Prediction of Hepatocellular Carcinoma Development in Korean Patients after Hepatitis C Cure with Direct-Acting Antivirals.

Background/Aims: With the wide application of direct-acting antivirals (DAAs) for hepatitis C virus infection, the number of patients achieving a sustained virologic response (SVR) will continue to increase. However, no consensus has been achieved on exempting SVR-achieving patients from hepatocellular carcinoma (HCC) surveillance. Methods: Between 2013 and 2021, 873 Korean patients who achieved SVR following DAA treatment were analyzed. We evaluated the predictive performance of seven noninvasive scores (PAGE-B, modified PAGE-B, Toronto HCC risk index, fibrosis-4, aspartate aminotransferase-to-platelet ratio index, albumin-bilirubin, and age male albumin-bilirubin platelet [aMAP]) at baseline and after SVR. Results: The mean age of the 873 patients (39.3% males) was 59.1 years, and 224 patients (25.7%) had cirrhosis. During 3,542 person-years of follow-up, 44 patients developed HCC, with an annual incidence of 1.24/100 person-years. Male sex (adjusted hazard ratio [AHR], 2.21), cirrhosis (AHR, 7.93), and older age (AHR, 1.05) were associated with a significantly higher HCC risk in multivariate analysis. The performance of all scores at the time of SVR were numerically better than those at baseline as determined by the integrated area under the curve. Time-dependent area under the curves for predicting the 3-, 5-, and 7-year risk of HCC after SVR were higher in mPAGE-B (0.778, 0.746, and 0.812, respectively) and aMAP (0.776, 0.747, and 0.790, respectively) systems than others. No patients predicted as low-risk by the aMAP or mPAGE-B systems developed HCC. Conclusions: aMAP and mPAGE-B scores demonstrated the highest predictive performance for de novo HCC in DAA-treated, SVR-achieving patients. Hence, these two systems may be used to identify low-risk patients that can be exempted from HCC surveillance.

A multicenter retrospective analysis: Factors influencing hepatic adverse events induced by immunotherapy in advanced liver cancer.

OBJECTIVES: To analyze the clinical characteristics and influencing factors of hepatotoxicity in patients with advanced hepatocellular carcinoma (HCC) treated with programmed cell death protein-1 (PD-1) inhibitors, and to provide a theoretical basis for the treatment of immune-related hepatotoxicity in patients with advanced HCC. METHODS: Retrospective analysis of clinical data of patients with advanced HCC from February 2021 to February 2023, in order to summarize and statistically analyze the influencing factors of immune-related liver adverse reactions. RESULTS: A total of 135 patients met the inclusion criteria, among whom 46 patients experienced varying degrees of immune-related liver adverse reactions, with an incidence rate of 34.1% (46/135). The time range of immune-related liver adverse reactions was 3-26 weeks, with a median time of 4 weeks. The age range of immune-related liver adverse reactions was 34-73 years, with a median age of 62 years. Statistical analysis of the influencing factors and liver adverse reactions showed that age, total bilirubin level, and Child-Pugh (C-P) grading were influencing factors for the occurrence of liver adverse reactions (p < .05), and among these three influencing factors, the proportion of males with ≥2 influencing factors was higher than that of females; liver function C-P B was an independent influencing factor for liver adverse reactions (p < .05). CONCLUSION: For male patients over 60 years old, with bilirubin levels ≥51 µmol/L and liver function C-P B, close observation of the occurrence of immune-related adverse reactions during treatment is recommended.

Brucellosis-associated hepatitis.

