Hepatobiliary Problems Research Articles

Global changes in gene expression related to Opisthorchis felineus liver fluke infection reveal temporal heterogeneity of a mammalian host response

The food-borne trematode Opisthorchis felineus colonizes bile ducts of the liver of fish-eating mammals including humans. Among chronically infected individuals, this opisthorchiasis involves hepatobiliary problems, including chronic inflammation, periductal fibrosis, biliary intraepithelial neoplasia, and even cholangiocarcinoma. Despite numerous studies at the pathomorphological level, the systemic response and cellular pathogenesis of these disorders are not well studied.To conduct in-depth research and to gain insights into the mechanism by which O. felineus infection causes precancerous liver lesions, we (i) applied a next-generation-sequencing–based technology (high-throughput mRNA sequencing) to identify differentially expressed genes in the liver of golden hamsters infected with O. felineus at 1 and 3 months postinfection and (ii) verified the most pronounced changes in gene expression by western blotting and immunohistochemistry.A total of 2151 genes were found to be differentially expressed between uninfected and infected hamsters (“infection” factor), whereas 371 genes were differentially expressed when we analyzed “time × infection” interaction. Cluster analysis revealed that sets of activated genes of cellular pathways were different between acute (1 month postinfection) and chronic (3 months postinfection) opisthorchiasis. This enriched KEGG pathways were “Cell adhesion molecules”, “Hippo signaling”, “ECM-receptor interaction”, “Cell cycle”, “TGF-beta”, and “P53 signaling”. Moreover, epithelial–mesenchymal transition was the most enriched (q-value = 2.2E-07) MSigDB hallmark in the set of differentially expressed genes of all O. felineus–infected animals. Transcriptomic data were supported by the results of western blotting and immunohistochemistry revealing the upregulation of vimentin, N-cadherin, and α-smooth muscle actin postinfection.Our data expand knowledge about global changes in gene expression in the O. felineus–infected host liver and contribute to understanding the biliary neoplasia associated with the liver fluke infection.

Gastrointestinal and hepatobiliary disorders of patients from countries with low to middle income: a retrospective observational study in a Swiss emergency department

IntroductionThe composition of Europe has changed drastically in recent decades, and a major contributing factor is the increasing wave of migrants and refugees from countries with low and middle income (LMIC). Switzerland’s resident foreigners make up about a quarter of its citizens. Gastrointestinal (GI)-hepatobiliary pathologies seen in emergency departments include a wide spectrum of interesting conditions, some of which are potentially fatal. The aim of this study was to investigate and analyze all records of adult patients from LMIC admitted to the emergency department (ED) of Bern University Hospital with alleged symptoms of the GI and hepatobiliary systems.Material and methodsAn observational retrospective study was conducted in a single center from 1 January 2013 to 31 December 2016 in LMIC adults who presented at the ED of Bern University with GI-hepatobiliary problems.ResultsAfter reviewing a total of 10,308 cases, 176 cases were found to have GI and hepatobiliary problems. Thirty-six percent (n = 63) of the urgent problems of LMIC patients were hepatobiliary disorders, and acute pancreatitis was the commonest disorder (n = 30, 17%). Female patients were 5.14 times more prone to cholecystolithiasis (gallstones) than male patients (p < 0.01). Likelihood of cholecystolithiasis was significantly higher for European than non-European patients (p < 0.05). Moreover, with increasing age there was an annual 6.0% decrease in likelihood of appendicitis (p < 0.01). Liver cirrhosis was also commoner in non-European patients (p < 0.001).ConclusionsTo our knowledge, this is the first analytical study of the epidemiological aspects of patients from LMIC who presented to a Swiss ED with GI-hepatobiliary problems. Validation from larger studies is warranted to reveal the actual burden of disease.

An audit of hepatobiliary diseases in a tertiary level intensive care unit in Nepal

