SYSTEMATIC REVIEW

The socio-economic impact of chronic pancreatitis:a systematic reviewThomas C. Hall MRCS,1 Giuseppe Garcea MD,2 M’Balu A. Webb PhD,3 Dhya Al-Leswas MRCS,1

Matthew S. Metcalfe MD2 and Ashley R. Dennison MD2

1Trainee Surgeon, 2Consultant Surgeon, 3Research Scientist, Department of Hepatobiliary and Pancreatic Surgery, University Hospitals ofLeicester, Leicester, UK

Keywords

chronic pancreatitis, economics, systematicreview

Correspondence

Dr Thomas C. HallDepartment of Hepatobiliary and PancreaticSurgeryUniversity Hospitals of LeicesterLeicester LE5 4PWUKE-mail: tch2@doctors.org.uk

Accepted for publication: 14 January 2014

doi:10.1111/jep.12117

AbstractRationale, aims and objectives Chronic pancreatitis (CP) is a progressive inflammatorydisorder with pain being the most frequent symptom. It is associated with loss of function,pancreatogenic diabetes and digestive enzyme deficiency. The impact of local complica-tions and loss of pancreatic function results in unknown and unreported costs. This studyattempts to identify both the direct and indirect costs associated with CP.Methods A MEDLINE literature review was performed for all relevant articles relating toany aspect of direct and indirect costs as a result of CP.Results In the UK, there are 12 000 admissions per annum of patients with CP at anestimated cost of £55.8 million. The costs for loss of pancreatic function are estimated at£45–90 million and $75.1 million for endocrine and exocrine function, respectively. Chronicpain contributes $638 million per year in costs. The protracted course of CP and paucity ofmonetary data make quantifying direct and indirect costs difficult. An estimate of direct andindirect costs is at £285.3 million per year. This equates to £79 000 per person per year.Conclusions Patients with CP consume a disproportionately high volume of resources.

IntroductionChronic pancreatitis (CP) is a progressive inflammatory disorder.It is characterized by the destruction of pancreatic secretory paren-chyma and its replacement by fibrous tissue, resulting in the loss ofendocrine and exocrine function. Although an uncommon condi-tion, its incidence is increasing perhaps due to rising alcoholconsumption, improved diagnostics and classification methods[1–3].

The main symptom of CP is usually pain [4]. Pain may occuras an acute exacerbation or as a constant disabling pain. Pain isthe cause of frequent hospital admissions, often necessitatinginterventional procedures. Despite extensive research, treatment ofCP remains mainly empirical. In addition to pain, exocrine defi-ciency, pancreatogenic diabetes, local pancreatic complicationsand psychosocial issues associated with the disease are additionaltherapeutic challenges placing a significant burden on the healthcare system.

The protracted and variable course of CP makes quantifyingdirect and indirect costs difficult. The economic burden of CP ispoorly defined in the literature. Although a number of studies havedemonstrated poor quality of life in patients with CP [5–7], fewhave examined the indirect costs of this to society. The purpose ofthis review is to collate both direct and indirect costs of CP, and tocalculate the socio-economic cost of CP.

MethodsA MEDLINE literature search was undertaken using keywords‘chronic pancreatitis’, ‘economics’, ‘social’, ‘costs’, ‘diabetes’,‘chronic pancreatitis and chronic pain’ and ‘incidence’. The inclu-sion criteria were studies examining any aspect of socio-economiccosts in CP. Search limits were English language manuscripts only.All articles retrieved had the references cross-checked to ensurecapture of cited pertinent articles.

The primary end point was total socio-economic costs of CP,both direct and indirect. Secondary end points were incidence,rates of hospital admission, costs of treating chronic pain, numbersrequiring intervention, and numbers developing exocrine andendocrine deficiency and the associated costs.

Direct costs were defined as the value of products (e.g. prescrip-tions) and services used in the management of CP. Indirect costsrelate to the monetary value of economic output lost because ofillness.

