A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of ALS-L1023 in Non-Alcoholic Fatty Liver Disease.

Preclinical data have shown that the herbal extract, ALS-L1023, from Melissa officinalis reduces visceral fat and hepatic steatosis. We aimed to assess the safety and efficacy of ALS-L1023 as the treatment of non-alcoholic fatty liver disease (NAFLD). We conducted a 24-week randomized, double-blind, placebo-controlled 2a study in patients with NAFLD (MRI-proton density fat fraction [MRI-PDFF] ≥ 8% and liver fibrosis ≥ 2.5 kPa on MR elastography [MRE]) in Korea. Patients were randomly assigned to 1800 mg ALS-L1023 (n = 19), 1200 mg ALS-L1023 (n = 21), or placebo (n = 17) groups. Efficacy endpoints included changes in liver fat on MRI-PDFF, liver stiffness on MRE, and liver enzymes. For the full analysis set, a relative hepatic fat reduction from baseline was significant in the 1800 mg ALS-L1023 group (-15.0%, p = 0.03). There was a significant reduction in liver stiffness from baseline in the 1200 mg ALS-L1023 group (-10.7%, p = 0.03). Serum alanine aminotransferase decreased by -12.4% in the 1800 mg ALS-L1023 group, -29.8% in the 1200 mg ALS-L1023 group, and -4.9% in the placebo group. ALS-L1023 was well tolerated and there were no differences in the incidence of adverse events among the study groups. ALS-L1023 could reduce hepatic fat content in patients with NAFLD.

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.

Langerhans Cell Histiocytosis with the Synchronous Invasion of Stomach and Colon in an Adult Patient: A Case Report.

Langerhans cell histiocytosis (LCH) is reported less frequently in adults than in children. The most common site of involvement in adults is the bone, accounting for 30-50% of cases. The gastrointestinal tract is very rare, accounting for approximately 2%. We present a case of Langerhans cell histiocytosis that simultaneously invaded multiple organs, including the stomach and colon, in an adult. A 37-year-old woman with no underlying disease complained of chest discomfort and a palpable right submandibular mass. A right Level II neck mass and mediastinal LN enlargement were confirmed on the pharynx and chest CT scan. Multiple subepithelial masses with central ulceration and erosion were observed in the corpus and fundus on the esophagogastroduodenoscopy and in the right colon on the colonoscopy. The histopathology findings were the same in each tissue biopsied from the stomach, colon, and right neck lymph nodes. Langerhans cells with classical reniform nuclei and prominent eosinophils invaded the normal glands, and S100 and CD1a were positive in the immunohistochemical stain. Gastrointestinal involvement of LCH in adults is rare, asymptomatic,and can involve multiple digestive organs simultaneously, so upper endoscopy and colonoscopy should be considered for a diagnosis.

Non-Inferior Efficacy of Tenofovir Disoproxil to Tenofovir Disoproxil Fumarate in Virologically Suppressed Chronic Hepatitis B Patients.

Purpose: Tenofovir disoproxil (TD), modified from tenofovir disoproxil fumarate (TDF), was developed as a salt-free formulation, removing fumarate to improve the ease of oral intake by reducing the tablet's size. We evaluated the maintenance of antiviral effects and overall safety profile of TD 245 mg after switching from TDF 300 mg in patients with chronic hepatitis B (CHB). Patients and Methods: CHB patients with HBV-DNA <69 IU/mL after ≥24 weeks of TDF therapy were enrolled. The primary efficacy endpoint was the HBV-DNA suppression rate (HBV-DNA <69 IU/mL) at week 48; We evaluated the non-inferiority (10% margin) of TD to TDF in terms of efficacy. Safety was assessed based on adverse events (AEs), laboratory tests, bone mineral density, and renal function abnormalities. Results: Overall, 189 subjects were randomized in a 2:1 ratio, and 117 and 66 subjects in the TD and TDF groups, respectively, completed the study. In the per-protocol set, the HBV-DNA suppression rate at week 48 was 99.1% and 100% in the TD and TDF groups, respectively. The lower limit of the 97.5% one-sided confidence interval for the intergroup difference in HBV-DNA suppression rate was -2.8%, which was greater than the prespecified margin of non-inferiority. The changes in creatinine clearance from baseline to week 48 was significantly less in the TD group and in the TDF group; -0.8 ± 9.8 versus -2.4 ± 12.8 mL/min, respectively (P=0.017). Conclusion: TD was non-inferior to TDF for maintaining viral suppression in CHB patients, showing the less decline of renal function.

