No therapies have been proven to increase survival after a hepatic encephalopathy (HE) episode. We hypothesize that two doses of albumin could improve 90-day survival rates after a HE episode. ...Methods: (1) A randomized double-blind, placebo-controlled trial (BETA) was conducted in 12 hospitals. The effect of albumin (1.5 g/kg at baseline and 1 g/kg on day 3) on 90-day survival rates after a HE episode grade II or higher was evaluated. (2) A meta-analysis of individual patient’s data for survival including two clinical trials (BETA and ALFAE) was performed. Results: In total, 82 patients were included. Albumin failed to increase the 90-day transplant-free survival (91.9% vs. 80.5%, p = 0.3). A competing risk analysis was performed, observing a 90-day cumulative incidence of death of 9% in the albumin group vs. 20% in the placebo (p = 0.1). The meta-analysis showed a benefit in the albumin group, with a lower rate of clinical events (death or liver transplant) than patients in the placebo (HR, 0.44; 95% CI, 0.21–0.82), when analyzed by a competing risk analysis (90-days mortality rate of 11% in the albumin group vs. 30% in the placebo, p = 0.02). Conclusions: Repeated doses of albumin might be beneficial for patient’s survival as an add-on therapy after an HE episode, but an adequately powered trial is needed.
Introduction: Human immunodeficiency virus (HIV) infection and cirrhosis are associated with a senescent phenotype that decreases telomere length. We evaluated the impact of hepatitis C virus (HCV) ...elimination on telomere length in patients with advanced HCV-related cirrhosis after sustained virological response (SVR), with all-oral direct-acting antiviral agents (DAAs). Methods: Prospective study of 60 HIV/HCV-coinfected and 30 HCV-monoinfected patients with advanced HCV cirrhosis (liver decompensation or liver stiffness measurement (LSM) ≥ 25 kPa, hepatic liver pressure gradient (HVPG) ≥ 10 mmHg, or Child–Pugh–Turcotte (CPT) ≥ 7). The relative telomere length (RTL) was quantified by real-time multiplex PCR (MMqPCR) on peripheral blood mononuclear cells at baseline and 48 weeks after HCV treatment. Generalized linear models (GLMs) adjusted for the most relevant clinical and epidemiological variables and mixed GLMs were used. Results: In comparison with HCV-monoinfected patients, HIV/HCV-coinfected patients were younger (p < 0.001), had lower body mass index (BMI) (p = 0.002), and had been exposed less frequently to interferons (p = 0.011). In addition, they were more frequently men (p = 0.011), smokers (p = 0.005), prior intravenous drug users (IVDUs) (p < 0.001), and alcohol abusers (p = 0.005). RTL was significantly lower in HIV/HCV-coinfected patients than in HCV-monoinfected patients, both at baseline (p < 0.001), and at the end of follow-up (p = 0.032). A significant RTL increase over time was found only for HIV/HCV-coinfected patients (p < 0.001), especially in those patients with compensated cirrhosis (p < 0.001). Conclusion: HCV eradication with all-oral DAAs was associated with an increase in telomere length in HIV/HCV-coinfected patients with advanced cirrhosis, particularly in compensated patients. This finding suggests that HCV clearance may have implications in age-related conditions in this population group.
The possibility of developing idiopathic portal hypertension has been described with thiopurine treatment despite compromises the prognosis of these patients, the fact its true prevalence is unknown.
...A cross-sectional study was conducted in a cohort of inflammatory bowel disease (IBD) patients followed at our unit, to determine the prevalence of diagnosis of idiopathic portal hypertension (IPH) and its relationship with thiopurine treatment.
At the time of the analysis, 927/1,419 patients were under treatment with thiopurine drugs (65%). A total of 4 patients with IBD type Crohn's disease with idiopathic portal hypertension probably related to the thiopurine treatment were identified (incidence of 4.3 cases per 1,000). Seventy-five percent of patients started with signs or symptoms of portal hypertension. Only one patient was asymptomatic but the diagnosis of IPH because of isolated thrombocytopenia is suspected. However, note that all patients had thrombocytopenia previously. Abdominal ultrasound with fibroscan, hepatic vein catheterization and liver biopsy were performed on all of them as part of the etiology of portal hypertension. In the abdominal ultrasound, indirect portal hypertension data were observed in all patients (as splenomegaly) cirrhosis was also ruled out. The fibroscan data showed significant liver fibrosis (F2-F3).
