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1.
Medicine (Baltimore) ; 99(2): e18626, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914044

RESUMO

Detection of the chronic kidney disease (CKD) progression can begin early intervention to improve the prognosis of severe non-alcoholic fatty liver disease (NAFLD). This bi-directional cross-sectional study evaluates the roles of fatty acid-binding protein (FABP) and retinol binding protein (RBP4), which are produced from inflamed liver, adipose tissue and immune cells, for the prediction of CKD progression in severe NAFLD. Ninety severe NAFLD patients with hypertension and proteinuria (NAFLDHTN) were enrolled and divided into CKD (n = 39) and non-CKD groups (n = 51). Among 39 NAFLDHTN patients, 18 cases were categorized as CKD progression group. In comparison with CKD stable group (n = 21), the positive correlation between fold change values of hepatic fibrotic score (KPa), urinary FABP4 or urinary RBP4 versus severity of albuminuria were noted among CKD progression group. On multivariate analysis, high body mass index (BMI, >25 kg/m), high hepatic fibrosis score (>9.5 KPa), high urinary level of vascular cell adhesion molecule-1 (VCAM-1, >2239 µg/g cr), high urinary level of FABP4 (>115 ng/g cr) and high urinary level of RBP4 (>33.5 mg/g cr) are 5 independent predictors for progressive CKD during 24 months of follow-up. Synergetic effect was noted among these 5 risk factors for the prediction of CKD progression in NAFLDHTN patients. The in vitro experiments revealed that both FABP4 and RBP4 directly enhanced albumin-induced ER stress and apoptosis of human renal tubular epithelial cell line HK-2 cells and human podocytes cell lines. Through clinical and experimental approaches, this study revealed new 5 synergetic predictors including high BMI, hepatic fibrosis score, urinary level of VCAM-1, urinary level of FABP4 and RBP4, for the CKD progression in severe NAFLD patients with hypertension and proteinuria.

2.
Endoscopy ; 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31858503
3.
J Chin Med Assoc ; 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31868860

RESUMO

BACKGROUND: Currently, evidence regarding the strategies of antibiotic use in patients with acute cholecystitis after receiving percutaneous cholecystostomy is limited. Hence, we aimed to investigate the outcomes in patients with inoperable acute cholecystitis receiving narrow or broad-spectrum antibiotics after percutaneous cholecystostomy. METHODS: Total 117 patients receiving percutaneous cholecystostomy were categorized into moderate and severe acute cholecystitis defined by the Tokyo guideline and then divided into Group A (narrow-spectrum antibiotic use) and Group B (broad-spectrum antibiotic use). The clinical outcomes and complications were analyzed. RESULTS: In moderate acute cholecystitis (n=80), Group A patients (n=62) had similar early recurrent rate (11.3% vs. 16.7%, p= 0.544) and a shorter length of hospital stay (13.4 ± 8.6 vs. 18.6 ± 9.4 days, p= 0.009) as compared with Group B patients (n=18). No in-hospital mortality occurred in moderate acute cholecystitis. In severe acute cholecystitis (n= 37), both groups had similar length of hospital stay (16.3 ± 12.2 vs. 20.9 ± 9.5 days, p= 0.051), early recurrent rate (0% vs. 16.7%, p= 0.105) and in-hospital mortality rate (5.3% vs. 16.7%, p= 0.340). Although Group B patients with severe cholecystitis had higher serum levels of Alk-P and higher proportion of underlying malignancy, ASA class IV and septic shock, the clinical outcomes were not inferior to patients in Group A. CONCLUSION: In moderate acute cholecystitis after percutaneous cholecystostomy, patients receiving narrow-spectrum antibiotics have comparable clinical outcomes as those treated with broad-spectrum antibiotics. However, in severe acute cholecystitis, broad-spectrum antibiotics might still be necessary to rescue these patients.

