Obesity increases the risk of clinical decompensation in cirrhosis, possibly by increasing portal pressure. Whether weight reduction can be safely achieved through lifestyle (LS) changes (diet and ...exercise) in overweight/obese patients with cirrhosis, and if weight loss reduces portal pressure in this setting, is unknown. This prospective, multicentric, uncontrolled pilot study enrolled patients with compensated cirrhosis, portal hypertension (hepatic venous pressure gradient HVPG ≥6 mm Hg), and body mass index (BMI) ≥26 kg/m2 in an intensive 16‐week LS intervention program (personalized hypocaloric normoproteic diet and 60 min/wk of supervised physical activity). We measured HVPG, body weight (BW) and composition, adipokines, health‐related quality of life, and safety data before and after the intervention. Changes in HVPG and BW were predefined as clinically relevant if ≥10% and ≥5%, respectively. Safety and BW were reassessed after 6 months. 60 patients were included and 50 completed the study (56 ± 8 years old; 62% male; nonalcoholic steatohepatitis etiology 24%; BMI 33.3 ± 3.2 kg/m2; Child A 92%; HVPG ≥10 mm Hg, 72%). LS intervention significantly decreased BW (average, –5.0 ± 4.0 kg; P < 0.0001), by ≥5% in 52% and ≥10% in 16%. HVPG also significantly decreased (from 13.9 ± 5.6 to 12.3 ± 5.2 mm Hg; P < 0.0001), by ≥10% in 42% and ≥20% in 24%. A ≥10% BW loss was associated with a greater decrease in HVPG (–23.7 ± 19.9% vs. –8.2 ± 16.6%; P = 0.024). No episodes of clinical decompensation occurred. Weight loss achieved at 16 weeks was maintained at 6 months; Child and Model for End‐Stage Liver Disease scores did not change. Conclusion: Sixteen weeks of diet and moderate exercise were safe and reduced BW and portal pressure in overweight/obese patients with cirrhosis and portal hypertension. (Hepatology 2017;65:1293‐1305).
Endoscopic variceal ligation plus beta‐blockers (EVL+BB) is currently recommended for variceal rebleeding prophylaxis, a recommendation that extends to all patients with cirrhosis with previous ...variceal bleeding irrespective of prognostic stage. Individualizing patient care is relevant, and in published studies on variceal rebleeding prophylaxis, there is a lack of information regarding response to therapy by prognostic stage. This study aimed at comparing EVL plus BB with monotherapy (EVL or BB) on all‐source rebleeding and mortality in patients with cirrhosis and previous variceal bleeding stratified by cirrhosis severity (Child A versus B/C) by means of individual time‐to‐event patient data meta‐analysis from randomized controlled trials. The study used individual data on 389 patients from three trials comparing EVL plus BB versus BB and 416 patients from four trials comparing EVL plus BB versus EVL. Compared with BB alone, EVL plus BB reduced overall rebleeding in Child A (incidence rate ratio 0.40; 95% confidence interval, 0.18‐0.89; P = 0.025) but not in Child B/C, without differences in mortality. The effect of EVL on rebleeding was different according to Child (P for interaction <0.001). Conversely, compared with EVL, EVL plus BB reduced rebleeding in both Child A and B/C, with a significant reduction in mortality in Child B/C (incidence rate ratio 0.46; 95% confidence interval, 0.25‐0.85; P = 0.013). Conclusion: Outcomes of therapies to prevent variceal rebleeding differ depending on cirrhosis severity: in patients with preserved liver function (Child A), combination therapy is recommended because it is more effective in preventing rebleeding, without modifying survival, while in patients with advanced liver failure (Child B/C), EVL alone carries an increased risk of rebleeding and death compared with combination therapy, underlining that BB is the key element of combination therapy. (Hepatology 2017;66:1219‐1231).
