Rapid progression to liver failure following pancreatoduodenectomy in an adolescent: A case report

Abstract

BACKGROUND

Pancreatoduodenectomy (PD) is a major surgical intervention that frequently leads to pancreatic exocrine insufficiency and subsequent malnutrition. A recognized but often indolent complication in adults is the development of malnutrition-associated steatohepatitis. While rare instances of progression to cirrhosis have been reported in adults, the trajectory of post-PD hepatic complications in pediatric and adolescent populations remains largely uncharacterized. This population’s unique physiological demands for growth and development may predispose them to more aggressive disease phenotypes.

CASE SUMMARY

We present the case of a 14-year-old male patient who underwent a pylorus-preserving PD in July 2019 for a benign solid-cystic lesion of the pancreatic head. The postoperative course was complicated by severe pancreatic exocrine insufficiency, manifesting as intractable steatorrhea and profound, progressive malnutrition, which was less effectively controlled possibly due to both insufficient enzyme replacement and poor adherence to pancreatic enzyme replacement therapy. Four years after surgery (June 2023), he developed hepatic steatosis that rapidly progressed to decompensated cirrhosis with portal hypertension. Despite aggressive nutritional rehabilitation and optimized pancreatic enzyme replacement therapy, his clinical condition continued to decline. He was readmitted in March 2025 with acute-on-chronic liver failure, culminating in multi-organ failure and death in April 2025, less than six years after his initial surgery. This case represents a rarely documented instance of fatal, rapidly progressive malnutrition-associated steatohepatitis leading to liver failure in an adolescent following PD.

CONCLUSION

Adolescent patients can progress to cirrhosis and liver failure post-pylorus-preserving PD, necessitating intensified dynamic monitoring of nutritional status and liver function.

Key Words: Adolescent; Pylorus-preserving pancreatoduodenectomy; Pancreatic exocrine insufficiency; Steatohepatitis; Cirrhosis; Acute-on-chronic liver failure; Case report

Core Tip: This report describes a 14-year-old male patient who developed cirrhosis and liver failure after pylorus-preserving pancreatoduodenectomy. Despite pancreatic enzyme replacement therapy, the patient experienced long-term refractory steatorrhea, severe malnutrition, and trace element deficiencies. Malnutrition-associated steatohepatitis and decompensated cirrhosis occurred 4 years postoperatively, followed by progression to liver failure and death from multi-organ dysfunction 2 years later. This case highlights that adolescent patients post-pylorus-preserving pancreatoduodenectomy, due to developmental growth demands, have specific and stringent requirements for pancreatic enzyme replacement and nutritional management. Inadequate management can lead to rapid, fatal progression to cirrhosis and liver failure.

INTRODUCTION

Non-alcoholic fatty liver disease, recently defined as metabolic dysfunction-associated fatty liver disease, is the most prevalent chronic liver disease globally[1]. Metabolic dysfunction-associated fatty liver disease is classically linked to insulin resistance and caloric excess, leading to hepatic triglyceride accumulation[2]. However, a distinct and increasingly recognized entity is malnutrition-associated steatotic liver disease, which arises from states of severe nutritional deficiency. This type of hepatic steatosis is frequently observed in the context of protein-energy malnutrition, inflammatory bowel disease, and, notably, after major gastrointestinal surgery, particularly pancreatic resection[2,3].

Pancreatoduodenectomy (PD) is the standard surgical approach for tumors of the pancreatic head and periampullary lesions. While effective in improving long-term survival, PD nearly always results in pancreatic exocrine insufficiency (PEI)[4]. The consequent fat malabsorption (steatorrhea) often leads to malnutrition and deficiencies in essential trace elements and vitamins. These metabolic alterations, in turn, can dysregulate hepatic lipid homeostasis and promote the development of hepatic steatosis[3]. There have been increasing reports of malnutrition-associated steatotic liver disease following PD, with a cumulative 5-year incidence reaching 30% in adults[3]. However, the clinical course in adults is typically benign and indolent, with only rare case reports describing severe or rapidly progressive disease[5]. Notably, to our knowledge, no cases of cirrhosis or liver failure have been documented in adolescents post-PD. Herein, we report a 14-year-old boy who, after pylorus-preserving PD (PPPD), developed severe PEI and malnutrition, leading to a rapid and relentless progression to steatohepatitis, decompensated cirrhosis, and ultimately fatal acute-on-chronic liver failure (ACLF). This case highlights the unique vulnerability of adolescents to this severe complication and underscores the urgent need for heightened vigilance and proactive management in this population.

