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Background: the efficacy of combination therapy with peginterferon plus ribavirin to eradicate viral infection in patients with chronic hepatitis C (CHC) is well established; moreover, it is able to arrest or even reverse liver fibrosis. Aims: to analyze the measurements of hepatic stiffness as an index of liver fibrosis using transient elastography (TE) in patients who underwent a sustained virological response (SVR) during long-term follow-up; comparing the changes in the severity of fibrosis with non-responders patients. Material and methods: after hepatic fibrosis was studied in three patients with CHC who underwent a SVR during long-term follow up, a prospective study was initiated in 24 patients with CHC who received combination therapy to compare the evolution of fibrosis in those with SVR and those who were non-responders. The genotype of hepatitis C virus (HCV) and the degree of viremia were determined. METAVIR scoring system was used for liver fibrosis. Hepatic stiffness was measured by TE. Results: of the initial three patients pre-treatment liver biopsies revealed active disease and fibrosis (stage 3) in two and mild fibrosis (stage 1) in one. After several years of follow up serum AST/ALT levels were normal and HCV RNA was undetectable in each case; in contrast to the baseline histological assessments of fibrosis, values for hepatic stiffness (3.4-6.9 KPa) were compatible with an absence of any appreciable hepatic fibrosis. In the prospective study, 8 patients underwent a SVR and 16 were non-responders. TE indicated that the severity of hepatic fibrosis in the SVR group improved in 7 (88%) patients, whereas in the non-responder it improved in only 4 (25%) (p < 0.05). The difference between development of severe fibrosis (F ≥ 3) in responders and non-responders was not significant (p = 0.23), possibly due to the small sample size. Conclusions: regression of hepatic fibrosis appears to be common in patients with CHC who undergo a SVR. TE is a simple non-invasive technique that enables multiple assessments of the severity of hepatic fibrosis to be made efficiently during long-term follow-up of patients with CHC who receive combination antiviral therapy.

Objetivos: la hemorragia digestiva baja (HDB) es una causa frecuente de ingreso hospitalario; pese a ello, no se conocen con exactitud los factores que influyen en su evolución. Los objetivos de este trabajo fueron comparar los cambios en el manejo de la HDB en nuestro Servicio entre los años 2005 y 2007, así como analizar diferentes parámetros que pudieran influir en su pronóstico. Pacientes y métodos: se incluyeron retrospectivamente todos los ingresos por HDB durante el periodo 2005-2006 y prospectivamente los del 2006-2007. En todos se realizó historia clínica, exploración -incluyendo tacto rectal- y análisis sanguíneo. Se realizó colonoscopia en la mayoría de los pacientes. Resultados: se incluyeron 137 pacientes en el 2005-2006: requirieron transfusión de hemoderivados el 36%. El 31% había presentado algún episodio de HDB previamente. El 62% presentó una evolución favorable. El tiempo desde el ingreso hasta la colonoscopia y la estancia media fueron de 4,1 y 10,2 días respectivamente. En el 2006-2007 se incluyeron 96 pacientes: requirieron transfusión el 42%. El 33% había presentado HDB previamente. La evolución fue favorable en el 67%. El tiempo hasta la colonoscopia y la estancia media fueron de 2,6 y 7,7 días respectivamente. Los divertículos fueron el hallazgo más frecuente en ambos periodos. Conclusiones: durante el 2006-2007 la estancia media de los pacientes con HDB ingresados en el Servicio de Aparato Digestivo se redujo respecto al 2005-2006 en un 25% y el tiempo de realización de la colonoscopia en un 37%; esto no logró más localizaciones del punto sangrante ni una disminución en la recurrencia de la hemorragia.Objectives: lower intestinal bleeding (LGIB) is a frequent reason for hospitalization; however, the prognostic factors have not been clearly defined. The aim of this paper was to analyze several clinical parameters and the management of this entity in our department from 2005 to 2007. Material and methods: all hospitalized patients with LGIB were retrospectively (2005-2006) and prospectively (2006-2007) included. Medical records, physical examination (anal digital examination included), blood testing, and colonoscopic examination (in most of patients) were performed. Results: 137 patients were included during 2005-2006: 36% of them required blood transfusion; thirty-one percent of patients showed previous episodes of LGIB, and 62% had a favorable outcome. Time from admission to colonoscopy was 4.1 days, and length of stay was 10.2 days. In the 2006-2007 study 96 patients were included: 42% of them required blood transfusion, thirty-three percent of patients showed previous episodes of LGIB, and 68% had a favorable outcome. Time from admission to colonoscopy was 2.6 days, and length of stay was 7.7 days. The most frequent etiology was diverticulosis in both studies. Conclusions: hospital length of stay and time from admission to colonoscopy in patients with LGIB was reduced by 25% and 37%, respectively, in the 2005-2006 period with regard to the 2006-2007 one; however, there were no more bleeding points or a decrease in bleeding recurrence.

