Clinical Journal of Gastroenterology

https://doi.org/10.1007/s12328-018-0881-1

CLINICAL REVIEW

Hypertriglyceridemia-induced pancreatitis: updated review of current

treatment and preventive strategies
Prashanth Rawla1   · Tagore Sunkara2 · Krishna Chaitanya Thandra3 · Vinaya Gaduputi4

Received: 10 May 2018 / Accepted: 14 June 2018

© Japanese Society of Gastroenterology 2018

Abstract
Hypertriglyceridemia (HTG) is an uncommon but well-established cause of acute pancreatitis (AP) comprising up to 7% of
the cases. The clinical course of HTG-induced pancreatitis (HTGP) is highly similar to that of AP of other etiologies with
HTG being the only distinguishing clinical feature. However, HTGP is often correlated with higher severity and elevated
complication rate. At present, no approved treatment guideline for the management of HTGP is available, although differ-
ent treatment modalities such as insulin, heparin, fibric acids, and omega 3 fatty acids have been successfully implemented
to reduce serum triglycerides (TG). Plasmapheresis has also been used to counteract elevated TG levels in HTGP patients.
However, it has been associated with complications. Following the management of acute phase, lifestyle modifications
including dietary adjustments and drug therapy are essential in the long-term management of HTGP and the prevention of
its relapse. Results from studies of small patient groups describing treatment and prevention of HTGP are not sufficient to
draw solid conclusions resulting in no treatment algorithm being available for effective management of HTGP. Therefore,
prospective randomized, active-controlled clinical studies are required to find a better treatment regimen for the management
of HTGP. Until date, one randomized clinical trial has been performed to compare clinical outcomes of different treatment
approaches for HTGP. However, further studies are required to outline a generalized and efficient treatment regimen for the
management of HTGP.

Keywords  Hypertriglyceridemia · Acute pancreatitis · Insulin · Heparin · Plasmapheresis · Recurrent pancreatitis

Introduction a local inflammation triggered by the activation of pancreatic

Acute pancreatitis (AP) secondary to HTG is an inflamma-
tory pancreatic disease presenting in patients with disorders
of lipid metabolism and is highly related to the subsequent
development of cardiovascular comorbidities [1, 2]. AP is
associated with several potential etiologies, most commonly
due to alcohol consumption and gallstones [3–5]. Starting as
* Prashanth Rawla
rawlap@gmail.com
1
Department of Internal Medicine/Hospitalist, SOVAH
Health, 320 Hospital Dr, Martinsville, VA 24115, USA
2
Division of Gastroenterology and Hepatology, The Brooklyn
Hospital Center, Clinical Affiliate of the Mount Sinai
Hospital, New York, NY 11201, USA
3
Department of Critical Care Medicine, Memorial Sloan
Kettering Cancer Center, New York, NY, USA
4
Division of Gastroenterology, SBH Health System, Bronx,
NY 19457, USA
proteolytic enzymes within the acinar tissue, it may progress
to systemic inflammation [6, 7]. Severe AP leading to organ
dysfunction is life-threatening and is one of the most com-
mon causes of morbidity and mortality in the world, with a
prevalence rate of 40 cases per 100,000 adults per year in the
United States (US) [3]. Hypertriglyceridemia (HTG) is an
uncommon, but well-established cause of AP in up to 7% of
the cases [8, 9]. The pathophysiological mechanism of HTG-
induced pancreatitis (HTGP) is presumed to be based on the
hydrolysis of triglycerides (TGs) by pancreatic lipase result-
ing in the release of damage-inducing free fatty acids. The
prevalence of AP development among dyslipidemia patients
is approximately 5% and 10–20% of patients with serum TG
levels higher than 1000 and 2000 mg/dl, respectively.
Although the clinical course of HTGP is often similar
to other forms of AP with the only distinguishing clinical
presentation observed initially being HTG [10, 11], the
complication rate observed is significantly higher in patients
with HTGP than in patients with other causes of AP [11,

