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.

Direct-Acting Antivirals Improve Treatment Outcomes in Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma Treated with Transarterial Chemoembolization: A Nationwide, Multi-center, Retrospective Cohort Study.

BACKGROUND AND AIMS: The influence of direct-acting antivirals (DAAs) on chronic hepatitis C (CHC)-related hepatocellular carcinoma (HCC) remains controversial. We investigated the effect of eradicating CHC using DAAs on treatment outcomes in patients with CHC-related HCC treated with transarterial chemoembolization (TACE). METHODS: This nationwide, multi-center, retrospective study recruited patients with CHC-related HCC treated with TACE as the first-line anti-cancer treatment, and who achieved a sustained virological response (SVR) using DAAs (DAA group) between 2006 and 2017. Patients achieving an SVR following interferon-based treatment (IFN group) and those without treatment (control group) were also recruited for comparison. RESULTS: A total of 425 patients were eligible for the study. Of these, 356 (83.8%), 26 (6.1%), and 43 (10.1%) were allocated to the control, IFN, and DAA groups, respectively. A multivariate analysis showed that liver cirrhosis, segmental portal vein thrombosis, and larger maximal tumor size independently predicted an increased risk of progression (all p < 0.05), whereas, the DAA group (vs. IFN and control groups) independently predicted a reduced risk of progression (hazard ratio (HR) = 0.630, 95% confidence interval 0.411-0.966, p = 0.034). The cumulative incidence rate of HCC progression in the DAA group was significantly lower than that in the IFN and control groups (p = 0.033, log-rank test). In addition, the DAA group (vs. IFN and control groups) was independently associated with a reduced risk of mortality (p = 0.042). CONCLUSIONS: DAA treatment provided significantly prolonged progression-free survival in patients with CHC-related HCC treated with TACE compared to that in patients administered IFN or no treatment.

Sarcopenia Is a New Risk Factor of Nonalcoholic Fatty Liver Disease in Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIM: Recently, sarcopenia has been proposed as an additional risk factor of nonalcoholic fatty liver disease (NAFLD), and there have been no studies in patients with inflammatory bowel disease (IBD). We aimed to analyze the clinical associations between sarcopenia and NAFLD in IBD patients. METHODS: From January 2004 to December 2017, a total of 488 IBD patients, with CT results, were classified according to the presence of NAFLD. Sarcopenia was assessed based on the muscle volume calculated by the total psoas muscle area in the third lumbar region divided by the square of the patient's height (m2). RESULTS: Among the 443 included patients, NAFLD was diagnosed in 49 patients (11.1%). Sarcopenia was noted in 34.9%; it was more common in the NAFLD group (51.0 vs. 33.0%; p = 0.019). In multivariate analysis, metabolic syndrome (odds ratio [OR], 8.63), hyperuricemia (OR, 4.66), small bowel resection (OR, 3.45), and sarcopenia (OR, 2.99) were significant risk factors of NAFLD in IBD patients. In addition, sarcopenia was an independent risk factor after adjustment for age, sex, and other metabolic factors (OR, 2.26). CONCLUSIONS: The prevalence of nonalcoholic fatty liver in IBD patients was 11.1%, and sarcopenia was an independent risk factor.

Circulating exosomal noncoding RNAs as prognostic biomarkers in human hepatocellular carcinoma.

Exosomal noncoding RNAs (ncRNAs) have unique expression profiles reflecting the characteristics of a tumor, and their role in tumor progression and metastasis is emerging. However, the significance of circulating exosomal ncRNAs in the prognosis of hepatocellular carcinoma (HCC) remains to be elucidated. We therefore determined the prognostic significance of circulating exosomal ncRNAs (miRNA-21 and lncRNA-ATB) for human HCC. This prospective study enrolled 79 HCC patients between October 2014 and September 2015. Exosomes were extracted from serum samples using the ExoQuick Exosome Precipitation Solution. To validate the isolation of the exosomes from serum, immunoblotting for exosome markers and characterization of nanoparticle using NanoSight were performed. NcRNAs were isolated from exosomes using the miRNeasy serum/plasma micro kit. Both circulating exosomal miRNA-21 and lncRNA-ATB were related to TNM stage and other prognostic factors, including the T stage and portal vein thrombosis. Multivariate analysis using the Cox regression test identified that both higher miRNA-21 and higher lncRNA-ATB were independent predictors of mortality and disease progression, along with larger tumor size and higher C-reactive protein (all p < 0.05). The overall survival and progression-free survival were significantly lower in patients with higher circulating levels of exosomal miRNA-21 (≥0.09) and lncRNA-ATB (≥0.0016) (log-rank test: p < 0.05). In conclusion, our study has provided strong evidence that circulating exosomal ncRNAs (miRNA-21 and lncRNA-ATB) are novel prognostic markers and therapeutic targets for HCC.

