Fiona M. Thompson Institute for Translational Medicine, University Hospitals Birmingham, Birmingham, UK Mental health facilities care for patients with a wide variety of conditions that may affect the liver, from patients with alcohol use disorders and acute delirium secondary to withdrawal, to those with body dysmorphic syndromes and eating disorders such as anorexia nervosa. Some liver diseases may present with psychiatric features; classically, Wilson’s disease but also hepatic encephalopathy. Many medications used for mental health indications may cause abnormalities of liver function or liver disease, and this can be made more complicated by polypharmacy and coexisting substance misuse. LFTs are better considered as markers of liver inflammation, the liver enzymes, alanine amino transferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP), and gamma‐glutamyl transferase (GGT) are all characteristically raised in the presence of hepatocyte damage and loss (AST and ALT are considered hepatocyte markers, while ALP and GGT are cholestatic markers, derived from cholangiocytes that line the bile ducts). Thus, they provide a snapshot of liver inflammation on the day the sample is taken, and do not necessarily provide any information about liver function or chronic liver disease. The serum bilirubin, albumin, and international normalized ratio (INR) may give more information about the synthetic capacity of the liver and therefore about underlying liver function. Abnormal LFTs therefore represent episodes of inflammation within the liver. There are many potential causes of abnormal liver function (including a significant proportion where no clear cause can be found). The importance of evaluating patients with abnormal LFTs is to try and identify those that may already have undiagnosed liver disease and those at risk of developing chronic liver disease, to enable appropriate treatment or lifestyle changes to be made to prevent further progression of disease and appropriate management of potential complications of chronic liver disease. Mental health practitioners may not consider requesting LFTs in many of their patients. However, routine tests should be performed for those who have a history of alcohol or substance misuse, particularly those with risk factors for viral hepatitis. If these patients are found to have abnormal liver function, they should be referred for further assessment. In addition, a number of commonly prescribed medications are metabolized in the liver and their use can be limited in the context of impaired liver function, while others require monitoring of LFTs as a precaution for use. Serum LFTs are likely to be requested in patients for whom these medications are considered. The most common drug‐induced liver injury (DILI) is idiosyncratic, dose independent, and not predictable. Drugs used in mental health that are commonly associated with abnormal liver function include antidepressants and atypical/typical antipsychotics. All antidepressants can cause liver injury. Mild abnormalities of liver function are reported in up to 3% of patients on antidepressants. However, liver toxicity requiring hospital admission is rare, with an estimated incidence of 1.28–4 cases/100 000 patient‐years. Risk factors for liver injury appear to include age, polypharmacy, and obesity. Pre‐existing liver damage may also play a role in some cases. Data are sparse and these may be underestimates; for older drugs, this information can only be found in case reports, while for newer medications the results of clinical trials as well as case reports are available. Life‐threatening or severe DILI has been reported for the monoamine‐oxidase inhibitor phenelzine, the tricyclic antidepressant imipramine, the selective serotonin reuptake inhibitor (SSRI) sertraline, the serotonin noradrenaline reuptake inhibitors venlafaxine and duloxetine, and serotonin‐2 antagonist/reuptake inhibitor trazodone, while the SSRIs citalopram and fluvoxamine are characterized by lower risk. Anti‐depressant‐associated liver injury can occur from several days up to six months after the beginning of treatment. It is generally hepatocellular rather than cholestatic, characterized by an increase in aminotransferase levels that normalize on drug withdrawal. In more severe cases, patients can also become jaundiced with synthetic dysfunction (prolonged INR) and there is a risk of fulminant hepatitis and acute liver failure. A cholestatic pattern of injury is more commonly associated with specific drugs (phenelzine, moclobemide, amitriptyline, mianserin, mirtazapine, and tianeptine), and tends to be slower to resolve. There are occasional reports of amitriptyline and imipramine causing prolonged cholestasis and vanishing bile‐duct syndrome. Table 16.1 Commonly used antidepressants and the patterns and proposed mechanisms of liver injury.
16
Mental Health and Neurology
Introduction
Unexplained Abnormal Liver Function Tests in Mental Health and Neurology Settings
Antidepressants
Drug
Class
Type of injury
Mechanism
Risk of liver injury
Phenelzine
MAOI
Cholestatic/hepatocellular
Metabolic
+++
Moclobemide
MAOI
Cholestatic/hepatocellular
Metabolic
++
Imipramine
TCA
Cholestatic/hepatocellular/vanishing bile‐duct syndrome
Direct toxicity or hypersensitivity
+++
Amitriptyline
TCA
Fulminant hepatitis/cholestasis
Immunoallergic
+++
Clomipramine
TCA
Hepatocellular
Immunoallergic
+
Fluoxetine
SSRI
Hepatocellular/cholestatic/mixed
Metabolic/idiosyncratic
+
Paroxetine
SSRI
Hepatocellular/cholestatic
Metabolic
+
Sertraline
SSRI
Hepatocellular/cholestatic/mixed
Immunoallergic
++
Citalopram, Escitalopram
SSRI
hepatocellular
Metabolic
+
Fluvoxamine
SSRI
Hepatocellular
Metabolic
+
Venlafaxine
SNRI
Hepatocellular, cholestatic
Idiosyncratic
++
Duloxetine
SNRI
Hepatocellular, cholestatic
Idiosyncratic
+++
Trazodone
SARI
Hepatocellular, mixed, cholestatic
Idiosyncratic
++
Mirtazapine
−
Hepatocellular, mixed
Metabolic
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