Can the pan-immune-inflammation value predict gram negative bloodstream infection-related 30-day mortality in solid organ transplant patients?

BACKGROUND: The recently used pan-immune-inflammation value (PIV) has not been adequately studied as a predictive marker for mortality in immunosuppressed patients. The aim of this study was to evaluate the usefulness of baseline PIV level as a predictor of 30-day mortality in solid organ transplant (SOT) recipients with gram negative bloodstream infections (GN-BSI). METHODS: This retrospective, cross-sectional study was conducted between January 1, 2019, and December 31, 2022, in 1104 SOT recipients. During the study period, 118 GN-BSI were recorded in 113 patients. Clinical, epidemiological, and laboratory data were collected, and mortality rates (30-day and all-cause) were recorded. RESULTS: The 113 recipients had a median age of 50 years [interquartile range (IQR) 37.5-61.5 years] with a male predominance (n = 72, 63.7%). The three most common microorganisms were as follows: 46 isolates (38.9%) of Escherichia coli, 41 (34.7%) of Klebsiella pneumoniae, and 12 (10.2%) of Acinetobacter baumannii. In 44.9% and 35.6% of the isolates, production of extended-spectrum beta-lactamases and carbapenem resistance were detected, respectively. The incidence of carbapenem-resistant GN-BSI was higher in liver recipients than in renal recipients (n = 27, 69.2% vs n = 13, 17.6%, p < 0.001). All-cause and 30-day mortality rates after GN-BSI were 26.5% (n = 30), and 16.8% (n = 19), respectively. In the group with GN-BSI-related 30-day mortality, the median PIV level was significantly lower (327.3, IQR 64.8-795.4 vs. 1049.6, IQR 338.6-2177.1; p = 0.002). The binary logistic regression analysis identified low PIV level [hazard ratio (HR) = 0.93, 95% confidence interval (CI) 0.86-0.99; p = 0.04], and increased age (HR = 1.05, 95% CI 1.01-1.09; p = 0.002) as factors associated with 30-day mortality. The receiver operating characteristic analysis revealed that PIV could determine the GN-BSI-related 30-day mortality with area under curve (AUC): 0.723, 95% CI 0.597-0.848, p = 0.0005. CONCLUSIONS: PIV is a simple and inexpensive biomarker that can be used to estimate mortality in immunosuppressed patients, but the results need to be interpreted carefully.

Changing trends in the etiology of liver transplantation in Turkiye: A multicenter study.

Background and Aim: This study aimed to identify the indications for liver transplantation (LT) based on underlying etiology and to characterize the patients who underwent LT. Materials and Methods: We conducted a multicenter cross-sectional observational study across 11 tertiary centers in Turkiye from 2010 to 2020. The study included 5,080 adult patients. Results: The mean age of patients was 50.3±15.2 years, with a predominance of female patients (70%). Chronic viral hepatitis (46%) was the leading etiological factor, with Hepatitis B virus infection at 35%, followed by cryptogenic cirrhosis (24%), Hepatitis C virus infection (8%), and alcohol-related liver disease (ALD) (6%). Post-2015, there was a significant increase in both the number of liver transplants and the proportion of living donor liver transplants (p<0.001). A comparative analysis of patient characteristics before and after 2015 showed a significant decline in viral hepatitis-related LT (p<0.001), whereas fatty liver disease-related LT significantly increased (p<0.001). Conclusion: Chronic viral hepatitis continues to be the primary indication for LT in Turkiye. However, the proportions of non-alcoholic fatty liver disease (NAFLD) and ALD-related LT have seen an upward trend over the years.

Evaluation of Overall Survival and Disease-Free Survival in Patients Receiving Liver Transplantation for Hepatocellular Carcinoma and Comparison of Living Versus Deceased Donor Liver Transplants: Results of 15 Years of Experience.

