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We read with great interest the article by van der Meer et al 1 recently published in Gut . They found that a simple algorithm based on demographic and readily available laboratory variables is able to predict long-term prognosis of patients with chronic HCV infection and well-compensated, advanced liver disease. Indeed, in this time and age, an accurate assessment of the outcome of patients with HCV infection and advanced fibrosis is of utmost importance as prognostic subclassification may help prioritise those who are in urgent need of antiviral treatment within an homogeneous group of patients who are equally candidates to therapy. The findings of this study are especially relevant as the results were validated in an independent cohort of patients with similar disease stage. The parameters identified in this study as predictors of …

Adalimumab Trough Levels and Response to Biological Treatment in Patients With Inflammatory Bowel Disease: A Useful Cutoff in Clinical Practice

Case Report A 65-year-old man presented with mildly elevated gamma-glutamyltranspeptidase (GGT) serum level on blood tests done for general check-up, and the finding of hepatomegaly and diffuse heterogeneity of the hepatic parenchyma on abdominal ultra sound. The patient’s history included essential hypertension treated with angiotensin converting enzyme-inhibitors. The patient had no other features of the metabolic syndrome and did not drink alcohol. Physical examination revealed a mildly enlarged liver with a smooth, non-tender margin and a regular surface. Serum GGT was 75 IU/L (normal: 11-50 IU/L); liver enzymes and testing for viral and autoimmune hepatitis were normal. Abdominal ultrasound showed diffuse hyperechoic liver echotexture with multiple, small hypoechoic lesions in both hepatic lobes, particularly evident in the hepatic dome. It also showed one 8-mm gallbladder stone with no intrahepatic and main bile duct dilation, and no signs of portal hypertension. Contrast-enhanced computed tomography showed small, multiple, round and irregular hypodense lesions in both hepatic lobes that did not enhance with contrast. Magnetic resonance imaging (MRI) and MR-cholangiography showed the presence of numerous small (

The Model for End-Stage Liver Disease (MELD) score is an important and well established tool for assessing prognosis in patients with liver cirrhosis. It has been suggested that the longitudinal evaluation of the MELD score may reflect the progression of liver failure more reliably and therefore be more useful in prognostic assessment.To assess the prognostic meaning of MELD score modifications in a cohort of cirrhotic patients in whom clinical and biochemical workup was carried out at least twice during a minimum interval of 30 days.Forty-six cirrhotic patients were longitudinally evaluated for a median follow-up of 365 days. After initial assessment, all the patients had at least one clinical and biochemical reevaluation during follow-up, which was performed no less than 1 month after initial evaluation. MELD was calculated at entry and at second evaluation. DeltaMELD was calculated as MELD at second evaluation minus MELD at entry. DeltaMELD/time was calculated as DeltaMELD divided by time elapsed between initial assessment and second evaluation expressed in months.During follow-up, 13 patients died (28%). The median interval between clinical evaluations was 120 days. MELD scores at entry (13 +/- 4 vs 16 +/- 6, P = 0.0516) and DeltaMELD (0 +/- 4 vs 4 +/- 2, P = 0.0028) were significantly different between patients who died and those who survived during the 1-year follow-up. All the patients who died during follow-up showed an increase of at least 1 unit in DeltaMELD/time (sensitivity = 100%), and all the patients who survived showed a decrease of more than 1 unit in DeltaMELD/time (specificity = 100%).Longitudinal evaluation of the MELD score provides important prognostic information that seems to complete the prognostic definition provided by "static" MELD. Prospective studies in larger series are needed to validate the prognostic use of MELD modifications over time.

Introduction Percutaneous endoscopic gastrostomy (PEG) is the method of choice for long-term nutrition in patients with longstanding eating difficulties due to pathological entities that impair swallowing. The feeding catheters are designed to be removed by external traction or by endoscopy. Aim To evaluate the feasibility of the cut-and-push method as a possible safe alternative to the pullout method for removal of soft PEG devices with a large caliber. Methods Patients with 20 French (Fr) or larger soft PEG system were enrolled for PEG removal by the cut-and-push technique. The replacement catheters were 2 Fr larger than the original ones. Patients were observed at 24 and 72 hours via home nursing care and then weekly for 1 month for signs of intestinal obstruction, tube leakage, or blockage. Results Seventy-nine patients (52 men; mean age 67 years) underwent the procedure: 42 due to leakage and 37 due to blockage. Mean time before tube removal was 4.8 months (range, 3-8). PEG devices were 20 Fr and 24 Fr in 57 (72.2%) and 22 (27.8%) cases, respectively. Collection of the inner component from stool was reported within 48 hours in 63 cases (80%). No cases of intestinal obstruction or other severe adverse events due to the inner component being eliminated throughout the intestine were observed in any patient during the study. Conclusions The cut-and-push method employed for removal of a soft PEG tube with a large caliber seems to be safe and can be performed when removal by external traction may determine the occurrence of peristomal complications or jeopardize PEG replacement.

Thrombocytopenia is common among patients with hepatitis C virus (HCV) infection and advanced fibrosis or cirrhosis, limiting initiation and dose of peginterferon-alfa (PEG) and ribavirin (RBV) therapy. The phase 3 randomized, controlled studies, Eltrombopag to Initiate and Maintain Interferon Antiviral Treatment to Benefit Subjects with Hepatitis C-Related Liver Disease (ENABLE)-1 and ENABLE-2, investigated the ability of eltrombopag to increase the number of platelets in patients, thereby allowing them to receive initiation or maintenance therapy with PEG and RBV.Patients with HCV infection and thrombocytopenia (platelet count75,000/μL) who participated in ENABLE-1 (n = 715) or ENABLE-2 (n = 805), from approximately 150 centers in 23 countries, received open-label eltrombopag (25-100 mg/day) for 9 weeks or fewer. Patients whose platelet counts reached the predefined minimal threshold for the initiation of PEG and RBV therapy (95% from ENABLE-1 and 94% from ENABLE-2) entered the antiviral treatment phase, and were assigned randomly (2:1) to groups that received eltrombopag or placebo along with antiviral therapy (24 or 48 weeks, depending on HCV genotype). The primary end point was sustained virologic response (SVR) 24 weeks after completion of antiviral therapy.More patients who received eltrombopag than placebo achieved SVRs (ENABLE-1: eltrombopag, 23%; placebo, 14%; P = .0064; ENABLE-2: eltrombopag, 19%; placebo, 13%; P = .0202). PEG was administered at higher doses, with fewer dose reductions, in the eltrombopag groups of each study compared with the placebo groups. More patients who received eltrombopag than placebo maintained platelet counts of 50,000/μL or higher throughout antiviral treatment (ENABLE-1, 69% vs 15%; ENABLE-2, 81% vs 23%). Adverse events were similar between groups, with the exception of hepatic decompensation (both studies: eltrombopag, 10%; placebo, 5%) and thromboembolic events, which were more common in the eltrombopag group of ENABLE-2.Eltrombopag increases platelet numbers in thrombocytopenic patients with HCV and advanced fibrosis and cirrhosis, allowing otherwise ineligible or marginal patients to begin and maintain antiviral therapy, leading to significantly increased rates of SVR. Clinical trial no: NCT00516321, NCT00529568.

