[Therapeutic update in hepatitis C]. / Actualización terapéutica en la hepatitis C.

Hepatitis C virus infection is a major health burden affecting 130-170 million people worldwide. Approximately 10-30% of those with chronic hepatitis C will progress to cirrhosis over 20-30 years. The development of new direct-acting antivirals has changed the management of the disease, allowing efficacious Interferon-free therapies superior to prior treatment regimens with minimal side effects, even in some subgroups previously thought to be difficult to cure such as cirrhotic patients.

Actualización terapéutica en la hepatitis C / Therapeutic update in hepatitis C

La infección por el virus de hepatitis C es un problema de salud que afecta a 130-170 millones de personas en todo el mundo. Aproximadamente un 10-30% de pacientes con hepatitis crónica C progresarán a cirrosis en 20-30 años. El desarrollo de nuevos agentes antivirales de acción directa ha cambiado el manejo de la enfermedad, permitiendo el tratamiento libre de Interferón con eficacia superior a los regímenes terapéuticos previos y mínimos efectos adversos, incluso en algunos subgrupos previamente considerados difíciles de curar como los pacientes cirróticos (AU)

Hepatitis C virus infection is a major health burden affecting 130-170 million people worldwide. Approximately 10-30% of those with chronic hepatitis C will progress to cirrhosis over 20-30 years. The development of new direct-acting antivirals has changed the management of the disease, allowing efficacious Interferon-free therapies superior to prior treatment regimens with minimal side effects, even in some subgroups previously thought to be difficult to cure such as cirrhotic patients (AU)

Vitamin D deficiency and vitamin D therapy in chronic hepatitis C.

BACKGROUND: Vitamin D has immunomodulatory properties, exerts an anti-hepatitis C virus (HCV) effect in vitro and improves response to interferon-based therapy in patients with chronic hepatitis C (CHC). Low serum levels of 25(OH) vitamin D [25(OH)D] are frequently found in CHC patients and seem to be related to more advanced stages of liver fibrosis. The study aims to establish the incidence of vitamin D deficiency in Spanish patients with CHC, its possible relation with features of liver damage and with the IL28B gene polymorphism, and the immediate effect of vitamin D therapy on CHC-related analytical variables. MATERIALS AND METHODS: Baseline serum 25(OH)D levels were measured in 108 consecutive CHC patients (60 men, age 54.3 ± 10.5 yrs). Results of transient elastography and of IL28B rs12979860C/T genotype were available in 89 and 95 patients, respectively. Forty one patients with insufficient levels of 25(OH)D received vitamin D supplements and were re-evaluated thereafter. RESULTS: Deficiency of vitamin D (< 20 µg/dL) and suboptimal levels (20-30 µg/mL) were detected in 36.1% and 40.9% of patients, respectively. No relationships were found between 25(OH)D levels and biochemical liver tests, fibrosis stage and IL28B genotype. Vitamin D therapy normalized 25(OH)D levels in all treated patients, but did not modify significantly HCV-RNA serum levels or biochemical tests. CONCLUSIONS: Vitamin D deficiency is common in Spanish patients with CHC but it is related neither to biochemical and virological variables nor with the fibrosis stage and IL28B polymorphism. Vitamin D therapy has no immediate effect on HCV-RNA serum levels.

Non-invasive evaluation of the fibrosis stage in chronic hepatitis C: a comparative analysis of nine scoring methods.

OBJECTIVE: Liver biopsy is an invasive procedure and new surrogate markers to assess fibrosis are needed. We performed a comparative external evaluation of nine non-invasive scores of liver fibrosis and tried to identify other potential biochemical markers of low-stage liver fibrosis in chronic hepatitis C (CHC). MATERIAL AND METHODS: We included 429 previously untreated consecutive patients from a single centre who underwent a liver biopsy between January 1999 and April 2009. Biopsies were evaluated for the stage of fibrosis according to the METAVIR scoring method. RESULTS: None of the evaluated scores were adequate to disclose null-low fibrosis due to a lack of specificity at the proposed cut-offs and the poor sensitivity of lower cut-offs. Serum ferritin and cholesterol values were found to be independently related to the fibrosis stage and their inclusion in the best performing scores at lower cut-off values (the APRI and King's scores) improved the sensitivity for null-low fibrosis by 8% with a specificity >or= 93%. CONCLUSIONS: Approximately 30% of patients with null-low fibrosis may be accurately identified by supplementing current scores with new independent variables (serum ferritin and cholesterol), thus obviating the need for a liver biopsy.

