Autonomous Interfacial Assembly of Polymer Nanofilms via Surfactant-Regulated Marangoni Instability.

Interfacial polymerization (IP) provides a versatile platform for fabricating defect-free functional nanofilms for various applications, including molecular separation, energy, electronics, and biomedical materials. Unfortunately, coupled with complex natural instability phenomena, the IP mechanism and key parameters underlying the structural evolution of nanofilms, especially in the presence of surfactants as an interface regulator, remain puzzling. Here, we interfacially assembled polymer nanofilm membranes at the free water-oil interface in the presence of differently charged surfactants and comprehensively characterized their structure and properties. Combined with computational simulations, an in situ visualization of interfacial film formation discovered the critical role of Marangoni instability induced by the surfactants via various mechanisms in structurally regulating the nanofilms. Despite their different instability-triggering mechanisms, the delicate control of the surfactants enabled the fabrication of defect-free, ultra-permselective nanofilm membranes. Our study identifies critical IP parameters that allow us to rationally design nanofilms, coatings, and membranes for target applications.

Prevalence and prognosis of acute pancreatitis in critically ill patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic issue. In addition to the well-known respiratory and fever symptoms, gastrointestinal symptoms have also been reported. This study aimed to evaluate the prevalence and prognosis of patients with COVID-19 infection complicated with acute pancreatitis in intensive care unit (ICU). METHODS: This was a retrospective observational cohort study, and patients aged 18 years or older, admitted into the ICU in a single tertiary center from January 1, 2020, to April 30, 2022 were enrolled. Patients were identified by electronic medical records and reviewed manually. The primary outcome was the prevalence of acute pancreatitis among ICU patients with COVID-19. The secondary outcomes were the length of hospital stay, need for mechanical ventilation (MV), need for continuous renal replacement therapy (CRRT), and in-hospital mortality. RESULTS: A total of 4133 patients, admitted into the ICU, were screened. Among these patients, 389 were infected by COVID-19, and 86 were diagnosed with acute pancreatitis. COVID-19 positive patients were more likely to present with acute pancreatitis than COVID-19 negative patients (odds ratio = 5.42, 95% confidence interval: 2.35-6.58, P < 0.01). However, the length of hospital stay, need for MV, need for CRRT, and in-hospital mortality were not significantly different between acute pancreatitis patients with and without COVID-19 infection. CONCLUSIONS: Severe COVID-19 infections may cause acute pancreas damage in critically ill patients. However, the prognosis may not differ between acute pancreatitis patients with and without COVID-19 infection.

Role of Microbiota-Derived Metabolites in Alcoholic and Non-Alcoholic Fatty Liver Diseases.

Chronic liver disease encompasses diseases that have various causes, such as alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). Gut microbiota dysregulation plays a key role in the pathogenesis of ALD and NAFLD through the gut-liver axis. The gut microbiota consists of various microorganisms that play a role in maintaining the homeostasis of the host and release a wide number of metabolites, including short-chain fatty acids (SCFAs), peptides, and hormones, continually shaping the host's immunity and metabolism. The integrity of the intestinal mucosal and vascular barriers is crucial to protect liver cells from exposure to harmful metabolites and pathogen-associated molecular pattern molecules. Dysbiosis and increased intestinal permeability may allow the liver to be exposed to abundant harmful metabolites that promote liver inflammation and fibrosis. In this review, we introduce the metabolites and components derived from the gut microbiota and discuss their pathologic effect in the liver alongside recent advances in molecular-based therapeutics and novel mechanistic findings associated with the gut-liver axis in ALD and NAFLD.

Prognostic Significance of Hemodynamic and Clinical Stages in the Prediction of Hepatocellular Carcinoma.

