The World Health Organization 2018 report stated that 2.3 billion persons over 15 years old consume alcohol, and a total of 3.0–3.3 million people died because of uncontrolled or harmful alcohol intake in 2016. Injuries, accidents, liver cirrhosis, and other medical disorders are mainly responsible for alco - hol-related disability and deaths. After emphasizing the importance of alco - hol-related disorders and necessary universal precautions, we focus on alcohol consumption features and alcohol-related cirrhosis and hepatocellular carci - noma in Turkiye. It is estimated that alcohol per se is responsible for 12% of cirrhosis and 10% of hepatocellular carcinoma cases. Additional factors such as hepatitis B virus and hepatitis C virus infections have markedly increased the risk of the development of hepatocellular carcinoma in alcoholic cirrhosis.

Solitary necrotic nodule of the liver (SNNL) is a rare benign lesion with uncertain etiology characterized by a “completely necrotic core” and a hyalinized capsule containing elastin fibers (Journal of Clinical Pathology 36:1181–1183, 1983). We report herein a 26-year-old woman with a previ- ous diagnosis of rheumatoid arthritis, systemic lupus erythematosus, and Sjögren’s syndrome and no history of malignancy who presented with a complaint of diarrhea of 1-year duration. In the abdominal ultrasound, mul- tiple paraaortic, portocaval, and ileal lymphadenopathies (LAPs) have been found with the largest one being 2 cm in size. The biopsy of the iliac LAP showed reactive nodular hyperplasia. An abdominal CT disclosed an inci- dental hypoechoic, heterogenous mass sized 27 × 27 mm close to segment VI of the liver. A trucut biopsy of this lesion was made, and clinicopatho- logic features of the specimen were compatible with a solitary necrotic nod- ule of the liver. Here, we discuss the diagnosis and the clinical course of this rare entity in light of current literature.

Hepatoportal sclerosis (HPS) is an idiopathic non-cirrhotic portal hyper - tension (INCPH) characterized by hypersplenism, portal hypertension, and splenomegaly. Hepatocellular carcinoma (HCC) is the most common form of liver cancer. Non-cirrhotic portal hypertension is an extremely rare cause of HCC. A 36-year-old woman was referred to our hospital with esophageal varices. All serologic tests for etiology were negative. Serum ceruloplasmin and serum Ig A-M-G were normal. In the follow-up, two liver lesions were identified on a triple-phase computer. The lesions had arterial enhancement but no washout in the venous phase. In the magnetic resonance imaging examination, differentiation in favor of HCC was considered at one of the lessions. Radiofrequency ablation therapy was first applied to a patient who had no signs of metastasis. Within 2 months, the patient underwent a living donor liver transplant. In explant pathology, well-differentiated HCC and HPS were considered the cause of non-cirrhotic portal hypertension. The patient has been followed without relapse for 3 years. The development of HCC in INCPH patients is still debatable. Despite the presence of liver cell atypia and pleomorphism in nodular regenerative hyperplasia liver speci- mens, a causal link between HCC and INCPH is yet to be established.

Background and Aim: The study aimed to investigate the effectiveness of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet values in predicting intrahepatic cholestasis of pregnancy (ICP) in the first trimester, together with the aspartate aminotransferase/platelet ratio index (APRI) score. Materials and Methods: This study consisted of a patient group diagnosed with ICP (n=49) and a control group (n=62). Laboratory tests of both groups were analyzed retrospectively. Results: The first-trimester APRI score and AST and ALT values were found to be statistically significantly higher than those of the control group. The platelet value was found to be statistically significantly lower in the study group, even though it was within the normal reference range. Conclusion: The first-trimester APRI score was found to be effective in predicting ICP. In addition, the first-trimester AST, ALT, and platelet values were found to be effective in predicting ICP diagnosed in the third trimester even though if not as much as the APRI score.

Background and Aim: Early diagnosis and treatment of chronic hepatitis B (CHB) disease are important for the prevention of complications such as cirrhosis and hepatocellular cancer. Liver biopsy is an invasive, complicated, and expensive diagnostic method, which is the gold standard for detecting fibrosis. The aim of this study was to investigate the role of these tests in predicting liver fibrosis and treatment decision. Materials and Methods: A total of 1051 patients diagnosed with CHB between 2010 and 2020 in the Gaziantep University Gastroenterology Department were ret- rospectively evaluated. AAR, API, APRI, FIB-4, KING score, and FIBROQ score were calculated at the time of onset diagnosis. In addition, the Zeugma score, a new formula that is thought to be more sensitive and specific, was determined. Nonin- vasive fibrosis scores were compared according to the biopsy results of the patients Results: In this study, the area values under the curve were 0.648 for the API score, 0.711 for the APRI score, 0.716 for the FIB-4 score, 0.723 for the KING score, 0.595 for the FIBROQ score, and 0.701 for the Zeugma score (p<0.05). No statis- tically significant difference was obtained for the AAR score. The KING, FIB-4, APRI, and Zeugma scores were the best indicators for detecting advanced fibrosis. For KING, FIB-4, APRI, and Zeugma scores, the cutoff value for the prediction of advanced fibrosis were ≥8.67, ≥0.94, ≥16.24, and ≥9.63 with a sensitivity of 50.52%, 56.77%, 59.64%, and 52.34%, specificity of 87.26%, 74.96%, 73.61%, and 78.11%, respectively (p<0.05). In our study, we compared the globulin and GGT parameters with fibrosis, which we used in the Zeugma score formula. Glob- ulin and GGT mean values were significantly higher in the fibrosis group (p<0.05). There was a statistically significant correlation between fibrosis and globulin and GGT values (p<0.05, r=0.230 and p<0.05, r=0.305, respectively). Conclusion: The KING score was found to be the most reliable method for the noninvasive detection of hepatic fibrosis in patients with chronic HBV. The FIB-4, APRI, and Zeugma scores were also shown to be effective in determining liver fibrosis. It was shown that the AAR score was not sufficient for detecting hepatic fibrosis. The Zeugma score, a novel noninvasive test, is a useful and easy tool to evaluate liver fibrosis in patients with chronic HBV and has better accuracy than AAR, API, and FIBROQ.

