The communication of a secondary care diagnosis of autoimmune hepatitis to primary care practitioners: a population-based study
© Varyani et al.; licensee BioMed Central Ltd. 2013
Received: 22 January 2013
Accepted: 13 April 2013
Published: 1 May 2013
Autoimmune Hepatitis is a chronic liver disease which affects young people and can result in liver failure leading to death or transplantation yet there is a lack of information on the incidence and prevalence of this disease and its natural history in the UK. A means of obtaining this information is via the use of clinical databases formed of electronic primary care records. How reliably the diagnosis is coded in such records is however unknown. The aim of this study therefore was to assess the proportion of consultant hepatologist diagnoses of Autoimmune Hepatitis which were accurately recorded in General Practice computerised records.
Our study population were patients with Autoimmune Hepatitis diagnosed by consultant hepatologists in the Queens Medical Centre, Nottingham University Hospitals (UK) between 2004 and 2009. We wrote to the general practitioners of these patients to obtain the percentage of patients who had a valid READ code specific for Autoimmune Hepatitis.
We examined the electronic records of 51 patients who had biopsy evidence and a possible diagnosis of Autoimmune Hepatitis. Forty two of these patients had a confirmed clinical diagnosis of Autoimmune Hepatitis by a consultant hepatologist: we contacted the General Practitioners of these patients obtaining a response rate of 90.5% (39/42 GPs). 37/39 of these GPs responded with coding information and 89% of these patients (33/37) used Read code J638.00 (Autoimmune Hepatitis) to record a diagnosis.
The diagnosis of Autoimmune Hepatitis made by a Consultant Hepatologist is accurately communicated to and electronically recorded by primary care in the UK. As a large proportion of cases of Autoimmune Hepatitis are recorded in primary care, this minimises the risk of introducing selection bias and therefore selecting cases using these data will be a valid method of conducting population based studies on Autoimmune Hepatitis.
Autoimmune hepatitis (AIH) is a chronic liver disease with an immune mediated aetiology. The disease is rare with an annual incidence of 1.9/100000  and has a bimodal age distribution with median age at diagnosis approximately 43 years . It is an uncommon but important disease due to the potential for decompensated cirrhosis and the requirement of an orthotropic liver transplant in otherwise young, healthy people. Recent data from a non-transplant centre in the UK has estimated the 10 year survival to be 82% .
The clinical features of AIH are complicated and require a strong clinical suspicion with contributory evidence such as a suggestive liver biopsy, auto-antibodies (anti-nuclear antibodies, anti-smooth muscle cell and anti-liver kidney microsomal antibodies) or an elevated Immunoglobulin G (IgG) titre. Liver biopsy should classically show active interface hepatitis with lymphocytic and plasma-cell infiltrates. There have been several scoring criteria formulated for diagnosis which include the original, revised and simplified  criteria by the International Autoimmune Hepatitis group. However, the consensus is that clinical diagnosis is most important .
As AIH is a relatively uncommon but important disease, it is difficult to obtain large cohorts of patients to study. Previous studies have used multiple hospital data collection methods, and the largest study so far has obtained 473 patients with Autoimmune Hepatitis . However, these methods are not without potential selection bias and considerable expense. The use of population-based databases may provide an alternative means of obtaining a large cohort of AIH patients. The strengths of databases include prospective, systematic collection of data including exposures, confounders and outcome information. However, their limitations include concerns about the validity of a diagnosis of Autoimmune Hepatitis within the database. The UK General Practice Research Database is one such population-based database. It has over 5 million currently registered patients  and it is therefore estimated would provide between 1000–2500 unique patients for studies of the epidemiology of Autoimmune Hepatitis. We have therefore aimed to validate the sensitivity of diagnosis of AIH in electronic primary care data in order to assess its usefulness for studying AIH.
The study population were all patients within the catchment area of Queens Medical Centre, Nottingham University Hospitals UK who were diagnosed by a Consultant Hepatologist with Autoimmune Hepatitis (AIH) between 2004 till 2009. We identified these patients from a list of liver biopsies discussed at a weekly liver biopsy meeting held in the Nottingham University Hospitals, Queens Medical Centre, the larger of the two major hospitals providing Hepatology services to Nottingham, UK). In addition there were a small number of biopsies of patients from nearby District General Hospitals which were reviewed at this meeting.