AIM: Brucellosis is a zoonotic infection that can affect almost every organ. A mild elevation of aminotransferase levels is usually observed in liver involvement. However, the development of clinical hepatitis is rare. In this study, we aimed to present the hospitalized cases with brucellosis hepatitis in our clinic in a 13-year period. METHODS: A hundred and three patients with significant hepatobiliary involvement, diagnosed by microbiological analysis, were included in the study. For the presence of hepatitis, it was required that the aminotransferases must be ≥ 5 times more than the upper limit and/or the total bilirubin level must be ≥ 2 mg/dl and/or the local hepatic lesion must be demonstrated. RESULTS: Of the cases, 35.9%, 17.5%, and 46.6% had clinical hepatitis, cholestatic hepatitis, and both clinical and cholestatic hepatitis, respectively. The most frequent symptom was fever (85.4%) while the most preferred treatment options were combinations containing aminoglycosides. It was observed that the mean time-interval to decrease to normal values of ALT, AST, and bilirubin values was 15.2 ± 7.8 days while the patients having their treatment regimens. In our study, which focused on liver involvement, it was found that a chronic liver disease did not develop in any of the cases. CONCLUSION: Our study showed that, even in the presence of hepatitis, clinical response and laboratory improvement were high with appropriate treatment. It was observed that the improvement in aminotransferases and total bilirubin values delayed in the cases with blood culture positivity, secondary organ involvement, and alanine aminotransferase/aspartate aminotransferase > 1.

Clinical Significance of Albumin-Bilirubin Grade in Thoracic Esophageal Squamous Cell Carcinoma.

INTRODUCTION: The albumin-bilirubin (ALBI) score evaluates liver dysfunction severity. However, this score had prognostic effects in patients with hepatocellular, pancreatic, and gastric carcinomas. We aimed to assess the predictive value of the ALBI score in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Data from 154 patients with ESCC who consecutively underwent neoadjuvant chemotherapy (NAC) and subtotal esophagectomy were retrospectively investigated. The ALBI score was calculated as pre-NAC ALBI and categorized into grades 1, 2a, 2b, and 3; low-ALBI group (n = 134) was assigned with ALBI grade 1 and the other grades were assigned to the high-ALBI group (n = 20). RESULTS: The pre-NAC ALBI was significantly associated with relapse-free survival (RFS) and overall survival (P = 0.003 and P = 0.014, respectively). Based on multivariate analysis, pre-NAC ALBI, pathological T factor, and N factor were identified as independent prognostic factors for poor RFS. Multivariate and univariate analyses limited to factors were obtained before treatment, indicating high pre-NAC ALBI as an independent prognostic factor of poor overall survival (P = 0.039) and RFS (P = 0.008). With respect to pathological response to NAC, patients in the high pre-NAC ALBI group had a significantly lower response than patients in the low pre-NAC ALBI group (P = 0.010). CONCLUSIONS: Our results suggested that the pre-NAC ALBI marker predicts the long-term outcome and pathological response to NAC in patients with ESCC consecutively undergoing NAC and a subtotal esophagectomy.

Association of Different Total Bilirubin Levels with Prognosis of Peritoneal Dialysis-Associated Peritonitis.

Background and Objectives: Peritoneal dialysis-associated peritonitis (PDAP) poses significant challenges in peritoneal dialysis (PD) patient management and outcomes. Total bilirubin has gained attention due to its antioxidant and immunomodulatory properties. However, its relationship with PDAP prognosis remains underexplored. Materials and Methods: We conducted a retrospective single-center study involving 243 PDAP patients stratified into tertile-based groups according to total bilirubin levels. The association between total bilirubin levels and treatment failure risk was investigated through statistical analyses and restricted cubic spline curve analysis. Results: Our analysis revealed a non-linear correlation between total bilirubin levels and PDAP treatment failure risk. At total bilirubin levels below 8.24 µmol/L, a protective effect was observed, while levels exceeding this threshold heightened the risk of treatment failure. Conclusions: This study unveils a dual role of total bilirubin in PDAP prognosis. Below a certain threshold, it confers protection, while higher levels exacerbate the risk of treatment failure. These findings emphasize the need for further investigation in larger, multicenter prospective studies to validate and elucidate the mechanisms behind bilirubin's impact on PDAP, potentially guiding the development of targeted therapeutic strategies.

