Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in virologically suppressed patient with chronic hepatitis B.

BACKGROUND AND AIM: Our study evaluated the outcomes of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) in patients with chronic hepatitis B (CHB). We assessed viral and biochemical responses as well as changes in the estimated glomerular filtration rate (eGFR) and bone mineral density (BMD). METHODS: This retrospective multicenter study included CHB patients who achieved virologic response (VR) (HBV DNA < 20 IU/mL) while on TDF and were subsequently switched to TAF between April 2018 and October 2021. RESULTS: This study included 309 patients with a median age of 59 years, and 42.1% were male. The mean duration of TDF and TAF administration were 54.0 and 37.5 months, respectively. All patients maintained VR after switching to TAF. Alanine aminotransferase (ALT) normalization rate significantly increased 6 months after switching (74.8%-83.5%; P = 0.008). Adjusted eGFR significantly improved at 6 months (+5.55 ± 10.52 mL/min/1.73 m2; P < 0.001) and 12 months (+6.02 ± 10.70 mL/min/1.73 m2; P < 0.001) after switching. In the subgroup of patients with renal impairment (eGFR < 60 mL/min/1.73 m2), significant improvement in renal function was observed at 6 months (+0.6 ± 10.5 mL/min/1.73 m2; P < 0.001) and 12 months (+1.0 ± 10.7 mL/min/1.73 m2; P < 0.001) after switching to TAF. In patients with osteoporosis (n = 182), switching to TAF resulted in significant improvement in spine and hip BMD at 12 months, with increases of 9.7% (95% CI: 7.0-12.5) and 9.4% (95% CI: 7.0-11.8), respectively. CONCLUSION: In this real-world study, switching to TAF was effective and safe in patients, with notable improvements in ALT levels, renal function, and BMD.

Validation of MELD 3.0 in patients with alcoholic liver cirrhosis using prospective KACLiF cohort.

BACKGROUND AND AIM: The Model for End-Stage Liver Disease (MELD) is a reliable prognostic tool for short-term outcome prediction in patients with end-stage liver disease. MELD 3.0 was introduced to enhance the predictive accuracy. This study assessed the performance of MELD 3.0, in comparison to MELD and MELD-Na, in patients with alcoholic liver cirrhosis. METHODS: This multicenter prospective cohort study comprised patients with alcoholic cirrhosis admitted for acute deterioration of liver function in the Republic of Korea between 2015 and 2019. This study compared the predictive abilities of MELD, MELD-Na, and MELD 3.0, for 30-day and 90-day outcomes, specifically death or liver transplantation, and explored the factors influencing these outcomes. RESULTS: A total of 1096 patients were included in the study, with a mean age of 53.3 ± 10.4 years, and 82.0% were male. The mean scores for MELD, MELD-Na, and MELD 3.0 at the time of admission were 18.7 ± 7.2, 20.6 ± 7.7, and 21.0 ± 7.8, respectively. At 30 and 90 days, 7.2% and 14.1% of patients experienced mortality or liver transplantation. The areas under the receiver operating characteristic curves for MELD, MELD-Na, and MELD 3.0 at 30 days were 0.823, 0.820, and 0.828; and at 90 days were 0.765, 0.772, and 0.776, respectively. Factors associated with the 90-day outcome included concomitant chronic viral hepatitis, prolonged prothrombin time, elevated levels of aspartate transaminase, bilirubin, and creatinine, and low albumin levels. CONCLUSION: MELD 3.0 demonstrated improved performance compared to previous models, although the differences were not statistically significant.

Empirical Treatment With Carbapenem vs Third-generation Cephalosporin for Treatment of Spontaneous Bacterial Peritonitis.

