New prognostic model for hospitalized patients with alcoholic cirrhosis and Maddrey's discriminant function <32.

BACKGROUND & AIMS: Few studies have investigated the prognosis of patients with non-severe alcoholic hepatitis (Non-SAH). The study aimed to develop a new prognostic model for patients with especially Non-SAH. METHODS: We extracted 316 hospitalized patients with alcoholic cirrhosis without severe alcoholic hepatitis, defined as Maddrey's discriminant function score lower than 32, from the retrospective Korean Acute-on-Chronic Liver Failure (KACLiF) cohort to develop a new prognostic model (training set), and validated it in 419 patients from the prospective KACLiF cohort (validation set). Prognostic factors for death and liver transplantation were analyzed to construct a prognostic model. RESULTS: Twenty-one and 24 patients died within 6 months in both sets, respectively. In the training set, the highest area under the curve (AUC) of conventional prognostic models was 0.765, 0.732, and 0.684 for 1-, 3-, and 6-month mortality, respectively. Refractory ascites, vasopressor use, and hyponatremia were independently associated with mortality of cirrhotic patients with Non-SAH. The new model consisted of four variables: past deterioration, neutrophil proportion > 70%, Na < 128 mmol/L, and vasopressor use. It showed the highest accuracy for short-term mortality in the training and validation sets (0.803 and 0.786; 0.797 and 0.776; and 0.789 and 0.721 for 1-, 3-, and 6-month mortality, respectively). CONCLUSION: There is a group of patients with high risk among those classified as Non-SAH. The new model will help stratifying cirrhotic patients with Non-SAH more accurately in terms of prognosis. The patients with high Non-SAH score need to monitor closely and might be considered for preemptive liver transplantation. TRIAL REGESTRATION: ClinicalTrials.gov identifier: NCT02650011.

The chronological changes in the seroprevalence of anti-hepatitis A virus IgG from 2005 to 2019: Experience at four centers in the capital area of South Korea.

Although universal vaccination has been administered to toddlers, South Korea has had periodic nationwide outbreaks of acute hepatitis A since the late 2000s. We examined the chronological changes in the seroprevalence of anti-hepatitis A virus (HAV) immunoglobulin G (IgG) over the past 15 years (2005-2019). We retrospectively collected data from 45,632 subjects who underwent anti-HAV IgG testing without evidence of acute HAV infection at four centers in the capital area of South Korea between January 2005 and December 2019. The seroprevalence of anti-HAV IgG was analyzed according to age and compared among seven age groups and five time periods. Additionally, age-period-cohort analyses were used to identify the age, period, and cohort effects of the seroprevalence of anti-HAV IgG. The mean age of the enrolled subjects was 39.2 ±â€…19.2 years, and the average anti-HAV IgG positivity rate was 66.4%. During the 15 years, the seroprevalence of anti-HAV IgG in people aged 0 to 19 years significantly increased over time (P < .001). In people aged 20 to 29 years, the seroprevalence slightly decreased to that of the early 2010s (31.3% in 2005-2007 to 19.7% in 2011-2013) but rebounded to 39.5% in 2017 to 2019. In contrast, the seroprevalence of anti-HAV IgG in those aged 30 to 49 years decreased over time (P < .001). The seroprevalence of anti-HAV IgG in those aged 20 to 39 years in 2017 to 2019 was still less than 40%. In addition, the seroprevalence of anti-HAV IgG in people aged 50 to 59 years has recently decreased. Since the introduction of the universal vaccination, the seroprevalence of anti-HAV IgG in children and young adults has gradually increased. However, the seroprevalence of anti-HAV IgG in people in their 20s remains low, and the seroprevalence of anti-HAV IgG in people in their 30s and 40s is gradually decreasing. Therefore, a new strategy for HAV vaccination is needed for those in their 20s to 40s.

