[Takayasu arteritis after COVID-19 infection in a 26-year-old female patient with Crohn's disease]. / Takayasu ­ Arteriitis nach COVID-19-Infektion bei einer 26 Jahre alten Patientin mit Morbus Crohn.

Extraintestinal manifestations, e.g. of the skin, joints or liver, are frequently found in Crohn's disease. We report about a 26-year-old female patient with longstanding Crohn's disease, who was admitted to our hospital with suspicion of an acute attack with suggestive symptoms and increased significantly inflammatory parameters. Shortly before, symptomatic COVID-19 disease (SARS-CoV-2 variant omicron) had been made. Comprehensive endoscopic and imaging diagnostics ruled out active Crohn's disease. However, inflammatory thickening of the aortic arch was seen, and a diagnosis of Takayasu arteritis (type II b) was made. Steroid therapy resulted in a rapid and sustained improvement of clinical symptoms. The occurrence of Takayasu arteritis is extremely rare outside Japan. An coincidence has been described in chronic inflammatory bowel diseases and is discussed as a possible extraintestinal manifestation. The occurrence of immune-mediated disease after COVID-19 disease has been described and may be triggered by the infection. Patients with inflammatory bowel disease may represent a special risk population.

Differentiation of Spontaneous Bacterial Peritonitis from Secondary Peritonitis in Patients with Liver Cirrhosis: Retrospective Multicentre Study.

Ascitic fluid infection is a serious complication of liver cirrhosis. The distinction between the more common spontaneous bacterial peritonitis (SBP) and the less common secondary peritonitis in patients with liver cirrhosis is crucial due to the varying treatment approaches. This retrospective multicentre study was conducted in three German hospitals and analysed 532 SBP episodes and 37 secondary peritonitis episodes. Overall, >30 clinical, microbiological, and laboratory parameters were evaluated to identify key differentiation criteria. Microbiological characteristics in ascites followed by severity of illness and clinicopathological parameters in ascites were the most important predictors identified by a random forest model to distinguish between SBP and secondary peritonitis. To establish a point-score model, a least absolute shrinkage and selection operator (LASSO) regression model selected the ten most promising discriminatory features. By aiming at a sensitivity of 95% either to rule out or rule in SBP episodes, two cut-off scores were defined, dividing patients with infected ascites into a low-risk (score ≥ 45) and high-risk group (score < 25) for secondary peritonitis. Overall, the discrimination of secondary peritonitis from SBP remains challenging. Our univariable analyses, random forest model, and LASSO point score may help clinicians with the crucial differentiation between SBP and secondary peritonitis.

[Costs of potentially outpatient endoscopic procedures in cases with a 1-day hospital stay versus a longer stay]. / Kosten potenziell ambulant erbringbarer endoskopischer Leistungen in Fällen mit 1-Tages-Verweildauer gegenüber einer längeren Verweildauer.

INTRODUCTION: The transfer of patient care and medical interventions that was previously provided on an inpatient basis to outpatient settings is a stated goal of health politics. It is unclear to what extent costs of an endoscopic procedure and the disease severity depend on the duration of inpatient treatment. We therefore examined whether endoscopic services for cases with a one-day length of stay (VWD) are comparably expensive to cases with a longer VWD. METHODS: Outpatient services were selected from the DGVS service catalog. Day cases with exactly one such gastroenterological endoscopic (GAEN) service were compared with cases with VWD>1 day regarding their patient clinical complexity levels (PCCL) and mean costs. Data from the DGVS-DRG project with §21-KHEntgG cost data from a total of 57 hospitals from 2018 and 2019 served as the basis. Endoscopic costs were taken from cost center group 8 of the InEK cost matrix and plausibility checked. RESULTS: A total of 122,514 cases with exactly one GAEN service were identified. Statistically equal costs were shown in 30 of 47 service groups. In 10 groups, the cost difference was not relevant (<10%). Cost differences >10% existed only for EGD with variceal therapy, insertion of a self-expanding prosthesis, dilatation/bougienage/exchange with PTC/PTCD in place, non-extensive ERCP, endoscopic ultrasound in the upper gastrointestinal tract, and colonoscopy with submucosal or full thickness resection, or foreign object removal. PCCL differed in all but one group. CONCLUSION: Gastroenterology endoscopy services provided as part of inpatient care but potentially performable on an outpatient basis are predominantly equally expensive for day cases as for patients with a length of stay greater than one day. The disease severity is lower. Calculated §21-KHEntgG cost data thus form a reliable basis for the calculation of appropriate reimbursement for hospital services to be provided as outpatient services under the AOP in the future.