BACKGROUND & AIMS: Third-generation cephalosporins (TGCs) are recommended as first-line antibiotics for treatment of spontaneous bacterial peritonitis (SBP). However, antibiotics against multidrug-resistant organisms (such as carbapenems) might be necessary. We aimed to evaluate whether carbapenems are superior to TGC for treatment of SBP. METHODS: We performed a retrospective study of 865 consecutive patients with a first presentation of SBP (275 culture positive; 103 with TGC-resistant bacterial infections) treated at 7 referral centers in Korea, from September 2013 through January 2018. The primary outcome was in-hospital mortality. We made all comparisons using data from patients whose baseline characteristics were balanced by inverse probability of treatment weighting. RESULTS: Of patients who initially received empirical treatment with antibiotics, 95 (11.0%) received carbapenems and 655 (75.7%) received TGCs. Among the entire study cohort, there was no significant difference in in-hospital mortality between the carbapenem (25.8%) and TGC (25.3%) groups (adjusted odds ratio [aOR], 0.97; 95% CI, 0.85-1.11; P = .66). In the subgroup of patients with high chronic liver failure-sequential organ failure assessment (CLIF-SOFA) scores (score of 7 or greater, n = 314), carbapenem treatment was associated with lower in-hospital mortality (23.1%) than in the TGC group (38.8%) (aOR, 0.84; 95% CI, 0.75-0.94; P=.002). In contrast, among patients with lower CLIF-SOFA scores (n = 436), in-hospital mortality did not differ significantly between the carbapenem group (24.7%) and the TGC group (16.0%) (aOR, 1.06; 95% CI, 0.85-1.32; P = .58). CONCLUSIONS: For patients with a first presentation of SBP, empirical treatment with carbapenem does not reduce in-hospital mortality compared to treatment with TGCs. However, among critically ill patients (CLIF-SOFA scores ≥7), empirical carbapenem treatment was significantly associated with lower in-hospital mortality than TGCs.

Prediction of Hepatocellular Carcinoma by On-Therapy Response of Noninvasive Fibrosis Markers in Chronic Hepatitis B.

INTRODUCTION: Antiviral therapy improves hepatic fibrosis and reduces hepatocellular carcinoma (HCC) incidence. This study aimed to evaluate whether on-therapy changes in scores for fibrosis index based on 4 factors and aspartate aminotransferase-to-platelet ratio index are associated with HCC development and establish an HCC risk score model incorporating noninvasive fibrosis marker (NFM) response. METHODS: This multicenter study recruited 5,147 patients with chronic hepatitis B (4,028 for derivation cohort and 1,119 for validation cohort) who were given entecavir/tenofovir for >12 months between 2007 and 2018. A risk prediction model for HCC was developed using predictors based on multivariable Cox models, and bootstrapping was performed for validation. RESULTS: The 10-year cumulative HCC incidence rates were 12.6% and 13.7% in the derivation and validation cohorts, respectively. The risk of HCC significantly differed with early NFM response, with a marked reduction in HCC risk in patients achieving a significant decrease in NFM by 12 months (P < 0.001). NFM response, sex, age, and cirrhosis were independently predictive of HCC. We developed the Fibrosis marker response, Sex, Age, and Cirrhosis (FSAC) score based on regression coefficients of each variable. For the 10-year prediction of HCC, FSAC showed higher C-index values than PAGE-B, modified PAGE-B, CU-HCC, and REACH-B (0.84 vs 0.77, 0.80, 0.77, and 0.67, respectively; all P < 0.005). The predictive performance of FSAC was corroborated in the validation cohort, with higher C-index than other models (all P < 0.050). DISCUSSION: On-therapy changes in NFM are an independent indicator of HCC risk. FSAC incorporating NFM response is a reliable risk score for risk estimation for HCC with better performance than other models.

Effectiveness of sorafenib dose modifications on treatment outcome of hepatocellular carcinoma: Analysis in real-life settings.