BACKGROUND & GOALS: Early identification of hepatocellular carcinoma (HCC) is associated with improved survival for patients with chronic liver disease (CLD). We evaluated the prognostic significance of hemodynamic stage (HS) and clinical stage (CS) in predicting HCC in CLD patients. METHODS: Between January 2006 and May 2014, 801 patients with CLD who underwent hepatic venous pressure gradient (HVPG) measurement were prospectively enrolled. HS was classified by HVPG (mm Hg) as follows: HS-1 (HVPG≤6), HS-2 (612 mm Hg (P=0.033, OR=2.17), CS>2 (P=0.039, OR=2.36), and alpha-fetoprotein (AFP; P=0.017, OR=1.01) were significant predictors of HCC development in all patients. For patients with cirrhosis, ascites aggravation (OR=2.51), HVPG >12 mm Hg (OR=2.46), and CS >2 (OR=2.62) were correlated with HCC development. Areas under receiver operating characteristic curves of the prediction-model, CS, HVPG score, and AFP were 0.797, 0.707, 0.701, and 0.653, respectively. CONCLUSIONS: HCC development correlates with advancing liver fibrosis or disease as measured by HS and CS. In addition, ascites aggravation and elevated AFP appears to be associated with increased incidence of HCC.

Comparison of the long-term efficacy between entecavir and tenofovir in treatment- naïve chronic hepatitis B patients.

BACKGROUND: There have been limited studies directly comparing the long-term efficacy between entecavir (ETV) and tenofovir disoproxil fumarate (TDF). This study was aimed to compare the long-term efficacy between them in treatment-naïve chronic hepatitis B (CHB). METHODS: Out of 345 CHB patients who received first line therapy with ETV (n = 200) or TDF (n = 145) in a cohort, 210 patients were analyzed using propensity score matching, at a ratio of 1:1. RESULTS: Two groups showed no difference in baseline characteristics. During the follow-up of 12 months, HBV DNA levels were similarly suppressed in both groups (ETV vs. TDF; -5.01 vs. -5.242 log10IU/mL, P = 0.559). At month 12, both groups showed no difference in terms of the serologic, biochemical and virologic (VR) response. In multivariate analysis, the initial virologic response at 3 months (IVR-3) was independent factor for VR at 1 year. During the long-term follow-up, HBV DNA levels were more strongly suppressed by TDF than ETV in hepatitis B e antigen (HBeAg) positive patients (P = 0.035), especially with high viral load (P = 0.012), although there was no significant difference in overall VR between two groups. The type of antivirals was not an independent factor for long-term VR. CONCLUSIONS: Although either ETV or TDF, overall, may show a comparable long-term antiviral efficacy in treatment-naïve CHB, TDF might be better regimen than ETV in the subgroup of HBeAg-positive CHB, especially with a higher HBV DNA levels.

Portal hypertensive gastropathy as a prognostic index in patients with liver cirrhosis.

BACKGROUND: Portal hypertensive gastropathy (PHG) is a frequently overlooked complication of liver cirrhosis (LC). The clinical implications of PHG as a prognostic factor of LC or a predictive factor for the development of hepatocellular carcinoma (HCC) have not been established. The aim of this study was to assess the clinical significance of PHG in patients with LC. METHODS: Patients with LC were prospectively enrolled and followed in a single tertiary hospital in the Republic of Korea. Baseline hepatic vein pressure gradient (HVPG) was measured, and esophagogastroduodenoscopy (EGD) was performed. The associations of PHG with HVPG, survival and the development of HCC were evaluated. RESULTS: A total of 587 patients were enrolled. The mortality rate was 20.3 % (n = 119), and HCC developed in 9.2 % (n = 54) during the follow-up period (32.6 ± 27.8 months). The grade of PHG was well correlated with HVPG (no PGH: median 9.2 [IQR: 7.2-16.7], mild PHG: 14.6 [10.1-19.3], and severe PHG: 17.3 [12.3-21.5], P < 0.001), as well as with Child-Pugh class, MELD score or survival. However, it was not associated with the development of HCC. The grade of PHG (HR 3.29, 95 % CI: 1.12-9.63, severe vs. no PHG) and Child-Pugh class (HR 3.53, 95 % CI: 1.79-6.97, Child C vs A) showed significant associations with mortality. CONCLUSION: PHG was well correlated with portal hypertension and could be used as a prognostic factor for LC but not for the prediction of HCC.

