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.

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.

Evaluation of the Effects of Immunosuppressive Drugs Following Liver Transplantation on Pregnancy Outcomes: A Retrospective Study.

BACKGROUND: Liver transplantations can be safely performed in women of reproductive age. Women with chronic liver disease may have infertility for various reasons, although fertility returns after recovering >90% of sexual disorders following liver transplantation. The present study examined the effects of immunosuppressive drugs used by women of reproductive age undergoing liver transplantation in our clinic on pregnancy and pregnancy outcomes and evaluated mortality and morbidity in this patient population. METHODS: Among the patients undergoing liver transplantation in our clinic between 1997 and 2020, those conceiving after liver transplantation were evaluated in the present study. Demographic data on maternal and newborn health, as well as mortality and morbidity, were recorded. Maternal transplant indications, graft type, the interval between transplantation and pregnancy, maternal age at pregnancy and the number of pregnancies, the number of living children, complications, delivery mode, immunosuppressive drugs, and blood levels were investigated. RESULTS: A total of 615 liver transplantations (353 from a living donor, 262 from a cadaveric donor) were performed in our clinic. Furthermore, 33 pregnancies occurred in 22 women following transplantation (17 living donor liver transplantations, 5 deceased donor liver transplantations), and the data of these patients were recorded. Tacrolimus and mycophenolate mofetil were used as immunosuppressive therapy. CONCLUSIONS: Liver transplantations can be safely performed in women of reproductive age if indicated, and these patients can be safely followed up throughout the pregnancy and during labor by a multidisciplinary team.

Complications and Long-Term Outcomes in Adult Patients Undergoing Living Donor Liver Transplantation Because of Fulminant Hepatitis.

BACKGROUND: The present study investigates the complications that may occur during long-term follow-up in patients aged 18 years and older undergoing living donor liver transplantation (LDLT) in our clinic because of fulminant hepatitis. METHODS: The study included patients aged 18 years and older with a minimum survival of 6 months who underwent an LDLT between June 2000 and June 2017. The demographic data of the patients were evaluated in terms of late-term complications. RESULTS: Of the 240 patients who met the study criteria, 8 (3.3%) underwent LDLT for fulminant hepatitis. The indication for transplantation in patients with fulminant hepatitis was cryptogenic liver hepatitis in 4 patients, acute hepatitis B infection in 2 patients, hemochromatosis in 1 patient, and toxic hepatitis in 1 patient. Of the 240 patients, 65 (27%) undergoing LDLT underwent a liver biopsy for suspected rejection because of an elevation in liver function test results during follow-up. Histopathologic scoring was carried out according to the Banff scoring system. A diagnosis of late acute rejection was made in only 1 of the 8 patients (12.5%) who underwent LDLT for fulminant hepatitis. CONCLUSION: Patients with fulminant hepatitis must be prepared for an LDLT, if available, while waiting for a cadaveric donor. The results of the present study suggest that LDLTs in patients with fulminant hepatitis are safe, and the outcomes are acceptable in terms of survival and complications.

Endoscopic and histological characteristics of small bowel tumors diagnosed by double-balloon enteroscopy.

BACKGROUND/AIMS: Double-balloon enteroscopy (DBE) allows for the diagnoses and treatment of small bowel tumors (SBTs). This study aimed to evaluate the utility of DBE for the diagnosis and treatment of SBTs. METHODS: Patients diagnosed with SBTs who underwent DBE were included in this study. According to their endoscopic appearances, they were categorized as polyps or masses, and according to their histological characteristics, they were categorized as benign or malignant SBTs. RESULTS: A total of 704 patients were retrospectively analyzed, and 90 (12.8%) were diagnosed with SBTs. According to their endoscopic appearance, 48 (53.3%) had polyps and 42 (46.7%) had masses. Additionally, 53 (58.9%) and 37 (41.1%) patients had malignant and benign SBTs, respectively, depending on their histological characteristics. Patients diagnosed with polyps were younger than those diagnosed with masses (p<0.001). Patients diagnosed with benign SBTs were younger than those diagnosed with malignant SBT (p<0.001). Overall, histological diagnosis was determined using DBE in 73 (81.1%) patients. CONCLUSION: DBE is a useful method for diagnosing SBTs. Additionally, the histological type of the lesion can be determined using DBE.

