TRPM5 rs886277 Polymorphism Predicts Hepatic Fibrosis Progression in Non-Cirrhotic HCV-Infected Patients.

BACKGROUND: TRPM5 (transient receptor potential cation channel subfamily M member 5) rs886277 polymorphism has been related to liver cirrhosis from different etiologies. The present study investigates the association of TRPM5 rs886277 polymorphism with liver fibrosis progression and cirrhosis development in chronic hepatitis C (CHC) patients. METHODS: We conducted a retrospective study of 208 non-cirrhotic patients with CHC, who had at least two liver stiffness measurements (LSM) with a separation of 12 months (baseline LSM (LSM1) and the last LSM (LSM2)). Two outcome variables were considered: (1) LSM2/LSM1 ratio; (2) cirrhosis progression (F4; LSM ≥ 12.5 kPa). DNA genotyping was done at the CeGen using a MassARRAY platform. RESULTS: The follow-up time was similar irrespective of the rs886277 genotype (46.4 months in TT genotype, 46.4 months in CT genotype, and 49.2 months in CC genotype; p = 0.649). The highest LSM increases were found in patients with CC genotype compared with TT and CT genotypes (p = 0.044 and p = 0.038, respectively). The cirrhosis progression was higher in patients with CC genotype than TT genotype (p = 0.033). Thus, the rs886277 C allele was associated with higher cirrhosis progression (adjusted odds ratio (aOR) = 2.64; p = 0.014). Moreover, rs886277 CC genotype was also related to higher values of LSM2/LSM1 ratio (adjusted arithmetic mean ratio a(AMR) = 1.31; p = 0.001) and cirrhosis progression (aOR = 4.33; p = 0.027). CONCLUSIONS: TRPM5 rs886277 polymorphism was associated with liver fibrosis progression and cirrhosis development among hepatitis C virus (HCV)-infected patients. Specifically, the rs886277 C allele and CC genotype were risk factors for advancing liver fibrosis and cirrhosis compared to the rs886277 T allele and CT/TT genotype, respectively.

MTHFR rs1801133 Polymorphism Is Associated With Liver Fibrosis Progression in Chronic Hepatitis C: A Retrospective Study.

Background: The MTHFR (methylenetetrahydrofolate reductase) rs1801133 polymorphism leads to higher circulating levels of homocysteine, which is related to several liver diseases. We aimed to evaluate the relationship between MTHFR rs1801133 polymorphism and liver fibrosis progression in HCV-infected patients. Methods: We conducted a preliminary retrospective cohort study in 208 non-cirrhotic HCV-infected patients. These subjects had at least two liver stiffness measurements (LSM), which were assessed using transient elastography, and no patient had cirrhosis at baseline. We analyzed the association between MTHFR rs1801133 and outcome variables using Generalized Linear Models. Results: HCV-infected patients were 47 years old, around 54% were males, a low frequency of high alcohol intake (13.5%) or prior use of intravenous drugs (10.1%). A total of 26 patients developed cirrhosis (LSM1 ≥ 12.5) during a median follow-up of 46.6 months. The presence of the rs1801133 C allele showed an inverse association with the LSM2/LSM1 ratio (adjusted AMR = 0.90; 95%CI = 0.83-0.98; p = 0.020) and the cirrhosis progression (adjusted OR = 0.43; 95%CI = 0.19-0.95; p = 0.038). Besides, rs1801133 CT/CC genotype had an inverse association with the LSM2/LSM1 ratio (adjusted AMR = 0.80; 95%CI = 0.68-0.95; p = 0.009) and the cirrhosis progression (adjusted OR= 0.21; 95%CI = 0.06-0.74; p = 0.015). Conclusions: MTHFR rs1801133 C allele carriers presented a diminished risk of liver fibrosis progression and development of cirrhosis than rs1801133 T allele carriers. This statement supports the hypothesis that MTHFR rs1801133 polymorphism appears to play a crucial role in chronic hepatitis C immunopathogenesis.

Características y supervivencia del carcinoma hepatocelular en hígado no cirrótico / Characteristics and survival of hepatocellular carcinoma in non-cirrhotic liver

Introducción: las características, cribado, y supervivencia del carcinoma hepatocelular (CHC) en pacientes sin cirrosis están menos definidas. Pacientes y métodos: se recogieron retrospectivamente (enero 2004-octubre 2018) los pacientes con CHC diagnosticados citohistológicamente sin cirrosis. Analizamos sus características, tratamiento y supervivencia. Resultados: de los 332 pacientes con CHC, 25 cumplían los criterios de inclusión (7,5%). Varones: 76%. Mediana de edad: 69,9 años. El virus de la hepatitis B (VHB) fue el principal agente etiológico de hepatopatía: 32%, seguido de la esteatohepatitis no alcohólica (EHNA): 20%. La fibrosis fue leve (0-1) en el 44%. El nódulo se descubrió por ecografía de seguimiento en el 32%, en el 60% fue casual, y 8% por síntomas. El estadio de Barcelona Clinic Liver Cancer (BCLC) fue 0 en 4%, A 88%, B 4%, y C 4%. El tratamiento inicial mayoritario fue la resección quirúrgica (76%), 8% rechazaron tratamiento, y se realizó etanolización, quimioembolización, sorafenib y tratamiento sintomático en el 4% para cada uno. El 21% de los pacientes operados presentó complicaciones, la mitad severas. La mediana de seguimiento fue 22,2 (2,9-150,6) meses, con remisión en el 56%. Mediana de supervivencia global: 57,4 +/- 29,8 meses. Supervivencia acumulada: 84% al año, 61,6% a los 3 años y 47,9% a los 5 años. Conclusión: el 7,5% de los CHC se desarrollaron sin cirrosis. El grado de fibrosis fue leve en casi la mitad. El VHB fue la causa principal, seguida de EHNA. El estadio de BCLC principal al diagnóstico fue el precoz. La cirugía fue el tratamiento más habitual. La supervivencia a los 5 años fue cercana al 50%