Comparison of eradication rates of moxifloxacin-rifabutin triple therapy and bismuth quadruple therapy as second-line regimens in patients with peptic ulcers.

Background: Bismuth quadruple (BQ) therapy is known to have poor patient compliance and a complex dosing method, and no appropriate third-line regimen exists if second-line BQ therapy fails. In Korea, some alternative regimens have shown unsatisfactory eradication rates. Therefore, we investigated the success rates of the second-line moxifloxacin-rifabutin triple (MRT) regimen and compared it with BQ regimen in subgroup analysis of peptic ulcer patients. Materials and Methods: This study was a retrospective study of 71 patients who underwent a second-line MRT for Helicobacter pylori after failing to clarithromycin triple regimen. To compare the eradication rate in gastric ulcer patients, 51 patients in the MRT group and 132 patients in BQ group were included. After age and sex propensity matching, 45 patients were included in each group (the alpha value and power were set at 0.05% and 77%, respectively). Results: The eradication rate in the MRT group was 69.0% (49/71) in the intention-to-treat (ITT) analysis and 77.8% (49/63) in the per-protocol (PP) analysis. These were significantly lower than the eradication rate in the BQ group (82.5%, p = 0.019 in the ITT analysis; 89.3%, p = 0.022 in the PP analysis). In subgroup analysis of peptic ulcer patients, the success rate of BQ group was significantly higher than that of MRT group in both ITT and PP populations (81.8% (108/132) vs. 60.8% (31/51) in the ITT populations, p = 0.004; and 90.0% (108/120) vs. 72.1% (31/43) in the PP populations, p = 0.010). Among the 14 patients with MRT therapy failure, 10 were eradicated with BQ as the third-line regimen. The eradication rate of the third-line BQ after the second-line MRT failure was 90.0% (9/10). Conclusion: Second-line MRT therapy was not as effective as BQ therapy, so it should be considered for limited use only when BQ is not available.

Ectopic peritoneal paragonimiasis mimicking tuberculous peritonitis: A care report.

BACKGROUND: The most common site of paragonimiasis is in the lungs. The migratory route passes through the duodenal wall, peritoneum, and diaphragm to the lungs; thus, the thoracic cavity and central nervous system, as well as the liver, intestine, and abdominal cavity may be involved. Here, we present a case of intraperitoneal paragonimiasis without other organ involvement, mimicking tuberculous peritonitis. CASE SUMMARY: A 57-year-old man presented with recurrent abdominal pain for 4 wk. Physical examination revealed tenderness in the right lower quadrant. Laboratory findings showed complete blood counts within the normal range without eosinophilia. Multiple reactive lymph nodes and diffuse peritoneal infiltration were noted on abdominal computed tomography (CT). There were no abnormalities on chest CT or colonoscopy. Intraoperative findings of diagnostic laparoscopy for the differential diagnosis of tuberculous peritonitis and peritoneal carcinomatosis included multiple small whitish nodules and an abscess in the peritoneum. Pathological reports confirmed the presence of numerous eggs of Paragonimus westermani (P. westermani). A postoperative serum enzyme-linked immunosorbent assay revealed P. westermani positivity. Persistent and repetitive history-taking led him to retrospectively recall the consumption of freshwater crab. After 3 d of treatment with praziquantel (1800 mg; 25 mg/kg), he recovered from all symptoms. CONCLUSION: In patients who require diagnostic laparoscopy for the differential diagnosis of tuberculous peritonitis and peritoneal carcinomatosis, repetitive history-taking and preoperative serologic antibody tests against Paragonimus may be helpful in diagnosing intraperitoneal paragonimiasis without other organ involvement.

Platelet-to-White Blood Cell Ratio Is Associated with Adverse Outcomes in Cirrhotic Patients with Acute Deterioration.