Controlling adverse events (AEs) through dose reduction can enhance drug adherence and treatment response. Currently, there is no guide for sorafenib dosing. The aim of this study was to evaluate whether sorafenib dosing could affect treatment outcomes. A total of 782 hepatocellular carcinoma (HCC) patients treated with sorafenib were evaluated for sorafenib dosing and its modifications via medical records at baseline and regular follow-up. Study outcomes included progression-free survival (PFS), overall survival (OS), sorafenib duration, cumulative dose, AEs and drug discontinuation. The median patient survival was 7.7 months. Overall, 242 (30.9%) patients underwent dose reduction and 121 (17.5%) discontinued sorafenib due to AEs. In multivariate analysis, dose reduction was identified to be independently predictive of PFS and OS. The 800-to-400 mg/day group provided significantly better PFS than the 800 mg/day-maintained group or the 800-to-600 mg/day group. Likewise, the 800-to-400 mg/day group resulted in a significantly better OS than other dosing. However, dose reduction to 200 mg/day led to significantly worse PFS and OS. Hand-foot skin reaction and drug discontinuation due to AEs were higher in the 800-to-600 mg/day group than the 800-to-400 mg/day group. The 800-to-400 mg/day group had significantly longer treatment duration and higher cumulative dose than the 800 mg/day-maintained group. Sorafenib dose reduction can improve HCC survival and increase patient tolerance and adherence coupled with longer duration and higher cumulative dose. Dose reduction from 800 to 400 mg/day than to 600 mg/day is recommended when clinically warranted. However, dose reduction to 200 mg/day is not recommendable.

Besifovir Dipivoxil Maleate 144-Week Treatment of Chronic Hepatitis B: An Open-Label Extensional Study of a Phase 3 Trial.

INTRODUCTION: Chronic hepatitis B (CHB) remains a major worldwide public health concern. Besifovir dipivoxil maleate (BSV) is a new promising treatment for CHB. However, long-term efficacy and safety have not yet been evaluated. Therefore, the goal of the study is to determine the antiviral efficacy and safety of BSV treatment over a 144-week duration (BSV-BSV) in comparison with those of a sequential treatment with tenofovir disoproxil fumarate (TDF) followed by a 96-week duration BSV administration (TDF-BSV). METHODS: After 48 weeks of a double-blind comparison between BSV and TDF treatments, patients continued the open-label BSV study. We evaluated antiviral efficacy and drug safety up to 144 weeks for BSV-BSV and TDF-BSV groups. The primary endpoint was a virological response (hepatitis B virus DNA < 69 IU/mL). RESULTS: Among the 197 patients enrolled, 170 and 158 patients entered the second-year and third-year open-label phase extensional study, respectively, whereas 153 patients completed the 144-week follow-up. The virological response rate over the 144-week period was 87.7% and 92.1% in BSV-BSV and TDF-BSV groups, respectively (P = 0.36). The rates of ALT normalization and HBeAg seroconversion were similar between the groups. No drug-resistant mutations to BSV were noted. Bone mineral density and renal function were well preserved in the BSV-BSV group and were significantly improved after switching therapy in TDF-BSV patients. DISCUSSION: This extensional study of a phase 3 trial (NCT01937806) suggests that BSV treatment is efficacious and safe for long-term use in treatment-naïve and TDF-experienced patients with CHB.

Efficacy and Safety of Besifovir Dipivoxil Maleate Compared With Tenofovir Disoproxil Fumarate in Treatment of Chronic Hepatitis B Virus Infection.

