Statin use decreases the risk of decompensation and mortality in patients with cirrhosis due to hepatitis C virus (HCV). Whether this beneficial effect can be extended to cirrhosis in the general ...population or cirrhosis due to other causes, such as hepatitis B virus (HBV) infection or alcohol, remains unknown. Statin use also decreases the risk of hepatocellular carcinoma (HCC) in patients with chronic HBV and HCV infection. It is unclear whether the effect can be observed in patients with pre‐existing cirrhosis. The goal of this study was to determine the effect of statin use on rates of decompensation, mortality, and HCC in HBV‐, HCV‐, and alcohol‐related cirrhosis. Patients with cirrhosis were identified from a representative cohort of Taiwan National Health Insurance beneficiaries from 2000 to 2013. Statin users, defined as having a cumulative defined daily dose (cDDD) ≥28, were selected and served as the case cohort. Statin nonusers (<28 cDDD) were matched through propensity scores. The association between statin use and risk of decompensation, mortality, and HCC were estimated. A total of 1350 patients with cirrhosis were enrolled. Among patients with cirrhosis, statin use decreased the risk of decompensation, mortality, and HCC in a dose‐dependent manner (P for trend <0.0001, <0.0001, and 0.009, respectively). Regression analysis revealed a lower risk of decompensation among statin users with cirrhosis due to chronic HBV (adjusted hazard ratio HR, 0.39; 95% confidence interval CI, 0.25‐0.62) or HCV infection (HR, 0.51; 95% CI, 0.29‐0.93). The lowered risk of decompensation was of borderline significance among statin users with alcohol‐related cirrhosis (HR, 0.69; 95% CI, 0.45‐1.07). Conclusion: Statin use decreases the decompensation rate in both HBV‐ and HCV‐related cirrhosis. Of borderline significance is a decreased decompensation rate in alcohol‐related cirrhosis. (Hepatology 2017;66:896–907).
This study aimed to investigate the survival outcomes of antiviral agents (direct-acting antivirals DAAs or interferon IFN) in patients with hepatitis C virus who underwent liver resection for ...primary hepatocellular carcinoma.
This retrospective single-center study included 247 patients, between 2013 and 2020, being treated with DAAs (n = 93), IFN (n = 73), or no treatment (n = 81). Overall survival (OS), recurrence-free survival (RFS), and risk factors were analyzed.
After a median follow-up time of 50.4 months, the rates of 5-year OS and RFS in the IFN, DAA, and no treatment groups were 91.5% and 55.4%, 87.2% and 39.8%, and 60.9% and 26.7%, respectively. One hundred and twenty-eight (51.6%) patients developed recurrence; recurrence was mostly (86.7%) intrahepatic, and 58 (23.4%) developed early recurrence, most of which received no antiviral treatment. The OS and RFS were similar between patients who received antiviral treatment before (50.0%) and after surgery, but longer survival was observed in patients achieving sustained virologic response. In multivariate analysis, antiviral treatment was protective for OS (hazard ratio HR 0.475, 95% confidence interval CI: 0.242-0.933) with significance but not RFS, in contrast to microvascular invasion (OS HR 3.389, 95% CI: 1.637-7.017; RFS HR 2.594, 95% CI: 1.520-4.008). In competing risk analysis, DAAs (subdistribution HR 0.086, 95% CI: 0.007-0.991) were protective against hepatic decompensation events but not recurrence events.
In patients with hepatitis C virus, antiviral treatment suggested OS benefit for primary hepatocellular carcinoma after resection, and DAAs might be protective against hepatic decompensation. Following adjustment for oncological factors, IFN and DAA treatment was not significantly advantageous relative to the other.
Background and Aim
The severity of liver dysfunction in hepatocellular carcinoma (HCC) is often estimated with Child–Turcotte–Pugh (CTP) classification or model for end‐stage liver disease (MELD) ...score. We aim to investigate the performance of albumin‐bilirubin (ALBI) and platelet‐albumin‐bilirubin (PALBI) grade, which are recently reported to be simple and objective measurements for liver reserve in HCC.
