Mistakes in mouse models of NASH and how to avoid them

Several animal models attempt to mirror each stage of human NAFLD

Nonalcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver disease worldwide that can manifest as nonalcoholic fatty liver (NAFL) or nonalcoholic steatohepatitis (NASH). Compared with NAFL, NASH poses a substantially higher risk of progression to advanced liver disease, cirrhosis and hepatocellular carcinoma (HCC). Given the lack of directed pharmacological therapies and the complex, multifactorial disease aetiology and pathology, NAFLD is expected to become the leading cause of end-stage liver disease in the coming decades.
 

Preclinical research aimed at elucidating the molecular mechanisms driving disease and identifying reliable biomarkers and potential treatments is critical and has gained significant attention in recent years. Several animal models attempt to mirror the histopathology and pathophysiology of each stage of human NAFLD, including the development of NASH and fibrosis, up to HCC development. Most in vivo studies use mouse models owing to their relatively low cost, short lifespan and ease of genetic manipulation, which allow for a level of experimental control that is not possible with human studies. Independent of each model’s inherent advantages and disadvantages, making a mistake when choosing, performing, or even analyzing results for a particular animal NASH model may jeopardize our ability to obtain accurate results or draw firm conclusions. 
Here, we discuss some mistakes commonly made in NASH preclinical research. We also consider the challenges and opportunities when selecting animal models for the study of NAFLD.

Mistakes in small bowel bleeding and how to avoid them

Definitive management of small bowel bleeding can pose formidable challenges

Over the past 17 years, the disruptive impact of technologies including small bowel capsule endoscopy (SBCE), device-assisted enteroscopy (DAE) and dedicated cross-sectional imaging has transformed the investigation and management of small bowel pathology. Although a small bowel source only accounts for 5–10% of all cases of gastrointestinal bleeding,1–2 definitive management of small bowel bleeding even in the current era of advanced imaging, can still pose formidable challenges.  

In this brief article, we highlight frequent mistakes made in the investigation and management of small bowel bleeding and discuss strategies for their avoidance. 

Mistakes in acute jaundice and how to avoid them

Jaundice—one of the major signs in medicine—can result from numerous conditions

Jaundice or icterus (derived from the ancient Greek word ikteros that described the yellow-breasted oriole bird) is not a diagnosis in itself but constitutes one of the major signs in medicine. Jaundice refers to the yellowish discoloration of tissue that occurs as a consequence of the deposition of bilirubin. This discoloration is a physical manifestation of a marked increase in serum bilirubin levels. Normal serum bilirubin values are <17 μmol/L; for jaundice to be perceived visually serum bilirubin levels need to be elevated to >40 μmol/L (equivalent to 2.5 mg/dL).

Most serum bilirubin is formed from the breakdown of the haem contained in senescent red blood cells by the reticuloendothelial system. Thus, unconjugated bilirubin is released in the bloodstream, where it is bound by albumin. Through the blood circulation bilirubin is moved to liver hepatocytes, where it undergoes further processing. In brief, bilirubin becomes conjugated in the hepatocytes through glucuronidation, which allows it to be excreted from the body (unconjugated bilirubin is water insoluble and cannot pass into the urine). Conjugated bilirubin forms one of the main components of bile and most of it passes through the biliary tree to the intestine. Unconjugated and conjugated bilirubin are reported in laboratory measurements as indirect and direct bilirubin, according to their chemical properties (i.e. reaction with reagents).1 Jaundice can be caused by abnormalities in any of the steps comprising the formation, metabolism and excretion of bilirubin. In addition, these processes may be functioning properly, but jaundice can be seen because of an obstruction of the biliary tree at any point, from its intrahepatic origins to its end at the ampulla of Vater. For this reason, it is clear that numerous conditions can result in jaundice. When faced with a patient presenting with jaundice a reasonable and careful diagnostic approach is, therefore, warranted to elucidate the underlying cause of this sign. Conventional wisdom may be that “jaundice by itself never killed anyone,” but it is imperative to find the cause as soon as possible, as prompt intervention saves lives in many cases.  Here, we outline several of the mistakes made when approaching a patient presenting with acute jaundice based on our clinical experience and published data. 