Background and Aim: Hepatic encephalopathy (HE) is a frequent compli- cation of liver diseases. Systemic inflammation is key for HE pathogenesis. The main goal of the study was to investigate the role of psychometric tests, critical flicker frequency (CFF), and comparative evaluation of inflammato- ry indicators for the diagnosis of covert HE (CHE). Materials and Methods: The study was a prospective, nonrandomized, case–control study with a total of 76 cirrhotic patients and 30 healthy vol- unteers. The West Haven criteria were used to determine the occurrence of CHE in cirrhotic patients. Psychometric tests were applied to healthy and cirrhotic groups. CFF, venous ammonia, serum endotoxin, IL-6, IL-18, tu- mor necrosis factor alpha (TNF-α) levels, and hemogram parameters were evaluated for cirrhotic patients. Results: CFF values and psychometric tests were found to accurately dis- criminate CHE positives from CHE negatives (p<0.05). When the control group was excluded, the digit symbol test and the number connection A test failed, unlike CFF and other psychometric tests. Using CFF, a 45 Hz cutoff value had 74% specificity and 75% sensitivity. Basal albumin levels (p=0.063), lymphocyte-to-monocyte ratio (LMR) (p=0.086), and neutro- phil-to-lymphocyte ratio (p 0.052) were significant, albeit slightly, among CHE groups. Basal albumin levels had 50% sensitivity and 71% specificity when 2.8 g/dL was used as a cutoff value to determine CHE. Conclusion: Both psychometric tests and CFF can be useful in diagnosing CHE. Using cytokine and endotoxin levels seems to be inadequate to diag- nose CHE. Using LMR and albumin levels instead of psychometric tests for diagnosing CHE can be promising.

Background and Aim: Metabolic dysfunction-associated fatty liver disease (MAFLD) is expected to be prevalent among kidney trans - plant recipients (KTRs). In this study, we evaluated the prevalence of MAFLD among KTRs, data that have not been investigated by any clin- ical study to date. Materials and Methods: We included a total of 52 KTRs and 53 age-, sex-, and BMI-matched individuals as the control group through prospective consecutive recruitment. We detected the presence of hepatic steatosis and liver fibrosis using the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) defined by FibroScan. Results: Among the KTRs, 18 (34.6%) had metabolic syndrome. The prevalence of MAFLD among the KTRs and controls was 42.3% and 51.9%, respectively (p=0.375). The CAP and LSM values did not dif- fer significantly between the KTRs and controls (p=0.222 and p=0.119). Among the KTRs, patients with MAFLD had significantly higher age, BMI, waist circumference, LDL, and total cholesterol levels (p<0.001, p=0.011, p=0.033, p=0.022, and p=0.029, respectively). In multivariable analysis, age was the only independent factor for MAFLD among the KTRs (OR: 1.120, 95% confidence interval (CI): 1.039–1.208). Conclusion: MAFLD among KTRs did not show a significantly higher prevalence compared to the normal population. Further clinical studies with larger populations are needed.

Background and Aim: Chronic liver disease (CLD) is a leading cause of morbidity and mortality worldwide with a wide etiological spectrum. Fi- broScan® is used for follow-up of fibrosis and steatosis. This single-cen - ter study aims to review the distribution of indications by referral to Fi - broScan®. Materials and Methods: Demographic characteristics, CLD etiolo - gies, and FibroScan ® parameters of the patients who were referred to our tertiary care center between 2013 and 2021 were retrospectively evaluated. Results: Out of 9345 patients, 4946 (52.93%) were males, and the medi- an age was 48 [18–88] years. Nonalcoholic fatty liver disease (NAFLD) was the most common indication (N=4768, 51.02%), followed by hepa- titis B (N=3194, 34.18%) and hepatitis C (N=707, 7.57%). Adjusting for age, sex, and CLD etiology, the results revealed that patients with old- er age (Odds ratio (OR)=2.908; confidence interval (CI)=2.597–3.256; p<0.001) and patients with hepatitis C (OR=2.582; CI=2.168–3.075; p<0.001), alcoholic liver disease (OR=2.019; CI=1.524–2.674, p<0.001), and autoimmune hepatitis (OR=2.138; CI=1.360–3.660, p<0.001) had increased odds of advanced liver fibrosis compared to NAFLD. Conclusion: NAFLD was the most common indication for referral to FibroScan®.