BACKGROUND & AIMS: Besifovir dipivoxil maleate (BSV) has activity against hepatitis B virus (HBV). We performed a phase 3 study to compare the antiviral efficacy and safety of BSV vs tenofovir disoproxil fumarate (TDF) in patients with chronic HBV infection in Korea. METHODS: We conducted a double-blind, non-inferiority trial of 197 patients with chronic HBV infection at 22 sites in South Korea, from November 2013 through February 2016. Patients were randomly assigned to groups given BSV (150 mg, n = 99) or TDF (300 mg, n = 98) for 48 weeks. We evaluated virologic responses to therapy (HBV DNA <69 IU/mL or 400 copies/ml), bone mineral density (BMD), and renal outcomes for safety analysis. The main efficacy endpoint was the proportion of patients with a virologic response at week 48. After 48 weeks, TDF was switched to BSV (150 mg) for an additional 48 weeks. RESULTS: After 48 weeks of treatment, 80.9% of patients given BSV and 84.9% of patients given TDF met the efficacy endpoint, indicating the non-inferiority of BSV to TDF. At week 96, 87.2% of patients in the BSV-BSV and 85.7% of patients in the TDF-BSV had a virologic response. At week 48, changes in hip and spine BMD differed significantly between the BSV and TDF groups, whereas the estimated glomerular filtration rate in the TDF group was significantly lower than that in the BSV group. However, at 96 weeks, there were no significant differences in BMD and estimated glomerular filtration rate between the BSV-BSV and TDF-BSV groups. CONCLUSIONS: BSV has antiviral efficacy comparable to that of TDF after 48 weeks of treatment, with durable effects for 96 weeks. BSV has a better safety profile than TDF, in terms of bone and renal outcomes. ClinicalTrials.gov no: NCT01937806.

Clinical outcomes after the introduction of direct antiviral agents for patients infected with genotype 1b hepatitis C virus depending on the regimens: A multicenter study in Korea.

BACKGROUND: A real-life study is essential outside clinical trials. The aim is to evaluate the clinical outcomes of direct acting agents (DAA) for patients with chronic hepatitis C (CHC) in real practice. METHODS: We analyzed 590 consecutively enrolled patients with CHC-1b who received DAAs since 2015, when DAAs were introduced in Korea. The patients were checked for resistance-associated variants (RAV) against nonstructural protein 5A inhibitors and then daclatasvir/asunaprevir or sofosbuvir based regimens were chosen. RESULTS: The frequency of patients with cirrhosis and prior hepatocellular carcinoma (HCC) was 29.2% and 4.7%, respectively. For the RAV test, 10% were positive and in 3.6% the result was "indeterminate." Overall, 518 patients were treated with a 24-week regimen of daclatasvir/asunaprevir, 72 patients (RAV positive 75%) were treated with 12 weeks regimen of ledipasvir/sofosbuvir or daclatasvir/sofosbuvir. The SVR12 was 94.0% in the daclatasvir/asunaprevir, 98.2% in the ledipasvir/sofosbuvir, and 100% in the daclatasvir/sofosbuvir group. A total of 93.3% of SVR12 in the RAV-"indeterminate" patients was not difference 95.0% in the RAV-negative patients. Up to 1 year, de novo HCC occurrence and recurrence developed in 2.6% and 17.8%, respectively. HCC was more frequent in cirrhotic patients than in noncirrhotic patients (P = 0.000). α Fetoprotein (AFP) level at the end of treatment was a predicting factor for de novo HCC. CONCLUSIONS: Optimizing the choice of DAAs according to RAV test resulted in high SVR among CHC-1b Korean patients. This real practice multicenter cohort study suggests the importance of AFP and HCC surveillance in cirrhotic patients even after successful HCV therapy.

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 and Safety of Tenofovir Disoproxil Fumarate in Treatment-Naïve Patients with Chronic Hepatitis B in Korea.

