Biomarker discovery for early detection of hepatocellular carcinoma in hepatitis C-infected patients.

Chronic hepatic disease damages the liver, and the resulting wound-healing process leads to liver fibrosis and the subsequent development of cirrhosis. The leading cause of hepatic fibrosis and cirrhosis is infection with hepatitis C virus (HCV), and of the patients with HCV-induced cirrhosis, 2% to 5% develop hepatocellular carcinoma (HCC), with a survival rate of 7%. HCC is one of the leading causes of cancer-related death worldwide, and the poor survival rate is largely due to late-stage diagnosis, which makes successful intervention difficult, if not impossible. The lack of sensitive and specific diagnostic tools and the urgent need for early-stage diagnosis prompted us to discover new candidate biomarkers for HCV and HCC. We used aptamer-based fractionation technology to reduce serum complexity, differentially labeled samples (six HCV and six HCC) with fluorescent dyes, and resolved proteins in pairwise two-dimensional difference gel electrophoresis. DeCyder software was used to identify differentially expressed proteins and spots picked, and MALDI-MS/MS was used to determine that ApoA1 was down-regulated by 22% (p < 0.004) in HCC relative to HCV. Differential expression quantified via two-dimensional difference gel electrophoresis was confirmed by means of (18)O/(16)O stable isotope differential labeling with LC-MS/MS zoom scans. Technically independent confirmation was demonstrated by triple quadrupole LC-MS/MS selected reaction monitoring (SRM) assays with three peptides specific to human ApoA1 (DLATVYVDVLK, WQEEMELYR, and VSFLSALEEYTK) using (18)O/(16)O-labeled samples and further verified with AQUA peptides as internal standards for quantification. In 50 patient samples (24 HCV and 26 HCC), all three SRM assays yielded highly similar differential expression of ApoA1 in HCC and HCV patients. These results validated the SRM assays, which were independently confirmed by Western blotting. Thus, ApoA1 is a candidate member of an SRM biomarker panel for early diagnosis, prognosis, and monitoring of HCC. Future multiplexing of SRM assays for other candidate biomarkers is envisioned to develop a biomarker panel for subsequent verification and validation studies.

Evaluation of the aspartate aminotransferase/platelet ratio index and enhanced liver fibrosis tests to detect significant fibrosis due to chronic hepatitis C.

BACKGROUND: The assessment of liver fibrosis in chronic hepatitis C patients is important for prognosis and making decisions regarding antiviral treatment. Although liver biopsy is considered the reference standard for assessing hepatic fibrosis in patients with chronic hepatitis C, it is invasive and associated with sampling and interobserver variability. Serum fibrosis markers have been utilized as surrogates for a liver biopsy. METHODS: We completed a prospective study of 191 patients in which blood draws and liver biopsies were performed on the same visit. Using liver biopsies the sensitivity, specificity, and negative and positive predictive values for both aspartate aminotransferase/platelet ratio index (APRI) and enhanced liver fibrosis (ELF) were determined. The patients were divided into training and validation patient sets to develop and validate a clinically useful algorithm for differentiating mild and significant fibrosis. RESULTS: The area under the ROC curve for the APRI and ELF tests for the training set was 0.865 and 0.880, respectively. The clinical sensitivity in separating mild (F0-F1) from significant fibrosis (F2-F4) was 80% and 86.0% with a clinical specificity of 86.7% and 77.8%, respectively. For the validation sets the area under the ROC curve for the APRI and ELF tests was, 0.855 and 0.780, respectively. The clinical sensitivity of the APRI and ELF tests in separating mild (F0-F1) from significant (F2-F4) fibrosis for the validation set was 90.0% and 70.0% with a clinical specificity of 73.3% and 86.7%, respectively. There were no differences between the APRI and ELF tests in distinguishing mild from significant fibrosis for either the training or validation sets (P=0.61 and 0.20, respectively). Using APRI as the primary test followed by ELF for patients in the intermediate zone, would have decreased the number of liver biopsies needed by 40% for the validation set. Overall, use of our algorithm would have decreased the number of patients who needed a liver biopsy from 95 to 24-a 74.7% reduction. CONCLUSIONS: This study has shown that the APRI and ELF tests are equally accurate in distinguishing mild from significant liver fibrosis, and combining them into a validated algorithm improves their performance in distinguishing mild from significant fibrosis.

