Secondary biliary cirrhosis of the liver: case from clinical practice

Presents a clinical case of a patient developing secondary biliary cirrhosis due to prolonged extrahepatic cholestasis caused by cholelithiasis and the presence of choledocholithiasis, which is rare. The article describes the characteristics of secondary biliary cirrhosis of the liver. The course of the disease is considered, the data of laboratory and instrumental studies carried out on the patient in various clinics are analyzed.

Difficulties in assessing the severity of liver dysfunction for obstructive jaundice

A literature review is devoted to the current classifications of liver failure that occurs in obstructive jaundice. Modern methods of diagnosis and criteria for determining the time of development and assessing the severity of this disease, model assessment and prognosis of acute liver failure are also considered. Attention is paid to assessing the severity and determining the timing of the development of liver failure in extrahepatic cholestasis. In addition, there is no common understanding of the role of liver compensatory mechanisms involved in the development of this condition. There are no generally accepted views on the surgical tactics of treatment of patients with obstructive jaundice complicated by liver failure. The limits of application of step-by-step treatment of patients with neoplastic obstructive jaundice have not been reliably determined. All these issues require further research, search for universal tools for assessing liver failure, predicting postoperative complications for choosing the optimal surgical treatment tactics.

STUDY OF THE ACTIVITY OF SOME RAT SERUM ENZYMES IN THE DYNAMICS OF EXTRAHEPATIC CHOLESTASIS

Extrahepatic cholestasis occurs with mechanical obstruction of the main extrahepatic or main intrahepatic ducts. The most common cause of extrahepatic cholestasis is common bile duct stones. This article describes hypertension in the bile ducts and acholysis developing in cholestasis, which cause serious functional and morphological changes in the liver and lead to the rapid growth of liver insufficiency. Thus, in the dynamics of extrahepatic cholestasis development there are significant shifts in blood serum of experimental animals, manifested by hyperfermentemia. These changes indicate the involvement of the liver in the pathological process, which naturally requires their correction.

The Lack of Nrf2 Causes Hepatocyte Dedifferentiation and Reduced Albumin Production in an Experimental Extrahepatic Cholestasis Model

The transcription factor Nrf2 modulates the initiation and progression of a number of diseases including liver disorders. The aim of this study was to evaluate whether Nrf2 mediates hepatic adaptive responses to cholestasis. Wild-type and Nrf2-null mice were subjected to bile duct ligation (BDL) or a sham operation. Various assessments were performed at different days after surgery. Significant genotype-dependent changes in liver size, biliary ductular reaction, hepatocyte proliferation, and fibrotic response were not observed. However, as cholestasis progressed to Day 15 post-BDL, hepatocytes in the wild-type mice exhibited a tendency to dedifferentiate, indicated by the very weak expression of hepatic progenitor markers: CD133 and fibroblast growth factor-inducible 14 (Fn14). During the same period, Nrf2 deficiency augmented this tendency, manifested by higher CD133 expression, earlier, stronger, and continuous induction of Fn14 expression, and markedly reduced albumin production. Remarkably, as cholestasis advanced to the late stage (40 days after BDL), hepatocytes in the wild-type mice exhibited a Fn14+ phenotype and strikingly upregulated the expression of deleted in malignant brain tumor 1 (DMBT1), a protein essential for epithelial differentiation during development. In contrast, at this stage, hepatocytes in the Nrf2-null mice entirely inhibited the upregulation of DMBT1 expression, displayed a strong CD133+/Fn14+ phenotype indicative of severe dedifferentiation, and persistently reduced albumin production. Collectively, our studies revealed that Nrf2 maintains hepatocytes in the differentiated state potentially via the increased activity of the Nrf2/DMBT1 pathway during cholestasis. These findings enable us to gain novel insight into how hepatocytes respond to cholestasis.New and NoteworthyWe found that, when hepatocytes are exposed to cholestasis, they exhibit a tendency of dedifferentiation. In this case, Nrf2 is highly activated to markedly up-regulate the expression of epithelial differentiation gene DMBT1, which potentially prevent hepatocytes from dedifferentiation. Our findings revealed a plastic property of hepatocytes in response to cholestasis and demonstrated a novel Nrf2/DMBT1 pathway likely controlling this property of hepatocytes.

Evaluation of the change in liver stiffness after biliary drainage in patients with extrahepatic cholestasis

Increased liver stiffness (LS) due to extrahepatic cholestasis has been reported to reduce after biliary drainage. As far as we know, it has not been evaluated whether the method of drainage makes a difference in the change in liver stiffness until now. The aim of the study was to answer this question. The patients planned for endoscopic biliary drainage (EBD) or percutaneous biliary drainage (PBD) were enrolled for over an 18-months’ time period. In those without chronic liver disease or liver tumor, liver stiffness was measured before and 10 days after the intervention, using acoustic radiation force impulse (ARFI) elastography. A total of 30 patients were included in the study excluding the ones not fulfilling the criteria and were divided into two groups: EBD group (n = 15) and PBD group (n = 15). The measurements were above the cut-off value for severe fibrosis (1.55 m/s) in all patients with a mean of 2.50 ± 0.72 m/s before drainage. The pre-drainage values of the PBD group were significantly higher than of the EBD group (2.79 ± 0.58 m/s vs 2.22 ± 0.74 m/s, p = 0.02). In all patients except 11, a significant reduction was observed in the stiffness values. The reduction with PBD was more significant than with EBD (p = 0.04). Percutaneous biliary drainage provided a more significant reduction in liver stiffness in patients with extrahepatic cholestasis. However, this result appears to be related to the nature of obstruction rather than the method of drainage, making the comparison weaker than expected from the original design.

