Tomografía computada y resonancia magnética en la patología de la vesícula biliar: más allá de la litiasis / Computed tomography and magnetic resonance in gallbladder patology: beyond lithiasis

Resumen La enfermedad de la vesícula biliar es una causa común de dolor abdominal. Si bien por lo general el dolor es secundario a la presencia de litiasis y colecistitis aguda, el espectro de la enfermedad es amplio e incluye anomalías congénitas, otros procesos inflamatorios y neoplasias. La tomografía computada (TC) y la resonancia magnética (RM) tienen un papel relevante en aquellos casos en los que la ecografía no es concluyente y en la planificación del tratamiento. Dentro de las anomalías congénitas, la forma en “gorro frigio” es la más frecuente. Los pólipos son en su mayoría lesiones benignas, siendo las características de malignidad un tamaño superior a 10 mm, solitario y sésil. La adenomiomatosis es reconocible por el engrosamiento de la pared vesicular y los componentes quísticos intramurales. Es importante reconocer el gas intramural e intraluminal en la colecistitis enfisematosa y los microabscesos y hemorragias intraluminales en la colecistitis gangrenosa debido a su alta morbilidad y mortalidad. La colecistitis xantogranulomatosa presenta nódulos intramurales que ocupan más del 60% del área de la pared engrosada y la conservación lineal del realce de la mucosa sin interrupción. El carcinoma vesicular se presenta como una lesión infiltrante que se extiende al hígado, un engrosamiento mural o una masa polipoide intraluminal.

Abstract Gallbladder disease is a common cause of abdominal pain. Although the pain is usually secondary to the presence of lithiasis and acute cholecystitis, the spectrum of the disease is broad and includes congenital anomalies, other inflammatory processes and neoplasms. Computed tomography (CT) and magnetic resonance (MRI) have a relevant role in those cases in which ultrasound is not conclusive and in treatment planning. Among the congenital anomalies, the “phrygian cap” shape is the most frequent. Polyps are mostly benign lesions, with the characteristics of malignancy being larger than 10 mm, solitary and sessile. Adenomyomatosis is recognizable by gallbladder wall thickening and intramural cystic components. It is important to recognize intramural and intraluminal gas in emphysematous cholecystitis and intraluminal microabscesses and hemorrhages in gangrenous cholecystitis because of its high morbidity and mortality. Xanthogranulomatous cholecystitis presents with intramural nodules occupying more than 60% of the thickened wall area and linear preservation of mucosal enhancement without interruption. Gallbladder carcinoma presents as an infiltrative lesion extending to the liver, a mural thickening or an intraluminal polypoid mass.

[Epidemiology of patients with hepatocellular carcinoma in a University hospital]. / Epidemiología de pacientes con hepatocarcinoma en un Hospital Universitario.

Hepatocellular carcinoma is the most common primary liver tumor, with 905 677 diagnosed cases and 830 180 deaths, in 2020 worldwide. In Argentina, it accounts for the 9th cause of death for cancer in men and the 10th in women. Unlike other highly-prevalent tumors, scientific evidence for most therapeutic options is limited mainly to small cohorts and retrospective studies. The aim of this study is to characterize and describe epidemiologically patients with diagnosis of hepatocellular carcinoma in the Italian Hospital of Buenos Aires during a 12-year period. Overall survival for our cohort was 58%, 46%, and 36% at 1, 3 and 5 years respectively. Average survival for patients receiving palliative treatment was 5 months, while for those who received either non-curative or curative treatment was 23 and 75 months respectively. Recurrence-free survival for those patients who underwent a curative treatment was 89%, 76% y 61% at 1, 3 and 5 years. A thorough analysis of etiology, risk factors, incidence, mortality and treatment was made. The study's importance lies in its large sample size, quantity and quality of data, and will most certainly stimulate the development of local studies in hepatocellular carcinoma.

