Review

Authors: Dev Katarey, Sumita Verma

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

Review

Authors: A Sokal, A Sauvanet, B Fantin...

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

Review

Authors: Gennaro D'Amico, Alberto Morabito, Mario D'Amico...

The clinical course of cirrhosis has been typically described by a compensated and a decompensated state based on the absence or, respectively, the presence of any of bleeding, ascites, encephalopathy or jaundice. More recently, it has been recognized that increasing portal hypertension and several major clinical events are followed by a marked worsening in prognosis, and disease states have been proposed accordingly in a multistate model. The development of multistate models implies the assessment of the probabilities of more than one possible outcome from each disease state. This requires the use of competing risks analysis which investigates the risk of several competing outcomes. In such a situation, the Kaplan-Meier risk estimates and the Cox regression may be not appropriate. Clinical states of cirrhosis presently considered as suitable for a comprehensive multistate model include: in compensated cirrhosis, early (mild) portal hypertension with hepatic venous pressure gradient (HVPG) >5 and <10 mmHg, clinically significant portal hypertension (HVPG ≥ 10 mmHg) without gastro-esophageal varices (GEV), and GEV; in decompensated cirrhosis, a first variceal bleeding without other decompensating events, any first non-bleeding decompensation and any second decompensating event; and in a late decompensation state, refractory ascites, sepsis, renal failure, recurrent encephalopathy, profound jaundice, acute on chronic liver failure, all predicting a very short survival. In this review, we illustrate how competing risks analysis and multistate models may be applied to cirrhosis.

Topics: Ascites; Disease Progression; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hepatic Encephalopathy; Humans; Hypertension, Portal; Jaundice; Liver Cirrhosis; Models, Theoretical; Portal Pressure; Predictive Value of Tests; Prognosis; Recurrence; Renal Insufficiency; Risk Assessment; Sepsis; Severity of Illness Index

PubMed: 28681347
DOI: 10.1007/s12072-017-9808-z

Review

Authors: Luis Burgos San Juan

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

Authors: Alain Nicolay, Anne-Marie Lorec, Guy Gomez...

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

Review

Authors: Dilip Gude, Batta Ramasubba Rayudu, Dharam Bansal...

Fetus-in-fetu is a rare congenital anomaly in which a malformed parasitic twin is found within the body of its partner. Less than 100 cases have been reported in published studies. Although it is a relatively benign condition, clinicians need to have a high index of suspicion for the associated complications that may arise. We report the case of an infant presenting with jaundice and steadily growing abdominal mass, who was diagnosed with fetus-in-fetu syndrome. We review the published studies and discuss the pathophysiology, complexities, and management options.

Topics: Female; Fetus; Humans; Infant; Jaundice; Male; Pregnancy

PubMed: 22705618
DOI: 10.5144/0256-4947.2012.427

Review

Authors: Peeyush Varshney, Vinay Kumar Kapoor

Hepato-pancreato-biliary (HPB) tuberculosis (TB) is a rare form of extra-pulmonary TB that poses a diagnostic dilemma and is a great masquerader of malignancy. It is almost always curable but requires a high degree of suspicion and corroboratory evidence to document its existence. Medline/PubMed was searched with keywords "hepatic", "liver", "biliary" and "pancreatic" with "tuberculosis". Data were gathered and analyzed. Common symptoms of HPB TB include jaundice, weight loss, abdominal pain and other constitutional symptoms that make it indistinguishable from malignancy. Imaging modalities such as ultrasonography, computed tomography, magnetic resonance imaging may reveal dilated intrahepatic biliary radicles, mass lesion, and biliary stricture or enlarged necrotic lymph nodes. Fine-needle aspiration cytology/biopsy, brush biopsy, acid-fast bacilli (AFB) staining and molecular testing may help clinch the diagnosis. Most cases require biliary drainage and initiation of anti-tubercular therapy (ATT) whereas surgery is reserved for medically refractory cases or fibrotic strictures. However, most cases are diagnosed post-operatively on histopathology where pre-operative diagnosis is malignancy. A high index of suspicion, coupled with streamlined investigations, may help identify patients pre-operatively to be managed with ATT as TB is completely curable with medical management in most of the cases.

PubMed: 39628501
DOI: 10.47717/turkjsurg.2024.6338

Review

Authors: Anup K Das

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

Authors: Rufino Mondejar, María Mayor Reyes, Enrique Melguizo Madrid...

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

Review

Authors: A L Schneider, H Köhler, B Röthlisberger...

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