Background & Aims There is no histologic classification system to determine prognoses of patients with alcoholic hepatitis (AH). We identified histologic features associated with disease severity and ...created a histologic scoring system to predict short-term (90-day) mortality. Methods We analyzed data from 121 patients admitted to the Liver Unit (Hospital Clinic, Barcelona, Spain) from January 2000 to January 2008 with features of AH and developed a histologic scoring system to determine the risk of death using logistic regression. The system was tested and updated in a test set of 96 patients from 5 academic centers in the United States and Europe, and a semiquantitative scoring system called the Alcoholic Hepatitis Histologic Score (AHHS) was developed. The system was validated in an independent set of 109 patients. Interobserver agreement was evaluated by weighted κ statistical analysis. Results The degree of fibrosis, degree of neutrophil infiltration, type of bilirubinostasis, and presence of megamitochondria were independently associated with 90-day mortality. We used these 4 parameters to develop the AHHS to identify patients with a low (0–3 points), moderate (4–5 points), or high (6–9 points) risk of death within 90 days (3%, 19%, and 51%, respectively; P < .0001). The AHHS estimated 90-day mortality in the training and test sets with an area under the receiver operating characteristic value of 0.77 (95% confidence interval, 0.71–0.83). Interrater agreement values were 0.65 for fibrosis, 0.86 for bilirubinostasis, 0.60 for neutrophil infiltration, and 0.46 for megamitochondria. Interestingly, the type of bilirubinostasis predicted the development of bacterial infections. Conclusions We identified histologic features associated with the severity of AH and developed a patient classification system that might be used in clinical decision making.
Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Most morbidity associated with the metabolic syndrome is related to vascular complications, in which ...endothelial dysfunction is a major pathogenic factor. However, whether NAFLD is associated with endothelial dysfunction within the hepatic vasculature is unknown. The aims of this study were to explore, in a model of diet-induced overweight that expresses most features of the metabolic syndrome, whether early NAFLD is associated with liver endothelial dysfunction. Wistar Kyoto rats were fed a cafeteria diet (CafD; 65% of fat, mostly saturated) or a control diet (CD) for 1 month. CafD rats developed features of the metabolic syndrome (overweight, arterial hypertension, hypertryglyceridemia, hyperglucemia and insulin resistance) and liver steatosis without inflammation or fibrosis. CafD rats had a significantly higher in vivo hepatic vascular resistance than CD. In liver perfusion livers from CafD rats had an increased portal perfusion pressure and decreased endothelium-dependent vasodilation. This was associated with a decreased Akt-dependent eNOS phosphorylation and NOS activity. In summary, we demonstrate in a rat model of the metabolic syndrome that shows features of NAFLD, that liver endothelial dysfunction occurs before the development of fibrosis or inflammation.
Background and Aims
The optimal treatment for gastric varices (GVs) is a topic that remains open for study. This study compared the efficacy and safety of endoscopic cyanoacrylate injection and ...balloon‐occluded retrograde transvenous obliteration (BRTO) to prevent rebleeding in patients with cirrhosis and GVs after primary hemostasis.
Approach and Results
Patients with cirrhosis and history of bleeding from gastroesophageal varices type 2 or isolated gastric varices type 1 were randomized to cyanoacrylate injection (n = 32) or BRTO treatment (n = 32). Primary outcomes were gastric variceal rebleeding or all‐cause rebleeding. Patient characteristics were well balanced between two groups. Mean follow‐up time was 27.1 ± 12.0 months in a cyanoacrylate injection group and 27.6 ± 14.3 months in a BRTO group. Probability of gastric variceal rebleeding was higher in the cyanoacrylate injection group than in the BRTO group (P = 0.024). Probability of remaining free of all‐cause rebleeding at 1 and 2 years for cyanoacrylate injection versus BRTO was 77% versus 96.3% and 65.2% versus 92.6% (P = 0.004). Survival rates, frequency of complications, and worsening of esophageal varices were similar in both groups. BRTO resulted in fewer hospitalizations, inpatient stays, and lower medical costs.
Conclusions
BRTO is more effective than cyanoacrylate injection in preventing rebleeding from GVs, with similar frequencies of complications and mortalities.
Alcoholic hepatitis (AH) frequently progresses to multiple organ failure (MOF) and death. However, the driving factors are largely unknown. At admission, patients with AH often show criteria of ...systemic inflammatory response syndrome (SIRS) even in the absence of an infection. We hypothesize that the presence of SIRS may predispose to MOF and death. To test this hypothesis, we studied a cohort including 162 patients with biopsy‐proven AH. The presence of SIRS and infections was assessed in all patients, and multivariate analyses identified variables independently associated with MOF and 90‐day mortality. At admission, 32 (19.8%) patients were diagnosed with a bacterial infection, while 75 (46.3%) fulfilled SIRS criteria; 58 patients (35.8%) developed MOF during hospitalization. Short‐term mortality was significantly higher among patients who developed MOF (62.1% versus 3.8%, P < 0.001). The presence of SIRS was a major predictor of MOF (odds ratio = 2.69, P = 0.025) and strongly correlated with mortality. Importantly, the course of patients with SIRS with and without infection was similar in terms of MOF development and short‐term mortality. Finally, we sought to identify serum markers that differentiate SIRS with and without infection. We studied serum levels of high‐sensitivity C‐reactive protein, procalcitonin, and lipopolysaccharide at admission. All of them predicted mortality. Procalcitonin, but not high‐sensitivity C‐reactive protein, serum levels identified those patients with SIRS and infection. Lipopolysaccharide serum levels predicted MOF and the response to prednisolone. Conclusion: In the presence or absence of infections, SIRS is a major determinant of MOF and mortality in AH, and the mechanisms involved in the development of SIRS should be investigated; procalcitonin serum levels can help to identify patients with infection, and lipopolysaccharide levels may help to predict mortality and the response to steroids. (Hepatology 2015;62:762–772)
Background and Aims
A hepatic venous pressure gradient (HVPG) decrease of 20% or more (or ≤12 mm Hg) indicates a good prognosis during propranolol/nadolol treatment but requires two HVPG ...measurements. We aimed to simplify the risk stratification after variceal bleeding using clinical data and HVPG.
