Liver Dysfunction In Patients Research Articles

Association of liver dysfunction with outcomes after percutaneous coronary intervention – a systematic review and meta-analysis

BackgroundLiver dysfunction is a known risk factor in the cardiovascular field. It specifically increases perioperative risk in patients undergoing coronary bypass surgery. Since percutaneous coronary intervention (PCI) is the much less invasive procedure for the treatment of coronary artery disease, we aimed to assess the relationship of liver dysfunction with outcomes in patients undergoing PCI.MethodsThree libraries were searched (MEDLINE, Web of Science and The Cochrane Library). We performed a meta-analysis of all studies in patients who underwent PCI that provided information on the presence or absence of liver dysfunction. Primary outcome was short-term mortality. Secondary outcomes were major adverse cardio- and cerebrovascular events (MACCE), bleeding and acute kidney injury. Random-effects model was applied.ResultsFive studies were selected and the data from 10,710,317 patients were included in the final analysis. In comparison with the absence of liver dysfunction, patients with liver dysfunction were associated with higher short-term mortality (OR 2.97, 95%CI 1.23–7.18, p = 0.02), higher MACCE (OR 1.42, 95%CI 1.08–1.87, p = 0.01), and higher bleeding (OR 2.23, 95%CI 1.65-3.00, p < 0.01). There was no significant difference regarding acute kidney injury (OR 1.20, 95%CI 0.50–2.87, p = 0.69).ConclusionsThe analysis suggests that liver dysfunction in patients undergoing PCI is independently associated with higher risk of short-term mortality and increased occurrence of MACCE and bleeding. However, there appears to be no association to acute kidney injury.

Probiotics may be useful for drug-induced liver dysfunction in patients with depression – A secondary analysis of a randomized clinical trial

Background & AimsThere is a need to identify new treatment options for depression with its comorbidities. Depression often coexists with liver steatosis and the two may share a pathophysiological overlap, including inflammation and microbiota changes. Probiotics might represent a safe option as an adjunctive therapy in patients with depression and possible liver steatosis. The paper presents the secondary analysis of a clinical trial of the effect of probiotic supplementation on the levels of non-invasive markers of liver steatosis and fibrosis in adult patients with depressive disorders. MethodsThe research had a two-arm, parallel-group, prospective, randomized, double-blind, controlled design on probiotics in depression. 116 participants received a probiotic preparation containing Lactobacillus helveticus Rosell®-52 and Bifidobacterium longum Rosell®-175 over 60 days. Here, data from 92 subjects was analyzed. The following were assessed: alanine aminotransferase (ALT), alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio, Hepatic Steatosis Index, Framingham Steatosis Index, as well as non-invasive biomarkers of liver fibrosis (AST to Platelet Ratio Index, Fibosis-4 Index), or baseline socio-demographic, clinical, and laboratory parameters. ResultsThe probiotics did not influence liver steatosis and fibrosis parameters compared with placebo (p=.940 for HSI). However, the subgroup analysis revealed significant differences in liver-related parameters when stratified by the main diagnosis group (better improvement in steatosis indices after probiotics in depressive episode than mixed depression and anxiety disorder patients) or psychotropic medications use (better improvement in ALT-based indices after probiotics in antidepressant-treated subjects than those non-antidepressant-treated). The interplay between probiotics, medications, clinical and metabolic profiles of depression, and the changes in liver-related parameters has been discussed. ConclusionsMultiple factors may modulate the postulated hepatoprotective properties of probiotics efficacy in patients with depression. Further studies with larger sample sizes, different probiotic strains, and longer intervention period are necessary to assess the real significance of probiotics for liver health in this population. ClinicalTrials.gov identifierNCT04756544.

Systemic Inflammatory Indices and Liver Dysfunction in Turner Syndrome Patients: A Retrospective Case-control Study.