13
Vol.:(0123456789)

12]. Moreover, morbidity (renal failure, shock, and infec-
tions) and mortality are reported to be significantly higher
in patients with HTGP than in AP patients of other patholo-
gies [10]. The initial treatment plan which includes nil-per-
os (NPO) and aggressive intravenous hydration for patients
with HTGP is similar to that of other causes of AP. Based
on the severity of HTG, the appropriate treatment regimen
is selected for further treatment [10, 11, 13].
Currently, no approved treatment guideline for the man-
agement of HTGP is available, although different treatment
modalities have been used to reduce serum TG levels. The
purpose of this review is to assess current treatment options
for management of HTGP and to identify available strategies
to prevent its relapse. A brief summary of the management
of HTGP is shown in Fig. 1.
Management strategies
Initial management
of hypertriglyceridemia‑induced pancreatitis
Targeting acute phase of AP is the key to successful manage-
ment of HTGP. It has been reported that almost 50% of the
mortality occurs in the acute phase of AP, which is defined
as the first 14 days from the onset. The possible cause of AP-
induced mortality includes systemic inflammatory syndrome
and failure of multiple organs [13]. Therefore, effective treat-
ment with rapid onset of action plays an important role in
Fig. 1  Brief summary of the management of HTGP
13
Clinical Journal of Gastroenterology
the initial management of HTGP to prevent morbidity and
mortality. Initial management of HTGP is similar to that
applied to treat AP of other etiologies, which includes bowel
rest with no oral intake, aggressive intravenous (IV) hydra-
tion, and symptomatic care including pain management [10,
13, 14]. Aggressive IV hydration, defined as 250–500 ml
per hour of isotonic crystalloid solution, preferably with
lactated Ringer’s solution should be given to all patients for
the first 24–48 h, unless there are cardiovascular and/or renal
comorbidities [15]. Bowel rest with no oral intake reduces
the excretion of pancreatic juices which is an integral part
of the initial management of a patient with HTGP. Enteral
nutrition also plays an important role by offering nutritional
support serving to reserve the intestine function and pro-
tect against the systemic inflammatory response syndrome,
which is the most frequent cause of increased incidences of
morbidity and mortality among patients with HTGP [10,
13, 14, 16].
Pain in the upper abdomen radiating to the back is the
most common symptom leading to the diagnosis of AP, and
thus, adequate analgesia is essential for the initial manage-
ment of HTGP. Meperidine has emerged as one of the better
alternatives in the management of pain among patients with
HTGP. However, its safety profile altered its prescribing
practices [13].
Following the initial management of HTGP, appropri-
ate measures to decrease serum TG levels are necessary
to abate the risk of relapse. Furthermore, maintaining TG
levels below 500 mg/dl has been shown to expedite clinical
Clinical Journal of Gastroenterology
improvement [17, 18]. Routine laboratory investigations
including thyroid stimulating hormone levels should be
performed to rule out the secondary causes of HTGP. In
addition, if familial hyperlipidemia is suspected, specific
laboratory tests can be carried out to identify the deficiency
of lipoprotein lipase (LPL) or Apo C-II [13, 14].
At present, there is no established treatment guideline
for the management of HTGP, although different treatment
modalities such as insulin, heparin, apheresis/plasmapher-
esis, anti-hyperlipidemic drugs including fibric acids, and
omega 3 fatty acids have been successfully implemented
to reduce serum TG levels in HTG patients [14, 19, 20].
Insulin, heparin, and apheresis/plasmapheresis treatments
to reduce elevated TG levels have been evaluated in several
case reports [11, 17, 21–24] and are further discussed in
this review.
The role of insulin administration in acute
hypertriglyceridemia‑induced pancreatitis
LPL is an enzyme expressed in capillary endothelial cells of
muscles and adipose tissues. It has a major role in the regula-
tion of fat metabolism as it hydrolyzes TG to glycerol and
fatty acids thereby catalyzing the breakdown of chylomicron
[25, 26]. Therefore, LPL is crucial for lowering serum TG