Background and Aim: Prevention of hepatitis B virus (HBV) reinfection is important for long-term outcomes following liver transplantation (LT). Hepatitis B immunoglobulin (HBIG) is used among recipients who have (i) native HBV disease, (ii) hepatitis B core antibody positivity (HBcAb positivity), or (iii) received HBcAb positive organs. Nucleos(t)ide analogue (NA) monotherapy is emerging for treating patients in this setting. There is no generalized consensus on the ideal dosage of HBIG. The aim of this study was to evaluate the efficacy of low-dose HBIG (1560 international unit [IU]) for post-LT HBV prevention. Materials and Methods: HBcAb positive patients who received either HBcAb positive or hepatitis B core antibody negative (HBcAb negative) organs and HBcAb negative patients who received HBcAb positive organs between January 2016 and December 2020 were reviewed. Pre-LT HBV serologies were collected. HBV-prophylaxis strategy included NA with/ without HBIG. HBV recurrence was defined as HBV deoxyribonucleic acid (DNA) positivity during the 1-year, post-LT follow-up. No HBV surface antibody titers were followed. Results: A total of 103 patients with a median age of 60 years participated in the study. Hepatitis C virus was the most common etiology. Thirty-seven HBcAb negative recipients and 11 HBcAb positive recipients with unde- tectable HBV DNA received HBcAb positive organs and underwent pro- phylaxis with 4 doses of low-dose HBIG and NA. None of the recipients in our cohort had a recurrence of HBV at 1 year. Conclusion: Low-dose HBIG (1560 IU) × 4 days and NA, for HBcAb positive recipients and HBcAb positive donors, appear to be effective in preventing HBV reinfection during the post-LT period. Further trials are needed to confirm this observation.

-

Recurrence is still a problem after liver transplant for hepatocellular carcinoma (HCC). We performed an updated systematic review and me ta-analysis of randomized controlled trials comparing tumor recurrence of mammalian target of rapamycin inhibitors (mTORi) versus Calci neurin inhibitor-based immunosuppression after liver transplantation for HCC. A systematic search was conducted in the following databas es: MEDLINE, EMBASE, and Cochrane Central Register of Control Trials databases. The Medical Subject Headings used in the search in cluded: “sirolimus,” “everolimus,” “mTORi,” “HCC,” “mTORi,” “he patic transplantation” “randomized controlled trials,” and “liver trans plantation (LT)”. Seven randomized controlled trials were included for meta-analysis. There were a total of 1,365 patients, with 712 of these patients receiving calcineurin inhibitors (CNIs) while 653 had received mTORi. Our meta-analysis revealed that patients that received mTO Ri-based immunosuppression had superior recurrence-free survival (RFS) at 1 year and 3 years with a hazard ratio of 2.02 and 1.36, re spectively. Meta-analysis also showed that within the first 3 years after LT for HCC, patients receiving CNIs-based immunosuppression have a higher recurrence than those receiving mTORi-based immunosuppres sion. Our meta-analysis revealed that recipients of mTORi-based immu nosuppression had a superior OS at 1 year and 3 years. mTORi-based immunosuppression is associated with decreased early recurrence and improved RFS and overall survival.

This study is written to report a case of 67-year-old female with known au toimmune hepatitis (AIH) who developed balance and walking difficulties. Clinical and imaging investigations were more suggestive of AIH suffering from lymphoproliferative disease. To identify the underlying suspected lym phoproliferative disease, series of brain scans were performed, which showed multiple brain lesions. This is a report on a striking case of multiple contrast enhanced brain lesions discovered in an AIH patient that was resolved upon withdrawal of azathioprine. Many side effects of azathioprine are acknowl edged around the world; however, to the very best of our knowledge, an article on azathioprine inducing suspected malignancy was never reported.

Fingolimod has been used for about ten years to treat multiple recurrent sclerosis. It has been reported that Fingolimod causes an elevation in liver enzymes. In this case report, the clinical and laboratory parameters im proved after discontinuation of the drug. However, there is no publication in the literature regarding acute liver failure and liver transplantation fol lowing Fingolimod treatment. In this article, we presented a 33 – year – old female patient who developed acute liver failure and underwent liver transplantation after Fingolimod treatment for recurrent multiple sclerosis.

Background and Aim: This study investigated the risk of the development of primary biliary cholangitis (PBC) in individuals who were incidentally identified as having positive antimitochondrial antibodies (AMA)-M2. Materials and Methods: We retrospectively reviewed extractable nuclear antibody (ENA) panel test results to identify the incidental AMA-M2- positive patients. Patients who filled the diagnostic criteria for PBC were excluded. AMA-M2-positive patients were further evaluated by physical examination, liver biochemistry, liver ultrasonography, and transient elas tography (TE) and were also closely followed. Results: We included 48 (n=45, 93% female) individuals with a median age of 49 (range: 20–69) years. The median follow-up duration was 27 months (range: 9–42) after the detection of AMA-M2. Thirty-three (69%) patients had concomitant autoimmune/inflammatory disorders. Twenty-eight (58%) individuals showed seropositivity for ANA, and 21 had (43%) positive AMA. Fifteen (31%) patients developed typical PBC according to the international PBC diagnostic criteria during the follow-up, and five of them (18%) had significant fibrosis (≥8.2 kPA) by TE at the time of PBC diagnosis. Conclusion: Two-thirds of the incidental AMA-M2-positive patients devel oped typical features of PBC after a median 27-month follow-up. Our re sults suggest that AMA-M2 patients should be closely followed up to detect the late development of PBC

