Cholestatic hepatitis as a possible new side-effect of oxycodone: a case report

<p>Abstract</p> <p>Introduction</p> <p>Oxycodone is a widely-used semisynthetic opioid analgesic that has been used for over eighty years. Oxycodone is known to cause side effects such as nausea, pruritus, dizziness, constipation and somnolence. As far as we are aware cholestatic hepatitis as a result of oxycodone use has not been reported so far in the world literature.</p> <p>Case presentation</p> <p>A 34-year-old male presented with cholestatic jaundice and severe pruritus after receiving oxycodone for analgesia post-T11 vertebrectomy. Extensive laboratory investigations and imaging studies did not reveal any other obvious cause for his jaundice and a liver biopsy confirmed canalicular cholestatis suggestive of drug-induced hepatotoxicity. The patient's symptoms and transaminases normalised on withdrawal of oxycodone confirming that oxycodone was the probable cause of the patient's hepatotoxicity.</p> <p>Conclusion</p> <p>We conclude that cholestatic hepatitis is possibly a rare side effect of oxycodone use. Physicians should be aware of the possibility of this potentially serious picture of drug-induced hepatotoxicity.</p

Measuring disease in dermatology: studies of objective and subjective methods

Itch lies second only to disturbance of body image as a reported symptom in dermatology. This study started by concentrating on improving the measurement of itch. Itch has a paired physical response, scratch. The pairing can be exploited: preliminary work by this unit had validated the use of wrist-worn movement-measuring machines called ‘accelerometers’ to measure itch-related movement (scratch and rub). The first part of this research developed use of these machines. Simple accelerometers (‘Actiwatch Plus’) were used to observe the pattern of variation of itch over clusters of nights and in different conditions. The accelerometer scores were able to identify controls’ scores from those with itchy disease. Considerable variation (56%) was discovered in objective score between subject and considerable variation was noted (46%) even within subject. More complex accelerometers, (‘DigiTrac’) which could potentially specifically identify itch-related movement on the basis of frequency of action derived from Fast Fourier Transform (FFT), were validated against the ‘gold standard’ measurement of itch-related movement, directly observed movement (via infra red video recording). It was necessary to characterise the ‘frequency of action’ of itch on video and, as an aside, the characteristics of human itch-related movement were compared to other mammals’ itch-related movement ‘frequency of action’. The ‘frequency of action’ and video data was used to enrich the DigiTrac readouts to improve specificity of itch-related movement detection. During the accelerometer studies, an unexpected finding came to light: objective score of itch was not related to subjective score. To try to explain the lack of relationship, a 42 day longitudinal study of atopic dermatitis patients’ subjective and objective scores was undertaken. The results demonstrated autocorrelation for subjective scores, but not for the objective scores but still did not fully explain the lack of relationship. In an effort to explain the disconnect between subjective and objective scores a second tranche of experiments and the second part of this research interrogated whether the methods with which we measure disease as a whole in dermatology are robust. One study investigated whether the way patients are asked about subjective symptoms in general was resistant to the effects of focusing and framing bias. The results were reassuring as they suggested that the commonly used and recommended symptom scoring systems were robust in the face of bias. In order to assess whether perspective or perception of disease explained the disconnect, a study was designed in collaboration with the Edinburgh College of Art. A series of computer-generated images of different psoriasis severities were created and used to assess how doctors and patients assessed disease-extent. This study showed that, whilst each group had a naturally divergent opinion of extent of disease, by scoring disease using the models it was possible to unify the perspective and perception of extent. Finally, an exploratory study to reduce recall bias to a minimum, in case this had caused the disconnect between objective and subjective, was undertaken. This employed a novel questionnaire, the Day Reconstruction Method

Primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology characterized by injury of the intrahepatic bile ducts that may eventually lead to liver failure. Affected individuals are usually in their fifth to seventh decades of life at time of diagnosis, and 90% are women. Annual incidence is estimated between 0.7 and 49 cases per million-population and prevalence between 6.7 and 940 cases per million-population (depending on age and sex). The majority of patients are asymptomatic at diagnosis, however, some patients present with symptoms of fatigue and/or pruritus. Patients may even present with ascites, hepatic encephalopathy and/or esophageal variceal hemorrhage. PBC is associated with other autoimmune diseases such as Sjogren's syndrome, scleroderma, Raynaud's phenomenon and CREST syndrome and is regarded as an organ specific autoimmune disease. Genetic susceptibility as a predisposing factor for PBC has been suggested. Environmental factors may have potential causative role (infection, chemicals, smoking). Diagnosis is based on a combination of clinical features, abnormal liver biochemical pattern in a cholestatic picture persisting for more than six months and presence of detectable antimitochondrial antibodies (AMA) in serum. All AMA negative patients with cholestatic liver disease should be carefully evaluated with cholangiography and liver biopsy. Ursodeoxycholic acid (UDCA) is the only currently known medication that can slow the disease progression. Patients, particularly those who start UDCA treatment at early-stage disease and who respond in terms of improvement of the liver biochemistry, have a good prognosis. Liver transplantation is usually an option for patients with liver failure and the outcome is 70% survival at 7 years. Recently, animal models have been discovered that may provide a new insight into the pathogenesis of this disease and facilitate appreciation for novel treatment in PBC

Primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease with a slowly progressive course. Without treatment, most patients eventually develop fibrosis and cirrhosis of the liver and may need liver transplantation in the late stage of disease. PBC primarily affects women (female preponderance 9–10:1) with a prevalence of up to 1 in 1,000 women over 40 years of age. Common symptoms of the disease are fatigue and pruritus, but most patients are asymptomatic at first presentation. The diagnosis is based on sustained elevation of serum markers of cholestasis, i.e., alkaline phosphatase and gamma-glutamyl transferase, and the presence of serum antimitochondrial antibodies directed against the E2 subunit of the pyruvate dehydrogenase complex. Histologically, PBC is characterized by florid bile duct lesions with damage to biliary epithelial cells, an often dense portal inflammatory infiltrate and progressive loss of small intrahepatic bile ducts. Although the insight into pathogenetic aspects of PBC has grown enormously during the recent decade and numerous genetic, environmental, and infectious factors have been disclosed which may contribute to the development of PBC, the precise pathogenesis remains enigmatic. Ursodeoxycholic acid (UDCA) is currently the only FDA-approved medical treatment for PBC. When administered at adequate doses of 13–15 mg/kg/day, up to two out of three patients with PBC may have a normal life expectancy without additional therapeutic measures. The mode of action of UDCA is still under discussion, but stimulation of impaired hepatocellular and cholangiocellular secretion, detoxification of bile, and antiapoptotic effects may represent key mechanisms. One out of three patients does not adequately respond to UDCA therapy and may need additional medical therapy and/or liver transplantation. This review summarizes current knowledge on the clinical, diagnostic, pathogenetic, and therapeutic aspects of PBC