Background: Hepatobiliary diseases account for significant proportion of admission in our intensive care unit, a semi-closed, 11 bedded mixed medical-surgical unit. This study was conducted to study the profile of patients with various hepatobiliary diseases who required intensive care unit admissions with the aim of identifying the need for a hepatobiliary critical care facility. Methods: A retrospective study was designed and all consecutive patients admitted with hepatobiliary problems from January 2013 till December 2013 were enrolled in the study.Results: Out of 467 patients admitted, there were 61 (13.06%) patients with hepatobiliary diseases. Out of 61 patients, there were 24 (39.3%) patients with medical cause for hepatobiliary disease and 37 (60.7%) patients with a surgical cause. The majority of the patients 52.45% were male. The overall mortality in these patients was 37.70%. The mortality in patients with surgical cause for the hepatobiliary disease was less (27.02%). Encephalopathy was a common condition leading to ICU admission. The common medical conditions were Cirrhosis secondary to Alcoholic Liver disease and Acute Fulminant Hepatic Failure. The commonest surgical conditions were Severe Pancreatitis, Post-Whipple's surgery, postoperative sepsis after Cholecystectomy, Liver Injury secondary to Road Traffic Accidents and Severe Cholangitis. Conclusion: The number of patients presenting to our multidisciplinary unit with hepatobiliary diseases is high and this group of patients have a high mortality. Though the numbers do not suggest an immediate need for a Hepatobiliary intensive care unit, the increasing trend suggests such a facility would be the need of time in near future.

The Role of Interventional Radiology in Diseases of the Hepatobiliary System

: Interventional radiology is a safe, less invasive therapeutic modality as compared with open surgery in the treatment of hepatobiliary diseases with less recovery time and significant side effects or damage to the adjacent normal tissues. Patients who have suffered hepatobiliary problems benefit from interventional radiology (IR) techniques. First-line modern imaging modalities, such as duplex ultrasonography, 3 and 4 phasic CT scan, and high-resolution MRI, have revolutionized the diagnosis and management of hepatobiliary diseases. Pioneers in this field have performed IR procedures, such as transjugular intrahepatic portosystemic shunt (TIPS), transjugular liver biopsy (TJLB), biliary stent, and embolotherapy, for the hepatobilliary system. Recently, interventional radiologists, in cooperation with gastrohepatologists, have even further promoted development of this field of medicine. For management of patients, we need collaboration between internists, gastroenterologists, oncologists, surgeons and interventional radiologists. This multidisciplinary management requires attendance of several health service providers. This review provides an overview of the interventional procedures for patients with hepatobiliary problems.

Effects of Alkaline mineral waters on experimental Wistar rats

Studies on a natural therapeutic mineral water aim to obtain scientific data with which to substantiate its medical use in prevention and improving the health status of patients with various disorders. The natural mineral water used in our experiments has been recommended by physicians to treat various pathologies such as digestive disorders (chronic gastritis with hyperacidity, gastric and duodenal ulcers, chronic colitis, chronic constipation), hepatobiliary problems (biliary dyskinesia, chronic hepatitis, chronic pancreatitis, cholecystitis), associated diseases: neurasthenia, migraine disorder. These recommendations are based on the general chemical content and physical properties of the water, studied few decades ago. Natural water quality is determined generally by all mineral or organic substances, dissolved gases, particulate matter and living organisms present in it. The chemical content of the water reveals the presence of some trace minerals, such as Li or B. In the light of the new knowledge about the role of these trace elements in organism, we designed an controlled experiment to obtain data about the changes that are produced by the ingestion of the alkaline mineral water in the biological status of Wistar rats and to extrapolate our findings at the human organism.

Clinico-demographic Characteristics of Patients with Cirrhosis of Liver : Experienced at a Tertiary Care Hospital

Cirrhosis of liver is one of the commonest hepatobiliary problems in Bangladesh as well as in global perspective. The purpose of the present study was to find out the clinico-demographic characteristics of liver cirrhosis patients admitted at a tertiary care hospital. Patients who are clinically suspected to have cirrhosis of liver, admitted in medicine units of Holy Family Red Crescent Medical College Hospital, Dhaka have been analyzed regarding clinical presentation and complications profile. Total 100 patients were included of which 84% were cirrhosis of liver, 7% were chronic active hepatitis, 3% were chronic persistent hepatitis, 2% were Wilson's disease with cirrhosis and 4% were hepatocellular carcinoma (HCC) on the top of cirrhosis of liver. The peak age incidence was between 31-50 years with male-female ratio of 4.88:1. History of jaundice (42%), parenteral medications (14%), infusion (6%) and abdominal surgery (4.0%) were important findings from patient's past history. History of alcohol intake was found in only 4% cases. Overall, weakness (78%), anorexia (72%), abdominal swelling (74%), weight loss (64%), ankle swelling (42%), low grade fever (35%) and yellowish discolouration of eyes, skin and urine (37%) were the most common symptoms. Common signs, revealed by clinical examination as a whole, were anaemia (55%), ascites (68%), oedema (52%), jaundice (34%), palpable spleen (55%) and hepatic facies (37%). Cirrhosis of liver most commonly occurs in middle aged male patients. Weakness, weight loss, anorexia, abdominal discomfort/dyspepsia and swelling of the abdomen are the most prevalent symptoms.

