Two-dimensional shear wave elastography for assessing liver fibrosis in patients with chronic liver disease: a prospective cohort study.

BACKGROUND/AIMS: The objective of this study was to determine whether the newly developed two-dimensional shear wave elastography (2D-SWE, RS85, Samsung-shearwave imaging) was more valid and reliable than transient elastography (TE) for predicting the stage of liver fibrosis. METHODS: The study prospectively enrolled a total of 116 patients with chronic liver disease who underwent 2D-SWE, TE, laboratory testing, and liver biopsy on the same day from two tertiary care hospitals. One patient with unreliable measurement was excluded. The measurement of 2D-SWE was considered acceptable when a homogenous color pattern in a region of interest of at least 10 mm was detected at 10 different sites. Diagnostic performance was calculated using area under the receiver operating characteristic curve (AUROC). RESULTS: Liver fibrosis stages included F0 (18%), F1 (19%), F2 (24%), F3 (22%), and F4 (17%). Interclass correlation coefficient for inter-observer agreement in 2D-SWE was 0.994 (95% confidence interval [CI], 0.988 to 0.997). Overall, the results of 2D-SWE and stages of histological fibrosis were significantly correlated (r = 0.601, p < 0.001). For The 2D-SWE showed good diagnostic ability (AUROC, 0.851; 95% CI, 0.773 to 0.911) comparable to TE (AUROC, 0.859; 95% CI, 0.781 to 0.916) for the diagnosis of significant fibrosis (≥ F2), and the cut-off value was 5.8 kPa. AUROC and optimal cut-off of 2D-SWE for the diagnosis of liver cirrhosis were 0.889 (95% CI, 0.817 to 0.940) and 9.6 kPa, respectively. TE showed similar diagnostic performance in distinguishing cirrhosis (AUROC, 0.938; 95% CI, 0.877 to 0.974; p = 0.08). CONCLUSION: 2D-SWE is comparable to TE in diagnosing significant fibrosis and liver cirrhosis with high reliability.

Clinical outcomes of patients with a single hepatocellular carcinoma less than 5 cm treated with transarterial chemoembolization.

BACKGROUND/AIMS: Transarterial chemoembolization (TACE) is performed for single hepatocellular carcinoma (HCC) that are not eligible for surgery or ablation therapy. We investigated the clinical outcomes of patients with a single HCC ≤ 5 cm treated with TACE. METHODS: This study analyzed 175 consecutive patients who underwent TACE as an initial treatment for single HCC ≤ 5 cm. Predictive factors for complete response (CR), recurrence after CR, and overall survival (OS) were evaluated. RESULTS: Total 119 patients (68%) achieved CR after TACE. Tumor size < 3 cm and hepatitis B virus infection were significant predictors of CR (p < 0.05). Recurrent HCC was detected in 73 patients (61.3%) after CR. Age > 65 years and absence of liver cirrhosis were predictive factors for non-recurrence after CR (p < 0.05). The OS for all patients was 80.7 ± 5.6 months, and the 1-, 3-, and 5-year OS rates were 88.1%, 64.8%, and 49.9%, respectively. In multivariate analysis for OS, CR (hazard ratio [HR], 0.467; 95% confidence interval [CI], 0.292 to 0.747) and Child class A (HR, 0.390; 95% CI, 0.243 to 0.626) were significant factors. The OS for the CR and Child class A group were 92 and 93.6 months, respectively, and that of the non-CR and Child B, C group were 53.3 and 50.7 months, respectively (p < 0.001). CONCLUSION: TACE can be a valid treatment in patients with a single HCC ≤ 5 cm not suitable for curative treatment, especially in patients with Child class A and CR after TACE.

Clinical significance of radiation-induced liver disease after stereotactic body radiation therapy for hepatocellular carcinoma.