CASE PRESENTATION

Chief complaints

A 14-year-old male patient was first admitted in March 2019 due to recurrent upper abdominal pain.

History of present illness

In March 2019, the patient presented to the Department of Hepatobiliary Surgery of a local general hospital with recurrent upper abdominal pain. Magnetic resonance imaging revealed pancreatic duct dilation and a solid-cystic lesion in the pancreatic head, suggestive of congenital pancreaticobiliary maljunction or intraductal papillary mucinous neoplasm. In July 2019, PPPD was performed. Postoperative pathology indicated chronic pancreatitis, ductal dilation, and periductal fibrosis with inflammatory cell infiltration. Following surgery, the patient developed persistent steatorrhea, progressive weight loss, and severe malnutrition. Although oral pancreatic enzyme replacement therapy (PERT) was administered, diarrhea was only partially alleviated. In June 2023, the patient was readmitted with bilateral lower limb pain and fever, accompanied by marked cachexia. Liver biopsy confirmed steatohepatitis with bridging fibrosis. Comprehensive supportive treatment, including albumin infusion, nutritional support, trace element supplementation, and gut microbiota modulation, was administered. Ascites resolved, and liver function showed transient improvement. In March 2025, the patient was readmitted with abdominal distension, oliguria, and progressively worsening jaundice. The chronological progression of the patient’s clinical course is summarized in the timeline shown in Figure 1.

Figure 1 Chronological progression of the patient’s clinical course is summarized in the timeline. PPPD: Pylorus-preserving pancreatoduodenectomy; NASH: Nonalcoholic steatohepatitis; CT: Computed tomography; MRI: Magnetic resonance imaging; IPMN: Intraductal papillary mucinous neoplasm.

History of past illness

The patient had no history of chronic liver disease, diabetes, hypertension, tuberculosis, or other infectious or metabolic diseases.

Personal and family history

The patient had no history of smoking or alcohol consumption. There was no family history of liver disease, metabolic syndrome, or other pancreatic/hepatic hereditary disorders.

Physical examination

Dynamic changes in the patient’s height, weight, and body mass index (BMI) from 2019 to 2025 are summarized in Table 1. He experienced a progressive deterioration in his nutritional status. Despite a normal pubertal growth spurt in height from 162 cm to 174 cm, his weight steadily declined from a preoperative 50 kg (BMI 19.1 kg/m²) to 42 kg (BMI 13.8 kg/m²) by June 2023. Upon admission in March 2025, the patient exhibited extreme emaciation (height 175 cm, weight 40.0 kg, BMI 13.1 kg/m²), pallor, but no scleral icterus, palmar erythema, or spider nevi. Abdominal examination revealed visible abdominal wall veins. The liver and spleen were not palpable. Edema was present in both lower limbs. Cardiopulmonary examinations were unremarkable.

Table 1 Dynamics of the patient’s clinical and laboratory parameters.

Item	March 27, 2019	June 30, 2019	June 15, 2023	March 6, 2025	Reference
Height (cm)	162	162	174	175	NA
Weight (kg)	50	37	41.8	40	NA
BMI (kg/m2)	19.1	14.1	13.8	13.1	18.5-24.0
ALT (U/L)	11.9	20.5	19.0	12	9-50
ALP (U/L)	261.9	151.1	72.0	96	45-125
TBIL (μmol/L)	13.1	7.1	37.3	85.4	5-21
ALB (g/L)	43.6	37.2	20.2	15.5	40-55
INR	NA	1.24	1.48	2.15	0.85-1.5
PTA (%)	NA	NA	51.4	32.9	70-150
CRP (mg/L)	78.09	3.20	23.98	4.91	0.068-8.2
Cr (μmol/L)	32.4	39.6	29	106	41-109
Ur (mmol/L)	3.8	3.2	0.6	10.8	2.8-7.2
AFP (ng/mL)	NA	1.60	2.9	5.2	< 9.0
WBC (109/L)	6.6	4.3	2.81	1.76	3.5-9.5
Hb (g/L)	94	109	71	22.0	130-175
PLT (109/L)	400	412	111	16	100-300
FPG (mmol/L)	4.8	10.9	3.64	6.31	3.9-6.1
TG (mmol/L)	0.56	0.76	0.59	0.42	< 1.7
TC (mmol/L)	2.25	2.71	1	0.62	< 5.2
HDL (mmol/L)	0.80	0.63	0.37	0.28	0.91-1.55
LDL (mmol/L)	1.23	1.45	0.51	0.32	< 3.4

BMI: Body mass index; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; TBIL: Total bilirubin; ALB: Albumin; INR: International normalized ratio; PTA: Prothrombin activity; CRP: C reactive protein; Cr: Creatinine; AFP: Alpha fetoprotein; WBC: White blood cell; Hb: Hemoglobin; PLT: Platelet; FPG: Fasting plasma glucose; TG: Triglyceride; TC: Total cholesterol; HDL: High-density lipoprotein; LDL: Low density lipoprotein; NA: Not applicable; Ur: Urea.

