Cholestatic Parameters Research Articles

Preoperative MRCP is not Associated with Lower Complication Rates but Shorter Hospital Stay in Laparoscopic Cholecystectomy

Abstract Background Laparoscopic cholecystectomy is a very common procedure and while preoperative magnetic resonance cholangiopancreatography (pMRCP) is widely used for detection of choledocholithiasis and preoperative planning, the benefits in patients with normal preoperative cholestatic parameters remain unclear. Aims We aimed to investigate a large cohort of patients after laparoscopic cholecystectomy to analyse the impact of pMRCP on complication rates. Methods This retrospective cohort study consecutively includes all patients receiving elective or acute laparoscopic cholecystectomy between 2010 and 2020. Exclusion criteria were conversion to open cholecystectomy and preoperatively elevated cholestatic parameters. Complication rates were recorded and patients stratified depending on the use of pMRCP for preoperative planning. Results 3163 patients underwent laparoscopic cholecystectomy between 2010 and 2020, 2568 of which showed normal cholestatic parameters preoperatively. Of these patients, 684/2568 (27%) were male and 1884/2568 (73%) female. The most frequent indications for laparoscopic cholecystectomy were cholecystolithiasis in 72% (1845/2568) of cases, followed by cholecystitis in 18% (465/2568). The majority of patients (2267/2568, 88%) indeed received pMRCP, while the remaining 301/2568 patients did not. Postoperative complication rates did not significantly differ between the two groups (396/2267 (17%) in the pMRCP group and 58/301 (19%) without pMRCP, p=0.469). One case of pancreatitis occurred in the pMRCP group, versus two reported cases in the other group. Interestingly, the length of hospital stay after cholecystectomy was significantly shorter in the group with pMRCP versus without (4 days (range 1-61 days) versus 7 days (range 1 – 66 days), respectively, p = 0.023). Conclusion Preoperative MRCP seems to not prevent complications in laparoscopic cholecystectomy, since postoperative complication rates were comparable between the two patient groups with and without pMRCP. However, postoperative hospital stay was significantly shorter in patients undergoing pMRCP compared to patients without pMRCP.

Deciphering the liver enigma: distinguishing drug-induced liver injury and metabolic dysfunction-associated steatotic liver disease—a comprehensive narrative review

Drug-induced liver injury (DILI) poses a complex and heterogeneous clinical challenge, which often resembles non-drug related acute or chronic liver diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). Furthermore, certain drugs can induce hepatic steatosis, which is considered a rare variant of hepatotoxicity. Additionally, the detection and diagnosis of DILI in patients with non-alcoholic liver disease present additional challenges that require attention. The importance of achieving an accurate diagnosis is highlighted by the different therapeutic approaches needed for each of these diseases. Nonetheless, as definitive diagnostic tests and distinct biomarkers often remain elusive, the differential diagnosis must rely on a combination of clinical, biochemical, histological, and immunophenotypic profiling. The diagnosis of hepatotoxicity is predicated upon the temporal nexus between the administration of a potentially hepatotoxic drug and the onset of hepatic injury, concomitantly excluding alternative hepatic pathologies. More frequently, this condition presents an acute course, with a more pronounced elevation of cytolytic and cholestatic parameters as compared to fatty liver disease. Advances in elucidating the underlying mechanisms hold promise for bolstering the diagnosis and management of these conditions. This article aims to thoroughly examine and emphasize the currently available scientific evidence to provide valuable insights into the diagnostic strategies for DILI, metabolic-associated liver disease, and drug-induced steatosis (DIS).