Thrombocytopenia may represent a barrier to optimal management of chronic liver disease patients undergoing invasive procedures, or who need to be treated with interferon-based antiviral therapy. Eltrombopag is a thrombopoietic drug that acts upon binding thrombopoietin receptor and stimulates megakaryocytopoiesis and platelet production.A summary of the preclinical studies and of studies carried out in patients with chronic liver disease with eltrombopag are presented in this paper. Data are based on abstracts from journal articles and international conferences found in a PubMed search of literature published up to November 2012.Eltrombopag has shown to be capable of reducing the need for platelet transfusion in thrombocytopenic patients with advanced liver disease undergoing invasive procedures and help increase the sustained virological response rate to interferon-based antiviral therapy in patients with chronic hepatitis C who were poor candidates to treatment because of thrombocytopenia. In chronic liver disease patients, the possible benefits of eltrombopag administration should be accurately weighed against the adverse events profile of the drug due to possible concerns regarding the occurrence of thromboembolic events and the potential for decompensation of chronic liver disease.

OBJECTIVES: Radiofrequency ablation (RFA) is widely performed for hepatocellular carcinoma (HCC). However, there has been no report on 10-year outcome of RFA. The objective of this study was to report a 10-year consecutive case series at a tertiary referral center. METHODS: We performed 2,982 RFA treatments on 1,170 primary HCC patients and analyzed a collected database. RESULTS: Final computed tomography images showed complete tumor ablation in 2,964 (99.4%) of 2,982 treatments performed for the 1,170 primary HCC patients. With a median follow-up of 38.2 months, 5- and 10-year survival rates were 60.2% (95% confidence interval (CI): 56.7–63.9%) and 27.3% (95% CI: 21.5–34.7%), respectively. Multivariate analysis demonstrated that age, antibody to hepatitis C virus (anti-HCV), Child-Pugh class, tumor size, tumor number, serum des-γ-carboxy-prothrombin (DCP) level, and serum lectin-reactive α-fetoprotein level (AFP-L3) were significantly related to survival. Five- and 10-year local tumor progression rates were both 3.2% (95% CI: 2.1–4.3%). Serum DCP level alone was significantly related to local tumor progression. Five- and 10-year distant recurrence rates were 74.8% (95% CI: 71.8–77.8%) and 80.8% (95% CI: 77.4–84.3%), respectively. Anti-HCV, Child-Pugh class, platelet count, tumor size, tumor number, serum AFP level, and serum DCP level were significantly related to distant recurrence. There were 67 complications (2.2%) and 1 death (0.03%). CONCLUSIONS: RFA could be locally curative for HCC, resulting in survival for as long as 10 years, and was a safe procedure. RFA might be a first-line treatment for selected patients with early-stage HCC.

The evaluated article assesses the effectiveness in clinical practice of surveillance with ultrasound (US) and α-fetoprotein (AFP) in patients at risk of developing hepatocellular carcinoma. After a median follow-up of 3.5 years, among the 442 enrolled patients with cirrhosis, 41 developed tumor (annual incidence, 2.8%). Twenty-three hepatocellular carcinomas were diagnosed at Barcelona Clinic Liver Cancer early stage (single tumor 20 ng/ml. Specificity was 91.5% for US and 90.5% for AFP. The combination of the tests increased the sensitivity to 90.2%, with a small decrease in specificity (83.3%). In a real-world setting, the combination of US and AFP would be the most effective for hepatocellular carcinoma surveillance.

Background In patients with chronic hepatitis C virus (HCV) infection, the presence of peripheral blood cytopaenia may represent an obstacle to pegylated interferon and ribavirin treatment. Aims To evaluate the prevalence of anaemia, neutropaenia and thrombocytopaenia potentially limiting initiation of pegylated interferon and ribavirin treatment in patients with chronic HCV infection who were otherwise eligible for antiviral therapy. Methods We studied 3059 consecutive anti-HCV and HCV-RNA positive patients referred to our centre to be evaluated for antiviral therapy from June 2002 to May 2011. The European Association for the Study of Liver HCV guidelines were applied to assess eligibility for antiviral therapy. Results In the study cohort, 1,521 patients (49.7%) were not eligible for treatment because of reasons different from haematological abnormalities. In the remaining 1,538 patients the overall prevalence of any peripheral blood cytopaenia potentially preventing patients from being treated with antiviral therapy was 15.1%. In particular, anaemia (haemoglobin level

To the Editor: We read with interest the letter by Marrero and El-Serag that calls for the inclusion of alpha-fetoprotein (AFP) in the American Association for the Study of Liver Diseases (AASLD) updated guidelines for the management of hepatocellular carcinoma (HCC).1, 2 However, we disagree with their conclusions and feel that the AASLD recommendation to perform HCC surveillance with ultrasonography (US) alone is supported by solid evidence.1, 2 The evidence supporting surveillance programs for HCC with liver US with or without AFP testing stems from the results of a randomized controlled trial and from cohort studies showing that surveillance improves both detection rate of early HCCs and patient survival.3-5 However, it is clear that the authors of the AASLD guidelines took into account the numerous limitations of AFP testing, and therefore it is no surprise that they did not include this serological marker in their HCC surveillance recommendations.2 In fact, although we may agree with Marrero and El-Serag that the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial is a suboptimal setting to assess the role of AFP for the early detection of HCC, this study had the precious gifts of providing prospectively collected data and to include a large population of patients who were mainly at risk of developing HCC.6 Furthermore, data were available both at HCC diagnosis and 1 year before, thus being as close as possible to everyday clinical practice and therefore providing the best evidence currently available.2, 6 In this study, the sensitivity of AFP at a cutoff of 20 ng/mL was low (i.e., 61%) at the time of HCC diagnosis, yet at 22% it was unacceptably low 12 months before, when HCC was likely present in the majority of patients.6 These results are strikingly similar to those obtained in a case-control study carried out in a completely different population, where a 20 ng/mL AFP cutoff showed 60% sensitivity for the diagnosis of HCC,7 although sensitivity was unacceptably low (i.e., approximately 50%) for single nodules and/or lesions smaller than 3 cm.8 We feel that the extensors of the updated AASLD guidelines did not ignore the “highest level of evidence for the efficacy of US combined with AFP in research studies”2 as affirmed by Marrero and El-Serag,1 but evaluated both efficacy and cost-effectiveness. Indeed, the combination of AFP and US leads to a mere 6%-8% increase in sensitivity for the detection of early HCC as compared to US alone, with a doubling in the rate of false-positives and at an unbearable increase (by 84%) in surveillance-related costs.9, 10 Therefore, AFP provides no additional benefit to US, as recently concluded even in the meta-analysis by the Marrero group,10 with a significant worsening of the cost-effectiveness of surveillance.9 To conclude, we feel that the use of AFP as a surveillance test for HCC should be regarded as a memory, and any effort to increase the awareness and application of the currently proposed surveillance guidelines among physicians in clinical practice should be embraced.