Transenteral bowel preparation for colonoscopy is more comfortable than the traditional method with no inferiority in efficacy.

BACKGROUND: Transenteral (TE) administration of a bowel cleanser prior to colonoscopy avoids the discomfort associated with drinking a large volume of unpalatable cleanser. AIM: To explore patient comfort, preference for future colonoscopy, the efficacy and adverse events associated with TE bowel preparation. METHODS: Bowel preparation is traditionally practised using polyethylene glycol (PEG) + ascorbic acid (ASC), which was the treatment used in the control group (peroral group; PO group). In the study group (TE group), PEG + ASC were administered directly to the third portion of the duodenum through a scope immediately after completing upper gastrointestinal endoscopy. RESULTS: A higher proportion of subjects in the TE group graded their degree of comfort as very or rather comfortable (28.4 % in the PO group, 65.1 % in the TE group; p = 0.000) and had greater preference for future colonoscopy (69.6 % in the PO group, 82.5 % in the TE group; p = 0.030), compared with the PO group. The TE group had non-inferiority in efficacy compared with the PO group (non-inferiority margin -15 %; lower limit of 95 % confidence interval for difference between success rates -6.4 %, when using the Aronchick Scale, and -7.1 % when using the Ottawa Scale). Nausea or vomiting were more prevalent during preparation in the PO group (46.1 vs. 17.5 %; p = 0.000), and dizziness was more common in the TE group (0 vs. 12.6 %; p = 0.000). CONCLUSIONS: TE preparation was found to be more comfortable than the traditional peroral method and not inferior in efficacy. The adverse events rate was acceptable.

Adefovir and lamivudine combination therapy in patients with entecavir-resistant chronic hepatitis B: antiviral responses and evolution of mutations.

OBJECTIVE: This study was designed to prospectively evaluate the antiviral responses and evolution of resistance mutations during adefovir (ADV) plus lamivudine (LMV) therapy in patients with entecavir (ETV)-resistant hepatitis B virus (HBV) infection. METHODS: Twenty chronic hepatitis B (CHB) patients who had been receiving ETV for more than 6 months and developed virologic breakthrough due to ETV resistance were consecutively enrolled. RESULTS: Patients received ADV plus LMV therapy for 12 months. The baseline mean serum HBV DNA level was 5.59 ± 1.28 log10 IU/ml. The rtT184L/I/A/F (50%), rtS202G (25%) and mixed ETV-resistant mutations (25%) were detected at enrollment. The mean reduction in serum HBV DNA levels from baseline to 12 months was -2.3 ± 1.06 log10 IU/ml (p < 0.001). Seventeen patients were followed up for the full 12 months, and complete virologic response (HBV DNA <20 IU/ml) was observed in 4 patients (23.5%). Among the remaining 13 patients who still had detectable HBV DNA, 7 patients showed disappearance of ETV-resistant mutations or reduction of the proportion of ETV-resistant mutants. An ADV- and LMV-resistant mutant (rtA181T) emerged in 2 patients (11.7%). CONCLUSIONS: ADV plus LMV combination therapy suppresses ETV-resistant mutants in the viral population and significantly reduces serum HBV DNA levels in ETV-resistant CHB patients.

Phylogenetic analyses of HBV pre-s/s genes in mother-child pairs with long-term infection by presumed vertical transmission.

Vertical transmission from mother to child, the main route of chronic hepatitis B virus (HBV) infection in the East Asia, is considered one of the most important predictors for the response to antiviral therapies as well as its complications such as cirrhosis and hepatocellular carcinoma. Therefore, it is critical in both etiologic and prognostic aspects to confirm whether or not chronic HBV infection is acquired vertically. This study investigated whether mother-to-child infection could be proved by the phylogenetic analyses of HBV pre-S/S genes ever since several decades have elapsed in mother-child pairs with presumed vertical transmission. The pre-S and S regions of HBVs were compared and analyzed phylogenetically in a total of 36 adults (18 mother-child pairs) with chronic HBV infection. All of the isolates of HBV were genotype C and serotype adr. The divergence between mothers and offsprings was 0 to 1.5%. Phylogenetic trees revealed that 17 of 18 pairs (94%) with presumed vertical transmission were grouped into the same cluster. Vertical transmission from mother to child could be strongly suggested even in adults with a history of several decades of HBV infection using the phylogenetic analyses of pre-S and S genes.

