Factors Associated with Large Renal Function Decline in Patients with Chronic Hepatitis C Successfully Treated with Direct-Acting Antiviral Therapy.

The findings regarding changes in renal function in patients with hepatitis C virus (HCV) infection treated with direct-acting antivirals (DAAs) are controversial. This study attempted to identify the factors associated with the large decline in renal function following DAA treatment. This retrospective cohort study included patients treated with DAAs at Chiayi and Yunlin Chang Gung Hospitals, Taiwan, from 1 January 2017 to 31 October 2020. Estimated glomerular filtration rate (eGFR) data were collected within 90 days prior to DAA therapy and 2 years after the confirmation of a sustained virologic response (SVR). We performed multiple logistic regression to evaluate the clinical or laboratory parameters associated with a large eGFR decline (≥10%). Among the enrolled 606 patients, the mean eGFR at the baseline and endpoint were 84.11 ± 24.38 and 78.88 ± 26.30 mL/min/1.73 m2, respectively (p < 0.001). The factors associated with a large eGFR decline 2 years after the SVR included hypertension (OR: 1.481; 95% CI: 1.010-2.173, p = 0.044) and a higher baseline eGFR (OR: 1.016; 95% CI: 1.007-1.024, p < 0.001). A higher albumin level reduced the risk of a large eGFR decline (OR: 0.546; 95% CI: 0.342-0.872, p = 0.011). In the patients with HCV treated with DAAs, a larger renal function decline was more commonly observed in those with hypertension, a lower (but within normal range) albumin level, and a higher baseline eGFR, while DAA treatment had no effect. The clinical significance of these findings has to be further defined. Although some risk factors associated with chronic kidney disease may be alleviated after DAA treatment, the regular control and follow-up of risk factors and renal function are still recommended in at-risk patients after HCV eradication.

Real-world efficacy and safety of pangenotypic direct-acting antivirals against hepatitis C virus infection in Taiwan.

Clinical trials showed pangenotypic direct-acting antivirals' (DAAs) excellent efficacy and safety when treating hepatitis C virus (HCV). Two pangenotypic regimens were examined, glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL), in a real-world Taiwanese setting, including all HCV patients treated with GLE/PIB or SOF/VEL from August 2018 to April 2020. The primary endpoint was sustained virologic response 12 weeks after treatment cessation (SVR12), including adverse events (AEs). A total of 1,356 HCV patients received pangenotypic DAA treatment during the study: 742 and 614 received GLE/PIB and SOF/VEL, respectively. The rates of SVR12 for GLE/PIB and SOF/VEL were 710/718 (98.9%) and 581/584 (99.5%), respectively, by per-protocol analysis, and 710/742 (95.7%) and 581/614 (94.6%), respectively, by evaluable population analysis. Eleven (GLE/PIB: 8, SOF/VEL: 3) did not achieve SVR12. The most common AEs for GLE/PIB and SOF/VEL were pruritus (17.4% vs. 2.9%), abdominal discomfort (5.8% vs. 4.4%), dizziness (4.2% vs. 2%), and malaise (3.1% vs. 2.9%). Laboratory abnormalities were uncommon; only < 1% exhibited elevated total bilirubin or aminotransferase levels with both regimens. Five drug discontinuations occurred due to AEs (bilirubin elevation: 3; dermatological issues: 2). Pangenotypic DAAs GLE/PIB and SOF/VEL are effective and well tolerated, achieving high SVR12 rates for patients with all HCV genotypes.

Incidence, risk factors and impact on virological response of anemia in chronic genotype 2 hepatitis C receiving sofosbuvir plus ribavirin.