Idiopathic portal hypertension following thiopurine treatment in IBD patients is a rare occurrence, but it must be borne in mind in the differential diagnosis for early diagnosis, especially in patients undergoing thiopurine treatment over a long period. The presence of thrombocytopenia is often the only predictor of its development in the preclinical stage.
prevalence of viral hepatitis (B and C) changes geographically. Our aim was to determinate the prevalence of hepatitis B (HBV) and hepatitis C virus (HCV) serological markers in healthy working ...population and to describe the epidemiological characteristics associated to its presence.
blood samples and epidemiological data of 5,017 healthy workers from Murcia and Madrid were recorded prospectively.
a total of 5,017 healthy volunteers participated. Mean age 39 ± 11 years, men predominance (73 %). Prevalence of serological markers of HCV and HBV was 0.6 % and 0.7 %. Age of patients with HCV antibody was significantly higher (43 + or - 9 years vs. 39 + or - 11 years; p = 0.03). We observed significant differences in liver test values (alanine aminotransferase ALT 64 ± 56 IU/L vs. 28 ± 20 IU/L; p < 0.001; aspartate aminotransferase AST (51 + or - 45 IU/L vs. 23 + or - 12 IU/L; p < 0.001) and in gamma-glutamyltransferase(GGT) value (104 + or - 122 IU/L vs. 37 + or - 46 IU/L; p < 0.001. The presence of HCV antibody was related significantly to previous transfusion (13 % vs. 5 %; p = 0.03), tattoos (29 % vs. 13 %; p < 0.01), intravenous drug addiction (13 % vs. 0.2 %; p < 0.001) and coexistence with people with positive HCV antibody (16 % vs. 4 %; p < 0.001). In HBV no differences in basal characteristics were observed with exception in AST values (29 + or - 15 IU/L vs. 23 + or - 12 IU/L; p < 0.01). Hepatitis B surface antigen (HBsAg) was related significantly to previous transfusion (15 % vs. 5 %; p < 0.01), tattoos (26 % vs. 14 %; p = 0.04) and coexistence with people with positive HBsAg (17 % vs. 4 %; p < 0.001).
Prevalence of serological markers in healthy working population is low. Risk factors for infection were previous transfusion and tattoos. Intravenous drug addiction was only a risk factor in HCV.
Liver enzyme elevation has been reported for SARS-CoV-2 disease (COVID-19) in heterogeneous cohorts, mainly from China. Comprehensive reports from other countries are needed. We dissect the pattern, ...evolution and predictive value of such abnormalities in a cohort from Madrid, Spain.
Retrospective study with prospective 14-day follow-up of 373 patients with confirmed COVID-19 in five Madrid hospitals, including 50 outpatients. COVID-19 severe course was defined as need of mechanical ventilation.
A total of 33.1% hospitalised patients showed baseline AST elevation and 28.5% showed ALT elevation, contrasting with 12% and 8% of outpatients (P≤0.001). Baseline AST, ALT and GGT levels correlated with LDH and C-reactive protein levels (CRP) (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 all). ALP and Bilirubin levels were rarely increased. Patients with elevated baseline AST displayed progressive normalization of this enzyme and increase in ALT and GGT levels. Patients with normal baseline AST showed a flattened evolution pattern with levels in range. Patients with a severe course of COVID-19 showed more frequently 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.
Mild liver enzyme elevation is associated with COVID-19 severity. Baseline AST is an independent predictor of severe COVID-19 course, while it tends to normalize over time. ALT and GGT show late elevation.
Thrombosis of the splenoportal axis not associated with liver cirrhosis or neoplasms is a rare disease whose prevalence ranges from 0.7 to 3.7 per 100,000 inhabitants. However, this entity is the ...second most common cause of portal hypertension. Prothrombotic factors are present as an underlying cause in up to 70% of patients and local factors in 10-50%. The coexistence of several etiological factors is frequent. Clinical presentation may be acute or chronic (portal cavernomatosis). The acute phase can present as abdominal pain, nausea, vomiting, fever, rectorrhagia, intestinal congestion, and ischemia. In this phase, early initiation of anticoagulation is essential to achieve portal vein recanalization and thus improve patient prognosis. In the chronic phase, symptoms are due to portal hypertension syndrome. In this phase, the aim of treatment is to treat or prevent the complications of portal hypertension. Anticoagulation is reserved to patients with a proven underlying thrombophilic factor.