AIMS: To evaluate the efficacy and safety of 144-week tenofovir disoproxil fumarate (TDF) therapy in treatment-naïve chronic hepatitis B (CHB) patients in Korean. METHODS: In total, 579 treatment-naïve CHB patients at 11 medical centers were enrolled retrospective and prospective from September 2015 to January 2016 by design (NCT02533544). We evaluated the complete virologic response (CVR) rate and the renal safety of TDF. RESULTS: The overall CVR rate was 69.4%, 87.0%, and 89.7% at weeks 48, 96, and 144, respectively. In the HBeAg-positive CHB patients, the CVR rate at weeks 48, 96, and 144 was 61.4%, 83.1%, and 89.6%, respectively. The rates of HBeAg loss and seroconversion at weeks 48, 96, and 144 were 16.6%, 23.5%, 34.1%, and 7.6%, 8.9%, 13.3%, respectively. In HBeAg-negative CHB patients, the CVR rate at weeks 48, 96, and 144 was 82.5%, 93.2%, and 90.0%, respectively. The rate of alanine aminotransferase normalization was 36.9%, 45.4%, and 46.8% at weeks 48, 96, and 144, respectively. Of the CHB patients, 0.9% showed an elevated creatinine (> 0.5 mg/dL from baseline). Age (≥ 60 years) was significantly associated with a decline in renal function at week 144 (P < 0.0001). Comorbidities (diabetes or hypertension) showed the tendency to reduce renal function (P = 0.0624). Hepatocellular carcinoma developed in 10 (1.7%) patients and was related to cirrhosis. CONCLUSIONS: TDF therapy induced sustained viral suppression and had a favorable safety profile over a 3-year period. However, close monitoring of renal function should be mandatory in treating CHB patients receiving TDF, particularly older patients.

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.

The association between a positive lactulose methane breath test and rectocele in constipated patients.

OBJECTIVES: Rectocele with constipation might be related to methane (CH4) producing intestinal bacteria. We investigated the breath CH4 levels and the clinical characteristics of colorectal motility in constipated patients with rectocele. METHODS: A database of consecutive female outpatients was reviewed for the evaluation of constipation according to the Rome III criteria. The patients underwent the lactulose CH4 breath test (LMBT), colon marker study, anorectal manometry, defecography and bowel symptom questionnaire. The profiles of the lactulose breath test (LBT) in 33 patients with rectocele (with size ≥ 2 cm) and 26 patients with functional constipation (FC) were compared with the breath test results of 30 healthy control subjects. RESULTS: The mean size of rectocele was 3.52 ± 1.06 cm. The rate of a positive LMBT (LMBT+) was significantly higher in patients with rectocele (33.3%) than in those with FC (23.1%) or healthy controls (6.7%) (p = 0.04). Breath CH4 concentration was positively correlated with rectosigmoid colon transit time in rectocele patients (γ = 0.481, p < 0.01). A maximum high pressure zone pressure > 155 mmHg was a significant independent factor of LMBT+ in rectocele patients (OR = 8.93, 95% CI = 1.14-71.4, p = 0.04). CONCLUSIONS: LMBT+ might be expected in constipated patients with rectocele. Moreover, increased rectosigmoid colonic transit or high anorectal pressure might be associated with CH4 breath levels. Breath CH4 could be an important therapeutic target for managing constipated patients with rectocele.

Effects of manipulation of the thorax and intensity of the pressure biofeedback unit on the superficial cervical flexors muscle during craniocervical flexion exercise.

[Purpose] This study examined the effects of manipulation of the thorax and the intensity of the pressure biofeedback unit on the superficial cervical flexors muscle during craniocervical flexion exercise. [Subjects and Methods] Thirty three subjects participated in the experiment. Thirty three healthy people without any orthopedic history were also selected. The subjects could monitor the pressure applied to cervical vertebra 3 of the craniocervical junction by markings on the pressure biofeedback unit. Craniocervical flexion exercise was performed for 20 seconds per pressure, and two minutes of rest was allowed after exercise to reduce muscle fatigue. [Results] Significant differences in the post-training gains in the sternocleidomastoid and scalene were observed between the thorax fixation group and thorax non-fixation group. The thorax fixation group showed that muscle activation of the sternocleidomastoid and scalene was increased when the pressure biofeedback unit intensity was 40 mmHg than when pressure biofeedback unit intensity was 20 mmHg and 30 mmHg in the post-hoc result. The thorax non-fixation group showed that muscle activation of the sternocleidomastoid and scalene was higher when the pressure biofeedback unit intensity was 40mmHg compared to that when the pressure biofeedback unit intensity was 20mmHg in the post-hoc result. [Conclusion] Craniocervical flexion exercise is a clinically effective method that reduces the superficial neck flexor muscle activation.

