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Clinical Medicine (London, England) Dec 2016Drug-induced liver injury (DILI) remains the most common cause of acute liver failure (ALF) in the western world. Excluding paracetamol overdose, nearly all DILI... (Review)
Review
Drug-induced liver injury (DILI) remains the most common cause of acute liver failure (ALF) in the western world. Excluding paracetamol overdose, nearly all DILI encountered in the clinical setting is idiosyncratic in nature because affected individuals represent only a small proportion of those treated with such drugs. In many cases, the mechanism for idiosyncrasy is immune-mediation and is often identified by genetic risk determined by human leukocyte antigen variants. In the absence of diagnostic tests and/or biomarkers, the diagnosis of DILI requires a high index of suspicion after diligently excluding other causes of abnormal liver tests. Antibiotics are the class of drugs most frequently associated with idiosyncratic DILI, although recent studies indicate that herbal and dietary supplements are an increasingly recognised cause. It is imperative that upon development of DILI the culprit drug be discontinued, especially in the presence of elevated transaminases (aspartate aminotransferase/alanine aminotransferase ratio ≥5 times the upper limit of normal) and/or jaundice. Risk factors for the development ALF include hepatocellular DILI and female gender, the treatment being supportive with some benefit of N-acetylcysteine in the early stages. In view of the poor transplant-free survival in idiosyncratic DILI, early consideration for liver transplant is mandatory.
Topics: Adult; Chemical and Drug Induced Liver Injury; Female; Humans; Liver; Male; Middle Aged
PubMed: 27956449
DOI: 10.7861/clinmedicine.16-6-s104 -
Journal of Visceral Surgery Dec 2019Acute cholangitis is an infection of the bile and biliary tract which in most cases is the consequence of biliary tract obstruction. The two main causes are... (Review)
Review
Acute cholangitis is an infection of the bile and biliary tract which in most cases is the consequence of biliary tract obstruction. The two main causes are choledocholithiasis and neoplasia. Clinical diagnosis relies on Charcot's triad (pain, fever, jaundice) but the insufficient sensitivity of the latter led to the introduction in 2007 of a new score validated by the Tokyo Guidelines, which includes biological and radiological data. In case of clinical suspicion, abdominal ultrasound quickly explores the biliary tract, but its diagnostic capacities are poor, especially in case of non-gallstone obstruction, as opposed to magnetic resonance cholangiopancreatography and endoscopic ultrasound, of which the diagnostic capacities are excellent. CT scan is more widely available, with intermediate diagnostic capacities. Bacteriological sampling through blood cultures (positive in 40% of cases) and bile cultures is essential. A wide variety of bacteria are involved, but the main pathogens having been found are Escherichia coli and Klebsiella spp., justifying first-line antimicrobial therapy by a third-generation cephalosporin. Systematic coverage of Enterococcus spp. and anaerobic infections remains debated, and is usually recommended, in case of severity criteria for Enterococcus severity levels, or anaerobic bilio-digestive anastomosis for anaerobes. Presence of a biliary stent is the only identified risk-factor associated with infections by multidrug-resistant pathogens. Along with antimicrobial therapy, endoscopic or radiological biliary drainage is a crucial management component. Despite improved management, mortality in cases of acute cholangitis remains approximately 5%.
Topics: Abdominal Pain; Acute Disease; Algorithms; Anti-Bacterial Agents; Biliary Tract; Cholangiopancreatography, Endoscopic Retrograde; Cholangitis; Cholestasis; Drainage; Fever; Humans; Jaundice; Prognosis; Severity of Illness Index
PubMed: 31248783
DOI: 10.1016/j.jviscsurg.2019.05.007 -
Clinical and Molecular Hepatology Jul 2023Acute-on-chronic liver failure is an acute deterioration of liver function manifesting as jaundice and coagulopathy with the development of ascites, with a high... (Review)
Review
Acute-on-chronic liver failure is an acute deterioration of liver function manifesting as jaundice and coagulopathy with the development of ascites, with a high probability of extrahepatic organ involvement and high 28-day mortality. The pathogenesis involves extensive hepatic necrosis, which is associated with severe systemic inflammation and subsequently causes the cytokine storm, leading to portal hypertension, organ dysfunction, and organ failure. These patients have increased gut permeability, releasing lipopolysaccharide (LPS) and damage-associated molecular patterns (DAMPS) in the blood, leading to hyper-immune activation and the secretion of cytokines, followed by immune paralysis, causing the development of infections and organ failure in a proportion of patients. Early detection and the institution of treatment, especially in the "Golden Window" period of 7 days, gives an opportunity for reversal of the syndrome. Scores like the Asian Pacific Association for the Study of the Liver (APASL) ACLF research consortium (AARC) score, a model for end stage liver disease (MELD), and the CLIF Consortium acute-on-chronic liver failure (CLIF-C ACLF) score can help in the prediction of mortality. Treatment strategy includes treatment of acute insult. Patients should be considered for early transplant with MELD score >28, AARC score >10, high-grade hepatic encephalopathy, and in the absence of >2 organ failure or overt sepsis to improve survival of up to 80% at five years. Patients, with no option of transplant, can be treated with emerging therapies like faecal microbial transplant, plasma exchange, etc., which need further evaluation.