Could lysosomal acid lipase enzyme activity be used for clinical follow-up in cryptogenic cirrhosis?

BACKGROUND: Cholesterol ester storage disease (CESD) is one of the rare causes that should be kept in mind in the etiology of cirrhosis. Recent studies detected that significantly reduced lysosomal acid lipase deficiency enzyme (LAL) in patients with cryptogenic cirrhosis (CC). Moreover, studies have evaluated that LAL activity is as effective as scoring systems in assessing the severity of cirrhosis. In this study, we aimed to investigate the CESD with LAL level and mutation analysis of LIPA gene in patients diagnosed with CC and to compare LAL activities between patients with CC and healthy volunteers. METHODS: Laboratory parameters and cirrhosis stage (CHILD and MELD) were recorded for the patient group included in the study. In addition, blood samples were taken from each case included in the study for LAL activity determination and LIPA gene analysis. RESULTS: A statistically significant decrease in LAL activity was found in patients diagnosed with CC compared to the healthy group. LIPA gene analysis did not detect CESD in any patient group. Correlation analysis showed a positive correlation between LAL activity and white blood cell and platelet counts in both healthy volunteers and CC patient groups. In the univariate and multivariate logistic regression analysis of the parameters associated with the MELD of ≥10 in patients with CC, significant relationship was found between the MELD of ≥10 and the LAL activity. DISCUSSION: In our study, LAL activity was significantly lower in CC patients than in the normal population. LAL activity level appears to be a parameter that can be used to assess the severity of cirrhosis.

Prevalence of Gastrointestinal Symptoms and Clinical Outcomes in Hospitalized Coronavirus Disease 2019 Patients: A Single-Center Study from Turkey.

BACKGROUND: In patients with coronavirus disease 2019, the gastrointestinal symptoms have been reported increasingly in addition to the respiratory system symptoms. The studies show that the prevalence of gastrointestinal system symptoms and how the gastrointestinal system contributes to the severity and prognosis of the disease is still not clear. This study aims to find the prevalence of gastrointestinal symptoms and the correlation between the gastrointestinal symptoms and the clinical results in hospitalized patients diagnosed with coronavirus disease 2019. METHODS: This study retrospectively analyzes patients diagnosed with coronavirus disease 2019 and hospitalized in the pandemic unit between March 2020 and August 2020 and compares their demographic and clinical characteristics, laboratory and radiologic findings, coronavirus disease 2019 treatments received, the clinical course of the disease, and the gastrointestinal symptoms. RESULTS: In our study, we included 322 patients diagnosed with coronavirus disease 2019 and hospitalized; 39 patients (12.1%) were admitted to the hospital with at least one gastrointestinal symptom (nausea and vomiting, diarrhea, abdominal pain, and the loss of taste). Nausea and vomiting are the most common gastrointestinal symptoms with a prevalence of 7.1%, followed by diarrhea with 2.8%, the loss of taste with 2.2%, and abdominal pain with 1.5%. The mean age and D-dimer levels of the patients showing gastrointestinal symptoms were lower than those who did not have any gastrointestinal symptoms. We did not find a significant correlation between the presence of the gastrointestinal symptoms and the severity of the disease, treatment received, risk of acute respiratory distress syndrome and septic shock, admission to the intensive care unit, the need for mechanical ventilation, the mortality rate or the length of hospitalization in the medical floor or the intensive care unit. CONCLUSION: In this study, we observed that 12.1% of coronavirus disease 2019 patients apply to the hospital due to gastrointestinal symptoms. Furthermore, the gastrointestinal symptoms do not seem to affect the severity and the course of the disease, it is important to identify coronavirus disease 2019 patients showing unusual symptoms such as the gastrointestinal symptoms at an early stage to protect healthcare professionals from infection risk.