BACKGROUND/PURPOSE: The major dose-limiting toxicity of ribavirin is hemolytic anemia. We investigated the incidence, risk factors and impact on virological response of anemia in chronic hepatitis C genotype 2 patients receiving sofosbuvir plus ribavirin therapy. METHODS: This was a retrospective real-world analysis of a single center including 293 chronic hepatitis C genotype 2 patients treated with sofosbuvir plus ribavirin for 12 weeks. Severe anemia was defined as hemoglobin concentration <10 g/dl. RESULTS: Treatment was completed in 285 (97%) of patients, of whom one withdrew due to severe anemia. Ribavirin dose reduction was required in 88 (30%) of patients. After excluding those with baseline hemoglobin <10 g/dl, 79 (29%) patients had developed severe anemia during therapy. Stepwise logistic regression analysis identified that chronic kidney disease (odds ratio [OR] = 3.970, p < 0.001), baseline hemoglobin level (OR = 0.475, p < 0.001) and baseline platelet count (OR = 0.992, p = 0.022) were independent factors. The sustained viral response 12 weeks off therapy (SVR12) rate was 93.9% in the per-protocol population. Multivariate analyses showed that history of hepatocellular carcinoma significantly reduced the efficacy of sofosbuvir plus ribavirin therapy (OR = 0.172, p = 0.001). Severe anemia, dose reduction or average dose (mg/kg/day) of ribavirin was not associated with SVR12. CONCLUSION: Severe anemia was not uncommon during sofosbuvir plus ribavirin therapy for chronic hepatitis C genotype 2 patients. Careful monitoring of anemia is necessary in patients with chronic kidney disease and low baseline hemoglobin level and platelet count.

Pretreatment Inflammation-Based Markers Predict Survival Outcomes in Patients with Early Stage Hepatocellular Carcinoma After Radiofrequency Ablation.

The prognostic significance of various systemic inflammation-based markers has been explored in different cancers after surgery. This study aimed to investigate whether these markers could predict outcomes in patients with early-stage hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA). One hundred eighteen patients with newly diagnosed HCC within the Milan criteria receiving RFA as initial therapy were retrospectively enrolled. Pretreatment inflammation-based markers including the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and prognostic nutritional index (PNI), together with other clinicopathologic parameters were collected. Cumulative overall survival (OS) and recurrence-free survival (RFS) were estimated by the Kaplan-Meier method and by multivariate analysis using Cox proportional hazard model. The 1-, 3-, and 5-year OS rates of patients were 90%, 67%, and 52%, respectively. Kaplan-Meier curves showed that baseline high NLR ≥ 2.5 (p = 0.006), low PNI < 40 (p = 0.005), history of end-stage renal disease (ESRD) (p = 0.005), non-Child-Pugh class A (p = 0.001) and elevated alpha-fetoprotein (AFP) ≥ 200 ng/mL (p = 0.005) significantly associated with the poor OS, whereas high PLR ≥ 100 did not. By multivariate analysis, high NLR ≥ 2.5 (hazard ratio (HR) 1.94; 95% confidence interval (CI), 1.05-3.59; p = 0.034), low PNI < 40 (HR 0.38; 95% CI, 0.20-0.72; p = 0.003), ESRD history (HR 3.60; 95% CI, 1.48-8.76; p = 0.005) and elevated AFP ≥ 200 ng/mL (HR 4.61; 95% CI, 1.75-12.13; p = 0.002) were independent factors. An elevated AFP level of ≥200 ng/mL was the significant factor associated with intrahepatic new RFS by univariate and multivariate analyses. In conclusion, pretreatment NLR and PNI are simple and useful predictors for OS in patients with early-stage HCC after RFA.

Upregulation of bone morphogenetic protein 1 is associated with poor prognosis of late-stage gastric Cancer patients.

