Approach to Liver Transplantation: Is There a Difference between East and West?

Liver transplantation (LT) remains the only curative treatment for end-stage liver disease as well as acute liver failure. With the exponential increase in organ demand due to the increasing incidence and prevalence of liver diseases, the need to overcome the supply and demand mismatch has arisen. In this review, we discuss the current universal status of LT, emphasizing various LT practices worldwide.

The frequency and clinical significance of antibodies to soluble liver antigen/liver pancreas in autoimmune hepatitis: a prospective single-center study.

BACKGROUND AND AIMS: Soluble liver antigen/liver pancreas antibodies (anti-SLA/LP) are specific markers for autoimmune hepatitis (AIH) that have been associated with a distinct clinical phenotype and a more aggressive form of AIH. We prospectively evaluated the frequency and clinical significance of anti-SLA/LP in Turkish patients with AIH. MATERIAL AND METHODS: We prospectively included patients diagnosed with AIH between January 2018 and May 2023. Autoantibodies were detected using by immunofluorescence and immunoblot. RESULTS: We included 61 (80%, female) AIH patients with a median age of 31 years (15-78) at the time of diagnosis. Anti-SLA/LP was detected in 20% ( n  = 12) of the patients. Baseline characteristics, treatment responses and outcomes were similar among anti-SLA/LP-positive and anti-SLA/LP-negative AIH patients. Anti-SLA/LP-positive patients had significantly higher biochemical response rates after 4 weeks (100 vs. 67%, P  = 0.027), 3 months (100 vs. 39%, P  < 0.001), 6 months (100 vs. 69%, P  = 0.041) of therapy but not after 12 months (100 vs. 76%, P  = 0.103) and at the end of follow-up (100 vs. 91%, P  = 0.328). Relapse rates following treatment response were similar in patients with and without anti-SLA/LP (22 vs. 23%, P  = 0.956). Second-line therapies (tacrolimus and mycophenolate mofetil) were given to seven (11%) patients, all were anti-SLA/LP-negative. Two of these progressed into end-stage liver disease and both underwent liver transplantation. CONCLUSION: Our study results suggest that anti-SLA/LP positivity does not entail clinically distinct or severe features in AIH. In our cohort, anti-SLA/LP-positive patients showed a quicker response to immunosuppressive therapy.

Experimental Study: The Effect Of 20% Intralipid Emulsion Therapy In Cerebral Ischemic Reperfusion.

BACKGROUND: This experimental study was conducted to investigate the effect of 20% Intralipid Emulsion (ILE) treatment on Cerebral Ischemia Reperfusion Injury (CIRI) after reperfusion in acute ischemic stroke. METHODS: In this experimental study, seven rats without any intervention (control group), seven rats (sham group) for which CIRI was created after the common carotid artery was ligated for 2 hours, and seven rats who were treated with 20% ILE after CIRI (CIRI + ILE group) were sacrificed after 24 hours, and histopathological findings were investigated. RESULTS: In rats that were not treated after CIRI, 52.7% had level-1, 32.7% had level-2. and 14.5% had level-3. histopathological findings. While 72.2% of the rats treated with ILE had level-1 and 27.8% had level-2 findings, no level-3 histopathological findings were detected in any of the rats. While no signs of coagulative necrosis, spongiosis of surrounding tissue and polymorphonuclear leukocytes were observed histopathological in any of the rats given ILE, there was no macrophages finding in 85.6% of the rats. ILE treatment also reduced the histopathological findings of eosinophilic neurons, astrogliosis, neovascularization, vascular thrombosis and mononuclear inflammatory cells. CONCLUSION: This study showed that 20% ILE treatment reduces the histopathological damage seen in cerebral ischemia and CIRI.

Practice patterns and considerations in liver transplantation from living donors with high BMI: A review.

