Total and individual PBC-40 scores are reliable for the assessment of health-related quality of life in Greek patients with primary biliary cholangitis.

Background: Primary biliary cholangitis (PBC) has been long associated with impairment of various aspects of health-related quality of life (HRQoL) with substantial differences among populations. This study evaluated for the first-time the HRQoL in Greek PBC patients in conjunction with clinical and laboratory parameters of patients. Methods: We analyzed prospectively collected data regarding the HRQoL by using the PBC-40 and SF-36 questionnaires in 374 Greek PBC patients and 131 age- and sex-matched non-PBC controls. Results: The PBC-40 questionnaire is a reliable tool for HRQoL assessment in Greek PBC patients (Cronbach's α > 0.7 for all domains). Implementation of PBC-40 and SF-36 demonstrated significant impairment of HRQoL in Greek PBC patients compared to controls (P < 0.001 for all comparisons). Emotional dysfunction, social impairment, and fatigue (100%, 80.5% and 78%, respectively) were amongst those with the highest, while cognitive dysfunction (32%) with the least impact on quality of life. Fatigue was associated with female sex (P = 0.02), longer disease duration (P = 0.01), presence of cirrhosis (P = 0.02) and positivity for PBC-specific ANA (P < 0.05), while social dysfunction with increased age (P < 0.001), longer disease duration (P < 0.001) and presence of cirrhosis (P = 0.004). Living in urban areas was linked to impaired social function (P = 0.04), cognition (P = 0.02), fatigue (P = 0.04) and increased total PBC-40 score (P = 0.01). Conclusions: Implementation of PBC-40 and SF-36 revealed impaired HRQoL in Greek PBC patients with fatigue, social and emotional dysfunction exerting the highest impact. However, total, and individual PBC-40 scores were lower than that reported in studies from Northern/Central Europe and Canada. Deranged HRQoL was associated with severity of liver disease and presence of PBC-specific ANA.

Enzymes of Fibrosis in Chronic Liver Disease.

Introduction: Liver fibrosis has been extensively studied at the cellular and molecular level, but very few data exist on the final enzymatic stages of collagen synthesis (prolyl hydroxylase, PH) and degradation (matrix metalloproteinases, MMPs), particularly in primary biliary cholangitis (PBC). Aim: We studied enzyme activities in liver tissue from patients with chronic liver diseases and compared them to normal livers. Patients: Eighteen patients with PBC of early and late stages (Ludwig's classification) and seven on treatment with ursodeoxycholate (UDCA) were studied and compared to 34 patients with alcoholic liver disease (ALD), 25 patients with chronic viral liver disease and five normal biopsies. Sera were available from a total of 140 patients. Methods: The tritiated water released from the tritiated proline was measured in PH assessment. 14C intact and heat-denatured collagen substrates were used to measure collagenase and gelatinases, respectively. 3H Elastin was the substrate for elastase. In serum, ELISAs were used for MMP-1, TIMP-1, and TIMP-2 measurements while MMP-2 and MMP-9 were estimated by zymography. Results: PH was significantly increased in early and late PBC. Collagenase was reduced only in the late stages (p < 0.01), where the ratio PH/collagenase was increased. UDCA treatment restored values to almost normal. Gelatinases were reduced in late stages (p < 0.05). In contrast to PBC and ALD fibrosis, collagen synthesis is not increased in viral fibrosis. The balance shifted towards collagen deposition due to reduced degradation. Interestingly, gelatinolytic activity is not impaired in ALD. Elastase was similar to controls in all diseases studied. TIMP-1 was reduced in early PBC and viral and alcoholic hepatitis and cirrhosis (p < 0.001). Conclusions: (1) There is evidence that collagen synthesis increases in the early stages of PBC, but the collagenolytic mechanism may compensate for the increased synthesis. (2) In viral disease, fibrosis may be due to decreased degradation rather than increased synthesis. (3) The final biochemical stages of liver fibrosis may be quantitatively different according to underlying etiology.

Nutritional Assessment of Greek Liver Cirrhosis Patients: Mini Nutritional Assessment Predicts Mortality.