Methods
Between 2002 and 2014, consecutive 3182 HCC patients were enrolled to follow up their survival. The area under receiver‐operator‐characteristic curve (AUC) was calculated to test the discriminatory powers over 1‐year, 3‐year, and 5‐year survival.
Results
Significant survival differences were found across all ALBI and PALBI grades (both P < 0.001). The majority (73%) of patients were CTP class A. Within CTP class A, ALBI revealed two prognostic groups while PALBI segregated three prognostic groups. The PABLI grade also identified three different survival groups for patients undergoing resection, ablation, and chemoembolization. Both ALBI and PALBI grade were capable of discerning survival among different HCC stages. The PALBI grade had significantly higher AUC compared with CTP classification and ALBI grade at 1, 3, and 5 years. For CTP class A patients, the PALBI grade was also associated with significantly higher AUC compared with ALBI grade at 1‐year and 3‐year intervals. The MELD score has the lowest AUC compared with other systems.
Conclusions
Both ALBI and PALBI grade are adequate models to assess liver dysfunction in HCC. The PALBI grade is consistently better in all patients, in patients with minimally decreased liver function, and in patients receiving different aggressive therapies.
Background
Liver functional reserve is a major prognostic determinant in patients with hepatocellular carcinoma (HCC). The albumin–bilirubin (ALBI) score is an objective method to assess the severity ...of cirrhosis in this setting. However, calculation of the ALBI score is complex and difficult to access in clinical practice. Recently, the EZ (easy)‐ALBI score was proposed as an alternative biomarker of liver injury. We aimed to evaluate the prognostic role of the EZ‐ALBI score in HCC from early to advanced stages.
Methods
A total of 3794 newly diagnosed HCC patients were prospectively enrolled and retrospectively analyzed. Independent prognostic predictors were determined by using the multivariate Cox proportional hazards model.
Results
The EZ‐ALBI score showed good correlation with the ALBI score (correlation coefficient, 0.965; p < 0.001). The correlation of the EZ‐ALBI score was highly preserved in different Child–Turcotte–Pugh (CTP) classifications, treatment methods, and Barcelona Clinic Liver Cancer (BCLC) stages (correlation coefficients, 0.90–0.97). In the Cox multivariate analysis, age >65 years, male sex, serum α‐fetoprotein >20 ng/ml, large or multiple tumors, total tumor volume >100 cm3, vascular invasion or distant metastasis, ascites, poor performance status, EZ‐ALBI grade 2 and 3, and noncurative treatments were independently associated with increased mortality (all p < 0.05). Moreover, EZ‐ALBI grade can stratify long‐term survival in patients with different CTP class, treatment strategy, and BCLC stage.
Conclusions
The EZ‐ALBI score is an easy and feasible method to evaluate liver functional reserve. As a new prognostic biomarker in HCC, the predictive power of the EZ‐ALBI grade is independent across different cancer stages and treatments.
Background and Aim
Size and number are major determinants of tumor burden in hepatocellular carcinoma (HCC). Patients with HCC undergoing transarterial chemoembolization (TACE) have variable outcomes ...due to heterogeneity of tumor burden. Recently, tumor burden score (TBS) was proposed to evaluate the extent of tumor involvement. However, the prognostic accuracy of TBS has not been well evaluated in HCC. This study aimed to assess its prognostic role in HCC patients undergoing TACE.
Methods
A total of 935 treatment‐naïve HCC patients receiving TACE were retrospectively analyzed. Multivariate Cox proportional hazards model was used to determine independent prognostic predictors.
Results
Tumor burden score tended to increase with increasing size and number of tumors in study patients. The Cox model showed that serum creatinine ≥ 1.2 mg/dL (hazard ratio HR: 1.296, 95% confidence interval CI: 1.077–1.559, P = 0.006), serum α‐fetoprotein ≥ 400 ng/dL (HR: 2.245, 95% CI: 1.905–2.645, P < 0.001), vascular invasion (HR: 1.870, 95% CI: 1.520–2.301, P < 0.001), medium TBS (HR: 1.489, 95% CI: 1.206–1.839, P < 0.001) and high TBS (HR: 2.563, 95% CI: 1.823–3.602, P < 0.001), albumin–bilirubin (ALBI) grade 2–3 (HR: 1.521, 95% CI: 1.291–1.792, P < 0.001), and performance status 1 (HR: 1.362, 95% CI: 1.127–1.647, P < 0.001) and status 2 (HR: 1.553, 95% CI: 1.237–1.948, P < 0.001) were associated with increased mortality. Patients with high TBS had poor overall survival in Barcelona Clinic Liver Cancer stage B/C and different ALBI grades.