Mistakes in capsule endoscopy and how to avoid them

Wireless technology means capsule endoscopy is well tolerated, but it is also a drawback

Capsule endoscopy is a noninvasive technique intended for studying the small bowel and/or colon. The capsule endoscope consists of a small, wireless, pill-sized camera that can be swallowed and allows direct visualization of the gastrointestinal mucosa. The design of the capsule differs depending on the part of the gastrointestinal tract to be studied. The small-bowel capsule has one optical dome and is generally used in patients who have suspected bleeding or to identify evidence of active Crohn’s disease. By contrast, the colon capsule has two optical domes, a higher frame rate and can be considered as an alternative to conventional colonoscopy, especially for cases when the examination was incomplete. There is also a new capsule with two optical domes that is designed for the panendoscopic study of both the small bowel and colon. 

The main characteristic of capsule endoscopy is the wireless technology, which enables it to be very well tolerated. However, this feature is also one of its drawbacks, as the capsule cannot be directly controlled by the physician. The capsule moves through the gut depending solely on intestinal motility, and the examiner is not able to drive it back and forth or to stop it to look more carefully at any finding. Moreover, the visualization relies heavily on the adequacy of intestinal cleansing as rinsing with water and aspiration are not possible. Capsule endoscopists should be aware of these shortcomings, as they directly affect the reading and diagnosis. Here we discuss frequent errors that are made when performing capsule endoscopy, based on the published literature and more than 15 years’ experience

Mistakes in clinical investigation of gastrointestinal motility & function

Symptoms related to abnormal motility and function are very common.

Symptoms related to abnormal gastrointestinal motility and function can occur from the moment food is swallowed to the time stool is passed into the toilet. A recent UEG survey indicated that dysphagia, heartburn, bloating, abdominal pain and changes to bowel habit are each reported by 5–15% of the general population.1 These symptoms are frequent reasons for seeking medical attention from general physicians and for referral to specialist gastroenterologists. Most patients with these symptoms do not have neoplasia, infection or inflammation on initial investigation, but rather so-called functional gastrointestinal symptoms.2,3

For patients with mild symptoms, negative tests provide reassurance and simple, symptomatic management might be all that is required (e.g. acid suppression, stool regulation). However, for those with severe symptoms that persist on therapy, ruling out life-threatening disease is not sufficient, and referral to the neurogastroenterology and motility (NGM) laboratory for physiological measurements is often indicated.

Clinical investigations aim to explain the cause of symptoms and establish a diagnosis that can guide rational treatment. Until recently, it could be argued that manometry, scintigraphy, breath tests and related tests rarely provided this information. As a result, only patients with suspected major motility disorders (e.g. achalasia, severe reflux disease or faecal incontinence) were routinely referred to the NGM laboratory for tests. Technological advances, such as high-resolution manometry (HRM), now provide objective measurements not only of motility, but also of function in terms of the movement (and digestion) of ingested material within the gastrointestinal tract. Furthermore, the ability to associate events (such as bolus retention, reflux or gas production) with symptoms provides an indication of visceral sensitivity and can identify what is causing patient complaints. Here, I discuss frequent mistakes in clinical investigation of gastrointestinal motility and function based on a series of consensus documents published by members of the International Working Group for Disorders of Gastrointestinal Motility and Function.

Mistakes in the endoscopic diagnosis and management of Barrett’s oesophagus and how to avoid them

Barrett’s oesophagus is the precursor to oesophageal adenocarcinoma, which carries a poor prognosis,1 and it is likely that all endoscopists and gastroenterologists will encounter Barrett’s oesophagus in their clinical practice.

Careful assessment and management of patients who have Barrett’s oesophagus with endoscopic surveillance and endoscopic endotherapy aim to reduce the risk of progression to invasive adenocarcinoma. Advances in endoscopic diagnosis and therapy should, therefore, help to reduce the risk of progression. As with all premalignant conditions and surveillance programmes,2 careful multidisciplinary management of the patient is important to reduce the risk of causing them to become unduly concerned. Here, we present some mistakes that in our experience are commonly made in the endoscopic diagnosis and management of Barrett’s oesophagus and give advice on how to avoid them. 

Mistakes in short bowel and how to avoid them

Short bowel manifests as high stomal output or diarrhoea, dehydration and malnutrition.

Short bowel is a condition that occurs after single or multiple intestinal resections. The incidence of short bowel in Europe is 2 per million of the population1–3 and it carries with it lifelong morbidity and mortality. The initial recognition and management of short bowel in the adult population tends to occur in the postoperative period and in the secondary care setting, where specialist input from clinicians experienced in short bowel is often lacking.