Motility abnormalities in irritable bowel syndrome.

BACKGROUND/AIMS: The intestinal pathophysiology in irritable bowel syndrome (IBS) is largely unknown. The lactulose breath test has been used to identify small bowel bacterial overgrowth in these patients. METHODS: We studied intestinal transit in patients with IBS using of the SmartPill® (SP) wireless pH/pressure recording capsule and performed lactulose breath tests to look for physiologic abnormalities. RESULTS: A total of 35/46 (76%) of the IBS patients had prolonged gastric emptying times. Constipation-predominant disease was associated with prolonged gut transit times. The mean hours ± SD for colonic transit time in the constipation group was 71.7 ± 61.1 (n = 13) compared with 22.5 ± 14.9 (n = 14) for diarrhea-predominant and 26.4 ± 21.5 (n = 20) for mixed clinical subtype (p = 0.0010). No correlation between small bowel transit time and abnormal breath hydrogen or methane excretion in the 46 combined patients with IBS was seen. CONCLUSIONS: Delayed gastric emptying was identified in IBS and in some patients may contribute to at least a component of their symptoms. Constipation-predominant IBS is associated with prolonged gut transit times. Otherwise, transit abnormalities do not appear to be important in IBS. Intestinal transit did not correlate with breath test results.

Perforating granulomatous dermatitis reaction to exogenous tattoo pigment: a case report and review of the literature.

: The majority of cutaneous hypersensitivity reactions to exogenous tattoo pigments can be histologically classified as lichenoid or granulomatous. The etiology is still uncertain but is generally accepted to be a delayed-type hypersensitivity reaction to either the pigment itself or its carrier solution. In this report, we review the literature concerning adverse reactions to tattoos. In addition, we describe the second case of a localized granulomatous dermatitis to the red dye within a tattoo that histologically resembled granuloma annulare. This is the first reported example of a perforating granuloma annulare-like reaction.

Time course of collagen peak in bile duct-ligated rats.

BACKGROUND: One of the most useful experimental fibrogenesis models is the "bile duct-ligated rats". Our aim was to investigate the quantitative hepatic collagen content by two different methods during the different stages of hepatic fibrosis in bile duct-ligated rats on a weekly basis. We questioned whether the 1-wk or 4-wk bile duct-ligated model is suitable in animal fibrogenesis trials. METHODS: Of the 53 male Wistar rats, 8 (Group 0) were used as a healthy control group. Bile duct ligation (BDL) had been performed in the rest. Bile duct-ligated rates were sacrificed 7 days later in group 1 (10 rats), 14 days later in group 2 (9 rats), 21 days later in group 3(9 rats) and 28 days later in group 4 (9 rats). Eight rats underwent sham-operation (Sham). Hepatic collagen measurements as well as serum levels of liver enzymes and function tests were all analysed. RESULTS: The peak level of collagen was observed biochemically and histomorphometricly at the end of third week (P < 0.001 and P < 0.05). Suprisingly, collagen levels had decreased with the course of time such as at the end of fourth week (P < 0.01 and P < 0.05). CONCLUSION: We have shown that fibrosis in bile duct-ligated rats is transient, i.e. reverses spontaneously after 3 weeks. This contrasts any situation in patients where hepatic fibrosis is progressive and irreversible as countless studies performed by many investigators in the same animal model.

Visualizing hepatitis C virus infections in human liver by two-photon microscopy.