Breath hydrogen and methane are associated with intestinal symptoms in patients with chronic pancreatitis.

BACKGROUNDS: The bacterial overgrowth might be associated with chronic pancreatitis. This study was to evaluate the prevalence and characteristics of small intestinal bacterial overgrowth (SIBO) in patients with chronic pancreatitis. METHODS: 36 patients with chronic pancreatitis and 49 healthy controls undergoing the hydrogen (H2)-methane (CH4) lactulose breath test (LBT) were reviewed. The LBT positivity (+) indicating the presence of SIBO, gas types, bowel symptom questionnaire, laboratory and radiologic results were surveyed. The LBT+ was (1) an increase in the breath H2 (≥20 ppm) or CH4 (≥10 ppm) over the baseline or (2) a baseline H2 (≥20 ppm) or CH4 (≥10 ppm) within 90 min after lactulose load. RESULTS: LBT+ was significantly higher in the patients (17/36) than in controls (13/49) (47.2% vs. 26.5%, P < 0.05). During LBT, the H2 levels between 0 and 105 min were significantly higher in patients than in controls. Among LBT+ patients, 11 (64.7%), 1 (5.9%), 5 (29.4%) were in the LBT (H2)+, (CH4)+, (mixed)+ groups, respectively. The LBT+ group had significantly higher scores of flatus than those of the LBT- group. Considering the subtypes of LBT, the LBT (mixed)+ group had higher symptom scores of significance or tendency in hard stool, strain, urgency, and flatus than LBT- group The laboratory and radiologic features were not significantly different between LBT+ and LBT- groups. CONCLUSIONS: SIBO is common in patients in chronic pancreatitis. Especially, excretions of mixed H2 and CH4 appear to be related with deterioration of intestinal symptoms.

Correlation of knee proprioception with muscle strength and spasticity in stroke patients.

[Purpose] The purpose of this study was to investigate the relationship of knee proprioception with muscle strength and spasticity in stroke patients. [Subjects and Methods] The subjects were 31 stroke patients. The subjects received an explanation of the procedures and methods and provided informed consent before the experiment. A measurement board was used to determine the the proprioception deficit of the knee as a proprioception test. The proprioception test consisted of a passive and active angle reproduction test. A manual muscle test and modified Ashworth scale were used to evaluate knee muscle strength and spasticity level. The data were analyzed using an independent t-test and Spearman correlation. [Results] The results of this study revealed a significant difference between the affected side and non-affected side in the passive angle reproduction test and a significant difference in the correlation of the proprioception level with muscle strength and spasticity level. [Conclusion] This study indicates that the knee proprioception level is associated with spasticity and muscle strength in stroke patients.

The effects of chest expansion resistance exercise on chest expansion and maximal respiratory pressure in elderly with inspiratory muscle weakness.

[Purpose] The aim of this study was to examine the effect of chest expansion resistance exercises (CERE) on chest expansion, maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) in elderly people with inspiratory muscle weakness. [Subjects] Thirty elderly people with inspiratory muscle weakness (MIP < 80% of the predicted value) were randomly and equally assigned to a chest expansion resistance exercise (CERE) group, core conditioning exercise (CCE) group, and control group. [Methods] The intervention was applied to the CERE group and CCE group five times per week, 30 minutes each time, for six weeks. A tapeline was used to measure upper and lower chest expansion. MIP and MEP before and after the intervention were measured and compared. [Results] There was significant improvement in upper and lower chest expansion and MIP after the intervention in both the CERE group and the CCE group, whereas the control group did not show any significant difference. MEP did not significantly change in any of the three groups after the intervention. [Conclusion] The CERE group underwent greater changes than the CCE group, which proves that the CERE is more effective for improving elderly people's chest expansion capacity and MIP in elderly people. Therefore, application of the CERE by therapists is recommended if the environment and conditions are appropriate for enhancement of chest expansion capacity and MIP in elderly people.

