[Show abstract][Hide abstract] ABSTRACT: To determine factors predictive of discordance in staging liver fibrosis using liver biopsy (LB) and acoustic radiation force impulse (ARFI) elastography in patients with chronic hepatitis B (CHB).
Consecutive patients with CHB who underwent LB and ARFI elastography on the same day from November 2010 to March 2013 were prospectively recruited from three tertiary hospitals.
We analyzed 105 patients (median age of 47 years). The F0-1, F2, F3, and F4 fibrosis stages were identified in 27 (25.7%), 27 (25.7%), 21 (20.0%), and 30 (28.6%) patients, respectively. The areas under the receiver operating characteristics curves for ARFI elastography in assessing ≥F2, ≥F3, and F4 was 0.814, 0.848, and 0.752, respectively. The discordance of at least one stage between LB and ARFI was observed in 68 patients (64.8%) and of at least two stages in 16 patients (15.2%). In a multivariate analysis, advanced fibrosis stage (F3-4) was the only factor that was negatively correlated with one-stage discordance (p=0.042). Moreover, advanced fibrosis stage was negatively (p=0.016) correlated and body mass index (BMI) was positively (p=0.006) correlated with two-stage discordance.
Advanced fibrosis stage (F3-4) was a predictor of nondiscordance between LB and ARFI elastography; BMI also influenced the accuracy of ARFI elastography.
Gut and Liver 06/2015; DOI:10.5009/gnl14391 · 1.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background & aims:
Few noninvasive methods can accurately identify esophageal varices (EVs) in patients with compensated cirrhosis. We developed and validated a novel, acoustic radiation force impulse (ARFI) elastography-based prediction model for high-risk EVs (HEVs) in patients with compensated cirrhosis.
A total of 143 patients with compensated cirrhosis between February, 2010 and February, 2013 (training set) and 148 between June, 2010 and May, 2013 (validation set) who underwent ARFI elastography and endoscopy were prospectively recruited. Independent predictors of HEVs were used to construct a prediction model.
Based on multivariate analysis, we developed two new statistical models, a varices risk score and ARFI-spleen diameter-to-platelet ratio score (ASPS), the latter of which was calculated as ARFI velocity × spleen diameter/platelet count. The area under receiver operating characteristic curve (AUROC) of the varices risk score and ASPS to predict HEVs were 0.935 (95% confidence interval [CI] 0.882-0.970) and 0.946 (95% CI 0.895-0.977), respectively. When ASPS, a simpler model with a higher AUROC, was applied in the validation set, acceptable diagnostic accuracy for HEVs was observed (AUROC = 0.814 [95% CI 0.743-0.885]). To detect HEVs, a negative predictive value of 98.3% was achieved at ASPS <2.83, whereas a positive predictive value of 100% was achieved at ASPS >5.28.
ASPS, a novel noninvasive ARFI-based prediction model, can accurately identify HEVs in patients with compensated cirrhosis. ASPS <2.83 may safely rule out the presence of HEVs, whereas patients with ASPS >5.28 should be considered for endoscopic examinations or appropriate prophylactic treatment.
PLoS ONE 03/2015; 10(3):e0121009. DOI:10.1371/journal.pone.0121009 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Unlabelled:
New definitions and criteria were released at the Baveno V consensus meeting. The purposes of this study were to verify Baveno V definitions and criteria for failure to control bleeding and to determine the usefulness of the combined use of the Adjusted Blood Requirement Index [ABRI: (number of blood units)/(final hematocrit-initial hematocrit)+0.01] with Baveno V criteria. In all, 246 consecutive liver cirrhosis patients with acute bleeding associated with portal hypertension were enrolled prospectively between January 2010 and October 2012. The treatment outcome on day 5 was assessed by endoscopy. For the ABRI calculation, two hematocrit levels were used as the initial hematocrit: the first level measured upon patient arrival (ABRI-A) and the lowest level measured before transfusion (ABRI-B). Treatment failures were identified in 53 patients, of whom 24 died. Based on repeated endoscopic findings, 29 patients were identified as treatment failures, while according to Baveno V criteria, 47 patients were regarded as treatment failures. The area under the receiver operating characteristic curve (AUROC) of Baveno V criteria was 0.906, and the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio were 83.0%, 98.4%, 93.6%, 95.5%, 53.41, and 0.17, respectively. The AUROC of Baveno V criteria was significantly greater than those of Baveno IV (P=0.0001) and Baveno II/III (P<0.0001) criteria. Adding ABRI-A or -B to Baveno V criteria resulted in a significant reduction of the AUROC (P<0.05).