BACKGROUND & AIMS: Although hepatitis C virus (HCV) is a common cause of cirrhosis and liver cancer, efforts to understand the pathogenesis of HCV infection have been limited by the low abundance of viral proteins expressed within the liver, which hinders the detection of infected cells in situ. This study evaluated the ability of advanced optical imaging techniques to determine the extent and distribution of HCV-infected cells within the liver. METHODS: We combined 2-photon microscopy with virus-specific, fluorescent, semiconductor quantum dot probes to determine the proportion of hepatocytes that were infected with virus in frozen sections of liver tissue obtained from patients with chronic HCV infection. RESULTS: Viral core and nonstructural protein 3 antigens were detected readily in liver tissues from patients with chronic infection without confounding tissue autofluorescence. Specificity was confirmed by blocking with specific antibodies and by tissue colocalization of distinct viral antigens. Between 7% and 20% of hepatocytes were infected in patients with plasma viral RNA loads of 10(5) IU/mL or greater. Infected cells were in clusters, which suggested spread of the virus from cell to cell. Double-stranded RNA, a product of viral replication, was abundant within cells at the center of such clusters, but often scarce in cells at the periphery, consistent with more recent infection of cells at the periphery. CONCLUSIONS: Two-photon microscopy provides unprecedented sensitivity for the detection of HCV proteins and double-stranded RNA. Studies using this technology indicate that HCV infection is a dynamic process that involves a limited number of hepatocytes. HCV spread between cells is likely to be constrained by host responses.

Non-invasive index of liver fibrosis induced by alcohol, thioacetamide and Schistosomal infection in mice.

BACKGROUND: Non invasive approaches will likely be increasing utilized to assess liver fibrosis. This work provides a new non invasive index to predict liver fibrosis induced in mice. METHODS: Fibrosis was generated by thioacetamide (TAA), chronic intake of ethanol, or infection with S. mansoni in 240 mice. Both progression and regression of fibrosis (after treatment with silymarin and/or praziquantel) were monitored. The following methods were employed: (i) The METAVIR system was utilized to grade and stage liver inflammation and fibosis; (ii) Determination of hepatic hydroxyproline and collagen; and (iii) Derivation of a new hepatic fibrosis index from the induced changes, and its prospective validation in a group of 70 mice. RESULTS: The index is composed of 4 serum variable including total proteins, gamma-GT, bilirubin and reduced glutathione (GSH), measured in diseased, treated and normal mice. These parameters were highly correlated with both the histological stage and the grade. They were combined in a logarithmic formula, which non-invasively scores the severity of liver fibrosis through a range (0 to 2), starting with healthy liver (corresponding to stage 0) to advanced fibrosis (corresponding stage 3).Receiver operating characteristic curves (ROC) for the accuracy of the index to predict the histological stages demonstrated that the areas under the curve (AUC) were 0.954, 0.979 and 0.99 for index values corresponding to histological stages 1, 2 and 3, respectively. Also, the index was correlated with stage and grade, (0.947 and 0.859, respectively). The cut off values that cover the range between stages 0-1, 1-2 and 2-3 are 0.4, 1.12 and 1.79, respectively. The results in the validation group confirmed the accuracy of the test. The AUROC was 0.869 and there was good correlation with the stage of fibrosis and grade of inflammation. CONCLUSION: The index fulfils the basic criteria of non-invasive marker of liver fibrosis since it is liver-specific, easy to implement, reliable, and inexpensive. It proved to be accurate in discriminating precirrhotic stages.

Prevalence of Barrett's esophagus in patients with or without GERD symptoms: role of race, age, and gender.

BACKGROUND: Gastroesophageal reflux disease is associated with a significantly increased risk of Barrett's esophagus (BE) and adenocarcinoma of the esophagus. Racial differences in the prevalence of BE are controversial. Our purpose was to study the prevalence of Barrett's esophagus in patients with and without gastroesophageal reflux disease (GERD) symptoms, and the differences between these two groups in terms of race, age, and sex. METHODS: Esophagogastroduodenoscopy (EGD) reports from the PENTAX EndoPRO database for the Endoscopy Unit at the University of Texas Medical Branch from 2005 to 2007 were reviewed. Four hundred and ten patients who underwent upper endoscopy because of GERD symptoms that were not responding to proton pump inhibitor (PPI) therapy or with alarm symptoms and 4,047 patients undergoing upper endoscopy for other reasons without GERD symptoms were identified. RESULTS: BE was significantly more common among males. The prevalence of BE was higher in patients with GERD symptoms than those without GERD symptoms. Overall, more cases of BE, dysplasia, and adenocarcinoma were found among the patients without GERD symptoms than those that underwent endoscopy because of GERD symptoms. The prevalence of BE among Caucasian, African American, Hispanic, and "other" groups with GERD symptoms were 5%, 2.56%, 4.4%, and 0%, respectively. The prevalence of BE among these racial groups without GERD symptoms were 1.9%, 0.9%, 1.57%, and 0.8%, respectively. The association between race and BE was not statistically significant (df = 3, P = 0.2628), including after adjusting for the presence of GERD symptoms (df = 3, P = 0.2947). Patients without GERD symptoms that presented with BE were significantly older than the patients without BE (P < 0.01). CONCLUSIONS: BE is a male-dominant disease. The prevalence of Barrett's esophagus was not significant different among Caucasian, Hispanics, and African Americans. Most of the patients with BE, dysplasia, and adenocarcinoma did not have GERD symptoms.

