Development and evaluation of a virtual reality driving test for patients with cirrhosis.

BACKGROUND: Patients with cirrhosis and especially those with HE may have impaired driving skills and may be prone to car accidents. This proof-of-concept study aimed to develop and evaluate the applicability of a virtual reality (VR)-based driving test in patients with cirrhosis. Additionally, the association between the results in the VR test and car accidents was investigated. METHODS: A short driving test using a VR head-mounted display (HTC Vive Pro Eye) was developed to simulate five hazardous situations. The patient has to pull the brake when the hazardous situations occur. The time from triggering the event to pressing the brake is recorded as reaction time. Total reaction time (TRT) is defined as the combined reaction time to all 5 events. Car accidents were assessed retrospectively (previous 12 months) and patients were followed prospectively for 6 months. Minimal HE (MHE) was diagnosed using Psychometric Hepatic Encephalopathy Score. RESULTS: In total, 112 outpatients with cirrhosis and 52 controls without cirrhosis were recruited. MHE was detected in 14% (n = 15). Patients with cirrhosis and MHE (5.67 s) had higher TRTs compared to patients without MHE (5.02 s) and controls without cirrhosis above the age of 50 (4.98 s) (MHE vs. no MHE or controls p<0.01, no MHE vs. controls: not significant). Seven patients reported car accidents during the twelve months prior to study inclusion. TRTs were numerically higher in patients with reported car accidents (p = 0.099). When patients who stopped driving for HE-related/cirrhosis-related reasons (n = 14) were added to the group of patients with accidents, then a longer TRT was significantly associated with the modeled outcome in univariable (p<0.01) and multivariable analyses (OR 2.83, p<0.01). Two car accidents occurred during follow-up. Both patients had TRTs above the 90th percentile. CONCLUSIONS: The VR driving test is easy and rapid to perform in patients with cirrhosis and could be helpful as a point-of-care tool for predicting car accidents.

Prediction of postembolization syndrome after transarterial chemoembolization of hepatocellular carcinoma and its impact on prognosis.

BACKGROUND: Postembolization syndrome (PES) represents the most frequent complication after transarterial chemoembolization (TACE) in patients with HCC. Given the vague definition as a symptom complex comprising abdominal pain, fever, and nausea, PES is diagnosed in heterogeneous patient cohorts with symptoms ranging from mild pain to severe deterioration of their general condition. This study aimed to evaluate predictive factors and the prognostic impact of PES with regard to different severity grades. METHODS: A total of 954 patients treated with TACE for HCC at the University Medical Centres Mainz and Freiburg were included in this study. PES disease severity was graded as mild, moderate, or severe according to a predefined combination of symptoms. Logistic regression models were used to identify independent predictors of PES. The prognostic impact of PES was evaluated by competing risk analyses considering liver transplantation as a competing risk. RESULTS: PES occurred in 616 patients (64.5%), but only 56 patients (5.9%) had severe PES, defined as moderate to severe abdominal pain requiring opioids in combination with fever and nausea. The largest tumor diameter was the strongest independent predictor of PES (OR = 1.21, 95% CI = 1.13-1.28), and severe PES (OR = 1.23, 95% CI = 1.14-1.33, p < 0.0001). Presence of liver cirrhosis was protective against PES (OR = 0.48, 95% CI = 0.27-0.84, p = 0.01). Furthermore, PES was independently associated with an impaired disease control rate (OR = 0.33, 95% CI = 0.16-0.69, p = 0.003) and severe PES with poor overall survival (subdistribution HR = 1.53, 95% CI = 0.99-2.36, p = 0.04). CONCLUSIONS: Tumor size and absence of liver cirrhosis are predictors of severe PES and associated with impaired prognosis in HCC patients after TACE.

Portal hypertension in patients with hepatocellular carcinoma and immunotherapy: prognostic relevance of CT-morphologic estimates.

BACKGROUND: Clinically significant portal hypertension (CSPH) has been identified as an important prognostic factor in patients with hepatocellular carcinoma (HCC) undergoing curative treatment. This study aimed to assess PH estimates as prognostic factors in patients with HCC treated with immunotherapy. METHODS: All patients with HCC treated with an immunotherapeutic agent in first or subsequent lines at our tertiary care center between 2016 and 2021 were included (n = 50). CSPH was diagnosed using the established PH score for non-invasive PH estimation in pre-treatment CT data (cut-off ≥ 4). Influence of PH on overall survival (OS) and progression-free survival (PFS) was assessed in uni- and multivariable analyses. RESULTS: Based on the PH score, 26 patients (52.0%) were considered to have CSPH. After treatment initiation, patients with CSPH had a significantly impaired median OS (4.1 vs 33.3 months, p < 0.001) and a significantly impaired median PFS (2.7 vs 5.3 months, p = 0.02). In multivariable Cox regression, CSPH remained significantly associated with survival (HR 2.9, p = 0.015) when adjusted for established risk factors. CONCLUSIONS: Non-invasive assessment of CSPH using routine CT data yielded an independent prognostic factor in patients with HCC and immunotherapy. Therefore, it might function as an additional imaging biomarker to detect high-risk patients with poor survival and possibly for treatment decision making.

Prediction and prevention of the first episode of overt hepatic encephalopathy in patients with cirrhosis.