Background and Aim: In chronic hepatitis B infection, antiviral therapy significantly reduces the incidence of complications. This study aimed to present real-life 12-month effectiveness and safety data for TAF. Materials and Methods: This Pythagoras Retrospective Cohort Study in cluded patients from 14 centers in Turkiye. The study presents 12-month results of 480 patients treated with TAF as initial therapy or after switching from another antiviral drug. Results: The study shows treatment of about 78.1% patients with at least one antiviral agent (90.6% tenofovir disoproxil [TDF]). The rate of unde tectable HBV DNA increased in both treatment-experienced and naive pa tients. In TDF-experienced patients, the rate of alanine transaminase (ALT) normalization increased slightly (1.6%) within 12 months, but the change was not statistically significant (p=0.766). Younger age, low albumin, and high body mass index and cholesterol were identified as risk factors for abnormal ALT after 12 months, but no linear relationship was detected. In TDF-experienced patients, renal and bone function indicators showed sig nificant improvement three months after the transition to TAF and remained stable for 12 months. Conclusion: Real-life data demonstrated effective virological and bio chemical responses with TAF therapy. After switching to TAF treat ment, gains in kidney and bone functions were achieved in the early period.

Background and Aim: Transarterial Chemoembolization (TACE) thera py is currently considered as first option therapy in the intermediate stage HCC. The purpose of our study is to assess the efficacy and prognostic factors related to the DEB- TACE therapy. Materials and Methods: The data from 133 patients with unresecetable HCC who were treated with DEB-TACE and followed between January 2011-March 2018 were retrospectively evaluated. To assess the efficacy of therapy, control imagings were performed at 30th and 90th days after the procedure. Response rates, survival outcomes, and prognostic factors were investigated. Results: According to the Barcelona staging system, 16 patients (13%) were in the early stage, 58 patients (48%) were in the intermediate stage and 48 patients (39%) were in the advanced stage. There were complete response (CR) in 20 patients (17%), partial response (PR) in 36 patients (32%), stable disease (SD) in 24 patients (21%) and progressed disease (PD) in 35 (30%) patients. Median follow-up time was 14 months (range 1-77 months). Median PFS and OS were 4 months and 11 months, re spectively. In multivariate analysis, posttreatment AFP ≥400 ng/ml was found to be an independent prognostic factor on both PFS and OS. Child Pugh classification and tumor size >7 cm were independent prognostic factors on OS. Conclusion: DEB-TACE is effective and a tolerable treatment method for unresectable HCC patients.

Background and Aim: Liver resection (LR) and liver transplantation (LT) are curative treatments for hepatocellular carcinoma (HCC). The main pur pose of this study was to compare the survival of LR and LDLT in patients with HCC within the Milan criteria. Materials and Methods: The results of the LR (n=67) and LDLT (n=391) groups were compared for overall survival (OS) and disease-free survival (DFS). Twenty-six of the HCCs in the LRs met the Milan and Child A cri teria. Also, 200 of the HCC patients in the LDLTs met the Milan criteria, of which 70 also met the Child A criteria. Results: Early mortality was higher in the LDLT group (13.9% vs 1.47%; p=0.003). The 5-year OS was higher in the LDLTs than the LRs, but not statistically significant (84.6% vs 74.2%; p=0.287). However, 5-year DFS was better in the LDLT group (96.8% vs 64.3%; p<0.001). When the LRs (n=26) and the LDLTs (n=70) that met both Milan and Child A criteria were compared, 5-year OS was similar (81.4% vs 74.2%; p=0.512), but DFS was better in the LDLTs (98.6% vs 64.3%; p<0.001). Conclusion: LR can be justified as the first-line treatment for HCC patients who meet Milan and Child A criteria in terms of early mortality and OS

-

Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease and is significantly associated with obesity, insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease. NAFLD has become the most prevalent chronic liver disease in Western countries, and the proportion of NAFLD-related cirrhosis among patients on liver transplantation waiting lists has increased. In light of the accumulated data about NAFLD, and to provide a common approach with multi-disciplines dealing with the subject, it has become necessary to create new guidance for diagnosing and treating NAFLD. This guidance was prepared following an interdisciplinary study under the leadership of the Turkish Association for the Study of the Liver (TASL), Fatty Liver Special Interest Group. This new TASL Guidance is a practical application guide on NAFLD and was prepared to standardize the clinical approach to diagnosing and treating NAFLD patients. This guidance reflects many advances in the field of NAFLD. The proposals in this guidance are meant to aid decision-making in clinical practice. The guidance is primarily intended for gastroenterology, endocrinology, metabolism diseases, cardiology, internal medicine, pediatric specialists, and family medicine specialists.

-

With the increasing incidence and prevalence of end-stage liver disease, demand for donor grafts continues to increase. Approaches on maximizing the potential donor grafts vary depending on the region. This review aims to summarize the current practice of liver transplantation with an emphasis on challenges encountered in developing countries.

Palliative care in decompensated cirrhotic patients is a developing concept which should be used in cirrhotic patients during the advanced and terminal stages. Hepatologists and liver transplant teams mostly ignore the patients palliative care issues while intensively dealing with the liver diseases and its complications. This review is a brief summary of the recently published guidance discussing the palliative care, symptom based treatments and end of life with a collaborative and standartized approach which is recom- mended to all health care workers of cirrhotic patients.