4.
Gastroenterol Res Pract ; 2019: 1743290, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31687012

RESUMO

Background: The use of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) carries a risk of renal function deterioration in cirrhotic patients with ascites. However, whether the long-term use of ACEis/ARBs is safe in cirrhotic patients without ascites remains unknown. Methods: In this nationwide cohort study, we identified 311,361 newly diagnosed cirrhotic patients between January 1997 and December 2013. To avoid indication and immortal time biases, patients receiving regular ACEi/ARB therapy, defined as the ACEi/ARB cohort, were matched to patients receiving regular calcium channel blockers (CCBs), defined as the CCB cohort, at a ratio of 1 : 1 by age, sex, and propensity scores for comorbidities and medications (2,188 patients in each cohort). Cumulative incidence rates and multivariate analyses of end-stage renal disease (ESRD) risk were adjusted for competing mortality. Results: The 10-year cumulative incidence rates of ESRD were 2.32% (95% confidence interval [CI]: 1.45-3.20) in the ACEi/ARB cohort and 1.70% (95% CI: 1.03-2.36) in the CCB cohort (P = 0.610). In multivariate analyses, ACEi/ARB use was not associated with a higher risk of ESRD in cirrhotic patients (hazard ratio [HR] = 1.15; 95% CI: 0.69-1.94, P = 0.591). In the sensitivity test, the 10-year cumulative incidence rates of ESRD in cirrhotic patients with ascites were 6.50% (95% CI: 0.54-12.46) and 1.24% (95% CI: 0.00-2.71) in ACEi/ARB and CCB cohorts, respectively (P = 0.090). Conclusions: Long-term ACEi/ARB use was not associated with a higher risk of ESRD in cirrhotic patients. However, the risk of ESRD tended to increase in cirrhotic patients with ascites.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31688303

RESUMO

OBJECTIVE: The use of nonselective beta blockers in cirrhotic patients experiencing complications is controversial. We aimed to investigate the association between propranolol treatment and outcomes for cirrhotic patients with hepatic encephalopathy. METHODS: Using data from the Taiwan National Health Insurance Research Database, we identified 4754 cirrhotic patients newly diagnosed with hepatic encephalopathy between 2001 and 2010. Among them, 519 patients received propranolol treatment and the other 519 patients without exposure to propranolol were enrolled into our study, both of which were matched by sex, age, and propensity score. The Kaplan-Meier method and time-dependent-modified Cox proportional hazards models were employed for survival and multivariate-stratified analyses. RESULTS: The median overall survival (OS) was significantly longer in the propranolol-treated cohort than in the untreated cohort (3.46 versus 1.88 years, P < 0.001). A dose-dependent increase in survival was observed (median OS: 4.49, 3.29, and 2.46 years in patients treated with propranolol more than 30 , 20-30 , and less than 20 mg/day, respectively [P < 0.001, P = 0.001, and P = 0.079 versus the untreated group]). In addition to reduce the risk of mortality (adjusted hazard ratio, 0.58; P < 0.001), propranolol also diminished the risk of sepsis-related death (adjusted hazard ratio, 0.31; P = 0.006) according to the multivariate analysis. However, the risk of circulatory or hepatic failure was nonsignificantly altered by propranolol treatment. CONCLUSION: Low dose of propranolol treatment was associated with a better OS in cirrhotic patients with hepatic encephalopathy and its effects were dose dependent.

6.
Clin Gastroenterol Hepatol ; 17(13): 2825, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31757367
7.
J Chin Med Assoc ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31714442

