Non-invasive prediction of post-sustained virological response HCC in HCV: A systematic review and meta-analysis.

Background: Despite advances in antiviral therapy for hepatitis C virus (HCV) infection, hepatocellular carcinoma (HCC) still develops even after sustained viral response (SVR) in patients with advanced liver fibrosis or cirrhosis. This meta-analysis investigated the predictive performance of transient elastography (TE) and fibrosis 4-index (FIB-4) for the development of HCC after SVR. Methods: We searched PubMed, MEDLINE, EMBASE, and the Cochrane Library for studies examining the predictive performance of these tests in adult patients with HCV. Two authors independently screened the studies' methodological quality and extracted data. Pooled estimates of sensitivity, specificity, and area under the curve (AUC) were calculated for HCC development using random-effects bivariate logit normal and linear-mixed effect models. Results: We included 27 studies (169,911 patients). Meta-analysis of HCC after SVR was possible in nine TE and 15 FIB-4 studies. Regarding the prediction of HCC development after SVR, the pooled AUCs of pre-treatment TE >9.2-13 kPa and FIB-4 >3.25 were 0.79 and 0.73, respectively. TE >8.4-11 kPa and FIB-4 >3.25 measured after SVR, maintained good predictive performance, albeit slightly reduced (pooled AUCs: 0.77 and 0.70, respectively). The identified optimal cut-off value for HCC development after SVR was 12.6 kPa for pre-treatment TE. That of TE measured after the SVR was 11.2 kPa. Conclusion: TE and FIB-4 showed acceptable predictive performance for HCC development in patients with HCV who achieved SVR, underscoring their utility in clinical practice for guiding surveillance strategies. Future studies are needed to validate these findings prospectively and validate their clinical impact.

Optimal cut-offs of transient elastography and magnetic resonance elastography in diagnosing advanced liver fibrosis in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis.

Background/aims: Opinions differ regarding transient elastography and magnetic resonance elastography (TE/MRE) cut-offs for diagnosing advanced fibrosis (AF) in patients with non-alcoholic fatty liver disease (NAFLD). We investigated the diagnostic performance and optimal cut-off values of TE and MRE for diagnosing AF. Methods: Literature databases, including Medline, EMBASE, Cochrane Library, and KoreaMed, were used to identify relevant studies published up to June 13, 2023. We selected studies evaluating TE and MRE regarding the degree of liver fibrosis using liver biopsy as the reference. The sensitivity, specificity, and area under receiver operating characteristics curves (AUCs) of the pooled data for TE and MRE for each fibrosis stage and optimal cut-offs for AF were investigated. Results: A total of 19,199 patients from 63 studies using TE showed diagnostic AUC of 0.83(95% confidence interval: 0.80-0.86), 0.83(0.80-0.86), 0.87(0.84-0.90), and 0.94(0.91-0.96) for ≥F1, ≥F2, ≥F3, and F4 stages, respectively. Similarly, 1,484 patients from 14 studies using MRE showed diagnostic AUC of 0.89(0.86-0.92), 0.92(0.89-0.94), 0.89(0.86-0.92), and 0.94(0.91-0.96) for ≥F1, ≥F2, ≥F3, and F4 stages respectively. The diagnostic AUC for AF using TE was highest at 0.90 with a cut-off of 7.1-7.9 kPa, and that of MRE was highest at 0.94 with a cut-off of 3.62-3.8 kPa. Conclusions: TE(7.1-7.9 kPa) and MRE(3.62-3.8 kPa) with the suggested cut-offs showed favorable accuracy for diagnosing AF in patients with NAFLD. This result will serve as a basis for clinical guidelines for non-invasive tests and differential diagnosis of AF.

Diagnostic Accuracy of Transient Elastography for Staging Liver Fibrosis in Autoimmune Liver Diseases: A Systematic Review and Meta-Analysis.