OBJECTIVE: Research comparing patients who received liver transplantation (LT) for hepatocellular carcinoma (HCC) has produced varying outcomes regarding survival and disease-free survival. The objective of this study is to determine the factors that influence the disease-free and overall survivals of those who have undergone LT for HCC and to compare the outcomes of living versus deceased donor liver transplants. MATERIALS AND METHODS: We retrospectively analyzed data on patients aged 18 and above who received LT for HCC from 2006 to 2022. Patients with a follow-up period of less than 6 months and who did not meet the University of California San Francisco criteria were excluded. The data from 58 patients were analyzed. We split the patients into living donor liver transplantation (LDLT) (group 1) and deceased donor liver transplantation (DDLT) (group 2). RESULTS: The mean age was 56 ± 8.1 years. There were 49 males and 9 females. The median of the alphafetoprotein (AFP) level and model for end-stage liver disease score was 10.1 ng/mL and 11, respectively. The 1-, 3-, 5-, and 10-year disease-free survival rates were 86%, 76.5%, 76.5%, and 76.5%, respectively. The survival rates for the same periods were 94.8%, 74.9%, 70.6%, and 67.4%. The receiver operating characteristic analysis revealed that AFP > 31.8 ng/mL and a total tumor size >3.85 cm raise the likelihood of HCC recurrence post-LT. CONCLUSION: Based on the current literature, the overall survival and disease-free survival rates are influenced by factors such as AFP value, total tumor number, and total tumor diameter. In our study, the AFP value and total tumor size had an impact on the recurrence of HCC, and the survival rates were comparable on LDLT and DDLT.

The efficacy and tolerability of glecaprevir/pibrentasvir treatment in a real-world chronic hepatitis C patients cohort.

Background and Aim: The aims of the present study were to evaluate the real-life efficacy and tolerability of glecaprevir (GLE)/pibrentasvir (PIB) in the treatment of patients with chronic hepatitis C (CHC). Materials and Methods: Between May 2019 and May 2022, 686 patients with CHC, treated with GLE/PIB combination from 21 participating centers in Turkiye, were enrolled in the study. Results: All patients were Caucasian, and their median age was 56 years. At the start of GLE/PIB treatment, the median serum Hepatitis C virus RNA and serum alanine amino transaminase (ALT) levels were 6.74 log10 IU/mL and 47 U/L, respectively. Fifty-three percent of the patients were infected with genotype 1b, followed by genotype 3 (17%). Diabetes was the more common concomitant disease. The sustained virological response (SVR12) was 91.4% with intent-to-treat analysis and 98.5% with per protocol analysis. The SVR12 rates were statistically significant differences between the patients who were i.v. drug users and non-user (88.0% vs. 98.8%, p=0.025). From the baseline to SVR12, the serum ALT levels and Model for End-Stage Liver Disease score were significantly improved (p<0.001 and p=0.014, respectively). No severe adverse effect was observed. Conclusion: GLE/PIB is an effective and tolerable treatment in patients with CHC.

Correlation of hepatitis B surface antigen expression with clinicopathological and biochemical parameters in liver biopsies: A comprehensive study.

BACKGROUND: Chronic viral B hepatitis (CHB) is a potentially life-threatening liver disease that may progress to liver failure and cirrhosis. Currently, although combinations of different laboratory methods are used in the follow-up and treatment of CHB, the failure of these procedures in some cases has led to the necessity of developing new approaches. In CHB, the intrahepatic expression pattern of viral antigens, including hepatitis B surface antigen (HBsAg), is related to different phases of inflammation. However, many studies have focused on the intracytoplasmic properties of HBsAg staining, and HBsAg positivity in liver tissue has not been evaluated by objective quantitative methods. AIM: To investigate the relationship of image analysis-based quantitative HBsAg expression and its staining patterns with clinicopathological factors and treatment in CHB. METHODS: A total of 140 liver biopsies from treatment-naïve cases with CHB infection were included in this study. Following diagnosis, all patients were treated with entecavir (0.5 mg) and followed up at three-month intervals. The percentage of immunohistochemical HBsAg (p-HBsAg) expression in the liver was determined in whole tissue sections of biopsies from each case by image analysis. The immunohistochemical staining pattern was also evaluated separately according to 3 different previously defined classifications. RESULTS: A positive correlation between p-HBsAg and serum levels of hepatitis B virus (HBV) DNA and HBsAg was observed (P < 0.001). The p-HBsAg value was significantly higher in younger patients than in older patients. When the groups were categorized according to the hepatitis B e antigen (HBeAg) status in HBeAg-positive cases, p-HBsAg was correlated with HBV DNA, hepatitis activity index (HAI) and fibrosis scores (P < 0.001). In this group, p-HBsAg and HBsAg expression patterns were also correlated with the viral response (VR) and the serological response (SR) (P < 0.001). Multivariate analysis revealed that p-HBsAg was an independent predictor of either VR or SR (P < 0.001). In HBeAg-negative patients, although HBsAg expression patterns were correlated with both HAI and fibrosis, no relationship was observed among p-HBsAg, clinicopathological factors and VR. CONCLUSION: In pretreatment liver biopsies, the immunohistochemical determination of HBsAg expression by quantitative methods, beyond its distribution within the cell, may be a good predictor of the treatment response, especially in HBeAg-positive cases.