Severe Acute Respiratory Syndrome Coronavirus-2 Antibody Responses in Hospitalized Patients with Coronavirus Disease 2019 in Daegu, Korea.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) started to spread in Daegu beginning at the end of February 2020. IgG and IgM antibodies against SARS-CoV-2 were measured in hospitalized patients with COVID-19 with moderate to severe symptoms to improve the understanding of antibody responses. METHODS: We enrolled 312 patients with COVID-19 admitted to seven hospitals located in Daegu. Using serum (or plasma) samples from patients with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infections, both IgG and IgM antibodies were measured using commercial enzyme-linked immunosorbent assay (R-FIND CO¬VID-19 ELISA, SG medical, Seoul, Korea). RESULTS: The median value from the initial diagnosis, confirmed by SARS-CoV-2 PCR, to the sampling date was 24 days (day 1 to 88). The total positive rate of IgG was 93.9% and the positive IgM rate was 39.4%, without considering the elapsed period after diagnosis. Positive IgG and IgM rates were highest at 100.0% and 59.0%, respectively, at 3 weeks (15 - 21 days). IgG showed a high positive rate of 79.3% even within 7 days after the initial diag-nosis of the disease and maintained a positive rate of 97.8% until after 8 weeks. CONCLUSIONS: Among hospitalized patients with COVID-19, IgG was detected from the beginning of the diagnosis and persisted for an extended time period.

Production of (-)-α-bisabolol in metabolically engineered Saccharomyces cerevisiae.

(-)-α-Bisabolol is a natural monocyclic sesquiterpene alcohol present in German chamomile and has been used as an ingredient of functional foods, cosmetics and pharmaceuticals. In this study, metabolic engineering strategies were attempted to produce (-)-α-bisabolol in Saccharomyces cerevisiae. The codon-optimized MrBBS gene coding for (-)-α-bisabolol synthase from Matricaria recutita was expressed in S. cerevisiae for (-)-α-bisabolol production. The resulting strain (DM) produced 9.5 mg/L of (-)-α-bisabolol in 24 h of batch culture. Additionally, the mevalonate pathway was intensified by introducing a truncated HMG1 gene coding for HMG-CoA reductase and ERG10 encoding acetyl-CoA thiolase. The resulting strain (DtEM) produced a 2.9-fold increased concentration of (-)-α-bisabolol than the DM strain. To increase the acetyl-CoA pool, the ACS1 gene coding for acetyl-CoA synthetase was also overexpressed in the DtEM strain. Finally, the DtEMA strain produced 124 mg/L of (-)-α-bisabolol with 2.7 mg/L-h of productivity in a fed-batch fermentation, which were 13 and 6.8 times higher than the DM strain in batch culture, respectively. Conclusively, these metabolically-engineered approaches might pave the way for the sustainable production of other sesquiterpenes in engineered S. cerevisiae.

Computed Tomography-Determined Body Composition Abnormalities Usefully Predict Long-term Mortality in Patients With Liver Cirrhosis.

OBJECTIVE: We evaluated the prognostic impacts of body composition components measured by computed tomography (CT) in patients with liver cirrhosis. METHODS: A total of 160 cirrhotic patients who underwent CT and hepatic venous pressure gradient measurements were retrospectively enrolled. Cross-sectional areas of skeletal muscle, visceral and subcutaneous fat, and mean CT attenuation of trabecular bone of the fourth lumbar vertebral level (L4HU) were measured. RESULTS: Multivariate analysis showed model for end-stage liver disease score [hazard ratio (HR), 1.086; 95% confidence interval (CI), 1.020-1.156; P = 0.010], hepatic venous pressure gradient (HR, 1.076; 95% CI, 1.021-1.135; P = 0.006), sarcopenia (HR, 1.890; 95% CI, 1.032-3.462; P = 0.039), and L4HU (HR, 1.960 for L4HU <145 Hounsfield units; 95% CI, 1.094-3.512; P = 0.024) were independently associated with long-term mortality. In patients with decompensated cirrhosis, subcutaneous adipose tissue index was the only independent predictor (HR, 0.984; 95% CI, 0.969-0.999; P = 0.039). CONCLUSION: Body composition abnormalities determined by CT are associated with long-term prognosis in cirrhotic patients.