Background/Aims: The assessment of liver fibrosis is crucial for managing autoimmune liver diseases such as primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC). However, data on the efficacy of noninvasive tests (NITs) for these diseases are limited. This meta-analysis evaluated the diagnostic accuracy of vibration-controlled transient elastography (VCTE) for staging fibrosis in patients with autoimmune liver disease. Methods: Searches were conducted in PubMed, Embase, CINAHL, Web of Science, and Cochrane Library databases to assess the diagnostic accuracy of VCTE against histology as the reference standard in adult patients with autoimmune liver disease. The summary area under the curve (sAUC) and diagnostic odds ratio were calculated for significant fibrosis (SF), advanced fibrosis (AF), and cirrhosis, defined as METAVIR stages F≥2, F≥3, and F=4, respectively, according to liver biopsy. Results: Fourteen articles were included, comprising 559 PBC patients from six studies, 388 AIH patients from five studies, and 151 PSC patients from three studies. VCTE demonstrated good performance for fibrosis staging in PBC, AIH, and PSC. In PBC, sAUCs of VCTE were 0.87 (95% confidence interval, 0.80-0.94), 0.89 (0.85-0.94), and 0.99 (0.96-1.00) for staging SF, AF, and cirrhosis, respectively. In AIH, the sAUCs were 0.88 (0.84-0.92), 0.88 (0.83-0.93), and 0.92 (0.88-0.96), respectively, while in PSC, they were 0.88 (0.82-0.95), 0.95 (0.90-1.00), and 0.92 (0.84-0.99), respectively. The cutoff values for AF were 7.5-17.9 kPa in PBC, 8.18-12.1 kPa in AIH, and 9.6 kPa in PSC. Conclusions: VCTE shows high diagnostic accuracy for staging liver fibrosis in patients with autoimmune liver diseases such as PBC, AIH, and PSC. This non-invasive and reliable method serves as a valuable tool for the evaluation and monitoring of fibrosis in these lifelong diseases.

Prevalence of clinically significant liver fibrosis in the general population: A systematic review and meta-analysis.

Background/Aims: Although important, clinically significant liver fibrosis is often overlooked in the general population. We aimed to examine the prevalence of clinically significant liver fibrosis using noninvasive tests (NITs) in the general population. Methods: We collected data from four databases (MEDLINE, Embase, Cochrane Library, and KoreaMed) from inception to June 13, 2023. Original articles reporting the prevalence of clinically significant liver fibrosis in the general population were included. The Stata metaprop function was used to obtain the pooled prevalence of liver fibrosis with NITs in the general population. Results: We screened 6,429 articles and included 45 eligible studies that reported the prevalence of clinically significant liver fibrosis in the general population. The prevalence of advanced liver fibrosis, using the high probability cutoff of the fibrosis-4 (FIB-4) index, was 2.3% (95% confidence interval [CI], 1.2-3.7%). The prevalence of significant liver fibrosis, advanced liver fibrosis, and liver cirrhosis, assessed using vibration-controlled transient elastography (VCTE) among the general population, was 7.3% (95% CI, 5.9-8.8%), 3.5% (95% CI, 2.7-4.5), and 1.2% (95% CI, 0.8-1.8%), respectively. Region-based subgroup analysis revealed that the highest prevalence of advanced fibrosis using the high probability cutoff of the FIB-4 index was observed in the American region. Furthermore, the American region exhibits the highest prevalence of significant liver fibrosis, advanced liver fibrosis, and liver cirrhosis, using VCTE. Conclusions: Previously undiagnosed clinically significant liver fibrosis is found in the general population through NITs. Future research is necessary to stratify the risk in the general population.

Risk Assessment of Hepatitis B virus-related Hepatocellular Carcinoma Development Using Transient Elastography: Systematic Review and Meta-analysis.