Association of low skeletal muscle mass with advanced liver fibrosis in patients with non-alcoholic fatty liver disease.

BACKGROUND AND AIM: Although low skeletal muscle mass (LSMM) is known to increase the risk of non-alcoholic fatty liver disease (NAFLD), limited reports have described the relationship between LSMM and advanced fibrosis. Here, we investigated the association between LSMM and advanced liver fibrosis in NAFLD patients. METHODS: Fatty liver was diagnosed using ultrasound, and appendicular skeletal muscle mass (ASM) was measured using bioelectrical impedance analysis. LSMM was defined in two ways: ASM/body weight percentage (LSMM-BW) and ASM/body mass index. Liver fibrosis stage was assessed by two models, the NAFLD fibrosis score and the Fibrosis-4 index, which determined low and high cutoff values (COVs). RESULTS: Of 10 711 NAFLD patients, 615 were diagnosed with LSMM-BW. LSMM patients were older (47.6 vs 52.5 years, P = 0.001) and had higher body mass index values (23.6 vs 29.1 kg/m2 , P < 0.001) and waist circumferences (80.1 vs 93.3 cm, P < 0.001) than non-LSMM patients. LSMM was an independent risk factor for advanced fibrosis assessed by a low COV for the Fibrosis-4 index regardless of its classification (adjusted for metabolic and lipid profiles and sex, odds ratio [OR], 1.27-2.01; all P < 0.05). LSMM was an independent risk factor for advanced fibrosis assessed by both COVs of NAFLD fibrosis score (adjusted for obesity, hypertension, lipid profile, and sex; OR, 1.64-2.01, P < 0.01 in the low COV group; OR, 2.68-3.12, P = 0.002 in the high COV group). CONCLUSIONS: Low skeletal muscle mass is associated with advanced fibrosis in NAFLD patients independent of metabolic risk factors.

Cholestatic Jaundice as a Paraneoplastic Manifestation of Prostate Cancer Aggravated by Steroid Therapy.

OBJECTIVE: To report a rare case of paraneoplastic jaundice as a manifestation of prostate cancer. CLINICAL PRESENTATION AND INTERVENTION: We report on a case of paraneoplastic syndrome in a 72-year-old man with prostate cancer that manifested with idiopathic jaundice. Although steroids can be used as treatment in patients with prostate cancer, they could exacerbate paraneoplastic jaundice. The jaundice that flared up after treatment with 40 mg prednisone was improved with antiandrogen treatment. CONCLUSION: Physicians should be aware of the possibility of paraneoplastic jaundice in patients with prostate cancer. Appropriate antiandrogen therapy should be considered for paraneoplastic jaundice in these patients.

Prospective validation of Baveno V definitions and criteria for failure to control bleeding in portal hypertension.

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). CONCLUSION: 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.

Comparative associations of MASLD and MAFLD with the presence and severity of coronary artery calcification.

We aimed to compare the associations of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) with coronary artery calcification (CAC). Patients who simultaneously underwent ultrasonography to diagnose hepatic steatosis and cardiac computed tomography to detect CAC were included. The presence and severity of CAC were defined with CAC-score thresholds of >0 and > 300, respectively, and patients were divided into the following groups: no MASLD or MAFLD (reference), MASLD-only, MAFLD-only, and overlapping groups. Overall, 1,060/2,773 (38.2%) patients had CAC, of which 196 (18.5%) had severe CAC. The MASLD and MAFLD prevalence rates were 32.6% and 45.2%, respectively, with an overlap of 30.7%. In an ASCVD risk score-adjusted model, both MASLD (adjusted odd ratios [aOR], 1.21; 95% confidence interval [CI], 1.02-1.44; p = 0.033) and MAFLD (aOR, 1.20; 95% CI, 1.01-1.42, p = 0.034) were associated with CAC, whereas only MASLD (aOR, 1.38; 95% CI, 1.01-1.89, p = 0.041) was associated with severe CAC. Compared to the reference group, the overlapping group showed an association with CAC (aOR, 1.22; 95% CI, 1.01-1.47; p = 0.038); however, the MASLD and MAFLD subgroups did not differ in their association with CAC. MASLD may predict a higher risk of ASCVD more effectively than MAFLD.