Liver function abnormalities have been reported in patients with Turner syndrome (TS); however, the pathophysiological mechanisms have not been well elucidated. Low-grade inflammation has been associated with metabolic dysfunction-associated steatotic liver disease. We studied systemic inflammatory indices [aspartate transaminase to lymphocyte ratio index (ALRI), aspartate transaminase to platelet ratio index (APRI), gamma-glutamyl transferase to platelet ratio (GPR), neutrophil-lymphocyte-ratio (NLR), and platelet lymphocyte ratio and examined their associations with the hepatic abnormalities observed in these subjects. We performed a retrospective analysis of the medical records of 79 patients with TS (mean age 32.5 ± 9.2 SD years) who were treated at the University Hospital of Nancy. Using matched-pair analyses based on age and body mass index (BMI), we compared 66 patients with TS (25.6 ± 7.3 years; BMI 25.9 ± 6.3 kg/m2) to 66 healthy control participants (24.7 ± 6.8 years; BMI 26 ± 6.7 kg/m2). Liver function abnormalities were present in 57% of the patients with TS. The ALRI, APRI, GPR, and NLR were significantly greater in patients with TS who presented with liver dysfunction than in patients with TS who had normal liver function. According to the matched-pair analyses, the ALRI, APRI, and GPR were greater in patients with TS than in healthy control participants. Logistic regression revealed that a diagnosis of TS was significantly associated with ALRI, APRI, and GPR and liver dysfunction. Noninvasive inflammatory indices (ALRI, APRI, and GPR) might be a promising indicators of liver dysfunction in patients with TS. Future prospective studies are needed to confirm our findings and to explore the clinical significance and prognostic value of systemic inflammatory indices in Turner syndrome.

Risk factors for liver dysfunction and their clinical importance after gastric cancer surgery

Postoperative hepatobiliary enzyme abnormalities often present as postoperative liver dysfunction in patients with gastric cancer (GC). This study aimed to identify the risk factors for postoperative liver dysfunction and their clinical impact after GC surgery. We retrospectively analyzed the data of 124 patients with GC who underwent laparoscopic or robotic surgery at Kyoto Prefectural University of Medicine between 2017 and 2019. Twenty (16.1%) patients with GC developed postoperative liver dysfunction (Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 ≥ Grade 3). Univariate analyses identified robotic surgery as a risk factor for postoperative liver dysfunction (P = 0.005). There was no correlation between the postoperative liver dysfunction status and postoperative complications or postoperative hospital stays. Patients with postoperative liver dysfunction did not have significantly worse overall survival (P = 0.296) or recurrence-free survival (P = 0.565) than those without postoperative liver dysfunction. Robotic surgery is a risk factor for postoperative liver dysfunction; however, postoperative liver dysfunction does not affect short or long-term outcomes.

A Case of Type 1 Diabetes Mellitus with Diabetic Ketoacidosis Presenting with Transient Severe Fatty Liver and Subsequent Liver Dysfunction.

Patients often present with severe fatty liver (FL) due to insulin deficiency at the onset of diabetic ketoacidosis (DKA). On the other hand, glycogenic hepatopathy (GH) is a possible cause of liver dysfunction in patients with DKA. We herein report a case of type 1 diabetes mellitus with severe FL at the onset of DKA, who demonstrated subsequent marked liver dysfunction after achieving an improvement of FL. As liver dysfunction persisted even after the FL improved, GH was suspected to be the cause of liver dysfunction. FL and GH have different prognoses and should therefore be differentiated using imaging studies and biopsies.

Albumin‑bilirubin grade is an independent prognostic factor for small lung cell cancer

Albumin‑bilirubin grade is an independent prognostic factor for small lung cell cancer

Impact of preoperative bloodstream infection on outcomes of pediatric liver transplant recipients treated for acute liver failure.