Background and Aims: Liver stiffness measurement (LSM) using transient elastography (TE) can assess fibrotic burden in chronic liver diseases. The systematic review and meta-analysis was conducted to determine whether LSM using TE can predict the risk of development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. Methods: A systematic literature search of the Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases (from January 2010 to June 2023) was conducted. Of the 1,345 individual studies identified, 10 studies that used TE were finally registered. Hazard ratios (HRs) and the 95% confidence interval (CIs) were considered summary estimates of treatment effect sizes of ≥ 11 kilopascal (kPa) standard for HCC development. Meta-analysis was performed using the restricted Maximum Likelihood random effects model. Results: Among the ten studies, data for risk ratios for HCC development could be obtained from nine studies. When analyzed for the nine studies, the HR for HCC development was high at 3.33 (95% CI, 2.45-4.54) in CHB patients with a baseline LSM of ≥ 11 kPa compared to patients who did not. In ten studies included, LSM of ≥ 11 kPa showed the sensitivity and specificity for predicting HCC development were 61% (95% CI, 50-71%) and 78% (95% CI, 66-86%), respectively, and the diagnostic accuracy was 0.74 (95% CI, 0.70-0.77). Conclusions: The risk of HCC development was elevated in CHB patients with TE-determined LSM of ≥11 kPa. This finding suggests that TE-determined LSM values may aid the risk prediction of HCC development in CHB patients.

Transient elastography for significant fibrosis in treatment-naïve CHB patients: A systematic review and meta-analysis.

Background and Aims: Accurate diagnosis of significant liver fibrosis in patients with chronic hepatitis B (CHB) is crucial when determining whether to initiate antiviral treatment (AVT). We conduct a meta-analysis to assess the diagnostic performance of transient elastography (TE) for significant liver fibrosis in AVT-naïve CHB patients with serum alanine transaminase (ALT) levels within 5-fold the upper limit of normal (ULN). Methods: The Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases were searched to identify studies that compared the performance of TE and liver biopsy (reference standard) when diagnosing significant liver fibrosis (≥ F2) in AVT-naïve CHB patients with ALT within 5-fold the ULN. A hierarchical summary receiver operating characteristic curve (HSROC) and bivariate model were performed to evaluate the diagnostic performance of TE in the meta-analysis. Results: Eight studies (2,003 patients) were included. The summary sensitivity and specificity for diagnosis of significant liver fibrosis were 0.78 [95% confidence interval (CI), 0.66-0.86] and 0.72 (95% CI, 0.60-0.82), respectively. The HSROC for the diagnosis of significant liver fibrosis was 0.81 (95% CI, 0.72-0.86). The optimal cut-off value of TE for diagnosis of significant liver fibrosis was 7.7 kPa with a sensitivity of 0.64 (95% CI, 0.50-0.76) and specificity of 0.83 (95% CI, 0.72-0.90). Conclusions: Our study demonstrated that TE has an acceptable diagnostic performance for significant liver fibrosis in AVT-naïve CHB patients with ALT within 5-fold the ULN.

Validation of Diagnostic Thresholds for Compensated Advanced Chronic Liver Disease Using Supersonic Shear Imaging.

Background The Society of Radiologists in Ultrasound (SRU) has proposed thresholds for acoustic radiation force impulse techniques to diagnose compensated advanced chronic liver disease (cACLD). However, the diagnostic performance of these thresholds has not been extensively validated. Purpose To validate the SRU thresholds in patients with chronic liver disease who underwent supersonic shear imaging and, if suboptimal diagnostic performance is observed, to identify optimal values for diagnosing cACLD. Materials and Methods This retrospective single-center study included high-risk patients with chronic liver disease who had liver stiffness (LS) measurements and had undergone endoscopy or liver biopsy between January 2018 and December 2021. Patients were randomly allocated to test and validation sets. cACLD was defined as varices at endoscopy and/or severe fibrosis or cirrhosis at liver biopsy. The diagnostic performance of the SRU guidelines was evaluated, and optimal threshold values were identified using receiver operating characteristic (ROC) curve analysis. Results A total of 1180 patients (median age, 57 years [IQR, 50-64 years]; 761 men), of whom 544 (46%) had cACLD, were included. With the SRU recommended thresholds of less than 9 kPa and greater than 13 kPa in the test set (n = 786), the sensitivity and specificity for ruling out and ruling in cACLD were 81% (303 of 374 patients; 95% CI: 77, 85) and 92% (380 of 412 patients; 95% CI: 89, 94), respectively. In ROC curve analysis, the identified optimal threshold values were less than 7 kPa and greater than 12 kPa, showing 91% sensitivity (340 of 374 patients; 95% CI: 88, 93) for ruling out cACLD and 91% specificity (373 of 412 patients; 95% CI: 87, 93) for ruling in cACLD, respectively. In the validation set (n = 394), the optimal thresholds showed 91% sensitivity (155 of 170 patients; 95% CI: 86, 95) and 92% specificity (206 of 224 patients; 95% CI: 88, 95). Conclusion Compared with the SRU guidelines, the dual LS threshold values of less than 7 kPa and greater than 12 kPa were better for diagnosing cACLD. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Barr in this issue.