Serial Observations of Muscle and Fat Mass as Prognostic Factors for Deceased Donor Liver Transplantation.

OBJECTIVE: Muscle depletion in patients undergoing liver transplantation affects the recipients' prognosis and therefore cannot be overlooked. We aimed to evaluate whether changes in muscle and fat mass during the preoperative period are associated with prognosis after deceased donor liver transplantation (DDLT). MATERIALS AND METHODS: This study included 72 patients who underwent DDLT and serial computed tomography (CT) scans. Skeletal muscle index (SMI) and fat mass index (FMI) were calculated using the muscle and fat area in CT performed 1 year prior to surgery (1 yr Pre-LT), just before surgery (Pre-LT), and after transplantation (Post-LT). Simple aspects of serial changes in muscle and fat mass were analyzed during three measurement time points. The rate of preoperative changes in body composition parameters were calculated (preoperative ΔSMI [%] = [SMI at Pre-LT - SMI at 1 yr Pre-LT] / SMI at Pre-LT × 100; preoperative ΔFMI [%] = [FMI at Pre-LT - FMI at 1 yr Pre-LT] / FMI at Pre-LT × 100) and assessed for correlation with patient survival. RESULTS: SMI significantly decreased during the preoperative period (mean preoperative ΔSMI, -13.04%, p < 0.001). In the multivariable analysis, preoperative ΔSMI (p = 0.016) and model for end-stage liver disease score (p = 0.011) were independent prognostic factors for overall survival. The mean survival time for patients with a threshold decrease in the preoperative ΔSMI (≤ -30%) was significantly shorter than for other patients (p = 0.007). Preoperative ΔFMI was not a prognostic factor but FMI increased during the postoperative period (p = 0.009) in all patients. CONCLUSION: A large reduction in preoperative SMI was significantly associated with reduced survival after DDLT. Therefore, changes in muscle mass during the preoperative period can be considered as a prognostic factor for survival after DDLT.

[Ossification of the Transverse Ligament of the Atlas on CT: Frequency and Associated Findings]. / CT를 이용한 환추횡인대 골화증의 빈도와 연관 소견.

Purpose: To determine the frequency of ossification of the transverse ligament of the atlas (OTLA) and to investigate the associated findings on cervical spine CT and plain radiography. Materials and Methods: We reviewed 5201 CT scans of the cervical spine of 3975 consecutive patients over an 11-year period for the presence of OTLA and compared them with those of age- and sex-matched controls. The frequency and associated findings of OTLA were investigated and statistically correlated. Results: The overall frequency of OTLA was 1.1% (45 of 3975 patients) and increased with age (p < 0.005). The frequency of OTLA in patients over 80 years was 12%. The space available for the spinal cord (SAC) was smaller in patients with OTLA (p < 0.005). Mineralization of the complex of the anterior atlantooccipital membrane and Barkow ligament, ossification of the ligamentum flavum, and kyphosis of the cervical spine positively correlated to the presence of OTLA (p < 0.005). Conclusion: OTLA was associated with age, SAC narrowing, cervical kyphosis, and ossification of other cervical ligaments and may be associated with degenerative spondylosis, systemic hyperostotic status, or mechanical stress or instability.

Combined effect of hepatic venous pressure gradient and liver stiffness on long-term mortality in patients with cirrhosis.