Methods
A total of 193 patients with cirrhosis (62% with ascites and/or hepatic encephalopathy HE) who were within 7 days of bleeding had their HVPG measured before and at 1‐3 months of treatment with propranolol/nadolol plus endoscopic band ligation. The endpoints were rebleeding and rebleeding/transplantation‐free survival for 4 years. Another cohort (n = 231) served as the validation set.
Results
During follow‐up, 45 patients had variceal bleeding and 61 died. The HVPG responders (n = 71) had lower rebleeding risk (10% vs. 34%, P = 0.001) and better survival than the 122 nonresponders (61% vs. 39%, P = 0.001). Patients with HE (n = 120) had lower survival than patients without HE (40% vs. 63%, P = 0.005). Among the patients with ascites/HE, those with baseline HVPG ≤ 16 mm Hg (n = 16) had a low rebleeding risk (13%). In contrast, among patients with ascites/HE and baseline HVPG > 16 mm Hg, only the HVPG responders (n = 32) had a good prognosis, with lower rebleeding risk and better survival than the nonresponders (n = 72) (respective proportions: 7% vs. 39%, P = 0.018; 56% vs. 30% P = 0.010). These findings allowed us to develop a strategy for risk stratification in which HVPG response was measured only in patients with ascites and/or HE and baseline HVPG > 16 mm Hg. This method reduced the “gray zone” (i.e., high‐risk patients who had not died on follow‐up) from 46% to 35% and decreased the HVPG measurements required by 42%. The validation cohort confirmed these results.
Conclusions
Restricting HVPG measurements to patients with ascites/HE and measuring HVPG response only if the patient’s baseline HVPG is over 16 mm Hg improves detection of high‐risk patients while markedly reducing the number of HVPG measurements required.
Background & Aims Noninvasive methods are needed to identify clinically significant portal hypertension (CSPH) and esophageal varices (EVs) in patients with compensated cirrhosis. We looked for ...markers of the presence of CSPH and EVs in patients with cirrhosis. Methods We performed a cross-sectional study that included a training set of 117 patients with compensated cirrhosis, confirmed by histology, from a tertiary referral center. Spleen diameter was measured by ultrasound, and liver stiffness (LS) was measured by transient elastography; endoscopy was used as the standard for detection of EVs, and measurements of hepatic venous pressure gradient were used as the standard for identifying CSPH. We assessed the ability of platelet count, spleen diameter, LS, and combinations of these factors (ie, ratio of platelet count to spleen size, and LS × spleen size/platelet count LSPS) to identify patients with CSPH and EV. The analysis included 2 new statistical models: the PH risk score and the varices risk score. Results were validated using an independent series of 56 patients with compensated patients from another center. Results LS was the best single noninvasive variable for identifying patients with CSPH (area under the receiver operating characteristic, 0.883; 95% confidence interval CI, 0.824–0.943; P < .0001). The area under the receiver operating characteristic value increased when LS was combined with platelet count and spleen size, either as LSPS (0.918; 95% CI, 0.872−0.965; P < .0001) or PH risk score (0.935; 95% CI, 0.893–0.977; P < .0001). More than 80% of patients were accurately classified using LSPS and PH risk score. Analyses of the varices risk score and LSPS were superior to all other noninvasive tests for identifying patients with EVs (area under the receiver operating characteristic, 0.909; 95% CI, 0.841−0.954 and 0.882; 95% CI, 0.810–0.935, respectively); they correctly classified 85% of patients in the training set and 75% in the validation set. Conclusions Combined data on LS, spleen diameter, and platelet count can be used to identify patients with compensated cirrhosis most likely to have CSPH and EV.
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