Conclusions
Tumor burden score is a feasible new prognostic surrogate marker of tumor burden in HCC and can well discriminate survival in patients undergoing TACE across different baseline characteristics.
The asymmetric mandibles of termites are hypothetically more efficient, rapid, and powerful than the symmetric mandibles of snap-jaw ants or termites. We investigated the velocity, force, precision, ...and defensive performance of the asymmetric mandibular snaps of a termite species, Pericapritermes nitobei. Ultrahigh-speed recordings of termites revealed a new record in biological movement, with a peak linear velocity of 89.7-132.4 m/s within 8.68 μs after snapping, which caused an impact force of 105.8-156.2 mN. High-speed video recordings of ball-strike experiments on termites were analysed using the principle of energy conservation; the left mandibles precisely hit metal balls at the left-to-front side with a maximum linear velocity of 80.3 ± 15.9 m/s (44.0-107.7 m/s) and an impact force of 94.7 ± 18.8 mN (51.9-127.1 mN). In experimental fights between termites and ant predators, Pe. nitobei killed 90-100% of the generalist ants with a single snap and was less likely to harm specialist ponerine ants. Compared with other forms, the asymmetric snapping mandibles of Pe. nitobei required less elastic energy to achieve high velocity. Moreover, the ability of P. nitobei to strike its target at the front side is advantageous for defence in tunnels.
HCV NS5A is a dimeric phosphoprotein involved in HCV replication. NS5A inhibitors are among direct‐acting antivirals (DAA) for HCV therapy. The Y93H mutant of NS5A is resistant to NS5A inhibitors, ...but the precise mechanism remains unclear. In this report, we proposed a Ser38‐His93‐Asn91 triad to dissect the mechanism. Using pymol 1.3 software, the homology structure of JFH1 NS5A was determined based on the dimer structure of genotype 1b extracted from the database Protein DataBank (www.ebi.ac.uk/pdbsum) with codes 1ZH1 and 3FQM/3FQQ. FLAG‐NS5A‐WT failed to form dimer in the absence of nonstructural proteins from subgenomic replicon (NS3‐5A); however, FLAG‐NS5A‐Y93H was able to form dimer without the aid of NS3‐5A. The Ser38‐His93‐Asn91 triad in the dimer of the Y93H variant predicts a structural crash of the cleft receiving the NS5A inhibitor daclatasvir. The dimerization assay revealed that the existence of JFH1‐NS5A‐1ZH1 and ‐3FQM homology dimers depended on each other for existence and that both NS5A‐WT 1ZH1 and 3FQM dimers cooperated to facilitate RNA replication. However, NS5A‐Y93H 1ZH1 alone could form dimer and conduct RNA replication in the absence of the 3FQM structure. In conclusion, this study provides novel insight into the functional significance of the Ser38‐His93‐Asn91 triad in resistance of the Y93H variant to NS5A inhibitors.
In wild‐type NS5A, Tyr93 (Y93) and Arg56 (R56) form stable cation‐π interactions, and Tyr93 binds to the heterocyclic rings of daclatasvir. Mutual repulsion occurs between His93 (H93) and Agr56 (R56) in the NS5A‐Y93H mutant, causing the imidazole ring of His93 to deviate from the site where the heterocyclic rings of daclatasvir are embedded.