BACKGROUND/AIMS: The aim of this study was to investigate parameters that predict radiation-induced liver disease (RILD) following stereotactic body radiotherapy (SBRT) in patients with hepatocellular carcinoma (HCC) and to identify the clinical significance of RILD. METHODS: We retrospectively reviewed the medical records of 117 HCC patients who were treated by SBRT from March 2011 to February 2015. RILD was defined as elevated liver transaminases more than five times the upper normal limit or a worsening of Child-Pugh (CP) score by 2 within 3 months after SBRT. All patients were assessed at 1 month and every 3 months after SBRT. RESULTS: Median follow-up was 22.5 months (range, 3 to 56) after SBRT. RILD was developed in 29 of the 117 patients (24.7%). On univariate analysis, significant predictive factors of RILD were pretreatment CP score (p < 0.001) and normal liver volume (p = 0.002). Multivariate analysis showed that CP score was a significant predictor of RILD (p < 0.001). The incidence of RILD increased above a CP score of 6 remarkably. The rate of recovery from RILD decreased significantly above a CP score of 8. Survival analysis showed that CP score was an independent prognostic factor of overall survival (p = 0.001). CONCLUSION: CP score is a significant factor to predict RILD in patients with chronic liver disease. RILD can be tolerated by patients with a CP score ≤ 7. However, careful monitoring of liver function is needed for patients with a CP score 7 after SBRT.

A prospective comparative assessment of the accuracy of the FibroScan in evaluating liver steatosis.

BACKGROUND/AIMS: Recent studies have demonstrated the utility of the FibroScan® device in diagnosing liver steatosis, but its usefulness has not been thoroughly appraised. We investigated the usefulness of the controlled attenuation parameter (CAP) in detecting and quantifying liver steatosis. METHODS: A prospective analysis was applied to 79 chronic liver disease patients who underwent a liver biopsy, a FibroScan investigation, ultrasonography, and hepatic steatosis index (HSI). The presence and degree of steatosis as measured by the FibroScan device, ultrasonography and HSI were compared with the results for the liver biopsy tissue. RESULTS: There was substantial concordance between the liver biopsy results and the CAP as evaluated by the kappa (κ) index test for detecting liver steatosis (κCAP = 0.77, P<0.001; κultrasonography = 0.60, P<0.001; κHSI = 0.47, P<0.001). The areas under the receiver operating characteristic curve (AUROCs) of the CAP, ultrasonography, and HSI were 0.899 [95% confidence interval (CI) = 0.826-0.972)], 0.859 (95% CI = 0.779-0.939), and 0.766 (95% CI = 0.655-0.877), respectively. The optimal CAP cutoff value for differentiating between normal and hepatic steatosis was 247 dB/m, which produced sensitivity and specificity values of 91.9% and 85.7%, respectively, as well as a positive predictive value of 85.0% and a negative predictive value of 92.3%. CONCLUSION: The CAP produces results that are highly concordant with those of a liver biopsy in detecting steatosis. Therefore, the CAP is a noninvasive and reliable tool for evaluating liver steatosis, even in the early stages.

Ginsenoside Rg3 restores hepatitis C virus-induced aberrant mitochondrial dynamics and inhibits virus propagation.

Hepatitis C virus (HCV) alters mitochondrial dynamics associated with persistent viral infection and suppression of innate immunity. Mitochondrial dysfunction is also a pathologic feature of direct-acting antiviral (DAA) treatment. Despite the high efficacy of DAAs, their use in treating patients with chronic hepatitis C in interferon-sparing regimens occasionally produces undesirable side effects such as fatigue, migraine, and other conditions, which may be linked to mitochondrial dysfunction. Here, we show that clinically prescribed DAAs, including sofosbuvir, affect mitochondrial dynamics. To counter these adverse effects, we examined HCV-induced and DAA-induced aberrant mitochondrial dynamics modulated by ginsenoside, which is known to support healthy mitochondrial physiology and the innate immune system. We screened several ginsenoside compounds showing antiviral activity using a robust HCV cell culture system. We investigated the role of ginsenosides in antiviral efficacy, alteration of mitochondrial transmembrane potential, abnormal mitochondrial fission, its upstream signaling, and mitophagic process caused by HCV infection or DAA treatment. Only one of the compounds, ginsenoside Rg3 (G-Rg3), exhibited notable and promising anti-HCV potential. Treatment of HCV-infected cells with G-Rg3 increased HCV core protein-mediated reduction in the expression level of cytosolic p21, required for increasing cyclin-dependent kinase 1 activity, which catalyzes Ser616 phosphorylation of dynamin-related protein 1. The HCV-induced mitophagy, which follows mitochondrial fission, was also rescued by G-Rg3 treatment. CONCLUSION: G-Rg3 inhibits HCV propagation. Its antiviral mechanism involves restoring the HCV-induced dynamin-related protein 1-mediated aberrant mitochondrial fission process, thereby resulting in suppression of persistent HCV infection. (Hepatology 2017;66:758-771).