Living Donor Liver Transplantation (LDLT) is a valuable solution to the shortage of donor organs for patients with end-stage liver disease. However, the eligibility of obese donors for LDLT remains a subject of debate. This literature review explores global practices and perceptions of LDLT, identifies donor eligibility criteria, and discusses special considerations and ethical caveats. The review highlights the need for standardized guidelines for donor selection, considering the global distribution of Body mass index and variations in population-specific criteria. It also emphasizes the importance of non-invasive testing and pre-operative optimization of liver steatosis for select obese donors. Furthermore, the review examines the outcomes and complications associated with obese donors in LDLT. The findings of this review contribute to the ongoing discussion on the inclusion of obese donors in LDLT and provide insights for future research and guideline development.

Clinical Outcomes of Older Patients with Non-Variceal Upper Gastrointestinal Bleeding Taking Anti-Thrombotic or Non-Steroidal Anti-Inflammatory Agents.

BACKGROUND/AIMS: Non-variceal upper gastrointestinal bleeding is a well-established complication of non-steroidal anti-inflammatory drugs and anti-thrombotics. Both medication groups are frequently used by older populations and increase the incidence of non-var- iceal upper gastrointestinal bleeding; however, their impact on etiology and outcomes of non-variceal upper gastrointestinal bleeding has not been well defined. We aimed to compare the etiology and outcomes of non-variceal upper gastrointestinal bleeding in older patients who use anti-thrombotics and non-steroidal anti-inflammatory drugs or do not use either of them. MATERIALS AND METHODS: This is a single-center prospective study of patients older than 65 years with non-variceal upper gastrointesti- nal bleeding. Endoscopic findings, laboratory values, blood transfusion, endoscopic treatment, re-bleeding, and 30-day mortality rates were recorded. RESULTS: A total of 257 patients (median age 77.7 ± 8.2, 59% male) were included. Re-bleeding occurred in 25 (10%) and the 30-day mortality rate was 40 (16%). There was no statistically significant difference between patients using anti-thrombotics, non-steroidal anti-inflammatory drugs or non-users for blood transfusion (P = .46), endoscopic hemostasis (P = .39), re-bleeding (P = .09), and 30-day mortality (P = .45). Peptic ulcer was the most common etiology in all groups (124, 48%). Although the incidence of peptic ulcer was similar between drug users and anti-thrombotic users (P = .75), the incidence of peptic ulcer was significantly higher in patients using non-steroidal anti-inflammatory drugs than in patients who did not use drugs (P = .05). When the patients were analyzed as using anti- thrombotic drugs or non-steroidal anti-inflammatory drugs or neither, no statistically significant difference was found between ulcer location, ulcer number, and ulcer size. CONCLUSION: Non-variceal upper gastrointestinal bleeding increasingly occurs in older populations with several comorbidities; non- steroidal anti-inflammatory drugs or anti-thrombotics do not seem to change the clinical outcomes among older patients with non- variceal upper gastrointestinal bleeding.

Comparison of normal saline and antiseptic solution effect on the early peristomal infection rates of patients with percutaneous endoscopic gastrostomy tubes: A randomized double-blind study.

BACKGROUND: This study's aim was to compare the efficacy of normal saline (NS) with that of antiseptic solution in early peristomal skin care after percutaneous endoscopic gastrostomy placement in terms of peristomal infection incidence. METHODS: This was a randomized controlled double-blind study conducted at a university hospital between December 2019 and April 2021. All patients who underwent percutaneous endoscopic gastrostomy and met the inclusion and exclusion criteria were included in the study. The study population consisted of 64 patients randomized to group 1: NS (n = 31) and group 2: 0.1% polyhexamethylene biguanide and 0.1% betaine (PHMB-B; n = 33). Daily peristomal skin care was performed for 7 days, starting 24 h after insertion. Peristomal skin was evaluated by two blinded investigators before each dressing, and findings were recorded. Data analysis was performed with descriptive statistics; chi-square analysis; and exact, Shapiro-Wilk, Mann-Whitney U, and Cochran Q tests. RESULTS: There was no statistically significant difference between the groups in terms of peristomal infection rates (group 1: 12.9%, group 2: 9.07%; P > 0.05). Redness increased from day 4 in group 1 and day 5 in group 2, and exudate increased from day 5 in both groups. There is a statistical difference in the number of patients between the days when redness and exudate appear and increase. CONCLUSION: Both NS and PHMB-B solutions can be preferred in peristomal care. However, NS may be the first choice for early peristomal care that does not show signs of infection, because it is not irritating and allergic and is cost-effective.