Mortality in patients with chronic hepatitis B treated with tenofovir or entecavir: A multinational study.

BACKGROUND AND AIM: The benefits of entecavir (ETV) versus tenofovir disoproxil fumarate (TDF) in reducing the development of chronic hepatitis B (CHB)-related hepatocellular carcinoma remain controversial. Whether mortality rates differ between patients with CHB treated with ETV and those treated with TDF is unclear. METHODS: A total of 2542 patients with CHB treated with either ETV or TDF were recruited from a multinational cohort. A 1:1 propensity score matching was performed to balance the differences in baseline characteristics between the two patient groups. We aimed to compare the all-cause, liver-related, and non-liver-related mortality between patients receiving ETV and those receiving TDF. RESULTS: The annual incidence of all-cause mortality in the entire cohort was 1.0/100 person-years (follow-up, 15 757.5 person-years). Patients who received TDF were younger and had a higher body mass index, platelet count, hepatitis B virus deoxyribonucleic acid levels, and proportion of hepatitis B e-antigen seropositivity than those who received ETV. The factors associated with all-cause mortality were fibrosis-4 index > 6.5 (hazard ratio [HR]/confidence interval [CI]: 3.13/2.15-4.54, P < 0.001), age per year increase (HR/CI: 1.05/1.04-1.07, P < 0.001), alanine aminotransferase level per U/L increase (HR/CI: 0.997/0.996-0.999, P = 0.003), and γ-glutamyl transferase level per U/L increase (HR/CI: 1.002/1.001-1.003, P < 0.001). No significant difference in all-cause mortality was observed between the ETV and TDF groups (log-rank test, P = 0.69). After propensity score matching, no significant differences in all-cause, liver-related, or non-liver-related mortality were observed between the two groups. CONCLUSIONS: Long-term outcomes of all-cause mortality and liver-related and non-liver-related mortality did not differ between patients treated with ETV and those receiving TDF.

Sex Differences in Treatment Response to Nucleos(t)ide Therapy in Chronic Hepatitis B: A Multicenter Longitudinal Study.