The 2022 International Consensus Classification (ICC) recategorized myeloid neoplasms based on recent advances in the understanding of the biology of hematologic malignancies, in which ...myelodysplastic syndrome (MDS) with blasts of 10%–19% is classified as MDS/acute myeloid leukemia (AML), MDS with mutated SF3B1, irrespective of the number of ring sideroblasts, as MDS‐SF3B1, and those with multi‐hit TP53 mutations as MDS with mutated TP53. In the analysis of 716 patients with MDS diagnosed according to the 2016 WHO classification, we found that 75.3% of patients remained in the MDS group based on the ICC, while 24.7% of patients were reclassified to the MDS/AML group after the exclusion of 15 patients who were classified to the AML group. Patients with MDS/AML showed a distinct mutational landscape and had poorer outcomes, compared to those with MDS. In the MDS group, patients with MDS‐SF3B1 had higher frequencies of DNMT3A and TET2 mutations than those with MDS, not otherwise specified, with single lineage dysplasia or multilineage dysplasia. Patients with mutated TP53 were associated with dismal outcomes, irrespective of the blast percentage. In conclusion, this study showed that the ICC facilitates efficient segregation and risk‐stratification of MDS which can help guide the treatment choice of patients with the disease.
Case allocation of MDS patients defined by 2016 WHO classification and 2022 ICC.
Background & Aims
Transarterial chemoembolization (TACE) is a standard treatment for Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC), but the outcome varied. This study ...aimed to develop a model to predict the outcome of TACE in HCC patients.
Methods
Consecutive 570 treatment‐naïve BCLC stage B HCC patients undergoing TACE as the initial treatment from 2007 to 2016 were retrospectively enrolled. Factors associated with survival were analysed. Patients undergoing TACE from 2007 to 2011 constituted the training cohort (n = 293), while patients undergoing TACE from 2012 to 2016 constituted the validation cohort (n = 277). Homogeneity and corrected Akaike information criterion (AICc) were compared between each prognostic model.
Results
A total of 1796 TACE sessions were performed for the 570 patients during the median follow‐up period of 18.3 months. By multivariate analysis, beyond up‐to‐11 criteria (hazard ratio HR = 1.694, P < .001), alpha‐foetoprotein >200 ng/mL (HR = 1.771, P < .001) and albumin‐bilirubin (ALBI) grade 2 or 3 (HR = 1.817, P < .001) were independent predictors of overall survival (OS) in the training cohort. An ALBI‐TAE model based on the three independent predictors of OS from the training cohort was developed to classify HCC patients into four subgroups. The performance of the ALBI‐TAE model was superior to other prognostic models with lowest AICc values and highest homogeneity in both the training and validation datasets as well as the overall cohort.
Conclusions
Albumin‐bilirubin grade is an important factor associated with survival in BCLC stage B HCC patients undergoing TACE. ALBI‐TAE model can be applied to select patients who can get most benefit from TACE.
Background and Aims
Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disorder with increasing global prevalence. The risk of IBD in patients with schizophrenia remains ...unclear. We aim to investigate the risk of new‐onset IBD in patients with schizophrenia compared with matched controls.
Methods
We conducted a retrospective, population‐based cohort study utilising patient data from the Taiwan National Health Insurance Research Database collected between January 1, 2001, and December 31, 2011. Patients diagnosed with schizophrenia by board‐certified psychiatrists without prior diagnosis of IBD were enrolled and matched to controls in 1:4 fashion by age, sex, residence, income level and medical comorbidities. Adjusted hazard ratios (HRs) for new‐onset IBD and sub‐analyses were determined using Cox regression analysis with adjustments.
Results
Among 116 164 patients with schizophrenia and 464 656 matched controls, overall incidence of IBD among patients was significantly higher (1.14% vs. 0.25%). Average age of IBD diagnosis was 46.82 among patients with schizophrenia, versus 55.30 among controls. The HR of developing IBD among patients was 3.28, with a 95% confidence interval (95% CI) 2.49–4.33. IBD risk was higher among patients with psychiatric admissions more than once per year (HR 7.99, 95% CI 5.25–12.15) compared to those hospitalised less frequently (HR 2.72, 95% CI 2.03–3.66).
Conclusions
This population‐based cohort study demonstrates a significant association between schizophrenia and subsequent IBD development. Patients with schizophrenia develop IBD at a younger age, and the risk increases with inadequately controlled schizophrenia. Physician vigilance and awareness of this correlation will improve IBD diagnosis and management among this vulnerable patient population.
Patients with schizophrenia are found with higher risk of subsequent inflammatory bowel disease development and earlier onset in a Taiwan nationwide longitudinal study.
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