Acute liver failure (ALF) is a component of multisystem organ failure that causes severe liver dysfunction in patients without underlying chronic liver disease. The patients with ALF are prone to have infections, including bacteremia. However, studies of the infectious impact for post liver transplantation (LT) in pediatric ALF are limited. We aimed to evaluate our current practice for pediatric LT cases of ALF with preoperative bacteremia. The records of all patients under 18 years old undergoing LT for ALF in our center from November 2005 to December 2021 were collected. They were divided into two groups: those with a preoperative bloodstream infection (BSI) and those without (NBSI). We compared the preoperative status and also reviewed the details of the BSI group. Intraoperative course and postoperative outcomes were also compared. There were 19 BSI patients and 66 NBSI patients. One BSI case was detected on the day of LT. This patient had no changes in vital signs and general condition. After evaluation and therapeutic intervention by pediatric infectious disease specialists, LT was performed on the same day. Five cases developed septic shock at the time of detection of BSI. All BSI patients were in stable condition on the operation day with proper interventions. There were no significant differences in mortality and hospital stay between both groups. LT might be able to be performed for pediatric ALF even with positive blood cultures. In addition, appropriate therapeutic intervention by specialists and patient's stable condition before LT are essential.

LIVER DYSFUNCTION IN PATIENTS WITH GOUT

LIVER DYSFUNCTION IN PATIENTS WITH GOUT

Clinical course of patients with hepatorenal tyrosinemia treated with nitisinone – a 10-year prospective cohort study

ntroduction: Untreated type 1 tyrosinemia, when manifesting in infancy, causes severe liver enlargement, or, later in the first year, damages the hepatic and renal tubular function, leading to developmental impairment. Nitisinone (NTBC) treatment has been able to control liver dysfunction in patients and the extrahepatic manifestations of HT1. The present study aimed to eval- uate the effect of nitisinone on the clinical course of patients with tyrosinemia type 1. Methods: This prospective 10-year cohort study focused on patients with type 1 tyrosinemia referred to Shiraz Pediatric Gastroenterology Clinic between March 20, 2010, and March 20, 2018. The clinical course of patients treated with nitisinone was evaluated. Statistical analysis was performed using SPSS 20 software. Results: This study included 145 patients. The results showed clear correlation between the severity of clinical complications of tyrosinemia and the proper use of the drug. The outcome among the patients taking the medications (95%) was observed to be good in 52.6%, while 12.6% of patients were on the waiting list, 32.6% had undergone transplantation, and 2.1% passed away. On the other hand, out of 54 patients who did not take NTBC, only 12% showed good outcomes, 6% were on the waiting list, 56% had undergone transplantation, and 26% died. Conclusion: The results of this study support the role of nitisinone in decreasing the complications of type 1 tyrosinemia and improving clinical symptoms, as well as reducing mortality in these patients. Keywords tyrosinemia type 1, nitisinone (NTBC), liver transplantation, tyrosine

Assessment of Liver Functions in Thalassaemia

Thalassaemias are a heterogenous group of genetic heritable disorders of haemoglobin synthesis, considered as the most common monogenic disorder in the world. This study was conducted to find out the role of iron overload- without concomitant viral hepatitis -as a cause of liver dysfunction in patients with β-thalassaemia major. One hundred six (106) patients with homozygous β-thalassaemia major and forty four (44) apparently healthy subjects were analyzed at the Thalassaemic Centre of Ibn Al-Atheer hospital in Mosul city in Iraq for the assessment of liver functions as reflected by the serum levels of bilirubin, AST, ALT and ALP and iron status as reflected by serum ferritin. The mean pretransfusional Hb was (87.33±13.84 g/L and 85.85±13.21 g/L) for thalassaemic males and females respectively. All thalassaemic patients showed elevated serum ferritin with a mean level of (3799.30±2343.68 ng/ml and 4100.61±1977.28 ng/ml) for thalassaemic males and females respectively. A significant increase in the serum levels of AST, ALT, ALP and bilirubin was found in thalassaemic patients with respect to control subjects. Serum ferritin showed a significant positive correlation with ALT in male and female patients. Hepatomegaly was found in 71.70% of the studied cases. A significant alteration in liver functions of thalassaemic patients shown by changes in biochemical markers and hepatomegaly, both with the close association between elevated ALT and iron overload, necessate re-evaluation of transfusion, Desferal doses and therapies other than blood transfusion.