Malnutrition is highly prevalent in liver cirrhosis (LC). It increases as the severity of the disease progresses and it is related to poor survival. The objectives of the study were the nutritional assessment of Greek LC patients, using various nutritional assessment and screening tools, and the comparison of their predictive value for mortality. In total, 137 (77 male) consecutive LC patients (median age: 67 years) were assessed with subjective global assessment (SGA) and mini nutritional assessment (MNA) questionnaires, anthropometrics, handgrip strength (HGS) tests, and bioelectric impedance analysis (BIA), in comparison to a control group of 148 healthy people. Disease severity was assessed using the model for end-stage liver disease (MELD) scores. Patients were followed up for a median of 19 months. Survival curves were calculated using the Kaplan-Meier method. In total, 60% and 43% of patients were of adequate nutritional status by SGA and MNA, respectively, which was confirmed by most anthropometric measurements. MNA and SGA scores correlated significantly with anthropometrics and BIA-derived parameters. Besides the MELD score, mid-arm circumference (MAC), triceps skinfold (TSF), BIA's phase angle (Pha), and MNA predicted mortality in cirrhotic patients. The nutritional assessment demonstrated an unexpectedly high prevalence of well-nourished LC patients. MNA was a strong predictor of mortality.

Buried Bumper Syndrome: A common complication of levodopa intestinal infusion for Parkinson disease.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is required for Levodopa/Carbidopa Intestinal Gel (LCIG) delivery in patients with advanced Parkinson's disease (PD) as well as for enteral feeding in a variety of neurological disorders. Buried Bumper Syndrome (BBS) is a serious complication of PEG. The frequency of BBS in patients receiving LCIG treatment has never been reported. OBJECTIVES: To compare the frequency of BBS in patients on LCIG treatment or on enteral feeding over the past 12 years and identify possible risk factors. METHODS: We reviewed prospectively recorded data from 2009 to 2020 on two case-series: LCIG-treated PD patients and non-PD patients on enteral nutrition. We identified all BBS incidences. Patients' characteristics, clinical manifestations, BBS management, possible risk factors and outcomes were analyzed. RESULTS: During the 12 years, 35 PD patients underwent PEG insertion for LCIG infusion, and 123 non-PD patients for nutritional support. There were eight cases of BBS in six PD patients (17.1%). Six of them were effectively managed without treatment discontinuation. Of the enteral feeding patients, only one developed BBS (0.8%) (p < 0.001). We identified inappropriate PEG site aftercare, weight gain, early onset PD, longer survival, treatment duration, dementia and PEG system design as potential risk factors for BBS development. CONCLUSIONS: BBS occurs more frequently in LCIG patients than in patients receiving enteral feeding. If detected early, it can be successfully managed, and serious sequalae or treatment discontinuation can be avoided. Regular endoscopic follow-up visits of LCIG-treated patients and increased awareness in patients and clinicians are recommended.

Hemophagocytic lymphohistiocytosis syndrome associated with Epstein-Barr infection in an immunocompetent patient. A case study.

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening rare disease resulting from the uncontrolled activation of the immune system, leading to unrestrained cytokine release and macrophage activation. It can be either hereditary or acquired due to infections, hematological disease or malignancy. CASE REPORT: We present the case of a 19-year old woman that presented with high fever and acute cholestatic hepatitis. She was initially admitted to the Gastroenterology department and the following days she developed respiratory distress and multiorgan insufficiency that necessitated intubation and support in the Intensive Care Unit. Fever, splenomegaly, hypertriglyceridemia, increased ferritin levels and hemophagocytosis in the bone marrow were found, thus, fulfilling the criteria of hemophagocytic lymphohistiocytosis. Laboratory examination was notable for positive serology (IgM and IgG) and PCR for EBV in the serum. An extensive workup including virology and immunologic workup, blood cultures, a CT of the thorax and the abdomen and a bone marrow biopsy did not reveal any cause of secondary HLH other than the EBV infection. The patient was treated with high dose corticosteroids and intravenous immunoglobulins with slow resolution of her symptoms. CONCLUSIONS: In patients with EBV infection who exhibit persistent high fever and unresponsiveness to antibiotics, the possibility of HLH should be considered. Early diagnosis and rapid initiation of appropriate treatment may avert an unfavorable outcome.

Association of smoking with liver fibrosis and mortality in primary biliary cholangitis.