Usefulness of AFP, AFP-L3, and PIVKA-II, and their combinations in diagnosing hepatocellular carcinoma.

Alpha-fetoprotein (AFP), Lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), and protein induced by vitamin K absence or antagonist-II (PIVKA-II) are widely used as tumor markers for the diagnosis of hepatocellular carcinoma (HCC). This study compared the diagnostic values of AFP, AFP-L3, and PIVKA-II individually and in combination to find the best biomarker or biomarker panel.Seventy-nine patients with newly diagnosed HCC and 77 non-HCC control patients with liver cirrhosis were enrolled. AFP, AFP-L3, and PIVKA-II were measured in the same serum samples using microchip capillary electrophoresis and a liquid-phase binding assay on an automatic analyzer. Receiver-operating characteristic curve analyses were also applied to all combinations of the markers.When the 3 biomarkers were analyzed individually, AFP showed the largest area under the receiver-operating characteristic curve (AUC) (0.751). For combinations of the biomarkers, the AUC was highest (0.765) for "PIVKA-II > 40 mAU/mL and AFP > 10 ng/mL." The combination of "PIVKA-II > 40 mAU/mL and AFP > 10 ng/mL and AFP-L3 > 10%" had worse sensitivity and lower AUC (P = 0.001). The highest AUC of a single biomarker was highest for AFP and of a combination was "PIVKA-II > 40 mAU/mL and AFP > 10 ng/mL," with this also being the case when the cut-off value of AFP and AFP-L3 was changed.Alpha-fetoprotein showed the best diagnostic performance as a single biomarker for HCC. The diagnostic value of AFP was improved by combining it with PIVKA-II, but adding AFP-L3 did not contribute to the ability to distinguish between HCC and non-HCC liver cirrhosis. These findings were not altered when the cut-off value of AFP and AFP-L3 was changed.

Predictive Factors for Complete Response and Recurrence after Transarterial Chemoembolization in Hepatocellular Carcinoma.

BACKGROUND/AIMS: To investigate the predictive factors for complete response (CR) and recurrence after CR in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE). METHODS: Among 691 newly diagnosed HCC patients, 287 were treated with TACE as a first therapy. We analyzed the predictive factors for CR, recurrence after CR, and overall survival (OS). RESULTS: Eighty-one patients (28.2%) achieved CR after TACE, and recurrence after CR was detected in 35 patients (43.2%). In multivariate analyses, tumor size (≤5 cm) and single nodularity were predictive factors for CR, with hazard ratios (HRs) of 0.35 (p=0.002) and 0.41 (p<0.001), respectively. Elevated serum α-fetoprotein (AFP) (>20 ng/mL) level and multinodularity exhibited significant relationships with recurrence after CR, with HRs of 2.220 (p=0.026) and 3.887 (p<0.001), respectively. Tumor size (>5 cm), multinodularity, elevated serum AFP (>20 ng/mL) level, Child-Turcotte-Pugh score (B and C), and portal vein thrombosis were significant factors for OS. CONCLUSIONS: In patients treated with TACE as a first therapy, tumor size (≤5 cm) and single nodularity were predictive factors for CR, and multinodularity and elevated serum AFP (>20 ng/mL) levels were predictive factors for recurrence after CR. These factors were also significant for OS.

Relationship between 25-Hydroxyvitamin D Levels and Liver Fibrosis as Assessed by Transient Elastography in Patients with Chronic Liver Disease.