The Baveno V criteria are good predictors of treatment failure of early-stage acute gastrointestinal bleeding in patients with portal hypertension, while the addition of ARBI does not improve the prediction accuracy of the outcome of bleeding.
[Show abstract][Hide abstract] ABSTRACT: Background/AimsSorafenib is recommended as a standard treatment for advanced hepatocellular carcinoma (HCC). We investigated the efficacy and safety of sorafenib as a first-line therapy in Korean patients with advanced HCC. 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. ResultsThe 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 (AFP) < 200 ng/mL (5.8 vs. 4.1 months), and the advent of hand-foot-skin reaction (HFSR) 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 AFP < 200 ng/mL (5.6 vs. 2.8 months) and the advent of HFSR 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-naïve HCC, how to select candidates with favorable outcomes should be further investigated.
Journal of Gastroenterology and Hepatology 02/2014; 29(7). DOI:10.1111/jgh.12542 · 3.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate the clinical characteristics of acute hepatitis A during a recent outbreak in Korea. Data of patients diagnosed with acute hepatitis A from 2007 to 2009 were collected from 21 tertiary hospitals retrospectively. Their demographic, clinical, and serological characteristics and their clinical outcomes were analyzed. A total of 4,218 patients (mean age 33.3 yr) were included. The median duration of admission was 9 days. The mean of the highest ALT level was 2,963 IU/L, total bilirubin was 7.3 mg/dL, prothrombin time INR was 1.3. HBsAg was positive in 3.7%, and anti-HCV positive in 0.7%. Renal insufficiency occurred in 2.7%, hepatic failure in 0.9%, relapsing hepatitis in 0.7%, and cholestatic hepatitis in 1.9% of the patients. Nineteen patients (0.45%) died or were transplanted. Complications of renal failure or prolonged cholestasis were more frequent in patients older than 30 yr. In conclusion, most patients with acute hepatitis A recover uneventfully, however, complication rates are higher in patients older than 30 yr than younger patients. Preventive strategies including universal vaccination in infants and active immunization of hepatitis A to adult population should be considered for prevention of community-wide outbreaks of hepatitis A in Korea.
Journal of Korean medical science 02/2014; 29(2):248-53. DOI:10.3346/jkms.2014.29.2.248 · 1.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hepatocellular adenoma (HCA) is one of the important complications of glycogen storage disease type Ia (GSD-Ia) because it can be transformed into hepatocellular carcinoma. Although surgical resection is a standard treatment of choice for solitary HCA, multiple HCAs in GSD-Ia patients present as therapeutic challenges for curative treatment. Therefore, treatment strategy according to malignant potential is important in management of HCAs in GSD-Ia. The authors present a case of histologically proven multiple HCAs without β-catenin mutations occurred in a GSD-Ia patient treated successfully with percutaneous radiofrequency ablation as a minimally invasive therapy.
World Journal of Gastroenterology 11/2013; 19(42):7480-7486. DOI:10.3748/wjg.v19.i42.7480 · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lamivudine resistance develops in up to 80% of patients with chronic hepatitis B (CHB) after 5 years of treatment. Cross-resistance between nucleos(t)ide analogues limits management options in these patients. To investigate the role of peginterferon alfa-2a as rescue therapy in these patients, the efficacy and safety of peginterferon alfa-2a between treatment-naïve patients and lamivudine-resistant patients with hepatitis B e antigen (HBeAg)-positive CHB were compared.
A total of 150 HBeAg-positive CHB patients were stratified according to prior treatment. Lamivudine-resistant patients (n=64) and treatment-naïve patients (n=86) received peginterferon alfa-2a once-weekly for 48 weeks and were followed-up for an additional 24 weeks. Primary endpoints were HBeAg loss and hepatitis B virus (HBV) DNA less than 100,000 copies/mL at end of follow-up.