A Novel Machine Learning-Based Point-Score Model as a Non-Invasive Decision-Making Tool for Identifying Infected Ascites in Patients with Hydropic Decompensated Liver Cirrhosis: A Retrospective Multicentre Study.

This study is aimed at assessing the distinctive features of patients with infected ascites and liver cirrhosis and developing a scoring system to allow for the accurate identification of patients not requiring abdominocentesis to rule out infected ascites. A total of 700 episodes of patients with decompensated liver cirrhosis undergoing abdominocentesis between 2006 and 2020 were included. Overall, 34 clinical, drug, and laboratory features were evaluated using machine learning to identify key differentiation criteria and integrate them into a point-score model. In total, 11 discriminatory features were selected using a Lasso regression model to establish a point-score model. Considering pre-test probabilities for infected ascites of 10%, 15%, and 25%, the negative and positive predictive values of the point-score model for infected ascites were 98.1%, 97.0%, 94.6% and 14.9%, 21.8%, and 34.5%, respectively. Besides the main model, a simplified model was generated, containing only features that are fast to collect, which revealed similar predictive values. Our point-score model appears to be a promising non-invasive approach to rule out infected ascites in clinical routine with high negative predictive values in patients with hydropic decompensated liver cirrhosis, but further external validation in a prospective study is needed.

Clinical implications of diabetes in chronic liver disease: Diagnosis, outcomes and management, current and future perspectives.

Diabetes mellitus (DM) is common in liver cirrhosis (LC). The pathophysiological association is bidirectional. DM is a risk factor of LC and LC is a diabetogenic condition. In the recent years, research on different aspects of the association DM and LC has been intensified. Nevertheless, it has been insufficient and still exist many gaps. The aims of this review are: (1) To discuss the latest understandings of the association of DM and LC in order to identify the strategies of early diagnosis; (2) To evaluate the impact of DM on outcomes of LC patients; and (3) To select the most adequate management benefiting the two conditions. Literature searches were conducted using PubMed, Ovid and Scopus engines for DM and LC, diagnosis, outcomes and management. The authors also provided insight from their own published experience. Based on the published studies, two types of DM associated with LC have emerged: Type 2 DM (T2DM) and hepatogenous diabetes (HD). High-quality evidences have determined that T2DM or HD significantly increase complications and death pre and post-liver transplantation. HD has been poorly studied and has not been recognized as a complication of LC. The management of DM in LC patients continues to be difficult and should be based on drug pharmacokinetics and the degree of liver failure. In conclusion, the clinical impact of DM in outcomes of LC patients has been the most studied item recently. Nevertheless many gaps still exist particularly in the management. These most important gaps were highlighted in order to propose future lines for research.

Serum electrolytes, osmolality, and cleansing quality after bowel prep for colonoscopy with a PEG solution containing ascorbic acid and electrolytes.

BACKGROUND: The cleansing procedure with PEG 3350 + ascorbic acid (PEG + Asc; Moviprep®) requires the additional ingestion of clear liquids. We aimed to determine the effects on serum electrolytes, osmolality and cleansing quality, and in a prospective "real world" trial. PATIENTS AND METHODS: Patients underwent a standardized split-dose bowel preparation for colonoscopy with PEG + Asc. Serum electrolytes and osmolality were measured before and after the prep procedure. The volume of prep solution (PA) and additional clear liquid (CL) was recorded. Prep quality was assessed using the Ottawa Bowel Prep Grading Scale (OBPS). The primary outcome measures were changes of serum electrolytes and osmolality during the cleansing procedure. A secondary end point was the OPBS. RESULTS: One hundred ninety-one of 219 patients entered the per protocol analysis. Prep quality was considered excellent in 57.6%, moderate in 20.9%, and insufficient in 21.5%. The number of patients with hyponatremia increased from 12 (6.3%) before to 25 (13.2%) after the prep procedure. Mean sodium concentration did not change significantly. The volume of CL correlated inversely with Na+ concentration (r = - 0.409, p < 0.01) and a worse OBPS (r = 0.198, p < 0.01). CONCLUSIONS: Bowel preparation with PEG-Asc in clinical routine is generally safe, but patients should be advised not to drink more than 2 l of clear liquid because of imminent electrolyte disturbances. Additionally, the quality of cleansing either remains unchanged or may even worsen.