BACKGROUND/AIMS: Both hepatic venous pressure gradient (HVPG) and liver stiffness (LS) are useful tools for predicting mortality in patients with cirrhosis. We investigated the combined effect of HVPG and LS on long-term mortality in patients with cirrhosis. METHODS: We retrospectively collected data from 103 patients with cirrhosis, whose HVPG and LS were measured between November 2009 and September 2013. The patients were divided into four groups according to the results of the HVPG and LS measurements. Long-term mortality and the risk factors for mortality were analyzed. RESULTS: Of the 103 patients, 35 were in group 1 (low HVPG and low LS), 16 in group 2 (high HVPG and low LS), 24 in group 3 (low HVPG and high LS), and 28 in group 4 (high HVPG and high LS). Over a median follow-up of 47.3 months, 18 patients died. The mortality rate of patients in group 4 was significantly higher than in the other three groups (vs. group 1, p = 0.005; vs. group 2, p = 0.049; vs. group 3, p = 0.004), but there were no significant differences in survival between groups 1, 2, and 3. In multivariable analyses, both HVPG and LS were identified as independent risk factors for mortality (hazard ratio [HR], 1.127, p = 0.018; and HR, 1.062, p = 0.009, respectively). CONCLUSION: In patients with cirrhosis, those with concurrent elevation of HVPG and LS had the highest long-term mortality rates. However, when either HVPG or LS alone was elevated, mortality did not increase significantly.

The Impact of Previous Acute Decompensation on the Long-Term Prognosis of Alcoholic Hepatitis in Cirrhotic Patients.

Recurrent episodes of liver injury may either waste hepatic reserve or induce tolerance to further injury. We aimed to investigate whether the previous acute decompensation (AD) in liver cirrhosis (LC) affects the long-term transplant-free survival of patients with alcoholic hepatitis (AH). The survival data of 894 alcoholic LC cohort who had been admitted with acute deterioration in 21 academic hospitals in Korea were prospectively followed up. Enrolled patients were divided into three groups: Group one, without AH; group two, with nonsevere AH; and group three, with severe AH. Although the baseline liver function was not different between the groups with or without previous AD, it was a significant predictor of poor long-term outcomes. The presence of previous AD negatively affected long-term overall survival (HR 1.62, 95% C.I. 1.20-2.18, p = 0.002) in groups one and two as a whole, independent of the Model for End-stage Liver Disease score. The three-month conditional survival was significantly worse in group three for up to 12 months in the presence of previous AD (p < 0.05). We concluded that not only the severity of AH, but also the prior AD is an important predictor of long-term outcomes in alcoholic LC patients with acute deterioration.

The New Cutoff Value of the Hepatic Venous Pressure Gradient on Predicting Long-Term Survival in Cirrhotic Patients.

BACKGROUND: This study aimed to determine the prognostic role of the categorized hemodynamic stage (HS) based on the hepatic venous pressure gradient (HVPG) in patients with portal hypertension. METHODS: Of 1,025 cirrhotic patients who underwent HVPG measurement, data on 572 non-critically-ill patients were collected retrospectively between 2008 and 2013. The following two HS categorizations were used: HS-1 (6-9, 10-12, 13-16, 17-20, and > 20 mmHg; designated as groups 1-5, respectively) and HS-2 (6-12, 13-20, and > 20 mmHg). Clinical characteristics, mortality rates, and prognostic predictors were analyzed according to the categorized HS. RESULTS: During the mean follow-up period of 25 months, 86 (15.0%) patients died. The numbers of deaths in HS-1 groups were 7 (6.3%), 7 (6.9%), 30 (18.0%), 20 (15.6%), and 22 (34.4%), respectively (P < 0.001). However, the traditional HVPG cutoffs of 10 and 16 mmHg did not improve the discrimination of mortality. In contrast, the mortality rates did differ significantly between the three HS-2 groups (P < 0.05). In the multivariate analysis, all models revealed that HS-2 was a common prognostic factor in predicting mortality. The mortality rates increased significantly according to HS-2 in patients with hypoalbuminemia (HVPG, 13-20 mmHg; hazard ratio [HR], 2.54 and HVPG > 20 mmHg; HR, 5.45) and intermediate model for end-stage liver disease (MELD) score (HVPG, 13-20 mmHg; HR, 3.86 and HVPG > 20 mmHg; HR, 8.77; P < 0.05). CONCLUSION: Categorizing HVPG values according to HS-2 is a useful prognostic modality in patients with portal hypertension and can play an independent role in predicting the prognosis in patients with hypoalbuminemia and an intermediate MELD score.

