This pathway is adapted from Newsome PN, Cramb R, Davison SM, et al. Guidelines on the management of abnormal liver blood tests. Gut 2018;67:6-19

Initial investigation for potential liver disease should include:

Bilirubin <div class="navybox"> <p><b>Bilirubin</b> exists in two forms, unconjugated and conjugated.</p> <ul> <li><b>Unconjugated hyperbilirubinaemia</b> is usually due to haemolysis or impaired conjugation. <ul> <li>The most common cause of an isolated elevated bilirubin concentration is Gilbert’s syndrome, which is an inherited disorder of metabolism and leads to impaired conjugation.</li> </ul> </li> <li><b>Conjugated hyperbilirubinaemia</b> is typically due to parenchymal liver disease or obstruction of the biliary system.</li> </ul> </div>   Albumin <div class="navybox"> <p><b>Albumin</b> is only produced by the liver, the serum albumin concentration is often considered as a marker of the synthetic function of the liver. However, albumin concentrations are reduced in many clinical situations, including sepsis, systemic inflammatory disorders, nephrotic syndrome, malabsorption and gastrointestinal protein loss.</p> </div>   ALT <div class="navybox"> <p><b>Alanine aminotransferase</b> is present in hepatocytes and is released into the blood stream in response to hepatocyte injury or death (hepatitis). ALT is considered more liver-specific than AST. However, the concentration of AST may be a more sensitive indicator of liver injury in conditions such as alcohol-related liver disease and in some cases of autoimmune hepatitis.</p> </div>   ALP <div class="navybox"> <p><b>Alkaline phosphatase</b> is produced mainly in the liver (from the biliary epithelium) but is also found in abundance in bone and in smaller quantities in the intestines, kidneys and white blood cells. Levels are physiologically higher in childhood, associated with bone growth, and in pregnancy due to placental production.</p> <p>Pathologically increased levels occur mainly in bone disease (eg, metastatic bone disease and bone fractures) and cholestatic liver disease—for example, primary biliary cholangitis, primary sclerosing cholangitis, common bile duct obstruction, intrahepatic duct obstruction (metastases) and drug-induced cholestasis. Furthermore, hepatic congestion secondary to right-sided heart failure can also lead to cholestasis (elevated ALP levels and/or bilirubin).</p> </div>   GGT <div class="navybox"> <p><b>γ-Glutamyltransferase</b> is abundant in the liver and also present in the kidney, intestine, prostate and pancreas but not in bone; therefore it can be useful in confirming that an elevated ALP is of liver and not bony origin. GGT is most commonly elevated as a result of obesity, excess alcohol consumption or may be induced by drugs.</p> </div>   FBC <div class="navybox"> <p>Check <b>FBC</b> if not already performed within the previous 12 months.</p> <p>A reduction in <b>platelets</b>, termed thrombocytopenia, is the most common haematological abnormality found in patients with chronic liver disease and is an indicator of advanced disease. Multiple factors culminate in a low platelet count: decreased production, splenic sequestration and increased destruction.</p> </div>

Initial response to abnormal liver blood tests pathway || NAFLD pathway || Alcohol-related liver disease pathway

Clinical assessment and response to abnormal liver blood tests:

Marked derangement or Unexplained clinical jaundice <div class="navybox"> <h3><b>Jaundice in adults</b></h3> <ul> <li>Can be caused by many disorders ranging from benign to life-threatening conditions such as Gilbert's syndrome and pancreatic cancer, respectively. <ul> <li>Although jaundice is not a particularly common presentation in general practice, it <span style="color: #ff0000;"><strong>usually indicates a serious underlying condition and requires urgent investigation</strong></span>. Malignancy, alcohol, and gallstone disease are important causes of jaundice in the UK.</li> <li><strong><span style="color: #ff0000;">Most adults presenting to primary care with jaundice should be admitted or referred to secondary care.</span></strong></li> <li><details> <summary><b>People presenting with jaundice should be admitted for same-day assessment if:</b></summary> <ul> <li>They are acutely unwell, for example if encephalopathy is suspected or they have a fever.</li> <li>Cholangitis is suspected.</li> <li>Bilirubin is greater than 100 micromol/L.</li> <li>Renal function is abnormal, or they are dehydrated.</li> <li>Clotting profile is abnormal.</li> <li>They are frail or have significant co-morbidities.</li> <li>Paracetamol overdose is suspected.</li> </ul> </details></li> <li><details> <summary><b>People presenting with jaundice who do not need admission should be referred to secondary care if:</b></summary> <ul> <li>Malignancy is suspected (refer using a suspected cancer pathway, for an appointment within 2 weeks).</li> <li>Blood tests show a cholestatic or obstructive picture.</li> <li>Blood tests show a hepatitic picture.</li> <li>Alcohol-related liver disease is suspected.</li> <li>Inherited or autoimmune liver disease is suspected.</li> </ul> </details></li> </ul> </li> <li>Assessment of a person presenting with jaundice includes: <ul> <li>Asking about: the duration of the current episode, previous episodes of jaundice, changes in stools and urine, itching, location and radiation of pain; systemic symptoms of fever, rigors, arthralgia, myalgia, rash, fatigue, nausea, vomiting, and weight loss; travel abroad; history of intravenous drug use or blood transfusion; exposure to hepatotoxic drugs; and occupation.</li> <li>Examination to assess vital signs and identify signs of chronic liver disease, lymphadenopathy, abdominal masses, tenderness, or ascites.</li> <li>Taking a urine sample to check for bilirubin.</li> <li>If the person is not acutely unwell requiring admission, carrying out blood tests including a full blood count, liver function tests, urea and electrolytes, clotting, and hepatitis screening (if risk factors are identified in the history).</li> <li>Depending on the results of initial blood tests, referral to secondary care or additional screening tests such as a full liver screen and imaging such as ultrasound scan may be appropriate.</li> </ul> </li> <li><strong><span style="color: #ff0000;">Red flags</span></strong> associated with jaundice include signs of hepatic encephalopathy (such as confusion), hepatic dysfunction (such as bruising), gastrointestinal blood loss and sepsis, marked abdominal pain or tenderness, vomiting, weight loss, and suspicion of paracetamol overdose.</li> </ul> <p style="text-align: right;"><a href="https://cks.nice.org.uk/topics/jaundice-in-adults/" target="_blank" rel="noopener"><strong>[SOURCE: NICE-CKS: Jaundice in adults]</strong></a></p> </div> or Suspicion of Malignancy ⇛ URGENT REFERRAL TO HOSPITAL INDICATED