Characteristics of liver function in patients with preeclampsia

BACKGROUND:Despite a significant number of studies devoted to the problem of preeclampsia, to date, a large number of issues related to the etiology, pathogenesis, and therapy for this pathology remain far from a final solution. That is why obstetricians always face the difficult task of developing rational tactics for the management and delivery of pregnant women with preeclampsia, one has to take into account all the risks to the health of both the mother and her unborn child. Therefore, relevant is the search for the most informative methods for diagnosing liver dysfunction with an increase in the severity of preeclampsia. The hepatobiliary system is known to carry a multifunctional load during gestation and is one of the first to respond to an increase in the severity of preeclampsia. It is, therefore, crucial to choose priority biochemical parameters of blood that reflect liver function in preeclampsia, which can be used as additional criteria for making an obstetric decision in order to prevent maternal and perinatal complications.
 AIM: The aim of this study was to analyze alterations in liver function in preeclampsia, in order to determine the criteria for the development of hepatic cell insufficiency as indicators of the transition to severe preeclampsia and multiple organ failure.
 MATERIALS AND METHODS:This study included 123 pregnant women, of which group I (n= 40) consisted of pregnant women with preeclampsia without changes in liver function, group II (n= 33) was made up of pregnant women with preeclampsia and impaired liver function, while group III (n= 50) only comprised pregnant women with normal pregnancy. All pregnant women underwent a biochemical blood test with the determination of the parameters of cytolysis (aspartate aminotransferase, alanine aminotransferase, glutamate dehydrogenase, De Ritis ratio), cholestasis (alkaline phosphatase, total and direct bilirubin, gamma-glutamyl transpeptidase, bile acids), and hepatic cell insufficiency (cholinesterase, total protein, albumin, urea, lactate dehydrogenase), as well as a clinical blood test and coagulation tests. Pregnant women with preeclampsia were observed in the intensive care unit, with vital functions monitored.
 RESULTS: The leading syndrome complex with increasing severity of preeclampsia was the cytolytic one, in which the levels of transaminases increased moderately with a predominance of alanine aminotransferase over aspartate aminotransferase activities (the De Ritis ratio was lesser than 1.0). With the development of hepatic cell insufficiency, aspartate aminotransferase activity dominated over alanine aminotransferase one (the De Ritis ratio was greater than 1.33). We also found an increase in glutamate dehydrogenase and lactate dehydrogenase activities and, among the cholestatic parameters, in the level of direct bilirubin. Hepatic cell insufficiency was characterized by a decrease in the activity of cholinesterase and decreased total protein and albumin concentrations. In the group of pregnant women with preeclampsia, we found a decrease in hemoglobin and platelet counts.
 CONCLUSIONS:Altered liver function in preeclampsia reflects an increase in the severity of the pathology and indicates the development of multiple organ failure. In its terminal stage, all syndrome complexes manifest themselves as cytolytic, cholestatic and hepatic cell insufficiencies.

Cardiohepatic syndrome and its prognostic predictive ability in patients with pulmonary arterial hypertension

With the development of progressive right ventricular dysfunction, pulmonary arterial hypertension (PAH) is one of the causes of type 2 cardiohepatic syndrome (CHS). Risk assessment, timely and effective management are crucial to improve survival in PAH. Thus, we aimed to evaluate the presence of CHS at diagnosis and its association with prognosis in patients with PAH. One hundred and eighteen consecutive incident patients with PAH between January 2013 and June 2021 were retrospectively included. The presence of CHS was assessed from blood tests taken during diagnostic evaluation and was defined as elevation of at least two of three cholestatic liver parameters; total bilirubin, alkaline phosphatase and gamma-glutamyl transferase. The primary endpoint was all-cause mortality. Patients were followed for a median period of 58 (32–96) months. 23.7% of the patients had CHS at diagnosis. Significantly more patients in CHS (+) group were in intermediate and high-risk categories according to 2015 ESC/ERS guideline, REVEAL 2.0 and REVEAL Lite 2 risk assessment methods (p = .02, .03 and <.001, respectively). The presence of CHS was identified as an independent predictor of mortality (HR: 2.17, 95% CI: 1.03–4.65, p = .03) along with older age (HR: 2.89, 95% CI: 1.50–5.56, p = .001) and higher WHO functional class (HR: 2.57, 95% CI: 1.07–6.22, p = .03). To conclude, presence of CHS at diagnosis in patients with PAH was associated with severe disease and poor prognosis independent of other well known risk factors. As a simple and easy parameter to assess from routinely taken blood tests, CHS should be evaluated in patients with PAH.

