HLA-G expression in gastric carcinoma: clinicopathological correlations and prognostic impact.

To analyze expression of human leukocyte antigen-G (HLA-G) in gastric adenocarcinoma and correlate its expression with histological and clinical variables. A continuous series of 94 unselected patients with gastric adenocarcinoma (stage I to III) were selected. All histological and clinical variables were collected including the intensity of intra- and peri-tumor lymphocytic infiltration. HLA-G expression was investigated using immunohistochemistry. All histological samples analyzed for HLA-G expression were taken from the primary gastric lesion and included non-neoplastic mucosa. Evaluation of HLA-G expression was performed on the transition zone between tumor and non-neoplastic mucosa, and the invasive front of the tumor and assessment was performed as follows: percentage of positive (strong expression vs weak) cells. A variable amount of HLA-G-positive tumor cells was found in 24 out of 94 cases (25.5%). No significant correlation was found between HLA-G expression and other clinicopathological variables (sex, age, stage, grade, histotype). The overall median survival was worse in patients with HLA-G-positive adenocarcinoma (24.3 months, CI95% 7.7-41.0) compared to those with HLA-G-negative tumors (66.3 months, CI95% 53.0-79.7; p < 0.0001). Two- and 5-year survival rates of HLA-G-negative patients were 88 and 44%, respectively, while were 42 and 11% in those HLA-G-positive. This trend was observed in all stages but was more marked in stage III. HLA-G expression is associated with poor survival in stage III gastric cancer patients and represents a possible immunoescape mechanism of cancer cells.

Reduced Expression of SMAD4 Is Associated with Poor Survival in Colon Cancer.

PURPOSE: SMAD4 loss is associated with the development of metastases and poor prognosis. We evaluated expression of SMAD4 protein and its association with tumor characteristics, including biomarkers and outcome in terms of relapse-free survival and overall survival. EXPERIMENTAL DESIGN: We used 1,564 stage II/III colon cancer samples from PETACC-3 to evaluate SMAD4 expression by immunohistochemistry. SMAD4 protein expression was validated by assessing mRNA expression using available expression array data. SMAD4 expression was also studied on 34 adenomas and 10 colon cancer liver metastases with their primaries. Loss of SMAD4 immunoreactivity was defined as focal or diffuse. Cases without SMAD4 loss were subdivided into those with strong and weak expression. RESULTS: SMAD4 protein expression was informative in 1,381/1,564 cases. SMAD4 loss was found in 293/1,381 (21%) cases. Of 1,088 cases without SMAD4 loss (79%), 530 showed weak and 558 strong expression. SMAD4 loss occurred also in adenomas, but less extensively than in carcinomas. Liver metastases followed mostly the expression pattern of the primary tumor. SMAD4 loss, including weak expression, identified patients with poor survival in stage II as well as III and in both treatment arms. SMAD4 loss was less frequent in tumors with microsatellite instability and more frequent in those with loss of heterozygosity of 18q. CONCLUSIONS: We conclude that clonal loss of SMAD4 expression in adenomas, carcinomas, and liver metastases increases with disease progression. SMAD4 loss, and to a lesser extent weak expression, is strongly associated with poor survival regardless of stage. Clin Cancer Res; 22(12); 3037-47. ©2016 AACR.

The Reliability of Endoscopic Biopsies in Assessing HER2 Status in Gastric and Gastroesophageal Junction Cancer: A Study Comparing Biopsies with Surgical Samples.

AIM: The aim of this study is to validate the accuracy of HER2 assessment on biopsies by comparing matched biopsy/surgical material from the same patients. METHODS: HER2 status was evaluated by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in 103 cases of gastric and gastroesophageal junction cancers in coupled biopsy and surgical material. RESULT: Complete concordance between IHC and FISH results on biopsy versus surgical samples was noted in 80% and 95% of cases, respectively. At comprehensive comparison, including IHC and FISH data on biopsy and surgical samples, 89% of biopsies were predictive of HER2 status in surgical samples, whereas 11% showed variable inconsistencies. The majority of these (10 of 12 cases) showed IHC score 0/1+ on biopsy but were all IHC positive and amplified at surgery; in particular, three (3 of 35; 8.5%) IHC score 0 and four (4 of 16; 25%) IHC score 1+ cases were FISH amplified on biopsy material also, whereas the remaining three cases were FISH non-amplified on biopsy. The percentage of cases, which were FISH amplified with IHC score 1+ or 2+ on biopsies, were similar (25% and 33%, respectively) and they also shared a similar grade of amplification. These data suggest that both IHC score 1+ and 2+ on biopsy material represent "equivocal cases" that may merit further investigation. CONCLUSIONS: The predictive value of HER2 IHC in biopsies is high. FISH analysis should be considered for IHC score 2+ and 1+ biopsy cases. Approximately 8% of cases will not be accurately predicted by biopsy evaluation.