Introduction: the characteristics, screening, and survival of hepatocellular carcinoma (HCC) for patients without cirrhosis have not been fully studied. Methods: A retrospective cohort study was performed in non-cirrhotic patients with histological HCC, between January 2004 and October 2018. Their characteristics, treatment, follow-up and overall survival were described. Results: 25 of the 332 patients with HCC met the inclusion criteria (7.5%), 76% were males and the median age was 69.9 years. The main etiology of liver disease was the hepatitis B virus (HBV) (32%), followed by non-alcoholic steatohepatitis (NASH) (20%). Liver fibrosis was mild (0-1) in 44% of cases. The nodule was diagnosed by ultrasonography in 32% of cases, 60% were found incidentally and 8% due to clinical symptoms. The Barcelona Clinic Liver Cancer (BCLC) staging was 0 in 4% of cases, A in 88%, B in 4% and C in 4%. The main initial treatment was surgical resection (76%) and 8% refused to be treated. Percutaneous ethanol injection, chemoembolization, sorafenib and palliative care were each performed in 4% of cases. There were some complications in 21% of patients treated with surgery, half of them were severe. The median follow-up was 22.2 (2.9-150.6) months and 56% were in remission and the median overall survival was 57.4 +/- 29.8 months. The overall cumulative survival at 1, 3 and 5 years was 84%, 61.6% and 47.9%, respectively. Conclusion: 7.5% of HCC presented without cirrhosis and almost half of patients had mild fibrosis. HBV was the main cause of HCC, followed by NASH. The most frequent BCLC stage at diagnosis was early stage and surgery was the most common treatment. Overall cumulative survival at 5 years was almost 50%

Characteristics and survival of hepatocellular carcinoma in non-cirrhotic liver.

INTRODUCTION: the characteristics, screening, and survival of hepatocellular carcinoma (HCC) for patients without cirrhosis have not been fully studied. METHODS: A retrospective cohort study was performed in non-cirrhotic patients with histological HCC, between January 2004 and October 2018. Their characteristics, treatment, follow-up and overall survival were described. RESULTS: 25 of the 332 patients with HCC met the inclusion criteria (7.5%), 76% were males and the median age was 69.9 years. The main etiology of liver disease was the hepatitis B virus (HBV) (32%), followed by non-alcoholic steatohepatitis (NASH) (20%). Liver fibrosis was mild (0-1) in 44% of cases. The nodule was diagnosed by ultrasonography in 32% of cases, 60% were found incidentally and 8% due to clinical symptoms. The Barcelona Clinic Liver Cancer (BCLC) staging was 0 in 4% of cases, A in 88%, B in 4% and C in 4%. The main initial treatment was surgical resection (76%) and 8% refused to be treated. Percutaneous ethanol injection, chemoembolization, sorafenib and palliative care were each performed in 4% of cases. There were some complications in 21% of patients treated with surgery, half of them were severe. The median follow-up was 22.2 (2.9-150.6) months and 56% were in remission and the median overall survival was 57.4 ± 29.8 months. The overall cumulative survival at 1, 3 and 5 years was 84%, 61.6% and 47.9%, respectively. CONCLUSION: 7.5% of HCC presented without cirrhosis and almost half of patients had mild fibrosis. HBV was the main cause of HCC, followed by NASH. The most frequent BCLC stage at diagnosis was early stage and surgery was the most common treatment. Overall cumulative survival at 5 years was almost 50%.

Impact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study.

: The Duffy antigen receptor for chemokines (DARC) rs12075 polymorphism regulates leukocyte trafficking and proinflammatory chemokine homeostasis. Hepatitis C virus (HCV)-mediated liver fibrosis is associated with an uncontrolled inflammatory response. In this study, we evaluate the association between the DARC rs12075 polymorphism and liver stiffness progression in HCV-infected patients. We carried out a retrospective cohort study (repeated measures design) in 208 noncirrhotic patients with chronic hepatitis C (CHC) who had at least two liver stiffness measurements (LSM) with a separation of at least 12 months. We used generalized linear models to analyze the association between DARC rs12075 polymorphism and outcome variables. During a follow-up of 46.6 months, the percentage of patients with stages of fibrosis F0/F1 decreased (p < 0.001), while LSM values and the percentage of patients with cirrhosis increased (p < 0.001). This pattern of changes was maintained in each of the groups of patients analyzed according to their rs12075 genotypes (AA or AG/GG). However, the variations in liver stiffness characteristics were lower in patients with the rs12075 AG/GG genotype (AG/GG versus AA). Thereby, in the adjusted analysis, patients with the rs12075 AG/GG genotype had a lower risk of an increased value of LSM2/LSM1 arithmetic mean ratio (AMR = 0.83; p = 0.001) and of an increase in LSM ≥ 5 kPa (odds ratio (OR) = 0.28; p = 0.009). Besides, patients with rs12075 AG/GG had a lower risk of cirrhosis progression (OR = 0.24; p = 0.009). No significant associations were found for an increase in LSM ≥ 10 kPa. We found an association between the DARC rs12075 single nucleotide polymorphism (SNP) and CHC progression. Specifically, patients with the DARC rs12075 AG/GG genotype had a lower risk of liver fibrosis progression and development of cirrhosis.

The Myeloid-Epithelial-Reproductive Tyrosine Kinase (MERTK) rs4374383 Polymorphism Predicts Progression of Liver Fibrosis in Hepatitis C Virus-Infected Patients: A Longitudinal Study.