Effect of Oral Zinc Supplementation on Serum Bilirubin Levels in Term Neonates With Hyperbilirubinemia Undergoing Phototherapy: A Double-blind Randomized Controlled Trial.

BACKGROUND: Background: Enterohepatic bilirubin circulation is one of the determinants of neonatal jaundice. OBJECTIVE: To evaluate the role of oral zinc in reducing serum bilirubin in term neonates with hyperbilirubinemia. STUDY DESIGN: Double-blind, randomized, placebo-controlled trial. PARTICIPANTS: 106 term neonates with jaundice within the phototherapy range admitted to a level III neonatal intensive care unit. INTERVENTION: Neonates were randomized and allocated to receive either oral zinc sulfate (5 mg/day) or matching placebo for 5 days. Both groups received conventional phototherapy as per American Academy of Pediatrics (AAP) guidelines. OUTCOMES: Primary: Reduction in total serum bilirubin levels at 24, 48, 72, and 96 hr after intervention. Secondary: Duration of phototherapy, and hospital stay. RESULTS: The mean (SD) total serum bilirubin levels in zinc and placebo groups were 15.3 (2.85) vs 17.1 (2.21) mg/dL (MD 1.74; P<0.001) at 24 h; 11.7 (4.46) vs. 14.62 (3.83) mg/dL (MD 2.89; P<0.001) at 48 h; 6.7 (4.77) vs 9.5 (3.70) mg/dL (MD 2.79; P <0.001) at 72 h; and 5.1 (3.95) vs 6.5 (3.70) mg/dL (MD 1,49; P=0.045) after 72 hr, respectively. The mean (SD) duration of phototherapy was significantly lower in zinc group than placebo group [ 53.42 (19.62) vs 71.4 (19.43) h; P<0.001]. There was no significant difference in hospital stay between the two groups [mean (SD) 81.05 (19.43) vs 86.25 (20.02) h; P= 0.227]. CONCLUSION: Oral zinc sulfate supplementation at a dose of 5 mg once a day along with phototherapy significantly reduced total and indirect serum bilirubin levels and also reduced the total duration of phototherapy required in the term neonatal hyperbilirubinemia, with minimal or no adverse effects.

Risk evaluation of ampicillin/sulbactam-induced liver injury based on albumin-bilirubin score.

BACKGROUND: Drug-induced liver injury (DILI) is an adverse reaction caused by ampicillin/sulbactam (ABPC/SBT). The albumin-bilirubin (ALBI) score is an index of hepatic functional reserve. However, the relationship between ABPC/SBT-induced DILI and ALBI score remains unknown; therefore, we aimed to elucidate the risk of ABPC/SBT-induced DILI based on the ALBI score. METHODS: This was a single-center, retrospective, case-control study using electronic medical records. A total of 380 patients were enrolled in the present study, and the primary outcome was ABPC/SBT-induced DILI. The ALBI score was calculated using serum albumin and total bilirubin levels. In addition, we performed COX regression analysis using age ≥75 years, dose ≥9 g/day, alanine aminotransferase (ALT) ≥21 IU/L, and ALBI score ≥-2.00 as covariates. We also performed 1:1 propensity score matching between non-DILI and DILI groups. RESULTS: The incidence of DILI was 9.5% (36/380). According to COX regression analysis, the adjusted hazard ratio for ABPC/SBT-induced DILI with an ALBI score ≥-2.00 was 2.55 (95% confidence interval: 1.256-5.191, P = 0.010), suggesting that patients with baseline ALBI score ≥-2.00 may be at high risk for ABPC/SBT-induced DILI. However, significant differences were not observed in cumulative risk for DILI between non-DILI and DILI patients regarding an ALBI score ≥-2.00 after propensity score matching (P = 0.146). CONCLUSION: These findings suggest that ALBI score may be a simple and potentially useful index for predicting ABPC/SBT-induced DILI. In patients with an ALBI score ≥-2.00, frequent liver function monitoring should be considered to prevent ABPC/SBT-induced DILI.