A41 FONTAN ASSOCIATED LIVER DISEASE: THE ROLE OF TRANSIENT ELASTOGRAPHY IN CHILDREN AND ADOLESCENTS

Abstract Background Non-invasive assessment of Fontan Associated Liver Disease (FALD) is of interest, but studies have yielded inconsistent results about the correlation of severity of disease with laboratory values and imaging. Transient elastography (TE) is a non-invasive imaging modality used commonly for liver stiffness measurement (LSM) and in Fontan patients it is hypothesized to reflect not only liver fibrosis but also venous congestion. Purpose To better define the potential role of TE for non-invasive assessment of the severity of FALD. Method This was a retrospective study conducted on patients’ medical records at CHU Sainte-Justine Hospital. Patients less than 18 years of age with FALD who had at undergone at least one LSM by TE between 1998-2021 were included. The relationship between LSM and liver function tests, hepatic ultrasound findings (including a cirrhosis score), cardiac catheterization results and histological fibrosis scores were analyzed. The impact of interventions during cardiac catherization on LSM were also studied. Result(s) A total of 54 patients (36 boys and 18 girls) with FALD were studied. Median age at Fontan surgery was 4.6 years (IQR 4.0 ─ 5.4 years). Higher LSM values significantly correlated with longer time from Fontan, higher total and direct bilirubin and GGT levels, higher INR, longer APTT, lower Factor V, and lower absolute lymphocyte count. Greater LSM was also significantly associated with the presence of heterogenous parenchymal echogenicity, irregular liver contours and greater ultrasonographic cirrhosis scores. Higher TE values were significantly correlated with higher wedged hepatic venous pressure and Fontan pressure. After catherization interventions that addressed stenoses, there was a statistically significant reduction in mean LSM (24.9±3.63 kPa vs 15.8±4.6 kPa, p=0.005). After closure of significant pulmonary collaterals, mean LSM tended to increase, but this difference did not reach statistical significance (19.1±1.9 kPa vs 24.6±3.5 kPa, p=0.2). At liver biopsy, significant direct correlation was found between LSM and the grade of sinusoidal fibrosis and LSM. TE with values &amp;gt;20 kPa were found to have higher grades of sinusoidal fibrosis, while values &amp;lt;20kPa had higher grades of sinusoidal dilatation. Conclusion(s) This study showed that TE allows to identify patients with higher cholestatic parameters, more severe liver fibrosis at biopsy and sonographic signs suggestive of cirrhosis. Moreover, it confirmed that liver congestion significantly contributes to LSM values. Interestingly, catheter interventions addressing pulmonary stenoses led to the improvement of TE measurements, giving hope for the reduction of hepatic venous congestion in these patients, which might have an effect on their FALD. Finally, the LSM threshold of 20 kPa could be useful clinically as a value above which fibrosis is likely to be significant, while if below could indicate a greater contribution from hepatic congestion. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Disease Status at Diagnosis in Danish Children with α 1 -antitrypsin Deficiency.

The aim of this cross-sectional study was to assess the state of disease at the time of diagnosis in Danish children with α 1 -antitrypsin deficiency as Denmark has a high prevalence of ZZ-homozygosity. Children either heterozygous, compound heterozygous, or homozygous for Z- and S-variants in the SERPINA1 -gene were included. Clinical characteristics, SERPINA1 -genotype, and blood serum (S) concentrations were recorded concurrently with genetic testing. Serum liver marker concentrations were compared using T tests and Wilcoxon-Mann-Whitney tests. Generalized estimating equation (GEE) linear regression models, both univariable and multivariable adjusted for age and sex, were applied to identify correlations with serum α 1 -antitrypsin (S-AAT). The relationship between S-AAT concentration and genotype was assessed using logistic regression with GEE. The study included 183 of 225 children genetically tested for alpha-1-antitrypsin deficiency (AATD). Of these, 36.6% were homozygous for the Z-variant. Of the heterozygotes, 89.7% had a ZM genotype and the remaining had either an MS genotype or were compound heterozygous. At diagnosis, ZZ-homozygous children had higher serum concentrations of liver enzymes and conjugated bilirubin, but lower concentrations of S-AAT compared with heterozygotes. Serum concentrations of conjugated bilirubin and liver enzymes were negatively associated with S-AAT. Children under 6 months of age had higher total S-bilirubin concentrations than children over 6 months of age. A low S-AAT concentration is a strong indicator of homozygosity, and homozygous children have higher enzymatic and cholestatic parameters compared with heterozygous children at diagnosis. This underlines the importance of measuring the S-AAT concentration in children with prolonged neonatal jaundice.

Defining Primary Sclerosing Cholangitis: Results From an International Primary Sclerosing Cholangitis Study Group Consensus Process

Defining Primary Sclerosing Cholangitis: Results From an International Primary Sclerosing Cholangitis Study Group Consensus Process

Altered faecal microbiome and metabolome in IgG4-related sclerosing cholangitis and primary sclerosing cholangitis

ObjectiveMultiple clinical similarities exist between IgG4-related sclerosing cholangitis (IgG4-SC) and primary sclerosing cholangitis (PSC), and while gut dysbiosis has been extensively studied in PSC, the role of the gut microbiota...