BACKGROUND: The myeloid-epithelial-reproductive tyrosine kinase (MERTK) is involved in hepatic steatosis, inflammation, and liver fibrosis. Here we evaluated the association between the MERTK rs4374383 single nucleotide polymorphism (SNP) and liver fibrosis progression in hepatitis C virus (HCV)-infected patients. METHODS: We performed a retrospective study (repeated measures design) in 208 patients who had liver stiffness measurement (LSM), which was assessed using transient elastography. No patient had cirrhosis at baseline (LSM ≥ 12.5 kPa). RESULTS: At baseline, 53.8% were male, the median age was 47.1 years, 13.5% reported a high intake of alcohol, 10.1% were prior injection drug users, 85.3% were infected with HCV genotype 1, and 22.6% had previously failed antiviral therapy (pegylated-interferon-alpha/ribavirin). During a median follow-up of 46.6 months, 26 patients developed cirrhosis. The rs4374383 G carriers had a higher risk of increasing LSM (adjusted arithmetic mean ratio (aAMR) = 1.14; p = 0.006) and a higher likelihood of having an increase in LSM greater than 5 kPa (ΔLSM ≥ 5 kPa) (adjusted odds ratio (aOR) = 2.37; p = 0.029), and greater than 7 kPa (ΔLSM ≥ 7 kPa) (aOR = 3.24; p = 0.032), after controlling for confounding. The SNP's association with cirrhosis progression was close to statistical significance (aOR = 2.18; p = 0.070). CONCLUSIONS: MERTK rs4374383 A carriers had a lower risk of liver fibrosis progression than G carriers, supporting the hypothesis that this SNP seems to have a critical role in the pathogenesis of liver disease in HCV-infected patients.

The IL7RA rs6897932 polymorphism is associated with progression of liver fibrosis in patients with chronic hepatitis C: Repeated measurements design.

The polymorphisms at the α-chain of the IL-7 receptor (IL7RA) have been related to T-cell homeostasis and development and may contribute to immune system deregulation. In the present study, we analyzed the association between IL7RA polymorphisms and the progression of liver fibrosis in patients infected with HCV. We carried out a retrospective study with a design consisting of repeated measurements in 187 HCV-infected patients, to study the risk prediction of liver fibrosis progression using genetic factors. We genotyped the rs6897932, rs987106 and rs3194051 IL7RA polymorphisms using the Agena Bioscience's MassARRAY. Transient elastography was used to measure liver stiffness. The used cut-offs were: <7.1 kPa (F0-F1), 7.1-9.4 kPa (F2; significant fibrosis), 9.5-12.4 kPa (F3; advanced fibrosis), and ≥12.5 kPa (F4; cirrhosis). All HCV genotypes were analyzed. The median of follow-up time was 47.9 months. Baseline liver stiffness measurement (LSM) values did not show significant statistical differences for IL7RA genotypes (p>0.05). In univariate analysis, the rs6897932 T allele had a positive relationship with an increase in LSM (arithmetic mean ratio (AMR) = 1.21 (95%CI = 1.08; 1.36); p = 0.001), progression to advanced fibrosis (F≥3) (odds ratio (OR) = 2.51 (95%CI = 1.29; 4.88); p = 0.006) and progression to cirrhosis (F4) (OR = 2.71 (95%CI = 0.94; 5.03); p = 0.069). In multivariable analysis, the rs6897932 T allele was related to a higher increase of LSM values during follow-up (adjusted AMR = 1.27 (95%CI = 1.13; 1.42); p<0.001) and higher odds of progression to advanced fibrosis [adjusted OR = 4.46 (95%CI = 1.87; 10.62); p = 0.001], and progression to cirrhosis [adjusted OR = 3.92 (95%CI = 1.30; 11.77); p = 0.015]. Regarding IL7RA rs987106 and rs3194051 polymorphisms, we did not find significant results except for the relationship between IL7RA rs987106 and the increase in LSM values [adjusted OR = 1.12 (95%CI = 1.02; 1.23); p = 0.015]. The IL7RA rs6897932 polymorphism seems to be related to increased risk of liver fibrosis progression in HCV-infected patients. Thus, the rs6897932 polymorphism could be related to the physiopathology of CHC and might be used to successfully stratify the risk of CHC progression.

PNPLA3 rs738409 polymorphism is associated with liver fibrosis progression in patients with chronic hepatitis C: A repeated measures study.

BACKGROUND: Host genetic background has been associated with liver fibrosis progression. OBJECTIVE: To analyze the association between the patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism and liver fibrosis progression in hepatitis C virus (HCV)-infected patients. STUDY DESIGN: In this retrospective cohort study, 187 patients with chronic HCV infection were included, who had at least two liver stiffness measurements (LSM) by transient elastography during the follow-up. Results were expressed in kilopascals (kPa). The analysis of genetic association was carried out according to additive model by using Generalized Linear Models. RESULTS: No patients had advanced fibrosis/cirrhosis at baseline. During a median follow-up time of 47.9 months, 15 patients developed advanced fibrosis and 17 cirrhosis. In multivariate analysis adjusted by the main clinical and epidemiological covariates, the rs738409 G allele was related to higher increase of LSM values during the follow-up (adjusted arithmetic mean ratio (aAMR) = 1.16 (95%CI = 1.04; 1.29); p = .006) and higher odds of having progression to advanced fibrosis [aOR = 2.03 (95%CI = 1.01; 4.06); p = .045], and progression to cirrhosis [aOR = 3.03 (95%CI = 1.26; 7.30); p = .014]. CONCLUSIONS: PNPLA3 rs738409 polymorphism appears to be related to the increased progression of liver fibrosis in HCV infected patients.

