The use of fully covered self-expandable metal stents in the endoscopic treatment of portal cavernoma cholangiopathy.

BACKGROUND AND AIMS: There are different therapeutic approaches for biliary strictures and reducing portal hypertension in patients with symptomatic portal cavernoma cholangiopathy (PCC). Endoscopic treatment includes endoscopic biliary sphincterotomy (EST), dilation of stricture with a biliary balloon, placement of plastic stent(s) and stone extraction. Fully covered self-expandable metal stent (FCSEMS) is placed as a rescuer in case of haemobilia seen after EST, dilation of stricture and removal of plastic stent rather than the stricture treatment itself. In this retrospective observational study, we sought to assess the clinical outcomes of FCSEMS as the initial treatment for PCC-related biliary strictures. MATERIALS AND METHODS: Twelve symptomatic patients with PCC both clinically and radiologically between July 2009 and February 2019 were examined. Magnetic resonance cholangiopancreatography (MRCP) and cholangiography were employed as the diagnostic imaging methods. Chandra-Sarin classification was used to distinguish between biliary abnormalities in terms of localization. Llop classification was used to group biliary abnormalities associated with PCC. Endoscopic partial sphincterotomy was performed in all the patients. If patients with dominant strictures 6-8-mm balloon dilation was first performed. This was followed by removal of the stones if exist. Finally, FCSEMS placed. The stents were removed 6-12 weeks later. RESULTS: The mean age of the patients was 40.9 ± 10.3 years, and 91.6% of the patients were male. Majority of the patients (n = 9) were noncirrhotic. Endoscopic retrograde cholangiopancreatography (ERCP) findings showed that 11 of the 12 patients were Chandra Type I and one was Chandra Type IIIa. All the 12 patients were Llop Grade 3. All patients had biliary involvement in the form of strictures. Stent placement was successful in all patients. FCSEMSs were retained for a median period of 45 days (30-60). Seven (58.3%) patients developed acute cholecystitis. There was no occurrence of bleeding or other complications associated with FCSEMS replacement or removal. All patients were asymptomatic during median 3 years (1-10) follow up period. CONCLUSIONS: FCSEMS placement is an effective method in biliary strictures in case of PCC. Acute cholecystitis is encountered frequently after FCSEMS, but majority of patients respond to the medical treatment. Patients should be followed in terms of the relapse of biliary strictures.

Psychometric tests, critical flicker frequency, and inflammatory indicators in covert hepatic encephalopathy diagnosis.

Background and Aim: Hepatic encephalopathy (HE) is a frequent complication 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 inflammatory 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 volunteers. 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, tumor necrosis factor alpha (TNF-α) levels, and hemogram parameters were evaluated for cirrhotic patients. Results: CFF values and psychometric tests were found to accurately discriminate 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 neutrophil-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 diagnose CHE. Using LMR and albumin levels instead of psychometric tests for diagnosing CHE can be promising.

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.

Baseline characteristics associated with survival in patients with hepatocellular carcinoma.

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 survival 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 tumors; platelet count; platelet-to-lymphocyte ratio; level of aspartate aminotransferase, 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.

Significance of detectable hepatitis B virus DNA in liver allograft tissue in long-term follow-up of liver transplant recipients.

Background and Aim: The objective of this study was to evaluate the long-term presence of hepatitis B virus (HBV) DNA in the liver grafts of liver transplant patients who received hepatitis B immunoglobulin (HBIg) plus oral antiviral hepatitis B virus prophylaxis and had negative HBV serum markers. Materials and Methods: Patients aged 18 years or older who underwent liver transplantation for HBV-related liver disease, had negative serum viral markers, and had a liver biopsy at least 3 years after liver transplantation were eligible for this study. Clinical, serological, and pathological data were retrospectively obtained from medical records. The HBV DNA of liver biopsy specimens was assessed using the polymerase chain reaction technique. Results: A total of 150 patients were included. A positive HBV DNA result was seen in 18 (12%) of the liver biopsies. The presence of intrahepatic HBV DNA was not associated with pre-transplantation serum viral markers, type of pre- or post-transplantation antiviral treatment, or post-transplantation immunosuppressive treatment. Conclusion: The findings suggest that while treatment with HBIg plus oral antiviral as post-transplantation HBV prophylaxis may result in a percentage of patients with persistent HBV DNA in the graft, the presence of HBV DNA in the liver graft may not be related to clinical HBV recurrence.

Predictive value of FibroScan in detecting liver fibrosis in HBeAg negative patients with chronic hepatitis B whose HBV DNA 2000-20000 IU/ml with ALT 1-2 times the upper limit of normal and those with HBV DNA >20000 IU/ml and normal ALT.