[Endoscopic tunneling procedures in achalasia and gastroparesis]. / Endoskopische Tunnelungsverfahren bei Achalasie und Gastroparese.

Since the first publication of peroral endoscopic myotomy (POEM) by Haruhiro Inoue et al. in 2008 in Japan, various novel endoscopic procedures have been established, which are performed after iatrogenic creation of a submucosal tunnel as a "new space" 1. Through the artificially formed access in the tela submucosa, interventions in the muscular layer of the esophagus and stomach can be performed while carefully sparing the mucosal layer 2. These include, peroral myotomy of the esophageal muscle layer in patients with achalasia (POEM) and myotomy of the pylorus in patients with gastroparesis (antropyloromyotomy, G-POEM). Further indications include splitting of Zenker diverticulum in POEM technique ("Z-POEM") as well as the removal of subepithelial tumors (STER: submucosal tunneling, endoscopic resection). The long-term therapeutic success (with > 80 % response) of these innovative procedures has now been proven by controlled studies, especially in achalasia 2 3 4 5 6.

Damage control strategy in perforated diverticulitis with generalized peritonitis.

BACKGROUND: The best treatment for perforated colonic diverticulitis with generalized peritonitis is still under debate. Concurrent strategies are resection with primary anastomosis (PRA) with or without diverting ileostomy (DI), Hartmann's procedure (HP), laparoscopic lavage (LL) and damage control surgery (DCS). This review intends to systematically analyze the current literature on DCS. METHODS: DCS consists of two stages. Emergency surgery: limited resection of the diseased colon, oral and aboral closure, lavage, vacuum-assisted abdominal closure. Second look surgery after 24-48 h: definite reconstruction with colorectal anastomosis (-/ + DI) or HP after adequate resuscitation. The review was conducted in accordance to the PRISMA-P Statement. PubMed/MEDLINE, Cochrane central register of controlled trials (CENTRAL) and EMBASE were searched using the following term: (Damage control surgery) AND (Diverticulitis OR Diverticulum OR Peritonitis). RESULTS: Eight retrospective studies including 256 patients met the inclusion criteria. No randomized trial was available. 67% of the included patients had purulent, 30% feculent peritonitis. In 3% Hinchey stage II diverticulitis was found. In 49% the Mannheim peritonitis index (MPI) was greater than 26. Colorectal anastomosis was constructed during the course of the second surgery in 73%. In 15% of the latter DI was applied. The remaining 27% received HP. Postoperative mortality was 9%, morbidity 31% respectively. The anastomotic leak rate was 13%. 55% of patients were discharged without a stoma. CONCLUSION: DCS is a safe technique for the treatment of acute perforated diverticulitis with generalized peritonitis, allowing a high rate of colorectal anastomosis and stoma-free hospital discharge in more than half of the patients.

Technical success, resection status, and procedural complication rate of colonoscopic full-wall resection: a pooled analysis from 7 hospitals of different care levels.

INTRODUCTION: Endoscopic full-thickness resection (eFTR) using the full-thickness resection device (FTRD®) is a novel minimally invasive procedure that allows the resection of various lesions in the gastrointestinal tract including the colorectum. Real-world data outside of published studies are limited. The aim of this study was a detailed analysis of the outcomes of colonoscopic eFTR in different hospitals from different care levels in correlation with the number of endoscopists performing eFTR. MATERIAL AND METHODS: In this case series, the data of all patients who underwent eFTR between November 2014 and June 2019 (performed by a total of 22 endoscopists) in 7 hospitals were analyzed retrospectively regarding rates of technical success, R0 resection, and procedure-related complications. RESULTS: Colonoscopic eFTR was performed in 229 patients (64.6% men; average age 69.3 ± 10.3 years) mainly on the basis of the following indication: 69.9% difficult adenomas, 21.0% gastrointestinal adenocarcinomas, and 7.9% subepithelial tumors. The average size of the lesions was 16.3 mm. Technical success rate of eFTR was achieved in 83.8% (binominal confidence interval 78.4-88.4%). Overall, histologically complete resection (R0) was achieved in 77.2% (CI 69.8-83.6%) while histologically proven full-wall excidate was confirmed in 90.0% (CI 85.1-93.7%). Of the resectates obtained (n = 210), 190 were resected en bloc (90.5%). We did not observe a clear improvement of technical success and R0 resection rate over time by the performing endoscopists. Altogether, procedure-related complications were observed in 17.5% (mostly moderate) including 2 cases of acute gangrenous appendicitis requiring operation. DISCUSSION: In this pooled analysis, eFTR represents a feasible, effective, and safe minimally invasive endoscopic technique.