Incidental Finding of a PSMA-Positive Pancreatic Cancer in a Patient Suffering from a Metastasized PSMA-Positive Prostate Cancer

An 82-year-old man suffering from prostate cancer that was scheduled for a radioreceptor-ligand therapy (RLT) presented with jaundice to our service. An abdominal ultrasound (US) revealed obstructive extrahepatic cholestasis due to a solid lesion located in the uncinate process of the pancreas. The Prostate Specific Membrane Antigen (PSMA) PET/CT prior to RLT showed multilocular PSMA positive tumor lesions in the lymph nodes, the lung and the pancreas. On request of the cancer board, an Endoscopic Ultrasound (EUS)-guided Fine-Needle Aspiration (FNA) of the pancreatic mass was performed revealing invasive pancreatic ductal adenocarcinoma incompatible with a prostate cancer metastasis leading to the diagnosis of a PSMA positive pancreatic ductal adenocarcinoma.

Hepatic Microhaemocirculation Dynamics in Experimental Extrahepatic Cholestasis

Aim. Investigation of hepatic microhaemocirculation effects in experimental extrahepatic cholestasis.Materials and Methods. Experiments were carried out with a mixed group of 48 white mongrel male rats. Extrahepatic cholestasis was modelled in rats with via the ligation of common bile duct.Results. Animals with ligated common bile duct showed abnormalities in peripheral hepatic circulation manifested by a complex of intravascular, vascular and paravascular changes, hepatic angioarchitectonics disturbance, a marked growth of parenchymal dystrophic lesions in the form of post-haemorrhagic foci. The disturbance was pronounced towards a virtual degradation of hepatic parenchyma and the growth of “numb” zones with ceased circulation.Conclusion. The trials revealed microcirculatory changes in the liver associated with rheological disturbance of blood and, subsequently, the toxic impact of failed metabolism.

Sphincter-preserving technologies in the surgical treatment of extrahepatic cholestasis in complicated cholelithiasis

Annotation. Extrahepatic cholestasis (EHC), caused by functional or organic disorders, always plays a key role in the pathogenetic mechanisms of the development of complicated forms of cholelithiasis caused by impaired bile outflow. Purpose of the work: to improve the immediate and long-term results of surgical treatment of patients with complicated cholelithiasis by intraoperative diagnosis of EHC and determination of the optimal parameters of dosed balloon dilatation aimed at maintaining the functional and anatomical integrity of the sphincter of Oddi (SО). During the period from 2014 to 2020, 181 patients were examined, who were operated on in the department of surgery of the digestive system of the State Institution “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”. The first group of patients (n=81, 44.75%) consisted of patients who underwent sphincter-preserving interventions, both antegrade (when performing laparoscopic cholecystectomy – LHE) and retrograde (when performing retrograde cholangiopancreatography – RCPG), the second group of patients (n=79, 43.64%) consisted of patients who underwent traditional sphincter-destructive staged interventions (total and subtotal papillotomy before or after LHE). The control group consisted of 21 patients (11.6%), in whom structural and functional abnormalities of SО were not detected during manodebitometry with X-ray verification, so they underwent LHE according to the standard technique. During the operation, all patients underwent manodebitometry, the indicators of which were compared with the data of X-ray cholangioscopy. The use of the combined method of manodebitometry in the intraoperative diagnosis of the main causes of various types of of extrahepatic cholestasis in complicated cholelithiasis (CL), made it possible to diagnose an organic disorder as the cause of the development of EHC in 34 (18.78%) patients and functional disorders of SО in 38 (20.99%) patients. The indicators of the cause of EHC in complicated cholelithiasis, established before the operation and clarified during the operation by X-ray studies, were compared with the indicators of manodebitometry in both groups of patients, while the indicator of manodebitometric coefficient in the control group was within 2.35-2.60 (Ме Q25; Q75) and on average 2.51. The use of the proposed diagnostic criteria for the manodebitometric coefficient and parameters of dosed balloon dilatation of large duodenal papilla (LDP) makes it possible to reduce the need for two-stage treatment of EHC in complicated cholelithiasis, to preserve the physiological passage of bile into the duodenum, preventing the formation of postoperative biliary hypertension by preserving the integrity of the sphincter apparatus of LDP and to reduce the amount postoperative complications and the number of staged surgical interventions by 25.92%.