HCV eradication in recurrent hepatitis C after liver transplantation normalizes enhanced endothelial activation.

The increased risk of cardiovascular disease (CVD) conferred by hepatitis C virus (HCV) is especially relevant after liver transplantation (LT), but its mechanism is still not well defined. This study aimed to evaluate the influence of HCV eradication in inflammatory and endothelial activation markers after LT. We evaluated inflammatory (TNF-alfa, IL-6, IL-8, and MCP-1) and endothelial activation (E-selectin, ICAM-1, VCAM-1, and MMP-9) markers before and after eradication in 45 LT recipients with HCV infection (LT+/HCV+) and 44 non-transplanted HCV-infected patients (LT-/HCV+). We also considered an additional group of 40 LT recipients without HCV infection (LT+/HCV-). LT+/HCV+ patients presented a higher endothelial activation status before eradication compared with LT+/HCV- patients. However, levels of E-selectin, ICAM-1, VCAM-1, and MMP-9 were comparable between LT+/HCV+ and LT-/HCV+ patients before eradication. HCV eradication decreased ICAM-1 (5466.55 pg/ml vs. 3354.88 pg/ml, P < 0.001) and VCAM-1 (10456.52 pg/ml vs. 6658.85 pg/ml, P < 0.001) levels in LT+/HCV+ and LT-/HCV+ patients. Remarkably, HCV eradication restored levels of endothelial activation markers of LT+/HCV+ patients compared with that of LT+/HCV- patients. HCV plays a major role in endothelial dysfunction after LT. Furthermore, HCV eradication restores endothelial activation despite the exposure to immunosuppressive therapy.

Mild AST elevation as an early sign of COVID-19 severity in a multicenter Madrid cohort.

INTRODUCTION: liver enzyme elevation has been reported in SARS-CoV-2 disease (COVID-19) in heterogeneous cohorts, mainly from China. Comprehensive reports from other countries are needed. In this study, we dissect the pattern, evolution, and predictive value of such abnormalities in a cohort from Madrid, Spain. METHODS: a retrospective study with a prospective 14-day follow-up of 373 patients with confirmed COVID-19 in five Madrid hospitals, including 50 outpatients. A COVID-19 severe course was defined as the need for mechanical ventilation. RESULTS: a total of 33.1 % of hospitalized patients showed baseline AST elevation and 28.5 % showed ALT elevation, compared with 12 % and 8 % of outpatients (p ≤ 0.001). Baseline AST, ALT and GGT levels correlated with LDH and C-reactive protein (CRP) levels (r ≤ 0.598, p < 0.005). AST elevation was associated with other severity markers such as male sex, lymphopenia, and pneumonia on X-Ray (p < 0.05 for all). ALP and bilirubin levels were rarely increased. Patients with elevated baseline AST showed a progressive normalization of this enzyme and an increase in ALT and GGT levels. Patients with normal baseline AST showed a flattened evolution pattern with levels within the range. Patients with a severe course of COVID-19 more frequently showed elevated baseline AST than those with a milder evolution (54.2 % vs. 25.4 %, p < 0.001). Age, AST and CRP were independent risk factors for a severe course of COVID-19. CONCLUSION: mild liver enzyme elevation is associated with COVID-19 severity. Baseline AST is an independent predictor of severe COVID-19 course, and tends to normalize over time. ALT and GGT show a late elevation.

Tacrolimus as an Effective and Durable Second-Line Treatment for Chronic Autoimmune Hepatitis: A Multicentric Study.

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.

Long-term outcomes and clinical impact of anti-HLA donor-specific antibodies (DSA) after liver transplantation: a prospective study in a pilot cohort.

