Domenico Risso

Progressive Liver Functional Impairment Is Associated with an Increase in AST/ALT Ratio

The ratio of serum aspartate aminotransferase toalanine aminotransferase (AST/ALT ratio) has beenproposed as a noninvasive method of assessing liverfibrosis and cirrhosis. Our aims were to confirm the usefulness of the AST/ALT ratio in diagnosingcirrhosis noninvasively as well as to verify theexistence of a relationship between the ratio and liverfunctional impairment. In all, 348 patients (177 with chronic hepatitis, 171 with cirrhosis) wereretrospectively evaluated and the AST/ALT ratio wasrelated to monoethyl glycine xylidide (MEGX) formation.Moreover, in a subgroup of 54 patients we analyzed the relationships among the AST/ALT ratio andindocyanine green clearance and half-life. The AST/ALTratio was able to separate patients with mild fibrosisfrom those with severe fibrosis and cirrhosis. The AST/ALT ratio, MEGX, prothrombin activity,and platelet count were selected by multivariateanalysis as variables associated with cirrhosis. TheAST/ALT ratio showed significant correlations both with MEGX formation and with indocyanine greenclearance and half-life. The alterations of indocyaninegreen kinetics, which depend upon liver blood flow anduptake, were likely due to progressive fibrosis. These findings might partially explain theincrease in the AST/ALT ratio as diseaseprogresses.

Leptin has no role in determining severity of steatosis and fibrosis in patients with chronic hepatitis C.

OBJECTIVE:The presence of steatosis is a common histological finding in patients with chronic hepatitis C (CHC). The causes of the severity of this condition are not yet clear, although both metabolic and viral factors supposedly are involved. In this study our aim was to examine the possible influence that leptin levels, hepatitis C virus (HCV) RNA levels, and hepatitis G virus (HGV) infection have on the severity of steatosis and on the presence and degree of fibrosis in patients with CHC.METHODS:One hundred eighty-two CHC patients with histological findings of steatosis were chosen from among a cohort of patients referred to our center for staging of liver disease. Among them 48 CHC patients were accurately selected so as to rule out possible confounding factors for the presence of steatosis (diabetes mellitus, hyperlipemia, obesity, alcohol). Leptin levels, HCV RNA levels, and HCV genotype, and the presence of HGV RNA were assessed in these patients and related to histological findings.RESULTS:We found that leptin levels in CHC patients were similar to those in healthy subjects. No relationship was found between leptin levels and severity of steatosis. HCV RNA levels, HCV genotype, and the presence of HGV infection were no different among CHC patients with various degrees of steatosis. Leptin was not related to different degrees of fibrosis, whereas higher viral load was the only parameter associated to higher fibrosis scores.CONCLUSIONS:These findings suggest that the degree of steatosis in patients with CHC does not seem to depend on serum leptin levels or on viral factors, at least as far as HCV viremia and genotype and HGV infection are concerned. The severity of fibrosis does not seem to be influenced by leptin levels, whereas HCV viral load does seem to play some role.

The 1-year and 3-month prognostic utility of the AST/ALT ratio and model for end-stage liver disease score in patients with viral liver cirrhosis

OBJECTIVE: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.

PREVIOUS HEPATITIS B VIRUS INFECTION IS ASSOCIATED WITH WORSE DISEASE STAGE AND OCCULT HEPATITIS B VIRUS INFECTION HAS LOW PREVALENCE AND PATHOGENICITY IN HEPATITIS C VIRUS-POSITIVE PATIENTS

Abstract: Background: Anti‐hepatitis C virus (anti‐HCV) patients with chronic liver disease (CLD) frequently show markers of previous hepatitis B virus (HBV) infection. Moreover, they may carry occult HBV infection. These features might influence clinical and biochemical features as well as stage of disease. Aim: To assess the prevalence and clinical associations of previous (positivity for anti‐HBs and/or anti‐HBc antibodies) and occult HBV infection (positivity for HBV‐DNA by nested‐PCR) in the serum of anti‐HCV‐positive, HCV‐RNA‐positive, HBsAg‐negative patients with various degrees of CLD seen at a tertiary referral centre. Patients: A total of 119 patients fulfilled the inclusion criteria (84 chronic hepatitis and 35 liver cirrhosis). Results: Forty‐eight patients (40.3%) showed markers of previous HBV infection. This feature was more frequent (P = 0.02) among cirrhotics (57%) as compared to chronic hepatitis patients (33%). Chronic hepatitis patients positive for markers of previous HBV infection had worse histology as compared to negative ones (grading: 6.4 ± 2.7 versus 4.6 ± 3.0, P = 0.004; staging: 1.6 ± 1.2 versus 1.0 ± 1.0, P = 0.01). Eight patients were positive for HBV‐DNA in serum (6.7%). No difference in the presence of occult HBV infection was seen between various degrees of liver disease (7.1% of chronic hepatitis, 5.7% of cirrhosis) and among patients who were positive (10.4%) or negative (4.2%) for markers of previous HBV infection. No significant biochemical, virological, or histological difference was observed between age, age at infection, duration of infection, marker patterns of previous HBV infection‐matched HBV‐DNA‐positive and negative chronic hepatitis patients. Conclusions: Our findings suggest that previous HBV infection among anti‐HCV patients is associated with worse disease stage. In these patients, the prevalence of occult HBV infection is low and there is no difference in distribution among patients with or without markers of previous HBV infection. Furthermore, it does not seem to be associated with disease stage. Lastly, at least among patients with chronic hepatitis, it does not seem to affect the severity of disease.