BACKGROUND/AIMS: Deficiencies of 25-hydroxyvitamin D (25(OH)D) are prevalent in patients with chronic liver disease (CLD). Liver fibrosis is the main determinant of CLD prognosis. The present study was performed to evaluate the correlation between 25(OH)D levels and liver fibrosis as assessed by transient elastography (TE) in patients with compensated CLD. METHODS: Serum 25(OH)D levels and liver stiffness were determined in a total of 207 patients who were subjected to the following exclusion criteria: patients with decompensated CLD; patients who had malignancies; patients who were taking medications; and patients who were pregnant. RESULTS: The most common etiology was chronic hepatitis B (53.1%). Advanced liver fibrosis (defined by TE [≥9.5 kPa]) was present in 75 patients (36.2%). There was a significant correlation between 25(OH)D deficiency and liver stiffness. Based on the multivariate analysis, the following factors were independently associated with advanced liver fibrosis: 25(OH)D deficiency (odds ratio [OR], 3.46; p=0.004), diabetes mellitus (OR, 3.04; p=0.041), and fibrosis-4 index (OR, 2.01; p<0.001). CONCLUSIONS: Patients with compensated CLD exhibit a close correlation between vitamin D level and liver stiffness as assessed by TE. Vitamin D deficiency was independently associated with advanced liver fibrosis.

Clinical Features of Drug-induced Liver Injury According to Etiology.

Drug-induced liver injury (DILI) is an increasingly common cause of acute hepatitis. We examined clinical features and types of liver injury of 65 affected patients who underwent liver biopsy according DILI etiology. The major causes of DILI were the use of herbal medications (43.2%), prescribed medications (21.6%), and traditional therapeutic preparations and dietary supplements (35%). DILI from herbal medications, traditional therapeutic preparations, and dietary supplements was associated with higher elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels than was DILI from prescription medications. The types of liver injury based on the R ratio were hepatocellular (67.7%), mixed (10.8%), and cholestatic (21.5%). Herbal medications and traditional therapeutic preparations were more commonly associated with hepatocellular liver injury than were prescription medications (P = 0.002). Herbal medications and traditional therapeutic preparations induce more hepatocellular DILI and increased elevations in AST and ALT than prescribed medications.

Predictive factors of contrast-enhanced ultrasonography for the response to transarterial chemoembolization in hepatocellular carcinoma.

BACKGROUND/AIMS: The predictive role of contrast-enhanced ultrasonography (CEUS) before performing transarterial chemoembolization (TACE) has not been determined. We assessed the possible predictive factors of CEUS for the response to TACE. METHODS: Seventeen patients with 18 hepatocellular carcinoma (HCC) underwent TACE. All of the tumors were studied with CEUS before TACE using a second-generation ultrasound contrast agent (SonoVue®, Bracco, Milan, Italy). The tumor response to TACE was classified with a score between 1 and 4 according to the remaining enhancing-tumor percentage based on modified response evaluation criteria in solid tumors (mRECIST): 1, enhancing tumor <25%; 2, 25%≤enhancing tumor<50%; 3, 50%≤enhancing tumor<75%; and 4, enhancing tumor≥75%). A score of 1 was defined as a "good response" to TACE. The predictive factors for the response to TACE were evaluated during CEUS based on the maximum tumor diameter, initial arterial enhancing time, arterial enhancing duration, intensity of arterial enhancement, presence of a hypoenhanced pattern, and the feeding artery to the tumor. RESULTS: The median tumor size was 3.1 cm. The distribution of tumor response scores after TACE in all tumors was as follows: 1, n=11; 2, n=4; 3, n=2; and 4, n=1. Fifteen tumors showed feeding arteries. The presence of a feeding artery and the tumor size (≤5 cm) were the predictive factors for a good response (P=0.043 and P=0.047, respectively). CONCLUSIONS: The presence of a feeding artery and a tumor size of less than 5 cm were the predictive factors for a good response of HCC to TACE on CEUS.

Use of (18)F-FDG PET to predict tumor progression and survival in patients with intermediate hepatocellular carcinoma treated by transarterial chemoembolization.