INTRODUCTION: the presence of donor-specific antibodies (DSA) is thought to affect survival of the allograft and patient after liver transplantation (LT). However, their significance is not well understood. PATIENTS AND METHODS: a prospective study was performed of 32 adult patients who underwent LT in 2011 to analyze the existence of DSA, associated risk factors and medium-term impact. Immunological determinations were performed immediately before LT and at three, six, 12 months and five years after LT. RESULTS: eight patients (24.2 %) presented pre-formed DSA. However, titers were negative in all patients five years after LT and there were no associated events. Eight out of 24 patients (33.3 %) developed de novo DSA. After five years, only two remained positive; both were class II with high mean fluorescence intensity (MFI) values at diagnosis (over 15,000). No association was found between the development of DSA and the risk of rejection, graft loss or death. However, an increase in liver stiffness values was observed in patients with persistent DSA, and focal sinusoidal deposition of C4d and moderate liver fibrosis were reported. CONCLUSION: the incidence of DSA is high after LT. In addition, the persistence of de novo DSA could be associated with silent liver fibrosis with a potential impact on graft outcomes.

Chronic Budd-Chiari syndrome in Behçet's disease successfully managed with transjugular intrahepatic portosystemic shunt: a case report and literature review.

Budd-Chiari syndrome (BCS) is characterized by an obstruction of hepatic venous outflow from small hepatic veins to inferior vena cava, caused by acute thrombosis or its fibrous sequellae. An underlying myeloproliferative neoplasm is present in 50% of cases. Clinical manifestations are widely variable, from asymptomatic to fulminant episodes. Long-term complications range from cirrhosis to hepatocellular carcinoma. Behçet's disease (BD) is a rare recurrent inflammatory multisystemic disorder characterized by recurrent skin-mucosa lesions and systemic involvement. Vascular involvement is observed in up to 40% of the patients with BD, and it is one of the major causes of mortality and morbidity. BCS is a rare complication of BD with a frequency of < 5% among patients with vascular involvement. Immunosuppressive treatment is the cornerstone for the management of vascular involvement in BD, while anticoagulant therapy has been an issue of debate. Transjugular intrahepatic portosystemic shunt (TIPS) in severe cases of BCS-of all causes- improves survival. However, there is scarce evidence about the role of TIPS in the setting of BCS in BD. We present a case of a vascular Behçet's disease associated with chronic Budd-Chiari syndrome with progression of thrombosis despite adequate anticoagulant and immunosuppressive treatment, successfully managed with TIPS.

Refractory hepatic encephalopathy in a patient with hypothyroidism: Another element in ammonia metabolism.

Hepatic encephalopathy (HE) remains a diagnosis of exclusion due to the lack of specific signs and symptoms. Refractory HE is an uncommon but serious condition that requires the search of hidden precipitating events (i.e., portosystemic shunt) and alternative diagnosis. Hypothyroidism shares clinical manifestations with HE and is usually considered within the differential diagnosis of HE. Here, we describe a patient with refractory HE who presented a large portosystemic shunt and post-ablative hypothyroidism. Her cognitive impairment, hyperammonaemia, electroencephalograph alterations, impaired neuropsychological performance, and magnetic resonance imaging and spectroscopy disturbances were highly suggestive of HE, paralleled the course of hypothyroidism and normalized after thyroid hormone replacement. There was no need for intervention over the portosystemic shunt. The case findings support that hypothyroidism may precipitate HE in cirrhotic patients by inducing hyperammonaemia and/or enhancing ammonia brain toxicity. This case led us to consider hypothyroidism not only in the differential diagnosis but also as a precipitating factor of HE.

Liver Transplantation for Hepatic Trauma: A Study From the European Liver Transplant Registry.

BACKGROUND: Liver transplantation is the most extreme form of surgical management of patients with hepatic trauma, with very limited literature data supporting its use. The aim of this study was to assess the results of liver transplantation for hepatic trauma. METHODS: This retrospective analysis based on European Liver Transplant Registry comprised data of 73 recipients of liver transplantation for hepatic trauma performed in 37 centers in the period between 1987 and 2013. Mortality and graft loss rates at 90 days were set as primary and secondary outcome measures, respectively. RESULTS: Mortality and graft loss rates at 90 days were 42.5% and 46.6%, respectively. Regarding general variables, cross-clamping without extracorporeal veno-venous bypass was the only independent risk factor for both mortality (P = 0.031) and graft loss (P = 0.034). Regarding more detailed factors, grade of liver trauma exceeding IV increased the risk of mortality (P = 0.005) and graft loss (P = 0.018). Moreover, a tendency above the level of significance was observed for the negative impact of injury severity score (ISS) on mortality (P = 0.071). The optimal cut-off for ISS was 33, with sensitivity of 60.0%, specificity of 80.0%, positive predictive value of 75.0%, and negative predictive value of 66.7%. CONCLUSIONS: Liver transplantation seems to be justified in selected patients with otherwise fatal severe liver injuries, particularly in whom cross-clamping without extracorporeal bypass can be omitted. The ISS cutoff less than 33 may be useful in the selection process.

