Outcomes and factors associated with relapse of vaccine-induced liver injury after SARS CoV-2 immunization: A nationwide study.

INTRODUCTION AND OBJECTIVES: Different patterns of liver injury have been reported in association with the SARS-CoV-2 vaccines. The aim of this study was to describe a nationwide cohort of patients with SARS CoV-2 vaccine-induced liver injury, focusing on treatment and the evolution after further booster administration. PATIENTS AND METHODS: multicentre, retrospective-prospective study, including subjects who developed abnormal liver tests within 90 days after administration of SARS-CoV-2 vaccination. RESULTS: 47 cases were collected: 17 after prime dose and 30 after booster. Age was 57 years, 30 (63.8 %) were female, and 7 (14.9 %) had a history of prior autoimmune hepatitis (AIH). Most cases were non-severe, though 9 (19.1 %) developed acute liver injury or failure (ALF). Liver injury tended to be more severe in those presenting after a booster (p=0.084). Pattern of liver injury was hepatocellular (80.9 %), mixed (12.8 %) and 3 (6.4 %) cholestatic. Liver biopsy was performed on 33 patients; 29 showed findings of AIH. Forty-one (87.2 %) patients received immunosuppressants, mostly corticosteroids (35/41). One required liver transplantation and another died due to ALF. Immunosuppression was discontinued in 6/41 patients without later rebound. Twenty-five subjects received at least one booster and 7 (28.0 %) relapsed from the liver injury, but all were non-severe. Recurrence was less frequent among patients on immunosuppressants at booster administration (28.6 % vs. 88.9 %, p=0.007). CONCLUSIONS: SARS CoV-2 vaccine-induced liver injury is heterogeneous but mostly immune-mediated. Relapse of liver injury after re-exposure to vaccine is frequent (28.0 %) but mild. Immunosuppression at booster administration is associated with a lower risk of liver injury.

Prognostic Value of Transient Elastography in Human Immunodeficiency Virus-Infected Patients With Chronic Hepatitis C.

BACKGROUND: Our objective was to study the prognostic value of liver stiffness (LS) in HIV-infected patients with chronic hepatitis C (CHC). METHODS: We analyzed HIV-infected patients with compensated CHC and at least 1 determination of LS. The primary outcome was the occurrence of liver-related events (LRE), namely, decompensation or hepatocellular carcinoma, whichever occurred first. We selected patients without sustained viral response (SVR) or end-of-treatment response (ETR) during follow-up and allocated them to an estimation cohort (EC) and a validation cohort (VC). RESULTS: The study population comprised 1292 patients. After a median follow-up of 5.8 years, 90 patients experienced LRE and 73 died. In the subgroup of 957 patients without SVR or ETR, the area under the receiver operating characteristic curves (AUROCs) (95% confidence interval [CI]) of LS for prediction of LRE in the EC (n = 634) and the VC (n = 323) were 0.87 and 0.88, respectively. The best cutoff value of LS to rule out LRE in the EC was 12 kPa, with a negative predictive value of 98.3% in the EC and 98.2% in the VC. Per each 1 kPa and 5 kPa increase above 12 kPa, the hazard ratio of LRE (taking into account death as a competing risk) was 1.07 (95% CI, 1.05-1.08) and 1.38 (95% CI, 1.31-1.46), respectively. CONCLUSIONS: Liver stiffness is very accurate for predicting LRE in coinfected patients. Patients with an LS <12 kPa had a 98% probability of not developing LRE after a median follow-up of almost 6 years. Above the 12-kPa cutoff, the hazard of LRE increases proportionally with LS.

[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.

Serum cystatin C: a non-invasive marker of liver fibrosis or of current liver fibrogenesis in chronic hepatitis C? .