Infección crónica por virus de la hepatitis B antígeno e negativo. Manejo en función de puntos de corte de glutámico-pirúvica transaminasa y ácido desoxirribonucleico del virus de la hepatitis B / Hepatitis B virus e antigen-negative chronic infection. Treatment based on glutamic pyruvic transaminase and hepatitis B virus deoxyribonucleic acid cut-off values

Objetivos: Buscar puntos de corte de la glutámico-pirúvica transaminasa (GPT) y de ADN del virus de hepatitis B (ADN-VHB) al diagnóstico, en pacientes con infección crónica VHB antígeno e negativo (AgHBe(-)), que puedan ser predictores de la evolución, pronóstico y/o de la necesidad de terapia antiviral. Métodos: Estudio observacional de cohortes retrospectivo de pacientes diagnosticados de infección crónica por VHB AgHBe(-) (2005-2012). Se investigó un punto de corte de GPT normal al diagnóstico que predijera la alteración de esta en la evolución, de ADN-VHB basal que predijera la elevación de este por encima de 2.000UI/ml, y de GPT y ADN-VHB como predictores de la necesidad de tratamiento, mediante curvas ROC. Resultados: Se incluyeron 126 pacientes (seguimiento: 42,1±21,5meses), de los cuales 93 tenían GPT normal al diagnóstico. En el análisis de curvas ROC el punto de corte de ADN-VHB que mejor predijo la elevación de este por encima de 2.000UI/ml fue 900UI/ml (sensibilidad: 90%; especificidad: 88%; VPP: 79%; VPN: 100%; precisión diagnóstica: 89%), y el que mejor predijo la alteración de GPT normal al diagnóstico posteriormente elevada fue 25mU/ml (sensibilidad: 95,4%; especificidad: 81,6%; VPP: 67%; VPN: 96%; precisión diagnóstica: 80,6%). Los pacientes con GPT 26-40mU/ml al diagnóstico presentaron más complicaciones o necesidad de tratamiento que aquellos con GPT≤25mU/ml (p<0,05). La combinación de GPT y ADN-VHB que maximizó la necesidad de tratamiento fue 38mU/ml de GPT y 6.000UI/ml de ADN-VHB (sensibilidad: 75%; especificidad: 93,4%; VVP: 60%; VPN: 96,6%). Conclusión: Los pacientes VHB AgHBe(-) con GPT<25mU/ml y ADN-VHB<9.000UI/ml al diagnóstico presentan buena evolución y podrían no requerir un seguimiento tan estrecho en los primeros años desde el diagnóstico (AU)

Objectives: To identify glutamic pyruvic transaminase (GPT) and hepatitis B virus DNA (HBV-DNA) cut-off values at diagnosis in patients with hepatitis B virus e antigen-negative chronic infection (HBeAg(-)), which may be predictors of clinical course, prognosis and/or the need for antiviral therapy. Methods: A retrospective and observational cohort study of patients diagnosed with HBeAg(-) chronic infection (2005-2012). A normal GPT cut-off value at diagnosis that predicts abnormal GPT values in the clinical course of the infection, a baseline HBV-DNA cut-off value that predicts an increase in HBV-DNA above 2,000IU/ml, and GPT and HBV-DNA as predictors of the need for treatment were investigated using ROC curves. Results: 126 patients were enrolled (follow-up: 42.1±21.5months), 93 of which had normal GPT levels at diagnosis. In the ROC curve analysis, 900IU/ml was found to be the HBV-DNA cut-off value that best predicted this value's increase above 2,000IU/ml (sensitivity: 90%; specificity: 88%; PPV: 79%; NPV: 100%; diagnostic precision: 89%), while 25mU/ml was the normal GPT cut-off value at diagnosis that best predicted subsequently elevated GPT levels (sensitivity: 95.4%; specificity: 81.6%; PPV: 67%; NPV: 96%; diagnostic precision: 80.6%). Patients with GPT 26-40mU/ml at diagnosis presented with more complications or required more treatment than subjects with GPT≤25mU/ml (P<.05). The combined GPT and HBV-DNA values that elicited the highest treatment need were 38mU/ml of GPT and 6,000IU/ml of HBV-DNA (sensitivity: 75%; specificity: 93.4%; PPV: 60%; NPV: 96.6%). Conclusion: HBeAg(-) patients with GPT<25mU/ml and HBV-DNA<900IU/ml at diagnosis have positive outcomes and may not require such stringent follow-up in the first years after diagnosis (AU)

Hepatitis B virus e antigen-negative chronic infection. Treatment based on glutamic pyruvic transaminase and hepatitis B virus deoxyribonucleic acid cut-off values. / Infección crónica por virus de la hepatitis B antígeno e negativo. Manejo en función de puntos de corte de glutámico-pirúvica transaminasa y ácido desoxirribonucleico del virus de la hepatitis B.