Nottingham University Hospitals has an electronic system for recording clinic letters and discharge information (NOTIS), which is accessible along with their laboratory, histopathology and microbiology results. Where possible, we obtained these electronic records for those patients with biopsy features of autoimmune hepatitis. We reviewed all patients who had a suggestion of autoimmune hepatitis on their biopsies and who were ever given a clinical label of Autoimmune Hepatitis. Those patients who had available hospital records demonstrating an initial diagnosis of AIH (by a Consultant Hepatologist) and through the course of their clinical encounter were shown not to have an alternative diagnosis became our cohort of patients with Autoimmune Hepatitis. As the course of their disease progressed, some of these patients received an alternative diagnosis or an additional diagnosis as part of an overlap syndrome. We maintained a record of these cases also.
Validation of clinical diagnosis
The simplified autoimmune hepatitis criteria [
ANA or SMA
ANA or SMA
> Upper normal limit
>1.1 Upper normal limit
Compatible with AIH
Typical of AIH
Assessment of diagnoses coded in general practice for the study population
General Practitioners in the UK use Read codes to code diagnoses. AIH is coded specifically by the two Read codes J63B.00 Autoimmune Hepatitis and J614111 Autoimmune Chronic Active Hepatitis. It can be coded non-specifically by numerous other codes.
We sent the General Practitioners (GPs) of all the patients we had defined as having AIH a letter asking them if these patients had a code for autoimmune hepatitis in their system and if so what code had been used. We also asked how this diagnosis had been communicated to the primary care team. A similar methodology has previously been used by our group for diverticular disease .
In the process of identifying patients with AIH, we also identified a cohort of patients who initially receive a diagnosis of AIH, but whose final diagnosis was different. These patients were not scored with the simplified autoimmune hepatitis score. However, letters were sent to their general practitioners asking them if they had READ codes for a range of liver diagnoses (including autoimmune hepatitis, chronic hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis) to assess the possibility of mislabelling them as autoimmune hepatitis. We similarly wrote to those GP surgeries who were caring for patients with any overlap syndrome i.e. PBC/PSC, PBC/AIH or PSC/AIH overlap syndromes.
We carried out this work as an audit registered within the NUH NHS Trust (Audit ID 1582).
Study population identified
We identified 51 biopsy reports between 2004 and 2009 in which the possibility of AIH was raised.
Age at diagnosis
Sex (% Female)
IgG > ULN (%)
SMA Positivity (%)
ANA Positivity (%)
Simplified autoimmune hepatitis score
Scores obtained by the simplified autoimmune hepatitis criteria
Autoimmune hepatitis scoring criteria
Number of patients with a particular score
Overall response rate
We sent 49 letters to General Practitioners and received 46 replies (an overall response rate of 95%). We were unable to send 2 letters because GP address information was not available to us, this was primarily because these biopsies were sent to the liver meeting to provide a second opinion, and then sent back to the local trust. Neither the biopsies nor the demographic information about the patients were retained beyond the meeting for these two biopsies.
Communication of a diagnosis of AIH
Responses obtained from the practices
J638.00 Autoimmune Hepatitis
J614100 Chronic Active Hepatitis
J614.00 Chronic Hepatitis
Free text box: Autoimmune hepatitis
Other diagnoses and overlap syndromes
Patients found to have another diagnosis (or an overlap syndrome)
Final consultant diagnosis
Read code in general practice
J638.00 Autoimmune Hepatitis
PSC/AIH overlap syndrome
J638.00 Autoimmune Hepatitis
J661700 Primary Sclerosis Cholangitis
PBC/PSC overlap syndrome
J616000 Primary Biliary Cirrhosis
J614.00 Chronic Hepatitis
Free text in clinic letter ?sclerosing cholangitis
J616000 Primary Biliary Cirrhosis
J616000 Primary Biliary Cirrhosis
J638.00 Autoimmune Hepatitis
PBC/AIH overlap syndrome
No letter received from GP
J661700 Primary Sclerosing Cholangitis
More than 300 studies have been performed to assess the positive predictive value of the coding of diseases for the presence of the coded diagnosis. These have in general found high positive predictive values in the order of 90% [7, 8]. It is likely that the same will be true for Autoimmune Hepatitis, but that is not what this study has examined. We in contrast have examined the sensitivity of the coded diagnosis of a chronic disease for its presence, and this to our knowledge has very rarely been done before .