BACKGROUND: Serum levels of cystatin C, an endogenous inhibitor of cysteine proteases, provide an alternative method to creatinine-based criteria for measuring glomerular filtration rate. Preliminary data suggested that serum cystatin C levels parallel with the stage of liver fibrosis in chronic liver disorders. Our aim has been to evaluate the possible role of serum cystatin C as a marker of liver fibrosis in hepatitis C virus (HCV)-induced chronic liver disease. MATERIAL AND METHODS: 100 consecutive patients (56 men, mean age 51.2 ± 9.5 yrs) with HCV-induced chronic liver disease, scheduled for their first liver biopsy and naïve for antiviral therapy were included. Liver fibrosis was evaluated with the METAVIR score. Serum cystatin C and standard laboratory tests were measured simultaneously. Patients with ethanol abuse (> 50 g/day), HBV or HIV coinfection or plasma creatinine ≥ 1.20 mg/dL were excluded. In addition, a second group of 16 patients fulfilling the same requisites and diagnosed with HCV-induced compensated cirrhosis by clinical evidence of portal hypertension was included. RESULTS: Serum cystatin C levels significantly increase from F0 to F2 fibrosis stages, remained stable in F3 and F4 stages and increased again in the group of non-biopsied compensated cirrhosis. Serum cystatin C levels were higher in patients with moderate-advanced necroinflammation in the liver biopsy. CONCLUSION: Serum cystatin C level may reflect current fibrogenic and necroinflammatory activities in chronic HCV-induced liver disease with normal renal function but can not be considered as a non-invasive marker of liver fibrosis.

Relation of IL28B gene polymorphism with biochemical and histological features in hepatitis C virus-induced liver disease.

BACKGROUND/AIMS: Polymorphism at the IL28B gene may modify the course of hepatitis C virus (HCV) chronic infection. Our aim was to study the influence of IL28B rs12979860 gene polymorphism on the biochemistry and pathology of HCV-induced disease in the clinical course from mild chronic hepatitis C to hepatocellular carcinoma. METHODS: We have determined the rs12979860 single nucleotide polymorphism (SNP) upstream IL28B gene in two groups of patients with HCV-induced chronic liver disease: 1) 268 patients (159 men) with biopsy-proven chronic hepatitis C, to analyse its relation with biochemical, virological and histological features; and 2) 134 patients (97 men) with HCV-related hepatocellular carcinoma. The distribution of the analysed SNP in hepatocellular carcinoma patients was compared with that found in untreated chronic hepatitis C patients. All patients were white and most were Spaniards. RESULTS: In multivariate analysis ALT values were higher (P = 0.001) and GGT values were lower (P<0.001) in chronic hepatitis C patients homozygotes for the major rs12979860C allele as compared with carriers of the mutated rs12979860T allele. Steatosis was more frequent (Odds ratio = 1.764, 95% C.I. 1.053-2.955) and severe (P = 0.026) in carriers of the rs12979860T allele. No relation was found between the analysed SNP and METAVIR scores for necroinflammation and fibrosis, and there were no differences in the distribution of the analysed SNP between hepatocellular carcinoma and untreated chronic hepatitis C patients. CONCLUSION: The IL28B rs12979860 polymorphism correlates with the biochemical activity and the presence and severity of liver steatosis in chronic hepatitis C.

Dispensación de preparados fitoterápicos en farmacias comunitarias de Sevilla / Dispensation of herbal products in community pharmacies in Sevilla

Los preparados a base de plantas medicinales desempeñan un papel importante en Atención Primeria de Salud. La población consciente de esta función, dirige su interés hacie el consumo de preparados fitoterápicos para la prevención y tratamiento de us enfermedades. LA transposición de la normativa europea de estos medicamentos por la AEMPS y el interés de los profesionales sanitarios por mejorar la calidad asistencial, nos dirigió a analizar la dispensación de estos fitopreparados en las farmacias comunitarias de Sevilla. Se realizó un estudio descriptivo observacional, basado en la aplicación de un cuestionario a los pacientes. Los resultados obtenidos manifiestan la necesidad de formación de los profesionales de salud en Fitoterapia, para que prevalezca la prescripción y el consejo profesional frente a la automedicación. Por otra parte, el conocimiento actualizado y la dispensación protocolizada de los preparados fitoterápicos beneficiaría a los pacientes con tratamientos asociados a otros fármacos y favorecería la detección de interacciones medicamentosas negativas (AU)

Herbal medicinal products play a major role in Primary Health Care. The population is aware of this role and is interested in the use of herbal products for the prevention and treatment of diseases. The transposition of European directive on these drugs by the Spanish Medicines Agency (AEMPS) and the interest of health professionals to improve the quality of care, led us to analyze the dispensation of herbal products in the community pharmacies of Seville. We performed a descriptive observational study, based on a questionnaire to patients. The results show the need for training health professionals in Phytotherapy, to encourage prescription and professional advice instead of self-medication. Moreover, the updating knowledge and the protocolised dispensation of herbal preparations benefit patients being already treated with other drugs, and enable the detection of adverse drug interactions (AU)

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.