BACKGROUND: Gastric cancer is the eighth most common cancer in Taiwan, with a 40% 5-year survival rate. Approximately 40% of patients are refractory to chemotherapy. Currently, the anti-HER2 therapy is the only clinically employed targeted therapy. However, only 7% patients in Taiwan are HER2-positive. Identifying candidate target genes will facilitate the development of adjuvant targeted therapy to increase the efficacy of gastric cancer treatment. METHODS: Clinical specimens were analyzed by targeted RNA sequencing to assess the expression levels of target genes. Statistical significance of differential expression and correlation between specimens was evaluated. The correlation with patient survival was analyzed as well. In vitro cell mobility was determined using wound-healing and transwell mobility assays. RESULTS: Expression of BMP1, COL1A1, STAT3, SOX2, FOXA2, and GATA6 was progressively dysregulated through the stages of gastric oncogenesis. The expression profile of these six genes forms an ubiquitously biomarker signature that is sufficient to differentiate cancer from non-cancerous specimens. High expression status of BMP1 correlates with poor long-term survival of late-stage patients. In vitro, suppression of BMP1 inhibits the mobility of the gastric cancer cell lines, indicating a role of BMP1 in metastasis. CONCLUSIONS: BMP1 is upregulated in gastric cancer and is correlated with poor patient survival. Suppression of BMP1 reduced gastric cancer mobility in vitro. Our finding suggests that anti-BMP1 therapy will likely augment the efficacy of standard chemotherapy and improve the treatment outcome.

Increased Abundance of Clostridium and Fusobacterium in Gastric Microbiota of Patients with Gastric Cancer in Taiwan.

Helicobacter pylori is recognised as a main risk factor for gastric cancer. However, approximately half of the patients with gastritis are negative for H. pylori infection, and the abundance of H. pylori decreases in patients with cancer. In the current study, we profiled gastric epithelium-associated bacterial species in patients with gastritis, intestinal metaplasia, and gastric cancer to identify additional potential pathogenic bacteria. The overall composition of the microbiota was similar between the patients with gastritis and those with intestinal metaplasia. H. pylori was present in half of the non-cancer group, and the dominant bacterial species in the H. pylori-negative patients were Burkholderia, Enterobacter, and Leclercia. The abundance of those bacteria was similar between the cancer and non-cancer groups, whereas the frequency and abundance of H. pylori were significantly lower in the cancer group. Instead, Clostridium, Fusobacterium, and Lactobacillus species were frequently abundant in patients with gastric cancer, demonstrating a gastric cancer-specific bacterial signature. A receiver operating characteristic curve analysis showed that Clostridium colicanis and Fusobacterium nucleatum exhibited a diagnostic ability for gastric cancer. Our findings indicate that the gastric microenvironment is frequently colonised by Clostridium and Fusobacterium in patients with gastric cancer.

High FIB-4 index as an independent risk factor of prevalent chronic kidney disease in patients with nonalcoholic fatty liver disease.

BACKGROUND: Growing evidence suggests that non-alcoholic fatty liver disease (NAFLD) is linked to an increased risk for chronic kidney disease (CKD); liver fibrosis with biopsy-proven NAFLD has also been shown to associate with an increased risk of CKD. This study compares the diagnostic performance of simple noninvasive tests in identifying prevalent CKD among individuals with ultrasonography-diagnosed NAFLD. METHODS: A total of 755 with ultrasonography-diagnosed NAFLD were included. Estimated glomerular filtration rate and noninvasive markers for hepatic fibrosis: aspartate transaminase to alanine transaminase ratio (AAR), aspartate transaminase to platelet ratio index (APRI), FIB-4 score, NAFLD fibrosis score (NFS) and BARD score were assessed. RESULTS: Binary logistic regression to generate a propensity score and receiver operating characteristic curves were developed for each of the noninvasive markers for predicting CKD, and the area under the receiver operating characteristic curve was greatest for FIB-4 score (0.750), followed by NFS (0.710), AAR (0.594), APRI (0.587), and BARD score (0.561). A cut-off value of 1.100 for FIB-4 score gave a sensitivity of 68.85% and a specificity of 71.07% for predicting CKD. The positive predictive value and negative predictive value were 37.50 and 90.05%, respectively. In multiple logistic regression analysis, only FIB-4 score ≧1.100 (OR 2.660, 95% CI 1.201-5.889; p = .016), older age, higher diastolic blood pressure and higher uric acid were independent predictors of CKD. CONCLUSIONS: High noninvasive fibrosis score is associated with an increased risk of prevalent CKD; the FIB-4 is the better predictor. With a cut-off value of 1.100 for FIB-4, it is useful in excluding the presence of CKD in patients with NAFLD.

Liver stiffness measurement in cirrhotic patient -- implications of disease activity and treatment efficacy.