Small Intestinal Bacterial Overgrowth and Helicobacter pylori : Can They Be Cause of Thrombocytopenia in Patients With Chronic Liver Disease?

Background/Aim: In patients with liver cirrhosis, the platelet count/spleen diameter ratio has been validated as a parameter for the noninvasive diagnosis of esophageal varices. Schistosoma infection is a frequent cause of portal hypertension in Middle Eastern countries, and is associated with the development of esophageal varices. In this study we aimed to evaluate the platelet count/spleen diameter ratio as a noninvasive tool for the prediction of the presence of esophageal varices in patients with schistosoma-related chronic liver disease. Patients and Methods: Forty-three patients with hepatosplenic schistosomiasis underwent upper digestive endoscopy to check for the presence of esophageal varices. Furthermore, all patients underwent abdominal ultrasonography, and maximum spleen diameter (in mm) was measured. The platelet count/spleen diameter ratio was calculated in all patients. Results: Esophageal varices were found in 31 patients (72%). Age and gender were not significantly different between patients with and without varices. In patients with varices, median platelet count (82,000/μL versus 172,000/μL, P < 0.0001) and platelet count/spleen diameter ratio (571 versus 1651, P < 0.0001) were significantly lower, while spleen diameter (147 mm versus 109 mm, P = 0.0006) was significantly larger. In multivariate analysis, the platelet count/spleen diameter ratio was the only parameter independently associated with the presence of varices (P < 0.0001). Conclusions: In this study we have validated the use of the platelet count/spleen diameter ratio for the noninvasive diagnosis of esophageal varices in patients with portal hypertension caused by schistosoma infection. In these patients, the platelet count/spleen diameter ratio might be used to allow better rationalization of medical resources and use of endoscopy.

Comment on Risk factors for exceeding the Milan criteria after successful radiofrequency ablation in patients with early-stage hepatocellular carcinoma. [Liver Transpl. 2014]

Patients with advanced liver disease often undergo invasive procedures, so the combination of thrombocytopenia, coagulopathy, and bleeding should be carefully assessed. We evaluated the prevalence of thrombocytopenia in a series of patients with liver cirrhosis who were being evaluated for orthotopic liver transplantation (OLT) and determined the number of invasive procedures and procedure-related incidences of bleeding in patients with thrombocytopenia.We studied 121 consecutive patients who were being evaluated for OLT. Thrombocytopenia was defined as a platelet count150,000/μL and severe thrombocytopenia as a platelet count75,000/μL. The presence of significant coagulopathy was defined as an international normalized ratio1.5. Invasive procedures and incidences of procedure-related bleeding were recorded for each patient.The prevalence of thrombocytopenia and severe thrombocytopenia were 84% and 51%, respectively. Among the 102 thrombocytopenic patients, 50 (49%) underwent an invasive procedure (32 with severe thrombocytopenia; 64%). Bleeding occurred in 10 of the patients who underwent an invasive procedure (20%). Among the 50 patients who underwent invasive procedure, 32 had severe thrombocytopenia and 18 had moderate thrombocytopenia. Bleeding occurred in 10 of the 32 patients (31%) with severe thrombocytopenia and in none of those with moderate thrombocytopenia. There was no difference in prevalence of significant coagulopathy between patients with severe thrombocytopenia who underwent invasive procedure and bled (3/10; 30%) and those who did not bleed (10/22; 45%).Thrombocytopenia has a high prevalence among patients with advanced liver disease. Bleeding related to invasive procedures occurs most frequently in patients with severe thrombocytopenia, whereas significant coagulopathy does not seem to be associated with bleeding.

Aliment Pharmacol Ther 31, 502–508 Summary Background There are few data in the literature regarding the long-term virological follow-up of chronic hepatitis C patients who obtain sustained virological response (SVR) to pegylated interferon (PEG-IFN) and ribavirin therapy. Aim To assess the durability of SVR to PEG-IFN and ribavirin therapy during long-term follow-up of chronic hepatitis C patients. Methods We evaluated a cohort of 231 chronic hepatitis C patients who had at least 48 weeks of follow-up after SVR to PEG-IFN and ribavirin treatment. Median duration of follow-up after SVR was 164 weeks, and exceeded 5 years in 30% of the cohort. Patients underwent consistent clinical, biochemical and virological evaluations every 6 months during follow-up. Results Sustained virological response was maintained in 211 patients (91%) while HCV-RNA became positive in two patients (

Background A consensus on the most reliable staging system for hepatocellular carcinoma (HCC) is still lacking but the most used is a revised Barcelona Clinic Liver Cancer (BCLC) system, adopted by the American Association for the Study of Liver Diseases (AASLD). We investigated how many patients are diagnosed in "very early" and "early" stage, follow the AASLD guidelines for treatment and whether their survival depends on treatment. Methods Data were collected in 530 "very early" and "early" HCC patients recruited by a multicentric Italian collaborative group (ITA.LI.CA). The Kaplan-Meier method was used to estimate overall survival and the log rank to test the statistical significance of difference between groups. Cox's multivariate stepwise regression analysis was used to pinpoint independent prognostic factors and the adjusted relative risks (hazard ratios) were calculated as well. A statistical analysis based on the chi-square test was used to identify significant differences in clinical or pathological features between patients. A P-value < 0.05 was considered statistically significant. Results "Very early" HCC were 3%; Cox multivariate analysis did not identify variables independently associated with survival. The patients following AASLD recommendations (20%) did not show longer survival. In "early" HCC patients (25%), treatment significantly modulated survival (p = 0.0001); the 28% patients treated according to the AASLD criteria survived longer (p = 0,004). The Cox analysis however identified only age, gender, number of lesions and Child class as independent predictors of survival. Conclusion patients with very early" HCC were very few in this analysis. In most instances they were not treated with the treatment suggested as the most appropriate by the AASLD guidelines and the type of treatment had no impact on survival, even though the number of patients was relatively low and part of the patients were diagnosed before the introduction of the guidelines: this analysis, therefore, might not be considered as conclusive and should be validated. The "early" stage group involved more patients, rarely treated according to the guidelines, both overall and also in those diagnosed after their publication; the survival was in part predicted by the type of treatment, with better results in those treated according to AASLD indications.