Postoperative liver dysfunction is associated with poor long-term outcomes in patients with colorectal cancer: a retrospective cohort study

BackgroundPostoperative hepatobiliary enzyme abnormalities often present as postoperative liver dysfunction in patients with colorectal cancer. This study aimed to clarify the risk factors of postoperative liver dysfunction and its prognostic impact following colorectal cancer surgery.MethodsWe retrospectively analyzed data from 360 consecutive patients who underwent radical resection for Stage I–IV colorectal cancer between 2015 and 2019. A subset of 249 patients with Stage III colorectal cancer were examined to assess the prognostic impact of liver dysfunction.ResultsForty-eight (13.3%) colorectal cancer patients (Stages I–IV) developed postoperative liver dysfunction (Common Terminology Criteria for Adverse Events version 5.0 CTCAE v5.0 ≥ Grade 2). Univariate and multivariate analyses identified the liver-to-spleen ratio on preoperative plain computed tomography (L/S ratio; P = 0.002, Odds ratio 2.66) as an independent risk factor for liver dysfunction. Patients with postoperative liver dysfunction showed significantly poorer disease-free survival than patients without liver dysfunction (P < 0.001). Univariate and multivariate analyses using Cox’s proportional hazards model revealed that postoperative liver dysfunction independently was a poor prognostic factor (P = 0.001, Hazard ratio 2.75, 95% CI: 1.54–4.73).ConclusionsPostoperative liver dysfunction was associated with poor long-term outcomes in patients with Stage III colorectal cancer. A low liver-to-spleen ratio on preoperative plain computed tomography images was an independent risk factor of postoperative liver dysfunction.

Effects of sodium glucose cotransporter 2 inhibitors and pioglitazone on FIB-4 index in metabolic-associated fatty liver disease.

The antidiabetic drugs sodium glucose cotransporter 2 inhibitors (SGLT2is) and thiazolidinediones have beneficial effects on the liver dysfunction of patients with nonalcoholic fatty liver disease and type 2 diabetes mellitus (T2DM). We aimed to determine the efficacy of these drugs for the treatment of liver disease in patients with metabolic dysfunction-associated fatty liver disease (MAFLD) and T2DM. We undertook a retrospective study of 568 patients with MAFLD and T2DM. Of these, 210 were treating their T2DM with SGLT2is (n=95), 86 with pioglitazone (PIO), and 29 with both. The primary outcome was the change in Fibrosis-4 (FIB-4) index between baseline and 96weeks. At 96weeks, the mean FIB-4 index had significantly decreased (from 1.79±1.10-1.56±0.75) in the SGLT2i group, but not in the PIO group. The aspartate aminotransferase to platelet ratio index, serum aspartate and alanine aminotransferase (ALT), hemoglobin A1c, and fasting blood sugar significantly decreased in both groups (ALT: SGLT2i group, -17±3IU/L; PIO group, -14±3IU/L). The bodyweight of the SGLT2i group decreased, but that of the PIO group increased (-3.2kg and +1.7kg, respectively). When the participants were allocated to two groups according to their baseline ALT (>30IU/L), FIB-4 index significantly decreased in both groups. In patients taking pioglitazone, the addition of SGLT2i improved liver enzymes but not FIB-4 index for 96weeks. Treatment with SGLT2i causes a larger improvement in FIB-4 index than PIO in patients with MAFLD over 96weeks.

The role of omega-3 polyunsaturated fatty acids in the intensive care unit.