Double Balloon Enteroscopy in a Pregnant Woman with Peutz-Jeghers Syndrome.

Peutz-Jeghers syndrome is an autosomal dominant disorder characterised by multiple hamartomatous polyps and muco-cutaneous pigmentation. Most polyps are found in the small intestine, especially in the jejunum. Enteroscopy with polypectomy is a reliable method to prevent polyp-related complications. A pregnant woman, who was diagnosed as a case of Peutz-Jeghers syndrome with a history of intestinal resection, was admitted to our clinic. Termination was recommended to the patient due to the possibility of polyps, causing obstruction during pregnancy. She underwent double balloon enteroscopy in the second trimester. Large polyps that could cause intussusception were removed and post-polypectomy bleeding was successfully controlled. This procedure was the first double balloon enteroscopy during pregnancy, reported in the literature. The procedure should be performed by experienced endoscopists, who can cope well with the complications in expert centres, as the procedure carries a high risk. Key Words: Double baloon enteroscopy, Pregnancy, Peutz-Jeghers syndrome, Polyps.

Evaluation of colon mucosa using screening colonoscopy and flexible spectral imaging color enhancement in patients with long lasting ulcerative colitis.

AIM: To determine which flexible spectral imaging color enhancement (FICE) channel best visualizes colon mucosa in ulcerative colitis (UC) and to compare FICE imaging with standard imaging. METHODS: The study enrolled patients with ulcerative colitis in remission who had inflammatory bowel disease for at least 8 years. All patients underwent screening colonoscopy. The entire colon, especially the suspicious areas in terms of dysplasia, were imaged with standard endoscopy and FICE. Random and target biopsies were obtained. Histopathological diagnosis was made and image patterns were evaluated. Seven endoscopists evaluated normal, colitis, and polyp images obtained with FICE. RESULTS: One hundred and twenty-three colon segments were evaluated and 1831 images were obtained from 18 patients. A total of 1652 images were FICE and 179 were standard images. Separate FICE images were obtained for normal colon mucosa, polypoid lesions, and colitis areas. Normal colon mucosa was best visualized using the second, sixth, and ninth FICE channel; polyps using the third, seventh, and ninth channel; and colitis using the second, third, and ninth channel. When all images were analyzed, the second and ninth channel were significantly better than the other channels. A total of 584 biopsies were obtained, including 492 (84.2%) random biopsies and 92 (15.7%) target biopsies. Random biopsies detected no dysplasia, but target biopsies detected low-grade dysplasia in three diminutive polyps. CONCLUSION: FICE was not significantly better at dysplasia screening than the standard procedure, but it effectively detected diminutive polyps and evaluated surface patterns without using magnification. FICE might contribute to the assessment of inflammation severity in patients with UC in clinical remission. However, more extensive studies are necessary to confirm these findings.

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.

The COVID-19 pandemic: Clinical practice advice for gastroenterologists, hepatologists, and liver transplant specialists.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a novel acute infectious disease that has rapidly reached staggering pandemic proportions. This review addresses gastroenterologists, hepatologists, liver transplant (LT) specialists, and health-care professionals working in the field of liver diseases and liver transplantation. It has been written based on a limited number of publications, recommendations of national and international liver and organ transplantation societies, and experiences of patients with COVID-19 around the world. The purpose of this review is to provide information addressing questions and concerns about COVID-19, to reveal the effects of the novel disease on patients with chronic liver disease and LT recipients, and to share information about ways in which this pandemic will affect clinical practices. We, the Turkish Association for the Study of the Liver (TASL), would like to remind you that this text is actually not a practical guide. It is imperative to act according to the standards set by health-care institutions and the Ministry of Health, Republic of Turkey.

Real-world efficacy and safety of Ledipasvir + Sofosbuvir and Ombitasvir/Paritaprevir/Ritonavir ± Dasabuvir combination therapies for chronic hepatitis C: A Turkish experience.