Background: The platelet-to-white blood cell ratio (PWR) is a hematologic marker of the systemic inflammatory response. Recently, the PWR was revealed to have a role as an independent prognostic factor for mortality in patients with hepatitis B virus (HBV)-related acute-on-chronic failure (ACLF) and HBV-related liver cirrhosis (LC) with acute decompensation (AD). However, the prognostic role of the PWR still needs to be investigated in LC patients with AD. In this study, we analyzed whether the PWR could stratify the risk of adverse outcomes (death or liver transplantation (LT)) in these patients. Methods: A prospective cohort of 1670 patients with AD of liver cirrhosis ((age: 55.2 ± 7.8, male = 1226 (73.4%)) was enrolled and evaluated for 28-day and overall adverse outcomes. Results: During a median follow-up of 8.0 months (range, 1.9−15.5 months), 424 (25.4%) patients had adverse outcomes (death = 377, LT = 47). The most common etiology of LC was alcohol use (69.7%). The adverse outcome rate was higher for patients with a PWR ≤ 12.1 than for those with a PWR > 12.1. A lower PWR level was a prognostic factor for 28-day adverse outcomes (PWR: hazard ratio 1.707, p = 0.034) when adjusted for the etiology of cirrhosis, infection, ACLF, and the MELD score. In the subgroup analysis, the PWR level stratified the risk of 28-day adverse outcomes regardless of the presence of ACLF or the main form of AD but not for those with bacterial infection. Conclusions: A lower PWR level was associated with 28-day adverse outcomes, indicating that the PWR level can be a useful and simple tool for stratifying the risk of 28-day adverse outcomes in LC patients with AD.

Quantification of liver extracellular volume using dual-energy CT for ruling out high-risk varices in cirrhosis.

PURPOSE: To determine the performance of quantification of liver extracellular volume fraction (fECV) using dual-energy CT (DECT) compared with CT imaging for ruling out high-riskesophageal varices(HRV) in cirrhotic patients. METHODS: We retrospectively analyzed 229 cirrhotic patients (training [n = 159] and internal validation cohorts [n = 70]) who underwent dual-source DECT, serum marker assessment, and esophagogastroduodenoscopy (EGD) from 2017 to 2020. The fECV score was measured using iodine maps from 3-minute delayed, equilibrium-phase images at 100/140 Sn kVp. The association of CT parameters and serum markers with HRV was investigated. Criteria combining the fECV score (≤ 25.1%) or CT imaging with platelet count (> 150,000/mm3) were created and compared to rule out HRV. RESULTS: In the training cohort, the fECV score (odds ratio (OR), 1.20; 95% confidence interval (CI), 1.09, 1.32) and CT imaging (OR, 28.21; 95% CI, 9.31, 85.93) were independent predictors of HRV, along with platelet count (OR, 0.85 and 0.78). Criteria combining the fECV score with platelet count showed significantly better performance than those combining CT imaging with platelet count in ruling out HRV (p < 0.001). Applying the criteria could have safely avoided an additional 10.7% and 8.6% of EGDs in the training and validation cohorts, respectively, achieving a final value of 36.5% and 35.7% spared EGDs (0 HRV missed) compared to CT imaging with platelet count. CONCLUSIONS: The combined DECT-based fECV score with platelet count is useful for ruling out HRV and can safely avoid more EGDs than CT imaging with platelet count.

Impact of acute kidney injury on mortality in patients with acute variceal bleeding.

BACKGROUND: The effect of acute kidney injury (AKI) on patients with acute variceal bleeding (AVB) using the recently proposed International Club of Ascites (ICA) criteria is unclear. This study aimed to evaluate the incidence of AKI using the ICA criteria and factors associated with the outcomes in cirrhotic patients with AVB. METHODS: This retrospective cohort study included data of cirrhotic patients with AVB from two centers in Korea. The association of the ICA criteria for AKI with 6-week mortality was analyzed through univariate and multivariate analyses using the Cox proportional hazard model. RESULTS: In total, there were 546 episodes of AVB in 390 patients, of which 425 and 121 episodes were due to esophageal and gastric variceal bleeding, respectively. Moreover, 153 patients fulfilled the ICA criteria for AKI, and 64, 30, 39, and 20 patients were diagnosed with stages 1a, 1b, 2, and 3, respectively. Conversely, 97 patients developed AKI within 42 days as per the conventional criteria. The 6-week mortality rate was significantly higher in patients with ICA-AKI than in patients without ICA-AKI; the occurrence of ICA-AKI was an independent factor for predicting the 6-week mortality. CONCLUSION: The ICA criteria could help diagnose renal dysfunction earlier, and presence of AKI is a predictor of mortality in patients with cirrhosis and AVB.

