The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology

Acute decompensation (AD) of cirrhosis is defined as the acute development of ascites, gastrointestinal hemorrhage, hepatic encephalopathy, infection or any combination thereof, requiring hospitalization. The presence of organ failure(s) in patients with AD defines acute-on-chronic liver failure (ACLF). The PREDICT study is a European, prospective, observational study, designed to characterize the clinical course of AD and to identify predictors of ACLF. A total of 1,071 patients with AD were enrolled. We collected detailed pre-specified information on the 3-month period prior to enrollment, and clinical and laboratory data at enrollment. Patients were then closely followed up for 3 months. Outcomes (liver transplantation and death) at 1 year were also recorded. Three groups of patients were identified. Pre-ACLF patients (n = 218) developed ACLF and had 3-month and 1-year mortality rates of 53.7% and 67.4%, respectively. Unstable decompensated cirrhosis (UDC) patients (n = 233) required ≥1 readmission but did not develop ACLF and had mortality rates of 21.0% and 35.6%, respectively. Stable decompensated cirrhosis (SDC) patients (n = 620) were not readmitted, did not develop ACLF and had a 1-year mortality rate of only 9.5%. The 3 groups differed significantly regarding the grade and course of systemic inflammation (high-grade at enrollment with aggravation during follow-up in pre-ACLF; low-grade at enrollment with subsequent steady-course in UDC; and low-grade at enrollment with subsequent improvement in SDC) and the prevalence of surrogates of severe portal hypertension throughout the study (high in UDC vs. low in pre-ACLF and SDC). Acute decompensation without ACLF is a heterogeneous condition with 3 different clinical courses and 2 major pathophysiological mechanisms: systemic inflammation and portal hypertension. Predicting the development of ACLF remains a major future challenge. ClinicalTrials.gov number: NCT03056612. Lay summary: Herein, we describe, for the first time, 3 different clinical courses of acute decompensation (AD) of cirrhosis after hospital admission. The first clinical course includes patients who develop acute-on-chronic liver failure (ACLF) and have a high short-term risk of death - termed pre-ACLF. The second clinical course (unstable decompensated cirrhosis) includes patients requiring frequent hospitalizations unrelated to ACLF and is associated with a lower mortality risk than pre-ACLF. Finally, the third clinical course (stable decompensated cirrhosis), includes two-thirds of all patients admitted to hospital with AD - patients in this group rarely require hospital admission and have a much lower 1-year mortality risk

PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis

Background & Aims: Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (ADNo ACLF), or with ACLF (AD-ACLF), defined by organ failure(s). Herein, we aimed to analyze and characterize the precipitants leading to both of these AD phenotypes. Methods: The multicenter, prospective, observational PREDICT study (NCT03056612) included 1,273 non-electively hospitalized patients with AD (No ACLF = 1,071; ACLF = 202). Medical history, clinical data and laboratory data were collected at enrolment and during 90-day follow-up, with particular attention given to the following characteristics of precipitants: induction of organ dysfunction or failure, systemic inflammation, chronology, intensity, and relationship to outcome. Results: Among various clinical events, 4 distinct events were precipitants consistently related to AD: proven bacterial infections, severe alcoholic hepatitis, gastrointestinal bleeding with shock and toxic encephalopathy. Among patients with precipitants in the AD-No ACLF cohort and the AD-ACLF cohort (38% and 71%, respectively), almost all (96% and 97%, respectively) showed proven bacterial infection and severe alcoholic hepatitis, either alone or in combination with other events. Survival was similar in patients with proven bacterial infections or severe alcoholic hepatitis in both AD phenotypes. The number of precipitants was associated with significantly increased 90day mortality and was paralleled by increasing levels of surrogates for systemic inflammation. Importantly, adequate first-line antibiotic treatment of proven bacterial infections was associated with a lower ACLF development rate and lower 90-day mortality. Conclusions: This study identified precipitants that are significantly associated with a distinct clinical course and prognosis in patients with AD. Specific preventive and therapeutic strategies targeting these events may improve outcomes in patients with decompensated cirrhosis. Lay summary: Acute decompensation (AD) of cirrhosis is characterized by a rapid deterioration in patient health. Herein, we aimed to analyze the precipitating events that cause AD in patients with cirrhosis. Proven bacterial infections and severe alcoholic hepatitis, either alone or in combination, accounted for almost all (96-97%) cases of AD and acute-on-chronic liver failure. Whilst the type of precipitant was not associated with mortality, the number of precipitant(s) was. This study identified precipitants that are significantly associated with a distinct clinical course and prognosis of patients with AD. Specific preventive and therapeutic strategies targeting these events may improve patient outcomes. (c) 2020 European Association for the Study of the Liver. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Elevated Colon Cancer Rates Linked to Prior Appendicitis: A Retrospective Cohort Study Based on Data from German General Practices