Normal small bowel length is 275–850 cm.4–7 It is accepted that when the length of small bowel is reduced to less than 200 cm it may be insufficient to enable adequate absorption of fluids and micronutrients. The symptoms of short bowel (often referred to in the literature as short bowel syndrome) are secondary to a reduction in intestinal surface area together with an increased motility of the remaining section of small bowel, with accompanying increased secretion into the lumen. These intestinal secretions vary in their electrolyte content and osmolality depending on the anatomical location, with the highest chloride and potassium loss from gastric secretions and high sodium loss from jejunal secretions.8 Clinically, short bowel manifests itself as a high stomal output or diarrhoea, dehydration and malnutrition. High stomal output or diarrhoea do not, however, necessarily equate immediately to short bowel; conversely, a small bowel longer than 200cm may be insufficient if it is diseased. Here, we discuss some of the pitfalls that are encountered in the recognition and management of short bowel and have suggested an algorithm for assessing and managing patients with a high stomal output. Although some of these pitfalls may appear obvious, they are addressed here because they are commonly encountered in clinical practice (summarised in table 1 at the end of the article).

Mistakes in paediatric IBD and how to avoid them

Better clinical outcomes are increasingly being sought in young people with IBD

Around 1 in 10 cases of inflammatory bowel disease (IBD) will present before adulthood, with the median age at presentation being 11–12 years.1 IBD in children and young people is associated with more extensive disease, increased disease activity and a higher rate of complications compared with adult-onset IBD.2 Worldwide, estimates of paediatric IBD prevalence rates are lacking, but data suggest its incidence is increasing.3


Risk factors for paediatric IBD include immigration to high prevalence regions, particularly to countries that have Westernised diets, increasing geographical latitude, and European ancestry (versus belonging to an indigenous population).4 The risk may also be higher in children of certain ethnicities (South Asian, Hispanic, and East Asian).5

While the pathophysiology and clinical presentation of paediatric IBD is well understood, the role of genetics and personalised treatment is currently the focus of a significant amount of international research. Better clinical outcomes—including optimal nutrition, improved growth, better quality of life and increased disease remission rates with decreased occurrence of complications—are increasingly being sought in children and young people with IBD.4

This article discusses mistakes commonly made when identifying, diagnosing and managing children whom are suspected or confirmed to have IBD. The mistakes and discussion are based on published evidence where possible, plus our clinical experience of looking after children with IBD.

Mistakes in tissue sampling during endoscopy and how to avoid them

Tissue acquisition is the most common manoeuvre performed during endoscopy.

Tissue sampling is the most common manoeuvre performed during endoscopic procedures and histological examination is part of almost every digestive disease investigation. The potential for mistakes is, therefore, widespread and knowledge of the adequacy of the indications and techniques used for tissue sampling during endoscopy, as well as the potential consequences, is indispensable for every gastroenterologist. As such, there are some questions that should always be posed before taking a biopsy sample or tissue acquisition during endoscopy: Why? What for? How? How many? (figure 1). This manuscript has been organized with these questions in mind. We’ve aggregated examples for the eight most frequent and most correctable mistakes made during tissue acquisition by endoscopy. In addition, most of the recommendations made in this article are supported by existing guidelines and evidence, with a few based solely on the authors’ experience. Figure 1 | Questions that should always be asked before a biopsy sample is taken or tissue acquired during endoscopy.

Mistakes in managing H. pylori infection and how to avoid them

Careful practice can overcome declining eradication rates for H. pylori treatment.

The sequelae of Helicobacter pylori infection, a known Group 1 carcinogen, can lead to significant morbidity and mortality worldwide. Billions of people are infected with H. pylori, but the incidence of H. pylori infection is declining in many parts of Europe, with a study from the Netherlands showing a decline in seroprevalence from 48% in subjects born between 1935 and 1946 to 16% in those born between 1977 and 1987.1

In recent years, however, eradication rates for H. pylori treatment have been falling, which has led to a large number of patients in the community having inadequately managed infections. Most of the problems that have led to the decline in the success of eradication treatment can be easily overcome through careful practice, supported by the robust framework provided by international guidelines. Careful practice includes the correct management of dyspepsia, the appropriate use of diagnostic tests for H. pylori, acceptable, efficacious treatments that enable good patient compliance and adequate follow up to insure eradication has been achieved in all cases. Here, we discuss the mistakes that are made when managing patients infected with H. pylori. Most of the discussion is evidence based, but where evidence is lacking the discussion is based on the authors’ clinical experience of more than 30 years in the field.