Can 'toxic' bilirubin be put to medical use?

New view of molecule's good side inspires plans to test it as treatment for a variety of illnesses.

Oral Delivery of Transformable Bilirubin Self-Assembled System for Targeted Therapy of Colitis.

Ulcerative colitis (UC) is a high incidence disease worldwide and clinically presents as relapsing and incurable inflammation of the colon. Bilirubin (BR), a natural antioxidant with significant anti-colitic effects, is utilized in preclinical studies as an intestinal disease therapy. Due to their water-insolubility, the design of BR-based agents usually involves complicated chemosynthetic processes, introducing various uncertainties in BR development. After screening numerous materials, it is identified that chondroitin sulfate can efficiently mediate the construction of BR self-assembled nanomedicine (BSNM) via intermolecular hydrogen bonds between dense sulfate and carboxyl of chondroitin sulfate and imino groups of BR. BSNM exhibits pH sensitivity and reactive oxygen species responsiveness, enabling targeted delivery to the colon. After oral administration, BSNM significantly inhibits colonic fibrosis and apoptosis of colon and goblet cells; it also reduces the expression of inflammatory cytokines. Moreover, BSNM maintains the normal level of zonula occludens-1 and occludin to sustain the integrity of intestinal barrier, regulates the macrophage polarization from M1 to M2 type, and promotes the ecological recovery of intestinal flora. Collectively, the work provides a colon-targeted and transformable BSNM that is simple to prepare and is useful as an efficient targeted UC therapy.

FUNCTIONAL STATE OF THE LIVER IN PULMONARY TUBERCULOSIS IN THE DYNAMICS OF PATHOGENETIC TREATMENT WITH A COMPLEX OF AMINO ACIDS.

OBJECTIVE: The aim: To investigate the in!uence of prescribing a complex of amino acids in pathogenetic therapy in patients with pulmonary tuberculosis on liver function. PATIENTS AND METHODS: Materials and methods: The study included 50 patients with drug susceptible TB and 50 patients with drug-resistant TB (multidrug-resistant and extensively drug-resistant). RESULTS: Results: The study included 50 patients with drug susceptible tuberculosis (TB) and 50 patients with drug-resistant TB. When comparing biochemical pa-rameters characterizing liver function in patients with drug-susceptible TB after 1 month of anti-tuberculosis therapy, it was found that patients receiving additional therapy with a complex of amino acids had a lower level of bilirubin, p <0.05. After 60 doses, patients receiving additional therapy with amino acids had significantly lower bilirubin levels alanine aminotransferase (ALT) and aspartate aminotransferase (AST), p <0.05. When comparing the biochemical parameters characterizing liver function in patients with drug-resistant tuberculosis after a month of anti-tuberculosis therapy, significantly higher protein level was found in the groups of patients receiving additional therapy with amino acids, as well as significantly lower ALT level, AST and creatinine p <0.05. CONCLUSION: Conclusions: The additional appointment of the complex of amino acids in the pathogenetic therapy of patients with pulmonary tuberculosis makes it possible to reduce the severity of hepatotoxic reactions manifested by the main parameters (AST, ALT, total bilirubin) and to increase the protein-synthetic function of the liver, which allows us to recommend their appointment to improve the tolerance of anti-tuberculosis therapy.

Chemotherapy-related hyperbilirubinemia in pediatric acute lymphoblastic leukemia: a genome-wide association study from the AIEOP-BFM ALL study group.