Real-world Effectiveness and Safety of Direct-acting Antiviral Agents in Patients with Chronic Hepatitis C Genotype 2 Infection: Korean Multicenter Study.

BACKGROUND: The advancement of treatment with direct-acting antiviral (DAA) agents has improved the cure rate of hepatitis C virus (HCV) infection close to 100%. The aim of our study was to assess the real-world effectiveness and safety of DAA regimens for the treatment of patients with chronic HCV genotype 2. METHODS: We retrospectively analyzed the clinical data of patients treated with sofosbuvir plus ribavirin (SOF + RBV) or glecaprevir/pibrentasvir (G/P) for chronic HCV genotype 2 infection at seven university hospitals in the Korean southeast region. RESULTS: SOF + RBV therapy produced an 89% and 98.3% sustained virologic response 12 week (SVR12) after treatment completion in the full analysis set and per-protocol set, respectively, and the corresponding values for G/P therapy were 89.5% and 99.2%, respectively. The difference between the treatments was probably because 6.2% (59/953) of patients in the SOF + RBV group did not complete the treatment and 9.8% (14/143) in the G/P group did not test HCV RNA after treatment completion. Adverse events (A/Es) were reported in 59.7% (569/953) and 25.9% (37/143) of the SOF + RBV and G/P groups, respectively. In the SOF + RBV group, 12 (1.26%) patients discontinued treatment owing to A/Es, whereas no patients discontinued treatment because of A/Es in the G/P group. CONCLUSION: In both treatment groups, SVR was high when treatment was completed. However, there was a high dropout rate in the SOF + RBV group, and the dropout analysis showed that these were patients with liver cirrhosis (LC; 43/285, 15.1%), especially those with decompensated LC (12/32, 37.5%). Therefore, an early initiation of antiviral therapy is recommended for a successful outcome before liver function declines. Furthermore, patients with decompensated LC who are considered candidates for SOF + RBV treatment should be carefully monitored to ensure that their treatment is completed, especially those with low hemoglobin and high alanine transaminase.

T2 mapping in gadoxetic acid-enhanced MRI: utility for predicting decompensation and death in cirrhosis.

OBJECTIVES: To determine whether T2 mapping in liver MRI can predict decompensation and death in cirrhotic patients. METHODS: This retrospective study included 292 cirrhotic patients who underwent gadoxetic acid-enhanced MRI, including T1 and T2 mapping at 10-min hepatobiliary phase by using the Look-Locker and radial turbo spin-echo sequences, respectively. T1 and T2 values of the liver and spleen were measured. The association of MR parameters and serum markers with decompensation and death was investigated. Risk models combining T2Liver, serum albumin level, and Model for End-Stage Liver Disease (MELD) score were created for predicting decompensation (T2Liver, < 49.3 versus ≥ 49.3 ms) and death (< 57.4 versus ≥ 57.4 ms). RESULTS: In patients with compensated cirrhosis at baseline and in the full patient cohort, 9.6% (19 of 197) and 5.1% (15 of 292) developed decompensation and died during the mean follow-up periods of 18.7 and 19.2 months, respectively. A prolonged T2Liver (hazard ratio (HR), 2.59; 95% confidence interval (CI), 1.26, 5.31) was independently predictive of decompensation along with the serum albumin level (HR, 0.28; 95% CI, 0.12, 0.68) and MELD score (HR, 1.34; 95% CI, 1.08, 1.66). T2Liver (HR, 2.61; 95% CI, 1.19, 5.72) and serum albumin level (HR, 0.46; 95% CI, 0.19, 1.14) were independent predictors of death. The mean times to decompensation (12.9 versus 29.2 months) and death (16.5 versus 29.6 months) were significantly different between the high- and low-risk groups (p < 0.001). CONCLUSION: T2Liver from T2 mapping can predict decompensation and death in patients with cirrhosis. KEY POINTS: • Liver T2 values from the radial turbo spin-echo (TSE) T2 mapping sequence with tiered echo sharing and pseudo golden-angle (pGA) reordering were significantly higher in decompensated cirrhosis than compensated cirrhosis. • Liver T2 values from the radial TSE T2 mapping sequence with tiered echo sharing and pGA reordering can predict decompensation and death in patients with cirrhosis. • T2 mapping is recommended as part of liver MRI examinations for cirrhotic patients because it can provide a noninvasive prognostic marker for the development of decompensation and death.