BACKGROUND: The outcome of primary biliary cholangitis (PBC) is affected by both genetic and environmental factors. OBJECTIVE: The aim of this study was to study the effect of smoking on liver histology and mortality in a genetically homogeneous population having PBC. PATIENTS AND METHODS: Smoking and drinking habits at diagnosis (based on standard criteria) were recorded in 171 Cretan patients with PBC (163 women). A total of 148 patients had a liver biopsy. Odds ratios were calculated with logistic regression analysis. Kaplan-Meier curves were used for mortality estimation. RESULTS: Smoking was associated with alcohol consumption of more than 20 g/day [adjusted odds ratio (AOR)=2.20, 95% CI: 1.029-4.099], severe steatosis (AOR=5.31, 95% CI: 2.019-9.919), and fibrosis stage F3-F4 (AOR=1.21, 95% CI: 1.015-3.031). Heavy smoking, years of passive smoking, and serious necroinflammatiοn were independent factors associated with advanced fibrosis after adjustment for sex, age, BMI, and alcohol consumption in multivariate analysis. For every pack-year increase in smoking intensity, there was a 3.2 times higher likelihood of advanced fibrosis (95% CI: 2.018-6.294). Increased mortality was found in smokers with advanced PBC. CONCLUSION: There is an association between smoking, whether active or passive, and advanced fibrosis in PBC. Mortality is increased in smokers with advanced disease at presentation.

GABAA receptor polymorphisms in alcohol use disorder in the GWAS era.

Alcohol use disorder (AUD) is a chronic, relapsing, neuro-psychiatric illness of high prevalence and with a serious public health impact worldwide. It is complex and polygenic, with a heritability of about 50%, and influenced by environmental causal heterogeneity. Risk factors associated with its etiology have a genetic component. GABA (γ-aminobutyric acid) is a major inhibitory neurotransmitter in mammalian brain. GABAA receptors are believed to mediate some of the physiological and behavioral actions of alcohol. In this critical review, relevant genetic terms and type and methodology of the genetic studies are briefly explained. Postulated candidate genes that encode subunits of GABAA receptors, with all the reported SNPs, are presented. Genetic studies and meta-analyses examining polymorphisms of the GABAA receptor and their association with AUD predisposition are presented. The data are critically examined with reference to recent GWAS studies that failed to show relations between GABAA receptors and AUD. Restrictions and perspectives of the different findings are discussed.

Screening for Hepatopulmonary Syndrome in Cirrhotic Patients Using Technetium 99m-macroaggregated Albumin Perfusion Lung Scan (Tc-MAA): Diagnostic Approach and Clinical Correlations.

BACKGROUND AND AIMS: The aims of this study were to prospectively screen cirrhotic patients with arterial blood gas test and albumin perfusion scan, identify those fulfilling the classic hepatopulmonary syndrome (HPS) criteria, correlate with clinical parameters, and evaluate the survival of patients with HPS compared with those without HPS in a genetically homogenous Cretan cirrhotic population. MATERIALS AND METHODS: Data on consecutive 102 patients within 1 year were collected and analyzed. All patients underwent a technetium 99m-macroaggregated albumin perfusion lung scan (Tc-MAA). Diagnosis of HPS was based on the presence of the quantitative index Tc-MAA≥6% and a [P(A-a)O2]≥15 mm Hg (≥20 mm Hg for patients over >64 y). RESULTS: In 94/102 patients, complete scintigraphic data were available. In total, 24 (26%) patients fulfilled the diagnostic criteria of HPS; 95.8% of them had mild-to-moderate HPS. In 8 patients the Tc-MAA scintigraphy could not be interpreted. There was no difference in HPS between decompensated (24.6%) and compensated cirrhosis (27.3%). In the multivariate analysis only the quantitative index was significant for the diagnosis of HPS (P=0.001, odds ratio; 95% confidence interval, 7.05; 2.27-21.87). Kaplan- Meier survival curves indicated a similar overall prognosis for patients diagnosed with HPS (P=0.105). CONCLUSIONS: HPS is a frequent complication of cirrhosis. Mild-to-moderate HPS has no significant effect on survival of cirrhotic patients. The quantitative Tc-MAA test is a reliable tool for diagnosis.