Distinctive Features of Hepatic Steatosis in Children: Is It Primary or Secondary to Inborn Errors of Metabolism?

PurposeThe incidence of hepatic steatosis among children has been increasing; however, data distinguishing simple steatosis from a more complex disorder are lacking.MethodsThis study identified the etiologies resulting in hepatic steatosis through a retrospective review of pediatric liver biopsies performed in the last 10 years. A total of 158 patients with hepatic steatosis proven by histopathological evaluation were enrolled in the study, and baseline demographic features, anthropometric measurements, physical examination findings, laboratory data, ultrasonographic findings, and liver histopathologies were noted.ResultsThe two most common diagnoses were inborn errors of metabolism (IEM) (52.5%) and nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) (29.7%). The three most common diseases in the IEM group were glycogen storage disorders, Wilson's disease, and mitochondrial disease. The rates of consanguineous marriage (75.6%; odds ratio [OR], 26.040) and positive family history (26.5%; OR, 8.115) were significantly higher (p=0.002, p<0.001, respectively) in the IEM group than those in the NAFLD/NASH group. Younger age (p=0.001), normal anthropometric measurements (p=0.03), increased aspartate aminotransferase levels (p<0.001), triglyceride levels (p=0.001), and cholestatic biochemical parameters with disrupted liver function tests, as well as severe liver destruction of hepatic architecture, cholestasis, fibrosis, and nodule formation, were also common in the IEM group.ConclusionParents with consanguinity and positive family history, together with clinical and biochemical findings, may provide a high index of suspicion for IEM to distinguish primary steatosis from the consequence of a more complex disorder.

Focal pancreatic lesions in autoimmune pancreatitis and weight loss

A 67-year-old male patient was admitted to hospital with upper abdominal pain, jaundice and pale stool for 2 weeks. Laboratory investigation showed highly elevated cholestatic parameters and transaminases but no...

Sex differences in clinical presentation and prognosis in patients with primary biliary cholangitis

Objectives: Primary biliary cholangitis (PBC) is a chronic inflammatory disease of the small intrahepatic bile ducts disproportionally affecting women. Timely diagnosis and treatment can often prevent progression to liver cirrhosis. We hypothesized PBC diagnosis in male patients is delayed and prognosis impaired. We, therefore, conducted a case–control study and compared clinical and prognostic features among male and female patients with PBC.Materials and methods: 49 male patients with PBC treated at a German tertiary care center between 2006 and 2017 were identified and compared to 98 age-matched female controls. Prospectively collected clinical/biochemical data were analyzed retrospectively. Liver biopsies were scored in a blinded fashion. Prognostic parameters were calculated using established prognostic scores (GLOBE, PBC-UKE). Statistical analysis was performed using Mann-Whitney test and Fisher´s exact test.Results: At PBC diagnosis, male patients reported significantly less PBC-associated symptoms as compared to female controls (34 versus 71%, p < .01). Compared to female patients, median time from onset of PBC-related symptoms and/or first reported elevated cholestatic biochemical parameters to PBC diagnosis was significantly increased in men (36 versus 12 months, p = .02). In addition, male patients underwent liver biopsy to establish PBC diagnosis more frequently, tended to show more advanced fibrosis and showed significantly poorer prognostic PBC score results. Hepatocellular carcinoma was only observed in male patients (n = 3).Conclusions: When compared to women, men with PBC suffer from less PBC-related symptoms, receive PBC diagnosis delayed and have a worse prognosis. Despite its rarity, the diagnosis of PBC should be considered in men with elevated cholestatic parameters.

Obstructive jaundice due to a blood clot after ERCP: a case report and review of the literature