A total of 65 (76%) treatment-naïve patients and 49 (77%) lamivudine-resistant patients completed treatment and 24 weeks of follow-up. Rates of HBeAg loss were comparable at end of follow-up between treatment-naïve patients and lamivudine-resistant patients (20.9% and 23.4%, respectively; p=0.8423). Similarly, rates of HBV DNA less than 100,000 copies/mL were comparable at end of follow-up between treatment-naïve patients and lamivudine-resistant patients (20.9% and 21.9%, respectively; p=1.000). There was no statistically significant difference in alanine aminotransferase normalization rates between treatment-naïve patients and lamivudine-resistant patients (36.0% and 29.7%, respectively; p=0.4848). One patient in each group achieved hepatitis B surface antigen (HBsAg) loss and seroconversion. The most common adverse events were those known to occur with peginterferon alfa-2a therapy and safety profiles were similar between both patient populations.
Peginterferon alfa-2a may be effective as a rescue therapy in patients with lamivudine-resistant HBeAg-positive CHB.
[Show abstract][Hide abstract] ABSTRACT: Chronic hepatitis C patients with advanced fibrosis have unsatisfactory sustained virological response (SVR) rates. Few data demonstrating the efficacy of combination therapy in chronic hepatitis C patients with advanced fibrosis in South Korea are available. The purpose of this study was to assess whether the stage of fibrosis impacts the efficacy of combination therapy for chronic hepatitis C.
We retrospectively reviewed data for a total of 109 patients with chronic hepatitis C, treated with peginterferon alfa and ribavirin. SVR according to the stage of liver fibrosis assessed by pretreatment liver biopsy and genotype results were analyzed.
Data from 66 genotype 1 patients (60.6%) and 43 genotype 2 or 3 patients (39.4%) among the 109 patients were analyzed. SVR rates for the genotype 1 patients were significantly lower for the stage 3-4 group (32.1%) than the stage 0-2 group (78.9%; P<0.001). SVR rates (92.0% for stage 0-2, 77.8% for stage 3-4, P=0.184) of genotype 2 or 3 patients were not significantly different according to fibrosis stage. Likewise, the frequency of adverse events was not significantly different according to fibrosis stage.
Compared to patients without advanced fibrosis, we can anticipate good SVR rates for genotype 2 or 3 patients with advanced fibrosis and they did not show an inferior tolerability for peginterferon and ribavirin combination therpy. Our results suggest that active treatment is needed for genotype 2 or 3 patients with advanced fibrosis.
Clinical and molecular hepatology 06/2013; 19(2):148-55. DOI:10.3350/cmh.2013.19.2.148
[Show abstract][Hide abstract] ABSTRACT: Occurrence of hypophosphatemic osteomalacia (HO) induced by administration of low-dose adefovir therapy is rare, and bone scintigraphy of the disease has rarely been reported. We report on bone scintigraphic findings in patients with HO. Multiple uptakes in ribs, spines, and lower extremities, suggesting multiple fractures, were observed on bone scintigraphy. Patients were diagnosed as HO associated with adefovir therapy. Owing to the same predilection sites, multiple uptakes on the axial skeleton can cause confusion with malignant metastatic disease; however, involvement of lower extremity skeletons can provide a scintigraphic clue for use in differentiation of HO from malignant osseous metastasis.
Clinical nuclear medicine 03/2013; 38(5). DOI:10.1097/RLU.0b013e3182868a7f · 3.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study evaluated the clinical outcomes of balloon-occluded retrograde transvenous obliteration (BRTO) for the treatment of hemorrhage from gastric varices (GV) in Korean patients with liver cirrhosis (LC).
We retrospectively analyzed data from 183 LC patients who underwent BRTO for GV bleeding in 6 university-based hospitals between January 2001 and December 2010.
