Outcome of COVID-19 in Patients With Autoimmune Hepatitis: An International Multicenter Study.

BACKGROUND AND AIMS: Data regarding outcome of COVID-19 in patients with autoimmune hepatitis (AIH) are lacking. APPROACH AND RESULTS: We performed a retrospective study on patients with AIH and COVID-19 from 34 centers in Europe and the Americas. We analyzed factors associated with severe COVID-19 outcomes, defined as the need for mechanical ventilation, intensive care admission, and/or death. The outcomes of patients with AIH were compared to a propensity score-matched cohort of patients without AIH but with chronic liver diseases (CLD) and COVID-19. The frequency and clinical significance of new-onset liver injury (alanine aminotransferase > 2 × the upper limit of normal) during COVID-19 was also evaluated. We included 110 patients with AIH (80% female) with a median age of 49 (range, 18-85) years at COVID-19 diagnosis. New-onset liver injury was observed in 37.1% (33/89) of the patients. Use of antivirals was associated with liver injury (P = 0.041; OR, 3.36; 95% CI, 1.05-10.78), while continued immunosuppression during COVID-19 was associated with a lower rate of liver injury (P = 0.009; OR, 0.26; 95% CI, 0.09-0.71). The rates of severe COVID-19 (15.5% versus 20.2%, P = 0.231) and all-cause mortality (10% versus 11.5%, P = 0.852) were not different between AIH and non-AIH CLD. Cirrhosis was an independent predictor of severe COVID-19 in patients with AIH (P < 0.001; OR, 17.46; 95% CI, 4.22-72.13). Continuation of immunosuppression or presence of liver injury during COVID-19 was not associated with severe COVID-19. CONCLUSIONS: This international, multicenter study reveals that patients with AIH were not at risk for worse outcomes with COVID-19 than other causes of CLD. Cirrhosis was the strongest predictor for severe COVID-19 in patients with AIH. Maintenance of immunosuppression during COVID-19 was not associated with increased risk for severe COVID-19 but did lower the risk for new-onset liver injury during COVID-19.

Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis.

BACKGROUND: We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH). PATIENTS AND METHODS: Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication. The clinical courses of COVID-19 were classified as (i)-no hospitalization, (ii)-hospitalization without oxygen supplementation, (iii)-hospitalization with oxygen supplementation by nasal cannula or mask, (iv)-intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v)-ICU admission with invasive mechanical ventilation or (vi)-death and analysed using ordinal logistic regression. RESULTS: We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17-85) years. At the onset of COVID-19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12-25.89) and thiopurines (aOR 4.78, 95% CI 1.33-23.50) for AIH was associated with worse COVID-19 severity, after adjusting for age-sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76-20.56) and tacrolimus (aOR 4.09, 95% CI 0.69-27.00) were also associated with more severe COVID-19 courses in a smaller subset of treated patients. CONCLUSION: Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID-19 was significantly associated with COVID-19 severity in patients with AIH.

Extrahepatic autoimmune diseases in primary biliary cholangitis: Prevalence and significance for clinical presentation and disease outcome.

BACKGROUND AND AIM: The prevalence and clinical significance of extrahepatic autoimmune diseases (EHAIDs) have not been evaluated in a large cohort of primary biliary cholangitis (PBC). METHODS: The medical records of 1554 patients with PBC from 20 international centers were retrospectively reviewed. Development of decompensated cirrhosis (ascites, variceal bleeding, and/or hepatic encephalopathy) and hepatocellular carcinoma were considered clinical endpoints. RESULTS: A total of 35 different EHAIDs were diagnosed in 440 (28.3%) patients with PBC. Patients with EHAIDs were more often female (92.5% vs 86.1%, P < 0.001) and seropositive for anti-mitochondrial antibodies (88% vs 84%, P = 0.05) and antinuclear antibodies and/or smooth muscle antibodies (53.8% vs 43.6%, P = 0.005). At presentation, patients with EHAIDs had significantly lower levels of alkaline phosphatase (1.76 vs 1.98 × upper limit of normal [ULN], P = 0.006), aspartate aminotransferase (1.29 vs 1.50 × ULN, P < 0.001), and total bilirubin (0.53 vs 0.58 × ULN, P = 0.002). Patients with EHAIDs and without EHAIDs had similar rates of GLOBE high-risk status (12.3% vs 16.1%, P = 0.07) and Paris II response (71.4% vs 69.4%, P = 0.59). Overall, event-free survival was not different in patients with and without EHAIDs (90.8% vs 90.7%, P = 0.53, log rank). Coexistence of each autoimmune thyroid diseases (10.6%), Sjögren disease (8.3%), systemic sclerosis (2.9%), rheumatoid arthritis (2.7%), systemic lupus erythematosus (1.7%), celiac disease (1.7%), psoriasis (1.5%), and inflammatory bowel diseases (1.3%) did not influence the outcome. CONCLUSIONS: Our study confirms that EHAIDs are frequently diagnosed in patients with PBC. The presence of EHAIDs may influence the clinical phenotype of PBC at presentation but has no impact on PBC outcome.

