Ilker Turan

The Model for End-stage Liver Disease Sodium (MELD-Na) score predicts mortality in liver transplant candidates. MELD 3.0 has been proposed as an improved model for estimating mortality risk. This study evaluated MELD 3.0’s predictive accuracy for short-term mortality among Turkish liver transplant candidates and compared its performance with MELD and MELD-Na scores. Patients listed both for deceased donor transplants and living donor transplants were analyzed in the study. The discriminative abilities of MELD, MELD-Na, and MELD 3.0 scores were assessed using the area under the receiver operating characteristic curve (AUROC). Comparisons between AUROC values used the DeLong test. The most predictive cutoff for MELD 3.0 was determined using the Youden index. Transplant-free survival was analyzed using the Kaplan–Meier method, with survival curves compared using the log-rank test. A total of 1689 patients were included in this nationwide, multicenter study. Hepatitis B was the leading cause of cirrhosis (29%, n=491), followed by metabolic dysfunction–associated steatohepatitis (20%, n=335). For 3-month mortality, MELD 3.0 had the highest AUROC (0.753), followed by MELD-Na (0.747) and MELD (0.725). The most predictive cutoff values were 18 for MELD and 21 for MELD-Na and MELD 3.0. Both MELD-Na and MELD 3.0 outperformed MELD ( p p =0.17). MELD 3.0 and MELD-Na demonstrated superior performance to MELD in predicting 3-month mortality among Turkish liver transplant candidates, though their predictive accuracy was comparable. Further refinements are needed to enhance MELD 3.0’s clinical utility.

Background and Aims: Ornidazole, a nitroimidazole antibiotic, is widely used for protozoal and anaerobic infections and is generally considered safe. However, ornidazole-induced liver injury (OILI) is an underrecognized yet potentially severe adverse reaction. This multicenter study aims to characterize the clinical features, histopathology, and outcomes of OILI to improve the awareness and management of this rare entity worldwide. Methods: We conducted a retrospective analysis of 101 patients with OILI from eight tertiary centers between 2006 and 2023. Cases were included based on liver enzyme elevations temporally linked to ornidazole and the exclusion of other causes. Causality was assessed using the Roussel Uclaf Causality Assessment Method (RUCAM) score. Clinical data, laboratory parameters, autoantibody profiles, histology, treatments, and outcomes were evaluated. Results: OILI was classified as highly probable in 42.6% of cases (n = 43), probable in 51.5% of cases (n = 52), and possible in 5.9% (n = 6) of cases. The predominant pattern was acute hepatocellular injury (83.2%) (n = 84). Autoimmune-like hepatitis occurred in 5% of cases (n = 5), with ANA positivity in 16.8% of cases (n = 17). Corticosteroids were used in 24.8% of cases (n = 25) and were associated with higher ANA positivity and a 20% (n = 5) relapse rate post-discontinuation. Recovery was achieved in 87.7% of cases (n = 88), while 7.9% of cases (n = 8) required liver transplantation and 4% (n = 4) died. Conclusions: Ornidazole can cause serious idiosyncratic liver injury, including autoimmune phenotypes, and should be considered in the differential diagnosis of acute hepatitis. Given the notable risk of liver failure and death, early recognition, drug discontinuation, and close monitoring are essential. In select cases, corticosteroids and plasmapheresis may be beneficial, though the evidence remains limited.

Background and Aim: The primary aim of this study was to investigate the concordance of Transient Elastography FibroScan® (FS) measurements, Fibrosis-4 (FIB-4), and the Aspartate Aminotransferase to Platelet Ratio Index (APRI) scores with each other and with liver biopsies in predicting histological fibrosis. Materials and Methods: In this single-center, cross-sectional, retrospec-tive collected data cohort study spanning seven consecutive years, simultaneous FS measurements, FIB-4, and APRI scores of 778 patients with different diagnoses who had undergone liver biopsy were evaluated. Results: A total of 417 (53.6%) of the patients were female. The median age was 51 years. The diagnoses were HBV (n=228), metabolic dysfunction-associated steatotic liver disease (MASLD) (n=185), HCV (n=58), cryptogenic (n=53), primary biliary cholangitis (n=40), autoimmune hepatitis (AIH) (n=28), overlap syndrome (OS) (n=23), multiple diag-noses (n=42), and other diagnoses (n=83). All three methods showed a strong correlation with histological fibrosis, and FS demonstrated a statistically significantly superior relationship compared to FIB-4 and APRI. In AIH and OS, FIB-4 and APRI scores do not show a consistent increase with histological stage; however, FS does. In MASLD, all three methods correlate with histologic stage, but FS measurements appear significantly superior. Conclusion: Although FIB-4, APRI, and FS correlate well with histological fibrosis, especially in MASLD, evaluation with FS, if available, should be preferred. In the evaluation of fibrosis in AIH and OS, laboratory-based indicators should be avoided.

