Hepatitis delta virus infection in Turkey: A meta-analysis of prevalence.

Objectives: Hepatitis delta virus (HDV) infection has been granted orphan disease status by the US Food and Drug Administration and the European Medicines Agency owing to its rarity and relatively limited research and treatment options. Turkey is considered an endemic country for the virus. We aimed to provide a current and updated country- and region-specific HDV infection prevalence. Methods: In this meta-analysis, we searched databases, including MEDLINE, PUBMED, EMBASE, and UlakBim (Turkish Medical Index) published between January 1, 2006, and December 31, 2022. We included blood donor studies, outpatient clinic studies that comprised patients without cirrhosis, and inpatient clinical studies that comprised patients with cirrhosis. Turkey was divided into three regions: West, Central, and East Turkey. Results: After a systematic assessment, 41 studies were included. Using a random-effects model, the estimated HDV prevalence among hepatitis B surface antigen-positive blood donors, outpatient clinic, and inpatient clinic patients were 3.37% (confidence interval [CI] 1.99-6.11), 5.05% (CI 4.00-6.23), and 29.06% (CI 10.45-51.79), respectively. The HDV prevalence among outpatient clinic patients in Western, Central, and Eastern regions were 3.38% (CI 2.47-4.44), 2.15% (CI 1.37-3.09), and 9.81% (CI 6.61-13.55), respectively. Conclusions: East Turkey continues to have a high burden of HDV. Public health efforts, such as screening, should be targeted accordingly.

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.

Non-invasive fibrosis markers for assessment of liver fibrosis in chronic hepatitis delta.

Assessment of liver fibrosis by non-invasive means is clinically important. Studies in chronic hepatitis delta (CHD) are scarce. We evaluated the performance of eight serum fibrosis markers [fibrosis-4 score (FIB-4), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), age-platelet index (API), AST-to platelet-ratio-index (APRI), Goteborg University Cirrhosis Index (GUCI), Lok index, cirrhosis discriminant score (CDS) and Hui score] in CHD and chronic hepatitis B (CHB). Liver stiffness was assessed by transient elastography (TE) in CHD. The ability of fibrosis markers to detect significant fibrosis and cirrhosis were evaluated in 202 CHB and 108 CHD patients using published and new cut-offs through receiver operating characteristics (ROC) analysis. The latter was also applied to obtain cut-offs for TE. APRI, Fib-4, API and Hui score were assessed for significant fibrosis, and APRI, GUCI, Lok index, CDS and AAR for cirrhosis determination. Fibrosis markers displayed weak performance in CHB for significant fibrosis with area under ROC (AUROC) curves between 0.62 and 0.71. They did slightly better for CHD. TE displayed an AUROC of 0.92 and performed better than serum fibrosis markers (p < 0.05 for fibrosis markers). For cirrhosis determination, CDS and Lok Index displayed an AUROC of 088 and 0.89 in CHB and GUCI, Lok index and APRI displayed AUROCs around 0.90 in CHD. TE displayed the best AUROC (0.95). Hence TE is superior to serum fibrosis markers for diagnosing significant liver fibrosis and cirrhosis. GUCI, Lok index and APRI displayed a reasonable performance in CHD, which needs further confirmation.

A single-center experience: Liver biopsy results during a year.

Background and Aim: Liver biopsy is the gold standard method for the diagnosis and treatment of liver diseases. In this study, we aimed to evaluate the results of liver biopsies performed in a year in our clinic. In addition, we also aimed if these liver biopsies could reveal the etiology of liver disease in patients with elevations of transaminases or/and alkaline phosphatase levels or liver masses. Materials and Methods: Patients who had liver biopsies for persistently elevated transaminases or/and alkaline phosphatase levels, protocol biopsies after liver transplantation, or liver masses in our hepatology clinic between 2011 and 2012 were included in the study. Liver biopsy decisions were made by experts during the hepatology council. Liver biopsies were previously performed using classical percutaneous liver biopsy or ultrasonography-guided Sonocan® liver biopsy sets. The pathology results of liver biopsies and clinical data of the matching patients were obtained from the liver biopsy record archives and patient files, respectively. Results: Totally, 479 liver biopsy results (male=252, 52.6%, mean age 49±14.5 years) were evaluated in the study. Of these patients, 432 (male=228) underwent percutaneous liver biopsy and 47 (male=24) underwent Sonocan® needle biopsy. The most common histopathologic diagnoses in the percutaneous liver biopsy group were chronic hepatitis B (n=127, 29.4%), normal histopathological findings (n=50, 11.6% and 32 of them were protocol biopsies after liver transplantation), and nonalcoholic steatohepatitis (NASH, n=41, 9.5%). The most common histopathologic diagnoses in the Sonocan® group were 25 liver metastasis out of 29 liver tumors (n=25, 53.2% of all) chronic hepatitis B (n=5, 10.6%), and NASH (n=3, 6.4%). Conclusion: In this study, diversity in liver biopsy results indicates the importance of histopathological evaluation. The most prevalent pathology in the liver biopsies was chronic hepatitis B, which is the most common chronic liver disease in Turkey. The metastatic liver tumor was the most common among the liver masses.