Solving difficult hepatobiliary problems in children

Most difficult hepatobiliary (HPB) problems in infancy and childhood result from pathological anatomical/mechanical derangements; therefore, surgery on the liver and bile ducts depends on a detailed understanding of liver structure, function and repair response to injury or disease. The surgeon must be aware of the very diverse range of anatomical variations. Perhaps key to improving the outcome of paediatric HPB surgery is centralised management and associating this with a paediatric liver transplant programme, which adds expertise and, frequently, the added benefit of adult HPB surgical input to paediatric surgical care. In the United Kingdom, this has resulted in excellent measurable benefit, particularly in the management of biliary atresia, but also of choledochal cysts, portal hypertension and liver tumours. These conditions are briefly discussed here, with focus on the technical aspects of operative management.

Gastrointestinal, Hepatobiliary, Pancreatic, and Iron-Related Diseases in Long-Term Survivors of Allogeneic Hematopoietic Cell Transplantation

Gastrointestinal and hepatobiliary problems in the second year after allogeneic hematopoietic cell transplant (HCT) are usually a continuation of symptoms of protracted acute graft-versus-host disease (GVHD), chronic GVHD, medication side effects, and infection related to immune suppression. As time passes, as tolerance develops, and as immunity improves, the frequency and severity of these problems wane, but new problems involving the gut and liver may arise, sometimes insidiously and sometimes decades after the transplant. Examples are esophageal strictures related to chronic GVHD, gallstones, cirrhosis caused by chronic hepatitis C, secondary malignancy, and rare cases of pancreatic atrophy. One very common complication of transplantation, iron overload, is often associated with substantial iron accumulation in the liver; however, the most troublesome complications are not hepatic but cardiac and endocrine-related.

Silymarin protects spinal cord and cortical cells against oxidative stress and lipopolysaccharide stimulation

Contusive spinal cord injury (SCI) is a devastating event which leads to a loss of neurological function below the level of injury. A secondary degenerative process is initiated following acute SCI. This secondary cascade provides opportunities for the delivery of therapeutic interventions. Silymarin, a widely used “liver herb”, is frequently used for the protection against various hepatobiliary problems. However, the effectiveness of silymarin in central nervous system (CNS), especially in spinal cord, is not firmly established. The present work evaluates the effects of silymarin and its major constituent, silybin, on oxidative stress and lipopolysaccharide (LPS) stimulation in primary neuronal/glial cell cultures and in vivo. Silymarin or silybin inhibited glial cell proliferation in a concentration-dependent manner. Furthermore, it protected glial cells against peroxide-induced reactive oxygen species (ROS) formation, ATP depletion, and cell damage. Interestingly, the inhibition of peroxide-induced ROS by silybin could be partially attenuated by inhibitors of NFκB or protein kinase C (PKC), suggesting an involvement of NFκB and PKC signaling pathways. In mixed neuronal/glial cell cultures from cerebral cortex or spinal cord, silymarin or silybin effectively attenuated peroxide-induced ROS formation, with silymarin being more effective than silybin, implicating other constituents of silymarin that may be involved. Consistently, silymarin reduced LPS-induced injures in spinal neuronal/glial cell cultures. In vivo, intrathecal administration of silymarin immediately after eliciting contusive SCI effectively improved hindlimb locomotor behavior in the rats. Taken together, silymarin or silybin shows promise in protecting the CNS cells from toxin- or injury-induced damages and might be used to treat head- or spinal cord-injuries related to free radical assault.

Article Commentary: Fundamentals of Liver Surgery for the Practicing General Surgeon

This review focuses on the common general surgical referral problem of an undefined liver lesion. Understanding the clinical context in which the patient presents allows one to narrow the differential diagnosis and develop a focused evaluation plan. Most often, MRI is the most helpful initial study to define the likely diagnosis. If the appropriate radiologic expertise exists locally, most of the diagnostic evaluation, if not all, is feasible by a practicing general surgeon. Likewise, understanding the fundamentals of liver anatomy and physiology will facilitate the general surgeons' ability to evaluate the patient's imaging and liver reserve to decide whether local surgical care can be done safely. If local care is not available or safe, referral to a hepatobiliary specialist is appropriate. Ultimately, it is most important for the general surgeon contemplating surgery on the liver to understand his or her own limitations and the limits of their institutions' capabilities in providing pre- and postoperative care. It is particularly important to understand the pitfalls associated with decision-making for complex hepatobiliary problems and when considering an operation on anybody with significant intrinsic liver disease. When faced with these scenarios, the practicing general surgeon should always raise the question: "Is this patient better served at a hepatobiliary center or one that offers liver transplant?" If yes, a phone call, if not a referral, to a tertiary center to discuss the case is reasonable before embarking on a potentially hazardous operation.