BACKGROUND/AIMS: (18)F-Fluorodeoxyglucose positron-emission tomography ((18)F-FDG PET) has been used to assess the biological behavior of hepatocellular carcinoma (HCC). In this study, we investigated the usefulness of (18)F-FDG PET for predicting tumor progression and survival in patients with intermediate Barcelona Clinic Liver Cancer (BCLC) intermediate-stage HCC treated by transarterial chemoembolization (TACE). METHODS: From February 2006 to March 2013, 210 patients treated with TACE, including 77 patients with BCLC intermediate-stage HCC, underwent examination by (18)F-FDG PET. (18)F-FDG uptake was calculated based on the tumor maximum (Tmax) standardized uptake value (SUV), the liver mean (Lmean) SUV, and the ratio of the Tmax SUV to the Lmean SUV (Tmax/Lmean). RESULTS: The mean follow-up period for the 77 patients (52 males, 25 females; average age, 63.3 years) was 22.2 months. The median time to progression of HCC in patients with a low Tmax/Lmean (< 1.83) and high Tmax/Lmean (≥ 1.83) was 17 and 6 months, respectively (p < 0.001). The median overall survival time of patients with a low and high Tmax/Lmean was 44 and 14 months, respectively (p = 0.003). Multivariate analysis revealed that the Tmax/Lmean was an independent predictor of overall survival (hazard ratio [HR], 1.96; 95% confidence interval [CI], 1.210 to 3.156; p = 0.006) and tumor progression (HR, 2.05; 95% CI, 1.264 to 3.308; p = 0.004). CONCLUSIONS: (18)F-FDG uptake calculated by the Tmax/Lmean using PET predicted tumor progression and survival in patients with BCLC intermediate-stage HCC treated by TACE.

Predictability of preoperative 18F-FDG PET for histopathological differentiation and early recurrence of primary malignant intrahepatic tumors.

OBJECTIVE: The limited studies with 18F-fluorodeoxyglucose (18F-FDG)-PET reported results and interpretations that differed between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHCC). We investigated the correlation between preoperative PET results and postoperative prognosis, including early (time-to-recurrence<6 months) tumor recurrence, and histopathological tumor differentiation in patients who had undergone surgery for primary malignant intrahepatic tumors, including HCC and IHCC. MATERIALS AND METHODS: We retrospectively reviewed 357 patients who had undergone curative surgery for malignant hepatic tumors, including primary HCC or IHCC, other than Klatskin tumors at a tertiary academic hospital between January 2005 and June 2012. All patients had undergone an 18F-FDG PET/computed tomography scan preoperatively and the maximum standardized uptake value of the tumor (max SUV tumor) and the tumor-to-nontumor SUV ratio (TNR) were calculated from 18F-FDG uptake. Histopathological differentiation grading was confirmed postoperatively. RESULTS: Among the patients, 115 cases with primary malignant intrahepatic tumors fulfilled the inclusion criteria. On univariate analysis, preoperative max SUV tumor and TNR showed a correlation with the overall and early tumor recurrence of HCC, but only max SUV tumor was associated with overall and early recurrence of IHCC (P<0.05). When considering postoperative histopathological differentiation, a correlation between max SUV tumor and TNR with HCC and between max SUV tumor and IHCC was found (P<0.05). However, on multivariate analysis, only early recurrence was associated with TNR in HCC and with max SUV tumor in IHCC. CONCLUSION: A preoperative 18F-FDG PET scan can be considered a useful reference for postoperative tumor recurrence and histopathological differentiation in cases of primary malignant intrahepatic tumors. 18F-FDG PET scan results should be interpreted separately for malignant liver tumors.

TRAIL enhances apoptosis of human hepatocellular carcinoma cells sensitized by hepatitis C virus infection: therapeutic implications.

Hepatitis C virus (HCV) infection causes chronic liver diseases leading to hepatocellular carcinoma (HCC) and liver failure. We have previously shown that HCV sensitizes hepatocytes to mitochondrial apoptosis via the TRAIL death receptors DR4 and DR5. Although TRAIL and its receptors are selective targets for cancer therapy, their potential against HCC with chronic HCV infection has not been explored yet. Here we show that HCV induces DR4/DR5-dependent activation of caspase-8 leading to elevation of apoptotic signaling in infected cells and also present TRAIL effect in HCV-induced apoptotic signaling. HCV induced proteolytic cleavage of caspase-9 by stimulating DR4 and DR5, resulting in subsequent cleavage of caspase-3. Further, HCV-induced proteolytic cleavage in caspase-8, caspase-9, and caspase-3 was enhanced in the presence of recombinant TRAIL. HCV-induced cleavage in caspase-9 and increase in caspase-3/7 activity was completely suppressed by silencing of either DR4 or DR5. Perturbing DR4/DR5-caspase-8 signaling complex by silencing DR4 and DR5 or by chemical inhibitor specific to caspase-8 led to decrease of HCV-induced cleavage of poly(ADP-ribose) polymerase (PARP), a substrate for caspase-3 during apoptosis, indicating the functional role of caspase-8 in HCV-induced apoptotic signaling network. Furthermore, TRAIL enhanced PARP cleavage in apoptotic response induced by HCV infection, indicating the effect of TRAIL for the induction of selective apoptosis of HCC cells infected with HCV. Given the importance of apoptosis in HCC development, our data suggest that HCV-induced DR4 and DR5 may be considered as an attractive target for TRAIL therapy against HCC with chronic HCV infection.