Background/Objective: The association between appendicitis and colon cancer is not yet fully understood. Previous studies have shown contradictory results. Currently, no population-based data from Germany are available with regard to the incidence of colon cancer following appendicitis. This study investigated the association between appendicitis and the incidence of colon cancer in Germany. Methods: In this retrospective cohort study, the incidence of colon cancer was compared for patients with appendicitis and patients without appendicitis, matched for age, sex, index year, average annual consultation frequency, and comorbidity. The aim of the study was to explore the relationship between appendicitis and the incidence of colon cancer. The evaluation was carried out using logistic regression analyses. Results: The study included 49,790 people with and without appendicitis, with a median age of 41 years. During a follow-up period of up to 15 years, 1.04% of cases with appendicitis and 0.60% of cases without appendicitis were newly diagnosed with colon cancer, with some 36.4% of colon cancer cases diagnosed within the first six months after appendicitis. Regression analyses revealed a significant association between appendicitis and colon cancer, particularly in men and in the age groups 41–50 (HR: 10.30; 95% CI: 1.03–43.82) and 18–30 years (HR: 8.17; 95% CI: 1.03–64.58). Conclusions: The present retrospective cohort study suggests an association between appendicitis and the incidence of colon cancer in Germany. Based on our results, we recommend offering a colonoscopy or at least a stool test within 12 months after appendicitis, especially for 18–50-year-olds and >60-year-olds in good general health

Portal Hypertensive Polyposis in Advanced Liver Cirrhosis: The Unknown Entity?

Background. Portal hypertension is a serious complication of liver cirrhosis. Objective. To identify relevant endoscopic findings in patients with advanced cirrhosis and consecutive portal hypertension. Methods. This was a retrospective study of liver transplant candidates who underwent upper gastrointestinal endoscopy between April 2011 and November 2015. Results. A total of 1,045 upper endoscopies were analyzed. Portal hypertensive gastric and duodenal polyps were frequently observed and were associated with thrombocytopenia (p = 0.040; OR: 2.4, 95% CI 1.04–5.50), Child-Pugh score > 6 (p = 0.033; OR: 2.3, 95% CI 1.07–4.92), Model for End Stage Liver Disease score > 16 (p = 0.030; OR: 4.1, 95% CI 1.14–15.00), and previous rubber band ligation (p < 0.001; OR = 5.2, 95% CI 2.5–10.7). These polyps often recurred after polypectomy; however, no malignant transformation occurred during the observational time until October 2017. The most common endoscopic finding was esophageal varices, observed in more than 90% of patients. Conclusion. Portal hypertensive polyposis is common in patients with advanced cirrhosis. Our data suggest that these polyps have benign characteristics

Achieving Complete Remission of Hepatocellular Carcinoma: A Significant Predictor for Recurrence-Free Survival after Liver Transplantation