Gastroplasty with endoscopic myotomy for the treatment of obesity.

Video 1Demonstration of the steps of gastroplasty with endoscopic myotomy for the treatment of obesity.

Ileocecal valve that cannot be intubated in Crohn's disease: is this a sign of poor prognosis?

BACKGROUND: In Crohn's disease (CD), the inability to intubate the ileocecal valve during colonoscopy may be associated with a poor disease prognosis. In this study, we aimed to compare the long-term outcomes of CD patients with and without ileocecal valve intubation during colonoscopy to assess its value as a prognostic parameter. METHODS: This retrospective study involved CD patients with isolated ileal involvement who underwent colonoscopy between 1993 and 2022. We compared the basic characteristics and long-term clinical outcomes of two groups of patients: those with intubated and non-intubated ileocecal valves during colonoscopy. RESULTS: Of the 155 participants, 97 (62.5%) patients' ileum could be intubated and 58 (37.5%) could not be intubated. The non-intubated group was younger at diagnosis (39 years versus 30.5 years, p = 0.002), but other baseline characteristics such as sex, smoking status, disease duration, perianal disease, and upper gastrointestinal involvements were similar. The non-intubated group had higher rates of steroid dependence (67.2% versus 46.4%; p = 0.012), biologic treatment (89.7% versus 58.8%; p < 0.001), CD-related hospitalization (81% versus 24.7%; p < 0.001), and major abdominal surgery (58.6% versus 15.5%; p < 0.001). In the logistic regression analysis, the positive predictors of successful ileum intubation were inflammatory type CD (OR: 14.821), high serum albumin level (OR: 5.919), and older age (OR: 1.069), while the negative predictors were stenosing (OR: 0.262) and penetrating (OR: 0.247) CD behavior. CONCLUSIONS: In Crohn's disease patients with isolated ileal involvement, ileocecal valve cannot be intubated during colonoscopy may indicate the severity of the disease.

Transcriptomic Analysis of Hepatitis B Infected Liver for Prediction of Hepatocellular Carcinoma.

Hepatocellular cancer (HCC) is a leading cause of cancer-related mortality worldwide, and chronic hepatitis B virus infection (CHB) has been a major risk factor for HCC development. The pathogenesis of HBV-related HCC has been a major focus revealing the interplay of a multitude of intracellular signaling pathways, yet the precise mechanisms and their implementations to clinical practice remain to be elucidated. This study utilizes publicly available transcriptomic data from the livers of CHB patients in order to identify a population with a higher risk of malignant transformation. We report the identification of a novel list of genes (PCM1) which can generate clear transcriptomic sub-groups among HBV-infected livers. PCM1 includes genes related to cell cycle activity and liver cancer development. In addition, markers of inflammation, M1 macrophages and gamma delta T cell infiltration are present within the signature. Genes within PCM1 are also able to differentiate HCC from normal liver, and some genes within the signature are associated with poor prognosis of HCC at the mRNA level. The analysis of the immunohistochemical stainings validated that proteins coded by a group of PCM1 genes were overexpressed in liver cancer, while minimal or no expression was detected in normal liver. Altogether, our findings suggest that PCM1 can be developed into a clinically applicable method to identify CHB patients with a higher risk of HCC development.

Training in Endoscopic Submucosal Dissection in the United States: The Current Paradigm.

Endoscopic submucosal dissection (ESD) training in Japan is pursued through a designated master-apprentice, organ-based stepwise training model. However, applying a similar program to the United States is not a practical strategy due to the significant differences in the training system and disease prevalence. To incorporate the ESD training into the current advanced endoscopy fellowship program, the use of recently developed techniques and technologies to improve the efficiency of ESD is ideal. The ESD training program in the United States should be prevalence-based, with increased involvement of trainees depending on their objectively assessed competency levels.