Hepatocellular carcinoma prevalence and mortality in a male state prison population.

OBJECTIVES: The incidence of hepatocellular carcinoma (HCC) in the United States has increased dramatically over the last two decades, largely because of an increase in the number of people with advanced hepatitis C virus (HCV) infection. U.S. prisoners are at high risk for HCC, given their elevated rates of HCV infection, comorbid hepatitis B virus (HBV) infection, and alcoholic liver disease. The purpose of our study was to examine the prevalence and mortality of HCC in the nation's largest state prison system. METHODS: The study population consisted of 325,477 male Texas Department of Criminal Justice (TDCJ) inmates who were incarcerated between January 1, 2003, and July 31, 2006. Information on medical conditions and demographic characteristics was obtained from an institution-wide medical information system. RESULTS: During the 3.5-year study period, 176 male TDCJ inmates (54 per 100,000) were diagnosed with HCC and 108 (33 per 100,000) died as a result of HCC. Inmates who were Hispanic, older, and infected with HCV, HBV, or human immunodeficiency virus had elevated rates of both HCC prevalence and mortality. After adjusting for all study covariates, HCC prevalence, but not mortality, was modestly elevated among inmates with diabetes. CONCLUSIONS: Our study showed that the Texas male prison population had a sevenfold higher prevalence of HCC than the general U.S. male population and a fourfold higher death rate from HCC. These findings likely reflect the high concentration of HCC-related risk factors, particularly HCV, among prisoners.

Non-invasive markers of hepatic fibrosis in patients co-infected with HCV and HIV: comparison of the APRI and FIB-4 index.

INTRODUCTION: The APRI and FIB-4 index are markers that have been proposed for the evaluation of hepatic fibrosis in patients co-infected with HIV and HCV. METHODS: We retrospectively compared these 2 indices in 81 co-infected patients staged by liver biopsy. RESULTS: The FIB-4 index was superior to the APRI for the differentiation of mild from significant fibrosis in both predictive values and area under the receiver operator curve (AUROC). The tests were comparable for the differentiation of mild/moderate from advanced fibrosis. CONCLUSION: These tests could be used to evaluate co-infected patients for treatment, and exclude those that do not need periodic screening for hepatocellular carcinoma.

Chronic hepatitis C is a common associated with hepatic granulomas.

AIM: To determine the most frequent etiologies of hepatic epithelioid granulomas, and whether there was an association with chronic hepatitis C virus (HCV). METHODS: Both a retrospective review of the pathology database of liver biopsies at our institution from 1996 through 2006 as well as data from a prospective study of hepatic fibrosis markers and liver biopsies from 2003 to 2006 were reviewed to identify cases of hepatic epithelioid granulomas. Appropriate charts, liver biopsy slides, and laboratory data were reviewed to determine all possible associations. The diagnosis of HCV was based on a positive HCV RNA. RESULTS: There were 4578 liver biopsies and 36 (0.79%) had at least one epithelioid granuloma. HCV was the most common association. Fourteen patients had HCV, and in nine, there were no concurrent conditions known to be associated with hepatic granulomas. Prior interferon therapy and crystalloid substances from illicit intravenous injections did not account for the finding. There were hepatic epithelioid granulomas in 3 of 241 patients (1.24%) with known chronic HCV enrolled in the prospective study of hepatic fibrosis markers. CONCLUSION: Although uncommon, hepatic granulomas may be part of the histological spectrum of chronic HCV. When epithelioid granulomas are found on the liver biopsy of someone with HCV, other clinically appropriate studies should be done, but if nothing else is found, the clinician can be comfortable with an HCV association.