Background. Liver transplantation (LT) is a curative treatment for hepatocellular carcinoma (HCC) and the underlying primary liver disease; however, tumor recurrence is still a major issue. Therefore, the aim of this study was to assess predictors and risk factors for HCC recurrence after LT in patients within and outside the Milan criteria with a special focus on the impact of different bridging strategies. Methods. All patients who underwent LT for HCC between 07/2002 and 09/2016 at the University Hospital of Muenster were consecutively included in this retrospective study. Database research was performed and a multivariable regression analysis was conducted to explore potential risk factors for HCC recurrence. Results. A total of 82 patients were eligible for the statistical analysis. Independent of bridging strategy, achieving complete remission (CR) was significantly associated with a lower risk for tumor recurrence (p = 0.029; OR = 0.426, 95% CI 0.198-0.918). A maximal diameter of lesion < 3 cm was also associated with lower recurrence rates (p = 0.040; OR = 0.140, 95% CI 0.022-0.914). Vascular invasion proved to be an independent risk factor for HCC recurrence (p = 0.004; OR = 11.357, 95% CI 2.142-60.199). Conclusion. Achieving CR prior to LT results in a significant risk reduction of HCC recurrence after LT independent of the treatment modalities applied

Pictorial Representation of Illness and Self Measure (PRISM): A Novel Visual Instrument to Quantify Suffering in Liver Cirrhosis Patients and Liver Transplant Recipients

BACKGROUND: The level of suffering of chronically ill patients does not necessarily correlate with illness severity. In this study, we evaluated the burden of suffering and its impact on health-related quality of life in liver transplant recipients and liver cirrhosis patients. MATERIAL AND METHODS: The Pictorial Representation of Illness and Self Measure (PRISM) was used to explore levels of suffering in outpatients of Münster University Hospital, Germany. Self-illness separation scores were analyzed as a measure of disease-specific burden of suffering. Health-related quality of life was measured using the Short Form Health Survey (SF-36). RESULTS: Data from 201 subjects were statistically analyzed. Median Self-illness separation scores for liver transplant recipients and patients with liver cirrhosis were 13.5 (minimum/maximum: 0.2/25.6) cm and 6.3 (0.1/25.6) cm (p<0.001), respectively. The median SF-36 Mental Component Summary and Physical Component Summary scores were 46.4 (12.5/66.2) and 40.1 (12.3/61.1), respectively. Higher health-related quality of life was associated with greater self–illness separation. Liver transplant recipients showed normal Mental Component Summary scores compared with the general German population; patients with liver cirrhosis had significantly lower Mental Component Summary scores. Physical Component Summary scores were significantly higher in liver transplant recipients than in patients with liver cirrhosis, but still lower than in the general population. CONCLUSIONS: PRISM is a novel, simple tool for measuring the illness burden in liver transplant recipients and patients with liver cirrhosis. This measure may help to identify patients at a higher risk of psychological disorders

Achieving Complete Remission of Hepatocellular Carcinoma: A Significant Predictor for Recurrence-Free Survival after Liver Transplantation

BACKGROUND: Liver transplantation (LT) is a curative treatment for hepatocellular carcinoma (HCC) and the underlying primary liver disease; however, tumor recurrence is still a major issue. Therefore, the aim of this study was to assess predictors and risk factors for HCC recurrence after LT in patients within and outside the Milan criteria with a special focus on the impact of different bridging strategies. METHODS: All patients who underwent LT for HCC between 07/2002 and 09/2016 at the University Hospital of Muenster were consecutively included in this retrospective study. Database research was performed and a multivariable regression analysis was conducted to explore potential risk factors for HCC recurrence. RESULTS: A total of 82 patients were eligible for the statistical analysis. Independent of bridging strategy, achieving complete remission (CR) was significantly associated with a lower risk for tumor recurrence (p = 0.029; OR = 0.426, 95% CI 0.198-0.918). A maximal diameter of lesion < 3 cm was also associated with lower recurrence rates (p = 0.040; OR = 0.140, 95% CI 0.022-0.914). Vascular invasion proved to be an independent risk factor for HCC recurrence (p = 0.004; OR = 11.357, 95% CI 2.142-60.199). CONCLUSION: Achieving CR prior to LT results in a significant risk reduction of HCC recurrence after LT independent of the treatment modalities applied

Recurrence of Hepatic Encephalopathy after TIPS: Effective Prophylaxis with Combination of Lactulose and Rifaximin