Novel single-operator through-the-scope traction device for endoscopic submucosal dissection: Outcomes of a multicenter randomized pilot ex-vivo study in trainees with limited endoscopic submucosal dissection experience (with video).

Objectives: Endoscopic submucosal dissection is a technically demanding procedure. The pilot study aimed to prospectively evaluate the efficacy and safety of a novel single-operator through-the-scope dynamic traction device among trainees with limited endoscopic submucosal dissection (ESD) experience. Methods: Randomized, controlled, pilot study comparing traction-assisted ESD (T-ESD) versus conventional ESD (C-ESD) in an ex-vivo porcine stomach model. Trainees were randomized to group 1 (T-ESD followed by C-ESD) and group 2 (C-ESD followed by T-ESD). Lesions were created on the gravity-dependent area of the stomachs. The primary outcome was submucosal dissection speed. Secondary outcomes included differences in en-bloc resection, adverse events, and workload, assessed by the National Aeronautical and Space Administration Task Load Index (NASA-TLX). Results: Five trainees performed two T-ESD and two C-ESD each, for a total of 20 procedures. Submucosal dissection speed was significantly faster in the T-ESD group compared to the C-ESD group (43.32 ± 22.61 vs. 24.19 ± 15.86 mm2/min; p = 0.042). En-bloc resection was achieved in 60% with T-ESD and 70% with C-ESD (p = 1.00). The muscle injury rate was higher in the C-ESD group (50% vs. 10%; p = 0.21) with 1 perforation reported with C-ESD and none with T-ESD. NASA-TLX physical demand was lower with T-ESD compared to C-ESD (4.5 ± 2.17 vs. 6.9 ± 2.50; p = 0.03). Conclusion: T-ESD resulted in faster submucosal dissection and less physical demand when compared to C-ESD, as performed by trainees in an ex-vivo gravity-dependent model. Future studies are needed to assess its role in human ESD cases.

Evaluation of Corneal Alterations After Short-Term Silicone Hydrogel Contact Lens Use by Confocal Microscopy.

Objectives: To evaluate the corneal subbasal nerve morphology, corneal sensitivity, and anterior segment alterations in short-term silicone hydrogel contact lens (SiHCL) users by confocal microscopy. Materials and Methods: The study included 25 right eyes of 25 male volunteers aged 25-30 years who had never used SiHCLs before. ocular surface disease index (OSDI), tear break-up time, Schirmer test, tear meniscus area, strip meniscometry tube, corneal sensitivity, and corneal subbasal nerve morphology were evaluated before and after 1 month of CL use. Results: OSDI was 10.6±1.1 before CL use and 17.2±1.2 after 1 month of CL use (p<0.01). Schirmer test distance was 16.3±2.3 mm before and 14.3±1.9 mm after 1 month of CL use (p>0.05). Tear film break-up time was 7.1±0.4 s before and 6.2±0.3 s after CL use (p>0.05). The tear meniscus area was 0.026±0.002 mm2 before and 0.024±0.001 mm2 after 1 month of CL use (p>0.05). Strip meniscometry tube results were 5.4±0.9 mm before and 4.9±0.8 mm after 1 month of CL use (p>0.05). Corneal sensitivity values were 3.2±0.4 mm before and 2.95±0.3 mm after 1 month of CL use (p>0.05). Dendritic cell density evaluated by confocal microscopy was 14.84±3.1 cells/mm2 before and 32.57±4.2 cells/mm2 after 1 month of CL use (p<0.01). Subbasal nerve tortuosity was 0.92±0.2 before and 1.03±0.2 after 1 month of CL use (p>0.05). Subbasal nerve density was measured as 4726±310 pixels/frame before and 4570±272 pixels/frame after 1 month of CL use (p>0.05). Conclusion: After a month of SiHCL use, no significant changes were observed in tear secretion, corneal sensitivity, tear meniscus volume, subbasal corneal nerve density, reflectivity, or tortuosity, while a significant increase was found in OSDI and dendritic cell density.