BackgroundEndoscopic retrograde cholangiopancreatography (ERCP) is one of the most frequently performed procedures for the treatment of biliary-pancreatic diseases. The most frequent complications of ERCP include pancreatitis, haemorrhage, perforation and cholangitis. While post-ERCP biliary bleeding leading to biliary obstruction is rare.Case presentationWe herein report a case of exceptional post-ERCP cholangitis due to a blood clot in the common bile duct (CBD). This case involves a 75-year-old woman with a history of recurring upper abdominal pain. Abdominal computerized tomography (CT) revealed dilatation of the extrahepatic bile duct with stones at the lower CBD. After ERCP, clearance of stones was obtained. The post-ERCP course was symptomatic with upper abdominal pain and a significant increase in cholestatic parameters. A second CT scan demonstrated a markedly dilated biliary tree with a longitudinal high-density image at the middle CBD. The patient was successfully treated with a repeated ERCP, and a blood clot was extracted. We also present a review of the literature published between 1985 and 2016 in PubMed. Four similar cases were reported during this period from France, Turkey, the USA and the UK, separately. Our case is the first reported in China.ConclusionsPost-ERCP biliary bleeding leading to biliary obstruction is rare. We describe a rare case of post-ERCP cholangitis due to a blood clot in the common bile duct (CBD), which is consistent with most clinical presentations of similar cases already described. An analysis of the possible pathophysiological mechanisms and a review of the current literature are provided. We attempt to attract clinicians’ attention to the differential diagnosis of post-ERCP obstruction. The complications might be severe or even fatal. The diagnosis of blood clot is based on clinical and laboratory data, particularly imaging. Repeated ERCP is often necessary and effective.

Reversible biliary occlusion in a small animal model: first description of a new technique.

BackgroundExperimental models with reversible biliary occlusion resulted in a high mortality of the animals, up to 20–60% according to the literature. Our aim was to assess a safe and valid technique for reversible biliary occlusion with a low mortality.MethodsWe randomized 30 rats into two groups: with bile duct occlusion (BDO, n=18) and with sham manipulation of the extrahepatic bile duct (control, n=12). We used a removable vascular clip for temporary occlusion of the extrahepatic bile duct. The clip was removed on postoperative day (POD) 2. On POD 2, 3, and 5, we measured the hepatocellular injury and metabolic function markers in serum. Activation of mononuclear cells (HIS36) and expression of regeneration markers [cytokeratin 19, hepatic growth factor (HGF)-α, and HGF-β] were determined by immunohistochemistry.ResultsThe survival rate was 96.67% (1/30); one animal died. The mortality in the BDO group was 6% (1/18) and that in the control group was 0% (0/12). BDO resulted in a sharp increase of hepatocellular injury and cholestatic parameters on POD 2 with a rapid decline till POD 3. Significantly strongest activation of Kupffer cells and expression of proliferation markers were found until POD 5 after BDO.ConclusionThe clip technique is a safe, cheap, and valid method for reversible biliary occlusion with an extremely low mortality.

T-tube Systematic Use in the Biliary Anastomosis: Comparison of Two Consecutive Series of Liver Transplantation

ObjectivesThe authors sought to check the frequency of biliary complications with the use of a T-tube. In 2012, throughout the year, it was carried out systematically in all liver transplantations regardless of the characteristics of the bile duct. Despite the long experience, biliary complications remain a common cause of postoperative morbidity and mortality. Material and MethodsIn this study we compared complications in 23 consecutive transplantation cases using T-tube biliary anastomosis during the year 2012 with 23 consecutive transplantation cases without T-tube during the year 2013. We evaluated postoperative complications and long-term outcomes (for 2 years to 3 years). ResultsOf the 23 patients with anastomosis with a T-tube, 2 patients (8.69%) had biliary stricture that required prosthesis by endoscopic retrograde cholangiopancreatography, 1 of them (4.34%) was operated by incorrect placement of the T-tube, and in 4 patients (17.39%) bile leakage (endoscopic retrograde cholangiopancreatography prostheses in 3 cases and hepaticojejunostomy in 1). During follow-up at 3 years, only 2 patients had minimal bile duct dilatation without clinical relevance. In the patients who underwent transplantation without a T-tube, 18 (78.26%) had no complications, 3 (13.04%) showed stenosis (prosthesis placement), and 2 (8.69%) had bile leakage (hepaticojejunostomy and prosthesis). During follow-up at 2 years to 3 years, no patient had biliary dilatation or alteration of cholestatic parameters. In the comparative study of both groups we found no statistically significant differences. ConclusionsWe have not seen an improvement in complications with the use of T-tube (69.56% vs. 78.23%) that encourage us to work systematically, although the small number of cases does not allow statistically significant conclusions.

Liver and cholestatic parameters as prognostic biomarkers of in-hospital MACE in patients with STEMI.