Impact of older age on the long-term survival in living-donor liver transplantation: A propensity score matching analysis.

BACKGROUND: Prevalence of the end-stage liver disease in the elderly patients indicating a liver transplantation (LT) has been increasing. There is no universally accepted upper age limit for LT candidates but the functional status of older patients is important in pre-LT evaluation. This study aimed to examine the impact of older age on survival after living donor liver transplantation (LDLT). METHOD: A total of 171 LDLT recipients were assessed in two groups: age ≥65 and < 65. To eliminate selection bias propensity score matching (PSM) was performed, and 56 of 171 recipients were included in this study. RESULTS: There were 20 recipients in the older group and 36 in the younger. The 1-, 3-, and 5-year survival rates were 65.0%, 60.0%, and 60.0% in group 1; 88.9%, 84.7%, and 71.4% in group 2, respectively. The 1-year survival was significantly lower in the older recipients; however, overall survival rates were similar between the groups. Of the 56 recipients, 15 (27%) deaths were observed in overall, and 11 (20%) in 1-year follow-up. The univariate regression analysis after PSM revealed that MELD score affected 1- year survival and the multivariate analysis revealed that age ≥65 years and MELD score were the predictors of 1-year survival. CONCLUSION: At first sight, before PSM, survival appeared to be worse for older recipients. However, we have shown that there were confounding effects of clinical variables in the preliminary evaluation. After the elimination of this bias with PSM, This study highlights that older recipients have similar outcomes as youngers in LDLT for long-term survival.

Endoscopic Findings of Gastro-Esophageal Reflux Disease in Elderly and Younger Age Groups.

Objective: To determine and compare the clinical features and endoscopic findings of gastro-esophageal reflux disease (GERD) in elderly and younger age groups. Materials and Methods: The clinical and endoscopic features were evaluated for all patients with GERD between January 2017 and September 2020. The criteria for inclusion were being aged over 65 and under 50 years and having an upper gastrointestinal endoscopy with reflux symptoms resistant to ppi theraphy. The exclusion criteria included prior surgery, age under 18 years, and pregnancy. The diagnosis of GERD was made according to the patients' symptoms. The SPSS 11.0 for Windows pocket program was used for statistical analysis. Results: Two hundred eighty-six patients aged over 65 years and 261 patients aged below 50 years were enrolled in this study. The mean age of the older group was 68.2 ± 4.5 years and the mean age of the young group was 38 ± 7.2 years. The male/female ratio was 5/3 and 2/1 in the young and older groups, respectively. The older patients had less severe and rare typical symptoms than the young patients. However, significantly more serious endoscopic findings were noted in the older patients compared with the younger patients. Conclusion: The older and young patients with GERD were predominantly male and typical reflux problems were less common in older patients with GERD. Older patients had more important endoscopic findings such as hernia, esophagitis, and cancer.

A Single-Center Experience in Portal Flow Augmentation in Liver Transplantation With Prior Large Spontaneous Splenorenal Shunt.