Recommendations for Hepatitis B Immunoglobulin and Antiviral Prophylaxis Against Hepatitis B Recurrence After Liver Transplantation.

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.

Determination of Turkish norms of psychometric tests for diagnosing minimal hepatic encephalopathy and proposal of a high sensitive screening test battery.

BACKGROUND: Psychometric hepatic encephalopathy score (PHES) needs local standardization. AIMS: This study aimed at standardizing PHES for Turkish patients and compare them with German norms; to determine minimal hepatic encephalopathy (mHE) prevalence with two different methods [PHES battery and Critical Flicker Frequency (CFF)] and to assess whether sub-tests of the battery can be used for screening for mHE. METHODS: Healthy volunteers (n = 816; 400 male) and cirrhotics (n = 124; 58 male) were included. For mHE diagnosis PHES score threshold was set at ≤ - 5 points and that of CFF at < 39 Hz. For comparing German and Turkish norms, datasets were combined. Multiple backward procedure was applied to assess effects of age, sex and education on single tests of the battery. Receiver operating characteristic (ROC) curves were created for assessing diagnostic capabilities of subtests of the battery. RESULTS: PHES norms for Turks were developed. MHE prevalence in compensated cirrhotics was 29.8% and 27.4% with PHES and CFF tests, respectively, with low compatibility (kappa coefficient 0.389); mHE prevalence decreased to 16% when both tests were combined. Turks performed worse vs Germans in the digit symbol (DS) and serial dotting (SD) subtests but performed better in other subtests. In ROC analyzes of subtests, the combination of DS + SD tests achieved an AUROC of 0.974 versus PHES. CONCLUSIONS: Use of two methods for diagnosing mHE is important for research purposes. From a clinical perspective, sensitivity with acceptable specificity may suffice for screening instruments for mHE. Combined use of DS and SD subtests of the PHES battery appears suitable for this purpose.

Histopathological evaluation of long-term tenofovir disoproxil fumarate treatment in patients with hepatitis be antigen-negative chronic hepatitis B.

BACKGROUND: Hepatitis B virus is a universal health problem. There are approximately 250 million people living with hepatitis B worldwide, and approximately 600000 of these people die every year due to the virus. AIM: To compare the pretreatment and post-treatment histopathological results of patients with hepatitis be antigen (HBeAg)-negative chronic hepatitis B (CHB) who had been receiving tenofovir disoproxil fumarate (TDF) treatment at our clinic for at least 5 years. METHODS: Patients with HBeAg-negative CHB who were being treated with TDF (245 mg/d) were included in the study. Liver biopsies of patients before TDF treatment and liver biopsies after 5 years of TDF treatment were retrospectively compared. RESULTS: A total of 50 HBeAg-negative CHB patients were included in the study (mean age: 47.9 ± 10.4 years, men: 27.54%). Histological improvement was observed in 78% (39) of the patients after 5 years of treatment. After the 5 years of treatment, the mean Ishak score of the patients was 1.3 ± 1.3, and the mean histologic activity index score was 4.1 ± 2.8. A 1.53 point reduction in Ishak fibrosis score was detected after long-term TDF treatment. CONCLUSION: Liver biopsies after 5 years of TDF treatment revealed a significant histological response and a regression of the necroinflammatory score compared to pretreatment liver biopsies. To better understand the effects of antiviral treatments on the improvement of liver histology, long-term studies involving larger numbers of patients are needed.