BACKGROUND: Characterization of clinical phenotypes in context with tumor and host genomic information can aid in the development of more effective and less toxic risk-adapted and targeted treatment strategies. To analyze the impact of therapy-related hyperbilirubinemia on treatment outcome and to identify contributing genetic risk factors of this well-recognized adverse effect we evaluated serum bilirubin levels in 1547 pediatric patients with acute lymphoblastic leukemia (ALL) and conducted a genome-wide association study (GWAS). PATIENTS AND METHODS: Patients were treated in multicenter trial AIEOP-BFM ALL 2000 for pediatric ALL. Bilirubin toxicity was graded 0 to 4 according to the Common Toxicity Criteria (CTC) of the National Cancer Institute. In the GWAS discovery cohort, including 650 of the 1547 individuals, genotype frequencies of 745,895 single nucleotide variants were compared between 435 patients with hyperbilirubinemia (CTC grades 1-4) during induction/consolidation treatment and 215 patients without it (grade 0). Replication analyses included 224 patients from the same trial. RESULTS: Compared to patients with no (grade 0) or moderate hyperbilirubinemia (grades 1-2) during induction/consolidation, patients with grades 3-4 had a poorer 5-year event free survival (76.6 ± 3% versus 87.7 ± 1% for grades 1-2, P = 0.003; 85.2 ± 2% for grade 0, P < 0.001) and a higher cumulative incidence of relapse (15.6 ± 3% versus 9.0 ± 1% for grades 1-2, P = 0.08; 11.1 ± 1% for grade 0, P = 0.007). GWAS identified a strong association of the rs6744284 variant T allele in the UGT1A gene cluster with risk of hyperbilirubinemia (allelic odds ratio (OR) = 2.1, P = 7 × 10- 8). TT-homozygotes had a 6.5-fold increased risk of hyperbilirubinemia (grades 1-4; 95% confidence interval (CI) = 2.9-14.6, P = 7 × 10- 6) and a 16.4-fold higher risk of grade 3-4 hyperbilirubinemia (95% CI 6.1-43.8, P = 2 × 10- 8). Replication analyses confirmed these associations with joint analysis yielding genome-wide significance (allelic OR = 2.1, P = 6 × 10- 11; 95% CI 1.7-2.7). Moreover, rs6744284 genotypes were strongly linked to the Gilbert's syndrome-associated UGT1A1*28/*37 allele (r2 = 0.70), providing functional support for study findings. Of clinical importance, the rs6744284 TT genotype counterbalanced the adverse prognostic impact of high hyperbilirubinemia on therapy outcome. CONCLUSIONS: Chemotherapy-related hyperbilirubinemia is a prognostic factor for treatment outcome in pediatric ALL and genetic variation in UGT1A aids in predicting the clinical impact of hyperbilirubinemia. TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov ; #NCT00430118.

Factors associated with lamotrigine concentration/dose ratio in individuals with bipolar disorders.

Monitoring of lamotrigine levels is recommended in epilepsy. However, in bipolar disorders (BD), no study has described the therapeutic range in daily practice and factors being associated to it. We used retrospective data of individuals with BD, treated with lamotrigine, and included in the FondaMental Advanced Centers of Expertise for Bipolar Disorders cohort. We extracted clinical and biological data and explored associations between these variables and lamotrigine concentration/dose (C/D) ratio. The database included 675 individuals who received lamotrigine at inclusion, whose main characteristics were female sex (68.3%) and BD type 2 (52.1%). Data about lamotrigine C/D ratio were available for 205 individuals. Lamotrigine C/D ratio was significantly associated with: Body Mass Index (BMI) (r=-0.159), estimated GFR (glomerular filtration rate) (r=-0.228), total bilirubin (r = 0.241) and at a trend level, antidepressant co-prescription (U = 3169). The model obtained was: lamotrigine C/D ratio = 1.736 - 0.013*BMI + 0.095*total bilirubin (UI/L) - 0.007*eGFR (ml/min) + 0.210*AST/ALT - 0.004*GGT (UI/L) + 0.014*age (year) + 0.303*currently smoking (yes or no) - 0.588*antidepressant co-prescription (yes or no) - 0.357*gender (F = 1.899, p = 0.057, adjusted R2 = 0.11) Information about plasma lamotrigine C/D ratio were available for only 205 out of the 675 individuals in the database and has been obtained from different laboratories. The representativeness of the included sample may be questionable. This is the first study providing information on a large sample of individuals with BD regarding factors associated with lamotrigine C/D ratio. This study allows to propose a model of lamotrigine C/D ratio that would deserve further replication.