This review provides an update on the actions of omega-3 polyunsaturated fatty acids (PUFAs) and presents the most recent findings from trials in patients in the intensive care unit (ICU) setting including relevant meta-analyses. Many specialized pro-resolving mediators (SPMs) are produced from bioactive omega-3 PUFAs and may explain many of the beneficial effects of omega-3 PUFAs, although other mechanisms of action of omega-3 PUFAs are being uncovered. SPMs resolve inflammation, promote healing and support antiinfection activities of the immune system. Since publication of the ESPEN guidelines, numerous studies further support the use of omega-3 PUFAs. Recent meta-analyses favor the inclusion of omega-3 PUFAs in nutrition support of patients with acute respiratory distress syndrome or sepsis. Recent trials indicate that omega-3 PUFAs may protect against delirium and liver dysfunction in patients in the ICU, although effects on muscle loss are unclear and require further investigation. Critical illness may alter omega-3 PUFA turnover. There has been significant discussion about the potential for omega-3 PUFAs and SPMs in treatment of coronavirus disease 2019. Evidence for benefits of omega-3 PUFAs in the ICU setting has strengthened through new trials and meta-analyses. Nevertheless, better quality trials are still needed. SPMs may explain many of the benefits of omega-3 PUFAs.

Liver Dysfunction in Hyperemesis Gravidarum

Aim: To determine the frequency of liver dysfunction in patients with hyperemesis gravidarum. Study design: It was a retrospective cross sectional study. Place and duration: This study was done in the gastroenterology department of Timergara Teaching Hospital over a period of 1 year i.e., from September 2021 to August 2022. Methods: 140 pregnant women admitted with diagnosis of hyperemesis gravidarum were included in this study after excluding liver disease. Data was collected from case files from the department of medical records. SPSS version 25 was used to analyze the data. Results: Liver dysfunction was seen in 55.2% of patients with hyperemesis gravidarum. The mean age of patients with hyperemesis gravidarum was found to be 24.4±5.35 years and most cases were found to be primigravida i.e., 72.8%. Mean gestational age was found to be 9.2± 1.9 weeks. No significant difference in liver dysfunction was seen in relation to BMI. Conclusion: Abnormal liver function tests is a common finding in cases of hyperemesis gravidarum which recover completely when resolution of hyperemesis occurs and needs no treatment. Key words: Hyperemesis gravidarum, nausea and vomiting of pregnancy, liver dysfunction, liver function tests. ALT, AST.

MiR-761-hepcidin/Gpx4 pathway contribute to unexplained liver dysfunction in polycystic ovary syndrome by regulating liver iron overload and ferroptosis

Aims: To investigate the underling mechanisms of liver dysfunction in patients with polycystic ovary syndrome (PCOS).Materials and methods: PCOS patients were enrolled according to the Amsterdam criteria while PCOS animal model was established by dihydrotestosterone (DHEA) sustained release tablet implantation on its neck. Further liver damage and iron overload were detected by HE and Prussian blue staining. The liver related enzymes, mRNA and protein levels of hepcidin and GPX4 were tested by ELISA, qRT-PCR and Western blot. RNA interference and miR-761 transfection were routinely performed while the regulation of miR-761 on hepcidin and GPX4 was confirmed by luciferase reporter gene analysis.Results: We found that a part of PCOS patients and animal model had unexplained liver damage, which is independent of nonalcoholic fatty liver disease (NAFLD) and accompanied by increased ferrum (Fe) deposition. Besides, the expression of hepcidin and GPX4 that is important effector proteins for ferroptosis was down regulated in liver, showing the importance of iron metabolism in this unexplained liver damage. Based on the miR-761-hepcidin/GPX4 axis, we systematically studied the effects of miR-761 on ferroptosis and Fe deposition, which further influence the phenotype and liver function of PCOS model. From both in vivo and in vitro levels, changes in PCOS disease phenotype and ferroptosis were observed through hierarchical antagonism or overexpression of miR-761, hepcidin and GPX4.Conclusions: our results provide a novel explanation for unexplained liver damage in PCOS and a potential therapeutic target.