A problem-oriented approach to liver disease in oncology patients

> Man sieht nur das , was man weiss – You only see what you know. (J.W. von Goethe, 1808) The disciplines of oncology, clinical pharmacology, and hepatology have seen...

Liver disease in cystic fibrosis

This review highlights recent developments in liver disease associated with cystic fibrosis. The broad spectrum of hepatobiliary problems in cystic fibrosis includes specific alterations ascribable to the underlying defect as well as lesions of iatrogenic origin or that reflect the effects of a disease process occurring outside the liver. Focal biliary cirrhosis, resulting from biliary obstruction and progressive periportal fibrosis, is the most clinically relevant problem, because extension of the initially focal fibrogenic process may lead to multilobular biliary cirrhosis, portal hypertension and eventually liver failure. Cystic fibrosis associated liver disease is presently classified among genetic cholangiopathies and results from lack or dysfunction of the cystic fibrosis transmembrane regulator at the apical membrane of bile duct cells. Major advances have been achieved regarding characterization of natural history, risk factors, diagnostic modalities and treatment options. Liver disease is a relatively frequent and early complication of cystic fibrosis. The pathogenesis is apparently multifactorial, with contributions from environmental and genetic determinants. Its impact on quality of life and survival will increase in future years, and its early detection and treatment will become increasingly important issues. Ursodeoxycholic acid is the only treatment currently available, but novel therapeutic options are being evaluated.

Abstract 531: Is Earlier Hepatitis A Associated with Abnormal Hepatic Response to Statin Therapy?

Hepatic enzyme elevation is low (< 3%) in large statin trials. Elevations are reversible after dose reduction or statin withdrawal. Very rare cases of hepatitis have been reported. No data are available how predisposing risk factors /diseases might influence hepatic statin response. Among the patients suffering from hepatic side effects during statin therapy 896 (477 m, 419 f; aged 31–76 years) admitted with (one or more) elevated hepatic enzyme, anamnestic data on hepatitis A, B, C, hepatic steatosis, alcohol abuse, hepatobiliary problems, abnormal enzymes (GOT, GPT, γGT) were assessed. The prevalence (% vs. % statin use in Austria) was for lovastatin n= 4; 0,2 (0,7), fluvastatin n = 111; 12,4 (14,0), simvastatin n = 297; 33,1 (34,8), pravastatin n = 82; 9,2 (11,8), rosuvastatin n = 69; 7,9 (1,5), atorvastatin n = 333; 37,2 (37,2). Only 41 patients (4,27%) had concomitant muscle complaints (21 cramps, 16 aches, 3 stiffness, 1 weakness), 12 (1,33%) CK elevation, 261 (29,13%) elevated isoprostane 8epiPGF 2α . Those with muscle complaints had normal CK levels and vice versa. Pretherapeutic findings (more than one possible) were hepatitis A 326 (36,4% !!), hepatitis B 7 (0,8%), hepatitis C 3 (0,3%), hepatic steatosis 141 (15,7%), alcohol abuse 104 (11,6%) and /or hepatobiliary problems 17 (1,9%). Abnormal enzymes GOT 116 (12,9%), GPT 113 (12,6%), γGT 147 (16,4%) persisted for < 1 week. Patients after hepatitis A had significantly (p < 0,001) higher transaminases as compared to the other patients. Withdrawal of the respective statin normalized transaminases within 4 weeks in 129 patients (14,4%), in only 7 elevation persisted for a longer period (up to 7 months). After 1 year all were in the normal range. Transaminase levels due to steatosis hepatis even sometimes showed improvement after statin therapy (mean: −12,7% GOT; −14,1 GPT; −16,0 γGT). Reexposure to another statin compound after a 4 weeks drug free interval caused recurrence of side effects in 87 patients (49 with earlier hepatitis A = 56,3%). Hepatitis A seems to represent a high risk for abnormal liver function response on statin therapy and reexposure to other compounds of this family. The combination of abnormal hepatic response with muscle complaints is very rare.