BACKGROUND & AIMS: It is unclear if there may be sex differences in response to nucleos(t)ide analogs including virologic response (VR), biochemical response (BR), complete response (CR), and hepatocellular carcinoma (HCC) incidence among hepatitis B patients. We compared nucleos(t)ide analog treatment outcomes by sex. METHODS: We performed a retrospective cohort study of 3388 treatment-naïve adult hepatitis B patients (1250 female, 2138 male) from the Real-World Evidence from the Global Alliance for the Study of Hepatitis B Virus consortium who initiated therapy with either entecavir or tenofovir from 22 sites (Argentina, Korea, Japan, Taiwan, and the United States). We used propensity-score matching to balance background characteristics of the male and female groups and competing-risks analysis to estimate the incidence and subdistribution hazard ratios (SHRs) of VR, BR, CR, and HCC. RESULTS: Females (vs males) were older (52.0 vs 48.6 y); less likely to be overweight/obese (49.3% vs 65.7%), diabetic (9.9% vs 13.1%), or cirrhotic (27.9% vs 33.0%); and had a lower HBV DNA level (5.9 vs 6.0 log10 IU/mL) and alanine aminotransferase level (91 vs 102 IU/L) (all P < .01). However, after propensity-score matching, relevant background characteristics were balanced between the 2 groups. Females (vs males) had similar 5-year cumulative VR (91.3% vs 90.3%; P = .40) and HCC incidence rates (5.1% vs 4.4%; P = .64), but lower BR (84.0% vs 90.9%; P < .001) and CR (78.8% vs 83.4%; P = .016). Males were more likely to achieve BR (SHR, 1.31; 95% CI, 1.17-1.46; P < .001) and CR (SHR, 1.16; 95% CI, 1.03-1.31; P = .016), but VR and HCC risks were similar. CONCLUSIONS: Sex differences exist for treatment outcomes among hepatitis B patients. Male sex was associated with a 16% higher likelihood of clinical remission and a 31% higher likelihood of biochemical response than females, while virologic response and HCC incidence were similar between the 2 groups.

Pretreatment gamma-glutamyl transferase predicts mortality in patients with chronic hepatitis B treated with nucleotide/nucleoside analogs.

Elevated serum gamma-glutamyl transferase (GGT) levels are associated with chronic hepatitis B (CHB)-related hepatocellular carcinoma. However, their role in predicting mortality in patients with CHB treated with nucleotide/nucleoside analogs (NAs) remains elusive. Altogether, 2843 patients with CHB treated with NAs were recruited from a multinational cohort. Serum GGT levels before and 6 months (Month-6) after initiating NAs were measured to explore their association with all-cause, liver-related, and non-liver-related mortality. The annual incidence of all-cause mortality was 0.9/100 person-years over a follow-up period of 17,436.3 person-years. Compared with patients who survived, those who died had a significantly higher pretreatment (89.3 vs. 67.4 U/L, p = 0.002) and Month-6-GGT levels (62.1 vs. 38.4 U/L, p < 0.001). The factors associated with all-cause mortality included cirrhosis (hazard ratio [HR]/95% confidence interval [CI]: 2.66/1.92-3.70, p < 0.001), pretreatment GGT levels (HR/CI: 1.004/1.003-1.006, p < 0.001), alanine aminotransferase level (HR/CI: 0.996/0.994-0.998, p = 0.001), and age (HR/CI: 1.06/1.04-1.07, p < 0.001). Regarding liver-related mortality, the independent factors included cirrhosis (HR/CI: 4.36/2.79-6.89, p < 0.001), pretreatment GGT levels (HR/CI: 1.006/1.004-1.008, p < 0.001), alanine aminotransferase level (HR/CI: 0.993/0.990-0.997, p = 0.001), age (HR/CI: 1.03/1.01-1.05, p < 0.001), and fatty liver disease (HR/CI: 0.30/0.15-0.59, p = 0.001). Pretreatment GGT levels were also independently predictive of non-liver-related mortality (HR/CI: 1.003/1.000-1.005, p = 0.03). The results remained consistent after excluding the patients with a history of alcohol use. A dose-dependent manner of <25, 25-75, and >75 percentile of pretreatment GGT levels was observed with respect to the all-cause mortality (trend p < 0.001). Pretreatment serum GGT levels predicted all-cause, liver-related, and non-liver-related mortality in patients with CHB treated with NAs.

Risk of Hepatitis C Virus Transmission through Acupuncture: A Systematic Review and Meta-Analysis.