Availability of hepatitis C diagnostics and therapeutics in European and Eurasia countries.

BACKGROUND: Treatment with direct acting antiviral agents (DAAs) has provided sustained virological response rates in >95% of patients with chronic hepatitis C virus (HCV) infection. However treatment is costly and market access, reimbursement and governmental restrictions differ among countries. We aimed to analyze these differences among European and Eurasian countries. METHODS: A survey including 20-item questionnaire was sent to experts in viral hepatitis. Countries were evaluated according to their income categories by the World Bank stratification. RESULTS: Experts from 26 countries responded to the survey. As of May 2016, HCV prevalence was reported as low (≤1%) in Croatia, Czech Republic, Denmark, France, Germany, Hungary, the Netherlands, Portugal, Slovenia, Spain, Sweden, UK; intermediate (1-4%) in Azerbaijan, Bosnia and Herzegovina, Italy, Kosovo, Greece, Kazakhstan, Romania, Russia, Serbia and high in Georgia (6.7%). All countries had national guidelines except Albania, Kosovo, Serbia, Tunisia, and UK. Transient elastography was available in all countries, but reimbursed in 61%. HCV-RNA was reimbursed in 81%. PegIFN/RBV was reimbursed in 54% of the countries. No DAAs were available in four countries: Kazakhstan, Kosovo, Serbia, and Tunisia. In others, at least one DAA combination with either PegIFN/RBV or another DAA was available. In Germany and the Netherlands all DAAs were reimbursed without restrictions: Sofosbuvir and sofosbuvir/ledipasvir were free of charge in Georgia. CONCLUSION: Prevalence of HCV is relatively higher in lower-middle and upper-middle income countries. DAAs are not available or reimbursed in many Eurasia and European countries. Effective screening and access to care are essential for reducing liver-related morbidity and mortality.

Ultrasound-guided direct intrahepatic portosystemic shunt in patients with Budd-Chiari syndrome: Short- and long-term results.

BACKGROUND AND AIMS: Budd-Chiari syndrome (BCS) is treated with anticoagulation therapy, transjugular intrahepatic portosystemic shunt (TIPS), angioplasty, and liver transplantation. TIPS is not always technically feasible, due to the complete hepatic venous thrombosis. Direct intrahepatic portosystemic shunt (DIPS) is an alternative method for decompression of portal hypertension. This is a retrospective, single-center study aiming to evaluate the outcome of ultrasound (US)-guided DIPS in patients with BCS. MATERIALS AND METHODS: Between 2003 and 2016, six patients with BCS were treated with US-guided DIPS. Polytetrafluoroethylene (PTFE)-covered stents were used in two patients and bare-metal stents in four patients. Mean follow-up time was 71.4 months (range: 21-164). Technical/clinical success, technical difficulties, and complications of DIPS were analyzed. RESULTS: Technical success without complications was achieved in all patients (100%). In one patient, DIPS was performed through the right femoral vein, without significant amelioration of portal hypertension (clinical success 83.3%). In four out of five patients, ascites and variceal bleeding resolved completely and in the other one ascites was relieved. Six- and 12-month primary patency rates were 100% in PTFE-covered stent group when compared with bare-metal stent group, the rates were 33% and 0%, respectively. CONCLUSION: US-guided DIPS is a safe and effective alternative technique for patients with BCS, with significant clinical improvement.

Long-term change in incidence and risk factors of cirrhosis and hepatocellular carcinoma in Crete, Greece: a 25-year study.