Mistakes in NAFLD and how to avoid them

Management of NAFLD requires a multidisciplinary approach.

Nonalcoholic fatty liver disease (NAFLD) is defined as the accumulation of excess fat (triglyceride) in the liver in the absence of excessive alcohol consumption. Disease severity ranges from simple steatosis (nonalcoholic fatty liver [NAFL]) to nonalcoholic steatohepatitis (NASH), fibrosis, or cirrhosis, with the potential to develop hepatocellular carcinoma (HCC) or require liver transplantation. 

NAFLD is believed to affect up to 25% of the Western population,1 and is fast becoming the leading reason for liver transplantation worldwide.2 It affects up to 70% of those who are obese,3 and is strongly linked to the metabolic syndrome. Management of NAFLD therefore requires a multidisciplinary approach, not only to identify those patients at risk of progressive liver disease, but also to improve long-term liver and cardiovascular morbidity and mortality.  Here, we highlight some of the mistakes commonly made by medical practitioners when managing NAFLD, and give an evidence-based (where possible) or experience-based approach to management of the condition.

Mistakes in medical management of IBD and how to avoid them

The subtleties and challenges of contemporary IBD management.

The prevalence of inflammatory bowel disease (IBD) is ~0.5%–1% and rising.1 In many healthcare systems, the frequency of IBD is too rare for it to be managed solely by primary care practitioners, but still common enough to fall within the caseload of general gastroenterologists. Whilst the disease may run a relatively quiescent course, some patients face years of severe, disabling symptoms. The relatively unpredictable prognosis of IBD, combined with the ability of its extraintestinal manifestations to impact multiple organ systems, requires a nimble and individual approach to patient management. Indeed, the treating clinician must liaise closely with colleagues in other disciplines, including nursing, surgery, radiology, histopathology and numerous other medical specialties.

Advances in our understanding of IBD pathogenesis and in diagnostic modalities, therapeutic options and surgical techniques for Crohn’s disease and ulcerative colitis have fundamentally altered the landscape of IBD management in the past two decades. The challenge for physicians treating IBD is to leverage these changes to improve patient outcomes, avoiding the many potential pitfalls. Here, we discuss some of the pitfalls that may await the treating clinican, drawing upon evidence when possible and on our clinical experience. If some of these pitfalls seem contradictory, this is deliberately so, to highlight the subtleties and challenges of contemporary IBD management. Many of the pitfalls may also seem somewhat obvious when taken in isolation, and yet we believe them to be relatively common, raising important questions around how we can configure and manage our services to avoid those problems that we all still encounter in practice.

Mistakes in cases on call and how to avoid them

Evaluating and managing GI cases on call is a difficult task.

It is a difficult task and a great responsibility to evaluate and manage patients with acute - and potentially life-threatening - clinical presentations. It is even more complex to achieve high standards of care for cases on call. Indeed, on-call gastroenterologists, hepatologists and endoscopists are faced with a wide and protean range of gastrointestinal, liver and pancreatic emergencies. 

The decision-making process for cases on call is mainly based on information received over the phone, on medical knowledge and clinical experience, and on the resources available. As the degree of confidence in any information given on call may vary, it is of tremendous importance to note, and to document, with precise timing, what has been communicated by, proposed to, and eventually decided with, multiple caregivers (i.e. nurses, emergency physicians, intensive care physicians, surgeons, radiologists etc.) Here, we discuss 10 mistakes that are often seen when managing GI cases on call. Most of the proposals are based on medical evidence, but others are formed from our own clinical experience. 

Mistakes in endoscopic resection and how to avoid them

Endoscopic resection is an advanced technique used to remove superficial lesions.

Endoscopic resection is a widespread, advanced endoscopic technique that can be used to remove superficial lesions in the gastrointestinal tract. Lesions present in all parts of the gastrointestinal tract, such as the oesophagus, stomach, duodenum, small intestine and, above all, colon, can be removed by endoscopic resection. Lesion detection and characterization, the use of appropriate resection devices and methods, and the management of malignant polyps are all important parts of a multistep process that requires training, experience, expertise and a multidisciplinary approach. 

The diagnostic and therapeutic mistakes discussed here are based on our endoscopic experience. We present the most important mistakes that are often seen in endoscopic resection in our practice and have major consequences for the patient. We propose, from our experience, a simple approach to avoid these mistakes.

