Effect of hypoalbuminemia on mortality in cirrhotic patients with spontaneous bacterial peritonitis.

Objectives: The impact of hypoalbuminemia on the short-term and long-term mortality of cirrhotic patients with spontaneous bacterial peritonitis (SBP), both with and without renal function impairment, remains insufficiently elucidated based on population-based data. Materials and Methods: We retrieved data from Taiwan's National Health Insurance Database encompassing 14,583 hospitalized patients diagnosed with both cirrhosis and SBP during the period from January 1, 2010, to December 31, 2013. Prognostic factors influencing 30-day and 3-year survival were computed. Furthermore, the impact of hypoalbuminemia on the mortality rate among SBP patients, with or without concurrent renal function impairment, was also assessed. Results: The 30-day mortality rates for patients with SBP, comparing those with hypoalbuminemia and those without, were 18.3% and 29.4%, respectively (P < 0.001). Similarly, the 3-year mortality rates for SBP patients with hypoalbuminemia and those without were 73.7% and 85.8%, respectively (P < 0.001). Cox proportional hazard regression analysis, adjusted for patients' gender, age, and comorbid conditions, substantiated that individuals with hypoalbuminemia exhibit an inferior 30-day survival (hazard ratio [HR]: 1.62, 95% confidence interval [CI]: 1.51-1.74, P < 0.001) and reduced 3-year survival (HR: 1.57, 95% CI: 1.50-1.63, P < 0.001) in comparison to those lacking hypoalbuminemia. Among SBP patients with renal function impairment, those presenting hypoalbuminemia also experienced diminished 30-day survival (HR: 1.81, 95% CI 1.57-2.07, P < 0.001) as well as reduced 3-year survival (HR: 1.70, 95% CI 1.54-1.87, P < 0.001). Likewise, in SBP patients without renal function impairment, the presence of hypoalbuminemia was associated with poorer 30-day survival (HR: 1.54, 95% CI 1.42-1.67, P < 0.001) and 3-year survival (HR: 1.53, 95% CI 1.46-1.60, P < 0.001). Conclusion: Among cirrhotic patients with SBP, the presence of hypoalbuminemia predicts inferior short-term and long-term outcomes, regardless of renal function.

The Risk of Hepatitis B Virus Reactivation in Rheumatoid Arthritis Patients Receiving Tocilizumab: A Systematic Review and Meta-Analysis.

BACKGROUND: Tocilizumab has demonstrated optimal efficacy and safety in patients with rheumatoid arthritis (RA) from clinical trials. However, the risk of hepatitis B virus reactivation (HBVr) in these patients remains uncertain because patients with underlying HBV have been excluded in phase III studies. METHODS: Systematical reviews were conducted on PubMed, Embase, and the Cochrane Central Register of Controlled Trials up to 21 February 2023. Random-effects meta-analysis was performed to calculate the pooled incidence of HBV reactivation. RESULTS: We included 0 clinical trials and 11 observational studies with a total of 25 HBsAg+ and 322 HBsAg-/anti-HBc+ RA patients. Among the HBsAg+ patients without antiviral prophylaxis, the pooled rate was 69.4% (95% CI, 32.9-91.3), with a median time of 4 months (range, 1-8 months) from tocilizumab initiated. Half of these patients with HBVr experienced hepatitis flare-up but no deaths. HBVr was eliminated with prophylaxis in this population. Among HBsAg-/anti-HBc+ patients, the pooled incidence of reactivation was 3.3% (95% CI, 1.6-6.7), with a median time of 10 months (range, 2-43 months) from tocilizumab initiated. HBVr was not associated with hepatitis flare-up and death. HBsAg-/anti-HBc+ patients without anti-HBs antibodies had a significantly higher risk of HBVr (Odds ratio, 12.20; 95% CI, 1.16-128.06). CONCLUSIONS: This systematic review indicated that the risk of HBVr in RA patients with anti-HBs-, HBsAg+, or HBsAg-/anti-HBc+ cannot be ignored but may be avoided. Clinicians should consider implementing appropriate antiviral prophylaxis and monitoring policies for RA patients to avoid unnecessary hepatic side effects from tocilizumab treatment.

HBV reactivation in HBsAg-/HBcAb+ rheumatoid arthritis patients receiving biologic/targeted synthetic DMARDs.