IgG4-related disease (IgG4-RD) is a fibro-inflammatory disease that can affect multiple organs. Autoimmune pancreatitis type 1 is a manifestation of IgG4-RD and can often mimic tumor-like masses. Autoimmune phenomena following COVID-19 mRNA vaccination are being increasingly reported. Currently, there are no cases in which IgG4-RD involving the hepatobiliary system has been reported following the COVID-19 vaccination. We present the first case of IgG4-RD and AIP type 1 to be associated with the mRNA- based COVID-19 vaccination.

Favipiravir (FPV) is an antiviral drug used in the treatment of severe acute respiratory syndrome coronavirus 2 infection. The main side effects of this drug are teratogenicity and hyperuricemia. Limited information is available on other side effects. Here, we aimed to present our toxic hepatitis case with prolonged jaundice after FPV treatment.

Liver transplantation is successfully achieved all over the world and in Turkiye. Similar to many middle and far east countries, donation from deceased donors has not reached the desired level in Turkiye. Therefore, in Turkiye, living donors have been frequently used for liver transplanta- tion. Although Turkiye is the leading country in Europe and one of the top three countries in the world executing LDLT, nationwide standardization of LDLT protocols, including donor and recipient evaluation and acceptance criteria, donor and recipient follow-up and reporting rules, and routine pe- riodic audits by the ministry of health authorities, has not been established. Therefore, we created a working group to study reviewing regulations of LDLT operation in Europe and the USA. The establishment and implemen- tation of standardization of LDLT operation will serve to improve the donor and recipient outcomes while preventing incomplete or incorrect practices. The guide prepared on this subject is presented in the Appendix.

Background and Aim: Portal vein thrombosis (PVT) is particularly de- tected in advanced liver cirrhosis patients. We aimed to analyze the risk factors for PVT in liver transplant candidates. Materials and Methods: Dataset for consecutive 165 cirrhotic patients who were evaluated for liver transplantation (LT) were retrospectively analyzed. We sorted patients into two groups: patients with PVT and patients without PVT. Included variables were age, sex, etiology of liver disease, body mass index, MELD-Na score, Child-Pugh score, clinical variables reflecting por- tal hypertension, and hepatocellular carcinoma. Univariate and multivariate logistic regression analyses were used to identify risk factors of PVT. Results: Of 165 LT candidates, 46 had PVT (27.9%). Ascites, thrombocy- topenia, history of variceal bleeding, and band ligation were risk factors for PVT in univariate analysis. In multivariate analysis, only a history of variceal bleeding (OR 3.45, 95% CI 1.02–11.6, p=0.046) significantly in- creased the risk of PVT. Conclusion: The previous history of variceal bleeding predicts PVT devel- opment in cirrhosis, suggesting that the severity of portal hypertension is a major predictive factor for PVT in patients with cirrhosis. Future prospec- tive studies are needed to risk stratifying cirrhosis patients prior to LT for future PVT development and to define the prophylactic role of anticoagu- lation in these patients.

Background and Aim: Several studies have suggested that treatment with direct-acting antivirals (DAAs) in patients with chronic hepatitis C virus (HCV) may be associated with an increased risk of developing hepatocel- lular carcinoma (HCC). We investigated the incidence and risk factors of HCC in HCV patients who achieved a sustained virologic response (SVR) following DAA therapies. Materials and Methods: The medical data of patients who were diagnosed with HCV and received DAA therapy in two tertiary centers in Turkey were retrospectively collected. Results: Among them, 75 patients (52.4%) were noncirrhotic and 68 pa- tients (47.6%) were cirrhotic. The overall SVR rate was 97.2% (139/143). It was 100% in noncirrhotic and 94.1% in cirrhotic patients. HCC was de- veloped in 5 (7.4%) patients, all of whom had baseline cirrhosis. The annual rate of HCC occurrence was 2.94%, and the 5-year cumulative incidence of HCC was 7.3%. The mean Child-Pugh score (CPS) and Model for End- Stage Liver Disease (MELD) score significantly decreased after DAA treat- ment (CPS 7.0 vs 5.9, p=0.001; MELD 10.8 vs 9.5, p=0.003). Conclusion: There was no significant increase in the rate of HCC in cir - rhotic HCV patients treated with DAAs. This treatment led to a remark- ably high SVR rate and lowered CPS and MELD scores in cirrhotic HCV patients.

Background and Aim: Chronic hepatitis B virus (HBV) infection is a ma- jor cause of hepatocellular carcinoma (HCC). Circulating cell-free DNA (cfDNA) methylation of tumor suppressor genes are emerging potential biomarkers in HCC. We aimed to evaluate the cfDNA methylation status of RASSF1 and CDKN2AIP genes in patients with liver cirrhosis (LC) with or without HCC caused by HBV. Materials and Methods: A total of 47 patients with HBV cirrhosis were included in the study. Patients were divided into two groups: HCC and LC (HCC+LC, n=22) and HBV cirrhosis only (LC, n=25). cfDNA was iso- lated from the plasma samples of the patients. Methylation analysis was performed for RASSF1 and CDKN2AIP genes. Results: Mean methylation percentage of CDKN2AIP gene was 0.001±0.004% in the HCC+LC group and 0.008±0.004 % in the LC only group. The mean methylation percentage of RASSF1 gene was 5.1±16.1% in the HCC+LC group and 9.7±25.9% in the LC only group. The methylation rate of CDKN2AIP was significantly lower in the HCC+LC group (p=0.027). A positive correlation was found with the absence of cfDNA methylation of CDKN2AIP gene in the presence of HCC (R=0.667, p=0.018). Conclusion: cfDNA methylation of CDKN2AIP and RASSF1 genes may provide important diagnostic information regarding the development of HCC in the setting of HBV cirrhosis.