El carcinoma hepatocelular (HCC) es el tumor primario más frecuente del hígado, con 905 677 casos diagnosticados en 2020, en todo el mundo, y 830 180 muertes. Es responsable de la novena causa de muerte por cáncer en los hombres y la décima en mujeres en Argentina. A diferencia de otros tumores de alta prevalencia, la evidencia científica acerca del HCC se limita principalmente a pequeñas cohortes y estudios retrospectivos. El objetivo de este estudio fue describir epidemiológicamente a aquellos pacientes con diagnóstico de HCC en el Hospital Italiano de Buenos Aires en un periodo de 12 años. La supervivencia global para nuestra cohorte fue de 58, 46 y 36% a 1, 3 y 5 años respectivamente. El promedio de supervivencia en pacientes con tratamiento paliativo fue de 5 meses, 23 para aquellos que recibieron tratamientos no curativos y 75 meses para los que recibieron tratamientos curativos. El porcentaje de pacientes libres de enfermedad a 1, 3 y 5 años fue de 89%, 76% y 61% respectivamente. Se realizó un estudio minucioso de la etiología, factores de riesgo, incidencia, mortalidad y tratamientos realizados. Su importancia yace en su tamaño muestral, calidad y cantidad de información disponible.

Epidemiología de pacientes con hepatocarcinoma en un hospital Universitario / Epidemiology of patients with hepatocellular carcinoma in a University hospital

Resumen El carcinoma hepatocelular (HCC) es el tumor primario más frecuente del hígado, con 905 677 casos diagnosticados en 2020, en todo el mundo, y 830 180 muertes. Es responsable de la novena causa de muerte por cáncer en los hombres y la décima en mujeres en Argentina. A diferencia de otros tumo res de alta prevalencia, la evidencia científica acerca del HCC se limita principalmente a pequeñas cohortes y estudios retrospectivos. El objetivo de este estudio fue describir epidemiológicamente a aquellos pacientes con diagnóstico de HCC en el Hospital Italiano de Buenos Aires en un periodo de 12 años. La supervivencia global para nuestra cohorte fue de 58, 46 y 36% a 1, 3 y 5 años respectivamente. El promedio de supervivencia en pacientes con tratamiento paliativo fue de 5 meses, 23 para aquellos que recibieron tratamientos no curativos y 75 meses para los que recibieron tratamientos curativos. El porcentaje de pacientes libres de enfermedad a 1, 3 y 5 años fue de 89%, 76% y 61% respectivamente. Se realizó un estudio minucioso de la etiología, factores de riesgo, incidencia, mortalidad y tratamientos realizados. Su importancia yace en su tamaño muestral, calidad y cantidad de información disponible.

Abstract Hepatocellular carcinoma is the most common primary liver tumor, with 905 677 diagnosed cases and 830 180 deaths, in 2020 worldwide. In Argentina, it accounts for the 9th cause of death for cancer in men and the 10th in women. Unlike other highly-prevalent tumors, scientific evidence for most therapeutic options is limited mainly to small cohorts and retrospective studies. The aim of this study is to characterize and describe epidemiologically patients with diagnosis of hepatocellular carcinoma in the Italian Hospital of Buenos Aires during a 12-year period. Overall survival for our cohort was 58%, 46%, and 36% at 1, 3 and 5 years respectively. Average survival for patients receiving palliative treatment was 5 months, while for those who received either non-curative or curative treatment was 23 and 75 months respectively. Recurrence-free survival for those patients who under went a curative treatment was 89%, 76% y 61% at 1, 3 and 5 years. A thorough analysis of etiology, risk factors, incidence, mortality and treatment was made. The study's importance lies in its large sample size, quantity and quality of data, and will most certainly stimulate the development of local studies in hepatocellular carcinoma.

Impact of Cholestasis on the Sensitivity of Percutaneous Transluminal Forceps Biopsy in 93 Patients with Suspected Malignant Biliary Stricture.

PURPOSE: The aim of this study was to determine the effect of hyperbilirubinemia in the sensitivity of percutaneous transluminal forceps biopsy (PTFB) in patients with suspected malignant biliary stricture. MATERIALS AND METHODS: Ninety-three patients with suspicion of malignant biliary stricture underwent percutaneous transhepatic cholangiography followed by PTFB. Sensitivity, specificity and predictive values were analysed based on the presence or absence of hyperbilirubinemia, defined as total bilirubin equal to, or higher than 5 mg/dL. Variables included demographic and clinical features, laboratory, tumour type and localization, stricture length, therapeutic approach and histopathology. Additionally, major morbidity and mortality were assessed. RESULTS: The overall sensitivity, specificity, positive predictive value and accuracy of PTFB were 61.1%, 100%, 100%, and 62.4%, respectively. Hyperbilirubinemia affected 57% of patients at the time of PTFB. There were 35 (37%) false negative results, none of them related to tumour type or localization, stricture length, or previous biliary intervention (i.e. PBBD (percutaneous biliary balloon dilatation), ERCP (endoscopic retrograde cholangiopancreatography)) (p > 0.05). However, when bilirubin was < 5 mg/dL, false negative results decreased globally (p = 0.024) and sensitivity increased significantly for intrahepatic and hilar localization, as well as for colorectal metastasis, gallbladder carcinoma, and pancreatic carcinoma. No major morbidity occurred. CONCLUSION: The sensitivity of percutaneous transluminal biopsy for diagnosis of malignant stricture may significantly increase if samples are obtained in the absence of hyperbilirubinemia, without adding morbidity to the procedure. LEVEL OF EVIDENCE: Level 3, Case- Control studies.