Small intestinal dysmotility in cirrhotic patients: correlation with severity of liver disease and cirrhosis-associated complications.

INTRODUCTION: Altered small intestinal motility has been observed in various manometry studies in patients with cirrhosis. Since small bowel manometry is available only in a few centers, interpretation of dysmotility in cirrhosis is controversial. PATIENTS AND METHODS: In this study, both fasting and postprandial manometric tracings of 24-hour antroduodenojejunal manometries were analyzed using both visual analysis and computer-aided analysis. RESULTS: In 34 patients (83 %), the mean migrating motor complex (MMC) cycle length was different compared with healthy controls. Phase II was prolonged in 27 patients (66 %), while phase I showed a reduced duration in 23 (56 %) and in phase III in 13 individuals (32 %). We also observed special motor patterns, e. g., migrating clustered contractions (MCCs) or retrograde clustered contractions (RCCs), which were present during fasting (69 %) and postprandial (92 %) motility, while none of the healthy controls showed any special motor patterns. Special motor patterns showed a significant correlation with the severity of cirrhosis (Child-Score; p > 0.05) and the existence of ascites (p < 0.05). DISCUSSION: This study in a large cohort of patients with cirrhosis by using 24-hour, solid state portable manometry showed in most individuals disturbances of cyclic fasting motility. Special motor patterns like RCCs during fasting and postprandial motility could be observed exclusively in the cirrhosis group, showing a significant correlation with severity of cirrhosis and the occurence of associated complications.

Overlap of concurrent extrahepatic autoimmune diseases is associated with milder disease severity of newly diagnosed autoimmune hepatitis.

BACKGROUND: Concurrent extrahepatic autoimmune disorders (CEHAID) are frequently observed in autoimmune hepatitis (AIH). It is not clear whether there is any prognostic significance of CEHAID on AIH. The aim of this study was to examine the prognostic impact of CEHAID and the correlation with the disease severity of AIH. METHODS: This study included 65 hospitalized subjects who fulfilled the accepted criteria for AIH during an 8-year period (2009-2016). All records were manually screened for presence of associated autoimmune diseases. Disease severity of AIH was assessed by liver laboratory tests including the ratio of aspartate aminotransferase to alanine aminotransferase (AST/ALT) and liver histology. RESULTS: Among the enrolled patients, 52 (80%) were female (median age 61 years, IQR 45-75). Fifty-six (86.2%) were classified as type-1 AIH. In 26 (40%) patients at least one additional extrahepatic autoimmune disease was diagnosed. Thirty-four subjects were referred to our hospital because of acute presentation of AIH (supposed by an acute elevation of hepatic enzymes) for subsequent liver biopsy resulting in initial diagnosis of AIH. This group was stratified into 3 subgroups: (A) AIH alone (n = 14); (B) overlap with primary biliary cirrhosis (PBC) / primary sclerosing cholangitis (PSC) (n = 11); and (C) with CEHAID (n = 9). AST/ALT ratio was the lowest in subgroup C (median 0.64, IQR 0.51-0.94; P = 0.023), compared to subgroup A (median 0.91, IQR 0.66-1.10) and subgroup B (median 1.10, IQR 0.89-1.36). Patients with AIH alone showed a trend to the highest grade of fibrosis (mean 2.3; 95% CI: 1.5-3.0) with no statistical significance compared to subjects with CEHAID (lowest grade of fibrosis; mean 1.5; 95% CI: 0.2-2.8; P = 0.380) whereas the ongoing inflammation was comparable. CONCLUSIONS: AST/ALT ratio and extent of fibrosis were lower in subjects with AIH and CEHAID, compared to subjects with only AIH. Therefore, the occurrence of CEHAID might be a predictor for lower disease severity of newly diagnosed acute onset AIH, possibly caused by an earlier diagnosis or different modes of damage.