BACKGROUND: No sequential long-term data exist for Greece on the etiological evolution and incidence of cirrhosis and hepatocellular carcinoma. Therefore, we studied their etiological evolution over a period of 25 years in the island of Crete. METHODS: We studied 812 cases of cirrhosis (561 male, median age 69 years) and 321 cases of hepatocellular carcinoma (234 male, median age 70 years) from the database of our Center. Cases were classified into five-year periods according to incidence and etiology (hepatitis B, hepatitis C, alcohol, alcohol plus viral, and non-alcoholic fatty liver disease). RESULTS: Overall, there was an increase in the incidence of hepatocellular carcinoma. A significant fourfold reduction in the incidence of hepatitis C-related cirrhosis was observed, which was degraded from first to third place as a risk factor for cirrhosis. Alcohol gradually became the first risk factor in cirrhosis (1990-94: 36.1%, 2010-14: 52.3%) and carcinoma, while the steepest increase in incidence of cirrhosis and carcinoma was associated with non-alcoholic fatty liver disease. CONCLUSIONS: The incidence of cirrhosis remained constant over the years, but the incidence of hepatocellular carcinoma increased during the last decade. Risk factors for cirrhosis and hepatocellular carcinoma have changed over the past 25 years in Crete. The initial high hepatitis C virus association has significantly decreased, with alcohol now ranking first among risk factors. Non-alcoholic fatty liver disease is continually increasing and is a prominent risk factor for cirrhosis and hepatocellular carcinoma.

Geoepidemiology of hepatocellular carcinoma in the island of Crete, Greece. A possible role of pesticides.

BACKGROUND & AIMS: Geoepidemiological data of hepatocellular carcinoma (HCC) are lacking. Crete has a genetically homogeneous population and is suitable for studies to identify a possible contribution of environmental factors in HCC. METHODS: Databases for HCC (316 cases), hepatitis B virus (HBV) (633) and hepatitis C virus (HCV) (392), constructed over the past 20 years in our Unit, were used. Data included place of birth and place of residence for the last 15 years. Hellenic Statistical Authority provided population statistics from 1980 to 2014. Time-spatial methods were applied in Gis-ArcMap 10 software. Spatial autocorrelation tests (Moran's index) detected differences between the spatial distribution to place of residence. Spatial density maps were created. Kriging Interpolation was applied, to produce prediction maps of HCC. RESULTS: Hepatitis C virus appears in areas of high prevalence while HBV is uniformly distributed. HCC is more prevalent in Eastern Crete. A spatial autocorrelation between HCC and either HCV (Moran's I = 0.88, P < 0.001) or HBV (I = 0.84, P < 0.02) was found as expected. However, there is a discrepancy in the South East of Crete, where a higher prevalence of HCC than expected was observed. This is an area where extensive use of pesticides in large green houses is practiced. CONCLUSIONS: Hepatocellular carcinoma is associated with the dispersion of HCV and HBVs. In an area with widespread use of pesticides, a higher than expected spatial distribution of HCC was detected.

Boceprevir for chronic HCV genotype 1 infection in treatment-experienced patients with severe fibrosis or cirrhosis: The Greek real-life experience.

BACKGROUND: The aim of our study was to evaluate the safety and efficacy of triple therapy using boceprevir (BOC) with pegylated interferon (pIFN)/ribavirin (RBV) in chronic hepatitis C (CHC) genotype 1 (G1) treatment-experienced patients with advanced fibrosis or compensated cirrhosis. METHODS: We report the Greek experience on the first CHC patients who received BOC-based regimen. From September 2011 to June 2012, 26 treatment-experienced CHC patients and G1 with bridging fibrosis or compensated cirrhosis received 48 weeks of BOC+pIFN+RBV antiviral therapy. Data on complete blood counts and HCV RNA levels were obtained prior to therapy, at treatment weeks 4, 8, 12, 24, 36, 48 and 24 weeks after the end of treatment. RESULTS: A full set analysis was performed in 25 of 26 patients. Nine patients (36%) achieved sustained viral response (SVR). Ten patients (40%) stopped the therapy because of futility rules and 3 (12%) due to adverse events. Four patients (16%) developed a virological breakthrough (3 of those presented futility rules as well) and 2 (8%) relapse. All patients who achieved SVR had G 1b, 6 (67%) were non-cirrhotic and 5 (55%) had >1 log decline in baseline HCV RNA levels at week 4 of the treatment. There were no deaths, while two patients were hospitalized due to side effects. CONCLUSION: The triple therapy with BOC+pIFN+RBV in this cohort of real-life treatment-experienced CHC G1 patients and advanced liver disease was safe offering cure in the majority of those who could tolerate and complete treatment under a close monitoring.

Clinical outcomes of compensated and decompensated cirrhosis: A long term study.