Results

Incidence of CP

Most recently, Jupp et al. collated epidemiological data from 14studies [8]. The number of studies investigating incidence were

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small and especially studies investigating changes in disease fre-quency over time. The studies suggest that the incidence of CP inEurope is 6–7 per 100 000. Studies from the USA and Japan havealso noted increases in incidence of the disease [9,10]. Dite et al.noted geographical differences in incidence, perhaps reflectingdifferences in alcohol consumption [1]. The authors also stated thatthe median time from the onset of the first subjective symptomsattributable to CP to diagnosis was 3.2 years (range 1–5 years).Mortality from CP is initially low. As the disease progresses,mortality steadily increases with duration. The 5-, 10- and 20-yearsurvival rate is 97%, 70–86.3% and 45–63%, respectively [8].

Admissions with CP and related complications

Five articles were identified examining the number of CP dis-charges per year [2,3,11–13]. Jaakkola and Nordback found theincidence of CP discharges between 1977 and 1989 increased from10.4 to 13.4 per 100 000 per year based on a Finnish population [2].In England and Wales, between 1962 and 1974, an increasingincidence of discharges in CPof 7–32.4 per million per year has alsobeen shown [3]. This increase correlated with the increase in percapita alcohol consumption. Yang et al. examined epidemiologicaldata on alcohol-related disease in the USA between 1988 and 2004and found the mean incidence of discharges to be 8.1 (confidenceinterval 7.7–8.6) per 100 000 per year [12]. They observed nochange in rates of discharges over the 17-year study period.

Data from the UK is lacking; however, Hospital Episode Statis-tics for 2009/2010 shows that there was in excess of 12 000 UKadmissions coded as ‘chronic pancreatic disease’, most as emer-gencies with a mean length of stay of 6.2 days [14]. From this data,a probable underestimate of cost based on a single day of emer-gency care and 5.2 days of prolonged ward care would equate tothe National Health Service (NHS) spending of £55.8 million.

Mullady et al. examined the number of patients with CP in theUSA who were admitted with pain [13]. Of the 414 patientsstudied, over 90% of them were hospitalized on at least one occa-sion for pain attributable to CP in their lifetime. Patients withconstant pain were more likely to have been hospitalized morethan 10 times in the preceding year than those with intermittentpain. Similarly, patients with intermittent pain were more likely tohave under two hospitalizations over their entire lifetime for painrelated to their CP, while those with constant pain patterns weremore likely to have more than 10 hospitalizations.

Costs of pancreatic insufficiency

Pancreatic endocrine insufficiency secondary to destruction ofacinar cells is an inevitable complication of CP. Depending onaetiology and duration, pancreatogenic diabetes (PD) develops in40–60% of patients with CP [15]. Its rates are highest in alcoholicand tropical types. At 10 and 25 years from diagnosis, 50% and83% of patients, respectively, develop this complication.

The complications of PD are similar to type II diabetes, exceptthat coronary artery disease is less common in PD [15]. The ratesof developing retinopathy, nephropathy, neuropathy and peripheralvascular disease are, however, similar. Glycaemic control is oftendifficult due to its brittle nature and proneness to hypoglycaemia.In patients with PD, the median survival is 25 years after diagno-sis. Mortality is frequently secondary to nephropathy.

In the NHS, diabetes and its related complications costs 10% ofthe total budget, equating to around £9 billion per year [16,17]. PDaccounts for 0.5–1% of all diabetes and therefore costs can beestimated at around £45–90 million per year. Its brittle naturemeans that this figure may underestimate the true value. In 2006,prescription costs for all-cause diabetes were £561.4 million [17].Extrapolating this for PD, prescription costs are estimated ataround £2.8–5.6 million a year. In addition, patients with all-causediabetes experience prolonged hospital stays compared withpatients with no diabetes, at a cost of 80 000 bed days per year. Ifwe assume that PD accounts for 0.5–1% of all diabetes, thisaccounts for 400–800 bed days per year. Calculations based on abed day cost of £225 [18] equate to £90 000–180 000 in prolongedstay costs.

Fifty-seven per cent of patients with CP take enzyme supple-ments [8]. Costs for all prescriptions in pancreatitis have beenestimated at $88.6 million in 2004 [19]. Pancreatic exocrineenzyme replacement constituted 84.8% of these costs, equating toaround $75.1 million a year.