Background and Aim: The aim of the present study was to examine the etiology of hepatocellular carcinoma (HCC) by underlying cause and deter- mine the characteristics and clinical features of patients with HCC. Materials and Methods: The study comprised 1802 HCC patients diag- nosed 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 extra- hepatic 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 character- istics 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.

Severe acute respiratory syndrome coronavirus 2 is a highly transmissible and pathogenic virus that leads to coronavirus disease 2019 (COVID-19). The preexisting liver diseases alter the course of COVID-19. Therefore, specific management strategies must be considered in individuals with chronic liver diseases (CLDs) and COVID-19. Autoimmune hepatitis (AIH) is a rare immune-mediated liver disease. Patients with AIH require life-long treatment with immunosuppressive drugs that may increase the risk of poor COVID-19 outcomes. The stage of underlying liver disease is another factor that can affect the clinical outcomes of COVID-19 in patients with AIH. In this review, we aim to provide relevant issues that will be helpful to clinicians in understanding and improving the clinical care for patients with AIH during the pandemic.

-

Hepatic myelopathy (HMy) is a rare neurological complication of liver cir- rhosis that involves spastic paraplegia caused by lateral cord demyelination especially due to the accumulation of some metabolites such as ammonia and manganese. We report a young adult woman presenting with spastici- ty and paraparesis in extremities after intrahepatic portosystemic shunting (TIPS) application and underwent deceased liver transplantation (LT). A 39-year-old woman underwent deceased LT because of cryptogenic liver cirrhosis. She underwent a TIPS procedure 5 years ago. After that, hepatic encephalopathy and spasticity appeared. She was on the waiting list for 3 years. Neurological findings after LT significantly decreased, but did not return to normal. After the emergence of neurological findings, the earlier LT can provide improvement in neurological findings.

D-penicillamine therapy is considered an effective and safe treatment for Wilson’s disease. Except for one experimental study, there has been no re- port in the literature about the development of disseminated intravascular coagulation (DIC) with the use of the drug. A 24-year-old female patient with Wilson’s disease, followed up with zinc and D-penicillamine treat- ment, was admitted to the emergency service because of oral mucosal bleeding and lethargy. Initial laboratory tests showed hemoglobin 7.1 g/dL (11.7-15.5), platelet 24×103 μL-1 (159-388), total bilirubin 18 mg/dL (0.3- 1.2), direct bilirubin 9.8 mg/dL (0-0.2), INR >10 (0.8-1.2), aPTT 64.5 s (22.5-32), fibrinogen 23 mg/dL (180-350), and factor 8 26.4% (70-150). Melena, hematemesis, and hematochezia were not present, and no active bleeding focus was detected on endoscopic evaluation. Upon meeting the DIC criteria, the patient underwent plasma exchange four times for the treat- ment of acute-on-chronic liver failure. Haemocomplettan-P, cryoprecipitate replacements were made as a supportive treatment for DIC. As the clini- cal bleeding continued despite plasma exchanges and factor replacement treatment, D-penicillamine was switched to trientine (1250 mg/day). After this change, the mucosal bleeding stopped, and DIC parameters improved. We suggest that if hemorrhagic complications develop on D-penicillamine treatment, the possibility of DIC induced by D-penicillamine activating the fibrinolysis should also be considered.

Background and Aim: We aimed to analyze the demographic, laboratory, and clinical characteristics of patients with HBeAg positive chronic hepati- tis B infection in tertiary care centers in Istanbul. Materials and Methods: We conducted an observational cohort with ≥18-year-old patients with HBeAg positive chronic hepatitis B infection, who were followed up in three tertiary care centers in Istanbul between January 2000 and August 2018, were evaluated by reviewing electronic and recorded files. The Ethical Committee of Istanbul Medipol University approved this study (Protocol no: 10840098-604.01.01-E.44136). During the polyclinic interview, consent was obtained from patients for analysis and publication. Results: The mean age of the 64 patients was 30 (range 18-39) years, and 50% (32) of them were males. The mean follow-up period of the patients was 67 (18-180) months. Twenty-four patients were treated with at least one antiviral in their follow-up, and only 2 (3.1%) of these patients developed HBeAg seroconversion without antiviral treatment. HBeAg (+) chronic hep- atitis B developed in 4 of the patients after the immune-active period. None of the patients and first-degree relatives had hepatocellular carcinoma (HCC). Conclusion: The rationality of antiviral treatment and HCC development risk in these patients still remains elusive