OBJECTIVES: To identify glutamic pyruvic transaminase (GPT) and hepatitis B virus DNA (HBV-DNA) cut-off values at diagnosis in patients with hepatitis B virus e antigen-negative chronic infection (HBeAg(-)), which may be predictors of clinical course, prognosis and/or the need for antiviral therapy. METHODS: A retrospective and observational cohort study of patients diagnosed with HBeAg(-) chronic infection (2005-2012). A normal GPT cut-off value at diagnosis that predicts abnormal GPT values in the clinical course of the infection, a baseline HBV-DNA cut-off value that predicts an increase in HBV-DNA above 2,000IU/ml, and GPT and HBV-DNA as predictors of the need for treatment were investigated using ROC curves. RESULTS: 126 patients were enrolled (follow-up: 42.1±21.5months), 93 of which had normal GPT levels at diagnosis. In the ROC curve analysis, 900IU/ml was found to be the HBV-DNA cut-off value that best predicted this value's increase above 2,000IU/ml (sensitivity: 90%; specificity: 88%; PPV: 79%; NPV: 100%; diagnostic precision: 89%), while 25mU/ml was the normal GPT cut-off value at diagnosis that best predicted subsequently elevated GPT levels (sensitivity: 95.4%; specificity: 81.6%; PPV: 67%; NPV: 96%; diagnostic precision: 80.6%). Patients with GPT 26-40mU/ml at diagnosis presented with more complications or required more treatment than subjects with GPT≤25mU/ml (P<.05). The combined GPT and HBV-DNA values that elicited the highest treatment need were 38mU/ml of GPT and 6,000IU/ml of HBV-DNA (sensitivity: 75%; specificity: 93.4%; PPV: 60%; NPV: 96.6%). CONCLUSION: HBeAg(-) patients with GPT<25mU/ml and HBV-DNA<900IU/ml at diagnosis have positive outcomes and may not require such stringent follow-up in the first years after diagnosis.

Liver stiffness measurement predicts liver-related events in patients with chronic hepatitis C: A retrospective study.

The management of patients with chronic hepatitis C (CHC) depends on their clinical stage. Thus, noninvasive early recognition of patients with CHC at high risk for developing liver-related events (LREs) is important because it ensures optimal preventative management strategies may be employed that can affect the course of CHC disease. Our aim was to determine whether liver stiffness measurement (LSM) in hepatitis C virus (HCV)-infected patients is associated with a risk of LREs, particularly in cirrhotic patients. We carried out a retrospective study on 343 HCV-infected patients stratified according to cirrhosis (LSM<12.5 kPa vs. LSM≥12.5 kPa), and the cirrhotic patient group (LSM≥12.5 kPa) was divided according to risk of esophageal varices (LSM <25 kPa vs. LSM≥25 kPa). For all patients, each incremental unit in the natural logarithm (Ln) of LSM was associated with 14.76 times higher risk of developing LREs (p<0.001). Patients with cirrhosis (LSM≥12.5 kPa) had a higher risk of LREs than patients without cirrhosis (LSM<12.5 kPa) [adjusted hazard ratio (aHR) = 30.97; p<0.001]. When only cirrhotic patients were analyzed (n = 60), each incremental unit in the Ln of LSM was associated with 10.56 times higher risk of developing LREs (p = 0.010). Patients with LSM≥25 kPa had a greater risk for LRE development compared to those with LSM<25 kPa (aHR = 3.65; p = 0.045). The AUROC for predicting the onset of LREs was 0.876 in all patients and 0.729 in cirrhotic patients. In conclusion, LSM was associated with an increased risk of developing LREs in HCV-infected patients, even within the group of cirrhotic patients.

CXCL9-11 polymorphisms are associated with liver fibrosis in patients with chronic hepatitis C: a cross-sectional study.

BACKGROUND AND AIMS: CXCL9-11 polymorphisms are related to various infectious diseases, including hepatitis C virus (HCV) infection. In this study, we analyzed the association between CXCL9-11 polymorphisms and liver fibrosis in HCV-infected patients. METHODS: We performed a cross-sectional study in 389 patients who were genotyped for CXCL9-11 polymorphisms (CXCL9 rs10336, CXCL10 rs3921, and CXCL11 rs4619915) using the Sequenom's MassARRAY platform. The primary outcome variable was the liver stiffness measurement (LSM). We established three cut-offs of LSM: LSM ≥ 7.1 kPa (F ≥ 2-significant fibrosis), LSM ≥ 9.5 kPa (F ≥ 3-advanced fibrosis), and LSM ≥ 12.5 kPa (F4-cirrhosis). RESULTS: Recessive, overdominant and codominant models of inheritance showed significant values, but the overdominant model was the best fitting our data. In this case, CXCL9 rs10336 AG, CXCL10 rs3921 CG and CXCL11 rs4619915 AG were mainly associated with lower values of LSM [(adjusted GMR (aGMR) = 0.85 (p = 0.005), aGMR = 0.84 (p = 0.003), and aGMR = 0.84 (p = 0.003), respectively]. Patients with CXCL9 rs10336 AG genotype had lower odds of significant fibrosis (LSM ≥ 7.1 kPa) [adjusted OR (aOR) = 0.59 (p = 0.016)], advanced fibrosis (LSM ≥ 9.5 kPa) [aOR = 0.54 (p = 0.010)], and cirrhosis (LSM ≥ 12.5 kPa) [aOR = 0.56 (p = 0.043)]. Patients with CXCL10 rs3921 CG or CXCL11 rs4619915 AG genotypes had lower odds of significant fibrosis (LSM ≥ 7.1 kPa) [adjusted OR (aOR) = 0.56 (p = 0.008)], advanced fibrosis (LSM ≥ 9.5 kPa) [aOR = 0.55 (p = 0.013)], and cirrhosis (LSM ≥ 12.5 kPa) [aOR = 0.57 (p = 0.051)]. Additionally, CXCL9-11 polymorphisms were related to lower liver stiffness under a codominant model of inheritance, being the heterozygous genotypes also protective against hepatic fibrosis. In the recessive inheritance model, the CXCL9 rs10336 AA, CXCL10 rs3921 CC and CXCL11 rs4619915 AA were associated with higher LSM values [(adjusted GMR (aGMR) = 1.19 (p = 0.030), aGMR = 1.21 (p = 0.023), and aGMR = 1.21 (p = 0.023), respectively]. Moreover, patients with CXCL9 rs10336 AA genotype had higher odds of significant fibrosis (LSM ≥ 7.1 kPa) [adjusted OR (aOR) = 1.83 (p = 0.044)] and advanced fibrosis (LSM ≥ 9.5 kPa) [aOR = 1.85 (p = 0.045)]. Furthermore, patients with CXCL10 rs3921 CC or CXCL11 rs4619915 AA genotypes had higher odds of advanced fibrosis (LSM ≥ 9.5 kPa) [aOR = 1.89 (p = 0.038)]. CONCLUSIONS: CXCL9-11 polymorphisms were related to likelihood of having liver fibrosis in HCV-infected patients. Our data suggest that CXCL9-11 polymorphisms may play a significant role against the progression of CHC and could help prioritize antiviral therapy.