Liver stiffness measurement (LSM) is a noninvasive method for the diagnosis of hepatic fibrosis. The aim of this study was to evaluate the effects of hepatitis activity and antiviral therapy on LSM in cirrhotic patients. Consecutive patients with compensated hepatic cirrhosis were enrolled for LSM. The medical records of hepatitis activity and antiviral therapy before enrollment were reviewed. Patients were stratified into inactive, fluctuating, and active groups by serial change of alanine transaminase level. For chronic hepatitis C, patients were stratified into sustained virological response (SVR) and non-SVR (NSVR) by effect of antiviral treatment. LSM results were compared among different groups. A total of 163 patients (mean age = 57.2 ± 11.0 years) were enrolled. The median (range) LSM values were 9.6 (4.2-20.6), 10.25 (3.9-49.6), and 15.75 (4.8-61.5) kPa in the inactive, fluctuating, and active groups, respectively. Patients in the active group had significantly higher LSM values. For chronic hepatitis C, median (range) LSM values were 16.6 (8.1-61.5), 22.9 (11.1-37.4), and 11.2 (3.9-27.0) kPa in patients without antiviral therapy, in NSVR, and in SVR groups, respectively. Patients with SVR had significantly lower LSM values. For chronic hepatitis B, median (range) LSM values were 11.8 (5.1-46.6), 16.85 (4.2-48), and 10.6 (4.3-46.4 kPa) kPa in patients without oral nucleos(t)ide analogue (NA) therapy, with NA < 12, and ≧12 months, respectively. There was a significantly lower LSM value in patients with NA therapy≧12 months. There were low LSM values in cirrhotic patients without hepatitis activity, as well as with SVR in chronic hepatitis C and long-term NA therapy in chronic hepatitis B.

The effects of cefazolin on cirrhotic patients with acute variceal hemorrhage after endoscopic interventions.

BACKGROUND: The American Association for the Study of Liver Diseases (AASLD) guidelines recommend that antibiotic prophylaxis should be instituted in any patient with cirrhosis and gastrointestinal hemorrhage, and that oral norfloxacin, intravenous ciprofloxacin, and ceftriaxone are preferable. However, the antimicrobial spectrum of the first generation of cephalosporins (cefazolin) covers a wide range of bacteria species, including community-acquired strains of Escherichia coli and Klebsiella pneumoniae, but their efficacy as prophylactic antibiotics in cirrhotic patients with acute hemorrhage was seldom warranted in the literature. This study aimed to explore the effects of cefazolin on the outcome of cirrhotic patients with acute variceal hemorrhage after endoscopic interventions. METHODS: A cross-sectional, retrospective chart review study was conducted on cirrhotic patients with acute variceal hemorrhage who underwent endoscopic procedures in a medical center. Cirrhotic patients who did not receive antibiotics were classified as group A (n = 63) while patients who received intravenous cefazolin 1 g q8 h for 2-7 days were classified as group B (n = 50). The end points were the prevention of infection, length of hospital stay, time of rebleeding, and death. RESULTS: A total of 113 patients were studied (male/female: 82/31; age: 56.8 ± 13.5 years). The incidence of infection (including proven infections) and bacteremia were significantly lower in group B patients (38.1% vs. 16.0%, P = 0.010; 17.5% vs. 4.0%, P = 0.026; 9.5% vs. 0%, P = 0.033, respectively). The no prophylactic antibiotics treatment was the independent risk factor. There was no significant difference between the two groups with respect to the source of bleeding, type of endoscopic intervention, length of hospital stay, and mortality. Actuarial probability of remaining free of early rebleeding (<7 days) was P = 0.105 by log-rank test for all cirrhosis patients and P = 0.085 for Child-Pugh class A patients. CONCLUSIONS: The use of cefazolin in cirrhotic patients after endoscopic interventions for acute variceal hemorrhage reduced infections. A trend of actuarial probability of remaining free of early rebleeding (<7 days) was observed, especially in Child-Pugh class A patients. This study may be hampered by the small sample size and more large-scale studies are mandatory.