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.

A single-center experience: Liver biopsy results during a year.

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 biopsies after liver transplantation, or liver masses in our hepatology clinic between 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 ultrasonography-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 percutaneous liver biopsy group were chronic hepatitis B (n=127, 29.4%), normal histopathological findings (n=50, 11.6% and 32 of them were protocol biopsies 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.

Steatotic and Steatohepatitic Hepatocellular Carcinomas: Features in a Series With Predominantly Viral Etiology.

Hepatocellular carcinomas (HCCs) with steatohepatitis and steatosis are reported with varying definitions and clinicopathologic features. We aimed to search the attributes of steatohepatitic hepatocellular carcinoma (SH-HCC) and steatotic-HCC in our series. A retrospective clinicopathologic analyses of 150 HCCs and immunostaining for C-reactive protein (CRP) and serum amyloid A (SAA) were performed. Tumors were reclassified as all SH-HCC, limited SH-HCC, typical SH-HCC (steatohepatitic features in >5%, 5% to 50%, and ≥50% of the tumor, respectively), steatotic-HCC, and classic HCC (C-HCC). Group comparisons were made using Kruskal-Wallis and Kaplan-Meier tests. The background etiology in all SH-HCCs was pure viral in 51.4%, nonalcoholic steatohepatitis (NASH)/alcoholic liver disease (ALD) alone/mixed in 34.3%, and unidentified in normal liver in 14.3%. All SH-HCCS (n=35, 23.3%) and typical SH-HCCs (n=13, 8.6%) had higher NASH/ALD. Limited SH-HCCs (n=22, 14.6%) had higher ALD (all P<0.05). Typical SH-HCCs tended to have more NASH (P=0.054). Steatotic-HCCs (n=13, 9%) and C-HCCs (n=102, 68%) had higher pure viral etiology and serum CRP (all P<0.05). CRP and SAA were positive in 69% and 27% of the tumors, respectively. SAA positivity correlated with ALD (P=0.026). In the overall group disease-free survival rates at 1, 5, 10, and 20 years were 97.0%, 82.3%, 79.6%, and 77.2%, respectively. Demographics, tumor characteristics, CRP and SAA positivity, and survival were similar between the groups (P>0.05). SH-HCC is heterogenous in terms of underlying etiologies, and can be seen in NASH/ALD, pure viral and noncirrhotic/normal background. The ≥50% cutoff for the definition of SH-HCC can lead to overlook ALD-related SH-HCC. Steatotic-HCC seems more similar to C-HCC rather than SH-HCC, but none of them feature as a different prognostic group.

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.

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.

Prospective randomized single-blind study of post-operative bleeding after minor oral surgery in patients with cirrhosis.

BACKGROUND/AIMS: The management of patients with cirrhosis requiring dental extractions is complicated due to an increased risk of post-operative bleeding. Topical hemostatic agents are usually required to control bleeding in these cases, as an adjunct to systemic measures of hemostasis. The aims of this randomized, prospective, single-blind clinical study are twofold. The primary aim is to compare the hemostatic efficacy of chitosan and surgicel in patients with cirrhosis after a tooth extraction, and the secondary aim is to assess the value of the current setting as a clinical model of post-operative bleeding following minor oral surgery. MATERIAL AND METHODS: Fifty patients with cirrhosis scheduled for a tooth extraction under local anesthesia were prospectively included in the study in a randomized fashion. Patients were blinded to the treatment group they were in. The cirrhosis classification, bleeding time, trauma score, and corrected bleeding time (during post-operative reviews) were recorded. Statistical evaluations were done. RESULTS: Study groups had an equal number of teeth extractions (40 teeth each). There were no statistically significant differences between the groups with respect to patient demographics, cirrhosis classification, trauma score, and bleeding time. No side effects were noted. CONCLUSION: Both Celox and Surgicel are effective for controlling bleeding and are safe after a tooth extraction in patients with cirrhosis.

Seroprevalence of hepatitis A,B, and C viruses in Turkish alcoholic cirrhotics and the impact of hepatitis B on clinical profile.