Introduction: detection of early-stage colorectal carcinoma (CRC) -( Dukes' A or B)- provides better survival rates in these patients. Thus, the effectiveness of screening programs in asymptomatic patients or of early diagnosis in symptomatic individuals has been postulated. The aim of this study was to establish whether a delay in diagnosis or other factors are related to CRC stage. Patients and methods: a retrospective study was performed on 96 patients with CRC. Age at diagnosis, gender distribution, intestinal disorders, diagnosis delay, primary sign and -regarding CRC- localization, stage (Dukes') and grade of differentiation (well differentiated; non-well differentiated; poorly differentiated) were recorded. Results: diagnosis delay was 185 ± 190 days. Patients delay in obtaining a diagnosis was 119 ± 158 days. In 40% of patients CRC was diagnosed at an early stage (Dukes' A or B), and in 13% CRC was poorly differentiated. The only factor with an independent effect on Dukes' stage was tumor differentiation (p: 0.0012). Distal location was associated with less advanced tumors without statistical significance (p: 0.156). Conclusion: based on the presented data, a greater effort regarding screening programs for healthy people seems warranted, as improved survival has been demonstrated when diagnosis delay is reduced, particularly in patients with the highest mean delay.Introducción: el diagnóstico precoz del cáncer colorrectal (estadios A y B de Dukes) consigue mejorar las tasas de supervivencia de estos pacientes. Con este objetivo se ha propuesto como estrategia acelerar el diagnóstico de enfermos sintomáticos o realizar cribados en enfermos asintomáticos. El objetivo de este trabajo es identificar los factores que influyen en la extensión tumoral del carcinoma colorrectal, especialmente la demora en el diagnóstico. Material y métodos: estudio prospectivo de una serie de 99 pacientes diagnosticados de carcinoma colorrectal en los que se analizaron las variables: edad, sexo, habito intestinal, ingesta de laxantes, signo o síntoma de presentación, localización tumoral, grados de Dukes, diferenciación histológica y demora diagnóstica definida como el tiempo transcurrido desde el comienzo de los síntomas hasta el diagnóstico endoscópico del tumor. Resultados: el 40% de los enfermos presentaban al momento del diagnóstico un estadio A o B de Dukes. Un 15% de los tumores eran de grado histológico "bien diferenciado' y un 13% "mal diferenciado'. La demora diagnóstica global fue de 185 ± 190 días de los que 119 ± 158 días se debieron al retraso del enfermo en acudir al médico. La única variable que influyó significativamente sobre la extensión tumoral fue el grado de diferenciación (p < 0,05). La localización distal se asoció a menor extensión sin alcanzar significación estadística (p = 0,1). Conclusión: de acuerdo a los datos presentados, parece razonable dirigir fundamentalmente nuestros esfuerzos hacia programas de cribado poblacional que han demostrado reducir significativamente la mortalidad, en lugar de tratar reducir una demora diagnostica que depende fundamentalmente del enfermo.