Background/Aims: Chronic hepatitis C is a major risk factor for liver cirrhosis, hepatocellular carcinoma, and hepatic failure. Although traditional practices, including acupuncture, tend to increase the risk of HCV infection, the association remains controversial. Therefore, the current meta-analytical study was undertaken to evaluate the risks of acupuncture and hepatitis C transmission. Methods: Two researchers independently screened studies from the databases encompassing the period from inception to May 12, 2022. Baseline demographics, HCV transmission OR, and 95% CIs were extracted, pooled, and analyzed using random-effect models. Subgroup analyses utilizing study design and ethnicity were performed. Heterogeneity and publication bias were analyzed using the Higgins I2 test and funnel plots, respectively. Results: In all, 28 studies with 194,826 participants (178,583 controls [91.7%] vs. 16,243 acupuncture users [8.3%]) were included in the final analysis. The pooled analysis showed that acupuncture users had a significantly higher HCV transmission rate than controls with heterogeneity (OR, 1.84 [1.46-2.32]; p<0.001; I2 =80%). In the subgroup analysis, both cross-sectional case-control (n=14; OR, 1.96 [1.47-2.61]; p<0.001; I2 =88%) and cross-sectional studies (n=12; OR, 1.85 [1.32-2.61]; p<0.001; I2 =0%) showed significantly higher HCV infection rates in the acupuncture group than in the control group. Both Asian and non-Asian acupuncture users showed a higher HCV transmission risk than the controls (all Ps<0.001). No significant publication bias was observed. Conclusions: Our findings indicate that acupuncture increases the risk of HCV transmission. Due to HCV's contagiousness, unsafe medical and social practices (including acupuncture) should be performed with caution.

Loco-regional therapies competing with radiofrequency ablation in potential indications for hepatocellular carcinoma: a network meta-analysis.

BACKGROUND/AIMS: There is no clear consensus on the relative ranking of interventional and radiation techniques with indications similar to those of radiofrequency ablation (RFA) for the treatment of early hepatocellular carcinoma (HCC). We used a network meta-analysis to compare the efficacy of non-surgical treatments for early HCC. METHODS: We searched databases for randomized trials assessing the efficacy of loco-regional treatments for HCCs ≤5 cm with no extrahepatic spread or portal invasion. The primary outcome was the pooled hazard ratio (HR) for overall survival (OS), and secondary outcomes included overall and local progression-free survival (PFS). A frequentist network meta-analysis was performed, and the relative ranking of therapies was assessed with P-scores. RESULTS: Nineteen studies comparing 11 different strategies in 2,793 patients were included. Chemoembolization plus RFA improved OS better than RFA alone (HR 0.52, 95% confidence interval [CI] 0.33-0.82; P-score=0.951). Cryoablation, microwave ablation, laser ablation, and proton beam therapy had similar effects on OS compared with RFA. For overall PFS, but not local PFS, only chemoembolization plus RFA performed significantly better than RFA (HR 0.61, 95% CI 0.42-0.88; P-score=0.964). Injection of percutaneous ethanol or acetic acid was significantly less effective than RFA for all measured outcomes, while no differences in progression outcomes were identified for other therapies included in the network. CONCLUSION: Our results suggest that chemoembolization combined with RFA is the best option for local treatment of early HCC. Cases with potential contraindications for RFA may benefit from a tailored approach using thermal or radiation modalities.

Pharmacological advances in the treatment of nonalcoholic fatty liver diseases : focused on global results of randomized controlled trials.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease globally, and its prevalence is rapidly increasing. Nonalcoholic steatohepatitis (NASH), a progressive form of NAFLD, is characterized by hepatocellular injury, inflammation, and fibrosis. Patients with NASH or severe fibrosis should be treated according to international NAFLD guidelines. Currently, regulatory agencies have not approved any pharmaceutical treatment for NAFLD. Vitamin E and pioglitazone are efficacious for NASH resolution; however, their benefits must be weighed against the reported risks. In a phase 2 trial, a glucagon-like peptide-1 agonist commonly used for diabetes and obesity was found to improve liver histology in patients with NASH. Furthermore, therapeutic agents targeting NASH pathogenesis, including bile acid signaling, insulin resistance, and lipid metabolism, are in various phases of clinical development. In this article, we review the benefits and drawbacks of current pharmacotherapy and the efficacy of upcoming treatments for NASH.