RESUMO

BACKGROUND: Immunosuppressant-related acceleration of fibrosis has been documents in chronic hepatitis C (CHC) patients who receive organ transplantation (Tx), sustained virological response (SVR) rates for these patients by pegylated interferon (IFN)-based therapy are generally poor and associated with unfavorable safety profiles. In addition IFN treatment varies by patient and poses a high risk of post-renal Tx graft rejection. This study was aimed to investigate the efficacy and safety of all oral direct acting antivirals (DAAs) for CHC patients following organ Tx. METHODS: 32 organ Tx (liver: 17, kidney: 13, kidney then liver: 1, heart: 1) patients with CHC on an oral DAA (paritaprevir/ritonavir, ombitasvir and dasabuvir: 11, daclatasvir and asunaprevir: 4, sofosbuvir-based: 17) were enrolled in the study. DAAs regimen was based by genotype/subtype, patient characteristics, drug interaction profiles, and health insurance coverage. RESULTS: Mean patient age was 61.4±9.5 years, 50.0%, male, and 15.6% with cirrhosis. 14 (43.7%) experienced unsuccessful IFN treatment. Genotype distribution was as follows: 1a: 6, 1b: 17, 2: 7, 3: 1 and 6: 1. Mean time between Tx and DAAs therapy was 77.3±11.0 months. Baseline HCV RNA before DAAs was 6.20±0.19 log10 IU/mL. After DAAs, the distribution of week 2 HCV RNA was as follows: < 15 IU/mL (53.1%), 15 to 50 IU/mL (15.6%), 50 to 100 IU/mL (6.3%), and > 100 IU/mL (25.0%), respectively. The rates of undetectable HCV RNA (< 15 IU/mL) at week 4 and end-of-treatment were 93.8% and 100%. Subjective adverse events during therapy were generally mild, which no treatment terminations. After post-treatment follow-up, all 32 patients (100%) achieved SVR12. CONCLUSION: Highly responsive treatment and favorable tolerability were achieved by all oral DAAs in this difficult-to-treat patient population.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31771822

RESUMO

BACKGROUND/PURPOSE: The treatment of chronic hepatitis C (CHC) has evolved from interferon (IFN)-based therapy to direct acting antivirals (DAAs). The effect of antiviral treatment on outcome of hepatocellular carcinoma (HCC) patients with CHC has not been well analyzed in Taiwan. METHODS: From April 2015 to May 2018, 199 HCC patients with CHC undergoing DAAs treatment, including 127 having prospectively longitudinal observation, were enrolled. Among them, 107 BCLC 0/A patients achieving curative treatment of HCC were further compared with a historical cohort of 42 HCC patients experienced pegylated interferon (Peg-IFN) plus ribavirin for CHC after curative treatment. RESULTS: The sustained virological response (SVR) rates were 95.0% in BCLC stage 0/A (114/120), 97.1% in BCLC B (68/70), and 77.8% in BCLC C (7/9). The median recurrence-free survivals (RFS) between the DAA and IFN arms were of no difference by counting either from antiviral treatment (29.3 mo vs 39.2 mo, p = 0.764) or from curative treatment (65.8 mo vs 44.0 mo, p = 0.130), respectively. Achievement of SVR was the key independent factor associated with RFS and overall survival. The pattern of recurrence was also similar between the DAA and IFN arms. For intermediate stage HCC patients, the median time to tumor progression was 9.2 months from the initiation of DAA therapy, and 90% of patients maintained in BCLC B till 12 months after the DAA treatment. CONCLUSIONS: The SVR is high within BCLC B HCV-HCC patients by DAAs treatment. The risk of HCC recurrence and progression is not increased by DAAs.

9.
Dig Dis Sci ; 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31659612

RESUMO

BACKGROUND: The survival of patients with advanced hepatocellular carcinoma (HCC) is highly variable due to heterogeneous tumoral characteristics. We proposed and validated an albumin-bilirubin (ALBI)-based model for HCC beyond Milan criteria, the ALBI-HOME, for these patients. METHODS: A total of 2186 patients were enrolled and randomly assigned to the derivation cohort (n = 1093) and validation cohort (n = 1093). Multivariate Cox proportional hazards model was used to determine significant prognostic factors in the derivation cohort. The performance of ALBI-HOME was evaluated in the validation cohort. RESULTS: In the Cox model, six factors were identified as independent predictors of poor survival: ALBI grade 2 [hazard ratio (HR) 1.848, 95% confidence incidence (CI) 1.556-2.195, p < 0.001], ALBI grade 3 (HR 3.266, 95% CI 2.531-4.215, p < 0.001), serum AFP ≥ 100 ng/ml (HR 1.482, 95% CI 1.279-1.717, p < 0.001), total tumor volume ≥ 250 cm3 (HR 1.503, 95% CI 1.294-1.746, p < 0.001), ascites (HR 1.400, 95% CI 1.187-1.561, p < 0.001), performance status 0-1 (HR 1.756, 95% CI 1.485-2.076 p < 0.001), and vascular invasion or metastasis (HR 2.110, 95% CI 1.809-2.0, p < 0.001). The ALBI-HOME is based on these six parameters, and the score ranges from 0 to 7. This model was associated with the best prognostic ability among different HCC staging systems to predict survival in patients beyond Milan criteria; its ability remained consistently stable in different treatment subgroups and viral etiologies. CONCLUSIONS: The proposed ALBI-HOME is a simple and feasible predictive model for HCC beyond Milan criteria. It demonstrates superior prognostic performance among the currently used staging systems and may help identify at-risk patients to undergo more aggressive treatments.