Topics: Humans; Severity of Illness Index; Acute-On-Chronic Liver Failure; End Stage Liver Disease; Prognosis; Hepatic Encephalopathy
PubMed: 36938601
DOI: 10.3350/cmh.2022.0103 -
Journal of Clinical Laboratory Analysis Feb 2018Hemolysis, Icterus, and Lipemia constituting the HIL index, are the most common causes of interference with accurate measurement in biochemistry. This study focuses on...
BACKGROUND
Hemolysis, Icterus, and Lipemia constituting the HIL index, are the most common causes of interference with accurate measurement in biochemistry. This study focuses on bilirubin interference, aiming to identify the analyses impacted and proposing a way to predict nominal interference-free analyte concentrations, based on both analyte level and Icterus Index (I ).
METHODS
Sixteen common analytes were studied: alanine aminotransferase (ALT), albumin (ALB), alkaline phosphatase (ALP), amylase (AMY), aspartate aminotransferase (AST), total cholesterol (CHOLT), creatinine (CREA, enzymatic method), fructosamine (FRUC), gamma-glutamyl transferase (GGT), HDL cholesterol (HDLc), total iron (Iron), lipase (LIP), inorganic phosphorus (Phos), total protein (PROT), triglycerides (TG), and uric acid (UA). Both the traditional 10% change in concentrations from baseline and the Total Change Level (TCL) were taken as acceptance limits. Nineteen pools of sera covering a wide range of values were tested on the Cobas® 6000 (Roche Diagnostics). I ranged from 0 to 60.
RESULTS
Eight analytes increased (FRUC and Phos) or decreased (CHOLT, CREA, HDLc, PROT, TG, and UA) significantly when I increased. FRUC, HDLc, PROT, and UA showed a linear relationship when I increased. A non-linear relationship was found for TG, CREA, and for CHOLT; this also depended on analyte levels. Others were not impacted, even at high I .
CONCLUSIONS
A method of estimating an interference-free value for FRUC, HDLc, PROT, Phos, UA, TG, and CREA, and for CHOLT in cases of cholestasis, is proposed. I levels are identified based on analytical performance goals, and equations to recalculate interference-free values are also proposed.
Topics: Bilirubin; Biomarkers; Blood Chemical Analysis; Hemolysis; Humans; Hyperlipidemias; Jaundice; Linear Models; Reproducibility of Results
PubMed: 28397988
DOI: 10.1002/jcla.22229 -
Biochemia Medica Jun 2021Total bilirubin tests are highly demanded in clinical laboratories. Since icteric index (I-index) has zero cost, we aimed to evaluate its clinical utility and...
INTRODUCTION
Total bilirubin tests are highly demanded in clinical laboratories. Since icteric index (I-index) has zero cost, we aimed to evaluate its clinical utility and cost-effectiveness to determine if total bilirubin is necessary to be tested. We took into account if haemolysis could interfere to icteric index determination.
MATERIAL AND METHODS
Retrospectively we reviewed I-index results in two cohorts (43,372 and 8507 non-haemolysed and haemolysed samples, respectively). All determinations were done using Alinity c chemistry analysers (Abbott Diagnostics). Receiver operating characteristic (ROC) curve was used to determine the optimal index cut-off to discriminate between normal and abnormal bilirubin concentration (20.5 µmol/L).
RESULTS
The ROC curve analysis suggested 21.4 µmol/L as the optimal I-index cut-off but differences in sensitivity and specificity were detected between patient derivation. For rejecting purpose, 15.4 µmol/L and 17.1 µmol/L I-index thresholds were selected based on patient derivation (inpatients and emergency room; and primary care and outpatients, respectively) with 97% sensitivity and 0.25% false negative results. Sensitivity was much lower in haemolysed samples. We selected 34.2 µmol/L I-index as threshold to detect hyperbilirubinemia with 99.7% specificity and 0.26% false positive results, independent of haemolysis. With the icteric index cut-offs proposed, we would save 66% of total bilirubin requested and analyse total bilirubin in around 2% of samples without total bilirubin requested.
CONCLUSIONS
This study supports the use of I-index to avoid bilirubin determination and to identify patients with hyperbilirubinemia. This work considers that the economic and test savings could help to increase the efficiency in clinical laboratories.