Objectives: to analyze scientific output from Spanish hospitals in relation to Helicobacter pylori infection. Methods: papers collected from the Medline database between January 1988 and December 2003 were selected. Our search strategy was: "Helicobacter pylori" [MeSH] AND ((Spain [AD] OR Espana [AD] OR Spanien [AD] OR Espagne [AD] OR Espanha [AD]) OR (Spanish [LA]) OR Spain). The following was analyzed: geographic area, Spanish or foreign publication, topic, and year of publication. Output and impact bibliometric markers were evaluated. Results: in all, 691 papers were identified, of which 241 were excluded. Number of papers went from 2 in 1988 to 47 in 2002 and 13 in 2003. There were more reports in Spanish versus foreign journals (58 vs. 42%). In the first 5 years the areas with greater output were associated with diagnosis and microbiology (33 and 20%), whereas therapy was the predominating subject during the last 5 years (27%). Original papers were most common among publications (69%). Hospitals with highest output included La Princesa (24%) and Ramón y Cajal (17.6%) in Madrid, and Parc Taulí in Barcelona (6.4%). Mean impact factor progressively increased from 1.826 in 1988 to 2.142 in 2002 and 2.493 in 2003. Conclusions: the production and impact of documents published by Spanish scientists regarding H. pylori infection considerably increased during the past two decades.Objetivos: analizar la producción científica procedente de hospitales españoles en relación con la infección por Helicobacter pylori. Métodos: se seleccionaron los artículos recogidos en la base de datos Medline entre enero de 1988 y diciembre de 2003. La estrategia de búsqueda fue: "Helicobacter pylori" [MeSH] AND ((Spain [AD] OR Espana [AD] OR Spanien [AD] OR Espagne [AD] OR Espanha [AD]) OR (Spanish [LA]) OR Spain). Se analizaron: área geográfica, publicación española o extranjera, área temática y año de publicación. Se evaluaron indicadores bibliométricos de producción y repercusión. Resultados: se identificaron 691 artículos, de los cuales se excluyeron 241. El número de artículos pasó de 2 en 1988 a 47 en 2002 y 13 en el 2003. Se publicó más en revistas españolas que en extranjeras (58 frente a 42%). En los primeros cinco años las áreas de mayor producción se relacionaron con el diagnóstico y la microbiología (33 y 20%), mientras que el tratamiento fue el área predominante en los últimos cinco (27%). El documento más común fue el original (69%). Los hospitales con mayor producción fueron el de La Princesa (24%) y Ramón y Cajal (17,6%) de Madrid y Parc Taulí de Barcelona (6,4%). El factor de impacto medio aumentó progresivamente desde 1,826 en 1.988 hasta 2.142 en 2002 y 2.493 en 2003. Conclusiones: la producción y repercusión de los documentos publicados por científicos españoles en relación con la infección por H. pylori se ha incrementado considerablemente en las dos últimas décadas.

Spain is worldwide leader in deceased donation rates per million habitants and count on a strong network of twenty-five liver transplant institutions. Although the access to liver transplantation is higher than in other countries, approximately 10% of patients qualifying for liver transplantation in Spain will die in the waiting list or would be excluded due to clinical deterioration. A robust waiting list prioritization system is paramount to grant the sickest patients with the first positions in the waiting list for an earlier access to transplant. In addition, the allocation policy may not create or perpetuate inequities, particularly in a public and universal healthcare system. Hitherto, Spain lacks a unique national allocation system for elective liver transplantation. Most institutions establish their own rules for liver allocation and only two autonomous regions, namely Andalucía and Cataluña, share part of their waiting list within their territory to provide regional priority to patients requiring more urgent transplantation. This heterogeneity is further aggravated by the recently described sex-based disparities for accessing liver transplantation in Spain, and by the expansion of liver transplant indications, mainly for oncological indications, in absence of clear guidance on the optimal prioritization policy. The present document contains the recommendations from the first consensus of waiting list prioritization for liver transplantation issued by the Spanish Society of Liver Transplantation (SETH). The document was supported by all liver transplant institutions in Spain and by the Organización Nacional de Trasplantes (ONT). Its implementation will allow to homogenize practices and to improve equity and outcomes among patients with end-stage liver disease.