Características y evolución de la infección crónica por virus de la hepatitis B antígeno e negativo / Characteristics and course of chronic hepatitis B e antigen-negative infection

OBJETIVO: Describir las características epidemiológicas, analíticas, histológicas y evolutivas de pacientes con infección crónica por VHB AgHBe-negativo. MATERIAL Y MÉTODOS: Estudio observacional de cohorte retrospectivo de pacientes diagnosticados de infección crónica VHB AgHBe-negativo (2005-2012) sin otras hepatopatías. RESULTADOS: Se incluyeron 138 pacientes con edad media de 40,5 ± 12,2 años, de los cuales el 54% eran mujeres. El 38% eran extranjeros, con incremento de estos en los últimos años (p < 0,001). Las transaminasas en el momento del diagnóstico eran normales en casi el 75% y el ADN-VHB < 2.000 UI/ml en el 56%. En los portadores inactivos existe una disminución progresiva de los niveles de ADN-VHB en el periodo de estudio. En el 47% se evaluó la fibrosis hepática por Fibroscan ® o biopsia hepática: el 55,4% resultó normal y el 6,1% reportó cirrosis. El 77,77% eran portadores inactivos. Precisaron tratamiento el 15,5% (20% por cirrosis y 80% por HBC AgHBe-negativo). Aclararon el AgHBs 5 pacientes (tasa anual 0,94%), presentando todos al diagnóstico ADN-VHB < 2.000 UI/ml. Cinco pacientes desarrollaron alguna complicación (3,6%), 4 de ellos carcinoma hepatocelular (CHC) (solo 2 presentaban cirrosis). Hubo un fallecimiento relacionado con el VHB (0,72%). CONCLUSIÓN: Entre los enfermos con infección crónica por VHB AgHBe-negativo predominan los portadores inactivos. Se produce un progresivo descenso de ADN-VHB en los primeros años tras el diagnóstico. Desarrollan poca morbimortalidad, especialmente si existe GPT normal y ADN-VHB bajo al diagnóstico. Un número no despreciable de pacientes precisa tratamiento. El CHC es la complicación más frecuente, incluso en pacientes sin cirrosis

OBJECTIVE: To describe the epidemiological, analytical and histological characteristics and clinical course of hepatitis B virus (HBV) carriers with negative HBe antigen. MATERIAL AND METHODS: Observational, retrospective cohort study of HBV carriers with negative HBe antigen (2005-2012), with no other causes of liver disease. RESULTS: One hundred and thirty-eight patients were included, with mean age 40.5 ± 12.2 years; 54% were women, and 38% were of foreign origin; the number of foreign patients significantly increased (P < .001) over the years. Transaminases were normal in nearly 75% and HBV-DNA was < 2,000 IU/ml in 56% of patients at diagnosis. There was a gradual decrease in HBV-DNA levels in inactive carriers over the study period. Fibrosis study was performed in 47% of patients by Fibroscan ® or liver biopsy: 55.4% normal histology and 6.1% cirrhosis. Just over three quarters of patients (77.77%) were inactive carriers. Treatment was required in 15.5% of patients (20% because of cirrhosis and 80% HBeAg-negative chronic hepatitis B). Five patients cleared HBsAg (annual rate .94%), all of whom presented HBV-DNA <2,000IU/ml at diagnosis. Five patients developed complications (3.6%), 4 of them hepatocellular carcinoma (HCC), of which only 2 had cirrhosis. There was 1 HBV-related death (.72%). CONCLUSION: Among HBV carriers with negative HBe antigen, inactive HBs-Ag carriers are predominant. HBV-DNA gradually decreases in the first few years after diagnosis. Morbidity and mortality are low, especially if glutamic pyruvic transaminase (GPT) is normal and HBV-DNA levels are low at diagnosis. Treatment is needed in a considerable number of patients. HCC is the most frequent complication, even in the absence of cirrhosis

Characteristics and course of chronic hepatitis B e antigen-negative infection. / Características y evolución de la infección crónica por virus de la hepatitis B antígeno e negativo.

OBJECTIVE: To describe the epidemiological, analytical and histological characteristics and clinical course of hepatitis B virus (HBV) carriers with negative HBe antigen. MATERIAL AND METHODS: Observational, retrospective cohort study of HBV carriers with negative HBe antigen (2005-2012), with no other causes of liver disease. RESULTS: One hundred and thirty-eight patients were included, with mean age 40.5±12.2 years; 54% were women, and 38% were of foreign origin; the number of foreign patients significantly increased (P<.001) over the years. Transaminases were normal in nearly 75% and HBV-DNA was <2,000IU/ml in 56% of patients at diagnosis. There was a gradual decrease in HBV-DNA levels in inactive carriers over the study period. Fibrosis study was performed in 47% of patients by Fibroscan® or liver biopsy: 55.4% normal histology and 6.1% cirrhosis. Just over three quarters of patients (77.77%) were inactive carriers. Treatment was required in 15.5% of patients (20% because of cirrhosis and 80% HBeAg-negative chronic hepatitis B). Five patients cleared HBsAg (annual rate .94%), all of whom presented HBV-DNA <2,000IU/ml at diagnosis. Five patients developed complications (3.6%), 4 of them hepatocellular carcinoma (HCC), of which only 2 had cirrhosis. There was 1 HBV-related death (.72%). CONCLUSION: Among HBV carriers with negative HBe antigen, inactive HBs-Ag carriers are predominant. HBV-DNA gradually decreases in the first few years after diagnosis. Morbidity and mortality are low, especially if glutamic pyruvic transaminase (GPT) is normal and HBV-DNA levels are low at diagnosis. Treatment is needed in a considerable number of patients. HCC is the most frequent complication, even in the absence of cirrhosis.