Of the 183 enrolled patients, 49 patients had Child-Pugh (CP) class A LC, 105 had CP class B, and 30 had CP class C at the time of BRTO. BRTO was successfully performed in 177 patients (96.7%). Procedure-related complications (e.g., pulmonary thromboembolism and renal infarction) occurred in eight patients (4.4%). Among 151 patients who underwent follow-up examinations of GV, 79 patients (52.3%) achieved eradication of GV, and 110 patients (72.8%) exhibited marked shrinkage of the treated GV to grade 0 or I. Meanwhile, new-appearance or aggravation of esophageal varices (EV) occurred in 54 out of 136 patients who underwent follow-up endoscopy (41.2%). During the 36.0±29.2 months (mean±SD) of follow-up, 39 patients rebled (hemorrhage from GV in 7, EV in 18, nonvariceal origin in 4, and unknown in 10 patients). The estimated 3-year rebleeding-free rate was 74.8%, and multivariate analysis showed that CP class C was associated with rebleeding (odds ratio, 2.404; 95% confidence-interval, 1.013-5.704; P=0.047).
BRTO can be performed safely and effectively for the treatment of GV bleeding. However, aggravation of EV or bleeding from EV is not uncommon after BRTO; thus, periodic endoscopy to follow-up of EV with or without prophylactic treatment might be necessary in LC patients undergoing BRTO.
Clinical and molecular hepatology 12/2012; 18(4):368-74. DOI:10.3350/cmh.2012.18.4.368
[Show abstract][Hide abstract] ABSTRACT: To determine whether bispectral index (BIS) monitoring is useful for propofol administration for deep sedation during endoscopic retrograde cholangiopancreatography (ERCP).
Fifty-nine consecutive patients with a variety of reasons for ERCP who underwent the procedure at least twice between 1 July 2010 and 30 November 2010. This was a randomized cross-over study, in which each patient underwent ERCP twice, once with BIS monitoring and once with control monitoring. Whether BIS monitoring was done during the first or second ERCP procedure was random. Patients were intermittently administered a mixed regimen including midazolam, pethidine, and propofol by trained nurses. The nurse used a routine practice to monitor sedation using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale or the BIS monitoring. The total amount of midazolam and propofol used and serious side effects were compared between the BIS and control groups.
The mean total propofol dose administered was 53.1 ± 32.2 mg in the BIS group and 54.9 ± 30.8 mg in the control group (P = 0.673). The individual propofol dose received per minute during the ERCP procedure was 2.90 ± 1.83 mg/min in the BIS group and 3.44 ± 2.04 mg in the control group (P = 0.103). The median value of the MOAA/S score during the maintenance phase of sedation was comparable for the two groups. The mean BIS values throughout the procedure (from insertion to removal of the endoscope) were 76.5 ± 8.7 for all 59 patients in using the BIS monitor. No significant differences in the frequency of < 80% oxygen saturation, hypotension (< 80 mmHg), or bradycardia (< 50 beats/min) were observed between the two study groups. Four cases of poor cooperation occurred, in which the procedure should be stopped to add the propofol dose. After adding the propofol, the procedure could be conducted successfully (one case in the BIS group, three cases in the control group). The endoscopist rated patient sedation as excellent for all patients in both groups. All patients in both groups rated their level of satisfaction as high (no discomfort). During the post-procedural follow-up in the recovery area, no cases of clinically significant hypoxic episodes were recorded in either group. No other postoperative side effects related to sedation were observed in either group.
BIS monitoring trend to slighlty reduce the mean propofol dose. Nurse-administered propofol sedation under the supervision of a gastroenterologist may be considered an alternative under anesthesiologist.
World Journal of Gastroenterology 11/2012; 18(43):6284-9. DOI:10.3748/wjg.v18.i43.6284 · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We evaluated changes in liver function parameters and risk factors for the deterioration of liver function 12 months after percutaneous radiofrequency ablation (RFA) therapy in patients with hepatocellular carcinoma (HCC).
The subjects in this retrospective study comprised 102 patients with HCC who had undergone RFA therapy and exhibited no recurrence of HCC 12 months thereafter. Serial changes in serum total bilirubin and albumin, prothrombin time, and Child-Pugh score were evaluated before RFA and 3, 6, 9, and 12 months thereafter. Deterioration of liver function was defined when the Child-Pugh score increased by at least 2 at 12 months after RFA therapy. We determined the factors related to aggravation of liver function after RFA therapy.