Clinicogenomic characteristics and synthetic lethal implications of germline homologous recombination-deficient hepatocellular carcinoma.

BACKGROUNDS AND AIMS: We performed an in-depth examination of pathogenic germline variants (PGVs) and somatic variants in DNA damage response (DDR) genes in hepatocellular carcinoma (HCC) to explore their clinical and genomic impacts. APPROACH AND RESULTS: We used a merged whole-exome or RNA sequencing data set derived from in-house ( n = 230) and The Cancer Genome Atlas ( n = 362) databases of multiethnic HCC samples. We also evaluated synthetic lethal approaches targeting mutations in homologous recombination (HR) genes using HCC cells selected from five genomic databases of cancer cell lines. A total of 110 PGVs in DDR pathways in 96 patients were selected. Of the PGV carriers, 44 were HR-altered and found to be independently associated with poorer disease-free survival after hepatectomy. The most frequently altered HR gene in both germline and somatic tissues was POLQ , and this variant was detected in 22.7% (10/44) and 23.8% (5/21) of all the corresponding carriers, respectively. PGVs in HR were significantly associated with upregulation of proliferation and replication-related genes and familial risk of HCC. Samples harboring PGVs in HR with loss of heterozygosity were most strongly correlated with the genomic footprints of deficient HR, such as mutation burden and denovoSig2 (analogous to Catalogue of Somatic Mutations in Cancer [COSMIC] 3), and poor outcome. Pharmacologic experiments with HCC cells defective in BRCA2 or POLQ suggested that tumors with this phenotype are synthetic lethal with poly(ADP-ribose) polymerase inhibitors. CONCLUSIONS: Our findings suggest that germline HR defects in HCC tend to confer a poor prognosis and result in distinctive genomic scarring. Tests of the clinical benefits of HR-directed treatments in the affected patients are needed.

Comparative Metabolomic Analysis of Moromi Fermented Using Different Aspergillus oryzae Strains.

Aspergillus oryzae (A. oryzae) is an important starter in the fermentation of koji and moromi. However, the effect of different A. oryzae strains on the quality of moromi has rarely been studied. For this reason, this study analyzed the physicochemical properties, enzyme activity, sensory quality, and metabolite profiles of moromi samples fermented using two strains (A. oryzae KCCM12012P (moromi-1) and KCCM12804P (moromi-2)), which were newly isolated from fermented soy foods, and compared them to those of a commercialized A. oryzae strain (control). Amino-type nitrogen contents of moromi-1 and moromi-2 samples were higher than that of control moromi, and their amylase and protease activities were also higher. Moreover, metabolite profiles of moromi were significantly altered according to strains. In particular, the levels of many amino acids, peptides, nucleotides, and acidic compounds were altered, which resulted in changes in the sensory quality of moromi. Although volatile compounds were not investigated, the results suggested that the quality of moromi was significantly different for newly isolated strains, especially A. oryzae KCCM12804P, and they were superior to the commercial strain in terms of taste-related substances. Therefore, these strains could be used as good starters to produce moromi and soy sauce with good sensory quality.

Cortisol secretory patterns in deep and moderate neuromuscular blockades in laparoscopic surgery under total intravenous anesthesia: A prospective, single-blinded, randomized controlled trial.