INTRODUCTION: The aims of this study were to detect the seroprevalence of hepatitis A, B, and C viruses in Turkish alcoholic cirrhotics, and to evaluate the impact of hepatitis B infection on clinical profile at first admittance. METHODOLOGY: Serological markers for hepatitis A, B, and C viruses in 300 alcoholic cirrhotics diagnosed between January 1994 and December 2012 were retrospectively reviewed. Among them, 148 eligible patients were divided into group 1 (HBsAg positive, n = 43) and group 2 (HBsAg and anti-HBc negative, n = 105). Clinical characteristics at first admittance of groups 1 and 2 were compared. RESULTS: The seroprevalence of anti-HAV total, HBsAg, and anti-HCV was found to be 91.5%, 16.3%, and 8.2%, respectively. The prevalence of hepatocellular carcinoma was higher in the HbsAg-positive group compared to HbsAg- and anti-HBc-negative group (16.3% vs. 2.9%, p = 0.007). Other clinical features were similar in the two groups. CONCLUSIONS: Alcoholic cirrhotics have higher frequencies of HBsAg and anti-HCV than the general population. These patients should be investigated for coexistent HBV and HCV infections, and HBV vaccination should not be neglected. Alcoholic cirrhotic patients with concomitant HBV infection should be closely screened for hepatocellular carcinoma.

Ornidazole-induced autoimmune hepatitis.

BACKGROUND/AIMS: Certain drugs including oxyphenisatin, methyldopa, nitrofurantoin, diclofenac, interferon, infliximab, pemoline, minocycline, atorvastatin, and rosuvastatin can induce hepatocellular injury that mimics autoimmune hepatitis. Whether drugs and herbs unmask or induce autoimmune hepatitis or simply cause a drug-induced hepatitis with accompanying autoimmune features is unclear. We describe the clinicopathologic details of eight cases with ornidazole-induced hepatitis with autoimmune features. MATERIAL AND METHODS: Patients who presented with acute hepatitis between February 2001 and March 2009 were reevaluated for the etiology of liver disease. Patients with acute viral hepatitis, metabolic liver disease, vascular liver disease such as Budd-Chiari syndrome, biliary obstruction, or alcohol consumption were excluded. The autoimmune hepatitis scores, which were calculated at the time of diagnosis according to the criteria of the International Autoimmune Hepatitis Group, were recorded. In addition, the simplified criteria of the same group were applied retrospectively to each patient. Patients with ornidazole-induced toxic hepatitis with autoimmune hepatitis were included to constitute the study group of this report. All patients underwent initial liver biopsy, and one patient underwent liver biopsy three years later. All biopsies were scored according to the hepatitis scoring system by Ishak et al. (10). RESULTS: Overall, eight patients (all female) were diagnosed as drug-induced autoimmune hepatitis. With the exception of one patient, all were treated with prednisolone 30 mg/day + azathioprine 50 mg/day. The prednisolone dose was tapered according to the decrease in the level of transaminases. A two-year treatment program was planned for all patients. CONCLUSIONS: Ornidazole may cause drug-induced autoimmune hepatitis. Withdrawal of the drug may not provide the recovery despite a rather long wait. Thus, immunosuppressive therapy may be suggested in these cases.

The relationship between HBV-DNA level and histology in patients with naive chronic HBV infection.

BACKGROUND: In patients with chronic hepatitis B (CHB) infection, precise definition of the hepatic fibrosis stage is the most important parameter to assess the risk of disease progression. Correlation between the prognosis of the CHB and the level of hepatitis-B virus DNA (HBV-DNA) is well considered in recent years. AIMS: The aim of this study is to investigate the relationship between serum HBV-DNA level and histology of the liver. We also wanted to determine a threshold level of HBV-DNA for differentiation of low and high risk patients for progression. METHODS: Two-hundred-fifty-nine patients with serum HBV-DNA level > 2000 copies/mL, determined by polymerase chain reaction (PCR), and biopsy proven naïve CHB infection were evaluated. Liver biopsies were evaluated histopathologically according to the Ishak scoring system. Laboratory values such as aspartate aminotransferase (AST), alanine aminotransferase ratio (ALT) were tested every 3 months and the highest value of each patient was evaluated. RESULTS: Mean age was 40 +/- 11 and 60% (155/259) of the patients were male. Mean laboratory values were as follows: AST: 52 +/- 46 U/L, ALT: 93 +/- 133 U/L, PLT: 224 +/- 60 1093)/l HBV DNA: 5.9 +/- 1.5 log copies/mL. In histological evaluation, mean inflammatory score was 4.34 +/- 2.72 and fibrosis score was 1.38 +/- 1.46. The fibrosis score was 0 or 1 in 63.3% (164/259) of the patients. The relationship between HBV-DNA level and histologic grade/stage was investigated and 15.000 copies/mL HBV DNA level was found as the threshold level to describe the activity of the disease. Fibrosis score was < 2 and/or grade < or = 5 in the patients who have HBV-DNA value below that level. CONCLUSION: In patients who have serum HBV-DNA level < or = 15000/copies/mL, histological activity was almost always low, and it seems that these patients do not need a liver biopsy regardless of hepatitis-B-e antigen (HBeAg) status.

