Indian Journal of Gastroenterology (March–April 2018) 37(2):77–78
https://doi.org/10.1007/s12664-018-0839-8
EDITORIAL
Progression of recurrent acute to chronic pancreatitis: More questions
than answers!
Rupjyoti Talukdar 1
Published online: 19 March 2018
# Indian Society of Gastroenterology 2018
Acute pancreatitis (AP) continues to pose a substantial chal- ongoing study from our institute also reveals that 10% of
lenge to clinicians and researchers. It has been proposed that patients with a single episode of AP and 28% with RAP even-
an index episode of AP could progress to recurrent AP (RAP) tually developed CP.
and may finally culminate into chronic pancreatitis (CP). This Since only a proportion of RAP progresses to CP, it be-
is the sentinel acute pancreatitis event (SAPE) hypothesis that comes speculative as to what determines the progression of
defines pancreatitis as a disease spectrum [1]. Even though RAP to CP. A recent study from the Dutch group involving
several clinical and bench studies have provided insights into 669 patients who survived the first episode of AP defined
the pathophysiology of the disease [2–5], there is still no mo- independent risk factors for the development of CP after an
dality to accurately predict the progression of RAP to CP. This index and recurrent AP [8]. RAP conferred an odds of 2.90
gap in understanding has likely, at least in part, precluded (95% CI 2.07 to 4.05) per episode for progression to CP.
development of any specific interventions that could prevent Among patients who had RAP as a risk factor, the other inde-
progression of RAP to CP or reverse the changes of CP. pendent risk factors for progression to CP were alcohol as the
In the current issue, Kalaria and colleagues have reported etiology (OR 4.85 [95% CI 2.04 to 11.52]) and development
their observations on the progression of RAP to CP in a ter- of necrotizing pancreatitis (OR 8.78 [95% CI 4.09 to 18.86]).
tiary care private hospital in western India [6]. They observed On the other hand, among patients who did not have RAP, the
the development of features of CP during a median period of independent risk factors were alcohol (OR 4.22 [95% CI 1.83
32 months in five out of 72 patients who had a single episode to 9.73]; p = 0.001) and idiopathic etiology (OR 3.98 [95% CI
of AP. 27.8% had RAP of which 13 (48.1%) developed fea- 1.64 to 9.65]; p = 0.002), current smoker (OR 2.90 [95% CI
tures of chronicity after a median of 47 months from the index 1.42 to 5.93]; p = 0.004), and necrotizing pancreatitis (OR
or sentinel episode. Chronicity was observed with a higher 6.65 [95% CI 3.40 to 13.01]; p < 0.001).
frequency among patients with alcoholic and idiopathic sub- It is now clearly established that the pathological hallmark
types. In a meta-analysis by Sankaran et al. in 2015 [7], the of CP is progressive fibrosis that is mediated by the activated
crude prevalence of RAP based on 11 studies (n = 8017) was pancreatic stellate cells (PSCs). PSC activation could be trig-
estimated to be 22% (95% CI 18% to 26%). However, on gered by several mediators including alcohol, smoking, and
analysis of the prospective studies only (nine studies, n = inflammatory cytokines such as interleukins, TGF-β, TNF-α,
1869), the pooled prevalence of RAP turned out to be 20% and PDGF, to name a few [9]. It was also shown in an exper-
(95% CI 15% to 25%). Five studies (n = 6826) in this meta- imental setting that application of pressure on PSCs could
analysis reported the subsequent diagnosis of CP after RAP, result in the generation of oxidative stress, which is known
which was reported to be 36% (95% CI 20% to 53%). On the to result in inflammation [10]. This observation could have an
other hand, 10% of patients who had a single episode of AP implication in patients with CP, in whom ductal and interstitial
subsequently developed CP. Unpublished data from an hypertension due to pancreatic ductal obstruction could result
in PSC activation. Interestingly, it has been shown in experi-
mental models of AP using L-arginine that there could be PSC
* Rupjyoti Talukdar activation and early fibrosis even after the first episode of AP
[11]. In our recent studies using human pancreatic acini, we
1 could show that PSC activation could occur even after bile
Pancreas Research Group, Asian Healthcare Foundation/Wellcome
DBT Labs, Asian Institute of Gastroenterology, 6-3-661 Somajiguda, acid-mediated injury [4]. However, clinical acute biliary
Hyderabad 500 082, India pancreatitis does not progress to CP. This implies that for
https://doi.org/10.1007/s12664-018-0839-8
EDITORIAL
Progression of recurrent acute to chronic pancreatitis: More questions
than answers!