Clinically significant portal hypertension (CSPH), defined as a hepatic venous pressure gradient (HVPG) ≥10 mmHg, persists 24 weeks after sustained virological response (SVR) in up to 78% of patients ...with HCV-related cirrhosis treated with direct-acting antivirals. These patients remain at risk of decompensation. However, long-term paired clinical and hemodynamic data are not available for this population.
We conducted a prospective multicenter study in 226 patients with HCV-related cirrhosis and CSPH who achieved SVR after antiviral therapy. Patients with CSPH 24 weeks after end of treatment (SVR24) were offered another hemodynamic assessment 96 weeks after end of treatment (SVR96).
All patients were clinically evaluated. Out of 176 patients with CSPH at SVR24, 117 (66%) underwent an HVPG measurement at SVR96. At SVR96, 55/117 (47%) patients had HVPG <10 mmHg and 53% had CSPH (65% if we assume persistence of CSPH in all 59 non-evaluated patients). The proportion of high-risk patients (HVPG ≥16 mmHg) diminished from 41% to 15%. Liver stiffness decreased markedly after SVR (median decrease 10.5 ± 13 kPa) but did not correlate with HVPG changes (30% of patients with liver stiffness measurement <13.6 kPa still had CSPH). Seventeen (7%) patients presented with de novo/additional clinical decompensation, which was independently associated with baseline HVPG ≥16 mmHg and history of ascites.
Patients achieving SVR experienced a progressive reduction in portal pressure during follow-up. However, CSPH may persist in up to 53–65% of patients at SVR96, indicating persistent risk of decompensation. History of ascites and high-risk HVPG values identified patients at higher risk of de novo or further clinical decompensation.
As a major complication of cirrhosis, clinically significant portal hypertension (CSPH) is associated with adverse clinical outcomes. Herein, we show that CSPH persists at 96 weeks in just over half of patients with HCV-related cirrhosis, despite HCV elimination by direct-acting antivirals. Despite viral cure, patients with CSPH at the start of antiviral treatment remain at long-term risk of hepatic complications and should be managed accordingly.
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•HVPG ≥10 mmHg persists 2 years after therapy in 53–65% of patients with HCV-related cirrhosis despite HCV eradication.•Changes in liver stiffness do not correlate with changes in HVPG after a sustained virological response.•Baseline HVPG ≥16 mmHg and ascites identify patients with persistent CSPH and risk of decompensation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Patients with hepatitis C virus-associated cirrhosis and clinical significant portal hypertension (CSPH, hepatic venous pressure gradient HVPG 10 mmHg or greater), despite achieving sustained ...virological response (SVR) to therapy, remain at risk of liver decompensation. We investigated hemodynamic changes following SVR in patients with CSPH and whether liver stiffness measurements (LSMs) can rule out the presence of CSPH.
We performed a multicenter prospective study of 226 patients with hepatitis C virus-associated cirrhosis and CSPH who had SVR to interferon-free therapy at 6 Liver Units in Spain. The portal pressure gradient was determined based on HVPG at baseline and 24 weeks after therapy; patients also underwent right-heart catheterization and LSM at these time points. Primary outcomes were effects of SVR on the hepatic, pulmonary, and systemic hemodynamics; factors related to HVPG ≥10% reduction and to CSPH persistence; and whether LSMs can rule out the presence of CSPH after SVR.
Most patients (75%) had esophageal varices, 21% were Child-B, and 29% had at least 1 previous episode of liver decompensation. Overall, HVPG decreased from 15 (IQR: 12–18) before treatment to 13 (10–16) mmHg after SVR (reduction of 2.1 ± 3.2 mmHg; P < .01). However, CSPH persisted in 78% of patients. HVPG decreased by 10% or more from baseline in 140 patients (62%). Baseline level of albumin below 3.5 g/dL was the only negative factor associated with an HVPG reduction of 10% or more. LSM decreased from 27 (20–37) kPa before treatment to 18 (14–28) kPa after SVR (P < .05). One third of patients with a reduction in LSM to below 13.6 kPa after SVR still had CSPH. A higher baseline HVPG and a lower decrease in LSM after treatment were associated with persistence of CSPH after SVR. Systemic hemodynamics improved after SVR. Interestingly, pulmonary hypertension was present in 13 patients at baseline and 25 after SVR, although only 3 patients had increased pulmonary resistance.