The Clinical Significance of Myosteatosis in Survival Outcomes in Patients with Hepatocellular Carcinoma Treated with Sorafenib.

The role of body composition parameters in sorafenib-treated hepatocellular carcinoma (HCC) patients is still not fully elucidated. Here, we aimed to evaluate the impact of computed tomography (CT)-based body composition parameters on the survival of such patients. In this multicenter study, we analyzed the data of 245 sorafenib-treated HCC patients from January 2008 to December 2019. Sarcopenia, visceral obesity, and myosteatosis were defined by using cross-sectional CT images at the third lumbar vertebra level. The effects of these parameters on overall survival (OS) and progression-free survival (PFS) were evaluated. The median age was 67.0 years (interquartile range: 61.0-78.0 year), and 211 patients (86.1%) were male. The median OS and PFS were 7.9 months and 4.8 months, respectively. Vascular invasion (hazard ratio (HR), 1.727; 95% confidence interval (CI), 1.258-2.371; p = 0.001), extrahepatic metastasis (HR, 1.401; 95% CI, 1.028-1.908; p = 0.033), alpha-fetoprotein level > 200 ng/mL (HR, 1.559; 95% CI, 1.105-2.201; p = 0.012), and myosteatosis (HR, 1.814; 95% CI, 1.112-2.960; p = 0.017) were associated with OS. Patient mortality was significantly higher in the group with two or more risk factors than in the group with fewer risk factors. In conclusion, myosteatosis may be a novel prognostic CT-based radiological biomarker in sorafenib-treated HCC patients.

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.

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.

Effect of direct-acting antivirals on disease burden of hepatitis C virus infection in South Korea in 2007-2021: a nationwide, multicentre, retrospective cohort study.

Background: It is unclear whether direct-acting antivirals (DAAs) treatment improves the disease burden in hepatitis C virus (HCV) infection. This study aimed to investigate the effect of DAA treatment on the reduction of disease burden in patients with HCV infection using individual participant data. Methods: This nationwide multicentre retrospective cohort study recruited patients with HCV infection from 29 tertiary institutions in South Korea. The data collection was done from medical records in each institution. The study included the untreated patients and the DAAs-treated patients and excluded those with a history of interferon-based treatments. Disease burden was the primary outcome, as represented by disability-adjusted life years (DALYs). Improvement in fibrosis after DAA treatment was assessed using APRI, FIB-4 index, and liver stiffness (LS) as assessed by transient elastography. Clinical outcomes were hepatocellular carcinoma (HCC), decompensation, and mortality. Findings: Between January 1, 2007, and February 17, 2022, data from 11,725 patients with HCV infection, 8464 (72%) of whom were treated with DAAs, were analysed. DAA treatment significantly improved APRI- (median 0.64 [interquartile range (IQR), 0.35-1.31]-0.33 [0.23-0.52], p < 0.0001), FIB-4- (median 2.42 [IQR, 1.48-4.40]-1.93 [1.31-2.97], p < 0.0001), and liver LS-based fibrosis (median 7.4 [IQR, 5.3-12.3]-6.2 [4.6-10.2] kPa, p < 0.0001). During the median follow-up period of 27.5 months (IQR, 10.6-52.4), 469 patients died (4.0%), 586 (5.0%) developed HCC, and 580 (4.9%) developed decompensation. The APRI-based DALY estimate was significantly lower in the DAA group than in the untreated group (median 4.55 vs. 5.14 years, p < 0.0001), as was the FIB-4-based DALY estimate (median 5.43 [IQR, 3.00-6.44] vs. 5.79 [3.85-8.07] years, p < 0.0001). The differences between the untreated and DAA groups were greatest in patients aged 40-60 years. In multivariable analyses, the DAA group had a significantly reduced risk of HCC, decompensation, and mortality compared with the untreated group (hazard ratios: 0.41 [95% confidence interval (CI), 0.34-0.48], 0.31 [95% CI, 0.30-0.38], and 0.22 [95% CI, 0.17-0.27], respectively; p < 0.0001). Interpretation: Our findings suggest that DAA treatment is associated with the improvement of liver-related outcomes and a reduction of liver fibrosis-based disease burden in patients with HCV infection. However, further studies using liver biopsy are needed to clarify the effect of DAA treatment on the reduction in the exact fibrosis-based disease burden beyond noninvasive tests. Funding: The Korea Disease Control and Prevention Agency.