10.
J Formos Med Assoc ; 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31542334

RESUMO

BACKGROUND/PURPOSE: Whether esophagogastric varices (EGV) can determine the outcome of patients with hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) remains unknown. This study aimed to assess the impact of EGV on the prognosis of HCC patients after TACE. METHODS: From 2007 to 2012, we retrospectively enrolled 251 treatment-naïve HCC patients who underwent TACE and received esophagogastroduodenoscopy when HCC was diagnosed. The prognostic factors were analyzed using a Cox proportional hazards model and propensity score-matching analysis. RESULTS: There were 120 (47.8%) patients with EGV. Compared to those without EGV, patients with EGV had worse liver functional reserve. After a median follow-up of 14.7 months (25th-75th percentiles, 6.4-35.6 months), 152 patients died. The cumulative 5-year overall survival (OS) rates were 11.2% and 38.8% in patients with and without EGV, respectively (p < 0.001). Multivariate analysis showed that presence of EGV, presence of ascites, tumor size >5 cm, serum alpha-fetoprotein >20 ng/mL, progressive disease by modified Response Evaluation Criteria in Solid Tumors, Assessment for Retreatment with TACE score ≥2.5, and higher albumin-bilirubin grades were the independent predictors of poor OS. Subgroup analysis also demonstrated that EGV was associated with poor OS in most of the subgroups. After propensity score matching, the EGV group still had a lower OS rate than their counterparts (p = 0.004). CONCLUSION: HCC patients with EGV had worse liver functional reserve compared to those without EGV. Moreover, EGV was an independent risk factor to predict poor prognosis in patients with HCC after TACE.

11.
Liver Int ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31505104

RESUMO

BACKGROUND & AIMS: The prognostic accuracy of individual hepatocellular carcinoma (HCC) patient in each Barcelona Clinic Liver Cancer (BCLC) stage is unclear. We aimed to develop and validate an albumin-bilirubin (ALBI) grade-based nomogram of BCLC to estimate survival for individual HCC patient. METHODS: Between 2002 and 2016, 3690 patients with newly diagnosed HCC were prospectively enrolled and retrospectively analysed. Patients were randomly split into derivation and validation cohort by 1:1 ratio. Multivariate Cox proportional hazards model was used to generate the nomogram from tumour burden, ALBI grade and performance status (PS). The concordance index and calibration plot were determined to evaluate the performance of this nomogram. RESULTS: Beta coefficients from the Cox model were used to assign nomogram points to different degrees of tumour burden, ALBI grade and PS. The scores of the nomogram ranged from 0 to 24, and were used to predict 3- and 5-year patient survival. The concordance index of this nomogram was 0.77 (95% confidence interval [CI]: 0.71-0.81) in the derivation cohort and 0.76 (95% CI: 0.71-0.81) in the validation cohort. The calibration plots to predict both 3- and 5-year survival rate well matched with the 45-degree ideal line for both cohorts, except for ALBI-based BCLC stage 0 in the validation cohort. CONCLUSIONS: The proposed ALBI-based nomogram of BCLC system is a simple and feasible strategy in the precision medicine era. Our data indicate it is a straightforward and user-friendly prognostic tool to estimate the survival of individual HCC patient except for very early stage patients.