"12 weeks' stopping rule" in the treatment of genotype 1 chronic hepatitis C: two prognostic categories under the same label?

OBJECTIVE: The current guidelines recommend maintenance of combined therapy for hepatitis C virus (HCV) genotype-1 chronic hepatitis when HCV-RNA is undetectable or < or = 2 log10 of baseline after 12 weeks of therapy. The aim of this study was to investigate whether the probability of obtaining sustained viral (SVR) response is similar when HCV-RNA is undetectable or is present at < or = 2 log10 level after 12 weeks of therapy. MATERIAL AND METHODS: Retrospective analysis was carried out in 208 HCV genotype-1 chronic hepatitis patients treated with pegylated interferon and ribavirin with available data on HCV viral load after 12 weeks of therapy and definite data on the results of therapy. RESULTS: Seventy-six (68.5%) out of 111 patients with undetectable HCV-RNA and 4 (11.8%) out of 34 patients with HCV-RNA < or = 2 log10 from baseline at week 12 reached SVR (odds ratio 16.29, 95% CI 5.08-67.12; p < 0.001). Sixty-three patients did not meet any of these criteria and therapy was discontinued. CONCLUSIONS: The "12-week stopping rule" includes two different categories of responders considered candidates for maintained therapy, but the probability of obtaining SVR is very low in patients with HCV-RNA that is still detectable at this time of treatment. We suggest that, in these partial responders, the prolongation of therapy should be decided on an individual basis.

[Utility of liver biopsy in the etiologic diagnosis of biochemical liver abnormalities of unknown cause]. / Utilidad de la biopsia hepática en el diagnóstico etiológico de las alteraciones de la analítica hepática de causa incierta.

INTRODUCTION: To establish the diagnostic usefulness of liver biopsy (LB) and its influence on the therapeutic approach in patients with persistent abnormal liver tests of unknown cause. METHODS: The 1135 LB performed between January 1999 and January 2007 were retrospectively evaluated. Patients with a strongly suspected diagnosis were excluded. One hundred and twelve patients with chronic elevation of aminotransferases (103 patients), gamma-glutamyltransferase (GGT) (7 patients) and ferritin (2 patients) were included in the analysis. RESULTS: The most common diagnoses were normal liver (35 patients, group 1), minimal changes (15 patients, group 2), bland steatosis (23 patients, group 3), non-alcoholic steatohepatitis (NASH) (17 patients, group 4), and chronic hepatitis (eight patients, group 5). Three patients had tuberculosis of the liver and the remaining 11 had other diagnoses. Ferritinemia was the only parameter significantly lower in group 1 than in groups 2 (p = 0.038), 3 (p = 0.023), and 4 (p < 0.001). Transaminase levels lacked discriminatory value except in chronic hepatitis (p = 0.008). Alkaline phosphatase levels (p = 0.003) were lower in group 4 than in group 1. Triglyceride levels were higher in group 3 (p = 0.009) and group 4 (p = 0.008) than in group 1. Ultrasonography detected steatosis in 28 of the 40 patients with fatty liver (specificity = 0.94; sensitivity = 0.70). CONCLUSIONS: LB modified the therapeutic approach only in the three patients with hepatic tuberculosis. LB confirmed ultrasonographic findings of steatosis and differentiated bland steatosis from NASH, but did not influence the therapeutic approach. Most patients with normal findings on ultrasonography had normal or near-normal biopsies. The indication for LB should be individualized.

Utilidad de la biopsia hepática en el diagnóstico etiológico de las alteraciones de la analítica hepática de causa incierta / Utility of liver biopsy in the etiologic diagnosis of biochemical liver abnormalities of unknown cause