Hepatic lymphocytes involved in the pathogenesis of pediatric and adult non-alcoholic fatty liver disease.

The immune response is critical in NAFLD pathogenesis, but the liver infiltrate's composition and the role of each T cell population is still up for debate. To characterize liver pathogenesis in pediatric and adult cases, frequency and localization of immune cell populations [Cytotoxic T Lymphocytes (CD8+), T helper Lymphocytes (CD4+), Regulatory T lymphocytes (Foxp3+) and Th17 (IL-17A+)] were evaluated. In portal/periportal (P/P) tracts, both age groups displayed a similar proportion of CD8+ and CD4+ lymphocytes. However, comparable Foxp3+ and IL-17A+ cell frequencies were observed in pediatric cases, meanwhile, in adults Foxp3+ was higher than IL-17A+ cells. Interestingly, IL-17A+ lymphocytes seemed to be nearly exclusive of P/P area in both age groups. In intralobular areas, both pediatric and adult cases showed CD8+ lymphocytes predominance with lower frequencies of CD4+ lymphocytes followed by Foxp3+ . Severe inflammation was associated with higher intralobular Foxp3+ lymphocytes (p = 0.026) in children, and lower P/P Foxp3+ and higher IL-17A+ lymphocytes in adults. All cases with fibrosis ≥ 2 displayed P/P low Foxp3+ and high IL-17A+ lymphocyte counts. Pediatric cases with worse steatosis showed high P/P CD4+ (p = 0.023) and intralobular CD8+ (p = 0.027) and CD4+ cells (p = 0.012). In NAFLD cases, the lymphocyte liver infiltrate composition differs between histological areas. Treg and Th17 balance seems to condition damage progression, denoting their important role in pathogenesis.

Early pancreatic cancer in IgG4-related pancreatic mass: A case report.

BACKGROUND: IgG4-related disease can manifest diversely, including autoimmune pancreatitis and IgG4-related cholangiopathy. We are reporting a very unusual cause of pancreatic cancer triggered in a previously unknown IgG4-related disease. CASE SUMMARY: A 75-year-old man was diagnosed with a 43 mm × 33 mm pancreatic head tumor after consulting for abdominal pain and jaundice. A pancreaticoduodenectomy was carried out uneventfully, and the histopathology report showed an early stage of acinar-cell pancreatic cancer. The patient reconsulted on the 30th postoperative day with fever, jaundice and asthenia. Magnetic resonance cholangiopancreatography evidenced an extense bile duct stricture. A percutaneous biliary drainage proved to be ineffective, even after exchanging it with larger bore drainage. Reviewing the surgical specimen, features compatible with IgG4-related disease were observed. Consequently, empiric treatment with steroids was initiated achieving excellent results. CONCLUSION: IgG4-related disease may cause chronic inflammation of the pancreas and can condition pancreatic malignancies.

Malignant transformation of hepatocellular adenoma in a young female patient after ovulation induction fertility treatment: A case report.

BACKGROUND: Hepatocellular adenoma (HCA) is a rare benign liver tumor usually affecting young women with a history of prolonged use of hormonal contraception. Although the majority is asymptomatic, a low proportion may have significant complications such as bleeding or malignancy. Despite responding to the hormonal stimulus, the desire for pregnancy in patients with small HCA is not contraindicated. However, through this work we demonstrate that intensive hormonal therapies such as those used in the treatment of infertility can trigger serious complications. CASE SUMMARY: A 33-year-old female with a 10-year history of oral contraceptive use was diagnosed with a hepatic tumor as an incidental finding in an abdominal ultrasound. The patient showed no symptoms and physical examination was unremarkable. Laboratory functional tests were within normal limits and tests for serum tumor markers were negative. An abdominal magnetic resonance imaging (MRI) was performed, showing a 30 mm × 29 mm focal lesion in segment VI of the liver compatible with HCA or Focal Nodular Hyperplasia with atypical behavior. After a total of six years of follow-up, the patient underwent ovulation induction treatment for infertility. On a following MRI, a suspected malignancy was warned and hence, surgery was decided. The surgical specimen revealed malignant transformation of HCA towards trabecular hepatocarcinoma with dedifferentiated areas. There was non-evidence of tumor recurrence after three years of clinical and imaging follow-up. CONCLUSION: HCAs can be malignant regardless its size and low-risk appearance on MRI when an ovultation induction therapy is indicated.