Comparison of Central Corneal Thickness Measurements with Four Different New Devices and Ultrasound Pachymetry.

Objectives: To assess the central corneal thickness (CCT) with 5 different devices, evaluate the repeatability of the devices, and determine the possible relationship between thickness values and sex. Materials and Methods: The study included 308 eyes of 154 patients (76 women, 78 men) between the ages of 18-30 who presented to the Ophthalmology Clinic of Mugla Sitki Koçman University Training and Research Hospital. Autorefractor (Topcon, Japan), ultrasound pachymetry (UP) (Ceniscan, USA), high-resolution Pentacam (Oculus, USA), anterior segment-optical coherence tomography (AS-OCT) (Optovue, USA), and Spectralis AS-OCT (Heidelberg, Germany) measurements were assessed. Results: The mean age of the study participants was 23.2±0.2 years and the mean CCT was 540±14.1 µm, with no statistically significant difference in CCT between sexes (p>0.05). Mean CCT values were 557.0±26.7 µm with the autorefractor, 543.6±32.9 µm with UP, 533.8±30.2 µm with the Oculus Pentacam, 519.8±30.1 µm with Optovue AS-OCT, and 547.5±31.6 µm with Heidelberg AS-OCT. Pairwise comparisons between devices showed that the Optovue AS-OCT gave significantly lower CCT measurements than the autorefractor and Heidelberg AS-OCT device (p=0.027 and p=0.033, respectively). The coefficient of repeatability for autorefractor, UP, high-resolution Pentacam, Optovue AS-OCT, and Heidelberg AS-OCT CCT measurements were 1.51%, 2.46%, 3.72%, 2.57%, and 3.34%, respectively. Conclusion: Measurements made with five different devices showed that CCT was comparable and clinically usable. However, it was determined that the Optovue AS-OCT showed lower CCT values compare to other devices. When compared in terms of repeatability, it was found to be lower in the Pentacam than other devices.

Novel articulating through-the-scope traction device.

Video 1Parts and functions of the novel articulating traction device with its application in gastric and colonic endoscopic submucosal dissection procedures.

Magnetic Resonance Imaging Predictors of Hepatocellular Carcinoma Progression and Dropout in Patients in Liver Transplantation Waiting List.

With the rising incidence of hepatocellular carcinoma (HCC), more patients are now eligible for liver transplantation. Consequently, HCC progression and dropout from the waiting list are also anticipated to rise. We developed a predictive model based on radiographic features and alpha-fetoprotein to identify high-risk patients. Methods: This is a case-cohort retrospective study of 76 patients with HCC who were listed for liver transplantation with subsequent liver transplantation or delisting due to HCC progression. We analyzed imaging-based predictive variables including tumor margin (well- versus ill-defined), capsule bulging lesions, volumetric analysis and distance to portal vein, tumor numbers, and tumor diameter. Volumetric analysis of the index lesions was used to quantify index tumor total volume and volumetric enhancement, whereas logistic regression and receiver operating characteristic curve (ROC) analyses were used to predict the main outcome of disease progression. Results: In univariate analyses, the following baseline variables were significantly associated with disease progression: size and number of lesions, sum of lesion diameters, lesions bulging the capsule, and total and venous-enhancing (viable) tumor volumes. Based on multivariable analyses, a risk model including lesion numbers and diameter, capsule bulging, tumor margin (infiltrative versus well-defined), and alpha-fetoprotein was developed to predict HCC progression and dropout. The model has an area under the ROC of 82%, which was significantly higher than Milan criteria that has an area under the ROC of 67%. Conclusions: Our model has a high predictive test for patient dropout due to HCC progression. This model can identify high-risk patients who may benefit from more aggressive HCC treatment early after diagnosis to prevent dropout due to such disease progression.

Characteristics of patients with hepatocellular carcinoma: A multicenter study.

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.