Evaluation of Escherichia coli pathotypes associated with irritable bowel syndrome.

Irritable bowel syndrome (IBS) affects 10%-20% of people. Increased numbers of Escherichia coli (E. coli) correlate with symptoms, and patients respond to antimicrobials targeting E. coli. We examined whether specific E. coli strains, phylogroups and pathotypes are associated with IBS. We evaluated 218 E. coli isolates from 33 IBS patients and 23 healthy controls. RAPD analysis revealed 89 E. coli strains (29 controls, 60 IBS), spanning the A, B1, B2 and D phylogroups. Strains were similarly enriched in virulence genes associated with extraintestinal pathogenic E. coli (ExPEC) and/or adherent-invasive E. coli (AIEC). Three strains harbored a diarrheagenic virulence gene (2 IBS, 1 control). Escherichia coli capable of invading epithelial cells or replicating in macrophages were detected in 53% of IBS and 50% controls, and 67% IBS and 45% controls respectively (P > 0.05). AIEC were identified in 33% of IBS patients vs 20% of controls (P = 0.35). Virulence genes ibeA, ColV and pduC were associated with intramacrophage persistence; ibeA and ColV were associated with epithelial invasion and AIEC pathotype (P < 0.05). IBS patients and controls are commonly colonized by E. coli that resemble ExPEC and display pathogen-like behavior in vitro, similar to CD-associated AIEC. The relationship of these resident pathosymbiont E. coli to IBS warrants further investigation.

The APRI may be enhanced by the use of the FIBROSpect II in the estimation of fibrosis in chronic hepatitis C.

BACKGROUND: Multiple serum markers to estimate hepatic fibrosis in chronic liver disease have been proposed. The AST/Platelet Ratio Index (APRI) is a simple biochemical index that has been shown to be useful and accurate in about 50% of patients with chronic hepatitis C. We determined if the combination of the APRI and the FIBROSpect II, a commercially available hepatic fibrosis marker that measures 3 components of the extracellular hepatic matrix, would further help distinguish mild from significant fibrosis in a group of patients with chronic hepatitis C. METHODS: In an outpatient setting, 93 consecutive patients were studied who were undergoing staging liver biopsy for chronic hepatitis C who had a liver biopsy length>or=1.5 cm. All had blood drawn at the time of the biopsy. Liver biopsies were staged for fibrosis by the Batts Ludwig criteria (F0-F4). Patients with previous anti-viral therapy, hepatocellular carcinoma, an organ transplant, or co-infection with HIV or hepatitis B were excluded. The APRI was calculated and FIBROSpect II determined. RESULTS: The AUC of the ROC curve for the APRI and FIBROSpect II were 0.887 and 0.879 respectively. Using cutoffs of or=1.2 for significant fibrosis, the APRI correctly estimated 19 of 20 patients with mild fibrosis for an NPV of 95.0%, and 31 of 33 patients with significant fibrosis for a PPV of 93.6%. The FIBROSpect II also works best utilizing 2 cutoffs, and using cutoffs of or=85 it correctly identified 18 of 18 patients with mild fibrosis and all 26 patients with significant fibrosis for an NPV and PPV of 100% for both. Among the 40 patients who could not be classified by the APRI, an additional 16 could be correctly classified using the FIBROSpect II with cutoffs of or=85. This lowered the indeterminate zone from 43.0 to 25.8%. By combining the APRI and the FIBROSpect II, the AUC for the ROC curve improved significantly to 0.931 (p=0.013). CONCLUSIONS: The APRI and the FIBROSpect II are both accurate tests for separating mild from significant fibrosis. By using the APRI as the initial screen, >50% of patients with mild or significant fibrosis can be correctly identified. If the patient falls in the indeterminate zone, then the more expensive FIBROSpect II could be obtained. This strategy could decrease the number of liver biopsies.