Impact of acute kidney injury on survival in patients with chronic hepatitis C: a retrospective cohort study.

BACKGROUND: Acute kidney injury (AKI) is expected to occur commonly in patients with chronic hepatitis C. In addition, AKI may affect the survival of patients with chronic hepatitis C. However, few studies are available on this topic. We aimed to evaluate the incidence of AKI in patients with chronic hepatitis C and investigate the factors related to overall mortality. METHODS: Between January 2005 and December 2018, 1252 patients with chronic hepatitis C virus (HCV) infection, defined as persistent HCV RNA for at least 6 months, were retrospectively enrolled at two centers. Of them, 1008, 123, and 121 patients had chronic hepatitis (CH), compensated cirrhosis (Com-LC), and decompensated cirrhosis (Decom-LC) or hepatocellular carcinoma (HCC) at entry, respectively. Factors associated with AKI and overall mortality were evaluated using the Cox proportional regression model. The Kaplan-Meier survival curves for the development of AKI and overall mortality were generated. RESULTS: Over a mean follow-up period of 5.2 years, 285 patients developed AKI, with an incidence rate of 4.35 per 100 person-years. The incidence of AKI increased gradually with progression of chronic hepatitis C: CH (3.32 per 100 person-years), Com-LC (5.86 per 100 person-years), and Decom-LC or HCC (17.28 per 100 person-years). The patients without AKI showed better survival rates at 14 years than the patients with AKI (94.2% vs. 26.3%, P < 0.001). In multivariate Cox regression analysis, AKI (hazard ratio, 6.66; 95% confidence interval, 4.26-10.41) remained an independent risk factor for overall mortality. CONCLUSION: AKI is common in patients with chronic HCV infection and is associated with significant overall mortality. Therefore, clinicians should carefully monitor the occurrence of AKI, which is an important predictor of mortality in patients with chronic hepatitis C.

Clinical significance of endothelial progenitor cells in patients with liver cirrhosis with or without hepatocellular carcinoma.

BACKGROUND AND OBJECTIVE: The role of endothelial progenitor cells in patients with cirrhosis has seldom been investigated. This study was conducted to assess the clinical significance of circulating endothelial progenitor cells in patients with liver cirrhosis with or without hepatocellular carcinoma. METHODS: A blood sample was collected once from patients with cirrhosis alone (n = 34) or cirrhosis and hepatocellular carcinoma (n = 46) and healthy controls (n = 27) for assessing levels of endothelial progenitor cells and vascular endothelial growth factor. Blood cells staining positive for CD34/CD133/KDR using flow cytometry were characterized as endothelial progenitor cells. Plasma vascular endothelial growth factor was quantified by ELISA. RESULTS: The levels of CD34/KDR-positive endothelial progenitor cells, CD133/KDR-positive endothelial progenitor cells, and vascular endothelial growth factor were higher in patients with cirrhosis ± hepatocellular carcinoma than in healthy controls (P = 0.017, P < 0.001 and P < 0.001, respectively). The levels of endothelial progenitor cells and vascular endothelial growth factor did not show statistical difference according to Child-Turcotte-Pugh class. There was a moderately significant correlation between vascular endothelial growth factor levels and hepatocellular carcinoma stage (ρ = 0.464, P = 0.001). Smoking, ascites, and portal vein thrombosis were independently related to lower levels of circulating CD34/KDR-positive endothelial progenitor cells, higher levels of CD133/KDR-positive endothelial progenitor cells, and higher levels of vascular endothelial growth factor, respectively (P = 0.041, P = 0.023, and P < 0.001, respectively). CONCLUSION: Circulating endothelial progenitor cells and plasma vascular endothelial growth factor levels were higher in patients with liver cirrhosis ± hepatocellular carcinoma compared to healthy controls. The increase in endothelial progenitor cells and vascular endothelial growth factor may have a possible role in the development of complications, especially ascites and portal vein thrombosis, or in progression of hepatocellular carcinoma.