Expression of matrix metalloproteinase-9 in predicting prognosis of hepatocellular carcinoma after liver transplantation.

Matrix metalloproteinases (MMPs) are known to play an important role in cell migration during cancer invasion by degrading extracellular matrix proteins. This study aimed to determine the role of MMP-9 in hepatocellular carcinoma (HCC) carcinogenesis. Eighty-nine cases who underwent liver transplantation for HCC in cirrhotic liver were selected for this study. The tumor characteristics such as nodule number, maximal diameter, portal vein invasion, and the preoperative alpha-fetoprotein levels were reviewed. The intensity of immunostaining and the percentage of immunoreactive cells with MMP-9 were evaluated. All patients were evaluated for HCC recurrence and/or death, and cause of death was noted. There was a lower survival and more recurrence risk among participants with 4 or more nodules exceeding 3 cm in diameter, with poorly differentiated tumor, and with large-vessel involvement. Eleven patients developed recurrent HCC (12.4%). Twelve patients died as a result of HCC (13.5%). Among 89 HCCs, the incidences of a weak (+) and moderate (++) expression of MMP-9 in carcinoma cells were 30.3% (23/89) and 43.8% (39/89), respectively. Increased expression and intensity of MMP-9 were found to be inversely associated with poor tumor differentiation (P = 0.016, P = 0.009, respectively). A significant correlation between expression and intensity of MMP-9 and large vascular invasion (P = 0.01, and P = 0.03) was also observed. As far as prognosis is concerned, increased immunoreactivity and intensity of MMP-9 were found to exert an unfavorable impact on overall survival rates (P < 0.01, P = 0.01, respectively) and recurrences (P = 0.001, P = 0.02). Multivariate analyses revealed that MMP-9 staining percentage (P = 0.007) and portal vein invasion (P = 0.002) were independent predictors of survival, whereas the only independent predictor of recurrences was portal vein invasion (P = 0.007). In this study, our results indicate a positive association between MMP-9 expression and histopathologic parameters that indicate poor prognosis. We conclude that together, MMP-9 staining percentage and portal vein invasion in HCC may aid to predict poor outcome. Nevertheless MMP-9 staining percentage is expected to be a potential predictive marker on survival and needs to be studied more in detail.

Macrophage migration inhibitory factor expression and MIF gene -173 G/C polymorphism in nonalcoholic fatty liver disease.

AIM: To investigate the macrophage migration inhibitory factor (MIF) expression and -173 G/C polymorphism of the MIF gene in nonalcoholic fatty liver disease (NAFLD). METHOD: Ninety-one patients with diagnosis of NAFLD and 104 healthy controls were included in the study. MIF -173 G/C polymorphism was detected using the PCR-restriction fragment length polymorphism based method. NAFLD was stratified as nonalcoholic steatohepatitis (NASH), probable NASH and steatosis, respectively in groups 1, 2 and 3, according to NAFLD Activity Score. MIF expression was detected by immunohistochemistry staining. RESULTS: Mean age of the patients was 50.1+/-9.6 years, and 54 of them were male. Serum alanine aminotransferase and aspartate aminotransferase were 50/83, 42/63 and 31/32, respectively in groups 1, 2 and 3, (P<0.05). Both the MIF expression of hepatocytes and mononuclear cells were more prominent in groups 1 and 2 than group 3. There was no correlation between MIF expression of hepatocytes and fibrosis stage. However, MIF expression of mononuclear cells significantly increased according to fibrosis stage (P<0.05, R : 0.2). There was no significant correlation between MIF genotype and MIF expression in the liver. CONCLUSION: MIF expression is significantly increased especially by mononuclear cells in liver tissue of patients with NASH secondary to inflammation. Thus, it should be considered as a consequence not a causal factor.