12.
Nutrients ; 11(9)2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31505759

RESUMO

Malnutrition is associated with adverse outcomes in patients with liver cirrhosis. Relevant data about nutrition risk in critically ill cirrhotic patients are lacking. The modified Nutrition Risk in Critically Ill (mNUTRIC) score is a novel nutrition risk assessment tool specific for intensive care unit (ICU) patients. This retrospective study was conducted to evaluate the prevalence and prognostic significance of nutrition risk in cirrhotic patients with acute gastroesophageal variceal bleeding (GEVB) using mNUTRIC scores computed on admission to the intensive care unit. The major outcome was 6-week mortality. One-hundred-and-thirty-one admissions in 120 patients were analyzed. Thirty-eight percent of cirrhotic patients with acute GEVB were categorized as being at high nutrition risk (a mNUTRIC score of ≥5). There was a significantly progressive increase in mortality associated with the mNUTRIC score (χ2 for trend, p < 0.001). By using the area under a receiver operating characteristic (ROC) curve, the mNUTRIC demonstrated good discriminative power to predict 6-week mortality (AUROC 0.859). In multivariate analysis, the mNUTRIC score was an independent factor associated with 6-week mortality. In conclusion, the mNUTRIC score can serve as a tool to assess nutrition risk in cirrhotic patients with acute GEVB.

13.
Int J Mol Sci ; 20(17)2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31454890

RESUMO

Patients suffering from liver cirrhosis are often complicated with the formation of portosystemic collateral vessels, which is associated with the progression of a splanchnic hyperdynamic circulatory state. Alleviating pathological angiogenesis has thus been proposed to be a feasible treatment strategy. Indole-3-carbinol (C9H9NO, I3C) and 3,3'-diindolymethane (DIM), formed by the breakdown of glucosinolate glucobrassicin, are prevalent in cruciferous vegetables and have anti-angiogenesis properties. We aimed to evaluate their influences on portal hypertension, the severity of mesenteric angiogenesis, and portosystemic collaterals in cirrhosis. Sprague-Dawley rats with common bile duct ligation (CBDL)-induced liver cirrhosis or sham operation (surgical control) were randomly allocated to receive I3C (20 mg/kg/3 day), DIM (5 mg/kg/day) or vehicle for 28 days. The systemic and portal hemodynamics, severity of portosystemic shunting, mesenteric angiogenesis, and mesenteric proangiogenic factors protein expressions were evaluated. Compared to vehicle, both DIM and I3C significantly reduced portal pressure, ameliorated liver fibrosis, and down-regulated mesenteric protein expressions of vascular endothelial growth factor and phosphorylated Akt. DIM significantly down-regulated pErk, and I3C down-regulated NFκB, pIκBα protein expressions, and reduced portosystemic shunting degree. The cruciferous vegetable byproducts I3C and DIM not only exerted a portal hypotensive effect but also ameliorated abnormal angiogenesis and portosystemic collaterals in cirrhotic rats.

14.
Biomed Res Int ; 2019: 4206795, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31380421

RESUMO

During sedated endoscopic examinations, upper airway obstruction occurs. Nasal breathing often shifts to oral breathing during open mouth esophagogastroduodenoscopy (EGD). High-flow nasal cannula (HFNC) which delivers humidified 100% oxygen at 30 L min-1 may prevent hypoxemia. A mandibular advancement (MA) bite block with oxygen inlet directed to both mouth and nose may prevent airway obstruction during sedated EGD. The purpose of this study was to evaluate the efficacy of these airway devices versus standard management. One hundred and eighty-nine patients were assessed for eligibility. One hundred and fifty-three were enrolled. This study randomly assigned eligible patients to three arms: the standard bite block and standard nasal cannula, HFNC, and MA bite block groups. EGD was performed after anaesthetic induction. The primary endpoint was the oxygen desaturation area under curve at 90% (AUCDesat). The secondary endpoints were percentage of patients with hypoxic, upper airway obstruction, and apnoeic and rescue events. One hundred and fifty-three patients were enrolled. AUCdesat was significantly lower for HFNC and MA bite blocks versus the standard management (p= 0.019). The HFNC reduced hypoxic events by 18% despite similar airway obstruction and apnoeic events as standard group. The MA bite block reduced hypoxic events by 12% and airway obstructions by 32%. The HFNC and MA groups both showed a 16% and 14% reduction in the number of patients who received rescue intervention, respectively, compared to the standard group. The HFNC and MA bite block may both reduce degree and duration of hypoxemia. HFNC may decrease hypoxemic events while maintaining nasal patency is crucial during sedative EGD. The MA bite block may prevent airway obstruction and decrease the need for rescue intervention.