Rupjyoti Talukdar 1
Published online: 19 March 2018
# Indian Society of Gastroenterology 2018
Acute pancreatitis (AP) continues to pose a substantial chal- ongoing study from our institute also reveals that 10% of
lenge to clinicians and researchers. It has been proposed that patients with a single episode of AP and 28% with RAP even-
an index episode of AP could progress to recurrent AP (RAP) tually developed CP.
and may finally culminate into chronic pancreatitis (CP). This Since only a proportion of RAP progresses to CP, it be-
is the sentinel acute pancreatitis event (SAPE) hypothesis that comes speculative as to what determines the progression of
defines pancreatitis as a disease spectrum [1]. Even though RAP to CP. A recent study from the Dutch group involving
several clinical and bench studies have provided insights into 669 patients who survived the first episode of AP defined
the pathophysiology of the disease [2–5], there is still no mo- independent risk factors for the development of CP after an
dality to accurately predict the progression of RAP to CP. This index and recurrent AP [8]. RAP conferred an odds of 2.90
gap in understanding has likely, at least in part, precluded (95% CI 2.07 to 4.05) per episode for progression to CP.
development of any specific interventions that could prevent Among patients who had RAP as a risk factor, the other inde-
progression of RAP to CP or reverse the changes of CP. pendent risk factors for progression to CP were alcohol as the
In the current issue, Kalaria and colleagues have reported etiology (OR 4.85 [95% CI 2.04 to 11.52]) and development
their observations on the progression of RAP to CP in a ter- of necrotizing pancreatitis (OR 8.78 [95% CI 4.09 to 18.86]).
tiary care private hospital in western India [6]. They observed On the other hand, among patients who did not have RAP, the
the development of features of CP during a median period of independent risk factors were alcohol (OR 4.22 [95% CI 1.83
32 months in five out of 72 patients who had a single episode to 9.73]; p = 0.001) and idiopathic etiology (OR 3.98 [95% CI
of AP. 27.8% had RAP of which 13 (48.1%) developed fea- 1.64 to 9.65]; p = 0.002), current smoker (OR 2.90 [95% CI
tures of chronicity after a median of 47 months from the index 1.42 to 5.93]; p = 0.004), and necrotizing pancreatitis (OR
or sentinel episode. Chronicity was observed with a higher 6.65 [95% CI 3.40 to 13.01]; p < 0.001).
frequency among patients with alcoholic and idiopathic sub- It is now clearly established that the pathological hallmark
types. In a meta-analysis by Sankaran et al. in 2015 [7], the of CP is progressive fibrosis that is mediated by the activated
crude prevalence of RAP based on 11 studies (n = 8017) was pancreatic stellate cells (PSCs). PSC activation could be trig-
estimated to be 22% (95% CI 18% to 26%). However, on gered by several mediators including alcohol, smoking, and
analysis of the prospective studies only (nine studies, n = inflammatory cytokines such as interleukins, TGF-β, TNF-α,
1869), the pooled prevalence of RAP turned out to be 20% and PDGF, to name a few [9]. It was also shown in an exper-
(95% CI 15% to 25%). Five studies (n = 6826) in this meta- imental setting that application of pressure on PSCs could
analysis reported the subsequent diagnosis of CP after RAP, result in the generation of oxidative stress, which is known
which was reported to be 36% (95% CI 20% to 53%). On the to result in inflammation [10]. This observation could have an
other hand, 10% of patients who had a single episode of AP implication in patients with CP, in whom ductal and interstitial
subsequently developed CP. Unpublished data from an hypertension due to pancreatic ductal obstruction could result
in PSC activation. Interestingly, it has been shown in experi-
mental models of AP using L-arginine that there could be PSC
* Rupjyoti Talukdar activation and early fibrosis even after the first episode of AP
[11]. In our recent studies using human pancreatic acini, we
1 could show that PSC activation could occur even after bile
Pancreas Research Group, Asian Healthcare Foundation/Wellcome
DBT Labs, Asian Institute of Gastroenterology, 6-3-661 Somajiguda, acid-mediated injury [4]. However, clinical acute biliary
Hyderabad 500 082, India pancreatitis does not progress to CP. This implies that for