Treatment of Patent Ductus Arteriosus in Premature Infants: Intravenous Paracetamol or Oral Ibuprofen?

BACKGROUND: The similarity in the mechanism of action between paracetamol and ibuprofen can cause similar side effects. However, in preterm neonates with feeding intolerance, intravenous (IV) paracetamol has replaced oral ibuprofen. Therefore, a comparison of the effectiveness and side effects is essential. METHODS: In this retrospective cohort study, the data of 118 preterm infants with a definite diagnosis of patent ductus arteriosus (PDA), including 59 patients who received oral ibuprofen and 59 patients who received IV paracetamol were analyzed. Laboratory evaluations of serum total and direct bilirubin, hemoglobin, and creatinine levels before and seven days after treatment were made. Using analysis of covariance (ANCOVA) and multiple multinomial logistic regression models, the effect of two treatment groups on the post-treatment variables as well as their efficacy comparison were evaluated. RESULTS: In both pre- and post-treatment periods, there was no significant association between echocardiography variables with treatment groups. The results from the ANCOVA model showed that the paracetamol and ibuprofen were followed by a significant decrease in the mean total bilirubin and Hct variables after treatment by 1.38 and 1.65 units, respectively. In addition, results from the Mann-Whitney U test revealed that the median Hb and K differences after and before treatment had a significant difference between the two treatment groups. Furthermore, based on the multiple multinomial logistic model results, the odds of complete arterial duct closure with IV paracetamol was 1.27 times higher than with oral ibuprofen, while in the oral ibuprofen group, the odds of closing was 1.44 times higher than the IV paracetamol group, but there was no statistically significant difference between the two groups. CONCLUSION: Intravenous paracetamol has equal efficacy compared to oral ibuprofen in the treatment of PDA. Also, it seems to be associated with a lower risk of hyperbilirubinemia following the treatment.

The association between serum ferritin and bilirubin with glycemic control among patients with type 2 diabetes mellitus.

Previous evidence has shown an association between serum ferritin and bilirubin levels in the development of type 2 diabetes mellitus (T2DM) and glycemic control. However, the evidence is scarce in Saudi Arabia. In this study, we aimed to evaluate the association between serum ferritin and bilirubin levels with glycemic control in patients with T2DM. This was a cross-sectional study that involved 153 patients with T2DM recruited from outpatient diabetes clinics. Participants were categorized into two groups: well-controlled and uncontrolled T2DM, based on their glycemic status. We focused on comparing the iron profile and bilirubin levels between these two groups and examining the influence of antidiabetic medications on these parameters. A total of 153 patients with T2DM were included (58.2% women and 41.8% men). In both univariate and multivariate analyses, ferritin levels did not have a statistically significant association with glycemic control. However, patients with well-controlled T2DM had a significantly higher median level of total bilirubin and direct bilirubin than those with uncontrolled T2DM. Only direct bilirubin showed a statistically significant association with FBG less than 130 mg/dl and HbA1c level less than 7.0%. Ferritin level was not associated with glycemic control in patients with T2DM. On the other hand, direct bilirubin level was an independent predictor of better glycemic control. Monitoring direct bilirubin levels could aid in predicting glycemic control in T2DM and could be a potential target for developing antidiabetic medications.

Bilirubin Prevents the TH+ Dopaminergic Neuron Loss in a Parkinson's Disease Model by Acting on TNF-α.