Liver function had deteriorated 12 months after RFA in 29 patients (28.4%). Serum albumin levels decreased significantly from before (3.7±0.1 g/dL, mean±SD) to 12 months after RFA therapy (3.3±0.1 g/dL, P=0.002). The Child-Pugh score increased significantly during the same time period (from 6.1±0.2 to 7.2±0.3, P<0.001). Pre-RFA thrombocytopenia (≤100,000/mm(3)) was revealed as a significant risk factor for the deterioration of liver function after RFA. However, no patients had episodes of bleeding as a complication of RFA.
Among the liver-function parameters, serum albumin level was markedly decreased in HCC patients over the course of 24 months after RFA therapy. A pre-RFA thrombocytopenia represents a major risk factor for the deterioration of liver function.
Clinical and molecular hepatology 09/2012; 18(3):302-8. DOI:10.3350/cmh.2012.18.3.302
[Show abstract][Hide abstract] ABSTRACT: In addition to hematopoietic effect, the erythropoietin is known as a multifunctional cytokine with anti-fibrosis and organ-protective activities. The purpose of this study was to evaluate the effect of recombinant human erythropoietin (rhEPO) on hepatic fibrosis and hepatic stellate cells (HSCs).
Carbon tetrachloride (CCl(4)) induced hepatic fibrosis mice models were used for in vivo study and HSCs line for in vitro study. CCl(4) and rhEPO (0, 200 or 1000 U/kg) was injected intraperitoneally in BALB/c mice three times a week for 4 weeks. Immunohistochemistry and immunoblotting were performed to evaluate expressions of transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (α-SMA), and fibronectin in explanted liver. Immunoblotting of α-SMA, phophorylated Smad-2 and Smad-2/3 was performed in HSCs treated with TGF-β1 and/or rhEPO.
Expressions of TGF-β1, α-SMA, and fibronectin were increased in CCl(4) injected mice livers, but significantly attenuated by co-treatment with CCl(4) and rhEPO. Co-treatment of rhEPO markedly suppressed fibrosis in Masson's trichrome compared with treatment of only CCl(4). TGF-β1 increased phosphorylated α-SMA, Smad-2 expressions in HSCs, which were decreased by rhEPO co-treatment.
Treatment of rhEPO effectively suppressed fibrosis in CCl(4)-induced liver fibrosis mice models. Anti-fibrosis effect of rhEPO could be related to inhibition of TGF-β1 induced activation of HSCs.
Chinese medical journal 09/2012; 125(17):3098-103. DOI:10.3760/cma.j.issn.0366-6999.2012.17.024 · 1.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To address a growing concern about drug-induced liver injury (DILI), a nationwide study was performed to investigate the significance of DILI in Korea.
From May 2005 to May 2007, cases of DILI (alanine transferase >3 × upper normal limit or total bilirubin >2 × upper normal limit) from 17 referral university hospitals were prospectively enrolled. Adjudication by the seven review boards was considered for the confirmation of causality and the Roussel Uclaf Causality Assessment Method (RUCAM) scale was used.
A total of 371 cases were diagnosed with DILI. The extrapolated incidence of hospitalization at university hospital in Korea was 12/100,000 persons/year. The causes included "herbal medications" (102, 27.5%), "prescription or non-prescription medications" (101, 27.3%), "health foods or dietary supplements" (51, 13.7%), "medicinal herbs or plants" (35, 9.4%), "folk remedies" (32, 8.6%), "combined" (30, 8.2%), "herbal preparations" (12, 3.2%), and others (8, 2.2%). Nine cases were linked to acetaminophen. The frequencies of hepatocellular, mixed, and cholestatic types were 76.3, 14.8, and 8.9%, respectively. A total of 234 cases met the criteria for Hy's law. Five patients died or underwent transplantation. Twenty-five cases (21 herbs and 4 medications) did not meet the time-to-onset criteria of the RUCAM.
DILI appears to be a highly relevant health problem in Korea. "Herbal medications" are the principal cause of DILI. A more objective and reproducible causality assessment tool is strongly desired as the RUCAM scale frequently undercounts the cases caused by herbs owing to a lack of previous information and incompatible time criteria.
The American Journal of Gastroenterology 06/2012; 107(9):1380-7. DOI:10.1038/ajg.2012.138 · 10.76 Impact Factor