Liver and cholestatic parameters are increased in ST-segment elevation myocardial infarction (STEMI). The aim of the present study was to evaluate the prognostic value of these parameters to predict in-hospital major adverse cardiac events (MACE) in patients after STEMI. Blood samples of patients with STEMI, who underwent percutaneous coronary intervention (PCI) and stent implantation, were retrospectively analysed and correlated with in-hospital events. The study population consisted of 847 consecutive patients (62·4±13·43years; 73·8% male). The total in-hospital MACE rate was 9·8%, driven by death of any cause (8·4%). The Mann-Whitney U-test revealed that liver and cholestatic parameters (alanine transaminase P<0·0001, aspartate transaminase P<0·0001, alkaline phosphatase (AP) P<0·0001, gamma-glutamyl transferase P=0·0006 and total bilirubin P=0·0023) were significantly higher in the MACE group. Further logistic regression analyses confirmed the correlation between MACE and all five laboratory markers, even after adjustment for age and heart enzymes. Logistic regression model revealed AP to be the best predictor for worth outcome (OR 1·0188; 95% CI 1·0118-1·0258; P<0·0001). Liver and cholestatic parameters are elevated in patients after STEMI. Increased AP is associated with in-hospital event rates.

Efficacy of the infusion hepatotropic drug remaxol in the pathogenetic therapy for cirrhotic stage chronic viral hepatitides

To investigate the impact of therapy with the infusion hepatoprotector remaxol on liver function in cirrhosis in the outcome of chronic viral hepatitides (CVH): HCV, HBV, HCV+HBV, and HBV+HDV. Sixty-five patients aged 26 to 76 years, who had been diagnosed as having liver cirrhosis (LC) in the outcome of CVH: HCV, HBV, HCV+HBV, and HBV+HDV were examined. During infusion therapy, every day 32 cirrhotic patients in the outcome of CVH B or C received intravenous remaxol 400 ml in a jetwise manner once daily for 11 days. A comparison group comprised 33 patients with the similar condition who had intravenous ademetionine 400 mg in a jetwise fashion during infusion therapy with crystalloids (400 ml of isotonic sodium chloride solution, Ringer's solution) for 11 days. After an infusion therapy cycle, the study group patients were recorded to have more significantly reduced cytolytic and cholestatic parameters. The pronounced hepatotropic effect of the drug was confirmed by the rate of a decline in the average concentrations of alanine aminotransferase, aspartate aminotransferase, and total bilirubin. In the study group patients, the relative values of a decrease in the levels of these biochemical parameters were 29, 29, and 40% versus 15, 20, and 9% in the control patients. Infusion therapy with remaxol in the combination treatment of the patients with viral LC not only improves liver function (reduces the degree of cytolysis, cholestasis), but also exerts a cytoprotective effect on peripheral blood cells (leukocytes, lymphocytes, platelets).

Prospective evaluation of ursodeoxycholic acid withdrawal in patients with primary sclerosing cholangitis

Ursodeoxycholic acid (UDCA) is no longer recommended for management of adult patients with primary sclerosing cholangitis (PSC). We undertook a prospective evaluation of UDCA withdrawal in a group of consecutive patients with PSC. Twenty six patients, all treated with UDCA (dose range: 10-15 mg/kg/day) were included. Paired blood samples for liver biochemistry, bile acids, and fibroblast growth factor 19 (FGF19) were collected before UDCA withdrawal and 3 months later. Liquid chromatography/tandem mass spectrometry was used for quantification of 29 plasma bile acid metabolites. Pruritus and health-related quality of life (HRQoL) were assessed with a 10-point numeric rating scale, the Medical Outcomes Study Short Form-36 (SF-36), and PBC-40 questionnaires. UDCA withdrawal resulted in a significant deterioration in liver biochemistry (increase of alkaline phosphatase of 75.6%; P<0.0001; gamma-glutamyl transpeptidase of 117.9%, P<0.0001; bilirubin of 50.0%, P<0.001; alanine aminotransferase of 63.9%, P<0.005; and aspartate aminotransferase of 45.0%, P<0.005) and increase of Mayo Risk Score for PSC (change from baseline of +0.5 point; P<0.003). Bile acid analysis revealed a significant decrease in lithocholic acid and its derivatives after UDCA withdrawal, but no effect on concentrations of primary bile acids aside from an increased accumulation of their taurine conjugates. After UDCA removal cholestatic parameters, taurine species of cholic acid and chenodeoxycholic acid correlated with serum FGF19 levels. No significant effect on HRQoL after UDCA withdrawal was observed; however, 42% of patients reported a deterioration in their pruritus. At 3 months, discontinuation of UDCA in patients with PSC causes significant deterioration in liver biochemistry and influences concentrations of bile acid metabolites. A proportion of patients report increased pruritus, but other short-term markers of quality of life are unaffected.

