[Show abstract][Hide abstract] ABSTRACT: Background & aim:
To investigate the prevalence, mortalities, and patient characteristics of Acute-on-chronic liver failure (ACLF) according to the AARC (Asian Pacific Association for the Study of the Liver ACLF Research Consortium) and European Association for the Study of the Liver CLIF-C (Chronic Liver Failure Consortium) definitions.
We collected retrospective data for 1470 hospitalized patients with chronic liver disease (CLD) and acute deterioration between January 2013 and December 2013 from 21 university hospitals in Korea.
Of the patients assessed, the prevalence of ACLF based on the AARC and CLIF-C definitions was 9.5% and 18.6%, respectively. The 28-day and 90-day mortality rates were higher in patients with ACLF than in those without ACLF. Patients who only met the CLIF-C definition had significantly lower 28-day and 90-day survival rates than those who only met the AARC definition (68.0% vs. 93.9%, P<0.001; 55.1% vs. 92.4%, P<0.001). Among the patients who had non-cirrhotic CLD, the 90-day mortality of the patients with ACLF was higher than of those without ACLF, although not significant (33.3% vs. 6.0%, P = 0.192). Patients with previous acute decompensation (AD) within 1- year had a lower 90-day survival rate than those with AD more than 1 year prior or without previous AD (81.0% vs. 91.9% or 89.4%, respectively, all P<0.001). Patients who had extra-hepatic organ failure without liver failure had a similar 90-day survival rate to those who had liver failure as a prerequisite (57.0% vs. 60.6%, P = 0.391).
The two ACLF definitions result in differences in mortality and patient characteristics among ACLF patients. We suggest that non-cirrhotic CLD, previous AD within 1 year, and extra-hepatic organ failure should be included in the ACLF diagnostic criteria. In addition, further studies are necessary to develop a universal definition of ACLF.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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).
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.
Preview · Article · Jun 2015 · Clinical and molecular hepatology
[Show abstract][Hide abstract] ABSTRACT: (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).
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).
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).
(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.
Preview · Article · May 2015 · The Korean Journal of Internal Medicine
[Show abstract][Hide abstract] ABSTRACT: EUS-guided fine needle aspiration (EUS-FNA) is one of the alternative methods for tissue sampling of liver solid mass. However, the diagnostic efficacy using cytology alone was limited. In this study, we evaluate the diagnostic accuracy of EUS-guided fine needle biopsy (EUS-FNB) as a percutaneous biopsy rescue for liver solid mass.
The EUS-FNB using core biopsy needle for liver solid mass was performed prospectively for patients who were failure to acquire a tissue or achieve a diagnosis using percutaneous liver biopsy. The primary outcome was the diagnostic accuracy of EUS-FNB for malignancy and specific tumor type. The secondary outcomes were the median numbers of passes required to establish a diagnosis, the proportions of patients in whom immunohistochemical (IHC) stain was possible and obtained adequate specimen, and safety of EUS-FNB.
Twenty-one patients (12 women; mean age, 63 years [range, 37-81]) underwent EUS-FNB for solid liver masses. The median number of needle passes was 2.0 (range, 1-5). On-site cytology and cytology with Papanicolaou stain showed malignancy in 16 patients (76.2%) and 17 patients (81.0%), respectively. In histology with hematoxylin and eosin (H&E) stain, 19 patients (90.5%) were diagnosed malignancy and optimal to IHC stain. The overall diagnostic accuracy for malignancy and specific tumor type were 90.5% and 85.7%, respectively. No complications were seen.
EUS-FNB with core biopsy needle for solid liver mass may be helpful in the management of patients who are unable to diagnose using percutaneous liver biopsy.
This article is protected by copyright. All rights reserved.