Liver Dysfunction in Patients with Systemic Lupus Erythematosus

Patients with systemic lupus erythematosus (SLE) frequently have elevated serum levels of liver enzymes. Hepatic abnormalities are suspected to be caused by hepatotoxic drugs, viral hepatitis, autoimmune hepatitis, fatty liver, and disease-related hepatitis. In the presenting cases, a drug-induced liver injury was diagnosed, which quickly returned to normal after the suspected causative medication was discontinued. Elevated liver enzymes are a major concern in SLE patients and should be thoroughly investigated.

Safety and efficacy of switching to pemafibrate from bezafibrate in patients with chronic liver disease.

Although fibrates were developed as lipid-lowering drugs, their efficacy against liver dysfunction in patients with cholestatic liver diseases, such as primary biliary cholangitis, primary sclerosing cholangitis, and fatty liver disease, has also been reported. Although fibrates act on some peroxisome proliferator-activated receptors (PPARs), pemafibrate is a novel selective PPAR-α modulator. The present study aimed to evaluate the safety and efficacy of switching from bezafibrate to pemafibrate in patients with chronic liver disease. We analyzed 58 patients with chronic liver disease who switched from bezafibrate to pemafibrate because of minor adverse effects and/or incomplete response. This study included 41 patients with cholestatic liver disease and 17 patients with non-alcoholic fatty liver disease. Reasons for switching to pemafibrate were renal function decline in 31 patients, hemoglobin decline in 17 patients, creatine kinase (CK) elevation in 11 patients, incomplete response of liver dysfunction in 39 patients, and incomplete response of hyperlipidemia in 13 patients. After 3months, although no significant change in CK was seen, hemoglobin and estimated glomerular filtration rate were significantly increased, and creatinine was significantly decreased. Significant decreases in hepatobiliary enzymes were seen in patients with cholestatic liver diseases, but not in patients with non-alcoholic fatty liver disease. No significant changes in serum lipids were observed. No patients discontinued pemafibrate due to adverse events. Switching to pemafibrate could improve adverse effects due to bezafibrate, and appeared effective against liver dysfunction in cholestatic liver disease patients with incomplete response to bezafibrate.

A prediction model for COVID-19 liver dysfunction in patients with normal hepatic biochemical parameters.

Coronavirus disease 2019 (COVID-19) patients with liver dysfunction (LD) have a higher chance of developing severe and critical disease. The routine hepatic biochemical parameters ALT, AST, GGT, and TBIL have limitations in reflecting COVID-19-related LD. In this study, we performed proteomic analysis on 397 serum samples from 98 COVID-19 patients to identify new biomarkers for LD. We then established 19 simple machine learning models using proteomic measurements and clinical variables to predict LD in a development cohort of 74 COVID-19 patients with normal hepatic biochemical parameters. The model based on the biomarker ANGL3 and sex (AS) exhibited the best discrimination (time-dependent AUCs: 0.60-0.80), calibration, and net benefit in the development cohort, and the accuracy of this model was 69.0-73.8% in an independent cohort. The AS model exhibits great potential in supporting optimization of therapeutic strategies for COVID-19 patients with a high risk of LD. This model is publicly available at https://xixihospital-liufang.shinyapps.io/DynNomapp/.