Review article: management of hepatic disease following haematopoietic cell transplant

Hepatic diseases are common complications of haematopoietic cell transplant. The causes are multiple: myeloablative conditioning regimens may cause sinusoidal injury; acute and chronic graft-versus-host disease lead to damaged hepatocytes and small bile ducts; microcrystalline deposits in the gall bladder can cause biliary symptoms; drug-induced liver injury is common; and the liver may be infected by viruses and fungi during the period of severe immune suppression that follows transplant. Pre-transplant evaluation and prevention of liver injury are often more useful than treatment of deeply jaundiced patients in improving transplant outcomes. This review covers pre-transplant evaluation, common hepatobiliary problems in the six months following transplant, and hepatic problems in long-term survivors.

The role of grey scale ultrasonography in the investigation of jaundice

Sixty-seven patients were prospectively studied using grey scale ultrasound (GSU) to assess its possible role as part of a jaundice investigation programme. All scans were performed by one radiologist, without clinical information. When intrahepatic ductal dilatation was found an attempt was made to establish the level and cause of obstruction. The calibre of the intrahepatic bile ducts was correctly reported in 66 patients (98 per cent). Forty-three proved to have extrahepatic cholestasis, 24 had intrahepatic cholestasis. No patient with intrahepatic cholestasis had dilated ducts seen on ultrasound. In 43 patients with obstructive jaundice, GSU accurately detected the level of obstruction in 28. This accuracy varied with the cause of obstruction. A direct indication of diagnosis was possible in 45 of the 67 patients. In a unit specializing in the management of complicated hepatobiliary problems, GSU has been shown to be accurate in differentiating extra- from intrahepatic jaundice. Being non-invasive, it appears ideally suited for use as a screening procedure, permitting selection of appropriate invasive investigations to provide complete preoperative imaging of the biliary tree. In patients with jaundice due to gallstones, GSU may be the only imaging technique required before surgery provided good operative cholangiography is available.

Fallgruben in der alltäglichen hepatobiliären Diagnostik

Hepatobiliary problems are not uncommon in general practice. Many cases can be solved on the basis of a thorough history, clinical examination, blood tests and abdominal ultrasound. The focus of this tutorial paper lies on a number of possible pitfalls in the workup of such problems, based on brief case histories. Atypical presentations of lithogenic biliary obstruction, with or without cholangitis, are discussed as a relatively frequent cause of management difficulties. Furthermore, certain caveats in the interpretation of tumor marker CA19-9, prothrombin time/INR, and ferritin are highlighted.

Magnetic resonance cholangiography in children

Magnetic resonance cholangiography has been shown to be useful in the evaluation of hepatobiliary problems in paediatric patients. Its clinical application in biliary atresia, choledochal cyst, cholelithiasis, bile plug syndrome and liver transplant are illustrated by the following cases.

Hepatobiliary problems in travelers returning from the tropics

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

Choledochal cysts in western adults: complexities compared to children.

Choledochal cysts occur most frequently in East Asian children and rarely in Western adults. Over the past two decades, pediatric treatment has been standardized, but relatively little information is available on the management of Western adults with choledochal cysts. Therefore the aims of this analysis were to compare the presentation, management, and late results of Western adults and children with choledochal cysts. Records were reviewed of patients with choledochal cysts at three academic institutions in Wisconsin. Fifty-seven patients were identified, and 51 of these patients (89%) were managed surgically. Thirty-one patients (54%) were adults, and the adults were more likely to be male (29% vs. 4%, P<0.02). Pain (81% vs. 42%, P<0.01) and cholangitis (35% vs. 15%) were more common in adults. Forty-one patients (71%) had type I cysts, but type IVa or V cysts with dilated intrahepatic ducts were more common in adults (39% vs. 15%, P=0.05). Seventeen adults had undergone biliary surgery prior to referral compared to only four children (59% vs. 15%, P<0.01). Preoperative endoscopic or percutaneous stents were employed more commonly in adults (42% vs. 15%, P<0.01). Hospital mortality was 0%, and morbidity was low in both adults and children (25% vs. 8%). An associated biliary malignancy correlated with age (P<0.05): 0 to 30 years (0%), 31 to 50 years (19%), and 51 to 70 years (50%). In addition, adults were more likely to have late problems with cholangitis (19% vs. 4%, P<0.07) and secondary biliary cirrhosis (13% vs. 4%). This analysis suggests that compared to children, Western adults with choledochal cysts are more likely to have (1) type IVA or V cysts, (2) undergone prior surgery, (3) preoperative biliary stents, (4) an associated biliary malignancy, and (5) late hepatobiliary problems. We conclude that surgery in Western adults with choledochal cysts is frequently complicated and should be performed by specialists in complex biliary surgery.

Acute abdomen: hepatobiliary problems

Acute abdomen: hepatobiliary problems