levels and enhancing its activity can be effective in reducing
elevated TG levels in HTG patients.
One of the modalities successfully used to reduce serum
TG levels in HTG patients is insulin. By stimulating LPL
activity, insulin effectively reduces TG levels and increases
the degradation of chylomicron. Insulin can be administered
subcutaneously or intravenously as a continuous infusion. It
has been reported that the IV route of administration is more
convenient compared to subcutaneous route of administra-
tion as it is easy to titrate the dose of insulin based on the
pharmacokinetic parameters. Intravenous insulin (0.1–0.4
unit/kg/h) as a continuous infusion was found effective in
patients with severe HTGP with and without type 2 diabetes
mellitus [14, 16]. Among non-T2DM patients, levels of TG
were reduced to less than 1000 mg/dl within 72 h of insulin
administration [17, 27]. Mikhail et al. reported that IV insu-
lin (3–9 units/h for 4 days) has decreased serum TG levels
from 7700 to 246 mg/dl in one patient without affecting the
normal concentration of blood glucose. In the same study, it
was observed in a second patient that serum TG levels were
down from 10,500 to 656 mg/dl after 4 days of treatment
using SC insulin administered every 4 h [28].
The efficacy of insulin administration to reduce TG lev-
els has been demonstrated in numerous case reports [17,
21, 22]. Thuzar et al. have described different treatment
approaches of patients admitted with severe HTG using IV
insulin, IV insulin with fasting and subcutaneous (SC) insu-
lin [21]. Treatment with IV insulin alone was found to lower
serum TG levels by 40% in 24 h. Combining insulin IV with
fasting resulted in substantial reduction of 87%, whereas SC
insulin resulted in a 23% reduction of serum TG levels in
24 h [21]. It is important to note that the number of patients
in the described case report was limited (5, 4, and 1, respec-
tively), and therefore, more data would be needed to make
substantial conclusions.
A similar treatment comparison was performed by Afari
et al., analyzing IV insulin, IV insulin with plasmapheresis
and SC insulin [22]. In line with the previous observations,
IV insulin has shown high efficacy as an 85% drop in TG
levels was observed upon discharge. A 92.6% TG reduction
was observed in patients treated with insulin IV in combi-
nation with plasmapheresis. However, a high complication
rate was reported in the latter patient group. Two of the three
patients treated with IV insulin in combination with plas-
mapheresis had complications including respiratory failure
and acute kidney disease. SC insulin was also shown to be
effective, resulting in an 85% TG reduction [22].
Apart from being effective as monotherapy, insulin has
demonstrated synergistic efficacy in the management of
HTGP [14]. Overall, insulin treatment is found to be effi-
cient and safe regimen in the treatment of HTGP based on
available case reports.
The role of heparin administration in acute
hypertriglyceridemia‑induced pancreatitis
Another treatment modality used to reduce serum TG levels
is heparin. The main pharmacological use of heparin is anti-
coagulation [29]. However, the role of heparin in the activa-
tion of LPL is also well-known pharmacological action [30].
Specifically, heparin stimulates the release of endothelial
LPL into circulation [31] which in-turn decreases in serum
TG level. An intravenous bolus dose of heparin has a signifi-
cantly greater intrinsic affinity for LPL, leading to decreased
levels of serum TG [32]. The result of several case reports
has suggested that the use of bolus dose (18 units/kg dosed
every 4–6 h) of intravenous heparin is more effective than
heparin administered as an IV infusion [30].
Despite heparin successfully reducing serum TG levels,
there are opposing views on the efficacy of heparin in HTG
treatment. Lack of efficacy of heparin in reducing TG levels
has been noted after repeated administration of heparin due
to unavailability of adequate LPL to hydrolyze chylomi-
crons, resulting in the inability of heparin to remove TGs
from plasma [30]. This is likely to be caused by hepatic
degradation of LPL, resulting in decreased LPL levels in
plasma [33]. This is further supported by studies showing
heparin depleting LPL and even causing gestational HTG
in one of the cases [34]. Altogether, this makes heparin a
questionable choice as monotherapy.
13