Hepatic encephalopathy (HE) is one of the most important complications of patients with liver cirrhosis. In addition, HE is associated with a dismal prognosis and has detrimental effects on patients' quality of life. Thus, it is of pivotal importance to identify patients at high risk for overt HE (OHE) in whom primary prophylaxis may be justified. In this narrative review, we aim to provide insight into predictors and prediction tools for a first-time episode of OHE and to scrutinize the current level of evidence of primary prophylaxis. In recent decades, several cognitive tests, composite scores, and blood-based biomarkers have been demonstrated to be predictive of a first-time episode of OHE. Among the best validated are the established tests for minimal HE, such as the Psychometric Hepatic Encephalopathy Score, determination of the critical flicker frequency, Stroop EncephalApp, or the Animal Naming Test. Individualized risk stratification using blood-based biomarkers and cross-sectional imaging (sarcopenia and spontaneous portosystemic shunts) is coming to the fore, but validation in larger multicenter cohorts is often lacking. On the basis of current evidence, a recommendation for primary prophylaxis of a first episode of OHE cannot be made in general. Only 2 studies have investigated the prevention of a first-time OHE episode as the primary endpoint. In this narrative review, we provide a concise overview of the current evidence levels on prediction tools and pharmacological prevention of a first episode of OHE. In addition, we give an outlook on future research targets to improve knowledge on this important topic.

Health literacy in gastrointestinal diseases: a comparative analysis between patients with liver cirrhosis, inflammatory bowel disease and gastrointestinal cancer.

Currently, there are only few data on health literacy in patients with chronic gastrointestinal diseases such as gastrointestinal cancer, inflammatory bowel disease (IBD) and, in particular, liver cirrhosis available. Moreover, head-to-head comparisons between patients with these different diseases are lacking. In this study, 379 patients were enrolled. Of these, 102 patients had gastrointestinal cancer, 86 had IBD, and 191 had cirrhosis. Health literacy was quantified using the Health Literacy Questionnaire (HLQ) developed by Osborne et al. (Swinburne University, Australia) and was compared between these three groups. Patients with cancer had the best health literacy across all nine subscales of the HLQ, while patients with cirrhosis had the poorest. In detail, patients with cirrhosis had significantly poorer health literacy than patients with cancer or IBD in subscales such as "feeling understood and supported by healthcare providers", "having sufficient information to manage my health", "appraisal of health information", "ability to actively engage with healthcare providers" or "understanding health information well enough to know what to do" (p < 0.05 for cirrhosis versus IBD or cancer, respectively). In conclusion, health literacy differs remarkably between patients with chronic gastrointestinal diseases such as cirrhosis, IBD or gastrointestinal cancers.

Immunonutritive Scoring in Patients With Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization: Prognostic Nutritional Index or Controlling Nutritional Status Score?

OBJECTIVES: The Prognostic Nutritional Index (PNI) and Controlling Nutritional Status (CONUT) score are immunonutritive scoring systems with proven predictive ability in various cancer entities, including hepatocellular carcinoma (HCC). We performed the first evaluation of the CONUT score for patients undergoing transarterial chemoembolization (TACE) and compared CONUT and PNI in the ability to predict median overall survival (OS). METHODS: Between 2010 and 2020, we retrospectively identified 237 treatment-naïve patients with HCC who underwent initial TACE at our institution. Both scores include the albumin level and total lymphocyte count. The CONUT additionally includes the cholesterol level. Both scores were compared in univariate and multivariate regression analyses taking into account established risk factors. In a second step, a subgroup analysis was performed on BCLC stage B patients, for whom TACE is the recommended first-line treatment. RESULTS: A high CONUT score and low PNI were associated with impaired median OS (8.7 vs. 22.3 months, p<0.001 and 6.8 vs. 20.1 months, p<0.001, respectively). In multivariate analysis, only the PNI remained an independent prognostic predictor (p=0.003), whereas the CONUT score lost its predictive ability (p=0.201). In the subgroup of recommended TACE candidates, both CONUT and PNI were able to stratify patients according to their median OS (6.6 vs. 17.9 months, p<0.001 and 10.3 vs. 22.0 months, p<0.001, respectively). Again, in the multivariate analysis, only the PNI remained an independent prognostic factor (p=0.012). CONCLUSION: Both scores were able to stratify patients according to their median OS, but only the PNI remained an independent prognostic factor. Therefore, PNI should be preferred when evaluating the nutritional status of patients undergoing TACE.

Multidisciplinary approach to the complex treatment for non-cirrhotic portal hypertension - case-report-based discussion.

Non-cirrhotic portal vein thrombosis (PVT) in patients with antiphospholipid syndrome (APS) is a rare complication, and the management has to be determined individually based on the extent and severity of the presentation. We report on a 37-year-old male patient with non-cirrhotic chronic PVT related to a severe thrombophilia, comprising APS, antithrombin-, factor V- and factor X-deficiency. Three years after the initial diagnosis of non-cirrhotic PVT, the patient presented with severe hemorrhagic shock related to acute bleeding from esophageal varices, requiring an emergency transjugular intrahepatic portosystemic stent shunt (TIPSS). TIPSS was revised after a recurrent bleeding episode due to insufficient reduction of the portal pressure. Additionally, embolization of the dilated V. coronaria ventriculi led to the regression of esophageal varices but resulted simultaneously in a left-sided portal hypertension (LSPH) with development of stomach wall and perisplenic varices. After a third episode of acute esophageal varices bleeding, a surgical distal splenorenal shunt (Warren shunt) was performed to reduce the LSPH. Despite anticoagulation with low molecular weight heparin and antithrombin substitution, endoluminal thrombosis led to a complete Warren shunt occlusion, aggravating the severe splenomegaly and pancytopenia. Finally, a partial spleen embolization (PSE) was performed. In the postinterventional course, leukocyte and platelet counts increased rapidly and the patient showed no further bleeding episodes. Overall, this complex course demonstrates the need for individual assessment of multimodal treatment options in non-cirrhotic portal hypertension. This young patient required triple modality porto-systemic pressure reduction (TIPSS, Warren shunt, PSE) and involved finely balanced anticoagulation and bleeding control.