Clinically useful diagnostic tool of contrast enhanced ultrasonography for focal liver masses: comparison to computed tomography and magnetic resonance imaging.

BACKGROUND/AIMS: To evaluate the diagnostic value of contrast (SonoVue(®)) enhancement ultrasonography (CEUS) and to compare this method with computed tomography (CT) and magnetic resonance imaging (MRI) in evaluating liver masses. METHODS: CEUS (n=50), CT (n=47), and MRI (n=43) were performed on 50 liver masses in 48 patients for baseline mass haracterization. The most likely impression for each modality and the final diagnosis, based on the combined biopsy results (n=14), angiography findings (n=36), and clinical course, were determined. The diagnostic value of CEUS was compared to those of CT and MRI. RESULTS: The final diagnosis of the masses was hepatocellular carcinoma (n=43), hemangioma (n=3), benign adenoma (n=2), eosinophilic abscess (n=1), and liver metastasis (n=1). The overall diagnostic agreement with the final diagnosis was substantial for CEUS, CT, and MRI, with κ values of 0.621, 0.763, and 0.784, respectively. The sensitivity, specificity, and accuracy were 83.3%, 87.5%, and 84.0%, respectively, for CEUS; 95.0%, 87.5%, and 93.8%, respectively, for CT; and 94.6%, 83.3%, and 93.0%, respectively for MRI. After excluding the lesions with poor acoustic sonographic windows, the sensitivity, specificity, and accuracy for CEUS were 94.6%, 87.5%, and 93.3%, respectively, with a κ value of 0.765. CONCLUSIONS: If an appropriate acoustic window is available, CEUS is comparable to CT and MRI for the diagnosis of liver masses.

Practical effect of sorafenib monotherapy on advanced hepatocellular carcinoma and portal vein tumor thrombosis.

BACKGROUND/AIMS: We investigated the effects of sorafenib monotherapy on advanced hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) in a clinical setting. METHODS: In total, 143 consecutive patients with unresectable HCC were treated with sorafenib. Among these patients, 30 patients with advanced HCC and PVTT (Vp3 or 4) were treated with sorafenib monotherapy. RESULTS: All patients had a performance status of 1 to 2 (Eastern Cooperative Oncology Group 1/2, 20/10) and Child-Pugh class A or B (A/B, 17/13). Eleven patients had modified Union for International Cancer Control stage IVA tumors, whereas 19 had stage IVB tumors. All patients had PVTT (Vp3, 6; Vp4, 24). Following sorafenib monotherapy, three patients (10.0%) had a partial response with PVTT revascularization, and nine (30.0%) had stable disease, with a disease control rate of 33.3%. The median overall survival was 3.1 months (95% confidence interval [CI], 2.70 to 3.50), and the median progression-free survival was 2.0 months (95% CI, 1.96 to 2.05). Fatigue and hand-foot skin reactions were the most troublesome side effects. CONCLUSIONS: A limited proportion of patients with advanced HCC and PVTT exhibited a remarkable outcome after sorafenib monotherapy, although the treatment results in this type of patient is extremely poor. Further studies to predict good responders to personalized therapy are warranted.

The risk factors for bleeding of fundal varices in patients with liver cirrhosis.