Clinical characteristics and outcomes of acute hepatitis a in Korea: a nationwide multicenter study.

The aim of this study was to investigate the clinical characteristics of acute hepatitis A during a recent outbreak in Korea. Data of patients diagnosed with acute hepatitis A from 2007 to 2009 were collected from 21 tertiary hospitals retrospectively. Their demographic, clinical, and serological characteristics and their clinical outcomes were analyzed. A total of 4,218 patients (mean age 33.3 yr) were included. The median duration of admission was 9 days. The mean of the highest ALT level was 2,963 IU/L, total bilirubin was 7.3 mg/dL, prothrombin time INR was 1.3. HBsAg was positive in 3.7%, and anti-HCV positive in 0.7%. Renal insufficiency occurred in 2.7%, hepatic failure in 0.9%, relapsing hepatitis in 0.7%, and cholestatic hepatitis in 1.9% of the patients. Nineteen patients (0.45%) died or were transplanted. Complications of renal failure or prolonged cholestasis were more frequent in patients older than 30 yr. In conclusion, most patients with acute hepatitis A recover uneventfully, however, complication rates are higher in patients older than 30 yr than younger patients. Preventive strategies including universal vaccination in infants and active immunization of hepatitis A to adult population should be considered for prevention of community-wide outbreaks of hepatitis A in Korea.

Does chronic hepatitis B infection affect the clinical course of acute hepatitis A?

The impact of chronic hepatitis B on the clinical outcome of acute hepatitis A remains controversial. The aim of present study was to evaluate the clinical characteristics of acute hepatitis A in cases with underlying chronic hepatitis B compared to cases of acute hepatitis A alone. Data on 758 patients with acute hepatitis A admitted at two university-affiliated hospitals were reviewed. Patients were classified into three groups: group A, patients with both acute hepatitis A and underlying chronic hepatitis B (n = 27); group B, patients infected by acute hepatitis A alone whose sexes and ages were matched with patients in group A (n = 54); and group C, patients with acute hepatitis A alone (n = 731). None of the demographic features of group A were significantly different from those of group B or C, except for the proportion of males and body weight, which differed from group C. When comparing to group B, clinical symptoms were more frequent, and higher total bilirubin and lower albumin levels were observed in group A. When comparing to group C, the albumin levels were lower in group A. There were no differences in the duration of hospital stay, occurrence of acute kidney injury, acute liver failure, prolonged cholestasis, or relapsing hepatitis. This study revealed that clinical symptoms and laboratory findings were less favorable for patients with acute hepatitis A and chronic hepatitis B compared to those with acute hepatitis A alone. However, there were no differences in fatal outcomes or serious complications.

Adding adefovir vs. switching to entecavir for lamivudine-resistant chronic hepatitis B (ACE study): a 2-year follow-up randomized controlled trial.

BACKGROUND: Management of lamivudine-resistant chronic hepatitis B (CHB) remains challenging, as inappropriate choice of treatment may cause multidrug resistance. Until now, randomized trials directly comparing adding adefovir and switching to entecavir monotherapy have not been reported. AIMS: This multicentre prospective randomized study was designed to compare the efficacy of these two strategies. METHODS: Two hundred and nineteen lamivudine-resistant CHB patients were randomized to either adefovir-lamivudine combination group or entecavir monotherapy group (n = 110 vs. 109), and followed up for 24 months. RESULTS: One hundred and eighty patients completed this study. At month 24, virological response rate [hepatitis B virus (HBV) DNA <60 IU/ml] was higher in the adefovir-lamivudine combination group compared with entecavir group (56.7% vs. 40%, P = 0.025), although biochemical and serological response rates were not significantly different. Genotypic resistance (9.2% vs. 24.6%, P = 0.005) and combined viral breakthrough (2.0% vs. 17.6%, P < 0.001) were more frequent in the entecavir group. However, by subgroup analysis, virological response rates were not significantly different between the two therapies in HBeAg-positive patients (44.9% vs. 35.7%, P = 0.268) or in patients with high baseline HBV DNA (≥7 log IU/ml) (40.7% vs. 31.3%, P = 0.320) at month 24. CONCLUSION: This study showed that adefovir-lamivudine combination provides significantly higher antiviral efficacy and the lower resistance rate compared with the entecavir monotherapy in the management of lamivudine-resistant CHB. However, it had limited efficacy in HBeAg-positive patients or in patients with high baseline HBV DNA.