Background: Genetic diagnosis of inherited platelet disorders (IPDs) is mainly performed by high-throughput sequencing (HTS). These short-read-based sequencing methods sometimes fail to characterize the genetics of the disease., Objectives: To evaluate nanopore long-read DNA sequencing for characterization of structural variants (SVs) in patients with IPDs., Methods: Four patients with a clinical and laboratory diagnosis of Glanzmann thrombasthenia (GT) (P1 and P2) and Hermansky-Pudlak syndrome (HPS) (P3 and P4) in whom HTS missed the underlying molecular cause were included. DNA was analyzed by both standard HTS and nanopore sequencing on a MinION device (Oxford Nanopore Technologies) after enrichment of DNA spanning regions covering GT and HPS genes., Results: In patients with GT, HTS identified only 1 heterozygous ITGB3 splice variant c.2301+1G>C in P2. In patients with HPS, a homozygous deletion in HPS5 was suspected in P3, and 2 heterozygous HPS3 variants, c.2464C>T (p.Arg822∗) and a deletion affecting 2 exons, were reported in P4. Nanopore sequencing revealed a complex SV affecting exons 2 to 6 in ITGB3 (deletion-inversion-duplication) in homozygosity in P1 and compound heterozygosity with the splice variant in P2. In the 2 patients with HPS, nanopore defined the length of the SVs, which were characterized at nucleotide resolution. This allowed the identification of repetitive Alu elements at the breakpoints and the design of specific polymerase chain reactions for family screening., Conclusion: The nanopore technology overcomes the limitations of standard short-read sequencing techniques in SV characterization. Using nanopore, we characterized novel defects in ITGB3, HPS5, and HPS3, highlighting the utility of long-read sequencing as an additional diagnostic tool in IPDs., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Liver transplant in patients with prior nonhepatic cancer is a matter of concern, needing further research, development, and consensus guidelines. This International Liver Transplantation Society/Sociedad Española De Trasplante Hepático consensus conference document focuses on the role of liver transplantation in patients with a prior history of nonhepatic cancer. This document addresses (1) the evaluation of transplant candidates with prior cancers based on the assessment of prognosis, the natural history of individual cancers, and the emerging role for circulating DNA and minimal residual disease in these patients; (2) the impact of prior treatments, including immunotherapy for prior malignancies; and (3) the surveillance of posttransplant cancer recurrence. The consensus statement is based on previously published guidelines, as well as a review of the current, relevant, published literature., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Autoimmune hepatitis (AIH) is a chronic liver disease able to progress to acute liver failure, cirrhosis, and liver cancer. A significant proportion of patients fail to first-line therapy or develop severe toxicity., Aims: To assess safety and effectiveness of tacrolimus as a second-line therapy in AIH patients., Methods: Multicentric retrospective study of AIH patients treated with tacrolimus for at least 3 months as a second-line therapy. Effectiveness was defined as complete normalization of transaminases and IgG., Results: A total of 23 AIH patients were included in the final analysis. In 13% of patients tacrolimus was initiated because of toxicity to previous first-line treatments and the rest were switched because of previous non-efficacy. Tacrolimus was effective in 18 patients (78%; 95%CI: 55.20-91.92%). The median time receiving tacrolimus was 16 months (IQR 20). There was a sustained response with a significant improvement in all liver enzymes and IgG on last follow-up. Only one patient discontinued tacrolimus at the third month because of severe neuropathy, and ototoxicity. Responders were significantly older at diagnosis of AIH (41 ± 13 vs. 27 ± 10 years old; p = 0.0496)., Conclusion: Tacrolimus is effective and well tolerated as a second-line therapy in patients with AIH., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Given the high waiting list mortality, there is a clear need to identify strategies to increase the number of livers for transplantation. Some strategies require policy changes, whereas others depend on a better understanding of available opportunities. We divided the strategies to increase the number of livers for transplantation into two categories-those aiming to increase the use of organs considered to be of suboptimal quality, and those aiming to increase the use of organs considered to be of suboptimal size. Enough evidence suggests that, if considered in the context of other donor and recipient variables, grafts from elderly donors are a safe option. The severity of steatosis, and not simply its presence, is an important factor in contemplating the utility of steatotic grafts. Use of organs that have steatosis together with other factors that define extended-criteria organs should be avoided, particularly prolonged cold ischaemia time. Donation after circulatory death has an important role in increasing the donor pool, given the wide availability of organs from donors with this cause of death. This type of donation is hampered by a higher risk of ischaemia-reperfusion injury than other types of donation, which can result in graft complications and potential graft loss. Different types of machine perfusion have the potential to overcome these issues, and further research is needed to establish the best techniques and most cost-effective models. Despite the scarcity of data, the availability of safe and highly effective antiviral therapies means that the use of donors infected with hepatitis C virus (HCV) in recipients who are HCV negative can be considered as a strategy to increase the donor pool. Although data on transplantations using livers from living donors in patients with a Model for End-Stage Liver Disease (MELD) score higher than 20-24 are scarce, outcomes are similar to those achieved in patients with lower MELD scores, at least in reference centres. Increased use of split livers is an option if donors and recipients are carefully selected., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Transarterial chemoembolisation (TACE), having demonstrated survival benefits, is the treatmentof choice in intermediate-stage hepatocellular carcinoma, although there is great heterogeneity in its clinical application., Material and Methods: A survey was sent to the Madrid Regional hospitals to assess applicability, indications and treatment protocols. The assessment was made overall and according to the type of hospital (groups A vs. B and C)., Results: Seventeen out of 22 hospitals responded (8/8 group A, 9/ 14 group B-C). All do/indicate transarterial chemoembolisation, 13/17 at their own facilities. Eight of the 17 hospitals have multidisciplinary groups (5/8 A, 3/9 B-C). Nine hospitals perform > 20 procedures/year (7 group A), and 6 from group B-C request/perform < 10/year. It is performed on an "on-demand" basis in 12/17. In 5 hospitals, all the procedures use drug-eluting beads loaded with doxorubicin. The average number of procedures per patient is 2. The mean time from diagnosis of hepatocellular carcinoma to transarterial chemoembolisation is ≤ 2 months in 16 hospitals. In 11/17 hospitals, response is assessed by computed tomography. Radiological response is measured without specific criteria in 12/17 and the other five hospitals (4 group A) assessed using standardised criteria., Conclusion: Uniformity among the Madrid Regional hospitals was found in the indication and treatment regimen. The use of DEB-TACE has become the preferred form of TACE in clinical practice. The differentiating factors for the more specialised hospitals are a larger volume of procedures, decision-making by multidisciplinary committees and assessment of radiological response more likely to be standardised.