The synergistic effect of the combination of heparin and
insulin has been noted in several case studies, and the com-
bination of heparin and insulin may be used as first-line
therapy for severe HTGP [32]. This treatment approach has
been reported by Berger et al., who have shown that the
combination of heparin and insulin can be used effectively
to treat severe HTGP [23]. Henzen et al. also showed suc-
cessful treatment of HTGP in five patients who were treated
with a combination of heparin and insulin for 3 days [35]
which resulted in decreased serum TG levels from 3822.2 to
888.8 mg/dl. In a small group of patients (n = 4), the mean
serum TG levels were reduced from 3500 to 849.7  mg/
dl within 72 h after treatment. Consistently, in all treated
patients, rapid improvement in clinical symptoms of AP has
been observed [32, 35]. A similar trend of successful treat-
ment with a combination of insulin and heparin was seen in
two cases with 50% reduction in TG levels within 24 h after
treatment with insulin and heparin IV infusion therapy [36].
Hence, augmenting LPL activity with the combination of
heparin and insulin would help in combating HTG rapidly in
patients with severe AP. The literature review results suggest
that combination of heparin and insulin can be used as a safe
and effective treatment modality in patients who were placed
on bowel rest and aggressive intravenous hydration, in the
management of HTGP. The efficacy of insulin and heparin
combination therapy was not yet evaluated in randomized,
active control, parallel clinical studies with adequate sample
size.
The role of plasma exchange
(apheresis/plasmapheresis) in acute
hypertriglyceridemia‑induced pancreatitis
It is known that TG themselves are not harmful. However,
they serve as a source of unsaturated fatty acids (UFA) in the
presence of LPL. Increased levels of TG resulting in the high
production of UFA from pancreatic LPL are responsible for
developing a severe form of AP [37]. Currently, the initial
therapy for most of the HTGP patients includes bowel rest
with no oral intake, IV fluids/hydration, and symptomatic
care including pain management together with modalities
to reduce TG levels.
However, this standard care of treatments may be insuf-
ficient among patients with severe acute HTGP [38]. In such
setting, the primary goal of treatment is to reduce excess
TG levels rapidly. It has been reported that the aphaeretic
treatment with rapid onset of action could be a viable option
for reducing elevated TG levels [39]. A series of recent case
studies showed that a significant improvement in clinical
symptoms was found after treatment with therapeutic plasma
exchange (TPE) in patients with severe HTGP. Based on the
results, it has been suggested that the TPE is the better treat-
ment alternative in patients with severe HTG(> 2000 mg/
13
Clinical Journal of Gastroenterology
dl) and it was also found effective in the treatment of the
severe form of HTGP according to the Revised Atlanta Clas-
sification [38]. It has been reported that TPE offers quicker
recovery not only because of its ability to remove TG levels
rapidly but also due to its significant effect on the inflam-
matory mediators such as Interleukin-1 and Tumor Necrosis
Factor-α [38].
Several lines of clinical evidence based on case studies
suggested that TPE is a viable option in patients with AP
induced by HTG. Moreover, TPE has an established role
in the prevention of HTGP [40, 41]. Ewald N et al. have
reported that single session of plasmapheresis could reduce
TG levels by up to 70% and provide a significant improve-
ment in clinical symptoms. In addition, plasmapheresis was
shown to offer significant clinical benefits concerning mor-
bidity and mortality [39]. Yeh et al. reported that plasma-
pheresis significantly reduced TG levels by up to 83% after
two sessions [14, 40]. Syed et al. reported that the HTGP
patients treated with a single session of plasmapheresis had
a mean reduction in TG levels of 89% [14, 24]. The aver-
age TG removal rates in patients with severe HTG after
treatment with plasmapheresis and TPE were 58 and 64%,
respectively. Several studies have shown TPE to induce a
substantial reduction in TG levels within 2 h of administra-
tion [40, 42]. Lennertz et al. reported that the TPE rapidly
decreased the levels of TG and cholesterol in five patients
with HTGP [43]. Piolot et al. suggested that the routine use
of TPE successfully prevented relapse attacks of HTGP in
two patients with severe HTGP with relapse AP [44]. How-
ever, few safety concerns have also been reported regarding
the use of TPE which includes allergic reaction and infusion-
related infection. Anaphylactic shock was also reported in
one patient treated with plasmapheresis.
Interestingly, recent studies have shown that plasma-
pheresis does not lead to improved outcome compared to
other treatment approaches. He et al. demonstrated in a ran-
domized trial with 66 HTGP patients that although high-
volume hemofiltration (HVHF) has enabled to reduce TG
levels in a matter of 9 h rapidly, the overall clinical outcome
was comparable to that of the patient group treated with
heparin and insulin [45]. A retrospective study by Miyamoto
et al. comparing the treatment of 10 HTGP patients with
plasmapheresis to the outcome of 20 HTGP patients receiv-
ing a different treatment has also concluded no superiority
in the clinical outcome of the first group [46].
Hypertriglyceridemia pancreatitis in pregnancy:
treatment options
In pregnant women, AP is uncommon with the preva-
lence rate of 1 case per 1000–12,000 pregnancies and has
been associated with an increased frequency of an abnor-
mal maternal outcome [47–49]. The levels of plasma
Clinical Journal of Gastroenterology