AIM: To study these characteristics and prognostic patterns in a Greek patient population. METHODS: We analyzed a large cohort of cirrhotic patients referred to the department of Gastroenterology and Hepatology and the outpatient clinics of this tertiary hospital, between 1991 and 2008. We included patients with established cirrhosis, either compensated or decompensated, and further decompensation episodes were registered. A data base was maintained and updated prospectively throughout the study period. We analyzed differences in cirrhosis aetiology, time to and mode of decompensation, hepatocellular carcinoma (HCC) occurrence and ultimately patient survival. RESULTS: Five hundreds and twenty-two patients with median age 67 (range, 29-91) years and average follow up 9 years-10 mo (range, 1-206 mo) were studied. Commonest aetiology was hepatitis C virus (HCV, 41%) followed by alcohol (31%). The median survival time in compensated cirrhotics was 115 mo (95%CI: 95-133), whereas in decompensated patients was 55 mo (95%CI: 36-75). HCV patients survived longer while HBV patients had over twice the risk of death of HCV patients. The median time to decompensation was 65 mo (95%CI: 51-79), with alcoholics having the highest risk (RR = 2.1 vs HCV patients). Hepatitis B virus (HBV) patients had the highest risk of HCC, alcoholics the lowest. Leading causes of death: liver failure, hepatorenal syndrome, sepsis and HCC progression. CONCLUSION: Cirrhosis aetiology and decompensation at presentation were predictors of survival. Alcoholics had the highest decompensation risk, HBV cirrhotics the highest risk of HCC and HCV cirrhotics the highest decompensation-free time.

Primary biliary cirrhosis in a genetically homogeneous population: disease associations and familial occurrence rates.

BACKGROUND: Primary biliary cirrhosis (PBC) is a disease with genetic and environmental pathogenetic background. Chemicals, infectious agents, hormone therapy, reproductive history and surgical interventions have been implicated in the induction of PBC. Familial PBC has been documented in first degree relatives (FDR). Most cohort studies are genetically heterogeneous. Our study aimed to determine eventual lifestyle or disease associations and familial occurrence rates in a genetically homogeneous and geographically defined population of PBC patients. METHODS: 111 consenting PBC patients, were compared with 115 FDR and 149 controls matched for age, sex, Cretan origin and residence. All participants completed a questionnaire regarding demographics, lifestyle, medical, surgical and reproductive history. Significant variables on the univariate analysis were analyzed by multivariate analysis using a forward step-wise logistic regression model. RESULTS: Dyslipidaemia was found in 69.4% of patients, 60% of FDR and 40.9% of controls (p < 0.0001 and p = 0.003 respectively), autoimmune diseases in 36.9% of patients, 30.4% of FDR and 13.4% of controls (p < 0.0001 and p = 0.011 respectively). Hashimoto's disease (p = 0.003), Raynaud syndrome (p = 0.023) and Sjögren syndrome (p = 0.044) were significantly associated with PBC. On multivariate analysis statistically significant associations were found with primary educational level (AOR 2.304, 95% CI 1.024-5.181), cholecystectomy (AOR 2.927, 95% CI 1.347-6.362) and the presence of at least another autoimmune disease (AOR 3.318, 95% CI 1.177-6.22). Cancer history was more frequent in patients than in controls (p = 0.033). Familial PBC was found to be 9.9%. CONCLUSIONS: Dyslipidaemia and autoimmune diseases were significantly increased not only in patients as expected but also in their FDR. An increased prevalence of malignancies was found in patients. Primary educational level, cholecystectomy and the presence of at least another autoimmune disease were found as putative risk factors for PBC. No association was found with smoking, urinary tract infection or reproductive history. The reported high familial occurrence of PBC could imply screening with AMA of FDR with at least another autoimmune disease.

Increased serum activin-A differentiates alcoholic from cirrhosis of other aetiologies.