Características de los pacientes con infección crónica por el virus de la hepatitis B. Análisis de una serie de 474 pacientes / Characteristics of patients with chronic hepatitis B virus infection. analysis of a series of 474 patients

Objetivo El objetivo de nuestro estudio fue conocer las características clínicas, analíticas, serológicas e histológicas de los portadores crónicos del virus de la hepatitis B en nuestra área. Material y métodos Se realizó un estudio de cohortes retrospectivo que incluyó pacientes mayores de 13 años portadores crónicos del AgHBs, valorados en nuestro servicio desde enero de 2000.ResultadosSe incluyeron 474 enfermos. Al diagnóstico el 55,49% fueron varones, con una edad media de 41,05±13,93 y GPT normal en el 57,17% de los casos, siendo el 87,76% AgHBe(−). Las coinfecciones VHC y VHD ocurrieron en el 3,62 y 1,86%, respectivamente. Se realizó biopsia hepática al 31,22%, presentando el 63,51% grados variables de inflamación-fibrosis, y el 12,84%, cirrosis. Los pacientes AgHBe(+) en comparación con los (−) fueron más jóvenes y presentaron mayor actividad de la enfermedad de forma estadísticamente significativa. Los pacientes en fase inmunotolerante fueron los más infrecuentes (5,26%), y los que presentaban HBC AgHBe(−) los (..) (AU)

Objective To determine the clinical, laboratory, serological and histologic characteristics of chronic hepatitis B virus carriers in our environment. Material and methods A retrospective cohort study was performed that included chronic AgHBs carriers aged more than 13 years attending our service since January 2000.ResultsA total of 474 patients were included. At diagnosis, 55.49% were men, with a mean age of 41.05±13.93 years. Alanine aminotransferase (ALT) levels were within the normal range in 57.17% of the patients, and 87.76% were AgHBe(−). Hepatitis C and D virus coinfection was found in 3.62% and 1.86%, respectively. Liver biopsy was performed in 31.22%; varying grades of inflammation-fibrosis were found in 63.51% and cirrhosis was found in 12.84%. Compared with AgHBe(−) patients, those who were AgHBe(+) were younger and had greater disease activity. This (..) (AU)

[Characteristics of patients with chronic hepatitis B virus infection. analysis of a series of 474 patients]. / Características de los pacientes con infección crónica por el virus de la hepatitis B. Análisis de una serie de 474 pacientes.

OBJECTIVE: To determine the clinical, laboratory, serological and histologic characteristics of chronic hepatitis B virus carriers in our environment. MATERIAL AND METHODS: A retrospective cohort study was performed that included chronic AgHBs carriers aged more than 13 years attending our service since January 2000. RESULTS: A total of 474 patients were included. At diagnosis, 55.49% were men, with a mean age of 41.05±13.93 years. Alanine aminotransferase (ALT) levels were within the normal range in 57.17% of the patients, and 87.76% were AgHBe(-). Hepatitis C and D virus coinfection was found in 3.62% and 1.86%, respectively. Liver biopsy was performed in 31.22%; varying grades of inflammation-fibrosis were found in 63.51% and cirrhosis was found in 12.84%. Compared with AgHBe(-) patients, those who were AgHBe(+) were younger and had greater disease activity. This difference was statistically significant. Patients in the immunotolerant phase were the least numerous (5.26%), while AgHBe(-) patients with chronic HBV infection were the most numerous (48.32%). Patients in the immunoreactive phase showed greater histological involvement (16.67% cirrhosis). A familial history of chronic HBV was found in 21.52%. The percentage of non-Spanish patients increased in the last few years and accounted for 18.78%. CONCLUSION: Chronic HBV infection in our environment occurs mainly in middle-aged persons. GPT values are normal in more than 50%, most are AgHBe(-), and approximately half are inactive carriers. The incidence of chronic infection has increased in the non-Spanish population in recent years.

Características clínicas, estadificación y tratamiento de los pacientes con carcinoma hepatocelular en la práctica clínica. Estudio prospectivo de una serie de 136 pacientes / Clinical characteristics, staging and treatment of patients with hepatocellular carcinoma in clinical practice. Prospective study of 136 patients

El carcinoma hepatocelular (CHC) es la causa más frecuente de muerte en pacientes cirróticos. No existen en España series prospectivas de un solo centro terciario sobre estos pacientes. Material y método Estudio prospectivo de pacientes diagnosticados de CHC. Se recogieron sus características clínicas y epidemiológicas, metodología diagnóstica, estadificación según el sistema de Barcelona Clinic Liver Cancer (BCLC) y tratamiento. Resultados Se incluyeron 136 pacientes. El 80,9% fueron varones. La edad media fue de 66,62 ± 11,68 años. El 91,2% eran cirróticos. En el 38,97% la etiología de la hepatopatía fue el virus de la hepatitis C (VHC). La sospecha diagnóstica se estableció mediante programa de cribado en un 63,2%. Los criterios no invasivos American Association for the Study of Liver Diseases (AASLD) fueron el principal método diagnóstico (73,5%). Se diagnosticaron en estadio precoz (0-A) el 58,1%, en B el 21,3%, en C el 12,5% y en D el 8,1%. Los pacientes en estadio precoz habían seguido una estrategia de cribado más frecuentemente que aquellos en estadio no precoz (79,75 versus 44,35%, p < 0,001). El 45,58% recibió un tratamiento inicial potencialmente curativo, siendo el más frecuente la inyección percutánea de alcohol (23,13%).ConclusionesLa mayoría de los pacientes con CHC en nuestro centro presentan una cirrosis hepática de base, cuya etiología más frecuente es el VHC. El cribado de los pacientes en riesgo permite diagnosticar un mayor número en estadio precoz, lo que se consigue en más de la mitad de los casos. El tratamiento inicial más empleado fue el percutáneo(AU)