Large portosystemic shunts may cause portal steal syndrome in liver transplantation (LT). Because of the possible devastating consequences of the syndrome, the authors recommend perioperative management of these large shunts. Fourteen adult recipients who underwent portal flow augmentation, including left renal vein ligation (LRVL), renoportal anastomosis (RPA), shunt ligation (SL), and splenic vein ligation (SVL) for large spontaneous splenorenal shunt (SSRS), are included in this study, and the results were analyzed. A total of 13 patients had a large SSRS, and in 1 patient, the large shunt was placed between the superior mesenteric vein and the right renal vein. LDLT was performed in 13 patients. LRVL (n = 5), SVL (n = 6), RPA (n = 2), SL (n = 1) were performed to the patients as graft inflow augmentation. The graft-recipient weight ratios (GRWR) were less than 0.8% in 5 patients (35.7%): 2 had LRVL, and 3 had SVL. Small-for-size syndrome (SFSS) occurred only in these 2 patients with LRVL (GRWR ≤0.8%) and, splenic artery ligation was performed for graft inflow modulation. No mortality or serious complications were reported during follow-up. We consider that in patients with large SSRS and small-for-size grafts, SVL can be performed safely and with satisfactory outcomes.

NSAID, antiaggregant, and/or anticoagulant-related upper gastrointestinal bleeding: Is there any change in prophylaxis rate after a 10-year period?

BACKGROUND/AIMS: Using proton-pump inhibitor (PPI) is a protective option for patients who require long-term non-steroidal anti-inflammatory drugs (NSAIDs) and antiaggregants. In our previous study, the rate of PPI use in prophylaxis was found to be 2%. Here we aimed to investigate whether there is a change in PPI use in prophylaxis in a similar patient group after 10 years. MATERIALS AND METHODS: The patients who followed up with upper gastrointestinal (GI) bleeding diagnosis between January 01, 2016 and December 31, 2017 were retrospectively evaluated. Patients who had malignancy or variceal hemorrhage were excluded. Ninety-six patients, who had taken NSAIDs, antiaggregants, or anticoagulants that were considered as the possible cause of bleeding, were included in the study. Risk groups for NSAID GI toxicity and PPI use rates in these patients were evaluated. RESULTS: Twenty (21%) of all patients with upper GI bleeding were using PPI. According to the pre-bleeding risk factor assessment, 86% of the patients were found to have moderate to high risk for NSAID-related GI bleeding, and 81% of these patients were not using PPI. PPI prophylaxis was not provided to 15 (75%) of the 20 patients with previous history of peptic ulcer bleeding. CONCLUSION: Despite many studies and recommendations on risk factors and prophylaxis for NSAID-related bleeding, prophylactic PPI use is still largely ignored by physicians. The rate of PPI use in the patient group of this study was found still quite insufficient.

The association of mean platelet volume levels with hypertensive retinopathy.

The pathophysiological mechanism of hypertensive retinopathy (HR) is not fully established. Elevated blood pressure alone does not fully account for the extent of retinopathy so other pathogenic mechanisms may be involved, such as increased platelet activation. Mean platelet volume (MPV) is a marker of platelet activation. Therefore, this study was designed to answer the following questions: Do MPV levels change in HR? and is there any relation between degree of HR and MPV levels? This study included newly diagnosed and 57 untreated essential hypertensive patients with HR. The hypertensive patients were divided into two groups according to the Keith, Wagener classification. Group 1 comprised 29 hypertensive patients with grade 1 HR with a mean age of 56.8 +/- 9.7 years. Group 2 comprised 28 hypertensive patients with grade 2 HR with a mean age of 58.1 +/- 10.3 years. Twenty-seven normotensive subjects who were the healthy participants and had undergone the check-up program were used as the control group. Fundoscopic examination, metabolic parameters and MPV levels were measured in all groups. The level of MPV in group 2 was significantly higher than in group 1 (8.9 +/-0 0.8 fl vs. 8.3 +/- 0.8 fl, p = 0.02) and the normotensive control group (8.9 +/- 0.8 fl vs 7.8 +/- 0.7 fl, p < 0.001). It was also higher in group 1 than in normotensive control group (8.3 +/- 0.8 fl vs.7.8 +/- 0.7 fl, p < 0.01). In addition, MPV showed a positive correlation with the degree of HR in the hypertensive group (r = 0.41, p = 0.015). Our study suggests that platelet activation, a mechanism known to be involved in vascular lesions, may promote the development of HR.

Effectiveness and safety of sofosbuvir/ledipasvir ± ribavirin treatment in liver and/or renal transplant patients with chronic hepatitis C: A single-center experience.