Common SPINK-1 mutations do not predispose to the development of non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is common in obese and diabetics. Serine protease inhibitor Kazal-1 (SPINK-1) protein is highly expressed in the liver and adipose tissue of diabetic and obese suggesting its role in NAFLD. SPINK-1 also behaves as an acute phase reactant protein. Some genetic factors including the genetic variations in SPINK-1 protein have been linked to chronic pancreatitis and diabetes. We therefore hypothesized that SPINK-1 mutations might be a risk factor for the development of NAFLD. METHODS: Liver biopsy proven fifty NAFLD cases (20 steatohepatitis, 30 diffuse fatty liver disease and 44 healthy controls were included to the study. Liver function tests were measured. Body mass index was calculated. Insulin resistance was determined by using a homeostasis model assessment (HOMA-IR). Ultrasound evaluation was performed for each subject. Common genetic mutations in the third exon of SPINK-1 gene were analyzed by direct sequencing method. RESULTS: We found two cases with a SNP at N34S location in NAFLD group (allele frequency %4). One subject with diffuse fatty liver disease and other with liver cirrhosis due to NAFLD had N34S mutation. No SNPs were detected in healthy controls. In conclusions, in limited number of patients SPINK-1 mutations were not considered as a risk factor alone for NAFLD development.

Reabsorption of ascites and the factors that affect this process in cirrhosis.

Ascites is one of the main features of liver decompensation in cirrhosis, and it is considered to be a dynamic process. In this study, we aimed to (1) measure the reabsorption rate of ascites; (2) evaluate whether these findings were related to features of ascites, hemodynamics, and serum measurements; and (3) examine morphologic changes in the diaphragm of cirrhotic patients. In all, 42 cirrhotic patients with ascites were enrolled in the study to comprise our study group. Using the dextran 70 test, patient ascites volumes and reabsorption rates were measured. Biopsies from the peritoneal side of the diaphragm were also processed for scanning electron microscopy and lymphatic immunohistochemical studies from the cirrhotic patients and control cadavers. The mean ascites reabsorption rate was 4.5 +/- 4.5 (0.18-14.6) mL/min, which correlated significantly with the calculated ascites volume (r = 0.75, P < 0.001). The mean ascites viscosity was 1.07 +/- 0.07 (0.99-1.17) centipoise, which demonstrated a high degree of negative correlation with the ascites reabsorption rate (r = -0.77, P < 0.001). Patients with a history of spontaneous bacterial peritonitis had significantly lesser ascites reabsorption rates than patients without this particular history. The size of lymphatic stomata in scanning electron microscopy depictions was increased, and lymphatic lacunae were dilated in immunohistochemical studies in the cirrhotic patients with ascites. However, these findings were not uniform in every cirrhotic patient with ascites. The volume and viscosity of ascites seem to influence its reabsorption rate. Additionally, previous episodes of spontaneous bacterial peritonitis may be responsible for the decreased ascites reabsorption rates observed in certain patient populations.

Association of TNF-alpha -308 polymorphism with the outcome of hepatitis B virus infection in Turkey.

BACKGROUND AND AIM: Cytokines play important roles in the regulation of immune response. The aim of the study was to investigate the association of the cytokine gene polymorphisms with persistence of hepatitis B virus (HBV) infection and the development of end-stage liver disease (ESLD) due to HBV infection. METHODS: The study involved 27 patients with end-stage liver disease due to HBV infection, 23 HBV carriers and 60 healthy controls. All genotyping (TNF-alpha, TGF-beta, IL-10, IFN-gamma) experiments were performed using sequence specific primers (PCR-SSP) by using commercial kit according to manufacturers' instructions. RESULTS: The frequencies of TNF-alpha -308 G/G and TGF-beta1 codon 10-25 T/C-G/G polymorphisms were significantly higher in HBV-infected individuals (patients+carriers) when compared with those of healthy controls (p: 0.02 and p: 0.004, respectively). The frequency of TNF-alpha -308 G/G polymorphism was significantly higher in the patients than those of the healthy controls (p: 0.02), whereas the frequency of TGF-beta1 codon 10-25 T/T-G/G polymorphism was lower (p: 0.028). On the other hand, TNF-alpha -308 G/G and TGF-beta codon 10-25 T/C-G/G polymorphisms were significantly more common in HBV carriers than the control group (p: 0.017 and p: 0.018, respectively). In addition, TNF-alpha -308 G allele frequency was significantly more common in HBV-infected individuals (patients+carriers) than those of healthy controls (p: 0.0007). TNF-alpha -308 G allele frequency was also found to be higher in patients or carriers when compared with those of healthy controls (p: 0.01 and p: 0.01, respectively). Statistically significant differences were still kept after Bonferroni correction of the p-values for only TNF-alpha -308 G allele frequency in patients or carriers (Pc). CONCLUSION: Our study suggests that TNF-alpha gene polymorphism in patients infected with HBV would result in relatively inefficient inhibition of HBV and development of ESLD, and therefore, may be valuable predictor determinants for the development of ESLD in patients with chronic HBV infection.

Living donor liver transplantation for hepatitis B cirrhosis.