Histone deacetylases (HDACs) influence many cellular processes, including the modulation of signal transducer and activator of transcription activity (STAT) in response to interferon (IFN). To identify genetic markers that help optimize the IL-28B prediction of chronic hepatitis C (CHC) sustained virological response (SVR), we evaluated 27 single-nucleotide polymorphisms (SNPs) in HDAC1-11. Three SNPs, rs3778216, rs976552 and rs368328 in HDAC2, HDAC3 and HDAC5, respectively, were independently associated with SVR (P<0.05). The addition of these three HDAC's SNPs to the IL-28B predictive model (area under the curve (AUC)=0.630) rendered an important improvement of AUC-receiver operating characteristic value (AUC=0.747, P=0.021). Chi-squared Automatic Interaction Detector (CHAID) analysis denoted the significance of the rs3778216 C/C genotype in identifying a group of good responders despite carrying IL-28B T allele (79.2% of SVR), whereas HDAC5 G allele characterized a subgroup with poor response rate (25.5%). However, HDAC3 rs976552 did not display a relevant role for the hierarchical classification of patients. Variables related to SVR in hepatitis C virus genotype 1 (HCV-1) cohort were the same of those obtained for the overall population. Interestingly, in non-HCV-1 patients (n=56) the HDAC2 C/C genotype was the unique predictive variable related to SVR (AUC=0.733, P<0.007). Thus, these preliminary results suggest the potential usefulness of combined IL-28B and HDAC genotyping for the CHC patients' classification by likelihood of an SVR.