Background Screening for esophageal varices (EV) is an important part of the diagnostic workup of cirrhotic patients. Aims To independently validate the use of the platelet count/spleen diameter ratio for the non-invasive diagnosis of EV in patients with HCV-related cirrhosis and in a sub-group of patients with compensated disease. Methods A platelet count/spleen diameter ratio cut-off value of 909 was evaluated for the diagnosis of EV in the whole population (n = 311) and in patients with compensated disease alone (n = 114). Compensated disease was defined as the absence of ascites as detected by abdominal ultrasound in patients who are not on diuretics and absence of hepatic encephalopathy. Results In the whole cohort (EV prevalence 49.5%), the platelet count/spleen diameter ratio 909 cut-off value had 96.9% positive predictive value, 100% negative predictive value, and 98.4% efficiency for EV diagnosis. In compensated cirrhotics (EV prevalence 26.3%), the platelet count/spleen diameter ratio 909 cut-off showed an excellent negative predictive value (100%) and a positive predictive value of 93.8%. for the diagnosis of EV. Conclusions In patients with HCV-related cirrhosis, the platelet count/spleen diameter may be proposed as a non-invasive tool for EV diagnosis, especially in financially deprived developing countries.

Management Strategy for Patients With Gastroesophageal Reflux Disease: A Comparison Between Empirical Treatment With Esomeprazole and Endoscopy-Oriented Treatment

A model developed by our group identified low platelets and advanced Child-Pugh class (CPC) as being associated with large varices.To validate a defined cut-off of plateletsor =80,000/microL in CPC-A for large varices and plateletsor =90,000/microL in CPC-B/C for any varices.Validation cohorts consisted of patients with cirrhosis undergoing screening for varices from Oregon Health and Science University (n=152), Indiana University (n=252), and Genoa, Italy (n=101). Similar clinical and laboratory data were collected as for the original cohort. To assess the ability of these cut-offs to predict presence of large and any varices, sensitivity, specificity, positive and negative predictive values, likelihood ratios, and the c-statistic were measured.The validation cohorts were statistically different from the original cohort with regards to CPC and prevalence of large varices. Combining the original (n=301) and validation cohorts resulted in a negative predictive value of 92.1% for plateletsor =80,000/microL in CPC-A for large varices and positive predictive value of 80.1% for plateletsor =90,000/microL in CPC-B/C for any varices. Combining the 4 cohorts yielded a c-statistic of 0.67 (95% confidence interval: 063-0.72). No other factors such as splenomegaly and Model for End-Stage Liver Disease score were identified as significant.This study confirms the validity of a previous model identifying low platelets and advanced CPC class as predictors of large varices. Despite combining the cohorts, no other risk factors were identified.

1In the general population, the current best estimate of the prevalence of NAFLD and NASH shows figures of 20% and 2‐3%, respectively. 2 However, great disparity exists among various estimates and this can be attributed to both patient selection and the methods used to assess prevalence of the disease. Despite objective flaws in the estimates of the disease, it is believed that NAFLD likely represents the most common liver disease in the Western world. NAFLD is considered a disorder of affluence due to its close association with obesity and metabolic disorders which, in turn, can be considered proxies for a sedentary lifestyle and unhealthy nutritional habits. Until recently, it was believed that the prevalence of NAFLD should have been lower in countries that had not been affected by globalization, and where physical inactivity and over-nutrition are uncommon. On the contrary, more recent studies from nonurbanized regions of India, China and Indonesia have clearly documented a significant prevalence of fatty liver in the general population. More importantly, they confirmed an association between NAFLD and metabolic disorders even in these not yet urbanized Eastern regions of the world. 3‐5 These studies have led to a greater awareness of the ‘epidemic’ of NAFLD in the AsiaPacific region, as well as of the specific risk factors and picture of disease in patients from this part of the world. 6,7 In a recent, large survey carried out on the Korean general population, the prevalence of the metabolic syndrome was 29.3% and 22.3% in the rural and urban community, respectively. 8 Although no precise estimates have been made regarding the prevalence of NAFLD in Korea, the prevalence of patients with cryptogenic hepatocellular carcinoma has significantly increased over the last decade, and these patients showed a parallel trend towards increased risk factors for NAFLD. 9 Therefore, it is not surprising that the presence of NASH is associated with an increasing body mass index (BMI) in this country too. In fact, in a series of 43 non-cirrhotic NAFLD Korean patients, BMI and the presence of obesity were the only predictors of NASH and BMI alone was associated with the presence of fibrosis in NASH patients.

It has been suggested that clinically relevant portal hypertension may affect the therapeutic management and prognosis of cirrhotic patients with hepatocellular carcinoma (HCC). Nevertheless, the importance of the presence of esophageal varices in these patients has not yet been addressed formally. In this study our aim was to evaluate the prevalence and prognostic relevance of the presence of esophageal varices in a large series of patients with HCC.The prevalence of esophageal varices was evaluated in 1153 HCC patients who were consecutively referred to 10 Italian centers (the Italian Liver Cancer group). Survival was calculated from the time of HCC diagnosis until death or until the most recent follow-up visit, and was evaluated according to the presence or absence of esophageal varices. The independent prognostic meaning of the presence of esophageal varices was evaluated further in a multivariate regression analysis.Esophageal varices were found in 730 patients (63.3%). Patients with varices showed significantly shorter survival times (P.0001) as compared with patients without varices. Death as a result of bleeding was more common in patients with varices (P = .0127). In multivariate analysis, the presence of esophageal varices was associated independently with poorer survival (adjusted relative risk, 1.25; 95% confidence interval, 1.06-1.48; P = .0095).More than half of the patients with HCC have esophageal varices. The presence of esophageal varices is associated with a higher risk of death from bleeding, and is an independent determinant of the patient's prognosis. This variable should be taken into account in the diagnostic and therapeutic work-up of HCC patients.