BACKGROUND: Activin-A is a molecule of the TGF superfamily, implicated in liver fibrosis, regeneration and stem cell differentiation. However, data on activins in liver diseases are few. We therefore studied serum levels of activin-A in chronic liver diseases. To identify the origin of activin-A, levels in the hepatic vein were also estimated. MATERIALS AND METHODS: Nineteen controls and 162 patients participated in the study: 39 with hepatocellular carcinoma (HCC: 19 viral associated and 20 alcohol associated), 18 with chronic hepatitis C (CHC), 47 with primary biliary cirrhosis (26 PBC stage I-II and 21 stage IV), 22 with alcoholic cirrhosis (AC, hepatic vein blood available in 16), 20 with HCV cirrhosis (hepatic vein blood available in 18) and 16 patients with alcoholic fatty liver with mild to moderate fibrosis but no cirrhosis. RESULTS: Activin-A levels were significantly increased (P < 0·001) in serum of patients with AC (median 673 pg/mL, range 449-3279), compared with either controls (149 pg/mL, 91-193) or patients with viral cirrhosis (189 pg/mL, 81-480), CHC (142 pg/mL, 65-559) PBC stage I-II (100 pg/mL, 59-597) and PBC stage IV (104 pg/mL, 81-579). Only patients with AC-associated HCC had significantly increased levels of activin-A (2403 pg/mL, 1561-7220 pg/mL). Activin-A serum levels could accurately discriminate AC from cirrhosis of other aetiologies and noncirrhotic alcoholic fatty liver with fibrosis. CONCLUSIONS: Increased serum levels of activin-A only in patients with alcohol-related cirrhosis or HCC suggest a possible role of this molecule in the pathophysiology of AC. Further research is warranted to elucidate its role during the profibrotic process and its possible clinical applications.

Epstein Barr virus hepatitis.

OBJECTIVES: Epstein-Barr Virus (EBV) infection has the potential to establish life-long, benign infections in their hosts. Although biochemical evidence of hepatocellular damage is common, jaundice is uncommon and complete recovery is the rule. The present study describes clinical characteristics and changes of liver function tests during the course of infectious mononucleosis. PATIENTS AND METHODS: All immunocompetent patients with hepatic dysfunction associated with acute EBV infection, cared for at the University Hospital of Heraklion, over a 6-year period, were identified and retrospectively studied. RESULTS: The study included 41 patients with a median age of 18.5 (15-51) years. Aspartate-aminotransferase (AST) and alanine-aminotransferase (ALT) were increased in an average maximum of 5-fold. Both transaminase levels started to rise 2 days after the clinical onset of the disease, and returned to normal after a period of 20 days. Alkaline-phosphatase (ALP), γ-glutamyltransferase (γ-GT) and bilirubin levels also increased above the normal values during the course of the disease and returned to normal after a period of 20, 30 and 22 days respectively. The changes of mean AST and ALT levels over time were statistically significant, while those of mean ALP, γ-GT and bilirubin levels over time were not. Anicteric cholestatic liver disease was observed in 24 patients (59%), while icteric only in 2 (6%). CONCLUSION: Liver involvement in acute EBV infection represents mild and self-limited hepatitis with predominantly cholestatic features.

Serum surrogate markers of liver fibrosis in primary biliary cirrhosis.

BACKGROUND: Hyaluronan, leptin, laminin and collagen IV have been used extensively for the assessment of liver fibrosis. The aim of this study was to assay these markers in the peripheral and hepatic vein blood of primary biliary cirrhosis (PBC) patients and to study their ability to discriminate early from advanced disease. METHODS: Sera from 62 PBC patients were compared to 60 controls, 44 chronic Hepatitis C, 38 hepatocellular carcinoma and 34 viral cirrhosis patients. Serum from the hepatic vein of 15 cirrhotic PBC patients and 17 patients with viral cirrhosis was also assayed. RESULTS: All disease groups had significantly increased levels of hyaluronan and collagen IV, compared to controls, while laminin was significantly increased only in viral cirrhosis. Hyaluronan levels were statistically different between early (54.5 ng/ml; 95%CI 27.3-426.9) and late PBC (154.5 ng/ml; 95%CI 55.3-764.4, p<0.05). The area under the curve (AUC) for the identification of late PBC was 0.74 for hyaluronan, 0.63 for leptin, 0.59 for laminin and 0.70 for collagen IV. Hyaluronan had high sensitivity and NPV in identifying late stages of PBC (96% and 90%, respectively). Short term UDCA had no effect on these markers. CONCLUSION: No single measurement can differentiate between advanced and early fibrosis in PBC. However serum hyaluronan is a promising single serum marker for longitudinal studies in PBC.