Chemotactic chemokines are important in the pathogenesis of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is one of the most frequently diagnosed disorders, affecting about 20% of the general population in Western countries. This syndrome poses an enormous socio-economic burden, impairs the quality of life substantially, and increases healthcare costs. IBS can be classified as either idiopathic (ID-IBS) with unknown etiology or post-infectious (PI-IBS), which develops after a bout of acute diarrhea or gastroenteritis. Little is known about the immunopathogenesis of these two forms of IBS. We evaluated various biomarkers in clinical samples of ID-IBS and PI-IBS patients with the goal to test the hypothesis that the immunologic presentations of these forms of IBS are similar, despite their apparent different etiologic origins. Sera and stool samples from PI-IBS, ID-IBS, and healthy volunteers were analyzed for relative amounts of 36 different biomarkers using the Proteome Profiler Human Cytokine Array Panel A Kit and quantitative ELISA. Our results demonstrated significantly high levels of chemotactic chemokines monocytes chemotactic protein-1 (CCL2) [p-value  = 0.003], macrophage inflammatory protein-1ß (CCL4) [p-value  = 0.010], and CXCL16 (p-value 0.001) in the sera and stools of both ID-IBS and PI-IBS patients. Furthermore, pro-inflammatory cytokines (IFN-γ, IL-1ß, and TNF-α) were significantly higher in IBS patients. Anti-inflammatory cytokines (IL-10, IL-4, and IL-13) were variable except IL-10, which was significantly higher in the healthy volunteers than the IBS patients. Remarkably, the amounts and expression pattern of these biomarkers were not significantly different between ID-IBS and PI-IBS. Thus, ID-IBS and PI-IBS present similar immunologic and clinical phenotypes, in spite of their different etiologic origins.

Role of simple biomarkers in predicting fibrosis progression in HCV infection.

AIM: To examine the accuracy of the aspartate aminotransferase (AST)/Platelet Ratio Index (APRI) and FIB-4, in predicting longitudinal changes in liver histology in hepatitis C virus (HCV) patients. METHODS: Patients that underwent repeat liver biopsies at least 1 year apart from 1999 to 2007 were identified. Liver fibrosis was staged on needle core biopsies evaluated by a single expert liver pathologist. Only laboratory values within 3 mo of the liver biopsies were used. RESULTS: Thirty-six patients met the inclusion criteria with 50% stage 1 on initial biopsy, 25% stage 2, and 22% stage 3. Nineteen of 36 (53%) had progression of fibrosis on repeat biopsies, while 16 (44%) showed no change in stage, and one (3%) showed improvement. Patients that showed progression of fibrosis had significantly higher alanine aminotransferase and aspartate aminotransferase levels than the group that did not show progression. A significant correlation was seen between change in stage of fibrosis and change in APRI (r² = 0.39, P = 0.00001) and a change in FIB-4 (r² = 0.31, P = 0.00004). A change in APRI (ΔAPRI) of 0.18 had 80% positive predictive value (PPV) and 67% negative predictive value (NPV) for progression of fibrosis. A change in FIB-4 (ΔFIB-4) of 0.39 had 75% PPV and 75% NPV for predicting progression of fibrosis. CONCLUSION: ΔAPRI and ΔFIB-4 parallel changes in fibrosis progression, and could be useful tools for clinicians in following patients with active chronic HCV infection.

Delayed type IV muscle flap in a feline model.

The concept of delaying a skin flap is well established and has been implemented into plastic surgery practice for years. Some investigators have delayed musculocutaneous flaps to improve the perforator inflow. To our knowledge, the concept of delaying a muscle flap had previously never been tested in a model with segmental pedicles. Five cats each underwent 3 sequential operations providing them with a sartorius muscle whose blood supply was a single distal pedicle. The opposite leg was used as a control. Our delayed type IV muscle flap demonstrated perfusion to the proximal tip of the sartorius muscle without necrosis or loss of muscle mass (P < 0.0001). The control showed no evidence of perfusion beyond the distal portion of the muscle when infused through the distal pedicle. The delayed flap can survive on a distal blood supply that would not be adequate in a single-stage procedure. This flap has an increased arc of rotation that may provide solutions to difficult reconstructive problems in the groin, lower abdomen, genitalia, knee, proximal leg, and might be suitable as a free flap.