cholesterol and serum TG in pregnant women are usually
higher (mostly in the third trimester) as compared to the
non-pregnant women due to the physiological alteration
that occurs following changes in sex hormones. At pre-
sent, no approved treatment guideline for the manage-
ment of HTGP is available for pregnant patients. The key
goal of the initial treatment among pregnant women is to
reduce the elevated serum TG levels. Initial management
of HTGP is similar to other causes of AP, which includes
bowel rest with no oral intake and IV fluids/hydration
for the acute phase of AP. Diet with low fat and rich in
omega-3 fatty acids is recommended to decrease elevated
serum TG levels. However, its impact on the acute phase
of AP is unclear [50, 51]. Treatment with insulin and hepa-
rin was also found effective in reducing serum TG levels
by activating LPL. Furthermore, there are different modal-
ities of treatment for HTG which include niacin, fibric
acid derivatives, and statins. However, it takes longer to
reach the lipid-lowering goal with these agents. In addi-
tion, niacin, fibric acid derivatives, statins, and heparin are
the pregnancy class/category C drugs, so these agents to
be administered only in the case of no effective alternative
treatment being available and after considering risk–ben-
efit ratio (benefits must outweigh the associated risk) [35,
50].
Among the available treatment options, omega-3 fatty
acids are one of the safe treatment options for pregnant
women with HTGP to decrease serum TG levels [52].
Therapeutic apheresis can be considered as the first-line
treatment option for pregnant women with HTGP. Basar
et al. reported that apheresis effectively reduced TG lev-
els. However, the treatment was associated with risks of
life-threatening conditions [53]. Similarly, Hang et  al.
reported plasmapheresis/apheresis preventing progres-
sion of HTGP and its relapse, but being associated with
increased risk of acute coronary events [54]. Additional
studies describe therapeutic plasma exchange (apheresis/
plasmapheresis) emerging as one of the important treat-
ment options in the acute phase of HTGP inducing a rapid
decrease in TG levels and playing an important role in
preventing severe episodes of HTGP- or HTG-induced
complication in pregnant women [55, 56]. A significant
fall in incidence of systemic inflammatory response syn-
drome (from 100 to 28.6%) and serum TG levels (from
20.36 to 5.23 mmol/l) was observed in patients treated
with plasmapheresis (P < 0.05 for each). In addition,
the patients who were treated with plasmapheresis had
a shorter hospital stay (17.3 ± 6.7 days) as compared to
the patients treated with non-plasmapheresis (37.0 ± 20.8
days). It has been reported that TPE was found efficient
and safe in pregnant women with HTGP associated with
systemic inflammatory response syndrome or multiple
organ dysfunction syndromes [57]. Overall, therapeutic
plasma exchange (apheresis/ plasmapheresis) is an effec-
tive and safe treatment option for pregnant women with
HTG-induced AP.
Prevention of hypertriglyceridemia‑induced
pancreatitis
To prevent relapse of HTGP, a multi-faceted approach is
essential for the effective management of HTGP. Most
importantly, lifestyle modifications including a diet with low
saturated fat and rich in omega-3 fatty acid, weight loss,
and avoiding alcohol together with controlling of second-
ary triggering factors such as diabetes and limit intake of
carbohydrates are the key part of successful management
of HTGP [19]. A meta-analysis executed by Kris-Etherson
et al. found a strong relationship between weight loss and
reduction in serum TG levels [14, 58]. Apart from the lipid-
lowering treatment, the patient should follow dietary coun-
seling for a better choice of food to reduce TG levels. In
addition, it is recommended to consult with an endocrinolo-
gist for effective management of blood lipid and glucose
levels. To prevent recurrent HTGP, the levels of TG should
be maintained below 500 mg/dl [19, 59]. Fibrates are one
of the most common treatment regimens for the patients of
dyslipidemia inducing the decrease in TG levels by stimu-
lating the release of LPL. HMG-CoA reductase inhibitors
such as statins should not be used as monotherapy for long-
term management of HTGP due to their weak TG-lowering
effect. Nevertheless, these inhibitors can be combined with
fibrates to have some synergistic benefit in patients with
severe HTGP not responding to fibrates as monotherapy [14,
19, 60]. Overall, fibrates are well tolerable. However, caution
should be taken when prescribing a combination of fibrates
and statin due to the risk of rhabdomyolysis or myopathy.
The risk of rhabdomyolysis or myopathy is attributed mainly
to an older class of fibrate derivative (gemfibrozil) than the
latest class of fibrates (fenofibric acid) [14, 19].
Anti-hyperlipidemic drugs such as niacin (vitamin B)
have a weak TG-lowering effect and act by reducing hepatic
secretion of VLDL and TG. Niacin also increases the level
of HDL and lowers the LDL levels. The use of niacin is
limited due to its associated side effects such as flushing,
gastrointestinal disturbance, and liver toxicity. Efficacy of
omega-3 fatty acids has also been established in the pro-
spective double-blinded clinical trial, suggesting a minimum
effective dose of omega-3 fatty acids of approximately 1 g
daily and showing a dose of 3–4 g daily to reduce the TG
levels by 30–50% in patients with HTG [14, 19, 20].
A series of case studies evaluated the effect of apheresis/
plasmapheresis/TPE in patients with recurrent HTGP. The
result of these case studies showed that apheresis/plasma-
pheresis/TPE is found efficient and safe in the prevention of
13