Chronic hepatitis B: The interplay between intrahepatic lymphocyte population and viral antigens in relation to liver damage.

In Chronic hepatitis B (CHB) infection, virus and immune response interplay is thought to be responsible for pathogenesis. Yet, the impact of each immune cell population and viral protein expression in liver damage is still unknown. Our aim was to study the interplay between intrahepatic immune response and viral activity in relation to CHB liver damage. Immunostaining was performed in 29 liver biopsies from untreated CHB patients to characterize liver infiltrate [Th (CD4+), CTL (CD8+), Treg (FoxP3+), Th17 (IL-17A+) and Th1 (T-bet+)] and viral antigen expression (HBsAg and HBcAg). Inflammatory activity and fibrosis were assessed using the HAI and METAVIR scoring system. All studied populations were identified in the portal-periportal (P-P) areas with a CD4+ lymphocyte predominance, while only CD8+ and FoxP3+ cells were observed in the intralobular area. Both P-P CD4+ and intralobular CD8+ cell frequencies were increased among severe hepatitis cases. Concerning HBsAg and HBcAg expression, a mutually exclusive pattern was observed. HBcAg was mainly detected among HBeAg-positive patients and was associated with hepatitis severity and higher frequency of P-P FoxP3+, intralobular CD8+ and FoxP3+ cells. HBsAg was identified among HBeAg-negative cases with less severe hepatitis grade and lower frequency of P-P CD4+ and intralobular FoxP3+ lymphocytes. In conclusion, the HBV antigen profile expression seen during CHB infection may be reflecting different stages of viral replication which impacts the host immune response and liver damage process. While HBcAg might be an inducer of a regulatory microenvironment, the intralobular CTL population seemed to have a key role in hepatitis severity.

α-lipoic acid reduces postreperfusion syndrome in human liver transplantation - a pilot study.

A double-blind randomized controlled trial was performed to compare the safety and efficacy of α-lipoic acid (ALA) in liver transplantation (LT). The grafts were randomized to receive ALA or placebo before the cold ischemia time. Furthermore, patients transplanted with the ALA-perfused graft received 600 mg of intravenous ALA, while patients with the nonperfused graft received the placebo just before graft reperfusion. Hepatic biopsy was performed 2 h postreperfusion. Blood samples were collected before, during and 1 and 2 days after reperfusion. Quantitative polymerase chain reaction (qPCR) analysis was performed on biopsies to assess genes involved in the response to hypoxia, apoptosis, cell growth, survival and proliferation, cytokine production and tissue damage protection. Nine of 40 patients developed postreperfusion syndrome (PRS), but seven of them belonged to the control group. There was a decrease in PHD2 and an increase in alpha subunit of hypoxia-inducible factor-1 (HIF-1α) and baculoviral IAP repeat containing 2 (Birc2) transcript levels in the biopsies from the ALA-treated versus the control group of patients. Additionally, plasma levels of alarmins were lower in ALA-treated patients than control patients, which suggests that ALA-treated grafts are less inflammatory than untreated grafts. These results showed that ALA is safe for use in LT, induces gene changes that protect against hypoxia and oxidative stress and reduces the appearance of PRS.