Abdominal Wall Thickness Affects Liver Stiffness Measurements by 2-D Shear Wave Elastography in Patients with Chronic Liver Disease.

This study was conducted to define the effect of abdominal wall thickness (AWT) and its composition on the level of confidence in liver stiffness (LS) measurements obtained with 2-D shear wave elastography (2-D-SWE) in patients with chronic liver disease. In this retrospective study, a total of 1291 patients who underwent LS measurement by 2-D-SWE were enrolled. The abdominal wall was divided into three layers: layer 1 extended from the skin to the subcutaneous fat layer; layer 2 was the muscle layer; and layer 3 extended from the peritoneum to the liver capsule (including the omental fat layer, if present). We regarded the sums of layers 1-3 and layers 1 and 3 as the AWT and non-muscular layer thickness (NMT). Age/sex/body mass index-adjusted multivariate logistic regression analysis was performed to identify factors influencing the level of confidence of LS measurements. Three hundred eighty-six patients (29.9%) were classified in the unreliable LS group (standard deviation/median LS > 0.1). The fourth quartile of AWT and third and fourth quartiles of NMT/AWT were significantly associated with unreliable LS values (odds ratios = 2.103, 1.753 and 1.695, respectively). In conclusion, high AWT and NMT/AWT ratios reduce the confidence in LS measurements obtained with 2-D-SWE.

Validation of the Korean Stroop Test in Diagnosis of Minimal Hepatic Encephalopathy.

The burden of minimal hepatic encephalopathy (MHE) is significant, but no universal criteria for diagnosis have been established. We aimed to validate the Korean Stroop Test for MHE screening. Chronic hepatitis B-related liver cirrhosis patients were recruited prospectively from 13 centers. The Korean Stroop Test consisted of two Stroop-off states (color and word) and two Stroop-on states (inhibition and switching). Accuracy adjusted psychomotor speed (rate correct score) of these tests were analyzed. Sex- and age- adjusted rate correct scores of these tests were rated as the Korean Stroop Score (K-Stroop score). MHE was diagnosed when Portosystemic Encephalopathy Syndrome Test (PHES) scores were below -4. A total of 220 liver cirrhosis patients and 376 healthy controls were enrolled. Prevalence of MHE was 20.6% in cirrhosis patients. Rate correct scores and the K-Stroop score showed significant differences between healthy controls, cirrhosis patients without MHE, and cirrhosis patients with MHE. The rate correct score of the K-Stroop score was 0.74 (95% Confidence Interval: 0.66-0.83, P < 0.001). Female gender and the K-Stroop score were significant for MHE diagnosis. The Korean Stroop Test is simple and valid for screening of MHE.

Long-term Outcomes of Antiviral Therapy in Patients With Advanced Chronic HBV Infection.

Hepatitis B virus (HBV) suppression with nucleot(s)ide analogue therapy reduces the risk of hepatic decompensation and hepatocellular carcinoma (HCC) in patients with advanced liver disease.1 In the present era of potent antiviral therapies, the prognostic significance of the serum HBV DNA level as a biological gradient has substantially diminished; the majority of treated patients achieve virologic suppression.2,3 After control of viremia, a higher baseline fibrosis level is a useful predictor for disease progression.4 Few "prospective" studies on the effects of antiviral agents, especially in chronic hepatitis B (CHB) patients with advanced liver disease, have been reported.

Long-term Prognosis of Acute-on-Chronic Liver Failure Survivors.