Background and Aim: Portal hypertension (PH) is a syndrome associ- ated with cirrhosis and characterized by a progressive increase in portal pressure, with consequent compensatory vascular dilation. Gastric vascular changes associated with oxidative and nitrosative stress characterize the clinical presentation of portal hypertensive gastropathy (PHG). In addition, the inflammatory process is considered an aggravating factor for severity by contributing to gastric tissue injury. The aim of this study was to investigate the synergistic anti-inflammatory and antioxidant action of N-acetylcyste- ine (NAC) in the stomach of rats with PH. Materials and Methods: Eighteen Wistar male rats were used in this ex- perimental protocol and were divided into three groups with six in each group: sham-operated (SO), partial portal vein ligation (PPVL), and PPVL + NAC. Treatment with NAC at a dose of 10 mg/kg (i.p.) was initiated on day 8 after surgery and continued for 7 days. We evaluated the expression of iNOS, NQO-1, HSP-90, and SOD by Western blot, as well as nuclear factor-kappa B (NF-κB) and tumor necrosis factor (TNF)-α staining by im- munohistochemistry, in the rat stomach. Results: The PPVL group exhibited increased expression of HSP-90, iNOS, SOD, and NQO-1 when compared with controls. NAC reduced the expression of all studied proteins. Similarly, NF-κB and TNF-α staining was increased in PPVL animals versus controls and reduced in PPVL + NAC versus PPVL animals, respectively. Conclusion: These results suggest the effectiveness of NAC as a dual an- ti-inflammatory and antioxidant in animals with experimental PHG induced by partial ligation of the portal vein.

Background and Aim: Hyaluronic acid (HA), a fundamental component of the extracellular matrix, is associated with chronic liver diseases. The aim of this study was to investigate quantitative HA measurement as a non- invasive marker for steatosis and fibrosis staging in nonalcoholic fatty liver disease (NAFLD) with biopsy evidence. Materials and Methods: In this study, 52 NAFLD patients with biopsy evidence and who met the inclusion criteria were included. Hepatic enzyme levels, HA levels, and other laboratory findings were examined. In addition, the degree of steatosis was determined via computed tomography (CT). Results: According to the degree of steatosis, HA levels were 29.17±22.66, 39.85±60.28, and 32.05±19.40, respectively, and no significant difference was found between the groups (p=0.584). In addition, HA levels were not found to be significant according to the degrees of steatohepatitis (p=0.860). However, a statistically significant relationship was found between steatosis levels detected by CT and biopsy (p<0.01). Conclusion: Serum HA level, other biochemical parameters, and steatosis severity measurement via CT did not appear to have any diagnostic value for nonalcoholic steatohepatitis. In this context, novel markers that may be useful for NAFLD diagnosis and severity assessment in risky individuals should be investigated.

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 biop- sies after liver transplantation, or liver masses in our hepatology clinic be- tween 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 ultra- sonography-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 percuta- neous liver biopsy group were chronic hepatitis B (n=127, 29.4%), normal histopathological findings (n=50, 11.6% and 32 of them were protocol biop- sies 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.

-

Hepatocellular carcinoma (HCC) accounts for some 80% of primary liver tumors. According to recent data, HCC is the sixth most common type of cancer and the third leading cause of cancer-related mortality worldwide. Risk factors for HCC include the presence of the hepatitis B virus, hepatitis C virus, non-alcoholic fatty liver disease, and exposure to noxious agents, such as alcohol, or toxins, such as aflatoxin, which are considered prevent- able etiologies of HCC. Monitoring strategies are needed for patients at risk of developing HCC. There is a consensus on routine monitoring of cirrhotic patients due to definitive evidence of a significantly high rate of progression to HCC; however, the appropriate surveillance of patients with advanced fibrosis remains a topic of discussion. Nevertheless, adherence to a strict observation protocol is the cornerstone of early detection and treatment with curative options for patients with a high risk of developing HCC. This review examines prevention strategies, risk factors, and surveillance based on current guidelines.

Graft Versus Host Disease (GVHD) is a severe immunological-clinico- pathological condition mediated by healthy T-lymphocytes in donor tis- sue against the immunosuppressed host tissue and rarely seen after solid organ transplantation (SOT). A 72-year old male patient underwent ca- daveric liver transplantation. On day 34 of the postoperative follow-up, the patient developed fever, generalized skin rash and hemorrhagic le- sions in the oropharynx. Skin biopsy was consistent with GVHD. Despite high-dose corticosteroid treatment, he died on postoperative day 51. Al- though it is seen rarely after liver transplantation, GVHD is an important clinical entity for which early diagnosis is critical due to its high rates of mortality.

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine carci- noma of the skin. Treatment for locoregional MCC includes local excision with regional lymphadenectomy, followed by adjuvant radiotherapy. Immune checkpoint inhibitors (ICI) have emerged as a breakthrough treatment of metastatic MCC. Nevertheless, T-cell immune response is triggered against self-antigens resulting in immune-mediated toxicities, including ICI-medi- ated hepatotoxicity. We report a case of recurrent metastatic MCC treated with avelumab, a PD-L1 inhibitor, with subsequent significant liver biochem- ical flare. The initial clinical diagnosis was ICI-mediated hepatotoxicity. Workup to rule out competing causes of liver injury came back negative. Hence, avelumab was discontinued, and the patient was initiated on steroid therapy with stepwise escalation. Owing to clinical and laboratory deteriora- tion, it was then decided to perform a percutaneous liver biopsy to document steroid-refractory ICI-mediated hepatotoxicity and/or rule out other causes of potential liver injury. The liver biopsy showed MCC tumor cells almost entirely infiltrating the hepatic parenchyma, confirmed by immunohisto- chemistry. At that point, steroid therapy was discontinued, and the patient was transitioned into palliative care. In conclusion, patients with apparent ICI-related hepatotoxicity should always be considered for a liver biopsy to exclude massive infiltrative malignancy as the true cause of liver dysfunction.