BACKGROUND AND AIM: Living donor liver transplantation (LDLT) has particular advantages for Turkey where hepatitis B virus (HBV) infection is the most common cause of cirrhosis, both because LDLT circumvents the difficulties encountered in the emerging world in providing deceased donor organs, and because it allows preemptive antiviral therapy. The aim of this study was to review one institution's experience with LDLT in patients with chronic HBV infection. METHODS: A total of 109 patients with chronic HBV infection underwent LDLT between September 1999 and June 2005, of whom 40 were coinfected with hepatitis D virus and 23 had hepatocellular carcinoma. Antiviral prophylaxis was attempted in all, beginning prior to transplantation with lamivudine or adefovir, and continuing after transplantation with low dose intramuscular hyperimmune B immunoglobulin (HBIg) plus lamivudine or adefovir. RESULTS: In a median follow up of 20 months (range 1-66 months), there was no donor mortality. One-year recipient survival was 90%, and in total 16 recipients died. None of the deaths was related to HBV. Recurrence of HBV infection was detected by reappearance of serum hepatitis B surface antigen in six patients (5.5%) at 5, 8, 12, 17, 34 and 46 months after transplantation, respectively. There was no influence of donor hepatitis B core antibody status on the likelihood of recurrence of HBV in the allograft. CONCLUSION: The results indicate that LDLT with antiviral treatment and low dose HBIg provides excellent results for donors and recipients.

Adefovir dipivoxil therapy in liver transplant recipients for recurrence of hepatitis B virus infection despite lamivudine plus hepatitis B immunoglobulin prophylaxis.

BACKGROUND: Treatment of post-transplantation recurrence of hepatitis B virus (HBV) infection despite prophylaxis with hepatitis B immunoglobulin (HBIG) and lamivudine combination therapy is not easy. Because HBV reinfection has a severe course and could result in graft failure in liver transplant recipients, prompt medication is essential. Herein is reported the authors' experience with adefovir dipivoxil (AD) therapy in 11 liver transplant recipients who had HBV reinfection despite the administration of lamivudine and HBIG. METHOD: Two-hundred and nine patients underwent liver transplantation (100 deceased donor liver transplantations [DDLT], 109 living donor liver transplantation [LDLT]) due to chronic hepatitis B infection between April 1997 and May 2005 in Ege University Medical School, Liver Transplantation Unit. Patients had prophylaxis with lamivudine and low-dose HBIG combination after liver transplantation. Treatment of recurrence consisted of AD 10 mg once a day and lamivudine 300 mg/daily and HBIG was discontinued in those patients. RESULTS: In total there were 11 HBV recurrences: five occurred in DDLT recipients and six in LDLT recipients, at a median follow up of 18 months (range, 6-48 months). In one of 11 patients, pretransplant HBV-DNA and HBeAg were positive. Three patients had a severe course and one patient had fibrosing cholestatic hepatitis. After AD treatment, HBV-DNA level decreased in all patients and became negative in seven patients. Two patients died due to hepatocellular carcinoma recurrence after 12 and 14 months of follow up. Serum creatinine level increased mildly in one patient and no other side-effect was observed, and all patients continued therapy. CONCLUSION: Adefovir dipivoxil is a safe, effective treatment option for post-transplant HBV recurrence even among patients with fibrosing cholestatic hepatitis caused by lamivudine-resistant HBV.

Liver biopsy: is the pain for real or is it only the fear of it?

Although percutaneous liver biopsy (PLB) has very low mortality and morbidity rates, it often is considered painful and frightening by the patients. This study was designed to grade the intensity of pain expected before the procedure and experienced during the procedure, and whether there is any correlation between pain and the emotional state of the patient. A total of 118 consecutive patients (aged 19-68 (mean, 44) years), who were undergoing PLB for the first time, were included in the study. Visual Analogue Scale (VAS) was used before the procedure, after the procedure to grade the degree of pain expected, and the degree of the pain experienced respectively. All the patients were evaluated by a questionnaire for their personality and emotional situation by using the Minnesota Multiphasic Personality Inventory Somatization Sub-scale (MMPI-SS). Mean VAS score for expected pain before the procedure was 60+/-20 and for the pain experienced during the procedure was 22+/-16 (P < 0.0001). Although the expected pain scores of female patients were significantly higher than males (66+/-22 vs. 55+/-17; P=0.003), there was no difference between female and male patients in the experienced pain scores. The procedure of PLB is expected to be more painful than it really is by the patients, especially by females. Calming the patients by informing them about the procedure and their diseases will probably diminish the expected pain.