Cardiac cachexia is associated with right ventricular failure and liver dysfunction

BackgroundThe mechanisms involved in cardiac cachexia remain poorly understood. We examined the association of right ventricular (RV) and hepatic dysfunction with cardiac cachexia. MethodsWe prospectively enrolled 118 patients with left ventricular ejection fraction (LVEF) ≤40%, which were subgrouped as follows: New York Heart Association (NYHA) class II (n=59), NYHA class III without cachexia (n=41) and NYHA class III with cachexia (n=18). All patients underwent blood collection, echocardiography and exercise testing. ResultsReduced systolic RV function (tricuspid annular plane systolic excursion [TAPSE] ≤15mm), was present in 80% of cachectic patients. When comparing NYHA class II patients vs. non-cachectic and cachectic NYHA class III patients we found a stepwise decrease in systolic RV function (TAPSE 19 [16–23] vs. 16 [13–19] vs. 14 [9–15] mm, respectively; p<0.001) and an increase in right atrial pressure (RAP; >10mmHg: 6.8 vs. 27.5 vs. 75.0%, respectively; p<0.001), indicating a higher degree of congestive right HF in cardiac cachexia. Systolic and diastolic function of the left ventricle did not differ between non-cachectic and cachectic patients in NYHA class III. Serum alkaline phosphatase and direct bilirubin correlated with TAPSE and RAP, and were highest in cachectic patients (all p≤0.002), suggesting cholestatic dysfunction due to liver congestion. In multivariable regression analysis, RV dysfunction, cholestatic liver parameters and albumin were independently associated with the presence of cardiac cachexia. ConclusionPatients with cardiac cachexia display a more pronounced degree of right HF, cholestatic liver dysfunction and hypoalbuminemia compared to non-cachectic patients of similar LVEF and NYHA class.

Ikterus und pathologische Leberwerte

Jaundice corresponds to elevated bilirubin- levels, whereat one has to distinguish between direct and indirect serum-bilirubin. In the present Mini Review causes and differential diagnosis of jaundice are outlined. Ultrasound-diagnostic plays a major role in identifying intrahepatic or extrahepatic jaundice. Attention is given to the differential diagnosis of elevated liver enzymes in presence of jaundice, pointing out the distinction between hepatocellular and cholestatic parameters as well as the differentiation in acute or chronic increase. Moreover, the consequences of liver enzyme elevations including further diagnostic procedures, are highlighted. Finally, possibilities and limitations of modern diagnostic tests for liver fibrosis are briefly overviewed.

Oblique Bile Duct Predisposes to the Recurrence of Bile Duct Stones

Background and Study AimsBile stones represent a highly prevalent condition and abnormalities of the biliary tree predispose to stone recurrence due to development of biliary stasis. In our study, we assessed the importance of an altered bile duct course for stone formation.Patients and Methods1,307 patients with choledocholithiasis in the absence of any associated hepatobiliary disease who underwent endoscopic retrograde cholangiopancreatography (ERCP) between 2002 and 2009 were analysed. The angle enclosed between the horizontal portion of the common bile duct (CBD) and the horizontal plane was measured (angle α). Oblique common bile duct (OCBD) was defined as a CBD with angle α<45°.Results103 patients (7.9%) were found to harbour OCBD and these were compared to 104 randomly selected control subjects. Compared to controls, OCBD patients were (i) significantly older (72±13 vs. 67±13, p<0.00001); (ii) more frequently underwent a cholecystectomy (p = 0.02) and biliary surgery (p = 0.003) prior to the diagnosis and (iii) more often developed chronic pancreatitis (p = 0.04) as well as biliary fistulae (p = 0.03). Prior to and after ERCP, OCBD subjects displayed significantly elevated cholestatic parameters and angle α negatively correlated with common bile duct diameter (r = -0.29, p = 0.003). OCBD subjects more often required multiple back-to-back ERCP sessions to remove bile stones (p = 0.005) as well as more ERCPs later on due to recurrent stone formation (p<0.05).ConclusionOCBD defines a novel variant of the biliary tree, which is associated with chronic cholestasis, hampers an efficient stone removal and predisposes to recurrence of bile duct stones.