Costs of surgical intervention

It is estimated that 50% of patients with CP require surgical inter-vention for pain management or for the management of compli-cations [20]. In total, approximately 700 surgical operations peryear are carried out in the UK for CP and its related complications[14]. These procedures range from radiological nerve root blocksto total pancreatectomy. To our knowledge no direct data exist forthe costs of these procedures.

Costs of pain

Chronic pain is associated with the poorest indices of quality oflife. It is associated with absenteeism, reduced productivity and ahigh risk of leaving the labour market [21]. These indirect costs aredifficult to quantify in the case of CP but there can be little doubtthat they will be vast. Estimates of the costs of pain in CP arearound $638 million annually, but this reflects an underestimate ofindirect costs [13] (Table 1).

In Sweden in 2003, the loss of production secondary to sickleave from chronic pain constituted 91% of the socio-economiccost, at Swedish Krona 87.5 billion (9.2 billion euros) [22]. Simi-larly, in Denmark, an estimated 1 million working days are lostannually secondary to chronic pain. The percentage of this costattributable to CP is unknown [23].

The study by Wehler et al. looked at 265 patients with CP [5].The group found that 14% of patients took disease-related earlyretirement and 13% had prolonged unemployment. Forty per centhad disease-related absence from work in the preceding 12months. In 17% of these, duration of absence was for up to amonth. To our knowledge, there is no data of indirect costs attrib-utable to CP from this lost productivity. In the USA, data of costssecondary to lost production from work-related absenteeism,reduced productivity, unemployment and premature mortalityfrom all-cause diabetes is $58 billion per year [24]. If we assumethat PD accounts for 0.5–1% of all diabetes, then indirect costscould be as high as $29–58 million from diabetes alone in CP.Again, the brittle nature of PD probably underestimates this and itdoes not take into account indirect costs due to chronic pain.

The cost of chronic pancreatitis T.C. Hall et al.

© 2014 John Wiley & Sons, Ltd.2

Collective direct and indirect costs incurredin CP

Figure 1 shows estimates of direct and indirect costs as a result ofCP. The estimated total cost is £285.3 million per year. With theassumption of a CP incidence of 6–7 per 100 000, based on the UKpopulation, there are 3600 patients with CP in any one year. Thisequates to a cost per year per person of £79 000.

DiscussionThe review aimed to collate direct and indirect costs of CP.Patients with chronic pain secondary to CP require frequent

in-hospital treatment, including intravenous opiate analgesics,bowel rest, total parenteral nutrition, celiac plexus blocks, endo-scopic stent therapy and occasionally surgical resection ordrainage procedures [25]. All of these interventions are associ-ated with significant direct and indirect hospital-based medicalcosts.

What is evident is that the lack of available data makes placinga collective monetary value of the disease difficult. Indirect costsof disease are an imprecise science and often they are hidden. CP,by the nature and aetiology of the disease, is difficult to treat andthe patients represent a difficult cohort due to the frequent occur-rence of alcohol, tobacco and opiate codependencies. Frequently,data from patients with CP are mixed together with alcohol-related

Table 1 Socio-economic costs of chronic pancreatitis

Frequency Costs

Incidence 6–7 per 100 000Admission rate 12 000 per year £55.8 millionEndocrine insufficiency 40–60% of patients with CP £45–90 million

£2.8–5.6 million per year for prescriptions£90 000−180 000 for prolonged inpatient stay

Exocrine insufficiency 57% require enzyme supplements $75.1 millionIntervention 50% of patients with CP have intervention Costs unknownPain $638 million per year (likely to be a huge underestimate)

lost productivity secondary to PD estimated at $29–58 million aloneTotal £55.8 million + £90 million + £9.5 million + £130 million = £285.3

million per year

Calculations based on the assumption of an exchange rate of £1 = US$ 1.6134 and population of USA at 4.9 times that of the UK. Likely representsa huge underestimate.CP, chronic pancreatitis; PD, pancreatogenic diabetes.

