Unexpectedly Rapid Onset of Severe Sarcopenia in an Elderly Diabetic Man following SGLT2i Administration: A Case Report.

Sarcopenia is characterized by the progressive loss of muscle mass, strength, and function and poses a significant health challenge among people with diabetes. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are the backbone of type 2 diabetes treatment. The interplay between SGLT2is and sarcopenia is an area of active research with inconclusive results. This article presents an unexpectedly rapid weight reduction, along with physical performance deterioration, in an elderly patient with type 2 diabetes, which led to treatment discontinuation. A bioelectrical impedance analysis confirmed severe sarcopenia development. Until more data are available, sarcopenia and body composition screening and monitoring may be warranted whenever SGLT2is are prescribed.

De Novo Metabolic Syndrome 1 Year after Liver Transplantation and Its Association with Mid- and Long-Term Morbidity and Mortality in Liver Recipients.

Background: Metabolic syndrome (MS) constitutes an important source of cardiovascular- and cancer-related morbidity and mortality in the general population. Limited information is available on whether these findings can be directly extrapolated to liver recipients. This study aimed to investigate the impact of post-transplant MS present 1 year after liver transplantation on survival rates, risk of major cardiovascular events (CVEs), and de novo malignancies. Methods: Adult deceased-liver-donor recipients who underwent transplantation in our centre between 2010 and 2019 and reached at least 1 year of post-transplantation follow-up were eligible. Results: Of 259 enrolled patients, 20% developed post-transplant MS 1 year after the procedure. The presence of post-transplant MS at 1 year did not affect all-cause mortality (p = 0.144) and risk of de novo malignancies (p = 0.198) in liver recipients. However, it was associated with an overall and time-dependent increase in the risk of major CVEs (p < 0.001). MASH aetiology of liver disease, pre-existing major CVEs, and development of de novo malignancy were independent predictors of all-cause mortality in liver recipients. Conclusions: New onset MS exerts a wide-ranging effect on the post-transplant prognosis of liver recipients. Obtaining optimal control over all modifiable metabolic risk factors is central to improving long-term outcomes in this population.

MASH Continues as a Significant Burden on Metabolic Health of Liver Recipients.

BACKGROUND: Metabolic complications are a recognized health concern in liver transplant recipients that result in inferior patient-reported outcomes. Patients with MASH are known to be disproportionately affected by metabolic diseases compared to other indications for transplantation. PURPOSE: The aim of this study was to investigate the incidence of metabolic abnormalities in liver recipients with specific focus on differences between patients transplanted for MASH and non-MASH-causes. PATIENTS AND METHODS: An observational, monocentric, and retrospective analysis was performed. Patients who received a cadaveric-donor-liver transplant between 2010 and 2019 were eligible. RESULTS: 282 patients were enrolled with a median age of 52 years (66.7% males). Metabolic dysfunction-associated steatohepatitis (MASH) led to liver transplant in 8.2% of cases. De-novo metabolic syndrome was diagnosed in 36% of the study population. Patients that underwent transplant owing to MASH showed significantly higher incidence of metabolic complications in both pre- and post-transplant period. Considerable differences were noted in the pattern of weight gain between patients transplanted for MASH and non-MASH patients. The MASH etiology (OR: 5.5; 95% CI: 1.624-22.868; P = .010), higher BMI at 1-year post-transplant (OR: 1.321; 95% CI: 1.214-1.449; P = <.001), and older age at transplant (OR: 1.038; 95% CI: 1.006-1.074; P = .022) were independently associated with new-onset metabolic syndrome in liver recipients. CONCLUSION: Metabolic complications were prevalent in liver recipients. Liver recipients with underlying MASH significantly surpassed patients transplanted for other indications in terms of metabolic complications incidence and demonstrated an unfavorable trajectory of weight gain post-transplant.

Evaluation of Long-Term Outcomes of Direct Acting Antiviral Agents in Chronic Kidney Disease Subjects: A Single Center Cohort Study.