Genotypic shift of the hepatitis A virus and its clinical impact on acute hepatitis A in Korea: a nationwide multicenter study.

BACKGROUND: The genotypic shift of hepatitis A virus (HAV) and its correlation with clinical course has not been evaluated in acute hepatitis A (AHA). METHODS: From June 2007 to May 2009, we prospectively enrolled 546 AHA patients. We performed a nested reverse transcriptase polymerase chain reaction (RT-PCR) using the serum samples in addition to phylogenetic analysis, then we compared patient clinical features. RESULTS: Among 351 successfully genotyped patients, we found genotype IIIA in 178 patients (51%) and IA in 173 patients (49%). The sequences of genotype IA are identical to previously reported Korean genotype IA, and the new IIIA genotype is closely related to NOR24/Norway. We retrospectively analyzed 41 AHA samples collected from 2000 to 2006 and found that all of them were genotype IA. Patients with genotype IIIA showed significantly higher levels of aspartate aminotransferase, higher levels of alanine aminotransferase, and lower platelet counts than patients with genotype IA when comparing baseline laboratory data or peak/lowest laboratory data during the disease course. However, there were no differences in duration of hospital stay, incidence of cholestatic hepatitis, acute kidney injury, and acute liver failure, or mortality between them. CONCLUSIONS: A genotypic shift of the HAV was identified in Korean AHA subjects, and genotype IIIA HAV has become endemic. Although there were significant differences in the biochemical responses of AHA between genotype IA and genotype IIIA patients, we did not detect any differences in clinical outcomes such as complications or mortality.

Serum S100B Levels in Patients with Liver Cirrhosis and Hepatic Encephalopathy.

Hepatic encephalopathy (HE) is one of the main complications of liver cirrhosis (LC) and is classified into minimal hepatic encephalopathy (MHE) and overt hepatic encephalopathy (overt HE). S100B is expressed mainly in astrocytes and other glial cells, and S100B has been reported to be associated with various neurological disorders. The present study aimed to investigate the diagnostic ability of serum S100B to discriminate the grade of HE and the parameters correlated with serum S100B levels. Additionally, we investigated whether serum S100B levels can be used to predict 1-year mortality in cirrhotic patients. In total, 95 cirrhotic patients were consecutively enrolled and divided into the following three groups: (i) without any types of HEs; (ii) with MHE; and (iii) with overt HE. The diagnosis of MHE was made by the Mini-Mental State Examination (MMSE) and Psychometric Hepatic Encephalopathy Score (PHES). Among the three groups, there were no significant differences in serum S100B levels regardless of HE severity. The clinical parameters correlated with serum S100B levels were age, serum bilirubin, and creatinine levels. The Model for End-Stage Liver Disease (MELD) score showed a significant positive correlation with serum S100B levels. The relationship between serum S100B levels and MELD score was maintained in 48 patients without any type of HE. Additionally, hyperammonemia, low cholesterol levels, and the combination of serum S100B levels ≥ 35 pg/mL with MELD score ≥ 13 were factors for predicting 1- year mortality. In conclusion, serum S100B level was not useful for differentiating the severity of HE. However, we found that serum S100B levels can be affected by age, serum bilirubin, and creatinine in cirrhotic patients and are associated with MELD scores. Additionally, serum S100B levels showed the possibility of predicting 1-year mortality in cirrhotic patients. These findings suggest that serum S100B levels may reflect liver dysfunction and prognosis in liver disease.