Performance of Simple Fibrosis Score in Non-Alcoholic Fatty Liver Disease with and without Type 2 Diabetes.

This cross-sectional study enrolled 267 patients with metabolic risk factors and established non-alcoholic fatty liver disease in the prospective cohort. The performance of fibrosis-4 (FIB-4) score (≥1.3) to diagnose advanced fibrosis using transient elastography (liver stiffness measurement [LSM] ≥8 kPa) was analyzed. Comparing patients with type 2 diabetes (T2D, n=87) and without (n=180), not FIB-4, but LSM was significantly higher in T2D (P=0.026). The prevalence of advanced fibrosis was 17.2% in T2D and 12.8% in non-T2D. FIB-4 exhibited higher proportion of false negatives in T2D patients (10.9%) than those without (5.2%). The diagnostic performance of FIB-4 was suboptimal in T2D (area under curve [AUC], 0.653; 95% confidence interval [CI], 0.462 to 0.844) compared to that in non-T2D (AUC, 0.826; 95% CI, 0.724 to 0.927). In conclusion, patients with T2D might be beneficial to conduct transient elastography without screening to avoid missing advanced fibrosis.

Clinical Implications for the Comprehensive Interpretation of Radiologic and Immunodiagnostic Tests in Patients Suspected of Parasitic Hepatic Cyst, a Rare Case in Korea.

Cystic echinococcosis (CE) is a representative neglected tropical disease (NTD) with increased morbidity and mortality but is ignored and overlooked in developed countries. Serological and radiographic findings are helpful in distinguishing these parasites; however, conflicting results of these can make it difficult to diagnose if medical knowledge of hepatic parasitic disease, including the etiology, features of imaging, and immunodiagnostic test, is not acquired. We report the case of a male patient with dyspepsia and right epigastric pain who had positive results for cysticercosis antibodies on immunodiagnostic examination. Abdominal ultrasonography revealed two huge communicating cystic lesions measuring 8-11 cm. Further evaluations for cysticercosis of the brain (neurocysticercosis) and eyes (intraocular cysticercosis) were unremarkable throughout the brain imaging test and fundus examination. A laparoscopic right hemi-hepatectomy was performed for diagnosis and treatment. On histopathological examination, diverse stages of Echinococcus granulosus were identified. Albendazole was administered postoperatively, and the patient was also followed up. We should be aware of the etiologies that have been prevalent in parasite infection thought to be the cause of hepatic cysts. Moreover, we make an effort to ascertain the patient's nationality, past travel experiences, and immediate environment, including any animals and pets. We present the case of a patient who was worried about the possibility of liver invasion of cysticercus due to the positivity of the cysticercosis antibody and was ultimately diagnosed with CE.

Impact of metabolic factors on risk of cardiovascular disease in nondiabetic metabolic dysfunction-associated fatty liver disease.

BACKGROUND AND AIM: Changing terminology of non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD) is recently proposed by expert panels based on metabolic dysregulations. However, clinical evidences for the risk of cardiovascular disease (CVD) in MAFLD are limited. The aim of this study is evaluating the association of cardiovascular risk in these two terminology and subgroups of MAFLD. METHODS: A total of 2133 individuals who underwent ultrasound and cardiac computed tomography contemporaneously were included at a single medical checkup center. Ultrasound was used to define fatty liver, and coronary artery calcification (CAC) defined a coronary artery calcium score above 0 was used to estimate the cardiovascular risk. RESULTS: Overall, 911 participants were diagnosed with fatty liver. In the unadjusted analysis, NAFLD (OR = 1.4, 95% confidence interval [CI] = 1.05-1.85, p = 0.019) and MAFLD (OR = 1.55, 95% CI = 1.29-1.86, p = 0.046) were significantly associated with CAC. However, in sex and age-adjusted analyses, only MAFLD was associated with CAC (adjusted OR [aOR] = 1.38, 95% CI = 1.14-1.69, p = 0.001). Of the three subgroups of MAFLD (diabetic, nondiabetic overweight/obese, and nondiabetic normal weight/lean with at least two metabolic abnormalities), only diabetic MAFLD was associated with CAC (aOR = 2.65, 95% CI = 1.98-3.55, p < 0.001). When the minimal number of metabolic risk abnormalities increased to three, nondiabetic normal-weight/lean MAFLD was associated with CAC (aOR = 1.35, 95% CI = 1.02-1.77, p = 0.034). CONCLUSION: Diabetic MAFLD predicted high-risk CVD phenotypes the best. Metabolic risk abnormalities in nondiabetic MAFLD patients were independently associated with the risk of CVD. The proposed diagnostic criteria for nondiabetic MAFLD need further investigation in terms of CVD risk.