This study aimed to evaluate the efficacy and safety of entecavir and/or tenofovir in compensated (CC) or decompensated (DC) hepatitis B cirrhotic patients in real-life clinical practice. Of the 48 patients, included between April 2007 and March 2010, 12 were DC. The mean age was 55 ± 12.2 years, 85.4% were Caucasians and 8 patients were HBeAg positive. Mean viral load was 5.2 ± 1.9 log(10) UI/mL. HBV-DNA undetectability at 3, 6, 12 and 24 months were 53.3%, 78.3%, 83.7% and 97.1%, respectively, similar in CC and DC. At 6 and 12 months, ≥ 80% of CC achieved ALT normalization, while only 42.9% and 71.4% in DC. After a median follow-up of 27.1 (0.7-45.3) months, 43 patients were Child Pugh Turcotte (CPT) class A (n = 39 at entry). In DC, progressive improvement in the MELD scores was observed: 12.73 (SD 4.5), 10.4 (SD 3.6) and 8.2 (SD 2.6), at baseline, 12 and 24 months, respectively. During follow-up, 7 patients died, 4 received liver transplantation and 5 developed hepatocellular carcinoma. In three out of four DC who died due to hepatic causes, these events occurred between the first 0.7 and 6.7 months, and all were CPT class C. Cumulative survival in CC vs. DC at 12 and 24 months were 94.4% vs. 66.7%, and 88.2% vs. 57.1%, respectively (log rank p = 0.03). No severe adverse events associated with entecavir or tenofovir were reported. In conclusion, in compensated and decompensated cirrhotic patients, entecavir and tenofovir were effective and well tolerated.

Primary sclerosing cholangitis is a chronic progressive disorder which involves the medium size and large ducts in the intrahepatic and extrahepatic biliary tree. The great majority of cases have underlying inflammatory bowel disease, mainly ulcerative colitis. A higher risk of colorectal cancer has been described among ulcerative colitis patients with primary sclerosing cholangitis. Here we report a case of a primary sclerosing cholangitis in a young male with a newly diagnosed ulcerative colitis presenting with colonic dysplasia. Surveillance for colorectal cancer should be strongly recommended in this group of patients., (Copyright © 2012. Published by Elsevier B.V.)

What Is Known and Objective: Interferon-alfa-based therapy is effective in the treatment of Hepatitis C. However, some patients fail to respond and others relapse, after initially responding. Our objective was to assess the efficacy, safety and predictive factors for sustained virological response (SVR) to peginterferon plus ribavirin in chronic hepatitis C patients who failed to interferon-alfa (IFNα)-based therapy., Methods: Seventy-five consecutive patients who failed to IFNα-based therapy were retreated with peginterferon plus ribavirin. Of these patients, 85% were infected by genotype 1. The primary endpoint was SVR., Results and Discussion: Of 75 non-responder (n = 54) or relapser patients (n = 21), 50 were previously treated with IFNα-monotherapy and 25 with IFNα plus ribavirin. Global SVR rate was 41.3%: for patients re-treated with IFNα the response was 48% whilst for those retreated with IFNα plus ribavirin, it was 28%. For previous non-responders the SVR rate was 37% and for relapsers it was 52.4%., What Is New and Conclusion: Retreatment with peginterferon plus ribavirin is an effective option for some chronic hepatitis C non-responder or relapser patients. Higher SVR rate was achieved in relapsers and in those patients who received IFNα monotherapy previously., (© 2010 Blackwell Publishing Ltd.)

Hepatitis B virus is considered one of the most significant environmental carcinogens in humans. Because the mechanisms of HBV replication and the development of hepatocellular carcinoma (HCC) are partially known, HBV-associated pathogenesis remains a challenge to increase its understanding. Evidence suggests that the regulatory protein hepatitis B virus X (HBx) mediates the establishment and maintenance of the chronic carrier state. HBx is a multifunctional and potentially oncogenic protein that is conserved among mammalian hepadnaviruses; it is produced very early after infection and throughout the chronic phase. HBx exerts its effects by interacting with cellular proteins and activating various signaling pathways. HBx stimulates the transcription of genes that regulate cell growth, apoptosis, and DNA repair. It also interacts with proteasome subunits and affects mitochondrial stability. Moreover, HBx participates in processes that are associated with the progression of chronic liver disease, including angiogenesis and fibrosis. This review discusses the function of HBx in the life cycle of HBV and its contribution to the pathogenesis of HCC., (Copyright © 2011 John Wiley & Sons, Ltd.)

Methotrexate (MTX) therapy may be effective in patients with rheumatoid arthritis (RA) or psoriasis due to its anti-inflammatory and immunosuppressive properties. Potential liver toxicity of MTX exists, but the incidence of MTX-specific lesions in liver biopsy of patients with RA and elevated serum transaminase levels is rare; however, severe hepatic damage may occurs unexpectedly in these patients. We describe the first documented case of an adult patient with RA who developed an acute flare of severe hepatitis after long-term therapy with MTX. Autoantibodies positivity, elevated serum IgG levels and compatible liver biopsy findings prompted us to diagnose autoimmune hepatitis, most probably triggered by a breakdown of immune tolerance induced by MTX. A complete remission was achieved in this patient with corticosteroids therapy.