Noninvasive assessment of esophageal varices (EV) may improve the management of patients with cirrhosis and decrease both the medical and financial burden related to screening. In this multicenter, international study, our aim was to prospectively validate the use of the platelet count/spleen diameter ratio for the noninvasive diagnosis of EV.A total of 218 cirrhotic patients underwent screening endoscopy for EV. Platelet count/spleen diameter ratio ((N/mm3)/mm) was assessed in all patients and its diagnostic accuracy was calculated. On the basis of previous results, a platelet count/spleen diameter ratio cutoff of 909 was applied to this population. The diagnostic accuracy of the platelet count/spleen diameter ratio was further evaluated for both severity and etiology of disease subgroups.Prevalence of EV was 54.1%. The platelet count/spleen diameter ratio had 86.0% (95% CI, 80.7-90.4%) diagnostic accuracy for EV, which was significantly greater as compared with either accuracy of platelet count alone (83.6%, 95% CI 78.0-88.3%, P= 0.038) or spleen diameter alone (80.2%, 95% CI 74.3-85.3%, P= 0.018). The 909 cutoff had 91.5% sensitivity (95% CI 85.0-95.9%), 67.0% specificity (95% CI 56.9-76.1%), 76.6% positive predictive value, 87.0% negative predictive value, 2.77 positive likelihood ratio, and 0.13 negative likelihood ratio for the diagnosis of EV. Accuracy of the platelet count/spleen diameter ratio was maintained for both severity and etiology of disease subgroups.The platelet count/spleen diameter ratio may be proposed as a safe and reproducible means to improve the management of cirrhotic patients who should undergo screening endoscopy for EV.

In patients with liver disease, thrombocytopenia is a clinical feature that may represent an obstacle to invasive diagnostic or therapeutic procedures, chemotherapy, and anti-viral treatment. Stimulation of the bone marrow is the most promising therapeutic intervention for thrombocytopenia in patients with chronic liver disease. The description of thrombopoietin and its (de)regulation in patients with chronic liver disease have disclosed new treatment opportunities. Indeed, pharmacologic treatment options for thrombocytopenia can be divided into treatments targeted at the thrombopoietin receptor (synthetic thrombopoietins and thrombopoietin-mimetic agents), and use of cytokines with general thrombopoietic potential. Unfortunately, use of synthetic thrombopoietin was hampered by the development of neutralizing antibodies, and thrombopoietin mimetic agents have not yet entered clinical studies. Interleukin-11 proved to be useful in increasing platelet count in patients with chronic liver disease, although its use is limited by side-effects. Erythropoietin has shown promising results in improving thrombocytopenia in cirrhotic patients. In patients with chronic liver disease, safe and well-tolerated treatments aimed at improving thrombocytopenia are still lacking. Larger studies are needed to evaluate and better characterize the thrombopoietic potential of erythropoietin. Human studies with thrombopoietin-mimetic agents are eagerly awaited in order to assess both effectiveness and safety of these drugs.

Proton pump inhibitors (PPIs) are the cornerstone in the treatment of gastresophageal reflux disease (GORD). PPIs are metabolized by the hepatic cytochrome P-450 enzymes (CYP-450). Rabeprazole is a PPI whose metabolism shows fewer interactions compared to other PPIs. In this study we evaluated the influence of rabeprazole administration on hepatic CYP-450 activity as measured by the (13)C-aminopyrine breath test ((13)C-ABT) in a group of patients with GORD. (13)C-ABT was performed on five GORD patients both before and after 1 week of rabeprazole administration (20 mg, b.i.d.). Pretreatment (13)C-ABT results were compared to posttreatment results. Pre- and posttreatment (13)C-ABT results for patients were compared to those obtained in five controls who did the test twice, with a 1-week interval in between. Before treatment, the (13)C-ABT results for the GORD patients did not significantly differ from those of healthy subjects. After treatment, we observed no significant modification of the (13)C-ABT in GORD patients compared to pretreatment values ((13)C-ABT %dose/hr, 10.56+/-1.31 versus 11.17+/-0.88; (13)C-ABT %cumulative dose, 8.08+/-1.11 versus 8.34+/-0.56). Posttreatment (13)C-ABT results were not significantly different from those obtained in controls at weekly repetition of the test. In patients with GORD, 1-week, full-dose rabeprazole does not display any significant interactions with CYP-450 activity.

The aims of the present study were to compare effects of sodium alginate and the antacid magaldrate anhydrous in adults with gastroesophageal reflux (GOR) symptoms. Patients with heartburn and/or acid regurgitation for at least 3 days in the week before the study started (n=203) were randomized to receive a single dose of sodium alginate or magaldrate anhydrous at the onset of symptoms during a 3-day run-in period. Patients with symptoms during the run-in (n=191) were rerandomized to receive a 14-day treatment with either drug given as four daily doses. A speed of actionor =30 min was significantly more frequent among patients in the alginate group (49.4% vs. 40.4%; P=0.0074). A trend toward a more prolonged duration of action (median: 16.5 vs. 12.7 hr) and a greater sum of the symptom intensity difference (median: 40.0 vs. 31.0) was observed in the sodium alginate group. Total disappearance of symptoms was reported in 81.6% and 73.9% of patients in the sodium alginate group and magaldrate group, respectively. We conclude that sodium alginate was faster than magaldrate in relieving GRO symptoms and showed a tendency toward a more prolonged duration of action and a higher level of efficacy.

Liver biopsy examination is the gold standard to diagnose the presence of cirrhosis. The aim of this study was to evaluate the accuracy of both 13 C-aminopyrine breath test ( 13 C-ABT) and 13 C-galactose breath test ( 13 C-GBT) in the noninvasive assessment of the presence of cirrhosis in patients with chronic liver disease.We evaluated 61 patients with chronic liver disease of diverse etiologies (21 compensated cirrhosis). All patients underwent 13 C-GBT and 13 C-ABT, and the results were expressed as a percentage of the administered dose of 13 C recovered per hour (%dose/h) and as the cumulative percentage of administered dose of 13 C recovered over time (%dose cumulative). Results were analyzed according to absence vs presence of cirrhosis.On average, 13 C-GBT %dose/h and %dose cumulative were decreased significantly in patients with compensated cirrhosis, and the same finding was observed for 13 C-ABT results from 30 to 120 minutes. 13 C-GBT %dose/h at 120 minutes had 71.4% sensitivity, 85.0% specificity, and 83.7% accuracy, whereas 13 C-ABT %dose cumulative at 30 minutes had 85.7% sensitivity, 67.5% specificity, and 77.1% accuracy for distinguishing between the 2 subgroups of patients. Combined assessment of 13 C-GBT and 13 C-ABT increased the diagnostic accuracy (80% positive predictive value) of either test alone and reached 92.5% specificity and 100% sensitivity for the diagnosis of cirrhosis.In patients with chronic liver disease, both 13 C-GBT and 13 C-ABT are useful for the diagnosis of cirrhosis. Combination of the tests increases the diagnostic yield of each test alone.