No preview · Article · Feb 2015 · Journal of Gastroenterology and Hepatology
[Show abstract][Hide abstract] ABSTRACT: Background/aimsTransient elastography (TE) has become an alternative to liver biopsy (LB). This study investigated the diagnostic performance of liver stiffness (LS) measurement using TE in Korean patients with chronic hepatitis B and C (CHB and CHC).Methods
From April 2006 to June 2014, 916 patients (567 CHB and 349 CHC) who underwent LB and TE at 15 centers were analyzed. The Batts and Ludwig scoring system was used for histologic assessment. Aspartate aminotransferase (AST)–to–platelet ratio indexes (APRI) were calculated. Area under the receiver operating characteristic curve (AUROC) was used.ResultsThe median age, LS value, and APRI score were 45 years, 8.8 kPa, and 0.61, respectively, in CHB patients versus 51 years, 6.8 kPa and 0.55, respectively in CHC patients. TE was significantly superior to APRI in CHB patients (AUROC 0.774 vs. 0.72 for ≥F2, 0.849 vs. 0.812 for ≥F3, and 0.902 vs. 0.707 for F4, respectively; all P<0.05). Furthermore, TE was significantly superior for predicting ≥ F3 stage (AUROC 0.865 vs. 0.840, P=0.009) whereas it was similar for predicting ≥ F2 and F4 stage (AUROC 0.822 vs. 0.796; 0.910 vs. 0.884; all P>0.05) in CHC patients. In CHB patients, optimal cutoff LS values were 7.8 kPa for ≥ F2, 8.2 kPa for ≥ F3, and 11.6 kPa for F4, versus 6.8 kPa, 8.6 kPa, and 14.5 kPa, respectively, in CHC patients.ConclusionsTE can accurately assess the degree of liver fibrosis in Korean patients with CVH. TE was superior to APRI for predicting each fibrosis stage.This article is protected by copyright. All rights reserved.
No preview · Article · Feb 2015 · Liver international: official journal of the International Association for the Study of the Liver
[Show abstract][Hide abstract] ABSTRACT: Tenofovir disoproxil fumarate (TDF) plays a pivotal role in the management of drug-resistant chronic hepatitis B. However, it remains unclear whether TDF-nucleoside analogue combination therapy provides better outcomes than TDF monotherapy. This study aimed to compare the efficacy of TDF monotherapy with that of TDF-nucleoside analogue combination therapy in patients with drug-resistant chronic hepatitis B.
This retrospective cohort study included 76 patients receiving TDF-based rescue therapy for more than 12 months. Suboptimal response was defined as serum HBV-DNA level of >60 IU/mL during prior rescue therapy. Multi-drug resistance was defined as the presence of two or more drug resistance-related mutations confirmed by mutation detection assay. The relationship between baseline characteristics and virologic response (HBV DNA <20 IU/mL) at 12 months were evaluated using logistic regression analysis.
Fifty-five patients (72.4%) were suboptimal responders to prior rescue therapy, and 26 (34.2%) had multi-drug resistance. Forty-two patients (55.3%) received combination therapy with nucleoside analogues. Virologic response at 12 months was not significantly different between the TDF monotherapy group and TDF-nucleoside analogue combination therapy group (p=0.098). The serum HBV DNA level was reduced to -4.49±1.67 log10 IU/mL in the TDF monotherapy group and to -3.97±1.69 log10 IU/mL in the TDF-nucleoside analogue combination therapy group at 12 months (p=0.18). In multivariate analysis, female sex (p=0.032), low baseline HBV-DNA level (p=0.013), and TDF monotherapy (p=0.046) were predictive factors for virologic response at 12 months.
TDF monotherapy showed similar efficacy to that of TDF-nucleoside analogue combination therapy in patients with drug-resistant chronic hepatitis B. (Korean J Gastroenterol 2015;65:35-42).
Preview · Article · Jan 2015 · The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi
[Show abstract][Hide abstract] ABSTRACT: The limited studies with F-fluorodeoxyglucose (F-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.
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 F-FDG PET/computed tomography scan preoperatively and the maximum standardized uptake value of the tumor (maxSUVtumor) and the tumor-to-nontumor SUV ratio (TNR) were calculated from F-FDG uptake. Histopathological differentiation grading was confirmed postoperatively.
Among the patients, 115 cases with primary malignant intrahepatic tumors fulfilled the inclusion criteria. On univariate analysis, preoperative maxSUVtumor and TNR showed a correlation with the overall and early tumor recurrence of HCC, but only maxSUVtumor was associated with overall and early recurrence of IHCC (P<0.05). When considering postoperative histopathological differentiation, a correlation between maxSUVtumor and TNR with HCC and between maxSUVtumor and IHCC was found (P<0.05). However, on multivariate analysis, only early recurrence was associated with TNR in HCC and with maxSUVtumor in IHCC.