Abstract Hepatocellular carcinoma (HCC) is the most frequent cause of mortality in patients with liver cirrhosis. There are no prospective series from a single tertiary hospital in Spain.Material and Methods We performed a prospective study of patients with HCC in our center. Clinical and epidemiological characteristics, diagnostic method, staging according to the Barcelona Clinic Liver Cancer (BCLC) system and treatment were analyzed.ResultsA total of 136 patients were included (80.9% men). The mean age was 66.62±11.68 years and 91.2% were cirrhotic. Hepatitis C virus (HCV) was the leading cause of liver disease (38.97%). The suspected diagnosis was established by a surveillance program in 63.2%. Noninvasive American Association criteria for the Study of Liver Diseases (AASLD) were the main diagnostic method (73.5%). According to the BCLC, 58.1% were in the early stage (0-A), 21.3% in stage B, 12.5% in stage C and 8.1% in stage D. Early stage patients had followed a surveillance program more frequently than those with non-early stages (79.75% versus 44.35%, p <0.001). Potentially curative initial treatment was used in 45.58%, the most common treatment being percutaneous ethanol injection (23.13%).ConclusionsMost patients with HCC in our hospital have cirrhosis, the most frequent cause being HCV. HCC surveillance in at-risk patients could increase diagnosis of HCC at an early stage. We achieved an early diagnosis in more than half of cases. The most common initial treatment was percutaneous th(AU)

Hallazgos endoscópicos y ecoendoscópicos en la linitis plástica rectal secundaria / Endoscopic and echoendoscopic findings in secondary linitis plastica of the rectum

La linitis plástica rectal es una infiltración tumoral intraparietal, subepitelial y circunferencial de la pared del recto que condiciona engrosamiento parietal y estenosis de la luz. Con frecuencia existe demora entre la aparición de los síntomas y el diagnóstico debido a que la linitis rectal simula un gran número de enfermedades y los hallazgos endoscópicos y las biopsias convencionales no son concluyentes, pues la mucosa en superficie suele no estar afectada. Presentamos los hallazgos endoscópicos y ecoendoscópicos de 2 pacientes con linitis rectal secundaria (AU)

Linitis plastica of the rectum consists of intraparietal, subepithelial and circumferential tumoral infiltration of the wall of the rectum leading to a constricted rectum with mural thickening. There is often a delay between symptom onset and diagnosis because this entity mimics a large number of diseases and the findings of endoscopy and conventional biopsies are non-conclusive since the surface mucosa is not usually affected. We present the endoscopic and echoendoscopic findings of two patients with secondary linitis plastica of the rectum (AU)

[Clinical characteristics, staging and treatment of patients with hepatocellular carcinoma in clinical practice. Prospective study of 136 patients]. / Características clínicas, estadificación y tratamiento de los pacientes con carcinoma hepatocelular en la práctica clínica. Estudio prospectivo de una serie de 136 pacientes.

UNLABELLED: Hepatocellular carcinoma (HCC) is the most frequent cause of mortality in patients with liver cirrhosis. There are no prospective series from a single tertiary hospital in Spain. MATERIAL AND METHODS: We performed a prospective study of patients with HCC in our center. Clinical and epidemiological characteristics, diagnostic method, staging according to the Barcelona Clinic Liver Cancer (BCLC) system and treatment were analyzed. RESULTS: A total of 136 patients were included (80.9% men). The mean age was 66.62 ± 11.68 years and 91.2% were cirrhotic. Hepatitis C virus (HCV) was the leading cause of liver disease (38.97%). The suspected diagnosis was established by a surveillance program in 63.2%. Noninvasive American Association criteria for the Study of Liver Diseases (AASLD) were the main diagnostic method (73.5%). According to the BCLC, 58.1% were in the early stage (0-A), 21.3% in stage B, 12.5% in stage C and 8.1% in stage D. Early stage patients had followed a surveillance program more frequently than those with non-early stages (79.75% versus 44.35%, p <0.001). Potentially curative initial treatment was used in 45.58%, the most common treatment being percutaneous ethanol injection (23.13%). CONCLUSIONS: Most patients with HCC in our hospital have cirrhosis, the most frequent cause being HCV. HCC surveillance in at-risk patients could increase diagnosis of HCC at an early stage. We achieved an early diagnosis in more than half of cases. The most common initial treatment was percutaneous therapy.

[Endoscopic and echoendoscopic findings in secondary linitis plastica of the rectum]. / Hallazgos endoscópicos y ecoendoscópicos en la linitis plástica rectal secundaria.

Linitis plastica of the rectum consists of intraparietal, subepithelial and circumferential tumoral infiltration of the wall of the rectum leading to a constricted rectum with mural thickening. There is often a delay between symptom onset and diagnosis because this entity mimics a large number of diseases and the findings of endoscopy and conventional biopsies are non-conclusive since the surface mucosa is not usually affected. We present the endoscopic and echoendoscopic findings of two patients with secondary linitis plastica of the rectum.