Currarino syndrome with pelvic neuroendocrine tumor diagnosed by post-mortem genetic analysis of tissue specimens.

Currarino syndrome (CS) is an autosomal dominant disorder of embryonic development characterized by the triad of anorectal abnormalities, partial sacral agenesis, and presacral mass. Mutations of the HLXB9 gene have been identified in most CS cases, but a precise genotype-phenotype correlation has not been described so far. We report the clinical case of a 44-year-old Caucasian woman with malignant neuroendocrine transformation of a pre-sacrococcygeal mass combined with bicornuate uterus, dermoid cyst of the ovaries, and chronic constipation. After the patient died, a sacrococcygeal malformation and anterior meningocele were diagnosed in her 22-year-old son. CS diagnosis was then retrospectively confirmed by molecular analysis of normal and pathological tissue specimens of the mother, with identification of a HLXB9 mutation (c.727C>T; p.R243W). CS should be considered, and genetic counseling recommended, to all patients with presacral masses. Since malignant neuroendocrine transformation of presacral mass in CS is a possible complication, even thought rare, close follow up in these patients is advisable.

Coeliac disease: the histology report.

To this day intestinal biopsy is justly considered the "gold standard" for the diagnosis of coeliac disease (CD). The aim of the authors in setting up these guidelines was to assist pathologists in formulating a more precise morphological evaluation of a duodenal biopsy in the light of clinical and laboratory data, to prepare histological samples with correctly oriented biopsies and in the differential diagnosis with other pathological entities and complications of the disease. A further intention was to promote the conviction for the need of a close collaborative relationship between different specialists namely the concept of a "multidisciplinary team".

Microscopic esophagitis in gastro-esophageal reflux disease: individual lesions, biopsy sampling, and clinical correlations.

Patients with non-erosive reflux disease may show microscopic damage. This study is aimed to describe distribution, sensitivity, and specificity of histological lesions (i.e., basal cell hyperplasia-BH, papillae elongation-PE, dilatation of intercellular spaces-DIS, intraepithelial eosinophils-IE, neutrophils, and erosions) and sampling criteria. Four groups were identified on the basis of symptoms, endoscopy, and pH monitoring: (1) erosive esophagitis (n = 48), (2) non-erosive esophagitis with abnormal pH (n = 59), (3) non-erosive esophagitis with normal pH (n = 12), and (4) controls (n = 20). Biopsies were taken at the Z-line and 2 and 4 cm above it. BH, PE, DIS, IE, neutrophils, and erosions were assessed. A global severity score was calculated on the basis of the above parameters and allowed the distinction of patients from controls with 80% sensitivity and 85% specificity. Lesions were more severe at Z-line than proximally and more expressed in erosive than in non-erosive disease, although more than 70% of latter patients still showed histological damage. Esophageal biopsy seems very attractive in non-erosive disease where it may contribute to diagnosis and play a role in the comparative evaluation of different therapies.

Rectal hepatoid carcinoma with liver metastases in a patient affected by ulcerative colitis.

BACKGROUND: Hepatoid tumors (HTs) are rare extra-hepatic neoplasms with the histological features, biochemical profile and, sometimes, even clinical course of hepatocellular carcinoma. We present a case of rectal hepatoid adenocarcinoma with metachronous liver metastases. METHODS: Four months after total procto-colectomy for a rectal adenocarcinoma (Astler-Coller C2), a 42-year-old man with ulcerative colitis showed hypoechoic masses in the hepatic parenchyma by abdominal ultrasonography. Carcinoembryonic antigen was normal, but alpha-fetoprotein was 32,000 microg/L. Fine-needle biopsy revealed that liver masses were positive for hepatocellular carcinoma. The patient underwent left hepatectomy and alcoholisation of a small deep nodule in segment 8. RESULTS: Immunohistochemistry and albumin mRNA in situ hybridization suggested that the nodules were metastases of a HT. The patient was well during the first 6 months and refused any adjuvant chemotherapy. He died from liver failure 19 months after initial diagnosis. CONCLUSIONS: HT is a rare colon cancer. The preoperative diagnosis of this tumor requires a high degree of suspicion, the availability of a panel of immunohistochemical markers, and a certain amount of luck. The prognosis is poor despite an aggressive and multimodal therapeutic strategy. So far, none of the hypotheses proposed about the origin and the biology of these tumors is convincing.

