomes of Hepatocellular Carcinoma with Obstructive Jaundice

Abstract: Background/Aims We investigated the treatment outcomes and prognostic factors of hepatocellular carcinoma (HCC) with obstructive jaundice.

Long-term outcomes of chronic hepatitis B virus infection in the era of antiviral therapy in Korea.

Abstract: Background and Aims Chronic hepatitis B (CHB) can progress to cirrhosis, hepatocellular carcinoma (HCC), and ultimately liver-related deaths. Recently, owing to potent antiviral therapy with minimal side-effects, sustained suppression of hepatitis B virus replication can be achieved, thereby preventing such complications. We aimed to reappraise clinical courses regarding disease progression in the era of antiviral therapy. Methods Between 2001 and 2005, treatment-naive Korean CHB patients without cirrhosis were enrolled and followed up for at least 5 years. During follow up, antiviral therapy was commenced according to Korean Association for the Study of the Liver guidelines, if eligible, and ultrasonography and laboratory and clinical assessment were performed regularly. Primary end-points were development of cirrhosis, hepatic decompensation, HCC, or liver-related deaths. Results Of 360 patients, 323 (89.7%) received antiviral therapy such as lamivudine (70.6%), entecavir (8.7%), or telbivudine (6.5%). During follow up, cirrhosis developed in 29 (8.1%), hepatic decompensation in 4 (1.1%), and HCC in 15 (4.2%) patients. Annual incidences of cirrhosis, hepatic decompensation, and HCC were 1.05%, 0.14%, and 0.53% per person-year, respectively. Age was an independent predictor for developing cirrhosis (hazard ratio [HR] 1.075, 95% confidence interval [CI] 1.037–1.116; P < 0.001), whereas age (HR 1.060, 95% CI 1.012–1.111; P = 0.014) and cirrhosis (HR 17.470, 95% CI 5.081–60.063; P < 0.001) were those for developing HCC. Conclusions In the era of antiviral therapy, overall clinical courses have been much improved since introduction of lamivudine in 1999. However, patients with older age or cirrhosis are still subject to HCC development despite appropriate antiviral therapy, necessitating cautious surveillance.

Liver Stiffness Value-Based Risk Estimation of Late Recurrence after Curative Resection of Hepatocellular Carcinoma: Development and Validation of a Predictive Model

Abstract: Background Preoperative liver stiffness (LS) measurement using transient elastography (TE) is useful for predicting late recurrence after curative resection of hepatocellular carcinoma (HCC). We developed and validated a novel LS value-based predictive model for late recurrence of HCC. Methods Patients who were due to undergo curative resection of HCC between August 2006 and January 2010 were prospectively enrolled and TE was performed prior to operations by study protocol. The predictive model of late recurrence was constructed based on a multiple logistic regression model. Discrimination and calibration were used to validate the model. Results Among a total of 139 patients who were finally analyzed, late recurrence occurred in 44 patients, with a median follow-up of 24.5 months (range, 12.4–68.1). We developed a predictive model for late recurrence of HCC using LS value, activity grade II-III, presence of multiple tumors, and indocyanine green retention rate at 15 min (ICG R15), which showed fairly good discrimination capability with an area under the receiver operating characteristic curve (AUROC) of 0.724 (95% confidence intervals [CIs], 0.632–0.816). In the validation, using a bootstrap method to assess discrimination, the AUROC remained largely unchanged between iterations, with an average AUROC of 0.722 (95% CIs, 0.718–0.724). When we plotted a calibration chart for predicted and observed risk of late recurrence, the predicted risk of late recurrence correlated well with observed risk, with a correlation coefficient of 0.873 (P<0.001). Conclusion A simple LS value-based predictive model could estimate the risk of late recurrence in patients who underwent curative resection of HCC.

Tenofovir disoproxil fumarate monotherapy for nucleos(t)ide-naïve chronic hepatitis B patients in Korea: data from the clinical practice setting in a single-center cohort.

Abstract: BACKGROUND/AIMS This study assessed the antiviral efficacy and safety of tenofovir disoproxil fumarate (TDF) for up to 12 months in Korean treatment-naive chronic hepatitis B (CHB) patients. METHODS A total of 411 treatment-naive CHB patients who had been treated with TDF for at least 3 months (median 5.6) were consecutively enrolled. Clinical, biochemical, virological parameters and treatment adherence were routinely assessed every 3 months. RESULTS The median age was 51.3 years, 63.0% of the patients were male, 49.6% were HBeAg (+), and 210 patients had liver cirrhosis. The median baseline HBV DNA was 5.98 (SD 1.68) log10 IU/mL. Among the patients completing week 48, 83.3% had a complete virologic response (CVR, <12 IU/mL by HBV PCR assay), and 88.2% had normalized levels of alanine aminotransferase (ALT). The cumulative probabilities of CVR at 3, 6, 9 and 12 months were 22.8%, 53.1%, 69.3% and 85.0%. During the follow-up period, 9.8% patients achieved HBeAg loss and 7.8% patients achieved HBeAg seroconversion. There was no virological breakthrough after initiating TDF. The most common TDF-related adverse event was gastrointestinal upset, and three patients discontinued TDF therapy. However, no serious life-threatening side effect was noted. CONCLUSIONS In a clinical practice setting, TDF was safe and highly effective when administered for 12 months to Korean treatment-naive CHB patients.

Dynamics of the liver stiffness value using transient elastography during the perioperative period in patients with valvular heart disease.

Abstract: Background/Aims Liver congestion due to heart failure in patients with valvular heart disease (VHD) can result in an overestimate of the liver stiffness (LS) as assessed by transient elastography (TE). This prospective pilot study investigated the dynamics of LS during the perioperative valve operation period.