Incidental raised liver enzymes <div class="navybox"> <p><b>In all adults with incidentally raised liver enzymes it is important to take a careful history and perform a targeted clinical examination to <u>look for the cause</u></b></p> <ul> <li>Liver enzymes can occasionally be raised owing to intercurrent illness, although when liver blood tests were repeated, 84% of tests remained abnormal on retesting after 1 month, and even at 2 years 75% remained abnormal.</li> <li>Thus, in a patient with abnormal liver blood tests it is not recommended to simply repeat the same panel of tests but to determine the cause unless there is a high index of clinical suspicion that it is a transient finding. </li> </ul> </div> ⇛ careful history + targeted clinical examination <div class="navybox"> <p><strong><u>Obtain a thorough clinical history, including:</u></strong></p> <ul> <li><strong>age and ethnicity</strong>/country of birth (to explore possible risk of hepatitis B or C);</li> <li><strong>specific symptoms</strong> (jaundice, abdominal pain, weight loss, pruritus, etc);</li> <li><strong>comorbidity</strong>;</li> <li><strong>drug history</strong> (prescribed, over the counter, herbal, injecting drug use, illicit);</li> <li><strong>travel history</strong>; occupational exposure; tick bites; muscle injury;</li> <li><strong>alcohol history</strong> (current and past intake in average units per week, consider AUDIT C);</li> <li>features of the <strong>metabolic syndrome</strong> (central obesity, hypertension, diabetes/insulin resistance and dyslipidaemia);</li> <li><strong>family history</strong> and other symptoms. <ul> <li>PSC should be considered for patients with raised cholestatic liver enzymes and a personal or family history of autoimmune disease or personal history of inflammatory bowel disease. No diagnostic or serological markers exist for PSC and MRI may be required at the outset.</li> </ul> </li> <li>For patients with more <strong>marked elevations in ALT (&gt;1000 U/L) other possible causes of viral hepatitis</strong> should be considered, including hepatitis A and E and cytomegalovirus.</li> </ul> <p><strong><u>Examinations should include: </u></strong></p> <ul> <li><strong>body mass index</strong> and an <strong>abdominal examination</strong> looking for hepatosplenomegaly, ascites, and other signs of chronic liver disease. </li> </ul> </div> +/- standard liver aetiology screen <div class="navybox"> <p><strong>In adults a standard liver aetiology screen should include:</strong></p> <ul> <li><strong>Abdominal ultrasound scan</strong></li> <li><u>Viral Hepatitis</u> <ul> <li><strong>Hepatitis B surface antigen AND Hepatitis C antibody</strong> (with follow-on polymerase chain reaction if positive)</li> </ul> </li> <li><u>Autoimmune liver disease (excluding PSC)</u> <ul> <li><strong>Anti-mitochondrial antibody, anti-smooth muscle antibody, antinuclear antibody</strong></li> <li><strong>Serum immunoglobulins</strong></li> </ul> </li> <li><u>Iron overload</u> <ul> <li><strong>Ferritin and transferrin saturation</strong></li> </ul> </li> </ul> <p><a href="https://gut.bmj.com/highwire/markup/215486/expansion?width=1000&amp;height=500&amp;iframe=true&amp;postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed" target="_blank" rel="noopener"><strong>Liver aetiology table (includes Extended liver aetiology panel)</strong></a></p> </div>