In a multicenter prospective study of patients with hepatitis C virus-associated cirrhosis, an SVR to all-oral therapy significantly reduced HVPG, compared with before treatment. Nevertheless, CSPH persists in most patients despite SVR, indicating persistent risk of decompensation. In this population, changes in LSM do not correlate with HVPG and cut-off values are not reliable in ruling out CSPH after SVR.
Spontaneous portosystemic shunts (SPSS) frequently develop in liver cirrhosis. Recent data suggested that the presence of a single large SPSS is associated with complications, especially overt ...hepatic encephalopathy (oHE). However, the presence of >1 SPSS is common. This study evaluates the impact of total cross-sectional SPSS area (TSA) on outcomes in patients with liver cirrhosis.
In this retrospective international multicentric study, CT scans of 908 cirrhotic patients with SPSS were evaluated for TSA. Clinical and laboratory data were recorded. Each detected SPSS radius was measured and TSA calculated. One-year survival was the primary endpoint and acute decompensation (oHE, variceal bleeding, ascites) was the secondary endpoint.
A total of 301 patients (169 male) were included in the training cohort. Thirty percent of all patients presented with >1 SPSS. A TSA cut-off of 83 mm2 was used to classify patients with small or large TSA (S-/L-TSA). Patients with L-TSA presented with higher model for end-stage liver disease score (11 vs. 14) and more commonly had a history of oHE (12% vs. 21%, p <0.05). During follow-up, patients with L-TSA experienced more oHE episodes (33% vs. 47%, p <0.05) and had lower 1-year survival than those with S-TSA (84% vs. 69%, p <0.001). Multivariate analysis identified L-TSA (hazard ratio 1.66; 95% CI 1.02–2.70, p <0.05) as an independent predictor of mortality. An independent multicentric validation cohort of 607 patients confirmed that patients with L-TSA had lower 1-year survival (77% vs. 64%, p <0.001) and more oHE development (35% vs. 49%, p <0.001) than those with S-TSA.
This study suggests that TSA >83 mm2 increases the risk for oHE and mortality in patients with cirrhosis. Our results support the clinical use of TSA/SPSS for risk stratification and decision-making in the management of patients with cirrhosis.
The prevalence of spontaneous portosystemic shunts (SPSS) is higher in patients with more advanced chronic liver disease. The presence of more than 1 SPSS is common in advanced chronic liver disease and is associated with the development of hepatic encephalopathy. This study shows that total cross-sectional SPSS area (rather than diameter of the single largest SPSS) predicts survival in patients with advanced chronic liver disease. Our results support the clinical use of total cross-sectional SPSS area for risk stratification and decision-making in the management of SPSS.
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•Total cross-sectional SPSS area (TSA) predicts survival in patients with advanced chronic liver disease.•The cut-off for TSA that is associated with worse survival corresponds to a single shunt of >10 mm diameter.•This study may impact on the clinical use of TSA/SPSS for risk stratification and decision-making in the management of patients with cirrhosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background & Aims Patients with cirrhosis with acute variceal bleeding (AVB) have high mortality rates (15%–20%). Previously described models are seldom used to determine prognoses of these patients, ...partially because they have not been validated externally and because they include subjective variables, such as bleeding during endoscopy and Child–Pugh score, which are evaluated inconsistently. We aimed to improve determination of risk for patients with AVB. Methods We analyzed data collected from 178 patients with cirrhosis (Child–Pugh scores of A, B, and C: 15%, 57%, and 28%, respectively) and esophageal AVB who received standard therapy from 2007 through 2010. We tested the performance (discrimination and calibration) of previously described models, including the model for end-stage liver disease (MELD), and developed a new MELD calibration to predict the mortality of patients within 6 weeks of presentation with AVB. MELD-based predictions were validated in cohorts of patients from Canada (n = 240) and Spain (n = 221). Results Among study subjects, the 6-week mortality rate was 16%. MELD was the best model in terms of discrimination; it was recalibrated to predict the 6-week mortality rate with logistic regression (logit, -5.312 + 0.207 • MELD; bootstrapped R2 , 0.3295). MELD values of 19 or greater predicted 20% or greater mortality, whereas MELD scores less than 11 predicted less than 5% mortality. The model performed well for patients from Canada at all risk levels. In the Spanish validation set, in which all patients were treated with banding ligation, MELD predictions were accurate up to the 20% risk threshold. Conclusions We developed a MELD-based model that accurately predicts mortality among patients with AVB, based on objective variables available at admission. This model could be useful to evaluate the efficacy of new therapies and stratify patients in randomized trials.
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