Nonalcoholic fatty liver disease: biomarkers as diagnostic tools for liver damage assessment in adult patients from Argentina.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease whose prevalence has been increasing constantly and linked to the global obesity epidemic. The NAFLD histologic spectrum ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma. Liver biopsy is the only reliable means to diagnose and stage NASH, but its invasive nature limits its use. Therefore, the prediction of hepatic injury by means of the development of new noninvasive tests represents a growing medical need. Our aim was to evaluate matrix deposition and cell-death markers, which correlate with liver injury in an NAFLD patient cohort. PATIENTS AND METHODS: Liver biopsies and serum from 34 NAFLD adult patients were analyzed. Histological parameters were evaluated. Matrix deposition [hyaluronic acid (HA) and tissue inhibitor of matrix metalloproteinase inhibitor-1 (TIMP-1)] and cell-death markers [cytokeratin-18 (M65) and caspase-cleaved cytokeratin-18 (M30)] were measured in serum samples. RESULTS: HA showed an association with fibrosis severity (P=0.03) and M30 with steatosis (P=0.013), inflammation (P=0.004), and fibrosis severity (P=0.04). In contrast, TIMP-1 and M65 showed no association with any histological parameter of liver injury. The evaluation of diagnostic accuracy showed good performance as less invasive markers of significant fibrosis of both HA (area under the receiver operating characteristic curve: 0.928) and M30 (area under the receiver operating characteristic curve: 0.848). CONCLUSION: Biomarkers are essential tools that may provide a quick and accurate diagnosis for patients with life-threatening NAFLD and NASH. HA and M30, together or determined sequentially, have been found to be straightforward tests that may be sufficient to predict significant fibrosis even in a primary care center of an underdeveloped country.

Chronic hepatitis C liver microenvironment: role of the Th17/Treg interplay related to fibrogenesis.

The role of the different lymphocyte populations in liver microenvironment of chronic hepatitis C (CHC) patients is still matter of debate. Since Th17 and Treg have opposite functions, their balance could affect disease progression. The aim was to explore liver microenvironment and its peripheral blood counterpart in adult CHC patients. CD4+ lymphocytes were predominant in the liver, with high Foxp3+ but low IL-17A+ frequency. IL-17A+ lymphocytes and IL-17A+/Foxp3+ ratio displayed association with advanced fibrosis (p = 0.0130; p = 0.0236, respectively), while Foxp3+ lymphocytes and IL-10 expression level inversely correlated with fibrosis severity (p = 0.0381, p = 0.0398, respectively). TGF-ß/IL-6 ratio correlated with IL-17A+/Foxp3+ ratio (p = 0.0036, r = 0.5944) and with IL-17A+ lymphocytes (p = 0.0093; r = 0.5203). TNF-α and TGF-ß were associated with hepatitis severity (p = 0.0409, p = 0.0321). Peripheral blood lymphocyte frequency was not associated with liver damage. There are functionally different immune cell populations actively involved in liver damage, but the liver cytokine milieu actually drives the pathogenesis. The intrahepatic Foxp3+ lymphocytes predominance beside the low IL-17A+ lymphocytes frequency, delineate a skewed IL-17A+/Foxp3+ balance towards Foxp3+ lymphocytes. However, the IL-17A+ lymphocytes association with advanced fibrosis denotes their role in the pathogenesis. Therefore, the interplay between Th17 and Treg conditions liver fibrogenesis.

Recreational Exposure during Algal Bloom in Carrasco Beach, Uruguay: A Liver Failure Case Report.

In January 2015, a 20-month-old child and her family took part in recreational activities at Carrasco and Malvín beaches (Montevideo, Uruguay). An intense harmful algae bloom (HAB) was developing along the coast at that time. A few hours after the last recreational exposure episode, the family suffered gastrointestinal symptoms which were self-limited except in the child's case, who was admitted to hospital in Uruguay with diarrhea, vomiting, fatigue, and jaundice. The patient had increased serum levels of liver enzymes and bilirubin and five days later presented acute liver failure. She was referred to the Italian Hospital in Buenos Aires, being admitted with grade II-III encephalopathy and hepatomegaly and requiring mechanical respiratory assistance. Serology tests for hepatitis A, B, and C, Epstein-Barr virus, and cytomegalovirus were negative. Laboratory features showed anemia, coagulopathy, and increased serum levels of ammonium, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin. Autoimmune Hepatitis Type-II (AH-II) was the initial diagnosis based on a liver kidney microsomal type 1 antibodies (LKM-1) positive result, and twenty days later a liver transplant was performed. The liver histopathology had indicated hemorrhagic necrosis in zone 3, and cholestasis and nodular regeneration, which were not characteristic of AH-II. LC/ESI-HRMS (liquid chromatography electrospray ionization high-resolution mass spectrometry) analysis of MCs in the explanted liver revealed the presence of Microsytin-LR (MC-LR) (2.4 ng·gr-1 tissue) and [D-Leu¹]MC-LR (75.4 ng·gr-1 tissue), which constitute a toxicological nexus and indicate a preponderant role of microcystins in the development of fulminant hepatitis.