Role of Brain Biomarkers S-100-Beta and Neuron-Specific Enolase for Detection and Follow-Up of Hepatic Encephalopathy in Cirrhosis before, during and after Treatment with L-Ornithine-L-Aspartate.

INTRODUCTION: Hepatic encephalopathy (HE), in the context of liver cirrhosis, seems to result from low-grade cerebral edema of the astrocytes. Serum brain biomarkers S-100-beta und neuron-specific enolase (NSE) are often elevated in brain injury. We hypothesized that neuromarkers S-100-beta and NSE can be used in the diagnosis of HE, compared with standardized diagnostic tools. MATERIAL AND METHODS: A prospective non-randomized intervention study was performed using L-ornithine-L-aspartate (LOLA) for HE treatment. Primary endpoint was the evaluation of neuromarkers S-100-beta and NSE for detection and diagnosis of follow-up of HE. As secondary endpoints, the efficacy of LOLA on the course of HE and the diagnostic role of Portosystemic-Encephalopathy-Syndrome score (PHES) and critical flicker frequency (CFF) were analyzed. For diagnosis of covert (CHE) and overt (OHE) HE, West-Haven criteria (WHC), PHES and CFF were assessed at study entry. LOLA was applied (20 g i.v.) for 6 days. At the end of the study, HE evaluation was repeated. S-100-beta, NSE and ammonia were assessed in each patient before, during and after therapy with LOLA. RESULTS: 30 patients were included. At study entry, CHE was diagnosed in 50% and OHE in 50% of all subjects. A total of 25 participants completed the study. After LOLA therapy, deterioration of HE occurred in <11%, while most patients showed improvement (e.g. improved CFF in 79%). No significant correlation with HE severity (as diagnosed by WHC, PHES and CFF) could be demonstrated for any biochemical parameter. In addition, there were no significant changes in brain biomarkers during the treatment period. DISCUSSION: While CFF as well as PHES showed good correlation with treatment response, S-100-beta and NSE did not significantly correlate with HE severity compared to proven diagnostic methods, and do not seem reliable biochemical markers for the follow-up under therapy.

INTRODUÇÃO: A encefalopatia hepática (EH) na cirrose é vista como o resultado de edema cerebral de baixo grau dos astrócitos. Biomarcadores cerebrais serológicos S-100-beta e enolase neurónio-específica (NSE) estão frequentemente elevados na lesão cerebral. A nossa hipótese é que os neuromarcadores S-100-beta e NSE podem ser usados no diagnóstico de EH, quando comparados com os meios diagnósticos standard. MATERIAL E MÉTODOS: Estudo prospectivo não randomizado foi realizado usando L-ornitina-L-aspartato (LOLA) no tratamento da EH. O endpoint primário foi a avaliação dos neuromarcadores S-100-beta e NSE para a deteção e vigilância da EH. Foram endpoints secundários a eficácia da LOLA no curso da EH e o papel diagnóstico do Portosystemic-Encephalopathy-Syndrome score (PHES) e do critical flicker frequency (CFF). Para o diagnóstico de EH oculta (EHO) ou declarada (EHD) foram avaliados os West-Haven criteria (WHC), PHES e CFF à entrada do estudo. LOLA foi administrada (20 g ev) por 6 dias. No fim do estudo os testes de EH foram repetidos. Os níveis de S-100-beta, NSE e amónia foram avaliados em todos os doentes antes, durante e após a terapêutica com LOLA. RESULTADOS: Foram incluídos 30 doentes no estudo. À entrada EHO foi diagnosticada em 50% e EHD nos restantes 50% dos participantes. Um total de 25 doentes completaram o estudo. Após a terapêutica com LOLA, verificou-se deterioração da EH em < 11%, enquanto a maioria dos doentes melhorou (melhoria CFF em 79%). Não se demonstrou nenhuma correlação significativa com a gravidade da EH (tendo em conta os WHC, PHES e CFF) para nenhum dos parâmetros bioquímicos. Para além disso, não se demonstraram variaões significativa nos biomarcadores cerebrais durante o período de tratamento. DISCUSSÃO: Apesar do CFF e do PHES apresentarem boa correlação com a resposta terapêutica, a S-100-beta e a NSE não se correlacionaram significativamente com a gravidade da EH quando comparado com os outros métodos diagnósticos standard, não parecendo ser marcadores bioquímicos úteos para a vigilância da resposta terapêutica.