Severity of liver disease among chronic hepatitis C patients: an observational study of 4594 patients in five European countries.

BACKGROUND AND AIM: Assessment of the severity of liver disease following infection with hepatitis C virus (HCV) is important in treatment selection and prognosis. As invasive liver biopsy procedures are regarded as the reference method to assess the stage of fibrosis, it is important to identify patient characteristics that are predictive of liver fibrosis severity. The aim of the study was to describe the distribution of liver severity scores, clinical characteristics, and physicians' assessment of fibrosis among HCV patients in five European countries. METHODS: This cross-sectional study retrospectively reviewed the medical records of patients who were chronically infected with HCV in 2006. Patients managed for HCV at any of 60 sites in France, Germany, Italy, Spain, and the UK were included. Data collected included patient demographics and clinical characteristics. A combination of univariate and multivariate regression analyses were used to identify predictors of fibrosis severity and factors associated with undergoing biopsy. RESULTS: Four thousand five hundred and ninety-four chronically infected HCV patients were included in this analysis. Management approaches differed between countries, with variations in biopsy use (59.3-18.4%) and preferred fibrosis scoring systems. Where histology results were available, 43.4%, 23.8%, and 32.9% had mild, moderate, and severe fibrosis, respectively. Factors associated with undergoing a biopsy included male gender and co-infection with hepatitis B virus. Chronic alcoholism, a lower first platelet count, and older age were predictors of increased liver fibrosis severity. CONCLUSIONS: These data suggest that there are major differences in how specialists manage their HCV patients across five major European countries.

[Prognostic value of a spontaneous bacterial peritonitis episode in cirrhotic patients in clinical practice]. / Valor pronóstico de un episodio de peritonitis bacteriana espontánea en pacientes cirróticos en la práctica clínica.

OBJECTIVES: To assess survival and predictive factors of mortality after an episode of spontaneous bacterial peritonitis (SBP) in cirrhotic patients and to analyze the diagnostic and therapeutic measures used. METHODS: We retrospectively reviewed the medical records of 158 consecutive episodes of SBP treated between January 2003 and December 2005. Survival was studied by Kaplan-Meier curves, compared by the log-rank test. Independent predictive factors of mortality were obtained by a Cox regression model, while independent predictive factors of in-hospital mortality were obtained by logistic regression analysis. RESULTS: A total of 80.4% of the SBP episodes occurred in men and the mean age was 61.23 +/- 12.49 years. The most frequent etiology of cirrhosis was viral (51.3%), followed by alcoholic (39.9%). The distribution of Child-Pugh classification was 5.7% (A), 63.3% (B) and 31% (C). Overall 3-year survival in the sample was 43.3%. Four variables were identified as independent predictive factors of in-hospital and 3-month mortality: renal impairment, hepatic encephalopathy, diagnosis of hepatocellular carcinoma (HCC) and mean arterial pressure (MAP) < 75 mmHg. At the end of the monitoring period, the results of the analysis were as follows: diagnosis of HCC, MAP < 75 mmHg, and age > 65 years. Microbiological detection was achieved in 21% of the episodes. The most frequent microorganisms detected were Escherichia coli in ascitic fluid and Staphylococcus aureus in blood cultures. CONCLUSIONS: SBP has a poor short- and long-term prognosis in cirrhotic patients. Independent predictive factors of short-term survival are renal impairment, hepatic encephalopathy, MAP < 75 mmHg, and the presence of HCC.