A preoperative F-FDG PET scan can be considered a useful reference for postoperative tumor recurrence and histopathological differentiation in cases of primary malignant intrahepatic tumors. F-FDG PET scan results should be interpreted separately for malignant liver tumors.
No preview · Article · Jan 2015 · Nuclear Medicine Communications
[Show abstract][Hide abstract] ABSTRACT: 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.
No preview · Article · Jan 2015 · Journal of Korean Medical Science
[Show abstract][Hide abstract] ABSTRACT: Hepatocellular carcinoma (HCC) is one of the major cancers with a high incidence and mortality in Korea. A Korean multidisciplinary collaborative committee consisting of hepatologists, radiologists, epidemiologists and family medicine doctors systematically reviewed clinical practice guidelines in the world and literatures. The level of evidence for each recommendation was assessed and discussed to reach a consensus. Meta-analysis was also conducted to evaluate the grade of recommendation for the five key questions. Several randomized controlled studies and cohort studies showed a survival gain associated with surveillance for those at risk of developing HCC. The target populations for HCC surveillance were identified as hepatitis B virus or hepatitis C virus carriers and cirrhotic patients, since numerous studies revealed that these patients have significantly higher risk of HCC compared with non-infected or non-cirrhotic controls. Individual surveillance strategy according to treatment history or degree of fibrosis in patients with viral hepatitis remains to be settled. Based on several cohort and randomized studies, a surveillance interval of six months was recommend. The starting age of surveillance was determined as 40 years from the epidemiologic data. Although ultrasonography (US) is the mainstay for detection of HCC, its sensitivity is not fully accepted. Measurement of serum alpha-fetoprotein can complement US examination, increasing the sensitivity of HCC detection. The recommendation for HCC surveillance is that those with hepatitis B virus (or hepatitis C virus) infection or cirrhosis should have liver US and serum alpha-fetoprotein measurement every six months from 40 years of age or at the time of diagnosis of cirrhosis.
Full-text · Article · Jan 2015 · Journal of the Korean Medical Association
[Show abstract][Hide abstract] ABSTRACT: Background/Aims
To investigate the association between the baseline profiles and dynamics of hepatitis B virus (HBV) DNA polymerase gene mutations and the long-term virological response of lamivudine (LAM)-adefovir (ADV) combination therapy in patients with LAM-resistant chronic hepatitis B.
Seventy-five patients who received LAM-ADV combination therapy for more than 12 months were analyzed. Restriction fragment mass polymorphism assays were used to detect and monitor the dynamics of LAM- and ADV-resistant mutations.
The median duration of LAM-ADV combination therapy was 26 months (range, 12 to 58 months). The baseline mutation profiles, rtM204I (p=0.992), rtM204I/V (p=0.177), and rtL180M (p=0.051), were not correlated with the cumulative virological response, and the baseline HBV DNA level (p=0.032) was the only independent predictive factor for cumulative virological response. Tests for LAM- and ADV-resistant mutations were performed in 12 suboptimal responders in weeks 48 and 96. The population of rtM204 mutants persisted or increased in 8 of 12 patients, and rtA181T mutants newly emerged as a minor population in four patients until 96 weeks. Nevertheless, the viral loads progressively decreased during rescue therapy, and these dynamics did not correlate with virological response.
The baseline profile and dynamics of LAM-resistant mutations during LAM-ADV combination therapy are not associated with a virological response.
[Show abstract][Hide abstract] ABSTRACT: Background & Aims
Both corticosteroid and pentoxifylline reduce short-term mortality in severe alcoholic hepatitis. However, few studies have directly compared the efficacy of pentoxifylline and corticosteroid in patients with this condition.
In this multicentre, open-labelled, randomised non-inferiority trial, we assigned 121 patients with severe alcoholic hepatitis (Maddrey’s discriminant function ⩾32) to receive either pentoxifylline (400 mg, 3 times daily, in 62 subjects) or prednisolone (40 mg daily, in 59 subjects). The primary end point was non-inferiority in survival at the 1 month time point for the pentoxifylline treatment compared with prednisolone.