Validation of Risk Scoring Systems in Ursodeoxycholic Acid-Treated Patients With Primary Biliary Cholangitis.

INTRODUCTION: Risk stratification based on biochemical variables is a useful tool for monitoring ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC). Several UDCA response criteria and scoring systems have been proposed for risk prediction in PBC, but these have not been validated in large external cohorts. METHODS: We performed a study on data of 1746 UDCA-treated patients with PBC from 25 centers in Europe, United States, and Canada. The prognostic performance of the risk scoring systems (GLOBE and UK-PBC) and the UDCA response criteria (Barcelona, Paris I, Paris II, Rotterdam, and Toronto) were evaluated. We regarded cirrhosis-related complications (ascites, variceal bleeding, and/or hepatic encephalopathy) as clinical end points. RESULTS: A total of 171 patients reached a clinical end point during a median 7 years (range 1-16 years) of follow-up. The 5-, 10- and 15-year adverse outcome-free survivals were 95%, 85%, and 77%. The GLOBE and UK-PBC scores predicted cirrhosis-related complications better than the UDCA response criteria. The hazard ratio (HR) for a 1 standard deviation increase was HR 5.05 (95% confidence interval (CI): 4.43-5.74, P < 0.001) for the GLOBE score and HR 3.39 (95% CI: 3.10-3.72, P < 0.001) for the UK-PBC score. Overall, the GLOBE and UK-PBC risk scores showed similar and excellent prognostic performance (C-statistic, 0.93; 95% CI: 0.91%-95% vs 0.94; 95% CI: 0.91%-0.96%). DISCUSSION: In our international, multicenter PBC cohort, the GLOBE and UK-PBC risk scoring systems were good predictors of future cirrhosis-related complications.

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.

Mean platelet volume is an important predictor of hepatitis C but not hepatitis B liver damage.

BACKGROUND: The mean platelet volume (MPV) is the most commonly used measure of platelet size and is a potential marker of platelet reactivity. In this study, we aimed to explore the relationship between hepatic histopathology in viral hepatitis and MPV levels, which are associated with platelet count and activity. MATERIALS AND METHODS: We performed a retrospective case-control study of baseline histological and clinical parameters in chronic hepatitis B and C patients in our tertiary reference center between January 2005 and January 2011. Two hundred and five chronic hepatitis B patients and 133 chronic hepatitis C patients who underwent liver biopsy were included in the study. The patients were divided into two groups: Chronic hepatitis B and chronic hepatitis C and were additionally divided into groups of two according to histological activity index (HAI) and fibrosis scores obtained by liver biopsy results (according to the Ishak scoring system). The clinical characteristics of chronic viral hepatitis patients, including demographics, laboratory (especially MPV), and liver biopsy findings, were reviewed. RESULTS: One hundred and forty-three patients were male (69.1%), and the mean age was 41.9 ± 12.75 with an age range of 18-71 years in hepatitis B patients. In the classification made according to HAI, 181 patients were in the low activity group (88.3%) and 24 in the high activity group (11.7%). In the evaluation made according to fibrosis score, 169 patients were found to have early fibrosis (82.4%) and 36 were found to have advanced fibrosis (17.6%). In patients with hepatitis B, there was no statistically significant difference in terms of their MPV values between the two groups, separated according to their degree of activity and fibrosis. Sixty-three patients were male (47.3%), and the mean age was 50.03 ± 12.75 with an age range of 19-75 years. In the classification made according to HAI, 109 patients were in low activity group (81.9%) and 24 in high activity group (18.1%). In the evaluation made according to fibrosis score, 101 patients were found to have early fibrosis (75.9%) and 32 have advanced fibrosis (24.1%). There was a statistically significant difference between the activity and fibrosis groups of the hepatitis C patients (P = 0.04 and P = 0.02, respectively). CONCLUSION: MPV values are more reliable in hepatitis C patients than hepatitis B for predicting the advanced damage in liver histology. This finding might be useful for the detection of early fibrosis and also starting early treatment, which is important in hepatitis C.