Incidence 6–7 per 100 000(~3600 in UK)

Exocrineinsufficiency

Endocrineinsufficiency

Admission rate

Intervention

Pain >80%

50%

57% requireenzyme

40−60%

12 000 per year

£285.3 millionper year

£55.8 million

£45−90million

$75.1 million

Unknown

$638 million

£18 400–37 300

Figure 1 Socio-economic costs of chronic pancreatitis.

T.C. Hall et al. The cost of chronic pancreatitis

© 2014 John Wiley & Sons, Ltd. 3

disease or acute pancreatitis, making CP-specific conclusionsimpossible. Co-morbidities (such as smoking and alcohol) arelikely to contribute significantly and these are inadequately definedin the literature.

The per annum cost of CP was estimated at £285.3 million andthis is likely to be an underestimate. Chronic pain forms a largepart of indirect costs to society and is the sentinel symptom of CP.Chronic pain studies often fail to focus on disease-specific out-comes and therefore the costs attributable from CP are unknown.Lower back pain in the UK, for example, had estimated indirectcosts of between £5 and £10.7 billion in 1998 [26]. CP, althoughless common, is associated with high rates of unemployment andabsenteeism, and will be associated with unknown but no doubtsignificant values for indirect costs.

Another unknown direct cost is that from surgical or radiologi-cal intervention. Although there are 700 procedures performedevery year for CP in the UK, the cost is unknown. The incidence ofCP is increasing and therefore costs will continue to rise.

There are a number of treatment options in the surgical arma-mentarium depending on the aetiology and specific abnormality ofthe gland. These include bypass procedures, duct decompression/drainage and resection (total or part). In randomized controlledtrials, surgery has been demonstrated to be superior in attaininglong-term pain control and improved quality of life compared withendoscopic treatment [27–29]. Studies have also shown that earlysurgical intervention is indicated before the gland is functionallyand morphologic irreversibly damaged [30,31].

Drainage procedures, such as the Frey procedure, and resec-tional intervention, such as the Beger technique, have been shownto provide long-term pain relief together with the preservation ofendocrine and exocrine function [32–34]. Resective surgery con-tinues to be the definitive treatment for severe disease and persis-tent pain. Previous studies have suggested that the costs of surgerycan be outweighed by the reduced direct costs of the illness interms of reduced health care costs, improved employment ratesand improved quality of life [7,35–37].

Total pancreatectomy has been shown to reduce chronic pain andthe number of admissions to the hospital [38]. The addition of anislet transplant may give further benefit in terms of glycaemiccontrol and reduce diabetic complications [39]. There is no specificevidence addressing the cost-effectiveness of pancreatectomy andislet auto transplantation compared with pancreatectomy alone.This can, however, be estimated by extrapolating from studiesrelating to islet allotransplantation. Beckwith et al. recently ana-lysed the cost-effectiveness of islet allotransplantation comparedwith standard insulin therapy in type 1 diabetes [40]. They foundthat for insulin therapy the cumulative cost per patient during a20-year follow-up period was $663 000 and cumulative effective-ness was 9.3 quality-adjusted life years (QALY), giving an averagecost-effectiveness ratio of $71 000 per QALY. Islet cell transplan-tation was more cost-effective than standard insulin treatment,having a cumulative cost of $519 000, a cumulative effectivenessof 10.9 QALY and an average cost-effectiveness ratio of $47 800per QALY.

CP is costly but precise costs are difficult to make due to thepaucity of available data. Interest in the economic impact of healthcare interventions has increased dramatically in recent years [41].Chronic conditions are costly. Despite CP occurring in a minorityof patients, they consume a disproportionate volume of resources.

Select early surgical intervention may ameliorate chronic pain,preserve or improve endocrine function and reduce hospital admis-sions. Although quantitative data do not exist, early surgery mayreduce both the indirect and direct costs of CP.

Conflict of interestThe authors declare no conflict of interest.

Author contributionsThe manuscript has been read and approved by all the authors.The requirements for authorship have been met, and each authorbelieves that the manuscript represents honest work.

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