Autoimmune intrahepatic cholangiopathy associated with antiphospholipid antibody syndrome.

We report the case of a 26-year-old woman who developed thrombophlebitis in her left leg in 2002, followed by fever, asthenia and headache in 2004. Antinuclear antibodies, antimitochondrial antibodies, anti-liver kidney microsome, anti-Smith, antiphospholipid (aPL) and antineutrophil cytoplasmic antibodies, as well as lupus- anticoagulant activity were positive. Systemic lupus erythematosus (SLE) with aPL syndrome was diagnosed and the patient was treated with azathioprine and heparin. Symptoms persisted and itching arose in the following months. The patient was admitted to our department in January 2005 for jaundice and skin rash. Elevated levels of acute phase proteins and cholestasis and liver necrosis indexes were present. Antinuclear antibodies, aPL and antimitochondrial antibodies (M5) antibodies were positive. Liver histology showed minimal focal hepatocyte necrosis, intrahepatic biliary stasis and intralobular inflammatory cell infiltrate. The absence of clinical signs that are characteristic of SLE as well as the failure to confirm antiSmith antibody positivity led us to rule out a diagnosis of SLE. On the basis of clinical, immunological and histological data, autoimmune intrahepatic cholangiopathy associated with primary aPL syndrome was diagnosed. The patient was treated with intravenous methylprednisolone followed by oral prednisone, warfarin and ursodeoxycholic acid. Liver necrosis and cholestasis indexes rapidly improved within 1 month and progressively reached the normal range. To our knowledge, this is the first description of a patient with an association of intrahepatic cholangiopathy and aPL, thus suggesting that autoimmune liver disease might associate with aPL syndrome.

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.

Hyaluronic acid and aspartate aminotransferase levels normalized by liver function can reflect sinusoidal impairment in chronic liver disease.

BACKGROUND/AIM: To evaluate the relationship between hyaluronic acid/aminopyrine breath test (HA/ABT) ratio and fibrosis score in chronic hepatitis, and between HA/ABT and clinical staging (child-turcotte-pugh'score, CTP; and model for end stage liver disease, MELD) in cirrhosis, as well as to evaluate the aspartate aminotransferase (AST)/ABT in relation to the HA/ABT. METHODS: We studied 48 patients with histologically proven chronic hepatitis C (CHC) and 35 patients with compensated cirrhosis (CIR). RESULTS: HA/ABT and AST/ABT showed a more significant correlation with the fibrosis score than HA or ABT or AST alone in the 48 CHC patients: r=0.568 (P<0.0001), r=0.610 (P<0.0001), r=0.450 (P=0.0021), r=-0.449 (P=0.0021), and r=0.472(P=0.0012), respectively. Progressive liver damage (fibrosis 1-2 vs fibrosis 3-6 vs cirrhosis) was significantly (P<0.05) reflected by both HA/ABT (mean+/-SEM: 4.0+/-0.9 vs 18.1+/-4.2 vs 149.9+/-33.1) and AST/ABT (6.3+/-1.8 vs 12.7+/-1.6 vs 42.1+/-14.6). A strong relationship was found between HA/ABT and AST/ABT (r=0.755 P<0.0001). In cirrhotic patients, the most significant relationship was observed between HA/ABT and CTP r=0.483 and P=0.0049, and MELD r=0.523 and P=0.0023. CONCLUSION: Considering that HA levels in chronic hepatitis depend on the progressive impairment of sinusoidal endothelial cells (SEC), related to progressive fibrosis, HA/ABT ratio would seem to be the most specific reflection of progressive impairment of the SEC. AST/ABT could be used as a possible surrogate of HA in identifying SEC impairment in chronic hepatitis.