15.
Liver Int ; 39(9): 1704-1712, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31319016

RESUMO

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.

16.
Biomed Res Int ; 2019: 6740616, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31321239

RESUMO

Identification of new pharmacological approaches to inhibit the excessive fat intake-induced steatohepatitis and chronic kidney disease (CKD) is important. High-fat diet (HFD)-induced steatohepatitis and CKD share common pathogenesis involving peroxisome proliferator-activated receptor (PPAR)-α and -δ. Elafibranor, a dual PPARα/δ agonist, can ameliorate the HFD-induced steatohepatitis. Nonetheless, the effects of HFD-induced CKD had not yet explored. This study investigated the effects of elafibranor (elaf) on the progression of HFD-induced CKD in mice. In vivo and in vitro renal effects were evaluated in HFD-elaf mice receiving 12 weeks of elafibranor (from 13th to 24th week of HFD feeding) treatment. In elafibranor-treated HFD mice, increased insulin sensitivity, reduced obesity and body fat mass, decreased severity of steatohepatitis, increased renal expression of PPARα, PPARδ, SIRT1, and autophagy (Beclin-1 and LC3-II) as well as glomerular/renal tubular barrier markers [synaptopodin (podocyte marker), zona occludin-1, and cubulin], reduced renal oxidative stress and caspase-3, and less urinary 8-isoprostanes excretion were observed. Aforementioned benefits of elafibranor were associated with low renal tubular injury and tubulointerstitial fibrosis scores, less albuminuria, low urinary albumin-to-creatinine ratio, and preserved glomerular filtration rate. Acute incubation of podocytes and HK-2 cells with elafibranor or recombinant SIRT1 reversed the HFD-sera-induced oxidative stress, autophagy dysfunction, cell apoptosis, barrier marker loss, albumin endocytosis, and reuptake reduction. Besides hepatoprotective and metabolic beneficial effects, current study showed that elafibranor inhibited the progression of HFD-induced CKD through activation of renal PPARα, PPARδ, SIRT1, autophagy, reduction of oxidative stress, and apoptosis in mice with steatohepatitis.

17.
J Chin Med Assoc ; 82(9): 693-698, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31356562

RESUMO

BACKGROUND: Based on the previously published results, 12 weeks of sofosbuvir (SOF) 400 mg/day plus ribavirin (RBV), the current direct antiviral agent regimen reimbursed by Bureau-of National-Health-Insurance (BNHI) of Taiwan for genotype-2 chronic hepatitis C (CHC), is suboptimal in efficacy, especially for difficult-to-treat subpopulations such as liver cirrhosis, previous interferon (IFN) treatment failure, and high viral-load. This study aimed to evaluate the efficacy and safety of SOF plus daclatasvir (DCV) for Taiwanese genotype-2 CHC patients. METHODS: Between March 2017 and December 2018, a total of 50 consecutive genotype-2 CHC patients who completed 12 weeks combination of SOF (400 mg/day) plus DCV (60 mg/day) with or without RBV by investigators were enrolled for analyses. When RBV was added, weight-based (800-1200 mg/day) approach was applied. Sustained virological response (SVR12) was defined by undetectable HCV RNA (<15 IU/mL) at the end and 12 weeks after completion of therapy. RESULTS: The mean age was 62.0 ± 11.4 years, 16 (32.0%) of them were males and 20 (40.0%) of them failed to previous IFN. Severity of liver diseases was as follows: ≤F2 fibrosis: 24.0%; F3 fibrosis: 40.0%, Child-Pugh A cirrhosis: 30.0%; and Child-Pugh B-C cirrhosis: 6.0%. The mean baseline HCV RNA level was 6.19 ± 0.91 log10 IU/mL and 30 (60.0%) had baseline HCV RNA ≥ 2 million IU/mL. The rates of undetectable HCV RNA (<15 IU/mL) at weeks 2, 4, and end-of-treatment were 40%, 94%, and 100%, respectively. Majority (66.7%) of patients with detectable HCV RNA at week 2 belonged to low-level viremia (<50 IU/mL). Subjective adverse events (AEs) and laboratory abnormalities were more common for patients combining RBV. Grades of AEs were generally mild and all patients finished therapy without interruption. After post-treatment follow-up, all 50 patients (100%) achieved SVR12. CONCLUSION: Our real-world cohort of Taiwan showed that a 12-week SOF/DCV-based treatment was well-tolerated and highly effective for genotype-2 CHC patients with or without liver cirrhosis.