Compartmentalization of hepatitis C virus variants in patients with hepatocellular carcinoma.

Chronic Hepatitis C Virus (HCV) infection is a major risk for hepatocellular carcinoma (HCC) development. HCV Core protein has been associated with the modulation of potentially oncogenic cellular processes and E2 protein has been useful in evolutive studies to analyze the diversity of HCV. Thus, the aim of this study was to evaluate HCV compartmentalization in tumoral, non-tumoral liver tissue and serum and to identify viral mutations potentially involved in carcinogenesis. Samples were obtained from four patients with HCC who underwent liver transplantation. Core and E2 were amplified, cloned and sequenced. Phylogenies and BaTS Test were performed to analyze viral compartmentalization and a signature sequence analysis was conducted by VESPA. The likelihood and Bayesian phylogenies showed a wide degree of compartmentalization in the different patients, ranging from total clustering to a more scattered pattern with small groups. Nevertheless, the association test showed compartmentalization for the three compartments and both viral regions tested in all the patients. Signature amino acid pattern supported the compartmentalization in three of the cases for E2 protein and in two of them for Core. Changes observed in Core included polymorphism R70Q/H previously associated with HCC. In conclusion, evidence of HCV compartmentalization in the liver of HCC patients was provided and further biological characterization of these variants may contribute to the understanding of carcinogenesis mediated by HCV infection. © 2016 Wiley Periodicals, Inc.

Interferon beta 1a-induced severe autoimmune hepatitis in patients with multiple sclerosis: report of two cases and review of the literature.

Type I interferons are potent cytokines that possess antiviral, immunomodulating and antiproliferative actions. The development of autoimmune hepatitis is a well recognized complication of treatment with alpha IFN in patients with chronic viral hepatitis. Yet, the occurrence in patients under treatment with beta IFN for other indications is controversial and its occurrence often underestimated. We report two cases of severe acute autoimmune hepatitis in two patients undergoing therapy with IFN beta 1a for multiple sclerosis who recovered under early immunosuppressive therapy.

Is recurrence rate of incidental hepatocellular carcinoma after liver transplantation similar to previously known HCC? towards a predictive recurrence score.

BACKGROUND: Incidental hepatocellular carcinoma (iHCC) generates uncertainty over risk of recurrence after liver transplantation (LT). AIM: To compare recurrence between iHCC and confirmed HCC diagnosed prior to transplant based on imaging criteria (cHCC). MATERIAL AND METHODS: Fifty-four HCC patients were analyzed from a series of 309 consecutive adult transplanted patients. We developed a recurrence predicting score (RPS) applying ORs based on pathologic risk variables. RESULTS: Incidence of iHCC was 4.8% (n = 15) and overall recurrence 12.9% (cHCC 15.4% and iHCC 7%; P = 0.39). Variables included in the RPS were: microvascular invasion OR 17.8 (1.78-178.97; P = 0.014: 2 points), neural invasion OR 15.5 (1.13-212.17; P = 0.04: 1.5 points), nuclear grade > II OR 9.3 (1.17-74.84; P = 0.035: 1 point), and beyond Up-to 7 criteria OR 13.1 (1.66-103.67; P = 0.015: 1.5 points). Two risk groups were identified: low risk for recurrence (0-1 point) and intermediate-high risk groups (2-6 points). Low risk category remained an independent predictor of recurrence: OR 0.11 (0.01-0.67; P = 0.017); AUROC of 0.75 (0.54-0.96). A tendency towards more patients categorized as low risk group among iHCC patients was observed (69.2%; P = 0.13). CONCLUSIONS: In this series iHCC was not associated to lower risk of recurrence when compared to cHCC. We propose application of an RPS as a clinical tool for recurrence risk estimation.

Serum apoptosis markers related to liver damage in chronic hepatitis C: sFas as a marker of advanced fibrosis in children and adults while M30 of severe steatosis only in children.