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.

Pragmatic strategies to address health disparities along the continuum of care in chronic liver disease.

Racial, ethnic, and socioeconomic disparities exist in the prevalence and natural history of chronic liver disease, access to care, and clinical outcomes. Solutions to improve health equity range widely, from digital health tools to policy changes. The current review outlines the disparities along the chronic liver disease health care continuum from screening and diagnosis to the management of cirrhosis and considerations of pre-liver and post-liver transplantation. Using a health equity research and implementation science framework, we offer pragmatic strategies to address barriers to implementing high-quality equitable care for patients with chronic liver disease.

Dynamic Assessment of Modified Quick Sequential Organ Failure Assessment in Acutely Deteriorated Patients with Chronic Liver Disease.

Background/Aims: Quick sequential organ failure assessment (qSOFA) has been suggested to identify those who have poor outcomes in patients with suspected infection. We aimed to evaluate the ability of the modified qSOFA (m-qSOFA) to identify high-risk patients in acutely deteriorated patients with chronic liver disease (CLD), especially acute-on-chronic liver failure (ACLF). Methods: We used the data of both Korean Acute-on-Chronic Liver Failure (KACLiF) and Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) cohorts. qSOFA was modified by replacing the Glasgow Coma Scale with hepatic encephalopathy, and m-qSOFA≥2 was considered high. Results: Patients with high m-qSOFA had a significantly lower 1-month transplant-free survival (TFS) in both cohorts and higher organ failure development in KACLiF than patients with low m-qSOFA (Ps<0.05). Subgroup analysis by ACLF showed that patients with high m-qSOFA had lower TFS than patients with low m-qSOFA. m-qSOFA was an independent prognostic factor (hazard ratios (HR)=2.604, 95% confidence interval (CI) 1.353-5.013, P=0.004 in KACLiF and HR=1.904, 95% CI 1.484-2.442, P<0.001 in AARC). The patients with low m-qSOFA at baseline but high m-qSOFA on the 7th day had a significantly lower 1-month TFS than the patients with high m-qSOFA at baseline but low m-qSOFA on the 7th day (52.6% vs. 89.4%, P<0.001 in KACLiF and 26.9% vs. 61.5%, P<0.001 in AARC). Conclusion: Baseline and dynamic changes in m-qSOFA were useful to identify patients with a high risk of organ failure development and short-term mortality among CLD patients with acute deterioration.

Reduced Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Receiving Long-Term Besifovir Therapy.

No information is available regarding the influence of besifovir (BSV), a new nucleotide analogue, on the occurrence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This study evaluated the reduced risk of HCC in patients undergoing BSV treatment. A total of 188 patients with CHB were treated with BSV for up to 8 years. We prospectively assessed the incidence of HCC compared with the risk from prediction models. During the follow-up, 5 patients developed HCC: 1 of 139 patients with non-cirrhotic CHB, and 4 of 49 patients with liver cirrhosis. We compared the HCC incidence in non-cirrhotic and cirrhotic patients with the predicted number derived from the REACH-B (risk estimation for HCC in CHB) model and GAG-HCC (guide with age, gender, HBV DNA, core promotor mutation, and cirrhosis) model, respectively. The standardized incidence ratio (SIR) was 0.128 (p = 0.039) at 7 years in non-cirrhotic CHB patients, and the SIR was 0.371 (p = 0.047) at 7.5 years in cirrhotic patients, suggesting a significantly decreased HCC incidence in both groups. HCC prediction was available for BSV-treated patients using existing models. In conclusion, BSV decreased the risk of HCC in patients with CHB, and prediction models were applicable. Clinical trial registry website and trial number: ClinicalTrials.gov no: NCT01937806.