The 1-month survival rate of patients receiving pentoxifylline was 75.8% (15 deaths) compared with 88.1% (7 deaths) in those, taking prednisolone, for a treatment difference of 12.3% (95% confidence interval, −4.2% to 28.7%; p = 0.08). The 95% confidence interval for the observed difference exceeded the predefined margin of non-inferiority (Δ15%) and included zero. The 6-month survival rate was not significantly different between the pentoxifylline and prednisolone groups (64.5% vs. 72.9%; p = 0.23). At 7 days, the response to therapy assessed by the Lille model was significantly lower in the prednisolone group (n = 58) than in the pentoxifylline group (n = 59): 0.35 vs. 0.50 (p = 0.012). Hepatitis complications, including hepatorenal syndrome and side effects, such as infection and gastrointestinal bleeding, were similar in the two groups.
The findings demonstrate that the efficacy of the pentoxifylline is not statistically equivalent to the efficacy of prednisolone, supporting the use of prednisolone as a preferred treatment option in patients with severe alcoholic hepatitis.
Full-text · Article · Oct 2014 · Journal of Hepatology
[Show abstract][Hide abstract] ABSTRACT: Background/aims:
Chronic hepatocellular damage is closely associated with hepatic fibrosis and fatal complication in most liver diseases. The aim of this study is to compare the efficacy and safety of biphenyl dimethyl dicarboxylate (DDB) and ursodeoxycholic acid (UDCA) in patients with abnormal ALT.
One-hundred thirty-five patients with elevated ALT were randomized to receive either 750 mg/day of DDB or 300 mg/day of UDCA for 24 weeks in 4 referral hospitals. Ninety-three (69%) patients had non-alcoholic steatohepatitits, 27 (20%) had alcoholic hepatitis, and 15 (11%) had chronic hepatitis. The primary end point was the rate of ALT normalization at week 24. The secondary endpoints were changes in AST, liver stiffness, and the incidence of adverse events.
A total of 101 patients completed 24 weeks of therapy. ALT normalization at week 24 was observed in 44 (80.0%) patients in DDB group and 16 (34.8%) in UDCA group (p<0.001). Higher mean reduction of ALT levels from baseline to 24 weeks was seen in DDB group compared with UDCA group (-70.0% vs. -35.9%, p<0.001). Normalization of AST level (p=0.53) and change in the liver stiffness (p=0.703) were not significantly different between the two groups. Severe adverse drug reaction occurred in 1 patient in DDB group but the subject continued therapy during the study period.
DDB was not inferior to UDCA for normalizing ALT level. Furthermore it was safe and well tolerated by patients with abnormal ALT.
Preview · Article · Jul 2014 · The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi
[Show abstract][Hide abstract] ABSTRACT: Choledocholithiasis is one of the causes of jaundice and may require urgent treatment. Endoscopic retrograde cholangiopancreatography (ERCP) has been the primary management strategy for choledocholithiasis. However, small stones can be overlooked during ERCP. The aim of this study was to evaluate the accuracy of intraductal ultrasonography (IDUS) for detecting choledocholithiasis in icteric patients with highly suspected common bile duct (CBD) stones without definite stone diagnosis on ERCP. Ninety-five icteric (bilirubin a parts per thousand yen3 mg/dL) patients who underwent ERCP for highly suspected choledocholithiasis without definite filling defects on cholangiography were prospectively enrolled in the present study. We evaluated the bile duct using IDUS for the presence of stones or sludge. Reference standard for choledocholithiasis was endoscopic extraction of stone or sludge. Bile duct stones were detected with IDUS in 31 of 95 patients (32.6 %). IDUS findings were confirmed by endoscopic stone extraction in all patients. The mean diameter of CBD stones detected by IDUS was 2.9 mm (range 1-7 mm). IDUS revealed biliary sludge in 24 patients (25.2 %) which was confirmed by sludge extraction in 21 patients (87.5 %). In dilated CBD, detection rate of bile duct stone/sludge based on IDUS was significantly higher than in non-dilated CBD (p = 0.004). IDUS is useful for the detection of occult CBD stone on ERCP in icteric patients with highly suspected CBD stones.
No preview · Article · Jul 2014 · Digestive Diseases and Sciences
[Show abstract][Hide abstract] ABSTRACT: 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.