Objective: In hepatitis B infection, it is difficult to make a treatment decision in patients with slightly elevated transaminases and HBV DNA level between 2000 and 20000 IU/ml, and in those with normal ALT, despite high levels of HBV DNA. Objectives: In HBeAg negative patients whose HBV DNA levels were between 2000 and 20000 IU/ml with ALT 1-2 times the upper limit of normal (ULN) and those with HBV DNA >20000 IU/ml and normal ALT, the concordance between liver fibrosis in biopsy and liver stiffness measured by transient elastography with FibroScan® (FS) was investigated, and diagnostic value of FS to predict the liver fibrosis was tested. Methods: The patients were selected from the outpatient hepatology clinics between the dates of November 2014 and October 2016 among those who were taken liver biopsy. Transient elastography was obtained within 3 months after liver biopsy. The diagnostic value of FS in detecting advanced fibrosis or moderate to advanced (MTA) fibrosis was investigated for each group. Results: In 38 patients with HBV DNA 2000-20000 IU/ml and ALT 1-2×ULN, advanced fibrosis was detected in only one patient (2.6%) on liver biopsy, sensitivity of FS to show advanced fibrosis is 100%, specificity 78.3%, and diagnostic accuracy rate 79%. The area under curve was determined to be 0.892. In detecting MTA fibrosis, these values are 100%, 62%, 71%, and 0.810, respectively. Of 79 patients with HBV DNA >20000 IU/ml and normal ALT, five had advanced (5.5%) and 18 had MTA (23%) fibrosis. Sensitivity of FS in detecting advanced fibrosis was 100%, specificity 87.8%, and accuracy 88.6%, and these values for MTA fibrosis were 85.7%, 81%, and 82.3%, respectively. Conclusion: Because of false negativity in a few patients with HBV DNA >20000 IU/ml in detecting MTA, FS may be combined with other non-invasive techniques. Negative predictive values of FS in predicting advanced or MTA fibrosis were very high, while positive predictive values were low. However, FS may save several patients from liver biopsy.

An Update on Usage of High-Risk Donors in Liver Transplantation.

The ideal management for end stage liver disease, acute liver failure, and hepatocellular carcinoma (HCC), within specific criteria, is liver transplantation (LT). Over the years, there has been a steady increase in the candidates listed for LT, without a corresponding increase in the donor pool. Therefore, due to organ shortage, it has been substantially difficult to reduce waitlist mortality among patients awaiting LT. Thus, marginal donors such as elderly donors, steatotic donors, split liver, and donors after cardiac death (DCD), which were once not commonly used, are now considered. Furthermore, it is encouraging to see the passing of Acts, such as the HIV Organ Policy Equity (HOPE) Act, enabling further research and development in utilizing HIV grafts. Subsequently, the newer antivirals have aided in successful post-transplant period, especially for hepatitis C positive grafts. However, currently, there is no standardization, and protocols are center specific in the usage of marginal donors. Therefore, studies with longer follow ups are required to standardize its use.

Low recurrence rate of hepatocellular carcinoma following ledipasvir and sofosbuvir treatment in a real-world chronic hepatitis C patients cohort.

The aims of the present study were to evaluate the efficacy and tolerability of ledipasvir/sofosbuvir (LDV/SOF) with or without ribavirin in the treatment of chronic hepatitis C (CHC) in patients with advanced liver disease and to analyse whether the use of LDV/SOF treatment is associated with a new occurrence of hepatocellular carcinoma (HCC) during and after LDV/SOF treatment. The Turkish Early Access Program provided LDV/SOF treatment to a total of 200 eligible CHC patients with advanced liver disease. The median follow-up period was 22 months. All patients were Caucasian, 84% were infected with genotype 1b, and 24% had a liver transplantation before treatment. The sustained virological response (SVR12) was 86.0% with ITT analysis. SVR12 was similar among patients with Child-Pugh classes A, B and C disease and transplant recipients. From baseline to SVR12, serum ALT level and MELD score were significantly improved (P < 0.001). LDV/SOF treatment was generally well tolerated. Only one patient developed a new diagnosed HCC. Seventeen of the 35 patients, who had a history of previous HCC, developed HCC recurrence during the LDV/SOF treatment or by a median follow-up of 6 months after treatment. HCC recurrence was less commonly observed in patients who received curative treatment for HCC compared with those patients who received noncurative treatment (P = 0.007). In conclusion, LDV/SOF with or without ribavirin is an effective and tolerable treatment in CHC patients with advanced liver disease. Eradication is associated with improvements in liver function and a reduced risk of developing a new occurrence of HCC.

Colorectal cancer and dysplasia risk of ulcerative colitis patients in a tertiary referral center in Turkey.