BACKGROUND/AIMS: This study aimed to evaluate the real-life efficacy and tolerability of direct-acting antiviral treatments for patients with chronic hepatitis C (CHC) with/without cirrhosis in the Turkish population. MATERIAL AND METHODS: A total of 4,352 patients with CHC from 36 different institutions in Turkey were enrolled. They received ledipasvir (LDV) and sofosbuvir (SOF)±ribavirin (RBV) orombitasvir/paritaprevir/ritonavir±dasabuvir (PrOD)±RBV for 12 or 24 weeks. Sustained virologic response (SVR) rates, factors affecting SVR, safety profile, and hepatocellular cancer (HCC) occurrence were analyzed. RESULTS: SVR12 was achieved in 92.8% of the patients (4,040/4,352) according to intention-to-treat and in 98.3% of the patients (4,040/4,108) according to per-protocol analysis. The SVR12 rates were similar between the treatment regimens (97.2%-100%) and genotypes (95.6%-100%). Patients achieving SVR showed a significant decrease in the mean serum alanine transaminase (ALT) levels (50.90±54.60 U/L to 17.00±14.50 U/L) and model for end-stage liver disease (MELD) scores (7.51±4.54 to 7.32±3.40) (p<0.05). Of the patients, 2 were diagnosed with HCC during the treatment and 14 were diagnosed with HCC 37.0±16.0 weeks post-treatment. Higher initial MELD score (odds ratio [OR]: 1.92, 95% confidence interval [CI]: 1.22-2.38; p=0.023]), higher hepatitis C virus (HCV) RNA levels (OR: 1.44, 95% CI: 1.31-2.28; p=0.038), and higher serum ALT levels (OR: 1.38, 95% CI: 1.21-1.83; p=0.042) were associated with poor SVR12. The most common adverse events were fatigue (12.6%), pruritis (7.3%), increased serum ALT (4.7%) and bilirubin (3.8%) levels, and anemia (3.1%). CONCLUSION: LDV/SOF or PrOD±RBV were effective and tolerable treatments for patients with CHC and with or without advanced liver disease before and after liver transplantation. Although HCV eradication improves the liver function, there is a risk of developing HCC.

Evaluation of fibrosis in chronic hepatitis C patients treated with direct-acting antivirals.

Background and Aim: This study is an evaluation of liver fibrosis measurements determined using transient elastography and aspartate aminotransferase-to-platelet ratio index (APRI) scores of patients diagnosed with chronic hepatitis C (CHC) who were treated with direct-acting antivirals (DAAs). Materials and Methods: The liver fibrosis measurements recorded using transient elastography, APRI scores, and the biochemical data from before and after treatment of 40 patients with CHC who were treated with DAA were reviewed. Patients who received paritaprevir+ritonavir/ombitasvir+dasabuvir were included in Group 1 (n=20), and patients who received sofosbuvir+ledipasvir±ribavirin in Group 2 (n=20). Results: The mean liver fibrosis measurement of the patients was 15.73±10.63 kPa (min-max: 5.20-45.00 kPa) before treatment and 2.56±8.84 kPa (min-max: 4.30-42.00 kPa) after treatment. There was a significant improvement in liver fibrosis with a regression of 20.16% at the end of treatment compared with the start (p=0.001) with no significant difference between treatment groups (p=0.542). The highest regression rate of 75% was seen in patients with F2 fibrosis at the end of treatment. Significant regression was also found in patients with F3 fibrosis, with a rate of 57.2%, and in those with F4 fibrosis, with a rate of 17.6% (p=0.035). Significant reduction was also observed in the APRI scores of patients at the end of treatment compared with the start of treatment (p<0.001), with no significant difference between treatment groups (p=0.328). Conclusion: Noninvasive assessments of CHC patients treated with DAA revealed regression in liver fibrosis measurements and APRI scores and significant improvements were seen in the stage of fibrosis in the early phases following treatment.

Analysis of socioeconomic status and other factors affecting patient-graft survival in patients undergoing liver transplantation.