Perception and Attitude of Turkish Gastroenterologists Toward Obesity: A Nationwide Survey Conducted by the Obesity Study Group of the Turkish Gastroenterology Association.

BACKGROUND/AIMS:  Gastroenterologists have an important role in the treatment and management of comorbidities related to obesity. Assessment of gastroenterologists' perception and attitude toward obesity was aimed in this study. MATERIALS AND METHODS:  Survey questions were determined for the study. An online questionnaire was prepared afterward. Participants were invited via e-mail by providing them with information about the study. It was ensured that those who accepted the study could access the questionnaire form with the relevant link. Participants who answered all questions were included in the study. RESULTS:  Totally 117 gastroenterologists were included in the study. The proportion of gastroenterologists who thought that obesity complicates the management of gastroenterological diseases and those who thought obesity as a factor that negatively affects the prognosis of gastroenterological diseases was determined as 88.9% and 95.7%, respectively. Among the obese patients, the proportion of those who applied diet therapy, exercise, pharmacotherapy, and endoscopic methods was 94%, 91.5%, 35%, and 37.6%, respectively. The rates of intragastric balloon therapy and intragastric botulinum toxin A injection were 30% and 21.4%, respectively. The proportion of those who agreed that obese patients lost a significant amount of weight with the treatment methods applied was 47.2%. The proportion of participants who agreed that long-term maintenance of weight loss was impossible for most obese patients was 59.8%. CONCLUSION:  To our knowledge, this is the first study that evaluates the perception and attitude of gastroenterologists toward obesity. Our study results show that gastroenterologists think that obesity is a chronic disease and that gastroenterologists should be involved in management of obesity.

Changing trends in the etiology of liver transplantation in Turkiye: A multicenter study.

Background and Aim: This study aimed to identify the indications for liver transplantation (LT) based on underlying etiology and to characterize the patients who underwent LT. Materials and Methods: We conducted a multicenter cross-sectional observational study across 11 tertiary centers in Turkiye from 2010 to 2020. The study included 5,080 adult patients. Results: The mean age of patients was 50.3±15.2 years, with a predominance of female patients (70%). Chronic viral hepatitis (46%) was the leading etiological factor, with Hepatitis B virus infection at 35%, followed by cryptogenic cirrhosis (24%), Hepatitis C virus infection (8%), and alcohol-related liver disease (ALD) (6%). Post-2015, there was a significant increase in both the number of liver transplants and the proportion of living donor liver transplants (p<0.001). A comparative analysis of patient characteristics before and after 2015 showed a significant decline in viral hepatitis-related LT (p<0.001), whereas fatty liver disease-related LT significantly increased (p<0.001). Conclusion: Chronic viral hepatitis continues to be the primary indication for LT in Turkiye. However, the proportions of non-alcoholic fatty liver disease (NAFLD) and ALD-related LT have seen an upward trend over the years.

Effect of Locoregional Treatments in Hepatocellular Carcinoma: What Are the Pathologic/Radiologic Milan Criteria?

OBJECTIVES: Milan criteria is the most commonly used criteria for patients with hepatocellular carcinoma awaiting liver transplant. The effects of locoregional therapy on downstaging or bridging before liver transplant on survival remain controversial. Considering that the tumor size may change with locoregional therapy and formalin fixation after explantation, we aimed to evaluate the effects of locoregional therapy on radiological and pathological Milan criteria and survival. MATERIALS AND METHODS: Demographic data, etiology, preoperative alpha-fetoprotein value, Child-Pugh and Model for End-Stage Liver Disease-Na scores, status of being inside or outside of radiological Milan criteria, status of being inside or outside of Milan criteria in explant (pathological Milan criteria), and the locoregional therapy types and combinations were evaluated for their effects on inclusion in Milan criteria and survival. RESULTS: During the study period, 396 patients underwent liver transplant at our center, with 97 because of cirrhosis and hepatocellular carcinoma. When we viewed patients according to preoperative radiologic evaluations, 67.9% were within Milan criteria and 32.1% were outside. When we viewed according to explant (pathological) evaluations, 80.7% of patients were within Milan criteria. Among 97 patients, 71 (73.2%) had locoregional therapy (22 [30.9%] for downstaging, 49 [69.0%] for bridging to transplant), and 12 patients (12.3%) were within Milan criteria on explant examination while outside of Milan criteria before LT. One-year, 3-year, and 5-year survival rates were 80.7%, 76.1%, and 71.6%, respectively. CONCLUSIONS: As a result of radiological evaluations, in patients who were outside of Milan criteria and underwent locoregional therapy, explant pathology within Milan criteria had a positive effect on survival; however, after locoregional therapy, there was no significant effect on survival in patients who were still outside of Milan criteria.