Assessment of sleep pattern and quality before and after liver transplantation using different methods.

BACKGROUND/AIMS: Sleep disorders (SDs) are frequently seen in patients with liver cirrhosis. Polysomnography (PSG), actigraphy, and electroencephalogram (EEG) are the common objective methods to diagnose SDs. The most commonly used subjective methods are the Pittsburgh sleep quality index (PSQI) and Epworth sleepiness scale (ESS). We aimed to evaluate the effect of liver transplantation (LTx) on SDs using a combination of objective (PSG and EEG) and subjective (PSQI and ESS) methods. MATERIALS AND METHODS: A total of 18 patients with cirrhosis on an LTx waiting list were included in this study. Patient clinical status and biochemical parameters were evaluated. All patients completed the validated Turkish forms of the PSQI and ESS before and 9 months after LTx. All patients underwent EEG and PSG before and 9 months after LTx. RESULTS: In total, 18 patients with liver cirrhosis (men: 12; 66.7%, mean age: 53.22±10.43 years) were included in this study. Pretransplant mean PSQI and ESS scores were 8.4±3.11 and 7.28±3.89, respectively; 9-month posttransplant mean PSQI and ESS scores were 4.5±2.8 and 4.72±2.91 (p<0.01), respectively. Before transplantation, metabolic encephalopathy was detected in 6 patients by EEG, whereas metabolic encephalopathy was detected in only 1 patient posttransplant. Posttransplantation PSG sleep duration (all stages) increased relative to pretransplant PSG values. Sleep latency and rapid eye movement latency were found to be reduced compared to the pretransplant values. CONCLUSION: This pilot study compared SDs in patients with pre- and post-LTx by combining the subjective and objective methods. Significant SD improvements were found at the 9th month.

Adult living donor liver transplantation from donors with Gilbert's syndrome: Is it safe?

BACKGROUNDS: We evaluate whether it is safe to accept donors with Gilbert's syndrome (GS) for a living donor liver transplantation (LDLT) or not. This study is the first controlled study to be conducted. METHODS: Between January 2004 and May 2014, 600 LDLTs which used right lobe liver grafts were performed in our center. Forty-five of the 600 donors had a GS diagnosis. For a control group, 99 donors without GS who had completed 1 year or more of follow-up were selected retrospectively and consecutively. The clinical results of the donors and recipients were then analyzed. RESULTS: A total of 45 donors with GS and 99 donors without GS were included. There were no significant differences in patient demographics, actual graft weight, remnant ratio, portal and ductal variations, pre-peri-post-operative liver enzymes. The donors with GS had significantly higher bilirubin levels compared with the control group at first reading, at maximal peak, and post-operative 1-7 days, 1st and 6th months (P < .001 for all readings). Post-operative complication ratio was 40% in GS, 34.3% in non-GS group. In GS and non-GS group, hospitalization period was 10.2 and 9.2 days, respectively. The 1-year donor survival rate was 100% for both groups and 1-year recipient survival was similar who have donors with GS and non-GS (93.3%; 92.9%, P = .93). CONCLUSIONS: The use of right lobe grafts from donors with GS appears to be safe for donor health.

Hepatocellular Carcinoma and Liver Transplantation: A Single-Center Experience.

BACKGROUND: Liver transplantation (LT) is the best treatment in selected patients with hepatocellular carcinoma (HCC). Morphologic criteria alone are not sufficient to predict survival. In this study, we investigated the clinical, biochemical, and pathologic factors affecting survival in patients who underwent LT due to HCC. METHODS: Between October 2011 and January 2018, 165 of 749 LT for HCC cases performed at the Memorial Atasehir Hospital were evaluated retrospectively. Survival, demographic characteristics and etiology, preoperative alpha-fetoprotein (AFP) level, Model for End-Stage Liver Disease (MELD) score, prognostic staging, and morphologic and histologic properties were evaluated. RESULTS: One hundred and thirty-nine cases of 165 were living donor liver transplantation (LDLT). The mean age was 57.7 ± 7.3 years, the mean follow-up period was 27.8 ± 20 months, and 41 patients (24%) died before follow-up. Recurrence of HCC was detected in 23 (14%) cases. Overall survival was 85%, 71%, and 64% for 1, 3, and 5 years, respectively. In terms of 1-, 3-, and 5-year survival within vs beyond Milan criteria was 90%, 80%, and 76% vs 75%, 66%, and 44%, respectively. In the University of California San Francisco criteria, it was 86%, 76%, and 70% vs 76%, 60%, and 30% compared with 1-, 3-, and 5-year survival. While histopathological poor differentiation and AFP elevation affected the course negatively. Good differentiation did not have a significant effect on survival. It was determined that poor differentiation, lymphovascular invasion, and an increased number of nodules significantly affected survival in both within and beyond cases. CONCLUSION: A transplant decision is controversial in patients with HCC with other than previously defined morphologic criteria. In these cases, AFP level and histologic differentiation determine survival. The results were not satisfactory in both high and/or poorly differentiated cases.