BACKGROUND/AIMS: The relationship between portal hemodynamics and fundal varices has not been well documented. The purpose of this study was to understand the pathophysiology of fundal varices and to investigate bleeding risk factors related to the presence of spontaneous portosystemic shunts, and to examine the hepatic venous pressure gradient (HVPG) between fundal varices and other varices. METHODS: In total, 85 patients with cirrhosis who underwent HVPG and gastroscopic examination between July 2009 and March 2011 were included in this study. The interrelationship between HVPG and the types of varices or the presence of spontaneous portosystemic shunts was studied. RESULTS: There was no significant difference in the HVPG between fundal varices (n=12) and esophageal varices and gastroesophageal varices type 1 (GOV1) groups (n=73) (17.1±7.7 mm Hg vs 19.7±5.3 mm Hg). Additionally, there was no significant difference in the HVPG between varices with spontaneous portosystemic shunts (n=28) and varices without these shunts (n=57) (18.3±5.8 mm Hg vs 17.0±8.1 mm Hg). Spontaneous portosystemic shunts increased in fundal varices compared with esophageal varices and GOV1 (8/12 patients [66.7%] vs 20/73 patients [27.4%]; p=0.016). CONCLUSIONS: Fundal varices had a high prevalence of spontaneous portosystemic shunts compared with other varices. However, the portal pressure in fundal varices was not different from the pressure in esophageal varices and GOV1.

The secondary prophylactic efficacy of beta-blocker after endoscopic gastric variceal obturation for first acute episode of gastric variceal bleeding.

BACKGROUND/AIMS: The most appropriate treatment for acute gastric variceal bleeding (GVB) is currently endoscopic gastric variceal obturation (GVO) using Histoacryl®. However, the secondary prophylactic efficacy of beta-blocker (BB) after GVO for the first acute episode of GVB has not yet been established. The secondary prophylactic efficacy of BB after GVO for the first acute episode of GVB was evaluated in this study. METHODS: Ninety-three patients at Soonchunhyang University Hospital with acute GVB who received GVO using Histoacryl® were enrolled between June 2001 and March 2010. Among these, 42 patients underwent GVO alone (GVO group) and 51 patients underwent GVO with adjuvant BB therapy (GVO+BB group). This study was intended for patients in whom a desired heart rate was reached. The rates of rebleeding-free survival and overall survival were calculated for the two study groups using Kaplan-Meyer analysis and Cox's proportional-hazards model. RESULTS: The follow-up period after the initial eradication of gastric varices was 18.14±25.22 months (mean±SD). During the follow-up period, rebleeding occurred in 10 (23.8%) and 21 (41.2%) GVO and GVO+BB patients, respectively, and 39 patients died [23 (54.8%) in the GVO group and 16 (31.4%) in the GVO+BB group]. The mean rebleeding-free survival time did not differ significantly between the GVO and GVO+BB groups (65.40 and 37.40 months, respectively; P=0.774), whereas the mean overall survival time did differ (52.54 and 72.65 months, respectively; P=0.036). CONCLUSIONS: Adjuvant BB therapy after GVO using Histoacryl® for the first acute episode of GVB could decrease the mortality rate relative to GVO alone. However, adjuvant BB therapy afforded no benefit for the secondary prevention of rebleeding in GV.

The usefulness of transient elastography, acoustic-radiation-force impulse elastography, and real-time elastography for the evaluation of liver fibrosis.

BACKGROUND/AIMS: Several noninvasive methods have recently been developed for the evaluation of liver fibrosis. The accuracy of transient elastography (TE), acoustic-radiation-force impulse (ARFI) elastography, and real-time elastography (RTE) in predicting liver fibrosis were evaluated. METHODS: Seventy-four patients who had undergone a liver biopsy within the previous 6 months were submitted to evaluation with TE, ARFI, and RTE on the same day. RESULTS: THERE WERE SIGNIFICANT CORRELATIONS BETWEEN FIBROSIS STAGE AND LIVER STIFFNESS MEASUREMENT (LSM) USING THE THREE TESTED METHODS: TE, r(2)=0.272, P=0.0002; ARFI, r(2)=0.225, P=0.0017; and RTE, r(2)=0.228, P=0.0015. The areas under the receiver operating characteristic curves (AUROC) for the diagnosis of significant fibrosis (≥F2, Metavir stage) by TE, ARFI, RTE, TE/platelet count (PLT), velocity of shear wave (Vs)/PLT, and elasticity score (Es)/PLT were 0.727, 0.715, 0.507, 0.876, 0.874, and 0.811, respectively. The AUROC for the diagnosis of cirrhosis by TE, ARFI, RTE, TE/PLT, Vs/PLT, and Es/PLT were 0.786, 0.807, 0.767, 0.836, 0.819, and 0.838, respectively. Comparisons of AUROC between all LSMs for predicting significant fibrosis (≥F2) produced the following results: TE vs. RTE, P=0.0069; ARFI vs. RTE, P=0.0277; and TE vs. ARFI, P=0.8836. Applying PLT, the ability of each LSM to predict fibrosis stage significantly increased: TE/PLT vs. TE, P=0.0004; Vs/PLT vs. ARFI, P=0.0022; and Es/PLT vs. RTE, P<0.0001. However, the ability to predict cirrhosis was not enhanced, combining LSM and PLT. CONCLUSIONS: TE and ARFI may be better methods for predicting significant liver fibrosis than RTE. This predictive ability increased significantly when accounting for platelet count. However, all of the measures had comparable efficacies for predicting cirrhosis.