ISOLATED ALTERATIONS OF BIOCHEMICAL MARKERS OF LIVER DAMAGE in a seemingly healthy patient can present a challenge for the clinician. In this review we provide a guide to interpreting alterations to liver enzyme levels. The functional anatomy of the liver and pathophysiology of liver enzyme alteration are briefly reviewed. Using a schematic approach that classifies enzyme alterations as predominantly hepatocellular or predominantly cholestatic, we review abnormal enzymatic activity within the 2 subgroups, the most common causes of enzyme alteration and suggested initial investigations.

Patients with inflammatory bowel disease have a higher risk of developing colorectal cancer. The main risk factors for colorectal cancer are not suitable targets for therapeutic intervention, and primary chemoprevention is an intriguing therapeutic option. The analogies between acetyl-salicylic acid and 5-amino-salicylic acid, and the results obtained by using acetyl-salicylic acid as a chemopreventive agent in patients with sporadic colorectal cancer have prompted the study of potential chemopreventive effects of 5-amino-salicylic acid in inflammatory bowel disease. The results of both epidemiological and experimental studies have shown that long-term 5-amino-salicylic acid treatments appear to have a chemopreventive effect. The evidence for this effect is provided by retrospective and case-control studies whose results, however, do not reach the highest grades for evidence-based recommendations. Nevertheless, these results are supported by a series of experimental studies demonstrating the multiplicity of actions of 5-amino-salicylic acid. Although data regarding the chemopreventive effect of 5-amino-salicylic acid may not be rigorous enough to meet the criteria for the highest evidence-based medicine recommendations, we feel that the argument to wait until we have Grade A evidence is not necessarily rational in this case, because discontinuation of 5-amino-salicylic acid treatment to perform a randomised controlled trial would be unethical secondary to their proven efficacy for maintenance treatment.

Background: The model for end-stage liver disease (MELD) score is a useful tool to assess prognosis in critically ill cirrhotic patients. However, its short-term prognostic superiority over the traditional Child–Turcotte–Pugh (CTP) score has not been definitely confirmed. The creatinine serum level is an important predictor of survival in patients with liver cirrhosis. Aims: To evaluate and compare the short-term prognostic accuracy of the CTP, the creatinine-modified CTP, and the MELD scores in patients with liver cirrhosis. Methods: CTP, creatinine-modified CTP, and MELD scores were calculated in a cohort of 145 cirrhotic patients. The creatinine-modified CTP was calculated as follows: we assessed the mean creatinine serum level and standard deviation (SD) of the 145 study patients, then assigned a score of 1 to patients with creatinine serum levels ≤ to the mean, a score of 2 to patients with creatinine levels between the mean and the mean+1 SD, and a score of 3 to patients with creatinine levels above the mean+1 SD. The creatinine-modified CTP was then calculated by simply adding each patients' creatinine score to their traditional CTP scores. We calculated and compared the accuracy (c-index) of the three parameters in predicting 3-month survival. Results: The creatinine-modified CTP score showed better prognostic accuracy as compared with the traditional CTP (P=0.049). However, the MELD score proved to be better at defining patients' prognosis in the short-term as compared with both the traditional CTP score (P=0.012) and the creatinine-modified CTP (P=0.047). The excellent short-term prognostic accuracy of the MELD score was confirmed even when patients with abnormal creatinine serum levels were excluded from the analysis (c-index=0.935). Conclusions: Adding creatinine values to the CTP slightly improves the prognostic usefulness of the traditional CTP score alone. The MELD score has a short-term prognostic yield that is better than what is provided by both the CTP and CTP creatinine-modified scores, even in cirrhotic patients who are not critically ill. The positive results obtained by using the MELD score were confirmed even after excluding patients with impaired renal function.

Background. Epidemiological studies have foreseen an increase in the incidence of hepatocellular carcinoma (HCC) in the near future and it is estimated that this trend will mostly affect hepatitis C virus (HCV) positive cirrhotic patients. Therefore, accuracy of HCC staging is an important clinical issue. Aim. To investigate the prognostic usefulness of a series of newly proposed HCC prognostic systems such as the Cancer of the Liver Italian Program (CLIP) score, the Groupe d'Etude et de Traitement du Carcinome Hepatocellulaire (GRETCH) model and the Barcelona Clinic Liver Cancer (BCLC) staging classification when compared with the usefulness of a known staging system such as the Okuda staging system in a group of anti-HCV positive cirrhotic patients with HCC seen at a single centre. Methods. Okuda stage, CLIP score, GRETCH model and BCLC stages were retrospectively computed in 81 anti-HCV positive cirrhotic patients with HCC. We evaluated and compared the ability of these methods to assess survival prognosis. Results. As of December 2001, 51 patients had died and overall median survival was 18 months. All the staging systems were able to identify various patient subgroups with different survival. The CLIP score, the GRETCH model and the BCLC staging classification were better at characterizing the 1-year prognosis of the patients when compared with the Okuda staging system, whilst the 3-year prognostic evaluation was improved only by using the CLIP score or the BCLC staging classification. Conclusions. The prognostic value and usefulness of the CLIP score, the GRETCH model and the BCLC staging classification was reproduced in a single-centre analysis of anti-HCV positive HCC cirrhotic patients. These scores provided a prognostic assessment of our patients which is superior to what was obtained by the Okuda staging system.

