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.

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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.

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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.