Gastrointestinal stromal tumors: clinical pathological review of a personal series.

The Authors report their experience on the management of gastrointestinal stromal tumors (GISTs). In addition to recent cases immediately diagnosed as GISTs, a pathological review of stored material from non-epithelial tumors of the gastrointestinal tract operated on over the past 20 years was performed. Twenty-three out of a total of 31 cases were shown to be positive for the immunophenotypic characteristics (CD117/CD34) of GISTs. Most cases (approximately 60%) were symptomatic, with hemorrhage being the most common presenting sign, followed by occlusion, pain and perforation. Asymptomatic cases were detected incidentally during procedures for other conditions. Diagnostic techniques (ultrasound, endoscopy, endoscopic ultrasound, X-ray, CT, MRI) allowed only the detection of wall (extraluminal) involvement. Apart from differentiating between benign and malignant, preoperative biopsy was seldom valuable. All cases were treated surgically, with intervention tailored to location and anatomical/surgical and anatomical/pathological features. Long-term follow-up was conducted in all patients and for most is still ongoing: five patients died from recurrent disease at varying intervals after surgery (from 17 to 102 months). Relationships between observed aggressiveness and risk were studied. Parameters that may prove useful for the early detection and appropriate management of these lesions are discussed.

Reassessment of the diagnostic value of histology in patients with GERD, using multiple biopsy sites and an appropriate control group.

BACKGROUND: Histology is generally considered as a tool of limited value in the diagnosis of gastro-esophageal reflux disease (GERD). AIM: To reevaluate the diagnostic role of histological alterations in GERD, using multiple biopsy sites and an appropriate control group. METHODS: We studied 135 patients with typical and atypical symptoms of GERD. They underwent upper GI endoscopy and Los Angeles classification was used for grading cases with mucosal breaks. Biopsies were taken at the Z-line, 2 and 4 cm above it. Microscopic esophagitis was identified by necrosis/erosion, neutrophil/eosinophil intraepithelial infiltration, basal cell hyperplasia, elongation of papillae, dilation of intercellular spaces and a score (range: 0-2) was given for each lesion. Twenty-four-hour esophageal pH monitoring was performed in each patient. Twenty subjects without reflux symptoms, and with normal endoscopy and pH testing were considered as controls. RESULTS: Histological alterations were found in 100 of 119 GERD patients (84%) and in 3 of 20 controls (15%) with a significant difference (p < 0.00001). Histology was abnormal in 96% of patients with erosive esophagitis and in 76% of patients with nonerosive reflux disease (NERD). The sum of scores of microscopic lesions found in all biopsy sites ranged from 0 to 22 and we identified a cut-off value (score 2) that distinguished efficiently controls from GERD patients. CONCLUSIONS: In contrast with previous reports on the marginal role of histology in patients with GERD, our study shows that this technique can be a useful diagnostic tool, particularly in patients with NERD, when biopsies are taken at two sites including Z-line and 2 cm above it.

Basophils infiltrate human gastric mucosa at sites of Helicobacter pylori infection, and exhibit chemotaxis in response to H. pylori-derived peptide Hp(2-20).

Basophils, which are normally confined to the circulation, can migrate to sites of allergic inflammation. Using the specific mAb, BB1, we detected basophil infiltration of the gastric mucosa of Helicobacter pylori-infected patients affected by moderate and severe gastritis. Basophils were not found in H. pylori-free individuals or in subjects with mild gastritis. The H. pylori-derived peptide, Hp(2-20), was a potent basophil chemoattractant in vitro, whereas the control peptide, Hp1, was ineffective. Basophils from peripheral blood of healthy volunteers expressed mRNA for the formyl peptide receptors, N-formyl-peptide receptor (FPR), FPR-like (FPRL)1, and FPRL2. Preincubation of basophils with FMLP or Hp(2-20) caused complete desensitization to a subsequent challenge with homologous stimulus. Incubation of basophils with a low concentration of FMLP, which binds with high affinity to FPR, but not to FPRL1 or FPRL2, did not affect the chemotactic response to Hp(2-20). In contrast, a high concentration of FMLP, which binds to FPRL1 and FPRL2, reduced the chemotactic response to Hp(2-20). The FPR antagonist, cyclosporin H, prevented chemotaxis induced by FMLP, but not by Hp(2-20). Hp(2-20) could be responsible, at least in part, for basophil infiltration of the gastric mucosa of H. pylori-infected patients presumably through the interaction with FPRL1 and FPRL2.