A Single-Center Experience: The Diagnostic Role of Peritoneoscopy in Patients with Exudative Ascites.

BACKGROUND AND AIM: The causes of exudative and transudative ascites can be detected through noninvasive methods nowadays. In selected cases, peritoneoscopy could be necessary for definitive diagnosis. In this retrospective study, we aimed to present the peritoneal biopsy results of patients who had exudative ascites with unclear etiology. MATERIALS AND METHODS: A retrospective analysis was performed in 86 patients who had exudative ascites of unclear etiology. All the patients showed abnormalities of the peritoneum or greater omentum as determined by abdominal ultrasonography and underwent peritoneoscopy between January 2012 and December 2015. Patient data were obtained from hospital records. RESULTS: Eighty-six patients (male: 22; 25.6%, mean age ± standard deviation: 57.97 ± 15.97) who had exudative ascites of unclear etiology were included to the study. The success rate of the procedures was 100% (86/86). A specific histopathological diagnosis was made in all patients, with an overall diagnostic accuracy of 100%. Among the 86 diagnosed patients, 43 (50%) were peritonitis carcinomatosa, 21 (24.4%) were tuberculous peritonitis, 14 (16.3%) were mesothelioma, 4 (4.7%) were chronical inflammation, and 1 (1.2%) was lymphoma. Three (3.5%) patients had normal peritoneal biopsy findings. DISCUSSION: Peritoneoscopy is a safe and efficient alternative method due to its high diagnostic capacity in selected patients who have exudative ascites of unclear etiology.

Correlation between neutrophil/lymphocyte ratio and Ranson score in acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is characterized by inflammation of the pancreas, elevated pancreatic enzymes, and abdominal pain. The neutrophil to lymphocyte ratio (NLR) is used as a marker of inflammation. In this retrospective study, we aimed to investigate novel early prognostic predictors of AP, such as NLR and its correlation with the Ranson score. METHODS: A total 435 patients (Male: 152; 34.9%, Age: 63.53 ± 17.22 years) were included in the study. Data were collected by two clinicians scanning the registered hospital records. RESULTS: Classification of the patients according to the aetiologies revealed gallstone(s) 58.6% (n = 255), hyperlipidaemia 2.2% (n = 9), viruses 0.7% (n = 3), malignancies 0.5% (n = 2), and alcohol 0.2% (n = 1). No reason was discovered in 37.9% (n = 165) of patients. Age, duration in the intensive care unit, serum aspartate aminotransferase (AST) levels, alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bilirubin, direct bilirubin, lactate dehydrogenase (LDH), white blood cell (WBC) count, neutrophil count, lymphocyte count, and the NLR were greater in the group with a Ranson score ≥3 than the group with a Ranson score <3. DISCUSSION: Quick diagnosis is essential in AP. Current scoring systems for AP diagnosis are complicated, whereas NLP is a simple, practical, and effective marker.

Association of LCT-13910 C/T Polymorphism and Colorectal Cancer.