We assessed the validity of the coding of AIH using a cohort of 42 patients with AIH and 7 patients with other diagnoses or an overlap syndrome whose biopsies were reviewed at the liver biopsy meeting at the Queens Medical Centre, Nottingham, UK, between 2004 and 2009. The diagnosis of AIH is complicated, as essentially there is no single pathognomonic feature  and the clinical context is of the utmost importance. Despite there being validated scoring criteria, the consensus of recent British Society of Gastroenterology guidelines on AIH is that this diagnosis requires considerable “clinical expertise”  and scoring should be used as an adjunct. We chose to use a consultant diagnosis of autoimmune hepatitis as our gold standard as had Yeoman . We had 42 patients available to us who had a clinical diagnosis of AIH as confirmed by the managing hepatologist, for whom we requested coding information from GPs. We received 39 responses, 37 of the patients had coded or free text information available for the diagnosis of autoimmune hepatitis. Two additional practices wrote back to us to state the patient had left the practice or that they patient was deceased and they no longer held their electronic or paper records (Table 4). Of the 37 GP practices which had information available on the electronic recording of patient data, 89% used a specific READ code for Autoimmune Hepatitis (J638.00 Autoimmune Hepatitis). Others had used non-specific codes which may be interpreted as other forms of liver disease or used free text (Table 4).
We believe therefore that the sensitivity of the coded diagnosis of Autoimmune Hepatitis for the detection of this condition in General Practice is 89% i.e. 89% of all people diagnosed with Autoimmune Hepatitis in hospital get a specific code in electronic primary care records for Autoimmune Hepatitis. This high sensitivity ensures that electronic records are unlikely greatly to underreport the incidence and prevalence of AIH and thus such records are suitable for studying the epidemiology of AIH in databases such as the General Practice Research Database, QResearch or the Health Improvement Network in the United Kingdom. Mediplus is a general practice database used in France, Austria and Germany; Holland uses PHARMO, IPCI and PALGO. In addition there are hospital based databases in England, Spain, Sweden Canada, Australia, Asia (China, Hong Kong, Japan, South Korea, Taiwan and Singapore), Latin America (Brazil, Argentina, Mexico, Venezuela, Peru, Chile). Evidence exists that data from the UKGPRD correlates with other databases in Europe e.g. fracture risk in coeliac disease was found to be increased to the same extent in both the UK GPRD  and in the Swedish National Inpatient Register  There are also Danish Registries which have been used to look at liver diseases .
Seven of the initial fifty patients were subsequently found to have other diagnoses, or overlap syndromes. We wrote to their general practitioners to assess the possibility of a miscoded diagnosis of AIH. If we were considering performing population-based studies, we would be able to exclude most of the overlap and misdiagnosed patients by excluding any person with a code for another form of liver disease as well as autoimmune hepatitis. 71% of these overlap syndromes or those with subsequent diagnoses were accurately coded.
A limitation of this study in the assessment of validity is that it assessed sensitivity of AIH alone. Other measures of diagnostic accuracy or utility include positive predictive value, specificity and negative predictive value. We believe the positive predictive value of AIH to be high in electronic primary care data because this has been shown to be the case in other gastrointestinal diseases such as Coeliac Disease, IBD, Cirrhosis  all of which require a similar diagnostic process to AIH including assessment in secondary care and a combination of clinical judgement, laboratory and histological results. Nonetheless further work looking at the positive predictive value of this diagnosis in the GPRD, validating against Hospital Episode Statistics records and/or the clinic letters/discharge information available to the General Practitioners would enhance our confidence in the value of these data. We believe the negative predictive value of a disease such as AIH which has an incidence of approximately 1.9/100 000 would be high simply because it is so uncommon. Other limitations include the lack of data on a therapeutic response, however, as this was a retrospective study there was insufficient information available to come to a valid conclusion about therapy.
All the patients were sourced via the liver biopsy meeting in Nottingham University Hospitals. In Nottingham it is unit policy to biopsy all patients in whom a diagnosis of AIH is made in view of the potentially lifelong therapy which is being embarked upon. Hence in Nottingham only patients who decline a biopsy will not be biopsied. The method chosen to obtain patients for the audit was recommended by the departmental hepatologists as it would be least likely to miss any cases. When compared to a non-transplant centre’s experience of autoimmune hepatitis in Sheffield, only 16 out our 245 cases did not have an initial biopsy, and eventually 7 underwent a biopsy .
Use of electronic primary care data for studying the epidemiology of Autoimmune Hepatitis will be an efficient means of studying this disease, enabling access to large population-based cohorts in order to answer some of the important questions of the contemporary natural history of this disease. Our results suggest, we will through such work be able to precisely quantify the incidence and prevalence of AIH without fear of grossly underestimating the disease as the sensitivity of the recording is so good. Equally, studies of aetiology and consequence should be able to provide much needed insights into this condition. Further work into the positive predictive value of this disease in electronic data is still required.
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