Tissue Circular RNA_0004018 and 0003570 as Novel Prognostic Biomarkers for Hepatitis B-Related Hepatocellular Carcinoma.

The clinical significance of hsa_circ_0004018 and hsa_circ_0003570 in patients with hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) is unclear. We aimed to explore the clinical significance and prognostic utility of these two circular RNAs (circRNAs) in patients with HBV-HCC. Based on 86 paired tissue samples of HCC and adjacent non-HCC, the relative expression profiles of hsa_circ_0004018 and hsa_circ_0003570 were determined using quantitative real-time polymerase chain reactions. The cut-off values were the median expression of each of the two circRNAs in 86 patients with HBV-HCC. The combination group comprised patients with high levels of the two circRNAs. Clinicopathological features, body composition profiles at the L3 level, and survival rates were investigated. The expression of hsa_circ_0004018 and hsa_circ_0003570 was downregulated in HCC tissues compared with non-HCC tissues. High expression levels of hsa_circ_0003570 (hazard ratio (HR), 0.437; p = 0.009) and hsa_circ_0004018 (HR, 0.435; p = 0.005) were inversely independent risk factors for overall and progression-free survival in patients with HBV-HCC, whereas the combination group was also an inversely independent risk factor for overall (HR, 0.399; p = 0.005) and progression-free survival (HR, 0.422; p = 0.003) in patients with HBV-HCC. The combination of hsa_circ_0003570 and hsa_circ_0004018 may be a potential prognostic biomarker for HBV-HCC.

The Clinical Courses and Prognosis of Cirrhotic Patients after First Acute Decompensation: Prospective Cohort Study.

BACKGROUND: The European Foundation for the Study of Chronic Liver Failure (EF-CLIF) consortium suggested that the clinical courses after acute decompensation (AD) stratify the long-term prognosis: stable decompensated cirrhosis (SDC), unstable decompensated cirrhosis (UDC), pre acute-on-chronic liver failure (pre ACLF), and ACLF. However, previous studies included patients with a history of previous AD and had limitations associated with identifying the clinical factors related to prognosis after the first AD. METHOD: The prospective Korean Acute-on-Chronic Liver Failure (KACLiF) cohort included cirrhotic patients who were hospitalised with first AD between July 2015 and August 2018. We analysed the factors associated with readmission after the first AD and compared the characteristics and prognosis among each subgroup to evaluate the risk factors for the occurrence of pre ACLF after AD. RESULT: A total of 746 cirrhotic patients who were hospitalised with first AD were enrolled. The subgroups consisted of SDC (n = 565), UDC (n = 29), pre ACLF (n = 28), and ACLF (n = 124). Of note, pre ACLF showed a poorer prognosis than ACLF. The risk factors associated with readmission within 3 months of first AD were non-variceal gastrointestinal (GI) bleeding, hepatic encephalopathy (HE), and high MELD score. Viral aetiology was associated with the occurrence of pre ACLF compared with alcohol aetiology regardless of baseline liver function status. CONCLUSION: Cirrhotic patients with first AD who present as non-variceal GI bleeding and HE can easily relapse. Interestingly, the occurrence of AD with organ failure within 3 months of first AD (pre ACLF) has worse prognosis compared with the occurrence of organ failure at first AD (ACLF). In particular, cirrhotic patients with viral hepatitis with/without alcohol consumption showed poor prognosis compared to other aetiologies. Therefore, patients with ACLF after AD within 3 months should be treated more carefully and definitive treatment through LT should be considered.

Deep Learning-Based Four-Region Lung Segmentation in Chest Radiography for COVID-19 Diagnosis.