THE ACTIVITY OF XANTHINE OXIDASE IN PLASMA IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: THE RELATIONSHIP BETWEEN HYPERURICEMIA, INSULIN RESISTANCE, AND LIVER DYSFUNCTION

We aimed to investigate the clinical implication of plasma xanthine oxidase (XO) activity in patients with type 2 diabetes mellitus (DM). Materials and methods. 127 patients were examined for type 2 DM (72 female and 55 male). Serum biochemical variables include aspartate aminotransferase (AST), alanine aminotransferase (ALT), fasting (FPG) and postprandial (PPG) plasma glucose, glycohemoglobin A1c (HbA1c), total cholesterol, triglyceride, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, creatinine (Cre) and serum urine acid (SUA) was measured with a conventional automated analyzer. The level of fasting insulin (IRI) was determined by the immuno-chemiluminescent method. Homeostasis model assessment of insulin resistance (IR) (HOMA-IR) index was calculated by the formula: HOMA-IR=fasting insulin (μmol/L)×FPG(mmol/L)/22.5. The plasma XO activity was determined by a photometric method. The rate of glomerular filtration (eGFR) was calculated according to CKD-EPI formulas. All statistical analyses were performed using STATISTICA software version 10.0. Results. The plasma lnXO activity was correlated with IRI (rs=0.52; P&lt;0.001) and HOMA‐IR (rs=0.51; P&lt;0.002). In addition, the plasma lnXO activity was correlated with BMI (rs=0.40; P&lt;0.001). In contrast, plasma lnXO activity was not correlated with age (rs=-0.07; P=0.61), HbA1c (rs=-0.11; P=0.41), FPG (rs=-0,4; P=0.74) and PPG (rs=-0.09; P=0.57). lnXO activity and indices of liver dysfunction or parameters closely related to SUA level in patients with type 2 DM: lnALT (rs=0.73; P&lt;0.001), lnAST (rs=0.69; P&lt;0.001), ALT/AST (rs=0.85; P&lt;0.001). The plasma lnXO activity was correlated with Cre (rs=-0.15; P=0.46) and eGFR (rs=0.13; P=0.34). In a series of multiple regression analyses, plasma lnXO activity was used as a dependent variable, and age, BMI, HbA1c, SUA, eGFR, lnAST, lnALT, IRI, and HOMA-IR as explanatory variables were carried out. When used as explanatory variables, the value of lnALT (Model 1) was an independent strong factor for determining plasma XO activity (R2=95.3%; P&lt;0.00001). When used as explanatory variables, the value of lnALT (Model 2) was also an independent strong factor for determining the plasma XO activity (R2=97.2%; P&lt;0.00001). We aimed to investigate the clinical implication of plasma xanthine oxidase (XO) activity in patients with type 2 diabetes mellitus (DM). Materials and methods. 127 patients were examined for type 2 DM (72 female and 55 male). Serum biochemical variables include aspartate aminotransferase (AST), alanine aminotransferase (ALT), fasting (FPG) and postprandial (PPG) plasma glucose, glycohemoglobin A1c (HbA1c), total cholesterol, triglyceride, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, creatinine (Cre) and serum urine acid (SUA) was measured with a conventional automated analyzer. The level of fasting insulin (IRI) was determined by the immuno-chemiluminescent method. Homeostasis model assessment of insulin resistance (IR) (HOMA-IR) index was calculated by the formula: HOMA-IR=fasting insulin (μmol/L)×FPG(mmol/L)/22.5. The plasma XO activity was determined by a photometric method. The rate of glomerular filtration (eGFR) was calculated according to CKD-EPI formulas. All statistical analyses were performed using STATISTICA software version 10.0. Results. The plasma lnXO activity was correlated with IRI (rs=0.52; P&lt;0.001) and HOMA‐IR (rs=0.51; P&lt;0.002). In addition, the plasma lnXO activity was correlated with BMI (rs=0.40; P&lt;0.001). In contrast, plasma lnXO activity was not correlated with age (rs=-0.07; P=0.61), HbA1c (rs=-0.11; P=0.41), FPG (rs=-0,4; P=0.74) and PPG (rs=-0.09; P=0.57). lnXO activity and indices of liver dysfunction or parameters closely related to SUA level in patients with type 2 DM: lnALT (rs=0.73; P&lt;0.001), lnAST (rs=0.69; P&lt;0.001), ALT/AST (rs=0.85; P&lt;0.001). The plasma lnXO activity was correlated with Cre (rs=-0.15; P=0.46) and eGFR (rs=0.13; P=0.34). In a series of multiple regression analyses, plasma lnXO activity was used as a dependent variable, and age, BMI, HbA1c, SUA, eGFR, lnAST, lnALT, IRI, and HOMA-IR as explanatory variables were carried out. When used as explanatory variables, the value of lnALT (Model 1) was an independent strong factor for determining plasma XO activity (R2=95.3%; P&lt;0.00001). When used as explanatory variables, the value of lnALT (Model 2) was also an independent strong factor for determining the plasma XO activity (R2=97.2%; P&lt;0.00001). When used as explanatory variables without parameters for liver functions, the value of HOMA‐IR was an independent factor for determining the plasma XO activity (Model 3) (R2=97.3%; P&lt;0.00001). These data suggest that the values of ALT and HOMA-IR, a clinical marker for hepatic IR, might be independent factors for directly influencing the plasma XO activity in patients with type 2 DM. Conclusions. The value of plasma xanthine oxidase activity was significantly correlated with indices of insulin resistance and liver dysfunction in patients with type 2 diabetes mellitus. The values of alanine aminotransferase and homeostatic model assessment for insulin resistance (HOMA-IR), a clinical marker for hepatic insulin resistance, might be independent factors for directly influencing the plasma xanthine oxidase activity in patients with type 2 diabetes mellitus.