BACKGROUND: The chronic kidney disease (CKD) population, including kidney transplant recipients (KTRs) and subjects on renal replacement therapy, is particularly vulnerable to unfavorable outcomes from chronic hepatitis C (CHC). Currently, there are oral direct-acting antiviral agents (DAAs) available to eradicate the virus with favorable short-term outcomes; however, their long-term effects are lacking. The aim of the study is to assess the long-term efficacy and safety of DAA therapy in the CKD population. METHODS: An observational, cohort single-center study was performed. Fifty-nine CHC subjects with CKD, treated with DAAs between 2016 and 2018, were enrolled in the study. Safety and efficacy profiles were assessed, including sustained virologic response (SVR), occult hepatitis C infection (OCI) incidence, and liver fibrosis. RESULTS: SVR was achieved in 96% of cases (n = 57). OCI was diagnosed only in one subject following SVR. Significant liver stiffness regression was observed 4 years after SVR compared to baseline values (Mdn = 6.1 kPa, IQR = 3.75 kPa; 4.9 kPa, IQR = 2.9 kPa), p < 0.001. The most common adverse events were anemia, weakness, and urinary tract infection. CONCLUSION: DAAs provide a safe and effective cure for CHC in both CKD patients and KTRs with a favorable safety profile in the long-term follow-up.

Are We on the Right Track for HCV Micro-Elimination? HCV Management Practices in Dialysis Centers in Poland-A National Cross-Sectional Survey.

Chronic hepatitis C (CHC) is prevalent in the hemodialysis-dependent population. Currently, all patients with CHC should be considered for treatment; however, many hemodialysis-dependent patients are still left untreated. Following HCV cure, accurate surveillance is mandatory to reduce liver-related mortality and prevent reinfection. We aimed to establish HCV management practices and barriers to HCV elimination in dialysis centers in Poland. Polish dialysis centers were surveyed via email. The HCV management strategies were investigated. Representatives of 112 dialysis centers responded, representing 43.1% of all dialysis centers in Poland and 43.4% of hemodialysis-dependent patients' volume. Most respondents were Heads of hemodialysis centers and board-certified nephrologists. The study demonstrated that in the vast majority of hemodialysis centers (91.6%), subjects are considered for antiviral treatment (AVT); however, many obstacles preventing patients from being prescribed AVT were identified; patients' reluctance to undergo AVT was most reported (60%). The majority of dialysis units neither evaluate patients with CHC for liver fibrosis (60.4%) nor screen them for hepatocellular carcinoma (53.5%). In conclusion, the presented study demonstrates that HCV management practices across Polish dialysis centers vary substantially. There is a need to optimize and streamline the HCV management infrastructure in the hemodialysis population in Poland.

Real-life comparison of efficacy and safety profiles of two prolonged-release tacrolimus formulations in de novo kidney transplant recipients: 24 months of follow-up.

INTRODUCTION: Calcineurin inhibitors constitute a cornerstone of immunosuppressive therapy in kidney transplant recipients. There are two main formulations of tacrolimus (Tac) which exhibit a prolonged-release mode of action: Advagraf® (MR-4) and Envarsus® (LCPT). However, they are not bioequivalent. Data comparing both once-daily prolonged-release formulations of Tac are insufficient. OBJECTIVE: The aim of the study was to compare safety and efficacy profiles of once-daily LCPT and MR-4 formulations of tacrolimus in adult kidney transplant recipients. PATIENTS AND METHODS: An observational, cohort single-center study was performed. One hundred fifteen kidney transplant recipients transplanted between 2016 and 2019 were enrolled to the study (59 vs 56, Envarsus® vs Advagraf®, respectively). Safety and efficacy profiles were assessed. RESULTS: Patient and graft survival at 12 and 24 months did not differ between the groups. There were no significant differences in serum creatinine at any timepoint. C/D ratio in the LCPT group was significantly higher at 12 and 24 months. Sepsis occurrence was more frequent in MR-4 group at 12 months. CONCLUSION: Both prolonged-release formulations of tacrolimus are safe and effective in immunosuppressive therapy in kidney transplant recipients.

Molnupiravir Outpatient Treatment for Adults with COVID-19 in a Real-World Setting-A Single Center Experience.

BACKGROUND: Molnupiravir is approved for the treatment of adult patients with mild to moderate COVID-19. The main goal of the treatment is to reduce hospitalization and mortality rate. This study aimed at the all-cause hospitalization and all-cause death assessment in patients at high risk of severe COVID-19 treated with molnupiravir. METHODS: This was a prospective, observational single center study. Non-hospitalized patients with SARS-CoV-2 infection, COVID-19 symptoms with the onset of up to 5 days, and at high risk of severe COVID-19 illness received molnupiravir based on attending physician decisions. RESULTS: In total, 107 patients were enrolled. Adverse events were reported in 28.0% of patients, with nausea and abdominal pain being the most commonly observed. No treatment-emergent AEs resulted in therapy discontinuation. Overall, 15 patients required hospitalization. During the observation, 2.8% (n = 3) of patients subsequently died. All deaths were considered to be related to COVID-19 complications. Age over 65 years, heart failure, and ischemic heart disease showed a significant correlation with the severe course of COVID-19. CONCLUSION: Molnupiravir may be perceived as an alternative treatment for patients with immunosuppression and advanced chronic kidney disease. Nevertheless, further studies are required to conclusively establish a role for molnupiravir in future COVID-19 treatment recommendations.