Leptin is an adipocyte-derived hormone involved in the homeostasis of body composition. An imbalance in leptin regulation has been observed in patients with liver cirrhosis. We aimed to assess serum and ascitic leptin levels in a group of patients with decompensated liver cirrhosis and to evaluate the relationship of these levels with tumor necrosis factor alpha (TNF-alpha). We assessed both serum and ascitic fluid leptin levels in a series of 16 consecutive patients with liver cirrhosis. We calculated the body mass index (BMI) and assessed body fat (BF) of all patients by means of bioelectric impedence analysis. Leptin levels were analyzed in relationship to biochemical indexes, TNF-alpha levels, and body composition. None of the patients had spontaneous bacterial peritonitis. Both serum and ascites leptin levels were correlated with BMI and BF. On average, ascitic fluid leptin levels (13.1 +/- 10.9 ng/ml) were twice as high as serum levels (7.0 +/- 6.4 ng/ml), and the ascitic fluid/serum ratio of leptin was1 in all patients. Serum and ascites leptin levels were positively correlated (rS = 0.675, P = 0.009), while no correlation was observed between leptin and TNF-alpha levels, both in serum and in ascites. Serum and ascites TNF-alpha were not correlated. The ascitic fluid leptin levels of cirrhotic patients with sterile ascites are on average two times higher than circulating levels of this hormone. Noteworthily, they correlate significantly with body composition. These findings seem to suggest that in patients with decompensated liver cirrhosis, intraabdominal production of leptin may contribute to the metabolic picture.

Thrombopoietin (Tpo) is an important regulator of megakaryocyte maturation and platelet production, and is mainly produced by the liver. A decrease in Tpo production is partly responsible for the thrombocytopenia observed in patients with chronic liver disease (CLD). The aim of this study was to evaluate the relationship between Tpo serum levels and liver function in patients with CLD related to hepatitis C virus (HCV) infection.We studied 37 patients with various degrees of HCV-related CLD. Of the patients, 17 had chronic hepatitis and 20 liver cirrhosis. Liver function was evaluated in all patients by the following hepatic blood flow dependent and independent tests that explore various hepatic metabolic functions: carbon-13 (13C)-aminopyrine breath test (13C-ABT), 13C-galactose breath test (13C-GBT), and monoethylglycinexylidide (MEGX) test. Liver function tests results were correlated with Tpo serum levels.Tpo serum levels were significantly lower in patients with liver cirrhosis (88 +/- 23 pg/ml) as compared to those in patients with chronic hepatitis (128 +/- 55 pg/ml, p=0.0031). However, they did not correlate with serum albumin, bilirubin, or prothrombin activity. Tpo serum levels showed a significant positive correlation with 13C-ABT results (hourly dose at 30 min, rs=0.489, p=0.002; cumulative dose at 120 min, rs=0.425, p=0.008). Moreover, they showed a fair, positive correlation with 13C-GBT hourly dose at 30 min (rs=0.366, p=0.028), and a trend toward a positive correlation with the various MEGX test sampling times (MEGX15, rs=0.314, p=0.059; MEGX30, rs=0.284, p=0.088; and MEGX60, rs=0.320, p=0.059).In this study we have shown that a progressive decline in liver function in patients with HCV-related CLD is paralleled by a decrease in Tpo production. The different correlations observed between Tpo and the various liver function tests suggests that this finding is mainly the result of a decrease in hepatic functional mass rather than dependent on alteration in splanchnic hemodynamic.

Background and aims: Cirrhotic patients frequently undergo screening endoscopy for the presence of oesophageal varices (OV). In the future, this social and medical burden will increase due to the greater number of patients with chronic liver disease and their improved survival. In this study, our aims were (1) to identify clinical, biochemical, and ultrasonographic parameters which might non-invasively predict the presence of OV in patients with liver cirrhosis; (2) to evaluate the reproducibility of the obtained results in a different, although related, further group of patients; and (3) to assess the predictiveness of the identified rules in patients with compensated cirrhosis. Methods: In the first part of the study we retrospectively evaluated the presence of OV in 145 cirrhotic patients, and in the second part we evaluated the reproducibility of the study results in a subsequent group of 121 patients. Finally, we evaluated these parameters in a subgroup of 145 patients with compensated disease. All 266 patients underwent a complete biochemical workup, upper digestive endoscopy, and ultrasonographic measurement of spleen bipolar diameter. Platelet count/spleen diameter ratio was calculated for all patients. Results: The prevalence rates of OV were 61% and 58% in the first and second groups of patients, respectively. In the first part of the study, we found that platelet count, spleen diameter, platelet count/spleen diameter ratio, and Child- Pugh class were significantly different among patients with or without OV, although the platelet count/spleen diameter ratio was the only parameter which was independently associated with the presence of OV in a multivariate analysis. A platelet count/spleen diameter ratio cut off value of 909 had 100% negative predictive value for a diagnosis of OV. This result was reproduced in the second group of patients as well as in patients with compensated disease. In a cost-benefit analysis, screening cirrhotic patients according to the “platelet count/spleen diameter ratio strategy” was far more cost effective compared with the “scope all strategy”. Conclusions: The platelet count/spleen diameter ratio is the only parameter which is independently associated with the presence of OV, and its negative predictive value is reproducible. Its use is of value even in the subgroup of patients with compensated disease, and it is also cost effective.

The aspartate aminotransferase-alanine aminotransferase ratio (AST/ALT ratio) has been used to noninvasively assess the severity of disease in patients with chronic liver disease (CLD). We previously demonstrated that progressive liver functional impairment is associated with an increase in the AST/ALT ratio.To evaluate the reproducibility and transportability of the AST/ALT ratio in a large cohort of patients with different degrees of hepatitis C virus (HCV)-related CLD, to confirm the correlation between progressive impairment of liver function and increase in the AST/ALT ratio, to evaluate whether diagnostic accuracy of the ALT/AST ratio can be improved by using it with other biochemical variables, and to assess the 1-year prognostic capability of the AST/ALT ratio in patients with liver cirrhosis.We retrospectively evaluated 252 patients with HCV-related CLD. The AST/ALT ratio was correlated with the degree of liver fibrosis in patients with chronic hepatitis and with the Child-Pugh score in patients with cirrhosis. All patients had undergone monoethylglycinexylidide (MEGX) testing to evaluate liver function. We assessed the prognostic ability of the AST/ALT ratio in a subset of 63 cirrhotic patients who were followed up for at least 1 year.The AST/ALT ratio was more frequently 1 or higher in cirrhotic patients (P.001). There was a significant correlation between MEGX values and the AST/ALT ratio (r(s) = -0.621, P.001). Multivariate stepwise logistic analysis showed that AST/ALT ratio, platelet count (PLT), MEGX values, and prothrombin activity were independently associated with the presence of cirrhosis. Combined assessment of the AST/ALT ratio and/or PLT obtained 97.0% positive predictive value and 97.9% negative predictive value for the diagnosis of cirrhosis. The AST/ALT ratio had 81.3% sensitivity and 55.3% specificity in identifying cirrhotic patients who died within 1-year of follow-up.The AST/ALT ratio is both reproducible and transportable in patients with HCV-related CLD. The AST/ALT ratio is correlated with both histologic stage and clinical evaluation. Progressive liver functional impairment is reflected by an increase in the AST/ALT ratio. Noninvasive evaluation by means of the combined AST/ALT ratio and PLT assessment misclassifies only a few cirrhotic patients. In cirrhotic patients, the AST/ALT ratio provides medium-term prognostic information that is no different from that provided by established prognostic scores.