PURPOSE: The activity of epithelial lactase (LCT) is associated with a polymorphism 13910 bp upstream in the lactase encoding gene. Because the association between the LCT-13910 polymorphism and the risk for colorectal cancer is not clear, we investigated the role of the LCT-13910 polymorphism as a potential risk factor for colorectal cancer and colorectal polyps in the Turkish population. METHODS: One hundred sixty-six subjects (74 with polyps, 44 with colorectal cancer, 48 controls), who had undergone a total colonoscopy between January 2012 and November 2012 in our endoscopy unit were genotyped for the LCT-13910 polymorphism by using the polymerase chain reaction and minisequencing. RESULTS: The CC genotype in the lactose gene 13910 locus, which is accepted as the genetic indicator of lactase deficiency, was determined as 83.7%. The CC genotype rate was determined as 89.1% in patients who had a history of lactose intolerance and 81.5% in those without a history of lactose intolerance (P = 0.236). No difference was detected between the patients who had colorectal polyp(s) and/or cancer and the controls with regard to the LCT-13910 polymorphism. No differences were determined between groups when they were compared with regard to the C or the T allele. CONCLUSION: No differences were detected between the patients who had colorectal polyp(s) and/or cancer and those with normal colonoscopy findings with regard to lactase gene polymorphisms. No differences were determined between the groups when they were compared with regard to the C or the T allele.

Diurnal changes of critical flicker frequency in patients with liver cirrhosis and their relationship with sleep disturbances.

BACKGROUND: We aimed to measure the diurnal changes of critical flicker frequency in healthy subjects and cirrhotic patients and to investigate their relationship with sleep disturbance. METHODS: Cirrhotic patients and healthy volunteers were included. All groups completed the Pittsburgh Sleep Quality Index and a simple sleep questionnaire. Sleep disturbance was defined as a Pittsburgh Sleep Quality Index score of >5. Critical flicker frequency was measured twice a day to detect diurnal abnormalities. RESULTS: Overall, 59 cirrhotic patients (54.2% males, Mean Age 59 ± 11 years) and 18 controls (39.9% males, Mean Age 58 ± 9 years) were included. Sleep disturbances were more common in cirrhotics (66.1%) than controls (38.9%, p<0.05). In cirrhotics, the critical flicker frequency was not related to decompensation. The nocturnal values were higher than the morning values in cirrhotics (64.4%), but not in controls (p<0.0001). Additionally, sleep disturbances were more common in cirrhotics who had higher nocturnal values (p<0.05). CONCLUSIONS: Changes in the diurnal critical flicker frequency were observed in cirrhotics but not in controls. Sleep disturbances in cirrhotics appear to be associated with deviations of the diurnal rhythm of critical flicker frequency rather than with clinical parameters such as the clinical stages of cirrhosis and the Model For End-Stage Liver Disease and Child-Pugh scores.

Sleep disorders in cirrhotics; how can we detect ?

BACKGROUND & AIMS: Sleep disorders (SDs) are common in cirrhotics and are often associated with hepatic encephalopathy. SDs negatively affect patients' daily activities and work efficiency. For this reason, early diagnosis is important. The methods used for diagnosis of SDs are not practical and need longer periods of application and evaluation. In this study, we aimed to investigate sleep disorders and related clinical parameters in cirrhosis and also wanted to investigate the using of Sleep Timing and Sleep Quality Screening questionnaire (STSQS), a simple form with a short application time, for diagnosis of SDs and its correlation with Pittsburg Sleep Quality Index (PSQI) form. METHODS: Cirrhotic patients and age-matched healthy volunteers were enrolled. Patients were excluded from this study if they had neuropsychiatric disease or used excessive alcohol or drugs known to affect sleep. Both groups completed validated Turkish form of PSQI and STSQS. SD was defined as PSQI score (0-21) of >5 or STSQS ≥5. RESULTS: One hundred and thirty-one cirrhotic patients and 18 healthy volunteers were enrolled. SDs in cirrhotics and control group were detected 56.5% and 27.8% by PSQI, 49.6% and 16.7% by STSQS respectively. SDs are the most frequent in the Child C patients, and the least frequent in the Child A patients (P > 0.05). No correlation was found between the MELD score and SDs. SDs were more common in cirrhotic patients with hypoalbuminaemia and low haemoglobin levels. In addition, the patients with decompensated cirrhosis had more frequently SDs than the patients with compensated cirrhosis. In the patient group, sleep latency and total sleep time, sleep parameters were correlated with SDs. STSQS had statistical significant correlation with PSQI for diagnosis of SDs. CONCLUSION: SDs are common in cirrhotics and STSQS could be an appropriate and practical method for diagnosis of SDS in these patients. We can use it in cirrhotic patients at outpatient clinics.