Utilization of HCV viremic donors in kidney transplantation: a chance or a threat?

Kidney transplantation is the treatment of choice in end-stage renal disease. The main issue which does not allow to utilize it fully is the number of organs available for transplant. Introduction of highly effective oral direct-acting antivirals (DAAs) to the treatment of chronic hepatitis C virus infection (HCV) enabled transplantation of HCV viremic organs to naive recipients. Despite an increasing number of reports on the satisfying effects of using HCV viremic organs, including kidneys, they are more often rejected than those from HCV negative donors. The main reason is the presence of HCV viremia and not the quality of the organ. The current state of knowledge points to the fact that a kidney transplant from an HCV nucleic acid testing positive (NAT+) donor to naive recipients is an effective and safe solution to the problem of the insufficient number of organs available for transplantation. It does not, however, allow to draw conclusions as to the long-term consequence of such an approach. This review analyzes the possibilities and limitations of the usage of HCV NAT + donor organs. Abbreviations: DAA: direct-acting antivirals; HCV: hepatitis C virus; NAT: nucleic acid testing; OPTN: Organ Procurement and Transplantation Network; KDIGO: Kidney Disease: Improving Global Outcomes; Ab: antigen; eGFR: estimated glomerular filtration rate; D: donor; R: recipient; CMV: cytomegalovirus; HBV: hepatitis B virus; UNOS: United Network for Organ Sharing; PHS: Public Health Service; EBR/GZR: elbasvir/grazoprevir; SVR: sustained virologic response; RAS: resistance-associated substitutions; SOF: soforbuvir; GLE/PIB: glecaprevir/pibrentasvir; ACR: acute cellular rejection; AR: acute rejection; DSA: donor-specific antibodies; KTR: kidney transplant recipients; AASLD: American Association for the Study of Liver Disease; IDSA: Infectious Diseases Society of America; PPI: proton pump inhibitors; CKD: chronic kidney disease; GN: glomerulonephritis; KAS: The Kidney Allocation system.

Multidirectional facets of obesity management in the metabolic syndrome population after liver transplantation.

The obesity pandemic has resulted in an increasing demand for liver transplantation and has significantly altered the profile of liver transplant candidates in addition to affecting posttransplantation outcomes. In this review, we discuss a broad range of clinical approaches that warrant attention to provide comprehensive and patient-centred medical care to liver transplant recipients, and to be prepared to confront the rapidly changing clinical challenges and ensuing dilemmas. Adipose tissue is a complex and metabolically active organ. Visceral fat deposition is a key predictor of overall obesity-related morbidity and mortality. Limited pharmacological options are available for the treatment of obesity in the liver transplant population. Bariatric surgery may be an alternative in eligible patients. The rapidly increasing prevalence of nonalcoholic fatty liver disease (NAFLD) is a global concern; NAFLD affects both pre- and posttransplantation outcomes. Numerous studies have investigated pharmacological and nonpharmacological management of NAFLD and some of these have shown promising results. Liver transplant recipients are constantly exposed to numerous factors that result in intestinal microbiota alterations, which were linked to the development of obesity, diabetes type 2, metabolic syndrome (MS), NAFLD, and hepatocellular cancer. Microbiota modifications with probiotics and prebiotics bring gratifying results in the management of metabolic complications. Fecal microbiota transplantation (FMT) is successfully performed in many medical indications. However, the safety and efficacy profiles of FMT in immunocompromised patients remain unclear. Obesity together with immunosuppressive treatment, may affect the pharmacokinetic and/or pharmacodynamic properties of coadministered medications. Individualized immunosuppressive regimens are recommended following liver transplantation to address possible metabolic concerns. Effective and comprehensive management of metabolic complications is shown to yield multiple beneficial results in the liver transplant population and may bring gratifying results in improving long-term survival rates.