Imaging plays an important role in assessing the severity of COVID-19 pneumonia. Recent COVID-19 research indicates that the disease progress propagates from the bottom of the lungs to the top. However, chest radiography (CXR) cannot directly provide a quantitative metric of radiographic opacities, and existing AI-assisted CXR analysis methods do not quantify the regional severity. In this paper, to assist the regional analysis, we developed a fully automated framework using deep learning-based four-region segmentation and detection models to assist the quantification of COVID-19 pneumonia. Specifically, a segmentation model is first applied to separate left and right lungs, and then a detection network of the carina and left hilum is used to separate upper and lower lungs. To improve the segmentation performance, an ensemble strategy with five models is exploited. We evaluated the clinical relevance of the proposed method compared with the radiographic assessment of the quality of lung edema (RALE) annotated by physicians. Mean intensities of segmented four regions indicate a positive correlation to the regional extent and density scores of pulmonary opacities based on the RALE. Therefore, the proposed method can accurately assist the quantification of regional pulmonary opacities of COVID-19 pneumonia patients.

Long-term effects of the changes in hepatic steatosis status on the risk of incident type 2 diabetes mellitus: A 15-year community-based prospective cohort study.

AIMS: We investigated the long-term effect of changes in hepatic steatosis on the risk of developing T2DM. METHODS: We evaluated 3510 participants from the 2001-2016 Korean Genome and Epidemiology Study. Those with significant alcohol consumption or T2DM during 2001-2004 were excluded. Steatosis was defined as non-alcoholic fatty liver disease-liver fat score (NAFLD-LFS) of over -0.64, and baseline values were assessed between 2001 and 2002. Differences in NAFLD-LFS (ΔLFS) and changes in steatosis status (no, intermittent [resolved or incident], and persistent steatosis) were assessed between 2003 and 2004. Changes in the risk of diabetes status were observed until 2016. RESULTS: Over 52,650 person-years of follow-up, T2DM developed in 296 participants (8.4%). The incidence of diabetes in those with no steatosis, intermittent steatosis, and persistent steatosis during follow-up increased by 5.1%, 14.1%, and 27.1% respectively. Multivariate-adjusted analysis revealed that the risk was higher in those with persistent steatosis than those with no steatosis and intermittent steatosis. Baseline NAFLD-LFS and ΔLFS was associated with increased risk of incident T2DM. CONCLUSIONS: Initial severity as well as aggravation of steatosis is an independent predictor of incident T2DM. Strategies aimed at reducing liver fat may prevent future development of diabetes among patients with NAFLD.

Effect of switching from nucleos(t)ide maintenance therapy to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: A randomized trial.

AIMS: Induction of a durable viral response is difficult to achieve in patients with chronic hepatitis B (CHB), even from long-term use of a nucleos(t)ide analogue (NA). This study investigated whether switching to peginterferon (PegIFN) alfa-2a after long-term NA therapy induced a durable viral response. METHODS: Patients with hepatitis B e antigen (HBeAg)-positive CHB who received any NA for at least 72 weeks and had a low level of HBV DNA (≤100 IU/mL) were randomized (1:1) to receive PegIFN alfa-2a (180 µg/week) or NA for 48 weeks. The primary endpoint was change in the hepatitis B surface antigen (HBsAg) titer during antiviral therapy. RESULTS: We randomized 149 CHB patients to the two groups. Compared to baseline, the HBsAg levels in both groups were not lower at week 12, but were lower after 24, 36, and 48 weeks (all p<0.001). The maximal HBsAg decline in the PegIFN alfa-2a group was at week 36 (0.50±0.88 log10 IU/mL), and this decline was smaller in the NA group (0.08±0.46 log10 IU/mL). The percentage of patients with HBeAg seroconversion at week 48 was also greater in the PegIFN alfa-2a group (15/75 [20.0%] vs. 5/74 [6.8%], p = 0.018). Multivariable analysis indicated the PegIFN alfa-2a group had a greater change in HBeAg seroconversion at week 48 (p = 0.027). Patients had relatively good tolerance to PegIFN alfa-2a therapy. CONCLUSIONS: CHB patients who switched to PegIFN alfa-2a for 48 weeks had a significantly lower HBsAg titer and increased HBeAg seroconversion relative to those who remained on NA therapy. TRIAL REGISTRATION: (ClinicalTrials.gov; NCT01769833).