Background: Transjugular intrahepatic portosystemic shunt (TIPS) implantation is an established procedure to treat portal hypertension with hepatic encephalopathy (HE) as a common complication. There is lack of evidence concerning HE prophylaxis after TIPS. Methods: N = 233 patients receiving TIPS between 2011 and 2018 at a German tertiary care center were included. Of them, 21% (n = 49) had a history of HE. The follow-up period was 12 months. The risk factors of post-TIPS HE were analyzed via multivariate analysis. The efficacy of prophylactic medication regimens was studied. The results show that 35.6% (n = 83) received no medication (NM), 36.5% (n = 85) received lactulose monoprophylaxis (LM), 2.6% (n = 6) rifaximin monoprophylaxis (RM) and 25.3% (n = 59) lactulose and rifaximin (LR) of which 64.4% received l-ornithin-l-aspartate (LOLA) additionally (LR + LOLA) and 36.6% did not (LRonly). Results: Multivariate analysis revealed higher age (p = 0.003) and HE episodes prior to TIPS (p = 0.004) as risk factors for HE after TIPS. LM has no prophylactic effect. LR prevents HE recurrence at 1, 3 and 12 months after TIPS (p = 0.003, p = 0.003, p = 0.006) but does not prevent HE in patients with no history of HE (p = 0.234, p = 0.483, p = 0.121). LR prevents HE recurrence compared with LM/NM (25.0% vs. 64.7%, p = 0.007) within 12 months after TIPS, whereas de novo occurrence is unaffected (p = 0.098). The additional administration of LOLA to LR has no benefit (LRonly: 25.0%, LR + LOLA: 29.7%, p = 0.780). Conclusions: Higher age and previous HE are risk factors post-TIPS HE. In patients with HE prior to TIPS, effective prophylaxis of HE is feasible via combination of lactulose and rifaximin with no additional benefit from LOLA

Lower ratio of liver volume and body weight is a negative predictor of survival after transjugular intrahepatic portosystemic shunt

Transjugular intrahepatic portosystemic shunt (TIPS) is the most effective measure to treat complications of portal hypertension. However, liver function may deteriorate after TIPS. Predictors of liver function and outcome after TIPS are therefore important for management of TIPS patients. The study aimed to evaluate the impact of liver volume on transplant-free survival (TFS) after TIPS, as well as the evolution of liver volume and its relationship with liver function after TIPS. A retrospective analysis of all consecutive patients who underwent TIPS in a tertiary care university liver center between 2012 and 2017 (n = 216) was performed; n = 72 patients with complete prior and follow-up (FU) computed tomography (CT) imaging studies were included in the study. Volumetry of the liver was performed by a semi-automatic 9-lobe image segmentation algorithm at baseline and FU (FU 1: 90–180 d; FU 2: 180–365 d; FU 3: 365–545 d; FU 4: 545–730 d; FU 5: >730 d). Output variables were total liver volume (TLV, cm3), left liver volume (LLV, cm3), right liver volume (RLV, cm3) and TLV/body weight ratio. CT derived liver volumes were correlated with liver function tests, portosystemic pressure gradient (PPG) measurements and survival. To assess predictors of liver volume change over time we fitted linear mixed models. Kaplan–Meier analysis was performed and validated by matched pair analysis followed by Cox regression to determine independent prognostic factors for survival. The median TLV at baseline was 1507.5 cm3 (773.7–3686.0 cm3). Livers with higher baseline liver volumes and larger TLV/weight ratios retained their volume after an initial loss while smaller livers continuously lost volume after TIPS. At the first follow-up period (90–180 d post-TIPS) lower liver volumes and TLV/weight ratios were associated with higher bilirubin levels. Within the final multivariable model containing time (days since TIPS), baseline INR and baseline TLV, the average loss of liver volume was 0.74 mL per day after TIPS. Twelve-month overall transplant-free survival was 89% and median overall TFS was 33 months. The median TFS for a baseline TLV/body weight ratio > 20 was significantly higher compared with ≤20 (40.0 vs. 27.0 months, p = 0.010) while there were no differences regarding the indication for TIPS or etiology of liver disease in the matched pair analysis. Lower TLV/weight ratios before TIPS were associated with shorter TFS and should therefore be critically considered when selecting patients for TIPS. In addition, this study provides first evidence of an effect of TIPS on subsequent liver volume change and associated liver function