OBJECTIVE: Successful treatment is possible with novel direct-acting oral antiviral agents in solid organ transplant patients with hepatitis C. In this study, the effectiveness and safety of sofosbuvir/ledipasvir ± ribavirin treatment in liver and/or renal transplant patients with chronic hepatitis C were evaluated. MATERIALS AND METHODS: A total of 23 liver and/or renal transplant patients who received sofosbuvir/ledipasvir ± ribavirin for chronic hepatitis C over 12 or 24 weeks were enrolled in the study. The treatment response, clinical and laboratory adverse effects, and effect on immunosuppressive drug levels were assessed. RESULTS: A total of 12 patients had undergone renal transplantation and 11 had undergone liver transplantation. All of the renal transplant patients and 91% of liver transplant patients had genotype 1. In total, 10 renal transplant patients and 4 liver transplant patients had treatment experience. Two renal transplant patients and one liver transplant patient had compensated cirrhosis. Nine renal transplant patients were on tacrolimus, and two were on cyclosporine; all of the liver transplant patients were on tacrolimus-based immunosuppressive therapy. While hepatitis C RNA was negative in 75% of renal transplant patients and 91% of liver transplant patients at week 4, it was negative in all of the patients at the end of treatment and 12 weeks after treatment. Significantly reduced hemoglobin levels were observed in patients administered ribavirin during treatment (p = 0.01). There were no significant differences between the baseline and treatment period values of mean creatinine, estimated glomerular filtration rate, bilirubin, and tacrolimus levels. There were no adverse effects leading to treatment discontinuation. CONCLUSION: Sofosbuvir/ledipasvir ± ribavirin is quite safe and effective in hepatitis C treatment after liver and/or renal transplantation.

Interstitial Pneumonitis Related to Pegylated Interferon Alfa-2a Treatment in a Patient with Chronic Hepatitis C.

Alkan E, Akin M, Adanir H, Tuna Y. Interstitial Pneumonitis Related to Pegylated Interferon Alfa-2a Treatment in a Patient with Chronic Hepatitis C. Euroasian J Hepato-Gastroenterol 2016;6(1):91-92.

Local Immune Response in Helicobacter pylori Infection.

There have been few studies concerning the cytokine profiles in gastric mucosa of Helicobacter pylori-infected patients with normal mucosa, chronic gastritis, and gastric carcinoma (GAC).In the present study, we aimed to elucidate the genomic expression levels and immune pathological roles of cytokines-interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, IL-10, transforming growth factor (TGF)-ß, IL-17A, IL-32-in H pylori-infected patients with normal gastric mucosa (NGM; control), chronic active gastritis (CAG), and GAC. Genomic expression levels of these cytokines were assayed by real-time PCR analysis in gastric biopsy specimens obtained from 93 patients.We found that the genomic expression levels of IFN-γ, TNF-α, IL-6, IL-10, IL-17A mRNA were increased in the CAG group and those of TNF-α, IL-6, IL-10, IL-17A, TGF-ß mRNA were increased in the GAC group with reference to H pylori-infected NGM group.This study is on the interest of cytokine profiles in gastric mucosa among individuals with normal, gastritis, or GAC. Our findings suggest that the immune response of gastric mucosa to infection of H pylori differs from patient to patient. For individual therapy, levels of genomic expression of IL-6 or other cytokines may be tracked in patients.

Acute brucellosis associated with leukocytoclastic vasculitis and splenic infarct.

Brucellosis is globally the most prevalent multisystem infection of zoonotic origin, while it is still one of the most important public health problems in Turkey as non-pasteurised milk and dairy products are consumed. Early diagnosis is vital to prevent the possibly lethal complications caused by the disease. However, diagnosis might be delayed as the disease does not have a single and typical manifestation and presents with various symptoms of different systems. Brucellosis and associated splenic infarct have rarely been studied, there being few cases in the literature. One of the rare involvements in this disease is dermatological involvement, which has been found in less than 10 percent of brucellosis cases. In this study, we discuss a 17 year old male patient who was admitted to our hospital due to fever, abdominal pain, arthralgia and rash on legs, diagnosed with brucellosis through brucellosis tube agglutination test and found to have splenic infarct upon examination and leukocytoclastic vasculitis according to the skin biopsies in the light of the present literature.