Hepatitis C virus genotype affects survival in patients with hepatocellular carcinoma.

BACKGROUND: There is currently no evidence that hepatitis C virus (HCV) genotype affects survival in patients with hepatocellular carcinoma (HCC). This study aimed to investigate whether the HCV genotype affected the survival rate of patients with HCV-related HCC. METHODS: We performed a retrospective cohort study using the data of patients with HCV-related HCC evaluated at two centers in Korea between January 2005 and December 2016. Propensity score matching between genotype 2 patients and non-genotype 2 patients was performed to reduce bias. RESULTS: A total of 180 patients were enrolled. Of these, 86, 78, and 16 had genotype 1, genotype 2, and genotype 3 HCV-related HCC, respectively. The median age was 66.0 years, and the median overall survival was 28.6 months. In the entire cohort, patients with genotype 2 had a longer median overall survival (31.7 months) than patients with genotype 1 (28.7 months; P = 0.004) or genotype 3 (15.0 months; P = 0.003). In the propensity score-matched cohort, genotype 2 patients also showed a better survival rate than non-genotype 2 patients (P = 0.007). Genotype 2 patients also had a longer median decompensation-free survival than non-genotype 2 patients (P = 0.001). However, there was no significant difference in recurrence-free survival between genotype 2 and non-genotype 2 patients who underwent curative treatment (P = 0.077). In multivariate Cox regression analysis, non-genotype 2 (hazard ratio, 2.19; 95% confidence interval, 1.29-3.71) remained an independent risk factor for death. CONCLUSION: Among patients with HCV-related HCC, those with genotype 2 have better survival.

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.

Chronic Hepatitis B Infection Is Significantly Associated with Chronic Kidney Disease: a Population-based, Matched Case-control Study.

BACKGROUND: Hepatitis B virus (HBV) infection leads to hepatic and extrahepatic manifestations including chronic kidney disease (CKD). However, the association between HBV and CKD is not clear. This study investigated the association between chronic HBV infection and CKD in a nationwide multicenter study. METHODS: A total of 265,086 subjects who underwent health-check examinations in 33 hospitals from January 2015 to December 2015 were enrolled. HBV surface antigen (HBsAg) positive cases (n = 10,048), and age- and gender-matched HBsAg negative controls (n = 40,192) were identified. CKD was defined as a glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 or proteinuria as at least grade 2+ of urine protein. RESULTS: HBsAg positive cases showed a significantly higher prevalence of GFR < 60 mL/min/1.73 m2 (3.3%), and proteinuria (18.9%) than that of the controls (2.6%, P < 0.001, and 14.1%, P < 0.001, respectively). In the multivariate analysis, HBsAg positivity was an independent factor associated with GFR < 60 mL/min/1.73 m2 along with age, blood levels of albumin, bilirubin, anemia, and hemoglobin A1c (HbA1c). Likewise, HBsAg positivity was an independent factor for proteinuria along with age, male, blood levels of bilirubin, protein, albumin, and HbA1c. A subgroup analysis showed that HBsAg positive men but not women had a significantly increased risk for GFR < 60 mL/min/1.73 m2. CONCLUSION: Chronic HBV infection was significantly associated with a GFR < 60 mL/min/1.73 m2 and proteinuria (≥ 2+). Therefore, clinical concern about CKD in chronic HBV infected patients, especially in male, is warranted.

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.

Clinical features of hepatitis B and C virus infections, with high α-fetoprotein levels but not hepatocellular carcinoma.