Background and Aim: This study examined the effects of black cumin seed oil treatment on oxidative stress and the expression of radixin and moesin in the liver of experimental diabetic rats. Materials and Methods: Eighteen rats were divided into 3 equal groups (control, diabetes, treatment). The control group was not exposed to any experimental treatment. Streptozotocin was administered to the rats in the diabetes and treatment groups. A 2.5 mL/kg dose of black cumin seed oil was administered daily for 56 days to the treatment group. At the conclusion of the experiment, the blood level of malondialdehyde (MDA) and glutathi- one (GSH) was measured. The expression level and the cellular distribution of radixin and moesin in the liver were analyzed. Results: The plasma MDA (3.05±0.45 nmol/mL) and GSH (78.49±20.45 μmol/L) levels in the diabetes group were significantly different (p<0.01) from the levels observed in the control group (MDA: 1.09±0.31 nmol/mL, GSH: 277.29±17.02 μmol/L) and the treatment group (MDA: 1.40±0.53 nmol/mL, GSH: 132.22±11.81 μmol/L). Immunohistochemistry and west- ern blotting analyses indicated that while the level of radixin was not sig- nificantly between the groups (p>0.05) and moesin expression was signifi- cantly downregulated (p<0.05) in the experimental group, the treatment was ineffective. Conclusion: The administered dose was sufficient to prevent oxidative stress, but was not sufficient to alleviate the effects of diabetes on moesin expression in hepatic sinusoidal cells.

Background and Aim: In this study, we aimed to assess the hemostatic and histopathological impacts of the Algan hemostatic agent (AHA) with the liver injury model. Materials and Methods: 24 male rats, 10-12 week old, were randomly divided into three equal groups (n=8) as control (physiological saline solu- tion), AHA liquid and AHA powder. A total of three iatrogenic cut injuries were performed on the anterior surface of the left liver lobe. After bleeding started, sponges soaked with physiological saline, AHA liquid, AHA pow- der were gently pressed on the injured area for 20 seconds in corresponding groups, respectively. The bleeding time was measured with a timer. Failure to stop bleeding after three consecutive applications was considered as a failure. Animals were euthanized at the tenth minute of the procedure. Left liver lobes were removed for histopathological examination. Results: Bleeding control success rates of AHA liquid were significantly higher than that of the AHA powder group, and both forms were more effec- tive than physiological saline. A superficial thick granulation tissue with en- trapped powder residual materials was detected in the AHA powder group. Liver parenchyma was intact in liquid and powder groups. Conclusion: AHA is a fast-acting and applicable hemostatic agent in the liver bleeding model. However, further comparative studies in various or- gans are needed.

Background and Aim: This study aimed to evaluate the changes in the clinical characteristics of chronic Hepatitis B (CHB) patients at the initia- tion of treatment over a 15-years period. Materials and Methods: The study included 659 treatment-naive CHB patients who started receiving nucleos(t)ide analogs between January 2006 and December 2020. The patients included in the study were divided into three groups of five years each, according to the start date of treatment. Results: The mean age was 46.2±14.5 years and 445 (67.5%) were male. Two hundred and five (31.1%) patients had cirrhosis. Hepatocellular carci- noma (HCC) developed in forty-one patients (6.2%). Compared to patients in Group 1, Group 2 were younger and had lower decompensated cirrhosis, HCC and ascites, had higher Child A cirrhosis (all p<0.05). Cirrhosis and esophageal varices were higher in patients in Group 3 compared to patients in Group 2 (all p<0.05). Entecavir or tenofovir use increased from 66.5% in Group 1 to 99.2% in Group 3 (p<0.05). Conclusion: The mean age at initiation of treatment for CHB patients in- creased. The patients had less cirrhosis. In the last 5 years, almost all pa- tients were treated with entecavir or tenofovir.

Background and Aim: Hepatocellular carcinoma (HCC) is one of the most common and most lethal cancers worldwide. The objective of this study was to investigate the relationship between basal parameters and survival characteristics in patients with HCC. Materials and Methods: The records of 1447 HCC patients of a tertiary center during the period 2000-2017 were screened retrospectively. The demographic details; basal clinical, laboratory, and radiological characteristics; treatments; and survival time were recorded and prognostic scores were calculated. Results: A total of 788 patients with HCC (male/female: 623/165; mean age: 60.5±10.9 years) were included in the study. The median length of sur- vival was 26.3 months (95% confidence interval [CI], 22.3-30.4 months). The 5-year survival rate was 28.1%. The number and diameter of the tu- mors; platelet count; platelet-to-lymphocyte ratio; level of aspartate ami- notransferase, alanine aminotransferase, and gamma-glutamyl transferase; portal and hepatic vein involvement; and an alpha-fetoprotein level of <9.6 ng/mL were found to be independently related to survival. Conclusion: The positive predictive value of the prognostic index derived from independent survival-related parameters for 5- and 10-year survival or overall survival was approximately 86%. Integration of this prognostic index to the criteria used in making treatment decisions for patients with HCC should be considered.

-