Topics: Bilirubin; Female; Hemolysis; Humans; Hyperbilirubinemia; Laboratories, Hospital; Male; Retrospective Studies
PubMed: 33927553
DOI: 10.11613/BM.2021.020703 -
Clinics and Research in Hepatology and... Mar 2022Little is known about bile acid transporter defects on the basolateral side of hepatocytes. In 2015 Vaz et al. published a first case of SLC10A1 mutation causing... (Review)
Review
INTRODUCTION
Little is known about bile acid transporter defects on the basolateral side of hepatocytes. In 2015 Vaz et al. published a first case of SLC10A1 mutation causing Na-taurocholate Co-transporting Polypeptide deficiency with hypercholanemia and normal bilirubin and Autotaxin levels. The index patient presented with failure to thrive, but without pruritus or jaundice. Several new cases have been published since, but the full spectrum of clinical presentation of mutations in SLC10A is not known. The primary aim of this review is to report a patient with a novel homozygous mutation and discuss the findings in the light of all other reported cases to date.
MATERIAL AND METHODS
We describe the findings of a patient with a previously unreported homozygous mutation and review all published cases to date in English on PubMed.
RESULTS
Our female patient born in 2002 presented with a feeding disorder and failure to thrive akin to the first description by Vaz. Workup suggested underlying liver disease although she did not complain of pruritus. Serum levels of aminotransferases, alkaline phosphatase, gamma-glutamyl transferase and bilirubin were normal. Plasma bile acids were chronically elevated, up to 150-fold. A first liver biopsy performed at 2 years of age showed unspecific findings with focal steatosis. Ursodeoxycholic acid treatment was introduced and the liver panel monitored regularly. At age 14, a second biopsy was performed, and histology was within normal limits. At this time, serum Autotaxin levels were found to be in normal range. Finally, genetic analysis revealed a homozygous 5 bp deletion in the gene SLC10A1 resulting in a premature stop codon predicted to lead to a complete NTCP loss of function. Most other reported cases to date carry the c.800C>T (p.Ser267Phe) mutation and are asymptomatic.
DISCUSSION
NTCP deficiency appears to have a benign course as most patients are asymptomatic. Many patients seem to present with transient neonatal jaundice. Large variations in total plasma bile acid levels are observed between patients; they may be linked to the underlying genetic mutation or to yet uncharacterized compensatory mechanisms. Longer follow-up is needed to evaluate the long-term consequences of this newly identified inherited disease of bile acid transport.
Topics: Adolescent; Bile Acids and Salts; Bilirubin; Child, Preschool; Failure to Thrive; Female; Humans; Infant, Newborn; Organic Anion Transporters, Sodium-Dependent; Peptides; Pruritus; Symporters; Taurocholic Acid
PubMed: 34757153
DOI: 10.1016/j.clinre.2021.101824 -
Revista Medica de Chile Feb 2008Cholangiocarcinoma is a malignant lesion of the bile duct epithelium. Its incidence and prevalence are low. It appears from the sixth decade of life and there is slight... (Review)
Review
Cholangiocarcinoma is a malignant lesion of the bile duct epithelium. Its incidence and prevalence are low. It appears from the sixth decade of life and there is slight male predominance. It is most frequently found in the confluence of the hepatic ducts, where it is called hilar cholangiocarcinoma or Klatskin tumor. Its etiology is unknown but there are predisposing conditions and environmental risk factors such as primary sclerosing cholangitis, Caroli's disease, bile duct malformations, industrial toxins and parasitic infections. The classic presentation of cholangiocarcinoma includes jaundice, weight loss and right upper quadrant pain. These, in addition to laboratory exams, endoscopical and imaging procedures, lead to the diagnosis. Hilar cholangiocarcinoma must be distinguished from other malignant or benign causes of biliary obstruction. Cholangiocarcinoma of the distal common bile duct must be differentiated from other periampullary tumors and intrahepatic cholangiocarcinoma can be confused with a hepatocellular carcinoma. Two classifications are used for clinical staging: TNM and Bismuth-Corlette. The best treatment is the complete surgical excision with negative histological margins, although the resectability index is low. The type and size of surgery depends on the location and extent of the tumor. Patients with unresectable tumors can be subjected to palliative procedures such as biliary-enteric bypass, endoscopic or pecutaneous stent placement. Chemotherapy is not effective. Recently, endoscopic phototherapy has emerged as a better alternative for palliative care.
Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Humans; Neoplasm Staging
PubMed: 18483680
DOI: No ID Found -
Journal of Global Infectious Diseases Apr 2014Ascariasis mainly contributes to the global helminthic burden by infesting a large number of children in the tropical countries. Hepato-biliary ascariasis (HBA) is... (Review)
Review
Ascariasis mainly contributes to the global helminthic burden by infesting a large number of children in the tropical countries. Hepato-biliary ascariasis (HBA) is becoming a common entity now than in the past owing to the frequent usage of ultrasonograms and endoscopic diagnostic procedures in the clinical practice. There are a variety of manifestations in HBA and diagnosis depends on a high index of suspicion in endemic areas coupled with subsequent confirmation by sonographic or endoscopic demonstration of the worm. Most of them present with acute abdomen and jaundice. Oriental or recurrent pyogenic cholangiopathy is possibly the result of HBA, commonly encountered in South-East Asian countries. Conservative treatment with anthelminthic agents is used in the majority. Failure to respond to medical therapy usually indicates the need for endoscopic or surgical interventions. Overall, mortality is low and prognosis is good, but many epidemiological and immunological aspects of Ascaris infection are unclear, meaning our understanding the disease and infection still remains incomplete. Therefore, it is difficult to definitely put down a fixed modality of treatment for HBA. This underscores the need for further studies as ascariasis has the potential to adversely affect the national socio-economy by compromising the health of children and adults alike with its sheer number.
PubMed: 24926166
DOI: 10.4103/0974-777X.132042 -
Journal of Minimal Access Surgery 2022Currently, there is no consensus on patient selection for ambulatory laparoscopic cholecystectomy (LC). This study is a systematic review of previously published patient... (Review)
Review
BACKGROUND
Currently, there is no consensus on patient selection for ambulatory laparoscopic cholecystectomy (LC). This study is a systematic review of previously published patient selection for ambulatory LC.
METHODS
A comprehensive search was done in PubMed, Web of Science, Embase and Google Scholar Database up to March 2020 to summarise previously reported medical or surgical selection criteria used for inclusion and exclusion of patients, as well as successful same-day discharge rates and readmission rate after discharge.
RESULTS
Fifty-nine studies with a total of 13,219 patients were included in this systematic review. In total, the median same-day discharge rate was 90% (range: 63%-99.4%), and median readmission rate was 2.22% (range: 0%-16.9%). The most considered medical criteria were American Society of Anesthesiologists classification I and II, age <70, and body mass index <35. Surgical criteria varied greatly. The top three accessible exclusion variables were (1) common bile duct stones, cholangitis, or jaundice (27 publications, 45.8%); (2) history of abdominal surgery (12 publications, 20.3%) and (3) history of pancreatitis (9 publications, 15.3%).
CONCLUSION
The results of the current study showed the variable patient selection in different centres, the medical aspect criteria may be expanded under adequate pre-anaesthetic assessment and preparation and the surgical aspect criteria should include more laboratory or imaging parameters to ensure the surgical safety.
PubMed: 35313430
DOI: 10.4103/jmas.jmas_255_21 -
American Family Physician Apr 2022Alcoholic hepatitis is a clinical syndrome characterized by acute-onset jaundice and liver enzyme abnormalities in the setting of long-term heavy alcohol use. High rates...
Alcoholic hepatitis is a clinical syndrome characterized by acute-onset jaundice and liver enzyme abnormalities in the setting of long-term heavy alcohol use. High rates of concomitant infections, systemic inflammation, and multiorgan failure lead to significant morbidity and mortality. Diagnosis of alcoholic hepatitis is primarily clinical, based on a consensus definition from the National Institute on Alcohol Abuse and Alcoholism. Initial workup should include chest radiography and cultures of peritoneal fluid, blood, and urine. Close monitoring for inflammation and organ failure is crucial throughout hospitalization. Laboratory-based prognostic scores, including Maddrey Discriminant Function and the Model for End-Stage Liver Disease, help determine disease severity and treatment options. Treatment for moderate disease primarily consists of supportive care, including alcohol cessation and nutritional support. Corticosteroids are recommended for severe alcoholic hepatitis. Responsiveness to corticosteroid therapy should be evaluated using the Lille score on day 7 of treatment. Hospital physicians should involve a multidisciplinary team, including substance abuse specialists, gastroenterologists or hepatologists, nephrologists, dietitians, and intensivists, as appropriate. Long-term follow-up should focus on abstinence from alcohol, management of underlying cirrhosis, and evaluation for liver transplantation if indicated. Pharmacologic treatment of alcohol use disorder can aid patients in maintaining abstinence from alcohol. The presence of underlying cirrhosis and continued alcohol use negatively impact long-term prognosis.
Topics: End Stage Liver Disease; Hepatitis, Alcoholic; Humans; Inflammation; Liver Cirrhosis; Severity of Illness Index
PubMed: 35426628
DOI: No ID Found