TASL Practice Guidance on the Clinical Assessment and Management of Patients with Nonalcoholic Fatty Liver Disease.

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.

Blood-Based Biomarkers in Afp Normal/Stable Hepatocellular Carcinoma: Diagnostic and Prognostic Relevance of Mir-10b for Patients on Liver Transplant List.

BACKGROUND: As a diagnostic criteria of hepatocellular carcinoma (HCC), the exact threshold of alpha-fetoprotein (AFP) is controversial. In additional, not all HCC tumors are AFP positive or secrete elevated amounts of AFP into the serum. However, the diagnosis of HCC is quite important on the liver transplant list. Therefore, the purpose of this study was to investigate the expression of circulating micro RNAs (miRNAs) in AFP-stable HCC patients. Thus, we aimed to determine a diagnostic biomarker in these patients. METHODS: Sixteen miRNAs were evaluated using a real-time quantitative reverse transcription polymerase chain reaction system in AFP-stable HCC and AFP-trending HCC patients. RESULTS: In our study, 46.7% (n = 28) of the patients diagnosed with HCC had stable/normal AFP levels. We detected that high expression of miR-24, miR-10b and the low expression of miR-143 were independently and significantly associated with HCC in AFP-stable compared with AFP trending (P < .05). Additionally, we demonstrated that the overexpression of miR-10b was associated with poor disease-free survival in HCC (P = 0.001). CONCLUSIONS: Although more clinical validations are needed for the diagnosis of HCC, our current results indicate that the coexistence of high expression of miR-10b and miR-24 may help clinicians adjust in the diagnosis of HCC in patients who are on the liver transplant list but awaiting biopsy for the diagnosis of HCC.

Does Liver Transplant Improve Neurological Symptoms in Wilson Disease? Report of 24 Cases.

OBJECTIVES: Wilson disease is an inherited disorder that results in copper accumulation in the tissues with liver injury and failure. Orthotopic liver transplant is one of the treatments of choice for this disease. The aim of this study was to compare the neurological symptoms, before and after orthotopic livertransplant, of patients with liver cirrhosis due to Wilson disease, who represent a special group of patients with liver failure. MATERIALS AND METHODS: Between 2007 and 2020, there were 24 patients with Wilson disease resistant to medical treatment who underwent deceased donor orthotopic livertransplant and were followed up for 1 year, 5 years, and 10 years for evaluation with neurological scoring systems. Patients were also evaluated for postoperative complications and survival. RESULTS: Of the 24 patients evaluated, there were 13 (54.2%) female patients and 11 (45.8%) male patients, and the mean age was 34 years (range, 14-57 years). One of the patients died from early postoperative sepsis. After orthotopic livertransplant, disease scores returned to normal in 16 patients and improved in the remaining patients. Before transplant, all patients required help in their daily activities. After transplant, there were significant improvements in some symptoms, and the patients became more independent in their daily lives. CONCLUSIONS: Our study shows that orthotopic liver transplant provides significant improvement in neurological symptoms and quality of life in patients with Wilson disease.

Myelitis After Liver Transplant: A Case Report.

We report a case of neurotoxicity as a side effect of a calcineurin inhibitor (tacrolimus), which is used as an immunosuppressive drug after liver transplant. Our patient had chronic hepatic failure due to Budd-Chiari syndrome and underwent a liver transplant after an appropriate deceased donor organ was obtained. After organ transplant surgery, he was kept under the effect of an immunosuppressive drug (tacrolimus) with daily control of the level of drug in his blood to avoid drug toxicity. Despite the level of drug in his blood being within the ideal range, the patient developed neurotoxicity that presented as weakness of his extremities. Appropriate diagnostic tests were done, and all proved that these signs and symptoms were related to the use of tacrolimus. Therefore, the drug was changed to cyclosporine. After a few months, the patient regained normal neurological functions of his extremities. We should take precautions to monitor neurological symptoms and signs while we administer calcineurin inhibitors.

Recommendations for Hepatitis B Immunoglobulin and Antiviral Prophylaxis Against Hepatitis B Recurrence After Liver Transplantation.