recurrent HTGP by decreasing the TG levels to 500 mg/dl.
Due to its rapid onset of action, it is a viable option in the
management of severe HTGP and its role in the prevention
of HTGP has also been established. To prevent relapse of
HTGP, effective long-term treatment is required to keep TG
levels below 500 mg/dl at all the times. Data on the long-
term efficacy of apheresis/plasmapheresis/TPE needs to be
gathered to draw a definitive conclusion whether long-term
treatment with apheresis/plasmapheresis/TPE will be able
to reduce the risk of recurrent episodes.
Conclusion
AP is a life-threatening inflammatory disorder of the pan-
creas which can be reversed. Although HTGP is the third
most common form of pancreatitis after alcohol and gall
stones, overall this disorder is quite rare. This results in the
available information being sparse and the limited number
of patients in the studies not allowing for generalization.
Due to the absence of specific treatment guidelines for HTG
AP, the HTGP patients are treated similarly to AP patients
of other etiologies.
Reducing serum TG levels using modalities like insulin
and heparin has proven to be effective; however, in the case
of heparin, care should be taken due to the potential oppos-
ing effect caused by depletion of LPL. Although plasma-
pheresis emerged as one of the effective treatment options
which rapidly reduces serum TG levels, it has been asso-
ciated with significant side effects, and its efficacy in the
management of HTGP has not been confirmed. Moreover,
recent studies have demonstrated that the rapid reduction of
TG levels does not necessarily give additional benefits to the
overall outcome of the treatment. This taken together with
its high cost makes plasmapheresis a less desirable approach
to HTGP treatment.
Finally, to prevent relapse of HTGP, a multi-faceted
approach is essential for effective management of HTGP.
Most importantly, lifestyle modifications including a diet
with low saturated fat and rich in omega-3 fatty acid, weight
loss, and avoiding alcohol are essential as a primary strategy.
Next, control of secondary triggering factors such as diabe-
tes and limiting the intake of carbohydrates are the key part
of successful management of HTGP.
As HTGP in its entity is a rare disorder, the available
patient data are limited. Retrospective studies analyzing
clinical outcomes of HTGP patients treated with different
modalities are of great value to increase our understanding
of the optimal treatment strategy for HTGP. The first rand-
omized clinical trial performed in the field has also provided
significant insights into the differences between different
HTGP treatments and progressing further in this direction
13
Clinical Journal of Gastroenterology
would be beneficial to propose a generalized and effective
approach for HTGP treatment in the future.
Author Contributions  Conception and design: PR, M.D; TS, M.D.
Analysis and interpretation: PR, M.D; TS, M.D; KCT, M.D, VG, M.D.
Drafting of the article: PR, M.D; TS, M.D; KCT, M.D, VG, M.D. Criti-
cal revision of the article: PR, M.D; TS, M.D; KCT, M.D, VG, M.D.
Final approval of the article: PR, M.D; TS, M.D; KCT, M.D, VG, M.D.
Funding  No funding to disclose.
Compliance with ethical standards 
Conflict of interest  Prashanth Rawla, Tagore Sunkara, Krishna Chait-
anya Thandra, and Vinaya Gaduputi declare that they have no conflict
of interest.
Human/animal rights  This study does not include any data about
human subjects.
Informed consent  This study does not involve human subjects and does
not apply to giving Informed Consent.
References
1. Lankisch PG, Apte M, Banks PA. Acute pancreatitis. Lancet.
2015;386:85–96.
2. Xiao AY, Tan ML, Wu LM, et al. Global incidence and mortality
of pancreatic diseases: a systematic review, meta-analysis, and
meta-regression of population-based cohort studies. Lancet Gas-
troenterol Hepatol. 2016;1:45–55.
3. Carr RA, Rejowski BJ, Cote GA, et al. Systematic review of
hypertriglyceridemia-induced acute pancreatitis: a more virulent
etiology? Pancreatol Off J Int Assoc Pancreatol. 2016;16:469–76.
4. Yadav D, Lowenfels AB. Trends in the epidemiology of the
first attack of acute pancreatitis: a systematic review. Pancreas.
2006;33:323–30.
5. Rawla P, Bandaru SS, Vellipuram AR. Review of infectious etiol-
ogy of acute pancreatitis. Gastroenterol Res. 2017;10:153–8.
6. Saluja AK, Donovan EA, Yamanaka K, et al. Cerulein-induced
in vitro activation of trypsinogen in rat pancreatic acini is medi-
ated by cathepsin B. Gastroenterology. 1997;113:304–10.