Parkinson's disease (PD), the fastest-growing movement disorder, is still challenged by the unavailability of disease-modifying therapy. Mildly elevated levels of unconjugated bilirubin (UCB, PubChem CID 5280352) have been shown to be protective against several extra-CNS diseases, and the effect is attributed to its well-known anti-oxidant and anti-inflammatory capability. We explored the neuroprotective effect of low concentrations of UCB (from 0.5 to 4 µM) in our PD model based on organotypic brain cultures of substantia nigra (OBCs-SN) challenged with a low dose of rotenone (Rot). UCB at 0.5 and 1 µM fully protects against the loss of TH+ (dopaminergic) neurons (DOPAn). The alteration in oxidative stress is involved in TH+ positive neuron demise induced by Rot, but is not the key player in UCB-conferred protection. On the contrary, inflammation, specifically tumor necrosis factor alpha (TNF-α), was found to be the key to UCB protection against DOPAn sufferance. Further work will be needed to introduce the use of UCB into clinical settings, but determining that TNF-α plays a key role in PD may be crucial in designing therapeutic options.

The Inhibitory Effect of Phycocyanin Peptide on Pulmonary Fibrosis In Vitro.

Phycocyanin is an excellent antioxidant with anti-inflammatory effects on which recent studies are growing; however, its specific target remains unclear. Linear tetrapyrrole compounds such as bilirubin have been shown to lead to the induction of heme oxygenase 1 expression in vivo, thus achieving antioxidant and anti-inflammatory effects. Phycocyanin is bound internally with linear tetrapyrrole phycocyanobilin in a similar structure to bilirubin. We speculate that there is probably a way of inducing the expression of heme oxygenase 1, with which tissue oxidative stress and inflammation can be inhibited, thus inhibiting pulmonary fibrosis caused by oxidative damage and inflammation of lung. By optimizing the enzymatic hydrolysis process, phycocyanobilin-bound phycocyanin peptide were obtained, and its in vitro antioxidant, anti-inflammatory, and anti-pulmonary fibrosis activities were investigated. The results show that the phycocyanobilin peptide was able to alleviate oxidative and inflammatory damage in cells through the Keap1-Nrf2-HO-1 pathway, which in turn relieved pulmonary fibrosis symptoms.

Safety and Efficacy of Direct-acting Antiviral Therapies for Chronic HCV Infection in Hemodialysis Patients.

BACKGROUND/AIM: The aim of this study was to determine the safety and efficacy of a direct-acting antiviral treatment, ombitasvir/paritaprevir/ritonavir and dasabuvir, without ribavirin, in a real-life setting. PATIENTS AND METHODS: We performed a prospective observational study including 108 patients undergoing hemodialysis for end-stage kidney disease, referred to our clinic for antiviral therapy for chronic hepatitis C virus infection. Patients received treatment with ombitasvir/paritaprevir/ritonavir and dasabuvir, for 12 weeks. Sustained virologic response (SVR) was defined as undetectable viremia at 12 weeks after the end of therapy. For safety analysis, we monitored serum levels of hemoglobin, albumin, total bilirubin, alanine-aminotransferase and aspartate- aminotransferase at the beginning and end of therapy, as well as at SVR. Verbal Numeric Rating Scale was used to assess the presence of nausea, headaches and fatigue. RESULTS: We noted a high prevalence of diabetic and hypertensive nephropathy as the underlying cause of chronic kidney disease. Most of the patients had F2 and F3 liver fibrosis (32.40% and 34.25%, respectively). The SVR rate was 96.2% (103/107 patients). We recorded an unrelated death after the completion of antiviral therapy. We found increased levels of nausea, headaches and fatigue at the end of therapy compared to at initiation, The presence and degree of symptoms did not correlate with the underlying cause of renal disease (p=0.72) nor with the degree of fibrosis (p=0.08). Minimal increases in transaminases and bilirubin were recorded at the end of treatment, with no statistical significance. CONCLUSION: Oral antiviral therapy with ombitasvir/paritaprevir/ritonavir and dasabuvir can be safely used in hemodialysis patients, with similar response rates compared to the general population.

Phycocyanin: Anti-inflammatory effect and mechanism.