The appropriate α-fetoprotein (AFP) level to confirm hepatocellular carcinoma (HCC) could be 100 ng/mL; however, the clinical significance of falsely elevated AFP in patients without HCC has not been fully studied. We investigated the clinical features and outcome of patients without HCC but with high AFP levels (100 ng/mL), especially with chronic hepatitis B (CHB) or C (CHC).The sample included 124 consecutive patients with CHB (n = 97) or CHC (n = 27), with AFP levels >100 ng/mL and without HCC at baseline. Multivariate Cox proportional regression analysis was performed to determine the factors associated with AFP normalization and HCC development.During the mean 52-month follow-up, the proportion of patients with CHB with AFP normalization (90.7%) was significantly higher than the proportion of patients with CHC (59.3%, P < 0.001). Initial aspartate aminotransferase levels (hazard ratio [HR] = 1.02 per 10 U/L increase, P = 0.021) and antiviral therapy (HR = 2.89, P < 0.001) were significantly associated with AFP normalization. Of the 16 (12.9%) patients who developed HCC, hepatitis B virus infection (HR = 10.82, P = 0.001), initiation of antiviral treatment postenrollment (HR = 0.23, P = 0.030), and AFP normalization within 12 months (HR = 0.13, P = 0.011) were associated with HCC development.CHB and CHC were the most common causes of falsely elevated AFP (>100 ng/mL). With either CHB or CHC, persistent AFP elevation (>12 months), regardless of antiviral treatment, might be an important marker of HCC development.

Usefulness of ascitic fluid lactoferrin levels in patients with liver cirrhosis.

BACKGROUND: Although elevated levels of lactoferrin provide a biomarker for inflammatory bowel diseases and colorectal cancer, the clinical significance of these elevated levels in ascitic fluid of patients with ascites caused by liver cirrhosis is limited. The aims of our study were to investigate the usefulness of ascitic fluid lactoferrin levels for the diagnosis of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis and to evaluate the association between lactoferrin levels and the development of hepatocellular carcinoma (HCC). METHODS: A total of 102 patients with ascites caused by cirrhosis were consecutively enrolled into the study, from December 2008 to December 2011. Ascitic fluid lactoferrin levels were quantified using a human lactoferrin enzyme-linked immunosorbent assay kit. RESULTS: The median ascitic fluid lactoferrin levels were significantly higher in patients with SBP than in those without SBP (112.7 ng/mL vs. 0.6 ng/mL; p < 0.001). The area under the receiver operator characteristic curve for the diagnosis of SBP was 0.898 (95 % confidence interval, 0.839-0.957, p < 0.001), with a sensitivity and specificity for a cut-off level of 51.4 ng/mL of 95.8 % and 74.4 %, respectively. Moreover, the incidence of HCC in the 78 patients without SBP was significantly higher in patients with high ascitic fluid lactoferrin levels (≥35 ng/mL) than in those with low ascitic fluid lactoferrin level (<35 ng/mL). CONCLUSIONS: Ascitic fluid lactoferrin level can be a useful diagnostic tool to identify SBP in patients with ascites caused by cirrhosis. Elevated ascitic fluid lactoferrin level in patients without SBP may be indicative of a developing hepatocellular carcinoma.

Prediction of the Risk of Hepatocellular Carcinoma in Chronic Hepatitis C Patients after Sustained Virological Response by Aspartate Aminotransferase to Platelet Ratio Index.

BACKGROUND/AIMS: Following sustained virological response (SVR) for chronic hepatitis C (CHC) infection, patients with advanced fibrosis require regular monitoring for hepatocellular carcinoma (HCC). The aspartate aminotransferase to platelet ratio index (APRI) is a simple noninvasive surrogate marker known to reflect fibrosis. METHODS: We retrospectively analyzed 598 patients who achieved SVR with interferonbased therapy for CHC. RESULTS: Over a median of 5.1 years of follow-up, there were eight patients diagnosed with HCC and a 5-year cumulative incidence rate of 1.3%. The median pretreatment APRI was 0.83, which decreased to 0.29 after achieving SVR (p<0.001). Both the pre- and posttreatment indices were associated with HCC development. The 5-year cumulative HCC incidence rates were 0% and 2.8% for patients with pretreatment APRI <1.0 and ≥1.0, respectively (p=0.001) and 0.8% and 12.8% for patients with posttreatment APRI <1.0 and ≥1.0, respectively (p<0.001). Pretreatment APRI at a cutoff of 1.0 had a 100% negative predictive value until 10 years after SVR. CONCLUSIONS: HCC development was observed among CHC patients who achieved SVR. The pre- and post-treatment APRI could stratify HCC risk, indicating that the APRI could be a useful marker to classify HCC risk in CHC patients who achieved SVR. However, given the small number of HCC patients, this finding warrants further validation.