The diagnostic significance of hepatitis C virus antibody levels for chronic hepatitis C virus infection.

BACKGROUND/AIMS: Although anti-hepatitis C virus (HCV) assay is widely used to screen for HCV infection, it has a high false-positive (FP) rate in low-risk populations. We investigated the accuracy of anti-HCV signal-to-cutoff (S/CO) ratio to distinguish true-positive (TP) from FP HCV infection. METHODS: We retrospectively analyzed 77,571 patients with anti-HCV results. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic accuracy of anti-HCV S/CO ratio in anti-HCV positive patients. RESULTS: Overall, 1,126 patients tested anti-HCV positive; 34.7% of patients were FP based on HCV RNA and/or recombinant immunoblot assay (RIBA) results. The age and sex-adjusted anti-HCV prevalence was 1.22%. We identified significant differences in serum aspartate transaminase and alanine transaminase levels, anti-HCV S/CO ratio, and RIBA results between groups (viremia vs. non-viremia, TP vs. FP). Using ROC curves, the optimal cutoff values of anti-HCV S/CO ratio for HCV viremia and TP were 8 and 5, respectively. The area under the ROC curve, sensitivity, specificity, positive and negative predictive values were 0.970 (95% CI, 0.959-0.982, p < 0.001), 99.7%, 87.5%, 87.4%, and 99.7%, respectively, for predicting HCV viremia at an anti-HCV S/CO ratio of 8 and 0.987 (95% CI, 0.980-0.994, p < 0.001), 95.3%, 94.7%, 97.1%, and 91.4%, respectively, for TP HCV infection at an anti-HCV S/CO ratio of 5. No patients with HCV viremia had an anti-HCV S/CO ratio below 5. CONCLUSION: The anti-HCV S/CO ratio is highly accurate for discriminating TP from FP HCV infection and should be considered when diagnosing HCV infections.

Clinical characteristics of patients with Mycoplasma pneumoniae-related acute hepatitis.

BACKGROUND/AIMS: Although the hepatobiliary manifestations of Mycoplasma pneumoniae infection have been described in several previous studies, controversies still remain. The aim of this study was to evaluate the clinical characteristics of patients with M. pneumoniae-related hepatitis and compare to those with M. pneumoniae infection but not hepatitis. METHODS: We reviewed the medical chart of patients diagnosed with M. pneumoniae infection serologically. RESULTS: Among the 117 patients with M. pneumoniae infection enrolled in the study, 25 showed acute hepatitis without any evidence of another cause. Patients with hepatitis presented with prodromal symptoms more frequently and also had a higher body temperature and C-reactive protein (CRP) levels than patients without hepatitis. Frequencies of respiratory tract involvement were not different between two groups. Clinical signs recovered within three weeks in both groups following the institution of antibiotic therapy. Multivariate analysis revealed that male sex, age <40 years, and high CRP levels were significantly linked to M. pneumoniae-related hepatitis. CONCLUSIONS: We found that acute hepatitis associated with M. pneumoniae occurred in about 21% of all M. pneumoniae infections, and gender, age, and CRP levels were factors related to the occurrence of M. pneumoniae-related hepatitis.

Prevalence of minimal change lesions in patients with non-erosive reflux disease: a case-control study.