Laboratory examinations

Serial changes in liver function, renal function, coagulation profile, and other biochemical parameters from 2019 to 2025 are shown in Table 1. There was a progressive decline in albumin, an increase in bilirubin, and a gradual worsening of coagulation parameters. Blood cell counts showed a progressive decrease. Random blood glucose was transiently elevated postoperatively in June 2019 (10.9 mmol/L), but subsequent fasting plasma glucose measurements were normal until March 2025, when a mild elevation was noted (6.31 mmol/L). Trace element deficiencies were evident: Serum zinc was 4.1 μmol/L (normal 10.7-17.7 μmol/L), and copper was 5.25 μmol/L (normal 10.99-21.98 μmol/L) in June 2023. Tests for endocrine disorders, autoimmunity, copper metabolism (Wilson’s disease), and viral hepatitis markers were unremarkable. Kayser-Fleischer rings were absent. Due to facility unavailability, fecal elastase-1 (FE-1) testing was not performed.

Imaging examinations

Abdominal computed tomography (CT) and magnetic resonance imaging from 2019 to 2022 showed normal liver morphology without signs of fibrosis or cirrhosis. Imaging in June 2023 revealed diffuse hepatic steatosis, blunt liver edges, and irregular contours, suggestive of cirrhosis, along with portal hypertension (portal vein diameter 16 mm, splenic vein dilation, collateral circulation), splenomegaly, and moderate ascites (Figure 2). Liver stiffness measurement (FibroScan) showed a value of 17.7 kPa, and the controlled attenuation parameter was 246 dB/m. Percutaneous liver biopsy performed in June 2023 demonstrated disrupted lobular architecture, extensive diffuse hepatocellular steatosis, portal fibrous septa formation, and bile duct proliferation with mild-to-moderate inflammatory activity, consistent with a diagnosis of steatohepatitis with bridging fibrosis (Figure 3).

Figure 2 Serial abdominal imaging findings at different time points. A: Preoperative contrast-enhanced abdominal computed tomography (CT) showing dilatation of the main pancreatic duct (yellow arrow) and a swollen pancreas (blue arrow). The liver parenchyma demonstrates homogeneous attenuation without evidence of hepatic steatosis or cirrhosis; B: Early postoperative contrast-enhanced abdominal CT demonstrating the pancreatic remnant at the surgical margin (white arrow) and the residual pancreatic body and tail (blue arrow). The liver parenchyma remains homogeneous, with no radiological features suggestive of hepatic steatosis or cirrhosis; C: Contrast-enhanced abdominal CT at the 4-year postoperative follow-up. Marked atrophy of the residual pancreatic body and tail is observed (blue arrow). Multiple dilated and tortuous vessels around the splenic vein and gastric fundus are present (orange arrow), and the main portal vein is widened to 16 mm (black arrow). The liver shows an irregular contour, altered lobar proportions, heterogeneous perfusion, and intrahepatic fat deposition, accompanied by splenomegaly; D: Contrast-enhanced abdominal magnetic resonance imaging at the 4-year postoperative follow-up demonstrating the pancreatic remnant (white arrow) and severe atrophy of the residual pancreatic body and tail (blue arrow). Prominent dilated collateral vessels around the splenic vein and gastric fundus are again noted (orange arrow), with enlargement of the main portal vein (black arrow, 16 mm). The liver exhibits an irregular surface, distorted lobar architecture, heterogeneous enhancement, abnormal hepatic fat metabolism, and splenomegaly.

Figure 3 Histopathological examination of the liver biopsy specimen obtained at the 4-year postoperative follow-up (hematoxylin and eosin staining). The liver tissue shows diffuse macrovesicular steatosis of hepatocytes (yellow arrow), accompanied by inflammatory cell infiltration predominantly composed of lymphocytes (blue arrow). Marked fibrous tissue proliferation is observed within the lobules and portal areas (white arrow), resulting in blurring of the normal lobular architecture. In addition, increased proliferation of small bile ducts is noted within hepatocytes and portal tracts, indicating advanced chronic liver injury with fibrotic remodeling.