BACKGROUND: Liver biopsy represents the gold standard for evaluating damage and progression in patients with chronic hepatitis C (CHC); however, developing noninvasive tests that can predict liver injury represents a growing medical need. Considering that hepatocyte apoptosis plays a role in CHC pathogenesis; the aim of our study was to evaluate the presence of different apoptosis markers that correlate with liver injury in a cohort of pediatric and adult patients with CHC. METHODS: Liver biopsies and concomitant serum samples from 22 pediatric and 22 adult patients with CHC were analyzed. Histological parameters were evaluated. In serum samples soluble Fas (sFas), caspase activity and caspase-generated neoepitope of the CK-18 proteolytic fragment (M30) were measured. RESULTS: sFas was associated with fibrosis severity in pediatric (significant fibrosis p = 0.03, advanced fibrosis p = 0.01) and adult patients (advanced fibrosis p = 0.02). M30 levels were elevated in pediatric patients with severe steatosis (p = 0.01) while in adults no relation with any histological variable was observed. Caspase activity levels were higher in pediatric samples with significant fibrosis (p = 0.03) and they were associated with hepatitis severity (p = 0.04) in adult patients. The diagnostic accuracy evaluation demonstrated only a good performance for sFas to evaluate advanced fibrosis both in children (AUROC: 0.812) and adults (AUROC: 0.800) as well as for M30 to determine steatosis severity in children (AUROC: 0.833). CONCLUSIONS: Serum sFas could be considered a possible marker of advanced fibrosis both in pediatric and adult patient with CHC as well as M30 might be a good predictor of steatosis severity in children.

The role of serum biomarkers in predicting fibrosis progression in pediatric and adult hepatitis C virus chronic infection.

BACKGROUND/AIMS: Liver biopsy represents the gold standard for damage evaluation, but noninvasive serum markers that mirror liver fibrosis progression are actual goals both in adults and especially in children. The aim was to determine specific serum markers that correlate with liver fibrosis progression during chronic HCV infection. METHODS: Liver biopsies and concomitant serum samples from 22 pediatric and 22 adult HCV patients were analyzed. Histological parameters were evaluated. On serum TGF-ß1, tissue inhibitor of matrix metalloprotein inhibitor-1 (TIMP-1), hyaluronic acid (HA) and aminoterminal peptide of procollagen type III (PIIINP) were tested. RESULTS: Significant fibrosis (F≥2) and advanced fibrosis (F≥3) represented 64% and 20%, respectively in children; while 54% F≥2 and 23% F≥3 in adults. Hyaluronic acid (p = 0.011) and PIIINP (p = 0.016) were related to worse fibrosis stages only in adults, along with TIMP-1 (p = 0.039) just in children; but TGF-ß1 was associated with mild fibrosis (p = 0.022) in adults. The AUROC of TIMP-1 in children to discriminate advanced fibrosis was 0.800 (95%IC 0.598-0.932). In adults, the best AUROCs were that of HA, PIIINP and TGF-ß1 [0.929 (IC95% 0.736-0.994), 0.894 (IC95% 0.689-0.984) and 0.835 (IC95% 0.617-0.957)], respectively. In children, according to the cut off (165.7 ng/mL) value for TIMP-1, biopsies could have been avoided in 72% (18/25). Considering the cut off for HA (109.7 ng/mL), PIIINP (9.1 µg/L), and TGF-ß1 (10,848.3 pg/mL), biopsies could have been avoided in 87% (19/22) of adult patients by using HA and 73% (16/22) using PIIINP or TGF-ß1. CONCLUSIONS: In adults given the diagnostic accuracy of HA, PIIINP, TGF-ß1, their combination may provide a potential useful tool to assess liver fibrosis. This first pediatric study suggests that TIMP-1 is clinically useful for predicting liver fibrosis in HCV patients.

[Gastrointestinal bleeding and intestinal perforation due to polyarteritis nodosa in a patient with celiac disease. A case report]. / Hemorragia digestiva y perforación intestinal secundarias a panarteritis nodosa en un paciente con enfermedad celiaca. Presentación de un caso.

Complications of celiac disease could present with intestinal perforation and rarely, gastrointestinal bleeding, which are usually secondary to nongranulomatous ulcerative jejunoileitis or T-cell lymphoma. We describe the case of a 66-year-old male patient with an 8-year history of celiac disease (CD) who presented with recurrent abdominal pain and gastrointestinal bleeding. Several tests were performed to find out possible complications associated to CD. Due to an overt gastrointestinal bleeding, an arteriography was performed and signs of polyarteritis nodosa were found. Vascular disease was aggressive, and despite multiple medical and surgical treatments the patient died. As arteriography is not usually performed for the study of the complications of CD, it is possible that the association between CD and PAN has been underdiagnosed.