APRI: an easy and validated predictor of hepatic fibrosis in chronic hepatitis C.

GOALS: To evaluate the aspartate aminotransferase/platelet ratio index (APRI) as a predictor of the presence or absence of significant fibrosis on liver biopsy of patients with chronic hepatitis C (HCV). BACKGROUND: The decision to treat HCV is often made on the basis of the presence or absence of significant fibrosis on the liver biopsy. Because liver biopsy is expensive and invasive a noninvasive marker to evaluate hepatic fibrosis would be useful. The APRI is an easy to calculate index that is one of several markers that have been proposed. STUDY: We retrospectively reviewed the charts of 339 patients with chronic HCV who had liver biopsies from January 2000 to March 2003. We subsequently evaluated 151 patients receiving pretreatment evaluation liver biopsies who had serum aspartate aminotransferase, platelets, routine liver function tests, and demographic data obtained. All liver biopsies were staged by the Batts Ludwig criteria. RESULTS: The area under the curve of the receiver operator characteristics of the calculated APRI compared with the liver biopsy demonstrated that the fibrosis score was 0.889 in the prospective group and 0.790 in the retrospective group. To achieve predictive values of approximately 90%, useful cutoffs were found at 0.40 and 1.5 in the retrospective study, and 0.42 and 1.2 in the prospective study leaving intermediate zones of 58.9% and 41.1%, respectively. In the prospective group, 34 of 36 patients with a value of <0.42 were accurately predicted as having mild fibrosis, whereas 50 of 54 patients with a value >1.2 were accurately predicted to have significant fibrosis. CONCLUSIONS: The APRI is a good estimator of hepatic fibrosis and was more accurate in a prospective group than a retrospective one. It potentially could be used to decrease the number of liver biopsies.

Scrotal and penile reconstruction using the vacuum-assisted closure device.

Fournier's gangrene is a necrotizing, soft tissue infection that spreads along the deep external fascial planes of the perineum, scrotum (or vagina), penis, thighs and lower abdomen. Due to the rapid progression of the disease, patients are frequently left with a large integumentary deficit. Treatment of the skin defect has been described in a multitude of ways including split-thickness skin grafting, burying the testes in the thighs, thigh flaps and a variety of myocutaneous and fasciocutaneous flaps. Many of the previously described techniques have worked well for smaller defects and for closure of wounds but fall short of aesthetic reconstruction of sexual organs. Described here is a technique using split-thickness skin grafts, with foam dressings as the bolster. This was performed using the vacuum-assisted closure device (Kinetic Concepts Inc, USA). This technique creates a natural appearing scrotum that holds the testes away from the body, in a physiological manner, and surfaces the penis with a natural appearance, in a functional manner. The technique results in nearly 100% graft take and greatly decreases length of hospital stay.

La gangrène aiguë de Fournier est une infection nécrosante des tissus mous, qui se propage le long des couches fasciales externes, profondes du périnée, du scrotum (ou du vagin), du pénis, des cuisses et de la partie inférieure de l'abdomen. Comme la maladie se propage rapidement, il en résulte souvent une perte de substance tégumentaire importante. On a tenté de bien des façons de compenser cette perte de substance, notamment par la greffe de demi-épaisseur, l'enfouissement des testicules dans les cuisses, les lambeaux de cuisse et différents types de lambeau myocutané ou fascio-cutané. Plusieurs des techniques précédentes conviennent bien aux petites pertes de substance ou à la fermeture de plaies, mais elles ne permettent pas une reconstruction esthétique des organes sexuels. Voici une technique de reconstruction réalisée à l'aide de lambeaux de demi-épaisseur, de pansements mousse utilisés comme support et d'un dispositif de fermeture à vide (Kinetic Concepts Inc. [États-Unis]). La technique donne une apparence naturelle au scrotum qui garde les testicules à distance du corps d'une manière physiologique et qui fait remonter le pénis à la surface d'une manière naturelle et fonctionnelle. La technique s'est soldée par la prise presque totale de la greffe et a considérablement réduit la durée du séjour à l'hôpital.