BACKGROUND/AIMS: Some minimal changes (MCs) are believed to have a certain relationship with gastroesophageal reflux (GERD). Nonetheless, the individual meaning of MC is still unclear. Our aim was to compare the overall and individual prevalence of MC between patients with non-erosive reflux disease (NERD) and healthy controls (HC). METHODS: Twelve endoscopic findings in the esophagogastric junction were prospectively compared between NERD (n = 64) and control (n = 104). RESULTS: Overall frequency of MC (≥ 1 out of 12 criteria) was higher in the NERD group (71.9%) than in the HC group (45.2%). In individual analysis, white mucosal turbidity, irregular Z-line, horizontal erosions, and mucosal protrusion of cardia were significantly more common in the NERD group compared to controls. Among them, only white mucosal turbidity was independently associated with the NERD group (OR 3.97, 95% CI 1.72-9.13). Individuals with male gender, reflux symptoms, higher height, current smoking, ethanol intake and hiatal hernia were more likely to have white mucosal turbidity compared to the group without white turbidity. CONCLUSIONS: MC could be a useful marker to support clinical diagnosis of GERD. White mucosal turbidity in particular might be a GERD-specific sign related to acid-induced mucosal damage.

Primary Biliary Cholangitis and Primary Sclerosing Cholangitis: Current Knowledge of Pathogenesis and Therapeutics.

Cholangiopathies encompass various biliary diseases affecting the biliary epithelium, resulting in cholestasis, inflammation, fibrosis, and ultimately liver cirrhosis. Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are the most important progressive cholangiopathies in adults. Much research has broadened the scope of disease biology to genetic risk, epigenetic changes, dysregulated mucosal immunity, altered biliary epithelial cell function, and dysbiosis, all of which interact and arise in the context of ill-defined environmental triggers. An in-depth understanding of the molecular pathogenesis of these cholestatic diseases will help clinicians better prevent and treat diseases. In this review, we focus on the main underlying mechanisms of disease initiation and progression, and novel targeted therapeutics beyond currently approved treatments.

A Multicenter Retrospective Study on Clinical Characteristics and Outcome of Pyogenic Liver Abscess Focusing Multidrug-Resistant Organisms.

The emergence of multidrug-resistant organisms (MDROs) is a growing problem worldwide. However, little is known about the incidence, clinical features and outcomes of pyogenic liver abscesses (PLAs) caused by MDROs. A retrospective study of 833 patients with PLA admitted from 2008 to 2017 was performed. MDROs were found in 55 (6.6%) patients, and extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae was the most common causative microorganism. To evaluate the clinical features of and risk factors for MDRO-induced PLAs, propensity score matching (PSM) was performed in a 1:3 ratio (55 patients with MDROs and 165 patients without MDROs). After PSM, previous hepatobiliary procedure, preadmission exposure to antibiotics and elevated alkaline phosphatase levels were independent risk factors for MDRO-induced PLA. Sixteen patients (7.3%) died during hospitalization. Admission to intensive care unit (ICU), inadequate initial antibiotic treatment and use of inotropic agents were factors predictive of mortality. Although the presence of MDROs was not associated with in-hospital mortality, inadequate initial antibiotic treatment was prescribed to a large portion of the patients with MDRO-induced PLAs. We conclude that initial empirical antibiotic therapy for PLA should be based on the possibility of infection with MDROs, and close monitoring is necessary for patients with risk factors for in-hospital mortality.

Platelet-to-White Blood Cell Ratio: A Feasible Biomarker for Pyogenic Liver Abscess.

The platelet-to-white blood cell ratio (PWR) has been reported to predict the severity of patients with various diseases. However, no previous studies have assessed the use of the PWR as a prognostic marker for pyogenic liver abscesses (PLA). This observational retrospective study was performed between January 2008 and December 2017, including 833 patients with PLA from multiple centers. The enrolled patients, on average, had a PWR of 17.05, and 416 patients had a PWR lower than 17.05. A total of 260 patients (31.2%) with PLA showed complications of metastatic infection, pleural effusion and abscess rupture. A low PWR level was identified as a strong risk factor for metastatic infection and pleural effusion. The low PWR group also had a longer hospital stay. In the multivariate analysis, old age, anemia, albumin and CRP levels and unidentified pathogens were significant factors for low PWR levels. A low PWR, old age, male sex, abscess size, albumin, ALP and unidentified causative pathogens showed significant associations with a hospital stay longer than 28 days. As a result, PLA patients presenting with a low PWR were shown to have more complications and a poor prognosis. Considering its cost-effectiveness, PWR could be a novel biomarker used to predict a prognosis of PLA.