BACKGROUND: Neuroendocrine stress response induces physiological changes depending on the type of surgery and anesthesia. Although the optimal depth of neuromuscular blockade for reducing this response remains unknown, deep neuromuscular blockade is known to improve the surgical environment. Therefore, we hypothesized that a patient's stress response would be lower in surgical procedures under deep neuromuscular blockade than under moderate neuromuscular blockade. METHODS: This prospective, randomized, single-blind study enrolled 72 patients who underwent laparoscopic gynecological surgery under general anesthesia and were assigned to group D (deep blockade: target train-of-four 0 and posttetanic count ≥ 1) or group M (moderate blockade: target train-of-four count 1-3). The primary endpoints were changing patterns in cortisol and adrenocorticotrophic hormone levels; the secondary endpoints were patient outcomes, such as hemodynamic variables, serum glucose level, postoperative pain in the postanesthesia care unit, and hospital stay. RESULTS: The baseline characteristics were comparable between the 67 patients included in the 2 groups (34 in group M and 33 in group D). Cortisol and adrenocorticotrophic hormone levels increased perioperatively in both groups but without significant intergroup differences. Serum glucose level increased perioperatively and decreased postoperatively, but without a significant intergroup difference. Postoperative pain, fentanyl requirement in the postanesthesia care unit, and hospital stay were also comparable. CONCLUSIONS: Compared with moderate neuromuscular blockade, deep neuromuscular blockade improved the surgical environment without significant intergroup differences in the hormonal stress response.

Direct-Acting Antivirals for HCV Treatment in Decompensated Liver Cirrhosis Patients: A Systematic Review and Meta-Analysis.

DAA therapy is known to clear hepatitis C virus infection in patients with decompensated cirrhosis (DC). However, the safety and benefits of DAA in DC remain unclear, especially with the use of protease inhibitors (PI). Therefore, we evaluated the efficacy and clinical safety of DAA in DC patients and observed whether there was a discrepancy between PI-based and non-PI-based treatment. We searched Ovid-Medline, Ovid-EMBASE, Cochrane Library, and three local medical databases through October 2021 to identify relevant studies on the clinical safety and effectiveness of DAA in DC patients. The outcomes were sustained virologic response (SVR), overall mortality, the incidence rate of hepatocellular carcinoma (HCC), adverse events, improvement or deterioration of liver function, and delisting from liver transplantation (LT). Two independent reviewers extracted the data from each study using a standardized form. The pooled event rate in DC patients and relative effect (odds ratio (OR)) of PI-treated versus non-PI-based DAA in DC patients were calculated using a random-effects model. In patients with DC, the SVR rate was 86% (95% CI 83-88%), the development of HCC 7% (95% CI 5-9%), and mortality 6% (95% CI 4-8%). Improvement in liver function was observed in 51% (95% CI 44-58%) of patients, and 16% (95% CI 5-40%) were delisted from LT. PI-based treatment showed a similar rate of serious adverse events (23% vs. 18%), HCC occurrence (5% vs. 7%), and mortality (5% vs. 6%) to that of non-PI-based DAA treatment in DC patients. HCC occurrence and mortality rates were low in patients with DC following DAA treatment. PI-based treatment in DC patients was relatively safe when compared to non-PI-based treatment. Overall, DAA improved liver function, which may have allowed for delisting from LT.

Therapeutic mechanisms and beneficial effects of non-antidiabetic drugs in chronic liver diseases.

The global burden of chronic liver disease (CLD) is substantial. Due to the limited indication of and accessibility to antiviral therapy in viral hepatitis and lack of effective pharmacological treatment in nonalcoholic fatty liver disease, the beneficial effects of antidiabetics and non-antidiabetics in clinical practice have been continuously investigated in patients with CLD. In this narrative review, we focused on non-antidiabetic drugs, including ursodeoxycholic acid, silymarin, dimethyl4,4'-dimethoxy-5,6,5',6'-dimethylenedixoybiphenyl-2,2'-dicarboxylate, L-ornithine L-aspartate, branched chain amino acids, statin, probiotics, vitamin E, and aspirin, and summarized their beneficial effects in CLD. Based on the antioxidant, anti-inflammatory properties, and regulatory functions in glucose or lipid metabolism, several non-antidiabetic drugs have shown beneficial effects in improving liver histology, aminotransferase level, and metabolic parameters and reducing risks of hepatocellular carcinoma and mortality, without significant safety concerns, in patients with CLD. Although the effect as the centerpiece management in patients with CLD is not robust, the use of these non-antidiabetic drugs might be potentially beneficial as an adjuvant or combined treatment strategy.