18.
Crit Care Med ; 82(10): 762-766, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31356569

RESUMO

BACKGROUND: Self-expandable metal stents (SEMS) are a widely accepted biliary endoprosthesis for patients with unresectable malignant biliary obstruction. Here, we identified predictors for the occlusion of SEMS in unresectable pancreatic cancer patients with biliary tract obstruction. METHODS: Patients with a distal malignant biliary obstruction caused by unresectable pancreatic cancer who received partially covered SEMS (PC-SEMS) placement for the first time between January 2003 and January 2016 were retrospectively enrolled for analysis. The rates of PC-SEMS occlusion were evaluated. The possible predictors of PC-SEMS occlusion were analyzed using Cox regression analysis. RESULTS: In total, 120 patients who received PC-SEMS for unresectable pancreatic cancer were identified. The rate of PC-SEMS occlusion was 37%. The median time to occlusion of PC-SEMS was 359 days. The major causes of occlusion included biliary sludge (61%) and tumor ingrowth (30%). Cox multivariate regression analysis revealed that inadequate alkaline phosphatase/gamma-glutamyl transferase decline (defined by a decrease of <50% within 2 wk after PC-SEMS placement) was the only independent predictor of stent occlusion (hazard ratio, 2.86; 95% CI, 1.28-6.25; p = 0.01) CONCLUSION:: Inadequate alkaline phosphatase/gamma-glutamyl transferase decline is a predictor of occlusion of first-time PC-SEMS placement in unresectable pancreatic cancer patients with biliary tract obstruction.

19.
J Chin Med Assoc ; 82(7): 535-540, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31274784

RESUMO

BACKGROUND: Antituberculosis (TB) drug-induced liver injury (ATLI) is a common adverse effect of anti-TB drugs. Whether regular monitoring of liver function can ameliorate ATLI has been widely debated. The current study aimed to investigate the liver test monitoring status of patients receiving anti-TB treatment in Taiwan, as well as the impact of scheduled liver function monitoring on the risk of ATLI. METHODS: Patients who received anti-TB treatment at our hospital between 2009 and 2017 were enrolled for retrospective analysis. RESULTS: A total of 1062 patients were included, and of them 469 (44.2%) received regular liver function monitoring (good monitoring group). ATLI was recognized in 100 (9.4%) patients. The good monitoring group detected more ATLI cases early compared with the poor monitoring group (14.7% vs 5.2%, and 21.4 vs 61.6 days, p < 0.01), with a lower peak serum alanine aminotransferase (276.1 vs 507.1 IU/L, p = 0.05). CONCLUSION: In the current study, less than half of all patients who received anti-TB drugs had their liver function monitored regularly. Scheduled monitoring of liver function could facilitate the early identification of more ATLI cases, thus leading to less liver injury. The implementation of periodic liver function monitoring tests in patients receiving anti-TB treatment should be re-emphasized and encouraged.

20.
J Chin Med Assoc ; 82(7): 595-598, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31274790

RESUMO

Treatment of chronic hepatitis C virus infection has evolved rapidly in recent years due to the invention of interferon-free direct antiviral agents (DAAs). However, evidence and recommendations for acute hepatitis C (AHC) virus infection by DAAs are still limited, especially for those whose disease presents with hepatic decompensation. Here, we report a case with genotype 1b AHC virus infection, complicated by hepatic decompensation and the patient received sofosbuvir and daclatasvir plus low dose ribavirin for 12 weeks. Serum hepatitis C virus RNA significantly declines after therapy and became undetectable at week 8 and it remained undetectable at 12 weeks after finishing therapy; sustained virological response was impressed. Our findings support that combination of sofosbuvir and daclatasvir plus ribavirin can be used for genotype 1b, AHC virus infection patients with overt hepatic decompensation.

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