Valor pronóstico de un episodio de peritonitis bacteriana espontánea en pacientes cirróticos en la práctica clínica / Prognostic value of a spontaneous bacterial peritonitis episode in cirrhotic patients in clinical practice

OBJETIVOS: Evaluar la supervivencia y los factores pronósticotras el diagnóstico de un episodio de peritonitis bacterianaespontánea (PBE) en pacientes cirróticos y las medidasdiagnosticadas y terapéuticas utilizadas.MÉTODOS: Se revisaron de manera retrospectiva los datos de158 episodios de PBE consecutivos durante el período deenero de 2003 a diciembre de 2005. Se procedió a un análisisde supervivencia mediante curvas de Kaplan-Meier, su comparaciónmediante el test de rangos logarítmicos, y valoraciónde los factores predictivos independientes mediante regresiónde Cox, y de mortalidad intrahospitalaria medianteregresión logística.RESULTADOS: El 80,4% de los episodios de PBE se produjoen varones, y la edad media fue de 61,23 ± 12,49 años. Laetiología de la cirrosis más prevalente fue viral (51,3%) seguidadel origen etílico (39,9%), y la distribución según laclasificación de Child-Pugh fue del 5,7% (A), 63,3% (B) y31% (C). La supervivencia global de la cohorte a los 3 añosdel seguimiento fue del 43,3%. Se determinaron como factoresindependientes asociados a mortalidad, tanto intrahospitalariacomo a los 3 meses tras la PBE el deterioro de funciónrenal, la presencia de encefalopatía hepática, laexistencia de carcinoma hepatocelular (CHC) y una presiónarterial media (PAM) < 75 mmHg, y a largo plazo la edad> 65 años, la existencia de CHC y la PAM < 75 mmHg. Seconsiguió el aislamiento microbiológico en el 20,3% de losepisodios. El microorganismo más frecuentemente aisladoen el líquido ascítico fue Escherichia coli y en hemocultivosStaphylococcus aureus.CONCLUSIONES: La PBE es un evento pronóstico importanteen la cirrosis hepática, y los factores independientes de mortalidada corto plazo son el deterioro de función renal, lapresencia de encefalopatía hepática, la existencia de CHC yPAM < 75 mmHg

OBJECTIVES: To assess survival and predictive factors ofmortality after an episode of spontaneous bacterial peritonitis(SBP) in cirrhotic patients and to analyze the diagnosticand therapeutic measures used.METHODS: We retrospectively reviewed the medical recordsof 158 consecutive episodes of SBP treated between January2003 and December 2005. Survival was studied by Kaplan-Meier curves, compared by the log-rank test. Independentpredictive factors of mortality were obtained by a Cox regressionmodel, while independent predictive factors of inhospitalmortality were obtained by logistic regressionanalysis.RESULTS: A total of 80.4% of the SBP episodes occurred inmen and the mean age was 61.23 ± 12.49 years. The mostfrequent etiology of cirrhosis was viral (51.3%), followed byalcoholic (39.9%). The distribution of Child-Pugh classificationwas 5.7% (A), 63.3% (B) and 31% (C). Overall 3-yearsurvival in the sample was 43.3%. Four variables were identifiedas independent predictive factors of in-hospital and 3-month mortality: renal impairment, hepatic encephalopathy,diagnosis of hepatocellular carcinoma (HCC) andmean arterial pressure (MAP) < 75 mmHg. At the end of themonitoring period, the results of the analysis were as follows:diagnosis of HCC, MAP < 75 mmHg, and age > 65 years.Microbiological detection was achieved in 21% of theepisodes. The most frequent microorganisms detected wereEscherichia coli in ascitic fluid and Staphylococcus aureus inblood cultures.CONCLUSIONS: SBP has a poor short- and long-term prognosisin cirrhotic patients. Independent predictive factors ofshort-term survival are renal impairment, hepatic encephalopathy,MAP < 75 mmHg, and the presence of HCC (AU)