The combination of hepatitis B immunoglobulin and potent nucleos(t)ide analogs after liver transplantation is considered as the standard of care for prophylaxis against hepatitis B virus recurrence. However, the recommended doses, route of administration, and duration of HBIG administration remain unclear. Moreover, hepatitis B immunoglobulin-free prophylaxis with potent nucleos(t)ide analogs has shown promising disease outcomes in preventing hepatitis B virus recurrence. The current recommendations, produced by the Turkish Association for the Study of the Liver, Acute Liver Failure and Liver Transplantation Special Interest Group, suggest a reduced need for hepatitis B immunoglobulin administration with effective long-term suppression of hepatitis B virus replication using potent nucleos(t) ide analogs after liver transplantation.

Elevated serum levels of caspase-cleaved cytokeratin 18 (CK18-Asp396) in patients with nonalcoholic steatohepatitis and chronic hepatitis C.

BACKGROUND: Caspase-cleaved cytokeratin 18 (CK18-Asp396) is released from hepatocytes during apoptosis. Recent studies have indicated that serum levels of CK18-Asp396 could be a clinically useful biomarker of chronic liver disease. To shed more light on the rate of hepatocyte loss by apoptosis in chronic liver disease, serum levels of CK18-Asp396 were examined in patients with nonalcoholic steatohepatitis (NASH) and chronic hepatitis C. MATERIAL/METHODS: Apoptotic CK18-Asp396 levels were quantified in sera from 35 patients with nonalcoholic steatohepatitis (NASH), 21 patients with chronic hepatitis C (HCV), and 18 healthy controls. RESULTS: Analysis of serum CK18-Asp396 levels showed an increasing trend starting from healthy controls (median: 54.5 U/l), to HCV patients (80.1 U/l), to patients with NASH (144.1 U/l, Kruskall-Wallis test: P<0.001). Post hoc analyses revealed that CK18-Asp396 levels were significantly higher in the NASH patients than in both HCV patients (P=0.008) and healthy controls (P<0.001). Moreover, the levels were significantly higher in patients with HCV than in control individuals (P<0.05). In patients with chronic HCV infection there was a significant positive correlation between serum CK18-Asp396 levels and AST (r=0.442, P<0.05), the ultrasonographic grade of steatosis (r=0.446, P<0.05), and the histological steatosis score (r=0.759, P<0.001). CONCLUSIONS: Although subject to future confirmation, these pilot findings seem to indicate that serum levels of caspase-cleaved cytokeratin 18 (CK18-Asp396) are higher in patients with NASH than in those with chronic HCV infection. These data suggest that NASH patients have an increased hepatocyte loss by apoptosis compared with chronic hepatitis C patients.

Acute myocardial infarction, ischemic cerebrovascular disease and variceal bleeding due to portal vein thrombosis in a patient with hereditary thrombophilia.

We report on a 43-year-old female patient with multiple thrombotic risk factors who, in a few months, developed acute myocardial infarction, an ischemic cerebrovascular event and variceal bleeding due to portal vein thrombosis. The factor V Leiden mutation was carried in heterozygous form, homocysteine was elevated at 19.6 micromol/l, and methylenetetrahydrofolate reductase C677T mutation was carried in homozygous form. Moderately increased plasma homocysteine level and a reduced protein S activity were evident. Anticardiolipin IgG antibodies were mildly positive. We conclude that the presence of multiple genetic and environmental risk factors greatly amplifies the risk of clinical thrombotic events.

Clinical significance of activity of ALT enzyme in patients with hepatitis C virus.

AIM: To investigate serum alanine aminotransferase (ALT) levels in relation to the clinical, biochemical, ultrasonographic and histological characteristics of patients with hepatitis C virus. METHODS: Duration of disease, HCV-RNA, liver steatosis, and the hepatitis activity index (HAI) were correlated with serum ALT in 36 patients with HCV. ALT values were also investigated in 16 control subjects without any liver diseases. RESULTS: In bivariate analyses, ALT levels correlated with duration of HCV infection (P < 0.01), HCV-RNA (P < 0.05), and the HAI (P < 0.01). Among the components of the HAI, ALT concentrations were significantly associated with periportal bridging/necrosis (P < 0.01) and fibrosis (P < 0.05). In multivariate analysis, periportal bridging/necrosis (beta = 0.508; P < 0.01), duration of HCV infection (beta = 0.413; P < 0.01), and HCV-RNA (beta = 0.253; P < 0.05) were independently associated with ALT activity. The normal ALT activity for men and women was < 23 IU/L and < 22 IU/L, respectively. CONCLUSION: In patients with HCV, alterations in the liver tissue as reflected by ALT elevation are mainly associated with periportal bridging/necrosis, viral load and duration of disease. A cut-off value < 23 IU/L distinguished with high diagnostic accuracy healthy controls from patients with HCV.