Background and Aim: This study aimed to identify the indications for liv-er transplantation (LT) based on underlying etiology and to characterize the patients who underwent LT. Materials and Methods: We conducted a multicenter crosssectional ob-servational 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 al-cohol-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

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 proto-col analysis. The SVR12 rates were statistically significant differences be-tween 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

Background and Aim: The aim of the present study was to examine the etiology of hepatocellular carcinoma (HCC) by underlying cause and determine the characteristics and clinical features of patients with HCC. Materials and Methods: The study comprised 1802 HCC patients diagnosed and followed up by Liver Diseases Outpatient Clinics in 14 tertiary centers in Turkey between 2001 and 2020. Results: The mean age was 62.3±10.7 years, and 78% of them were males. Of the patients, 82% had cirrhosis. Hepatitis B virus (HBV) infection was the most common etiology (54%), followed by hepatitis C virus (HCV) infection (19%) and nonalcoholic fatty liver disease (NAFLD) (10%). Of the patients, 56% had a single lesion. Macrovascular invasion and extrahepatic spread were present in 15% and 12% of the patients, respectively. The median serum alpha-fetoprotein level was 25.4 ng/mL. In total, 39% of the patients fulfilled the Milan Criteria. When we compared the characteristics of patients diagnosed before and after January 2016, the proportion of NAFLD-related HCC cases increased after 2016, from 6.6% to 13.4%. Conclusion: Chronic HBV and HCV infections remain the main causes of HCC in Turkey. The importance of NAFLD as a cause of HCC is increasing.

The ideal management for end stage liver disease, acute liver failure, and hepatocellular carcinoma (HCC), within specific criteria, is liver transplantation (LT). Over the years, there has been a steady increase in the candidates listed for LT, without a corresponding increase in the donor pool. Therefore, due to organ shortage, it has been substantially difficult to reduce waitlist mortality among patients awaiting LT. Thus, marginal donors such as elderly donors, steatotic donors, split liver, and donors after cardiac death (DCD), which were once not commonly used, are now considered. Furthermore, it is encouraging to see the passing of Acts, such as the HIV Organ Policy Equity (HOPE) Act, enabling further research and development in utilizing HIV grafts. Subsequently, the newer antivirals have aided in successful post-transplant period, especially for hepatitis C positive grafts. However, currently, there is no standardization, and protocols are center specific in the usage of marginal donors. Therefore, studies with longer follow ups are required to standardize its use.

The combination of hepatitis B immunoglobulin and potent nucleos(t)ide analogs after liver transplantation is considered as the standard of care for prophylaxis against hepatitis B virus recurrence. However, the recommended doses, route of administration, and duration of HBIG administration remain unclear. Moreover, hepatitis B immunoglobulin-free prophylaxis with potent nucleos(t)ide analogs has shown promising disease outcomes in preventing hepatitis B virus recurrence. The current recommendations, produced by the Turkish Association for the Study of the Liver, Acute Liver Failure and Liver Transplantation Special Interest Group, suggest a reduced need for hepatitis B immunoglobulin administration with effective long-term suppression of hepatitis B virus replication using potent nucleos(t) ide analogs after liver transplantation.

Background and Aim: The objective of this study was to evaluate the long-term presence of hepatitis B virus (HBV) DNA in the liver grafts of liver transplant patients who received hepatitis B immunoglobulin (HBIg) plus oral antiviral hepatitis B virus prophylaxis and had negative HBV serum markers. Materials and Methods: Patients aged 18 years or older who underwent liver transplantation for HBV-related liver disease, had negative serum viral markers, and had a liver biopsy at least 3 years after liver transplantation were eligible for this study. Clinical, serological, and pathological data were retrospectively obtained from medical records. The HBV DNA of liver biopsy specimens was assessed using the polymerase chain reaction technique. Results: A total of 150 patients were included. A positive HBV DNA result was seen in 18 (12%) of the liver biopsies. The presence of intrahepatic HBV DNA was not associated with pre-transplantation serum viral markers, type of pre- or post-transplantation antiviral treatment, or post-transplantation immunosuppressive treatment. Conclusion: The findings suggest that while treatment with HBIg plus oral antiviral as post-transplantation HBV prophylaxis may result in a percentage of patients with persistent HBV DNA in the graft, the presence of HBV DNA in the liver graft may not be related to clinical HBV recurrence.

Background and Aim: Hepatitis E virus (HEV) may cause chronic liver disease in solid organ transplant recipients. We determined HEV seroprevalence and associated factors in liver transplant recipients. Materials and Methods: Patients followed at the outpatient clinic of liver transplantation between January 2019 and January 2020 were screened retrospectively for HEV serology (HEV immunoglobulin M [IgM] and HEV immunoglobulin G [IgG]). Results: Of the 150 patients (male/female, 104/46; age, 55.4±13.2 years), anti-HEV IgG was positive in 31 (20.7%), and anti-HEV IgM was negative in all. The mean time after liver transplantation (72 [48%] deceased and 78 [52%] living donors) was 81±78.5 months. Drinking water consisted of carboy and tap water in 88 (58.7%) and 62 patients (41.3%), respectively. Of the patients, 120 (80%) and 30 (20%) lived in urban and rural areas, respectively. On comparison, the difference between positive and negative anti-HEV IgG groups in terms of age, place of birth, water supply, and donor type was statistically significant (p=0.007, p=0.000, p=0.034, and p=0.049, respectively). Conclusion: HEV seroprevalence was more frequent in liver transplant recipients compared with the normal population. Older age, water supply, and place of birth were risk factors for HEV seroprevalence.