Mediastinal chondrosarcoma.

The authors report a rare case of primary chondrosarcoma of the anterior mediastinum showing unusual pathological and clinical features, namely 1) the lack of any anatomical relationship between the tumor and cartilage-containing organs, and 2) an indolent behavior with long-term survival. In spite of early disease recurrence and repeated surgery, the patient is in good health five years after primary surgery. The reported case suggests that 1) primary chondrosarcomas of the anterior mediastinum may have a better prognosis than previously recognized, 2) the disease can remain confined within the chest for as long as five years, and 3) repeated surgery may contribute to long-term survival.

Autoimmune hepatitis revealed by atorvastatin.

Cases of acute hepatitis induced by statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have been reported. A 65-year-old woman was admitted to our hospital because of fatigue, jaundice and altered liver function tests while on treatment with atorvastatin. On the basis of clinical, serological and histological findings, a score leading to a diagnosis of autoimmune hepatitis was reached. We suggest that atorvastatin may have revealed an underlying autoimmune hepatitis.

The human marginal zone B cell.

This study describes the features of the marginal zone (MZ) B cells of human tonsils and spleens and compares them with those of the follicular mantle (FM) B cells from the same tissues. The two B cell subpopulations displayed marked differences in phenotype, in response capacity to T cell-independent antigens and polyclonal B cell activators, and in presentation of antigens to T cells. FM B cells expressed surface CD5, and hence should be considered as B1 cells by current nomenclature. Fractionation of MZ B cells according to the presence or absence of surface IgD revealed the presence of two subsets. These subsets were characterized by different properties, including the presence of Ig V(H) gene mutations and the response capacity to TI-2 antigens, this latter property being associated with IgD-positive cells. Comparison of the data with those reported for mice revealed that human MZ B cells had strong analogies with both the murine MZ and B1 cells. In contrast, human B1 cells (that is, CD5-positive FM cells) were considerably different, an observation that should prompt further studies. Indeed, B cells with characteristics analogous to those of murine B1 cells were detected in small but definite proportions in the peripheral blood and tonsils. If the current distinction into B1 and B2 cells has to be maintained also for humans, it is likely that only these CD5-positive cells rather than the FM B cells should be called B1 cells.

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.

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.

Validity and clinical utility of the aspartate aminotransferase-alanine aminotransferase ratio in assessing disease severity and prognosis in patients with hepatitis C virus-related chronic liver disease.

BACKGROUND: 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. OBJECTIVES: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Monitoring of liver metabolic function during interferon-alpha therapy and its relationship to treatment outcome in chronic hepatitis C patients.

BACKGROUND/AIMS: Interferon is considered the cornerstone in the therapy of chronic hepatitis C patients. Experimental studies have shown that interferon administration may influence liver metabolic activity. However, data concerning the monitoring of liver metabolic function during a therapeutic course of interferon in chronic hepatitis C patients are scanty. The MEGX (monoethylglycinexylidide) test has been used in diagnostic and prognostic assessment of chronic liver disease as a quantitative liver function test. In this study our aim was to non-invasively monitor liver function in chronic hepatitis C patients during a course of interferon-alpha therapy and to evaluate whether the presence of modifications in liver metabolic function might influence the therapeutic outcome. METHODOLOGY: We studied 22 patients with biopsy-proven chronic hepatitis C before, during (1st, 3rd and 6th month of therapy), and three months after interferon-alpha (3 million units thrice weekly for six months) using MEGX test to monitor liver function. RESULTS: During the longitudinal study no significant differences were observed between pretreatment MEGX30 values and those obtained during interferon treatment or at the end of follow-up, both considering patients together or grouped according to treatment outcome (Responders vs. Non-responders). Analysis of the MEGX30 variations during therapy showed that they were evenly distributed between responder and non-responder patients. Furthermore, during interferon therapy none of the patients reached a MEGX30 value compatible with severely impaired liver function. CONCLUSIONS: Our results suggest that although a discrete prevalence of modifications in liver metabolic function occurs in chronic hepatitis C patients during interferon therapy they do not seem to have clinical relevance or influence therapeutic outcome.