The hepatitis C virus (HCV) is one of the most important causal agents of liver disease. Genotype 4 is responsible for 20% of chronic hepatitis and in several countries of the Mediterranean area it has been reported that the prevalence is increasing. The HCV infection develops to chronicity in more than 90%, 20% may have cirrhosis and 5-10% develop hepatocellular carcinoma. There has been speculation about a possible association of genotype 4 with the development of hepatocellular carcinoma, but it seems related to other concomitant causes of liver disease. Treatment is based on the use of pegylated interferon α-2a (180 mg/week) or pegylated-interferon α-2b (1.5mg/kg/wk) plus ribavirin (1000-1200 mg/day) for one year. With this regimen, there have been reported sustained virological response (SVR) rates around 65%. There are differences in the SVR rates according to the degree of fibrosis, associated concurrent infections and the presence of specific serologic markers. Nitazoxanide has been used in combination with the classic combination therapy, achieving an improvement in the results., (Copyright © 2010 Elsevier España, S.L. All rights reserved.)

Aim: To assess the clinical, biochemical and virological long-term outcome in chronic hepatitis C (CHC) patients with a sustained virological response (SVR) after peginterferon (PEG-IFN) plus ribavirin combination therapy., Methods: One hundred and fifty three patients with a SVR after treatment with PEG-IFN plus ribavirin were included in a 5-year follow-up study in a single Spanish center, based on standard clinical practice. Clinical anamnesis, biochemical analysis, hepatitis C virus RNA and alpha-fetoprotein measurement, ultrasonography and transient elastography were performed annually., Results: The mean follow-up period of the 153 patients was 76 ± 13 mo after they obtained a SVR. Five patients (3.26%) presented with cirrhosis before treatment and 116 (75.8%) had genotype 1. No patient showed evidence of hepatic decompensation. One patient (0.65%) developed a hepatocellular carcinoma at month 30 after achieving SVR. There were no virological relapses during this follow-up period. Persistently elevated alanine aminotransferase was found in only one patient (0.65%). At the end of the 5-year follow-up, the mean value of transient elastography was 7 ± 4.3 kPa (F1). There were no deaths and no other tumors., Conclusion: The long-term outcome of 153 CHC patients with SVR to PEG-IFN plus ribavirin was good. No evidence of a virological relapse was seen. One patient (0.65%) developed a hepatocellular carcinoma.

The porphyries are a group of metabolic disorders characterized by deficiencies in the activity of enzymes involved in the biosynthesis of heme. In erythropoietic protoporphyria (EPP), in the majority of cases an autosomal dominant disease, there is a mutation of the gene that encodes ferrochelatase (FECH). FECH deficiency is associated with increased concentrations of protoporphyrin in erythrocytes, plasma, skin and liver. The prevalence of this inherited disorder oscillates between 1:75 000 and 1:200 000. Clinical manifestations of EPP appear in early infancy upon first exposure to the sun. Nevertheless, approximately 5%-20% of patients with EPP develop liver manifestations. Retention of protoporphyrin in the liver is associated with cholestatic phenomena and oxidative stress that predisposes to hepatobiliary disease of varying degrees of severity, such as cholelithiasis, mild parenchymal liver disease, progressive hepatocellular disease with end-stage liver disease and acute liver failure. Liver damage is the major risk in EPP patients, so surveillance and frequent clinical and biochemical liver follow-up is mandatory. The diagnostic approach consists in detecting increased levels of protoporphyrin, decreased activity of FECH and genetic analysis of the FECH gene. A variety of non-surgical therapeutic approaches have been adopted for the management of EPP associated with liver disease, but none of these has been shown to be unequivocally efficacious. Nevertheless, some may have a place in preparing patients for liver transplantation. Liver transplantation does not correct the constitutional deficiency of FECH. Consequently, there is a risk of recurrence of liver disease after liver transplantation as a result of continuing overproduction of protoporphyrin. Some authors recommend that bone marrow transplantation should be considered in liver allograft recipients to prevent recurrence of hepatic disease.