GOALS: We aimed to investigate significant factors influencing the long-term prognosis of patients who survived acute-on-chronic liver failure (ACLF). BACKGROUND: The mortality of ACLF is predominantly affected by the organ failure severity. However, long-term outcomes of patients who survive ACLF are not known. STUDY: A cohort of 1084 cirrhotic patients who survived for more than 3 months following acute deterioration of liver function was prospectively followed. ACLF was defined by the European Association for the Study of the Liver Chronic Liver Failure Consortium definition. RESULTS: The mean follow-up duration was 19.4±9.9 months. In the subgroup of patients without previous acute decompensation (AD), ACLF occurrence did not affect long-term outcomes. However, in patients with previous AD, ACLF negatively affected long-term transplant-free survival even after overcoming ACLF (hazard ratio, 2.00, P=0.012). Previous AD was the significant predictive factor of long-term mortality and was independent of the Model for End-stage Liver Disease score in these ACLF-surviving patients. Organ failure severity did not affect transplant-free survival in patients who survived an ACLF episode. CONCLUSIONS: A prior history of AD is the most important factor affecting long-term outcomes following an ACLF episode regardless of Model for End-stage Liver Disease score. Prevention of a first AD episode may improve the long-term transplant-free survival of liver cirrhosis patients.

Efficacy of Pegylated Interferon Monotherapy versus Sequential Therapy of Entecavir and Pegylated Interferon in Hepatitis B e Antigen-Positive Hepatitis B Patients: A Randomized, Multicenter, Phase IIIb Open-Label Study (POTENT Study).

BACKGROUND: Until now, various types of combined therapy with nucleotide analogs and pegylated interferon (Peg-INF) in patients with hepatitis B patients have been tried. However, studies regarding the benefits of de novo combination, late-add on, and sequential treatment are very limited. The objective of the current study was to identify the efficacy of sequential treatment of Peg-INF after short-term antiviral treatment. METHODS: Between June 2010 and June 2015, hepatitis B e antigen (HBeAg)-positive patients (n = 162) received Peg-IFN for 48 weeks (mono-treatment group, n = 81) and entecavir (ETV) for 12 weeks with a 48-week course of Peg-IFN starting at week 5 of ETV therapy (sequential treatment group, n = 81). The primary endpoint was HBeAg seroconversion at the end of follow-up period after the 24-week treatment. The primary endpoint was analyzed using Chi-square test, Fisher's exact test, and regression analysis. RESULTS: HBeAg seroconversion rate (18.2% vs. 18.2%, t = 0.03, P = 1.000) and seroclearance rate (19.7% vs. 19.7%, t = 0.03, P = 1.000) were same in both mono-treatment and sequential treatment groups. The rate of alanine aminotransferase (ALT) normalization (45.5% vs. 54.5%, t = 1.12, P = 0.296) and serum hepatitis B virus (HBV)-DNA <2000 U/L (28.8% vs. 28.8%, t = 0.10, P = 1.000) was not different in sequential and mono-treatment groups at 24 weeks of Peg-INF. Viral response rate (HBeAg seroconversion and serum HBV-DNA <2000 U/L) was not different in the two groups (12.1% vs. 16.7%, t = 1.83, P = 0.457). Baseline HBV-DNA level (7 log10U/ml vs. 7.5 log10U/ml, t = 1.70, P = 0.019) and hepatitis B surface antigen titer (3.6 log10U/ml vs. 4.0 log10U/ml, t = 2.19, P = 0.020) were lower and predictors of responder in mono-treatment and sequential treatment groups, respectively. CONCLUSIONS: The current study shows no differences in HBeAg seroconversion rate, ALT normalization, and HBV-DNA levels between mono-therapy and sequential therapy regimens. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01220596; https://clinicaltrials.gov/ct2/show/NCT01220596?term=NCT01220596&rank=1.