BACKGROUND: Rheumatoid arthritis (RA) patients seropositive for hepatitis B core antibody (HBcAb) and negative for hepatitis B surface antigen (HBsAg) are at risk of hepatitis B virus (HBV) reactivation when treated with biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs). The study aims to investigate the risk in this population. METHODS: From January 2004 through December 2020, 1068 RA patients undergoing b/tsDMARDs therapy and 416 patients with HBsAg-/HBcAb+ were enrolled. Factors associated with HBV reactivation were analysed. RESULTS: During 2845 person-years of follow-up, 27 of 416 (6.5%,9.5 per 1000 person-years) patients developed HBV reactivation, with a cumulative rate of HBV reactivation of 3.5% at 5 years, 6.1% at 10 years and 24.2% at 17 years. The median interval from beginning b/tsDMARDs to HBV reactivation was 85 months (range: 9-186 months). The risk of HBV reactivation varied by type of b/tsDMARD, with rituximab having the highest risk (incidence rate: 48.3 per 1000 person-years), followed by abatacept (incidence rate: 24.0 per 1000 person-years). In multivariate analysis, rituximab (adjusted hazard ratio [aHR]: 15.77, 95% confidence interval [CI]: 4.12-60.32, p = .001), abatacept (aHR: 9.30, 1.83-47.19, p = .007), adalimumab (aHR: 3.86, 1.05-14.26, p = .04) and negative baseline HBV surface antibody (anti-HBs, <10 mIU/mL) (aHR: 3.89, 1.70-8.92, p < .001) were independent risk factors for HBV reactivation. CONCLUSION: HBsAg-/HBcAb+ RA patients are susceptible to HBV reactivation during b/tsDMARD therapy. Those with negative baseline anti-HBs and those on certain b/tsDMARDs, such as rituximab, abatacept and adalimumab, have high reactivation risks. Risk stratification and management should be based on the patient's baseline anti-HBs titre and type of therapy.

Prognostic factors of cirrhotic patients with invasive fungal infections.

Fungal infection (FI) is a life-threatening condition in cirrhotic patients. However, a population-based study is required to determine the short-term mortality of these patients. The Taiwan National Health Insurance Database was used to enroll 1214 cirrhotic patients with FIs who were hospitalized between January 1, 2010 and December 31, 2013. Among them, 165 were diagnosed with invasive FIs. The overall 30-day and 90-day mortality rates for patients with invasive FIs were 25.7% and 49.9%, respectively (P < .001). After adjusting for sex, age, and other comorbidities, the following 90-day mortality prognostic factors were statistically different: renal function impairment (hazard ratio = 1.98, 95% confidence interval = 1.05-3.70, P = .034), concurrent with bacterial infections (hazard ratio = 1.75, 95% CI = 1.07-2.88, P = .027). Half of the cirrhotic patients died within 90-daysdue to invasive FIs, highlighting the importance of renal function impairment and concurrent with bacterial infections as an important prognostic factor.

The Predictive Role of Hepatitis B Biomarkers on HBV Reactivation following Direct-Acting Antiviral Therapy in HBV/HCV Coinfected Patients.

Hepatitis B and C (HBV/HCV) coinfected patients have a potential risk of hepatitis B reactivation (HBVr) after direct-acting antivirals (DAAs) treatment. The study intends to investigate the predictive role of HBV biomarkers in HBVr. Forty-six HBV/HCV coinfected patients receiving DAAs were enrolled. All patients completed treatment and follow-up to the 12th-week post-DAA treatment (P12). Blood samples were measured for HBV biomarkers, including hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg), and HBV pregenomic RNA (HBV pgRNA). The predictive factors for HBVr after DAA treatment were analyzed. Among 31 patients without nucleot(s)ide analogue (NA) treatment, seven (22.5%, 7/31) developed HBVr without hepatitis flare-up. Patients with HBVr had higher HBsAg titers than those without HBVr from baseline to P12 (p = 0.008, 0.009, 0.004, and 0.006 at baseline, week 4, end of treatment, and P12, respectively). The baseline HBsAg level was the only predictive factor associated with HBVr (HR, 2.303; 95% CI, 1.086−4.882; p = 0.030). In predicting HBVr, a baseline HBsAg titer > 20 IU/mL had a sensitivity, specificity, positive predictive value, and negative predictive value of 85.7%, 75.0%, 50%, and 94.7%, respectively. No patient had HBVr if the baseline HBsAg titer was <8 IU/mL. Serum HBcrAg and HBV pgRNA levels had no role in predicting HBVr. In conclusion, HBV/HCV coinfected patients are at risk of HBVr after DAA treatment. The baseline HBsAg level was the predictive factor associated with HBVr. Patients with a baseline HBsAg titer < 8 IU/mL can be considered as not having HBVr.

Neutrophil gelatinase-associated lipocalin partly reflects the dynamic changes of renal function among chronic hepatitis C patients receiving direct-acting antivirals.

BACKGROUND: Changes in renal function in chronic hepatitis C (CHC) patients receiving direct-acting antivirals (DAAs) are controversial. The evolution of neutrophil gelatinase-associated lipocalin (NGAL) in these patients remains unclear. METHODS: A total of 232 CHC patients receiving DAA at Dalin Tzu Chi Hospital from May 2016 to February 2019, were enrolled in this retrospective study. Grade 2/3 renal function deterioration, defined as a decrease in eGFR between 10% and 50% from baseline (BL) to 12 weeks after the end of treatment (P12), was investigated for its association with BL characteristics. The changes in renal function and NGAL levels were also analyzed at the SOF-base or nonSOF-base DAA. RESULTS: Sixty-two patients (26.7%) had grade 2/3 renal function deterioration at P12 after DAA therapy. Univariate analysis showed that it was associated with age (P = 0.038). Multivariate analysis indicated that age (OR = 1.033, 95% CI: 1.004-1.064, P = 0.027), sex (male; OR = 2.039, 95% CI: 1.093-3.804, P = 0.025), ACEI/ARB use (OR = 2.493, 95% CI: 1.016-6.119, P = 0.046), and BL NGAL (OR = 1.033, 95% CI: 1.001-1.067, P = 0.046) positively correlated with grade 2/3 renal function deterioration. Furthermore, eGFR was decreased (P = 0.009) and NGAL was increased (P = 0.004) from BL to P12 in CHC patients receiving SOF-based DAA. CONCLUSIONS: Of the CHC patients receiving DAA therapy, 26.7% had grade 2/3 renal function deterioration at P12, and it was associated with older age, gender being male, ACEI/ARB use, and higher BL NGAL levels. In addition, NGAL might be a biomarker of nephrotoxicity at P12 in patients receiving SOF-based DAA.