Background: hepatitis C virus infection-related cirrhosis is a major risk factor for the development of hepatocellular carcinoma. Hepatocellular carcinoma in anti-hepatitis C virus positive cirrhotics shows an increasing prevalence with ageing, although it is not clear whether the age of the patients can be considered a critical factor in the overall assessment of severity of disease or in the choice of therapeutic procedures and prognosis. Objective: to evaluate the influence of older age on modality of presentation, therapeutic choices, outcome, and survival in anti-hepatitis C virus patients with hepatocellular carcinoma. Methods: we retrospectively evaluated 75 anti-hepatitis C virus positive cirrhotic patients with hepatocellular carcinoma consecutively referred to our unit. Patients were sub-divided into two sub-groups according to their age (-65 or 065 years) at tumor diagnosis. The characteristics of the patients and of hepatocellular carcinoma, therapeutic procedures, and survival were then analyzed. Results: median age of the patients was 68 years and mean duration of infection was 24 years. Clinical characteristics of older hepatocellular carcinoma patients were no different from those of younger ones. Hepatocellular carcinoma was more frequently of diffuse type in patients aged -65 years. However, therapeutic options were no different between the two sub-groups of patients, and a similar proportion of patients did not undergo therapy in either group. Overall, 1- and 2-year survival rates were 73% and 51%, respectively. After a mean follow-up of 21 months a higher number of patients aged -65 years died (p=0.002). Moreover, Kaplan-Meier curves showed longer survival in patients aged 065 years (p=0.002). Lastly, diffuse type of hepatocellular carcinoma and tumor staging were the variables independently associated with worse survival in multivariate regression analysis. Conclusions: hepatocellular carcinoma appears in older anti-hepatitis C virus positive cirrhotic patients showing long duration of infection. Older age of the patients does not seem to influence therapeutic options, and more importantly does not exclude patients from treatment. Lastly, older patients seem to have better prognosis most likely due to hepatocellular carcinoma characteristics, since hepatocellular carcinoma seems to present with more unfavourable characteristics in younger cirrhotic patients.

OBJECTIVES: The AST/ALT ratio has shown good diagnostic accuracy in patients with chronic viral liver disease. However, its prognostic utility has never been tested. Recently, the Model for End-Stage Liver Disease (MELD) has been proposed as a simple and effective tool to predict survival in patients with liver cirrhosis. The aims of this study were to assess the 3-month and 1-yr prognostic ability of the AST/ALT ratio in a series of patients with virus-related liver cirrhosis, and to evaluate the relationship between the AST/ALT ratio and the MELD score and to compare their prognostic ability. METHODS: The AST/ALT ratios and MELD scores of 99 patients with liver cirrhosis of viral etiology (73 patients with hepatitis C virus and 26 with hepatitis B virus) who had been followed-up for at least 1 yr were retrospectively calculated and correlated with the patients’ 3-month and 1-yr prognosis. Receiver operating characteristic curves were used to determine the AST/ALT ratio and the MELD score cut-offs with the best sensitivity (SS) and specificity (SP) in discriminating between patients who survived and those who died. Univariate survival curves were estimated by the Kaplan-Meier method using the cut-offs identified by means of receiver operating characteristic curves. RESULTS: AST/ALT ratios and MELD scores showed a significant correlation (rs = 0.503, p = 0.0001). In all, 8% and 30% of the patients had died after 3 months and 1 yr of follow-up, respectively. AST/ALT ratios and MELD scores were significantly higher among the patients who died during both 3-month and 1-yr follow-up. An AST/ALT ratio cut-off of 1.17 had 87% SS and 52% SP, whereas a MELD cut-off of 9 had 57% SS and 74% SP in discriminating between patients who survived and those who died after 1 yr. The combined assessment of the AST/ALT ratio and/or MELD score had 90% SS and 78% SP. Survival curves of the patients showed that both parameters clearly discriminated between patients who survived and those who died in the short term (AST/ALT ratio, p = 0.0094; MELD score, p = 0.0089) as well as in the long term (AST/ALT ratio, p < 0.0005; MELD score, p = 0.004). CONCLUSIONS: In patients with virus-related cirrhosis, the AST/ALT ratio has prognostic capability that is not significantly different from that of an established prognostic score such as MELD. Combined assessment of the two parameters increases the medium-term prognostic accuracy.

Liver transplantation is nowadays the therapeutic option for end-stage liver disease. Correct disease staging is the main step towards improving the timing of listing for liver transplantation so as to avoid premature or late entry. The need for correct prognostic evaluation is due to the limited number of donors and to the increasing number of patients awaiting transplantation. Our aim was to verify whether Child-Pugh's score might be improved by adding the monoethylglycinexylidide (MEGX) formation test and/or serum bile acid determination.We evaluated 182 cirrhotic patients (44 Child-Pugh class A, 97 class B, and 41 class C) of mixed aetiology referring to a tertiary care centre for functional staging of liver disease. These patients were prospectively followed-up for 12-72 months. During this period, 45 patients died, 46 received a transplant, and 91 survived without transplantation. The end-point of analysis was either survival or liver disease-related death at the 6th, 12th, 18th and 24th months of follow-up. The 46 transplanted patients were excluded from the study upon transplantation.In our study, a cut-off for Child-Pugh's score8 confirmed its usefulness, especially in short-term prognostic prediction, while mid- and long-term prediction improved by almost 10% by using the combination of a Child- Pugh's score8 and an MEGX value15 mg/l. Cox's multi-variate regression analysis indicated that MEGX values either with Child-Pugh's score or with prothrombin activity and ascites were independent prognostic variables.Besides confirming that Child-Pugh's score as the basis of prognostic evaluation of cirrhotic patients, these results suggest that the MEGX test might be a complement to the original score when a patient is being evaluated for a liver transplantation programme.