Super anticorrosion of aluminized steel by a controlled Mg supply.

The current anticorrosion strategy makes use of coatings to passively protect the steel, which faces increasing challenge due to the tightened environmental regulations and high cost. This paper reports a new method for achieving a super anticorrosion function in Al-Si alloys through Mg nano-metallurgy, which was characterized by real-time synchrotron measurements. The unique function is based on the formation of an amorphous and self-charge-compensated MgAl2O4-SiO2 phase between the grain boundaries to help prevent the penetration of oxygen species through the grain boundaries. Through this, the corrosion resistance of pristine aluminized steel could be improved almost 20 fold. An analysis of the phases, microstructures of the Mg-coated aluminized layer and corrosion products consistently supported the proposed mechanism. This charge-compensated corrosion resistance mechanism provides novel insight into corrosion resistance.

Tenofovir disoproxil fumarate monotherapy is superior to entecavir-adefovir combination therapy in patients with suboptimal response to lamivudine-adefovir therapy for nucleoside-resistant HBV: a 96-week prospective multicentre trial.

BACKGROUND: A complete virological response is closely related to the long-term outcome of patients with chronic hepatitis B and prevention of emerging HBV mutations. We aimed to evaluate the efficacy of tenofovir disoproxil fumarate (TDF) monotherapy compared to entecavir-adefovir dipivoxil (ETV-ADV) combination therapy in patients with suboptimal responses to long-term lamivudine-adefovir dipivoxil (LAM-ADV) therapy for nucleoside analogue-resistant chronic hepatitis B. METHODS: Patients (n=60) were randomized to TDF monotherapy or ETV-ADV combination therapy for 96 weeks. All patients had the rt204I/V mutation and serum HBV DNA was measured (>60 IU/ml) during LAM-ADV therapy. The primary end point was a complete virological response (HBV DNA <20 IU/ml) at week 96. RESULTS: The median duration of prior LAM-ADV rescue therapy was 43 (7-108) months. A complete virological response was achieved in 86.6% and 53.3% of patients in the TDF and ETV-ADV groups, respectively, at week 96 (P=0.005). Reduction in serum HBV DNA was significantly greater in the TDF group than in ETV-ADV group (-3.2 ±1.2 versus -2.6 ±1.2; P=0.01). Hepatitis B e antigen loss (22.2% versus 16.6%; P=0.731) and biochemical responses (76.7% versus 73.3%; P=0.766) were not different between the TDF and ETV-ADV groups. No newly emerged mutations were detected. Both therapies demonstrated favourable safety profiles. CONCLUSIONS: TDF therapy achieved a better complete virological response than ETV-ADV therapy in chronic hepatitis B patients with suboptimal response to long-term LAM-ADV rescue therapy. (KCT0000627).

Validation of prognostic scores to predict short-term mortality in patients with acute-on-chronic liver failure.

BACKGROUND AND AIM: The aim of this study was to validate the chronic liver failure-sequential organ failure assessment score (CLIF-SOFAs), CLIF consortium organ failure score (CLIF-C OFs), CLIF-C acute-on-chronic liver failure score (CLIF-C ACLFs), and CLIF-C acute decompensation score in Korean chronic liver disease patients with acute deterioration. METHODS: Acute-on-chronic liver failure was defined by either the Asian Pacific Association for the study of the Liver ACLF Research Consortium (AARC) or CLIF-C criteria. The diagnostic performances for short-term mortality were compared by the area under the receiver operating characteristic curve. RESULTS: Among a total of 1470 patients, 252 patients were diagnosed with ACLF according to the CLIF-C (197 patients) or AARC definition (95 patients). As the ACLF grades increased, the survival rates became significantly lower. The areas under the receiver operating characteristic of the CLIF-SOFAs, CLIF-C OFs, and CLIF-C ACLFs were significantly higher than those of the Child-Pugh, model for end-stage liver disease, and model for end-stage liver disease-Na scores in ACLF patients according to the CLIF-C definition (all P < 0.05), but there were no significant differences in patients without ACLF or in patients with ACLF according to the AARC definition. The CLIF-SOFAs, CLIF-C OFs, and CLIF-C ACLFs had higher specificities with a fixed sensitivity than liver specific scores in ACLF patients according to the CLIF-C definition, but not in ACLF patients according to the AARC definition. CONCLUSIONS: The CLIF-SOFAs, CLIF-C OFs, and CLIF-C ACLFs are useful scoring systems that provide accurate information on prognosis in patients with ACLF according to the CLIF-C definition, but not the AARC definition.