Mistakes in GORD diagnosis and how to avoid them

Conditions to be aware of to avoid making an erroneous diagnosis of GORD

According to the Montreal definition, “[gastro-oesophageal reflux disease (GORD)] is a condition which develops when the reflux of stomach contents causes troublesome symptoms and/or complications.”1 GORD has a negative effect on quality of life and is frequently encountered in clinical practice, with an estimated prevalence of around 24% in Europe.2 In the US, GORD-related healthcare costs account for $9 billion per year.3 A variety of symptoms are associated with GORD—heartburn and regurgitation are typical symptoms, while chest pain, cough and sore throat are considered atypical symptoms—but none is pathognomonic.

In case of a typical presentation of GORD in a young patient, and in the absence of alarm signs (e.g. bleeding, dysphagia, weight loss), it is common practice to treat the GORD without investigation. In other cases, upper gastrointestinal endoscopy is usually the first-line examination, more to rule out mucosal complications than to make a positive diagnosis of GORD. Although the presence of erosive oesophagitis is specific to GORD, most patients in whom GORD is suspected based on their clinical presentation have normal endoscopy findings. In this situation, ambulatory reflux monitoring (either pH or pH-impedance monitoring) may be required to identify reflux episodes, to link them with symptom occurrence and then to confirm the clinical diagnosis of GORD. Another common clinical presentation is a patient with symptoms suggestive of GORD that persist despite proton pump inhibitor (PPI) therapy. Indeed 20–60% of patients with GORD-suggestive symptoms are not satisfied with PPI therapy.4,5 After evaluating a patient’s compliance with their treatment, complementary examinations are indicated to determine if resistance to treatment is secondary to persistent GORD, to reflux hypersensitivity or to an erroneous diagnosis of GORD.

Here, we report 10 conditions that clinicians should be aware of to avoid making an erroneous diagnosis of GORD. The discussion draws on a combination of published data and clinical experience.

Mistakes in CT for the acute abdomen and how to avoid them 

There are many pitfalls to be aware of when requesting/interpreting abdominal CT scans

Abdominal CT (computed tomography) is among the most common imaging tests performed for the investigation of acute abdominal pathology. There are many pitfalls that clinicians and radiologists should be aware of when requesting these studies and interpreting the findings.

This article covers ten mistakes frequently made with abdominal CT, focusing on gastrointestinal tract and hepatobiliary pathology. These mistakes and their discussions are based on the available literature where possible and thereafter on our clinical experience. 

Mistakes in the use of PPIs and how to avoid them

PPIs are frequently prescribed—being knowledgeable about them is fundamental. 

Proton pump inhibitors (PPIs) inhibit gastric acid secretion by blocking the gastric hydrogen potassium ATPase (H-K-ATPase). When omeprazole, the first PPI, became available in 1988, it soon appeared to be more effective than H2 antagonists, and PPIs rapidly became one of the most prescribed drug classes worldwide.1

PPIs have proven highly efficient for the management of gastro-oesophageal reflux disease (GORD), gastroduodenal ulcers and in the treatment of Helicobacter pylori infections. PPIs are, however, also commonly prescribed for chronic complaints of dyspepsia and upper abdominal discomfort, for which there is no proof that gastric acid is an underlying pathophysiological factor. Lately, the safety of long-term PPI use has been the subject of debate, because chronic use of PPIs has been linked to several complications, such as vitamin and mineral malabsorption, pneumonia, gastrointestinal infections and dementia.2  For anyone working in gastroenterology, having knowledge of one of the most prescribed drugs in this field is fundamental. As such, we address nine frequently made mistakes when it comes to the use of PPIs, and also hope to disprove some of the misconceptions about PPI use. 

Mistakes in alcoholic liver disease and how to avoid them

ALD is multifaceted—its management poses many difficulties and pitfalls.

Alcohol consumption is the most prevalent aetiology for liver cirrhosis in Europe and the third leading risk factor for overall mortality.1,2 In fact, alcoholic liver cirrhosis accounts for almost half a million deaths a year worldwide, corresponding to 50% of all cases of cirrhosis, according to the World Health Organization (WHO).3 Alcoholic liver disease (ALD) is multifaceted, with several cofactors influencing its progression. Patients abusing alcohol can simultaneously have viral hepatitis B or C, or a genetic disease, such as alpha-1 antitrypsin deficiency or haemochromatosis.