Baseline thrombopoietin level is associated with platelet count improvement in thrombocytopenic chronic hepatitis C patients after successful direct-acting antiviral agent therapy.

BACKGROUND: Thrombocytopenia can rapidly improve in chronic hepatitis C (CHC) patients receiving direct-acting antiviral agents (DAA). The role of baseline (BL) thrombopoietin (TPO) in this phenomenon is unclear. METHODS: From June 2016 to February 2019, a total of 104 CHC patients receiving DAA, with a sustained virologic response and BL thrombocytopenia, at Dalin Tzu Chi Hospital, were enrolled in this retrospective study. Significant platelet count improvement and platelet count improvement ratio were analyzed for correlation with BL TPO. RESULTS: This cohort included 40 men (38.5%). Seventy-two (69.2%) patients had advanced fibrosis. The platelet count [median (range)] increased from 110.5 (32-149) × 103/µL at BL to 116.5 (40-196) and 118.0 (35-275) × 103/µL at end of treatment (EOT) and 12 weeks after EOT (P12), respectively, (EOT vs. BL, P < 0.001; P12 vs. BL, P < 0.001). BL TPO was positively correlated with significant platelet count improvement (P < 0.001), platelet count improvement ratio at EOT (P = 0.004), and P12 (P < 0.001). The area under the receiver operating characteristic curve and optimal cutoffs (pg/ml) were 0.77 (95% confidence interval, 0.67-0.86) and 120, respectively, for significant platelet count improvement prediction. The sensitivity, specificity, and accuracy were 88.6%, 71.7%, and 78.8%, respectively. CONCLUSIONS: BL TPO level might be a useful marker for predicting significant platelet count improvement in thrombocytopenic patients after successful DAA therapy.

Regulatory T Cell Function Modulated After Successful Direct-Acting Antiviral Treatment for Chronic Hepatitis C Patients.

BACKGROUNDS: Regulatory T cells (Tregs) affect the pathogenesis of chronic hepatitis C (CHC) infection. AIMS: This study evaluated the function of Tregs in CHC patients receiving the standard direct-acting antiviral agents (DAA) treatment. METHODS: CHC patients (n = 20) who received DAA treatment, clinical data, and function of Tregs were checked at baseline, Week 4, end of treatment (EOT), and 12 weeks after EOT (SVR 12). Treg-mediated inhibition was measured. The cytokine expression and fold change of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-10, and transforming growth factor (TGF)-ß with/without Treg inhibition were also detected. RESULTS: The cohort included 14 females with a mean age of 59.8 ± 11.5 years. Nineteen had HCV genotype 1. The HCV RNA level was 6.17 ± 0.70 log IU/mL. All patients reached the sustained virologic response. The frequency of CD4+Foxp3+T cells decreased from baseline to EOT and returned at SVR 12. The inhibitory function of Tregs decreased during treatment and then restored (baseline vs. EOT, P = 0.0393; EOT vs. SVR 12, P = 0.0052). The cytokine expression and fold change of IFN-γ and TNF-α were highest at EOT and then decreased at SVR 12. The fold change of IL-10 was lowest at EOT and then increased at SVR 12. The fold change of TGF-ß was significantly increased at Week 4 and SVR 12 compared to baseline. CONCLUSIONS: The frequency and inhibitory function of Tregs declined gradually from baseline to EOT and then increased from EOT to SVR 12 in CHC patients receiving DAA therapy. The expression of IFN-γ, TNF-α, IL-10, and TGF-ß parallelled Treg function.

Epidural abscess caused by Veillonella parvula: Case report and review of the literature.

Veillonella parvula, an anaerobic, Gram-negative coccus is part of the normal flora of the oral, gastrointestinal, respiratory, and genitourinary tracts in humans and animals. We herein present a case of epidural abscess caused by V. parvula in a 68-year-old man with sinus squamous cell carcinoma who presented with a 3-week history of low back pain. Blood and pus cultures were positive for Veillonella spp. After sequencing of the 16S ribosomal DNA, the pathogen was identified as V. parvula. Surgical debridement was performed following which the patient received intravenous administration of amoxicillin/clavulanate. To our knowledge, there are only seven reported cases of spinal infection caused by Veillonella spp. and these are reviewed here.