As the host defense response to various injuries and pathogens in the body, inflammation can remove damaged cells and pathogens in the host organism and protect the body. However, excessive inflammation may cause damage to normal tissue cells while removing pathogens, which in turn cause numerous inflammatory diseases and adversely affect the human health. Phycocyanin is an active substance extracted from algae; it has outstanding antioxidant and anti-inflammatory activities, and can effectively inhibit various diseases caused by inflammation. This review systematically summarizes recent applications of phycocyanin against various inflammatory diseases in lung, liver, cardiovascular, and cerebrovascular systems. In addition, possible anti-inflammatory action pathways of phycocyanin are reviewed to canvass the anti-inflammatory mechanism. At last, based on the existing research, phycocyanobilin in phycocyanin is proposed as a bilirubin analog by inducing heme oxygenase 1 in vivo to suppress inflammation.

[Autoimmune haemolytic anemias]. / Autoimmunhämolytische Anämien.

Autoimmune haemolytic anemia (AIHA) is defined as the immune-mediated destruction of red blood cells. In most cases, antibodies that target surface antigens on erythrocytes lead to their premature degradation in the spleen or, less commonly, in the liver. The term includes a heterogenous group of diseases, which differ largely in pathophysiology and treatment. The two most common entities are warm AIHA and cold AIHA. Diagnostic testing involves the analysis of haemolytic markers like lactate dehydrogenase, haptoglobin and unconjugated bilirubin as well as a hemoglobin and reticulocytes. In case of a haemolytic anemia, further testing like a blood smear and a direct antiglobulin test should follow. As diagnostic testing and treatment of AIHA are complex, affected patients should always be referred to a hematologist.In warm AIHA, mainly IgG autoantibodies bind to their antigen on the erythrocyte surface at body temperature, leading to their premature destruction in the spleen. First line treatment options include the administration of steroids which mitigate the destruction of red blood cells by macrophages in the spleen. In contrast, IgM autoantibodies in cold AIHA lead to intravasal agglutination of erythrocytes and complement activation. The IgM antibodies have their highest affinity below body temperature which is why patients experience symptoms mainly in cold-exposed body areas. Although the IgM antibodies dissolve at body temperature, the complement-loaded erythrocytes are destroyed in the liver. Therapeutic options include protection from cold and immunosuppressive agents or complement inhibition.

A phase III randomized, controlled trial of nedaplatin versus cisplatin concurrent chemoradiotherapy in patients with cervical cancer.

BACKGROUND: We evaluated the non-inferiority of nedaplatin-based and cisplatin-based concurrent chemoradiotherapy in cervical cancer patients. DESIGN: Patients aged 28-82 years with pathologically diagnosed cervical cancer (stage IB-IVA) were randomly chosen for the study. Patients in both the cisplatin and nedaplatin groups received radiotherapy and weekly intravenous nedaplatin 30 mg/m2 or cisplatin 40 mg/m2 concurrently. RESULTS: One hundred and sixty patients who received treatment between 10 May 2018 and 31 August 2020 were included. The 3-year overall survival in the nedaplatin group (median 30.5 months) was not significantly different from that in the cisplatin group (28.5 months; hazard ratio 0.131, 95% confidence interval 0.016-1.068; P = 0.058). No significant differences in hematological toxicity were observed between the two groups. Vomiting (40 versus 61), nausea (44 versus 67), and anorexia (52 versus 71) were more common in the cisplatin group whereas effects on liver function, including total bilirubin (7 versus 3), alanine aminotransferase (7 versus 2), and aspartate aminotransferase (6 versus 2), were more common in the nedaplatin group. Four patients in the cisplatin group had grade I creatinine elevation, whereas none in the nedaplatin group had abnormal creatinine levels. Two patients in the nedaplatin group discontinued concurrent chemotherapy because of infusion, and one patient in the cisplatin group discontinued treatment because of infusion-induced dizziness. CONCLUSIONS: Our findings suggest that nedaplatin has a milder gastrointestinal reaction but a more significant effect on liver function than cisplatin. In patients with cervical cancer, nedaplatin-based concurrent chemoradiotherapy could serve as an alternative treatment to cisplatin.