Letter to the editor: Successful treatment of multidrug-resistant hepatis C after >12 months of continuous therapy with direct-acting antivirals.

To the editor, We read the study by Trudeau et al., which presented a patient case with a history of multiple failed treatments who ultimately achieved sustained virological response (SVR) after an extended course of direct‐acting antiviral (DAA) regimens.1 However, we have some concerns about this conclusion. First, patients with hepatitis C virus (HCV) and cirrhosis may be subject to more medical and lifestyle monitoring after initial diagnosis and are vulnerable to many confounding factors. Recent study showed that common drug–drug interactions exist in glecaprevir–pibrentasvir (GLE‐PIB) or sofosbuvir–velpatasvir (SOF‐VEL) such as proton‐pump inhibitors, histamine‐2 receptor antagonists, and lipid‐lowering agents, which will affect the efficacy of GLE‐PIB or SOF‐VEL.2 In this study, no clear statement about the medical monitoring was shown. Moreover, interferon‐based combination regimes for patients with liver cirrhosis may have a higher risk of treatment‐associated serious adverse events.3 This study just regarded SVR as an important treatment outcome of the patient with HCV. However, the safety evaluation and complication after extended DAA therapies were not mentioned in the study. Secondly, the volatile regimens through the treatment process makes readers confused, and no evidence supports it. For example, at week 4 posttreatment initiation, the patient had an undetectable viral RNA level and remained negative for the duration of treatment, but the therapy was immediately changed to SOF‐VEL at week 12 for no powerful reason. Moreover, the previously “failed” treatment regime have many common drugs with the current treatment regime, which cannot exclude the possibly subsequent and positive impact of previous treatments on patients. Thirdly, the patient contracted coronavirus disease 19 (COVID‐19) during this course of therapy, which severely influences the antiviral and survival outcome. A multicenter cohort study showed that there is a close association between chronic HCV and COVID‐19.4 The mechanism of liver dysfunction in patients with COVID‐19 includes direct cytopathic effects, immune reaction and cytokine storm‐related multiorgan failure, hypoxia‐reperfusion dysfunction, and drug‐induced liver injury because of the various drugs used for COVID‐19 treatment.5 The treatment outcomes of the patient with HCV may be affected by the influence of COVID‐19 or the cotreatment of COVID‐19. In conclusion, whether extending treatment necessary to successfully induce a durable response among patients with previous treatment failures remains unclear.