Introducción: Se discute la eficacia diagnóstica de la biopsia hepática (BH) y su influencia sobre la decisión terapéutica en sujetos con alteración persistente de la bioquímica hepática de causa desconocida. Métodos: Revisión de los 1.135 protocolos de BH realizadas desde el 1 de enero de 1999 hasta el 31 de enero de 2007. Se descartaron los casos con sospecha etiológica firme, y se seleccionó a 112 pacientes con elevación persistente de las transaminasas (103 casos), aislada de gammaglutamil-transpeptidasa (7 casos) e hiperferritinemia (2 casos). Resultados: Diagnósticos más frecuentes: normal (grupo 1, 35 casos), cambios mínimos (grupo 2, 15 casos), esteatosis simple (grupo 3, 23 casos), esteatohepatitis no alcohólica (EHNA) (grupo 4, 17 casos) y hepatitis crónica (grupo 5, 8 casos). Tres pacientes tenían tuberculosis y otros, 11 diagnósticos. La ferritina fue el único parámetro más bajo en el grupo 1 frente a los grupos 2 (p = 0,038), 3 (p = 0,023) y 4 (p < 0,001). Las transaminasas carecen de valor discriminativo salvo para la hepatitis crónica (p = 0,008). La fosfatasa alcalina (p = 0,003) era más baja en la EHNA que en el grupo con biopsia normal. Los triglicéridos estaban elevados en la esteatosis simple (p = 0,009) y en la EHNA (p = 0,008). La ecografía reveló la presencia de esteatosis en 28 de los 40 pacientes con infiltración grasa (especificidad de 0,94 y sensibilidad de 0,70). Conclusiones: La BH sólo modificó la actitud terapéutica en los 3 pacientes con tuberculosis. La BH confirma el diagnóstico ecográfico de infiltración grasa y diferencia esteatosis simple de EHNA, pero no modifica la actitud terapéutica. La mayoría de los sujetos con ecografía normal no tienen alteraciones significativas en la BH, cuya indicación debe ser individualizada

Introduction: To establish the diagnostic usefulness of liver biopsy (LB) and its influence on the therapeutic approach in patients with persistent abnormal liver tests of unknown cause. Methods: The 1135 LB performed between January 1999 and January 2007 were retrospectively evaluated. Patients with a strongly suspected diagnosis were excluded. One hundred and twelve patients with chronic elevation of aminotransferases (103 patients), gamma-glutamyltransferase (GGT) (7 patients) and ferritin (2 patients) were included in the analysis. Results: The most common diagnoses were normal liver (35 patients, group 1), minimal changes (15 patients, group 2), bland steatosis (23 patients, group 3), non-alcoholic steatohepatitis (NASH) (17 patients, group 4), and chronic hepatitis (eight patients, group 5). Three patients had tuberculosis of the liver and the remaining 11 had other diagnoses. Ferritinemia was the only parameter significantly lower in group 1 than in groups 2 (p = 0.038), 3 (p = 0.023), and 4 (p < 0.001). Transaminase levels lacked discriminatory value except in chronic hepatitis (p = 0.008). Alkaline phosphatase levels (p = 0.003) were lower in group 4 than in group 1. Triglyceride levels were higher in group 3 (p = 0.009) and group 4 (p = 0.008) than in group 1. Ultrasonography detected steatosis in 28 of the 40 patients with fatty liver (specificity = 0.94; sensitivity = 0.70). Conclusions: LB modified the therapeutic approach only in the three patients with hepatic tuberculosis. LB confirmed ultrasonographic findings of steatosis and differentiated bland steatosis from NASH, but did not influence the therapeutic approach. Most patients with normal findings on ultrasonography had normal or near-normal biopsies. The indication for LB should be individualized

Polymorphisms of the glutathione S-transferases mu-1 (GSTM1) and theta-1 (GSTT1) and the risk of advanced alcoholic liver disease.

OBJECTIVE: The aim of this study was to determine whether null genotypes for glutathione transferase mu-1 (GSTM1) and theta-1 (GSTT1) influence the risk of development of advanced alcoholic liver disease. MATERIAL AND METHODS: GSTM1 and GSTT1 genotypes were identified on DNA through multiple analysis with polymerase chain reaction in 153 subjects diagnosed with advanced alcoholic liver disease and in 241 healthy controls. RESULTS: The frequency of the GSTM1 null genotype was not different between patients and controls (36.6% versus 41.1%, non-significant). The GSTT1 null genotype was more frequently found in patients than in controls (32% versus 22%, odds ratio 1.67, 95% CI 1.03-2.71, p =0.027). Moreover, patients were more likely to be simultaneous carriers of both GSTM1 and GSTT1 null genotypes (odds ratio 4.30, 95% CI 1.89-9.97, p =0.0003). CONCLUSIONS: The GSTT1 null genotype is more frequent among patients with advanced alcoholic liver disease than in controls. The coincidence of this genotype with the GSTM1 null genotype is four times more likely in patients. We suggest that polymorphisms affecting the activity of the glutathione S-transferase isoforms M1 and T1 may be associated with the risk of developing chronic severe ethanol liver damage.