13C-galactose breath test and 13C-aminopyrine breath test for the study of liver function in chronic liver disease

BACKGROUND AND AIMS 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Noninvasive ratio indexes to evaluate fibrosis staging in chronic hepatitis C: role of platelet count/spleen diameter ratio index.

Objectives.  Noninvasive evaluation of fibrosis is an on‐going effort in the management of chronic hepatitis C. This study was planned to noninvasively evaluate fibrosis staging.

A simple approach to noninvasively identifying significant fibrosis in chronic hepatitis C patients in clinical practice

Background Identification of the presence of significant fibrosis is an important part of the diagnostic work-up of patients with chronic hepatitis C (CHC). Aim To evaluate the performance of the aspartate to alanine aminotransferase ratio (AST/ALT ratio) and platelet count in reducing the number of liver biopsies and diagnosing the presence/absence of significant fibrosis in a large cohort of patients with CHC seen at 2 tertiary referral centers. Methods Liver biopsies of 409 patients with CHC were evaluated. Staging was carried out by means of the Ishak and METAVIR scores in the Italian and US series, respectively. Prevalence of significant fibrosis was 43%. Receiver operating characteristic curves were used to identify AST/ALT ratio and platelet count cutoffs with the highest accuracy for the diagnosis of significant fibrosis. These cutoffs were used to devise a diagnostic algorithm for reducing the number of liver biopsies and diagnosing/ruling out significant fibrosis. Results AST/ALT ratios increased and platelet counts decreased as liver fibrosis worsened. Both AST/ALT ratio (c-index=0.747) and platelet count (c-index=0.733) had high accuracy for the diagnosis of significant fibrosis. The use of AST/ALT ratio and platelet count cutoffs in a diagnostic algorithm would have avoided liver biopsy in 68.9% of the patients and would have correctly identified the absence/presence of significant fibrosis in 80.5% of these cases. Conclusions In clinical practice, the use of simple, reproducible, and inexpensive parameters such as the AST/ALT ratio and platelet count can reduce the need for liver biopsy in a substantial proportion of patients with CHC.

Can the MEGX test and serum bile acids improve the prognostic ability of Child-Pugh's score in liver cirrhosis?

BACKGROUND 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-Pughs score might be improved by adding the monoethylglycinexylidide (MEGX) formation test and/or serum bile acid determination. METHODS 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. RESULTS In our study, a cut-off for Child-Pughs score < 8 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- Pughs score > 8 and an MEGX value < 15 mg/l. Coxs multi-variate regression analysis indicated that MEGX values either with Child-Pughs score or with prothrombin activity and ascites were independent prognostic variables. CONCLUSIONS Besides confirming that Child-Pughs 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.

Impact of evidence-based medicine on the treatment of patients with unresectable hepatocellular carcinoma

Aliment Pharmacol Ther 31, 493–501

Increased Levels of γGT Suggest the Presence of Bile Duct Lesions in Patients with Chronic Hepatitis C

Damage to bile ducts in chronic hepatitis C is a characteristic histological lesion. Moreover, the presence of abnormal levels of γGT in these patients is also a common finding. Assessing whether the presence of bile duct lesions is indicated by biochemical abnormalities or whether virological characteristics can influence their development may help in the definition of clinical–histological relationships in chronic hepatitis C. In this study we evaluated the relationships among routine biochemical parameters, serum bile acids, and pi-class glutathione S-transferase levels, and the presence of bile duct lesions in 60 patients with chronic hepatitis C. Furthermore, we assessed whether the presence of bile duct lesion might be related to HCV genotype, HCV-RNA serum levels, and positivity for HGV-RNA. We found that γGT was the only parameter related to the presence of bile duct lesions. Although a trend towards higher serum bile acids and pi-class glutathione S-transferase levels was observed in patients with bile duct lesions, this trend did not reach statistical significance. Different HCV genotypes and RNA levels, and HGV-RNA positivity did not seem to influence the presence of bile duct damage. In conclusion we found that γGT levels point out the presence of bile duct lesions in patients with chronic hepatitis C. Since we observed a different pattern of alteration of γGT, serum bile acids, and pi-class glutathione S-transferase, we suggest that these various biochemical alterations reflect a more complex damage to bile duct structures, which is not likely represented by the common assessment of bile duct lesions. Viral factors such as HCV genotype and RNA levels as well as HGV-RNA positivity are probably not the main cause of this histological damage.