Should colonoscopy be performed in patients with cryptogenic liver abscess?

BACKGROUND/AIM: The interruption of a mucosal barrier by colon cancer or a polyp can lead to the development of a liver abscess. This study aimed to evaluate the possible contribution of colon cancer to the development of liver abscess and the necessity of colonoscopy in patients presenting with cryptogenic liver abscess. METHODS: We reviewed the medical records of 268 patients diagnosed with liver abscess between January 2001 and April 2010. Among cases with no definite cause of liver abscess, differences between patients with and without colon cancer were evaluated in terms of clinical, laboratory, imaging, and microbiological findings. RESULTS: Pyogenic liver abscess with no apparent etiology was encountered 163 patients; colonoscopy was performed in 121 of these 163 patients. The tumor diagnosis was confirmed by total colonoscopy in 12/163 (7.4%) patients with adenocarcinoma and 8/163 (4.9%) patients with high-grade dysplasia. Nine patients were diagnosed with stage I, two patients with stage II, and one with stage III disease according to the tumor, nodes, and metastases (TNM) staging system for colorectal cancer. The prevalence of incidental colon cancer in patients with pyogenic liver abscess was significantly higher than that of normal individuals who underwent colonoscopy (0.8%, 90/11,272) at our health care center. CONCLUSIONS: Colon cancer may be one etiology of liver abscess. Colonoscopy should be considered in patients with pyogenic liver abscess with not an apparent primary source of infection.

Cyclooxygenase-2 and vascular endothelial growth factor in chronic hepatitis, cirrhosis and hepatocellular carcinoma.

BACKGROUND/AIMS: Cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) are up-regulated in hepatocellular carcinoma (HCC). To investigate the levels of COX-2 and VEGF expression in chronic hepatitis (CH), cirrhosis, and HCC. METHODS: The immunohistochemical expressions of COX-2 and VEGF were evaluated in tissues from patients with CH (n=95), cirrhosis (n=38), low-grade HCC (LG-HCC; n=6), and high-grade HCC (HG-HCC; n=29). RESULTS: The COX-2 expression scores in CH, cirrhosis, LG-HCC, and HG-HCC were 3.3±1.9 (mean±SD), 4.2±1.7, 5.5±1.0, and 3.4±2.4, respectively (CH vs. cirrhosis, P=0.016; CH vs. LG-HCC, P=0.008; LG-HCC vs. HG-HCC, P=0.004), and the corresponding VEGF expression scores were 0.9±0.8, 1.5±0.7, 1.8±0.9, and 1.6±1.1 (CH vs. cirrhosis, P<0.001; CH vs. LG-HCC, P=0.011; LG-HCC vs. HG-HCC, P=0.075). Both factors were correlated with the fibrosis stage in CH and cirrhosis (COX-2: r=0.427, P<0.001; VEGF: r=0.491, P<0.001). There was a significant correlation between COX-2 and VEGF in all of the tissue samples (r=0.648, P<0.001), and between high COX-2 and VEGF expression scores and survival (COX-2: P=0.001; VEGF: P<0.001). CONCLUSIONS: The expressions of both COX-2 and VEGF are significantly higher in cirrhosis and LG-HCC than in CH. High COX-2 and high VEGF expressions are associated with a high survival rate.