[Prognostic significance and economic burden of hepatic encephalopathy in liver cirrhosis in German hospitals based on G-DRG data]. / Mortalität und ökonomische Auswirkungen der hepatischen Enzephalopathie bei Leberzirrhose in deutschen Krankenhäusern auf der Basis von G-DRG-Kostendaten.

INTRODUCTION: Hepatic encephalopathy (HE) represents a frequent complication of liver cirrhosis with negative effects on patients' lives. The prevalence of clinical HE is estimated to be between 30-45 %. Regardless of its clinical and prognostic relevance HE is considered to be underdiagnosed. METHODS: Beyond a systematic analysis of mortality of HE, we investigated the economic impact and reimbursement situation for HE in patients with liver cirrhosis in Germany. For the retrospective analysis, anonymized data (2011-2015) concerning expenses and diagnoses (§â€Š21-4 KHEntgG) were obtained from 74 participating hospitals of the Diagnosis Related Groups (DRG) Project of the German Gastroenterological Association (DGVS). Furthermore, results were compared with case data from all German hospitals provided by the German Federal Authority on Statistics (Statistische Bundesamt (Destatis), Wiesbaden). RESULTS: In participating hospitals 59 093 cases with liver cirrhosis were identified of which 14.6 % were coded as having HE. Hospital mortality was threefold increased compared to cirrhosis-patients without HE (20.9 versus 7.5 %). Cases with cirrhosis as well as the proportion with HE increased over time. Compared to all patients with cirrhosis, reimbursement for HE patients produced a deficit (of up to 634 € for HE grade 4). DISCUSSION: Mortality is threefold increased in patients with cirrhosis when an additional HE is diagnosed. Hospitals participating in the DGVS-DRG-project coded 2 % more HE cases among their cirrhosis cases than the rest of hospitals either because of a selection bias for greater disease severity or because of better coding quality. At present, reimbursement for HE patients on the basis of F-DRG-system produced a deficit.

Frequency of Polyps and Adenocarcinoma in Colon Interposition After Esophagectomy in Adulthood - A Systematic Review.

BACKGROUND/AIM: Colon interposition counts among the most common techniques for reconstruction after esophagectomy. Availability of data on metachronous mucosal pathologies is weak. The aim of this review was to identify all reports on the development of metachronous adenoma and adenocarcinoma in colon interposition after esophagectomy in adulthood. MATERIALS AND METHODS: A comprehensive search was conducted in MEDLINE/PubMed, Science Direct, Cochrane Library, Bayerische Staatsbibliothek München. All studies reporting on patients who received colon interposition as substitute after esophagectomy in adulthood for benign and malignant reasons were included. RESULTS: Five retrospective studies were included, reporting on 1016 patients. Therein, no interval lesion was identified. One further study, which formally must be excluded for a misfit to inclusion criteria reports on three interval carcinomas within 365 patients. Because these lesions were the only ones found within a cohort analysis, results were supplementary reported in this review. Additionally, 31 case reports including 32 patients with benign (n=7) or malignant (n=25) findings were analyzed. Median age was 63.5 years (interval carcinoma) and 69 years (benign lesion). Benign and malignant lesions were diagnosed after a median of 8.5 years. CONCLUSION: Due to the rareness of respective cohort studies, the frequency of metachronous lesions cannot be calculated accurately. The estimated rate of interval carcinoma is 0-0.22%. Life-long endoscopic surveillance of patients with colon interposition is recommended.

[Updated S2k-Guideline "Complications of liver cirrhosis". German Society of Gastroenterology (DGVS)]. / Aktualisierte S2k-Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) "Komplikationen der Leberzirrhose".

This guideline provides evidence-based key recommendations for diagnosis and therapy of complications of liver cirrhosis and upgrades the 2011 version. An interdisciplinary team of medical experts and patient support groups developed the guideline following the AWMF recommendations for evidence based consensus guidelines. New chapters concerning diagnosis and therapy of hepatic encephalopathy were added.