BACKGROUND/AIMS: Patients with ulcerative colitis (UC) are at increased risk of colorectal cancer (CRC). High-grade dysplasia (HGD) and low-grade dysplasia (LGD) are premalignant conditions. The aim of this study is to evaluate the risk of CRC/dysplasia in patients with UC, and the related risk factors. MATERIALS AND METHODS: Medical records of 1659 patients dating between 1993 and 2016 were scanned from an inflammatory bowel disease database. A total of 801 patients with UC who underwent at least one colonoscopic procedure with at least 1-year follow-up period were included in the study. Clinical, endoscopic, and histopathological data were assessed. RESULTS: The mean disease duration was 6.7±6.6 years. The total disease duration was 5334 person-years duration (pyd), and 34% of patients had the disease for 8 years or longer. The prevalence of UC-associated CRC was 0.7%, and the prevalence of dysplasia was 0.85%. The overall incidence of CRC was determined to be 1.1/1000 pyd. The cumulative risk of CRC was 0.3% at 10 years, 1.3% at 20 years, and 5.9% at 30 years. The Cox regression analysis indicated that primary sclerosing cholangitis (HR:13.677, 95% CI:2.6-70.8, p = 0.012) was an independent risk factor for developing UC-associated CRC. CONCLUSION: This study underlined the low risk of CRC and dysplasia in patients with UC in a tertiary referral center in the western part of Turkey. Primary sclerosing cholangitis was found to be the most important risk factor for the development of CRC in patients with UC. Identification of risk factors is important to categorize patients into subgroups to know which patients will require frequent surveillance.

Rare cause of weight loss in a kidney transplant recipient: iron overload.

Various reasons such as malignancies and chronic infections may cause weight loss in kidney transplant patients. In this report, iron overload as a rare cause of weight loss in a kidney transplant patient is presented. Forty-seven-year-old male patient who transplanted from a deceased donor 5 years ago was hospitalized because of 20 kg of weight loss. In medical history, he had history of hemodialysis for 89 months and received 100-300 mg of intravenous iron therapy per week before transplantation and transfused eight units of blood. In physical examination, weight and height were 45 kg and 185 cm, respectively. Respiratory and cardiac auscultation was normal. Laboratory results revealed as follow: glucose 76 mg/dL, urea 60 mg/dL, creatinine 1.35 mg/dL, aspartate aminotransferase 74 U/L, alanine aminotransferase 77 U/L, C-reactive protein 2.59 mg/dL, albumin 3.3 g/dL, globulin 3.4 g/dL, white blood cells 3200/mm(3), hemoglobin 13.1 g/dL and platelets 190,000/mm(3). Chest and abdominal tomography didn't reveal any pathology. Portal Doppler ultrasound showed signs of early cirrhosis. Viral and autoimmune hepatitis markers were negative. Ferritin was 5300 ng/mL and transferrin saturation was 82%. In liver biopsy, hemosiderosis was diagnosed and heterozygous H63D gene mutation was detected. Totally, 19 units of phlebotomy were performed. Liver function tests and serum ferritin decreased gradually. At outpatient follow-up in 6 months, he returned to former weight. In conclusion, there can be several causes of weight loss in kidney transplant patients. Iron overload can come across as a rare cause of weight loss. In these patients, ferritin levels should be checked and diagnosis should be clarified by liver biopsy and gene mutation analysis.

Evaluation for Helicobacter pylori in Meckel's diverticulum by using real-time PCR.

BACKGROUND: Although Helicobacter pylori (H. pylori) has been identified in heterotopic gastric mucosa of Meckel's diverticulum, controversial results are reported in the pertinent literature. AIMS: The aim of this study was to evaluate for the presence of H. pylori histologically using hematoxylin-eosin and Toluidine Blue in Meckel's diverticulum and by real-time TaqMan polymerase chain reaction (PCR) in those with heterotopic gastric mucosa. METHODS: The study included 21 consecutive patients who had undergone resection of Meckel's diverticulum at our hospital between 1995 and 2007. The paraffin-embedded tissues were retrieved and reviewed for the presence of histological abnormalities and H. pylori-like organisms and for the presence or absence of heterotopic mucosa. H. pylori was sought in those cases that contained heterotopic gastric mucosa using real-time TaqMan PCR to amplify a fragment of the 23S ribosomal RNA (rRNA) gene of H. pylori. RESULTS: Upon histological examination, heterotopic gastric mucosa was found to be present in 12 cases. H. pylori was not identified in any of the sections examined. A genomic PCR product was also not obtained in real-time PCR study. CONCLUSIONS: We have confirmed that colonization of H. pylori, if it occurs at all, is exceedingly rare in heterotopic gastric mucosa of Meckel's diverticulum.

A cerebrovascular event after single-dose administration of recombinant factor VIIa in a patient with esophageal variceal bleeding.

Upper gastrointestinal bleeding (UGIB) is a life-threatening complication of cirrhosis that develops from esophageal varices in almost 70% of patients. The mortality rate from the bleeding episodes is reported to be 30% [1-4]. Standard management of UGIB of cirrhotic patients is vasoactive therapy combined with endoscopic procedures such as endoscopic sclerotherapy and band ligation [5]. Currently, it is reported that recombinant activated fVIIa (Novoseven, NovoNordisc) can correct the prothrombin time in decompensated cirrhotic patients and also can be used safely in Child's B and C cirrhotic patients with UGIB [6-8]. Herein, we describe the first case report in the literature of a cerebrovascular event after the administration of a single dose of fVIIa in a cirrhotic patient with esophageal variceal bleeding.