Serum cystatin C level: An excellent predictor of mortality in patients with cirrhotic ascites.

BACKGROUND AND AIM: Although serum cystatin C level is considered a more accurate marker of renal function in patients with liver cirrhosis, its prognostic efficacy remains uncertain. This study aimed to evaluate the prognostic efficacy of serum cystatin C level in patients with cirrhotic ascites. METHODS: Patients with cirrhotic ascites from 15 hospitals were prospectively enrolled between September 2009 and March 2013. Cox regression analyses were performed to identify independent predictive factors of mortality and development of type 1 hepatorenal syndrome (HRS-1). RESULTS: In total, 350 patients were enrolled in this study. The mean age was 55.4 ± 10.8 years, and 267 patients (76.3%) were men. The leading cause of liver cirrhosis was alcoholic liver disease (64.3%), followed by chronic viral hepatitis (29.7%). Serum creatinine and cystatin C levels were 0.9 ± 0.4 mg/dL and 1.1 ± 0.5 mg/L, respectively. Multivariate analyses revealed that international normalized ratio and serum bilirubin, sodium, and cystatin C levels were independent predictors of mortality and international normalized ratio and serum sodium and cystatin C levels were independent predictors of the development of HRS-1. Serum creatinine level was not significantly associated with mortality and development of HRS-1 on multivariate analysis. CONCLUSION: Serum cystatin C level was an independent predictor of mortality and development of HRS-1 in patients with cirrhotic ascites, while serum creatinine level was not. Predictive models based on serum cystatin C level instead of serum creatinine level would be more helpful in the assessment of the condition and prognosis of patients with cirrhotic ascites.

Coefficient of Variance as Quality Criterion for Evaluation of Advanced Hepatic Fibrosis Using 2D Shear-Wave Elastography.

OBJECTIVES: To compare the diagnostic performance for advanced hepatic fibrosis measured by 2D shear-wave elastography (SWE), using either the coefficient of variance (CV) or the interquartile range divided by the median value (IQR/M) as quality criteria. METHODS: In this retrospective study, from January 2011 to December 2013, 96 patients, who underwent both liver stiffness measurement by 2D SWE and liver biopsy for hepatic fibrosis grading, were enrolled. The diagnostic performances of the CV and the IQR/M were analyzed using receiver operating characteristic curves with areas under the curves (AUCs) and were compared by Fisher's Z test, based on matching the cutoff points in an interactive dot diagram. All P values less than 0.05 were considered significant. RESULTS: When using the cutoff value IQR/M of 0.21, the matched cutoff point of CV was 20%. When a cutoff value of CV of 20% was used, the diagnostic performance for advanced hepatic fibrosis ( ≥ F3 grade) with CV of less than 20% was better than that in the group with CV greater than or equal to 20% (AUC 0.967 versus 0.786, z statistic = 2.23, P = .025), whereas when the matched cutoff value IQR/M of 0.21 showed no difference (AUC 0.918 versus 0.927, z statistic = -0.178, P = .859). CONCLUSIONS: The validity of liver stiffness measurements made by 2D SWE for assessing advanced hepatic fibrosis may be judged using CVs, and when the CV is less than 20% it can be considered "more reliable" than using IQR/M of less than 0.21.