Background: The efficacy of combination therapy with peginterferon plus ribavirin to eradicate viral infection in patients with chronic hepatitis C (CHC) is well established; moreover, it is able to arrest or even reverse liver fibrosis., Aims: To analyze the measurements of hepatic stiffness as an index of liver fibrosis using transient elastography (TE) in patients who underwent a sustained virological response (SVR) during long-term follow-up; comparing the changes in the severity of fibrosis with non-responders patients., Material and Methods: After hepatic fibrosis was studied in three patients with CHC who underwent a SVR during long-term follow up, a prospective study was initiated in 24 patients with CHC who received combination therapy to compare the evolution of fibrosis in those with SVR and those who were non-responders. The genotype of hepatitis C virus (HCV) and the degree of viremia were determined. METAVIR scoring system was used for liver fibrosis. Hepatic stiffness was measured by TE., Results: Of the initial three patients pre-treatment liver biopsies revealed active disease and fibrosis (stage 3) in two and mild fibrosis (stage 1) in one. After several years of follow up serum AST/ALT levels were normal and HCV RNA was undetectable in each case; in contrast to the baseline histological assessments of fibrosis, values for hepatic stiffness (3.4-6.9 KPa) were compatible with an absence of any appreciable hepatic fibrosis. In the prospective study, 8 patients underwent a SVR and 16 were non-responders. TE indicated that the severity of hepatic fibrosis in the SVR group improved in 7 (88%) patients, whereas in the non-responder it improved in only 4 (25%) (p < 0.05). The difference between development of severe fibrosis (F > or = 3) in responders and non-responders was not significant (p = 0.23), possibly due to the small sample size., Conclusions: Regression of hepatic fibrosis appears to be common in patients with CHC who undergo a SVR. TE is a simple non-invasive technique that enables multiple assessments of the severity of hepatic fibrosis to be made efficiently during long-term follow-up of patients with CHC who receive combination antiviral therapy.

Recently, new information relating to the potential relevance of chronic hepatic inflammation to the development and progression of hepatocellular carcinoma (HCC) has been generated. Persistent hepatocellular injury alters the homeostatic balance within the liver; deregulation of the expression of factors involved in wound healing may lead to the evolution of dysplastic lesions into transformed nodules. Progression of such nodules depends directly on the development and organization of a vascular network, which provides the nutritional and oxygen requirements to an expanding nodular mass. Angiogenic stimulation promotes intense structural and functional changes in liver architecture and physiology, in particular, it facilitates transformation of dysplasia to nodular lesions with carcinogenic potential. HCC depends on the growth and spreading of vessels throughout the tumor. Because these vascular phenomena correlate with disease progression and prognosis, therapeutic strategies are being developed that focus on precluding vascular expansion in these tumors. Accordingly, an in-depth study of factors that promote and support pathological angiogenesis in chronic hepatic diseases may provide insights into methods of preventing the development of HCC and/or stimulating the regression of established HCC.

Background: Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. Unresectable disease patients have median survival of few months. There is a substantial need for novel treatments for patients with advanced HCC., Aim: To provide an update review of mechanism of hepatocarcinigenesis and systemic therapies for HCC and the relevant role of Sorafenib in patients with advanced disease., Methods: A Medline search was performed to identify pertinent original research and review articles. Selected references in these articles were also evaluated., Results: Systemic chemotherapy for HCC has been quite ineffective. Preclinical studies demonstrated that Raf/MAPK-ERK kinase (MEK)/Extracellular signal regulated kinase (ERK) pathway has a role in HCC. HCC tumours are highly vascularized and vascular endothelial growth factor (VEGF) augments HCC development and metastasis. Sorafenib blocks tumour cell proliferation by targeting Raf/MEK/ERK signalling and exerts an antiangiogenic effect by targeting VEGF receptors-2/3 and platelet derived growth factor receptor beta tyrosine kinases., Conclusions: Currently available therapies are not effective for patients with advanced HCC. Sorafenib has demonstrated for the first time to prolong survival in patients with advanced HCC, and it is the new reference standard for systemic treatment in these patients.