7. Naruse S. Molecular pathophysiology of pancreatitis. Int Med.
2003;42:288–9.
8. Kota SK, Kota SK, Jammula S, et  al. Hypertriglyceridemia-
induced recurrent acute pancreatitis: a case-based review. Indian
J Endocrinol Metab. 2012;16:141–3.
9. Searles GE, Ooi TC. Underrecognition of chylomicronemia as a
cause of acute pancreatitis. CMAJ. 1992;147:1806–8.
10. Ewald N. Hypertriglyceridemia-induced acute pancreatitis. Clin
Lipidol. 2013;8:587–94.
11. Adiamah A, Psaltis E, Crook M, et al. A systematic review of the
epidemiology, pathophysiology and current management of hyper-
lipidaemic pancreatitis. Clin Nutr. 2017. https:​ //doi.org/10.1016/j.
clnu.2017.09.028.
12. Anderson F, Thomson SR, Clarke DL, et al. Dyslipidaemic pan-
creatitis clinical assessment and analysis of disease severity and
outcomes. Pancreatol Off J Int Assoc Pancreatol. 2009;9:252–7.
13. Zarnescu NO, Barbu ST, Zarnescu Vasiliu EC, et al. Management
of acute pancreatitis in the early stage. Maedica. 2015;10:257–63.
14. Lebenson J, Oliver T. Hypertriglyceride induced acute pan-
creatitis. Prof. Luis Rodrigo (Ed.), ISBN: 978-953-307-984-4,
Clinical Journal of Gastroenterology
InTech, Available from: http://www.intec​hopen​.com/books​/acute​
-pancr​eatit​is/hyper​trigl​yceri​de-induc​ed-acute​-pancr​eatit​is. 2012.
Accessed 3 Apr 2018.
15. Tenner S, Baillie J, DeWitt J, et al. American College of Gastro-
enterology guideline: management of acute pancreatitis. Am J
Gastroenterol. 2013;108:1400–15 (1416).
16. Khan R, Jehangir W, Regeti K, et  al. Hypertriglyceridemia-
induced pancreatitis: choice of treatment. Gastroenterol Res.
2015;8:234–6.
17. Coskun A, Erkan N, Yakan S, et al. Treatment of hypertriglycer-
idemia-induced acute pancreatitis with insulin. Przeglad Gastro-
enterol. 2015;10:18–22.
18. Toskes PP. Hyperlipidemic pancreatitis. Gastroenterol Clin N Am.
1990;19:783–91.
19. Scherer J, Singh VP, Pitchumoni CS, et al. Issues in hypertri-
glyceridemic pancreatitis: an update. J Clin Gastroenterol.
2014;48:195–203.
20. Hooper L, Thompson RL, Harrison RA, et al. Risks and benefits
of omega 3 fats for mortality, cardiovascular disease, and cancer:
systematic review. BMJ. 2006;332:752–60.
21. Thuzar M, Shenoy VV, Malabu UH, et al. Extreme hypertriglyc-
eridemia managed with insulin. J Clin Lipidol. 2014;8:630–4.
22. Afari ME, Shafqat H, Shafi M, et  al. Hypertriglyceridemia-
induced pancreatitis: a decade of experience in a community-
based teaching hospital. Rhode Island Med J. 2015;98:40–3.
23. Berger Z, Quera R, Poniachik J, et al. Heparin and insulin treat-
ment of acute pancreatitis caused by hypertriglyceridemia. Expe-
rience of 5 cases]. Revista Medica de Chile. 2001;129:1373–8.
24. Syed H, Bilusic M, Rhondla C, et al. Plasmapheresis in the treat-
ment of hypertriglyceridemia-induced pancreatitis: a community
hospital’s experience. J Clin Apheresis. 2010;25:229–34.
25. Eckel RH. Lipoprotein lipase. A multifunctional enzyme
relevant to common metabolic diseases. New Engl J Med.
1989;320:1060–8.
26. Goldberg IJ. Lipoprotein lipase and lipolysis: central roles
in lipoprotein metabolism and atherogenesis. J Lipid Res.
1996;37:693–707.
27. Poonuru S, Pathak SR, Vats HS, et al. Rapid reduction of severely
elevated serum triglycerides with insulin infusion, gemfibrozil and
niacin. Clin Med Res. 2011;9:38–41.
28. Mikhail N, Trivedi K, Page C, et al. Treatment of severe hyper-
triglyceridemia in nondiabetic patients with insulin. Am J Emerg
Med. 2005;23:415–7.
29. Gray E, Hogwood J, Mulloy B. The anticoagulant and antithrom-
botic mechanisms of heparin. Handb Exp Pharmacol 2012:43–61.
30. Maccia M. Mechanism for Heparin’s ability to lower TGs in
hypertriglyceridemia. 2015. https​://www.ebmco​nsult​.com/artic​
les/hepari​ n-mechan​ ism-reduce​ -trigly​ cerid​ es-hypert​ rigly​ cerid​ emia​
-treat​ment. Accessed on 02 April 2018.
31. Korn ED. Clearing factor, a heparin-activated lipoprotein lipase.
I. Isolation and characterization of the enzyme from normal rat
heart. J Biol Chem. 1955;215:1–14.
32. Kuchay MS, Farooqui KJ, Bano T, et al. Heparin and insulin in
the management of hypertriglyceridemia-associated pancrea-
titis: case series and literature review. Arch Endocrinol Metab.
2017;61:198–201.
33. Nasstrom B, Olivecrona G, Olivecrona T, et al. Lipoprotein lipase
during continuous heparin infusion: tissue stores become partially
depleted. J Lab Clin Med. 2001;138:206–13.
34. Watts GF, Cameron J, Henderson A, et al. Lipoprotein lipase defi-
ciency due to long-term heparinization presenting as severe hyper-
triglyceridaemia in pregnancy. Postgrad Med J. 1991;67:1062–4.