Evaluation of leukocyte esterase and nitrite strip tests to detect spontaneous bacterial peritonitis in cirrhotic patients.

AIM: To investigate the diagnostic efficacy of leukocyte esterase and nitrite reagent strips for bedside diagnosis of spontaneous bacterial peritonitis (SBP). METHODS: A total of 63 consecutive patients with cirrhotic ascites (38 male, 25 female) tested between April 2005 and July 2006 were included in the study. Bedside reagent strip testing was performed on ascitic fluid and the results compared to manual cell counting and ascitic fluid culture. SBP was defined as having a polymorphonuclear ascites count of >or= 250/mm(3). RESULTS: Fifteen samples showed SBP. The sensitivity, specificity, positive and negative predictive values of the leukocyte esterase reagent strips were; 93%, 100%, 100%, and 98%, respectively. The sensitivity, specificity, positive and negative predictive value of the nitrite reagent strips were 13%, 93%, 40%, and 77%, respectively. The combination of leukocyte esterase and nitrite reagents strips did not yield statistically significant effects on diagnostic accuracy. CONCLUSION: Leukocyte esterase reagent strips may provide a rapid, bedside diagnostic test for SBP.

Soluble forms of extracellular cytokeratin 18 may differentiate simple steatosis from nonalcoholic steatohepatitis.

AIM: To investigate whether serum levels of two soluble forms of extracellular cytokeratin 18 (M30-antigen and M65-antigen) may differentiate nonalcoholic steatohepatitis (NASH) from simple steatosis in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: A total of 83 patients with suspected NAFLD and 49 healthy volunteers were investigated. Patients with suspected NAFLD were classified according to their liver histology into four groups: definitive NASH (n=45), borderline NASH (n=24), simple fatty liver (n=9), and normal tissue (n=5). Serum levels of caspase-3 generated cytokeratin-18 fragments (M30-antigen) and total cytokeratin-18 (M65-antigen) were determined by ELISA. RESULTS: Levels of M30-antigen and M65-antigen were significantly higher in patients with definitive NASH compared to the other groups. An abnormal value (> 121.60 IU/L) of M30-antigen yielded a 60.0% sensitivity and a 97.4% specificity for the diagnosis of NASH. Sensitivity and specificity of an abnormal M65-antigen level (> 243.82 IU/L) for the diagnosis of NASH were 68.9% and 81.6%, respectively. Among patients with NAFLD, M30-antigen and M65-antigen levels distinguished between advanced fibrosis and early-stage fibrosis with a sensitivity of 64.7% and 70.6%, and a specificity of 77.3% and 71.2%, respectively. CONCLUSION: Serum levels of M30-antigen and M65-antigen may be of clinical usefulness to identify patients with NASH. Further studies are mandatory to better assess the role of these apoptonecrotic biomarkers in NAFLD pathophysiology.

High prevalence of irritable bowel syndrome and upper gastrointestinal symptoms in patients with chronic renal failure.

BACKGROUND: Gastrointestinal symptoms and psychiatric disorders are common among patients with chronic renal failure since uremia affects all systems as well as the gastrointestinal tract. Irritable bowel syndrome (IBS) is a frequent functional disorder worldwide. We aimed to evaluate the frequency of IBS and upper gastrointestinal symptoms in patients with chronic renal failure (CRF). The relationships between IBS, sex and additional psychiatric disorders in the same patient group were determined and results were compared with controls. METHODS: Ninety-three hemodialysis (HD) and 35 peritoneal dialysis (PD) patients and 51 healthy volunteers were enrolled in this cross-sectional study. They completed the questionnaires that were later evaluated to determine the frequency of IBS in HD, PD and control groups; the frequency of depression and anxiety in these three groups and their relationship to sex. Symptoms of upper gastrointestinal system and their relation to sex were also investigated in all groups. RESULTS: In this study, we have demonstrated that prevalence of IBS in patients with chronic renal failure on hemodialysis or peritoneal dialysis is higher than the controls though the type of dialysis does not seem to influence the IBS prevalence itself. Epigastric pain was more prevalent in HD patients than PD patients. CONCLUSIONS: The present study suggests that though IBS is common in patients with CRF, it is generally underestimated. Type of dialysis does not seem to change the clinical picture much. Accompanying mood disorders must also be taken into consideration.