Background and Aim: Liver transplantation is performed in increasing numbers due to advances in surgical techniques and the introduction of diverse immunosuppressive drugs. The present study aims to analyze the effects of socioeconomic status and education level on patient and graft survival, in addition to all these factors. Material and Methods: All patients aged 18 years and above who underwent consecutive liver transplantation at the Liver Transplantation Unit of Department of General Surgery at the Dokuz Eylül University Hospital and whose data were available were included in this study. Results: Incompliance was noted in 68.3% of the 278 patients. On the other hand, patient compliance did not have a significant effect on graft and patient survival. However, decreased levels in the parameters, such as education status, vocational status and socioeconomic status, were found to be correlated with patient compliance. A significant correlation was not found between these factors and patient and graft survival. Conclusion: Although a direct effect of socioeconomic status on patient and graft survival could not be shown the significant association of vocational status and education status which determine socioeconomic level with parameters other than patient and graft survival may affect the success of liver transplants.

Acute liver failure after bariatric surgery.

Obesity is a crucial health problem that is common today and may lead to systemic organ dysfunctions. In its treatment, bariatric surgeries are applied with increasing frequency and provide patients lose weight. However, it causes some complications in the post-operative period. Two of these rarely complications are acute liver failure and long-term chronic liver disease. Here, we present a case that died due to acute liver failure after bariatric surgery. If severe malnutrition persists in these patients, reversal surgery should be performed.

The Role of Log Odds of Positive Lymph Nodes in Predicting the Survival after Resection for Ampullary Adenocarcinoma.

Lymph node metastasis is a important factor on survival in ampullary adenocarcinoma. Log odds of positive lymph nodes (LODDS) is a novel prognostic indicator on lymph node status. We aimed to evaluate the prognostic impact of LODDS for the patients with ampullary adenocarcinoma who underwent R0 pancreaticoduodenectomy. The study includes 42 patients.. LODDS was calculated as "log (number of metastatic lymph nodes+0.5)/(number of total harvested nodes - metastatic lymph nodes+0.5)". LODDS subgroups were created based on their LODDS value: LODDS1(LODDS≤ - 1.5), LODDS2(-1.5 < LODDS≤ - 1.0), LODDS3(-1.0 < LODDS≤ - 0.5), LODDS4(LODDS> - 0.5). The mean survival time was 72.7 ± 7.82 months. Survival rates for 1, 3 and 5 years were 93%, 65% and 45%, respectively. The mean LODDS value was -1.0466 ± 0.51. LODDS subgroups show strong correlation with Overall Survival(OS). The mean survival were 114.8, 81.8, 56.6 and 25.6 months in LODDS subgroups 1, 2, 3 and 4, respectively (Log-rank; p = 0.002), in addition LOODS values shows correlation with perineural invasion and micro vascular invasion (p = 0.015 and p = 0.001 respectively). Findings in our patient group support the hypothesis that LODDS subgroups correlate with OS, and that value of LODDS has considerable role in prediction of OS as well.

Prevalance of Celiac Disease in Patients with Inflammatory Bowel Disease in Turkish Population.

BACKGROUND: Celiac disease (CD) and inflammatory bowel disease (IBD) involve inflammation of the gastrointestinal lumen, which environmental, genetic, and immunological factors have a role in their pathogenesis. The prevalence of celiac disease in IBD ranges from 0% to 14%. In this study, our aim was to determine the prevalence of CD in IBD patients followed by us who are attending the hospital or outpatient clinic over a period of time of seven years. METHODS: Seven hundred and fifty nine patients (425 M, 334 F, mean age: 46.75, 396 ulcerative colitis (UC), 363 Crohn's disease (CrD)) diagnosed and followed up for IBD between January 2009 and July 2016 were evaluated retrospectively, and clinical, demographic, laboratory, and endoscopic data were collected. RESULTS: CD was investigated in 79 (%10.4) inflammatory bowel disease patients according to symptoms, and in 5.06% (n = 4) of them, we diagnosed CD. The most common indication for investigating for CD was iron deficiency anemia unreponsive to iron supplementation. CONCLUSIONS: We did not find an increased prevalance of celiac disease in Turkish IBD patients in this study. In the presence of refractory iron deficiency anemia without any other cause in IBD patients, investigations for celiac disease should be considered.