Alcohol consumption is usually assessed in pure grams per day and has a direct relationship with liver damage. Daily alcohol consumption of >30 g for men and >20 g for women is considered the cut-off volume at which there is a risk of developing alcohol-related liver disease.4 Besides volume, the pattern of consumption is also a significant factor, with heavy episodic drinking (HED) defined as an intake of 60 g or more of pure alcohol on at least one occasion in the past 30 days. Regarding HED, there is scarce information on the threshold to be applied to this pattern of drinking.5 Although the relationship between alcohol consumption and ALD is well defined, it must be acknowledged that severe disease only develops in a fraction of those who consume excessive amounts of alcohol. Nonetheless, the disease course is very much influenced by the pattern of drinking, with periods of abstinence or heavy drinking clearly altering its progression.5 ALD can present in different stages, ranging from steatosis to more severe disease, such as the clinical syndrome of alcoholic hepatitis, or decompensated liver cirrhosis, which is sometimes complicated by liver cancer. In the setting of alcoholic hepatitis, several scores, such as the Maddrey discriminant function, Glasgow alcoholic hepatitis score (GASH) and ABIC, may be used to evaluate disease severity, predict short-term survival, and decide on the need for specific treatment. Later on, the Lille score, which includes the reduction in serum bilirubin levels at day 7, evaluates the response to prednisolone after one week, in order to decide whether to continue or stop treatment.5 Despite being a frequent disease, the different aspects of ALD mean that its management still poses many difficulties and pitfalls. In this article we discuss frequent mistakes in ALD, based on the current guidelines and some paradigmatic real-life cases. 

Mistakes in EoE and how to avoid them

EoE is the second-most frequent cause of chronic oesophagitis.

Eosinophilic oesophagitis (EoE) is a chronic immune-mediated inflammatory condition that is confined to the oesophagus. Clinically, EoE is characterized by symptoms of oesophageal dysfunction; histologically, by eosinophil-predominant inflammation.1,2 At present, EoE is the second-most frequent cause of chronic oesophagitis (gastro-oesophageal reflux disease [GORD] is the primary cause) and the foremost cause of dysphagia and food impaction in young adults and children.

The first descriptions of EoE date back to the early 1990s,3,4 but at that time the condition was largely underappreciated and treated as GORD. Recognition of EoE grew with the rapid increase of paediatric and adult patients diagnosed since 2003, but so did confusion surrounding diagnostic criteria and treatment. The first consensus guidelines for the diagnosis and management of EoE were published in 2007 and were instrumental in bringing EoE to light as a distinct new condition.5 Since 2007, the diagnostic criteria for EoE have constantly and rapidly changed. New evidence for therapeutic agents has mounted, especially during the past 5 years. Here, we discuss the critical pitfalls that frequently occur in daily practice when dealing with EoE patients. The discussion is evidence based and in line with the recommendations included in the updated guidelines for diagnosis and management of EoE in children and adults.6

Mistakes in liver function test abnormalities and how to avoid them

Liver function tests (LFTs) are routinely used to screen for liver disease, but the assessment of LFTs can be challenging. The LFT itself must be clearly understood and the results interpreted in light of the specific clinical setting.

Liver function tests (LFTs) are routinely used to screen for liver disease. A correct interpretation of LFT abnormalities may suggest the cause, severity, and prognosis of an underlying disease. Once the diagnosis has been established, sequential LFT assessment can be used to assess treatment efficacy.

Abnormal LFTs are frequently encountered in clinical practice, since elevation of at least one LFT occurs in more than 20% of the population.1 Many patients with abnormal LFTs, however,  do not suffer from structural liver disease, since these tests can be influenced by factors unrelated to significant liver damage or liver function loss. During normal pregnancy, for example, serum albumin levels fall due to plasma volume expansion, and alkaline phosphatase (ALP) levels rise due to placental influx. Patients who have elevated transaminase levels may not suffer from liver disease, but rather from cardiac or skeletal muscle damage. Conversely, patients who suffer from advanced liver disease, such as chronic hepatitis or compensated liver cirrhosis, may have normal LFTs.

In short, the assessment of LFTs can represent a challenge for physicians. The observations above demonstrate the need for a firm understanding of the individual LFT, and the ability to interpret the results in the light of a specific clinical setting. Such an understanding is not merely a goal on its own, but may serve as a template to avoid mistakes in interpreting LFT abnormalities. In the following sections, we discuss several mistakes frequently made in the interpretation of LFTs and how to avoid them. Most of the discussion is evidence based, but where evidence is lacking the discussion is based on extensive clinical experience.
<1 2>