35. Henzen C, Rock M, Schnieper C, et al. Heparin and insulin in
the treatment of acute hypertriglyceridemia-induced pancreatitis.
Schweizerische medizinische Wochenschrift. 1999;129:1242–8.
36. Jain D, Zimmerschied J. Heparin and insulin for hypertri-
glyceridemia-induced pancreatitis: case report. Sci World J.
2009;9:1230–2.
37. Click B, Ketchum AM, Turner R, et al. The role of apheresis
in hypertriglyceridemia-induced acute pancreatitis: a systematic
review. Pancreatol Off J Int Assoc Pancreatol. 2015;15:313–20.
38. Gavva C, Sarode R, Agrawal D, et  al. Therapeutic plasma
exchange for hypertriglyceridemia induced pancreatitis: a rapid
and practical approach. Transfus Apheresis Sci Off J World
Apheresis Assoc Off J Eur Soc Haemapheresis. 2016;54:99–102.
39. Ewald N, Kloer HU. Severe hypertriglyceridemia: an indication
for apheresis? Atherosclerosis Suppl. 2009;10:49–52.
40. Yeh JH, Chen JH, Chiu HC. Plasmapheresis for hyperlipidemic
pancreatitis. J Clin Apheresis. 2003;18:181–5.
41. Yeh JH, Lee MF, Chiu HC. Plasmapheresis for severe lipemia:
comparison of serum-lipid clearance rates for the plasma-
exchange and double-filtration variants. J Clin Apheresis.
2003;18:32–6.
42. Chait A, Brunzell JD. Chylomicronemia syndrome. Adv Int Med.
1992;37:249–73.
43. Lennertz A, Parhofer KG, Samtleben W, et al. Therapeutic plasma
exchange in patients with chylomicronemia syndrome complicated
by acute pancreatitis. Therap Apheresis Off J Int Soc Apheresis
Jpn Soc Apheresis. 1999;3:227–33.
44. Piolot A, Nadler F, Cavallero E, et al. Prevention of recurrent
acute pancreatitis in patients with severe hypertriglyceridemia:
value of regular plasmapheresis. Pancreas. 1996;13:96–9.
45. He WH, Yu M, Zhu Y, et al. Emergent triglyceride-lowering ther-
apy with early high-volume hemofiltration against low-molecular-
weight heparin combined with insulin in hypertriglyceridemic
pancreatitis: a prospective randomized controlled trial. J Clin
Gastroenterol. 2016;50:772–8.
46. Miyamoto K, Horibe M, Sanui M, et al. Plasmapheresis therapy
has no triglyceride-lowering effect in patients with hypertriglyc-
eridemic pancreatitis. Intensive Care Med. 2017;43:949–51.
47. Stimac D, Stimac T. Acute pancreatitis during pregnancy. Eur J
Gastroenterol Hepatol. 2011;23:839–44.
48. Papadakis EP, Sarigianni M, Mikhailidis DP, et al. Acute pancrea-
titis in pregnancy: an overview. Eur J Obstetr Gynecol Reproduct
Biol. 2011;159:261–6.
49. Altun D, Eren G, Cukurova Z, et al. An alternative treatment in
hypertriglyceridemia-induced acute pancreatitis in pregnancy:
plasmapheresis. J Anaesthesiol Clin Pharmacol. 2012;28:252–4.
50. Serpytis M, Karosas V, Tamosauskas R, et  al. Hypertri-
glyceridemia-induced acute pancreatitis in pregnancy. JOP.
2012;13:677–80.
51. Martin JM, Stapleton RD. Omega-3 fatty acids in critical illness.
Nutr Rev. 2010;68:531–41.
52. Greenberg JA, Bell SJ, Ausdal WV. Omega-3 Fatty Acid supple-
mentation during pregnancy. Rev Obstet Gynecol. 2008;1:162–9.
53. Basar R, Uzum AK, Canbaz B, et al. Therapeutic apheresis for
severe hypertriglyceridemia in pregnancy. Arch Gynecol Obstet.
2013;287:839–43.
54. Hang Y, Chen Y, Lu LX, et al. Acute hyperlipidemic pancreatitis
in a pregnant woman. World J Emerg Med. 2013;4:311–3.
55. Ewald N, Kloer HU. Treatment options for severe hypertriglyc-
eridemia (SHTG): the role of apheresis. Clin Res Cardiol Suppl.
2012;7:31–5.
56. Nasa P, Alexander G, Kulkarni A, et al. Early plasmapheresis in
patients with severe hypertriglyceridemia induced acute pancrea-
titis. Indian J Crit Care Med Peer Rev Off Publ Indian Soc Crit
Care Med. 2015;19:487–9.
57. Huang C, Liu J, Lu Y, et al. Clinical features and treatment of
hypertriglyceridemia-induced acute pancreatitis during preg-
nancy: a retrospective study. J Clin Apheresis. 2016;31:571–8.
13

58. Kris-Etherson PM, Pearson TA, Wan Y, et al. High-monounsatu-
rated fatty acid diets lower both plasma cholesterol and triacylg-
lycerol concentrations. Am J Clin Nutr. 1999;70:1009–15.
59. Christian JB, Arondekar B, Buysman EK, et al. Clinical and eco-
nomic benefits observed when follow-up triglyceride levels are
less than 500 mg/dL in patients with severe hypertriglyceridemia.
J Clin Lipidol. 2012;6:450–61.
13
Clinical Journal of Gastroenterology
60. Expert Panel on Detection E, and Treatment of High Blood Cho-
lesterol in Adults. Executive Summary of The Third Report of The
National Cholesterol Education Program (NCEP). Expert panel
on detection, evaluation, and treatment of high blood cholesterol
in adults (adult treatment panel III). JAMA 2001;285:2486–97.