FINAL DIAGNOSIS

ACLF, post-PD status, PEI, severe malnutrition and trace element deficiency.

TREATMENT

Following PPPD in 2019, PERT was initiated with a compound digestive enzyme capsule containing pepsin (25 mg), papain (50 mg), diastase (15 mg), ursodeoxycholic acid (25 mg), cellulase (15 mg), trypsin (2550 USP units), amylase (2550 USP units), and lipase (412 USP units). The initial dosage was one capsule three times daily before meals.

In May 2020, enteric-coated compound pancreatin tablets (each containing 50 mg pancreatin and 50 mg pig bile extract) were added to the regimen at a dose of one tablet three times daily before meals. Due to the complexity of taking multiple capsules per meal and gastrointestinal side effects, adherence was inadequate according to the patient and his mother. Following the diagnosis of cirrhosis in June 2023, the dosage of compound pancreatin tablets was increased to two tablets per meal three times daily. Additionally, intensive patient and family counseling was provided to enhance compliance. Comprehensive nutritional support was also implemented, including a high-calorie, high-protein diet, intravenous albumin administration, and fat-soluble vitamin supplementation.

Upon admission for ACLF in March 2025, the management strategy included diuretics, albumin and fresh frozen plasma transfusions, correction of anemia and coagulopathy, measures to elevate platelet and leukocyte counts, hepatoprotective agents, and antimicrobial therapy.

OUTCOME AND FOLLOW-UP

The patient was irregularly followed up at the Department of Hepatobiliary Surgery of a local hospital after PPPD in 2019. Following the cirrhosis diagnosis in June 2023, he was repeatedly hospitalized at our institution for malnutrition, hypoalbuminemia, and refractory ascites. In March 2025, he was readmitted with edema and oliguria and was diagnosed with ACLF complicated by multi-organ dysfunction. The patient ultimately died in-hospital in April 2025 due to hepatic and multi-organ failure.

DISCUSSION

The reported incidence of malnutrition-associated steatotic liver disease after PD in adults varies widely across studies. Approximately 20%-40% of PD patients may develop new-onset fatty liver on imaging or histology within months to years postoperatively[3]. This incidence depends on factors such as the extent of pancreatic resection, surgical technique, postoperative nutritional status, and surgical indication (benign vs malignant disease)[6]. Total pancreatectomy is associated with a higher risk of steatotic liver disease, reaching 50%-74% within 1 year and up to 63% in long-term follow-up[7]. Patients with pancreatic malignancy tend to experience more significant weight loss postoperatively and have a relatively higher incidence of steatotic liver disease compared with patients with benign disease[8]. Surgical technique is also associated with steatotic liver disease risk; duodenum-preserving pancreatic head resection carries a significantly lower risk compared to PPPD, with an odds ratio of only 0.11 for steatotic liver disease in the duodenum-preserving pancreatic head resection group[9].

Only a few case reports have described progression to end-stage liver disease in adults post-PD. Owa et al[10] reported a 65-year-old male who developed cirrhosis 8 years after PD for suspected intraductal papillary mucinous neoplasm, and died 10 years postoperatively due to concurrent hepatocellular carcinoma. Miura et al[11] reported a 57-year-old female with type 2 diabetes who developed malnutrition-associated steatohepatitis, leading to acute liver failure, hepatic encephalopathy and death just 5 months post-PD. Sim et al[12] also reported a patient who developed severe steatohepatitis and progressed to decompensated cirrhosis 5 months post-PD, which improved with nutritional support.

Although PD is rarely performed in children and adolescents, available limited data suggest comparable short-term survival and complication rates to adults, with possibly lower incidences of PEI and malnutrition-associated steatotic liver disease[13,14]. To our knowledge, the rapid and fatal progression to cirrhosis and liver failure following PPPD has not been reported in adolescent patients. The present case highlights the potential for such a severe and accelerated clinical course in this population, underscoring the need for heightened clinical vigilance.

The core mechanism of malnutrition-associated steatotic liver disease after PD involves fat malabsorption due to PEI, leading to increased hepatic de novo lipogenesis[3]. Vagal nerve disruption and altered intestinal anatomy may also predispose to small intestinal bacterial overgrowth and dysbiosis[8]. Partial loss of endocrine function may cause early postoperative glucose intolerance[15]. In our case, refractory diarrhea, progressive malnutrition, and transient hyperglycemia indicated severe metabolic and gut microbiota disturbances. Similarly, severe weight loss and malnutrition were key factors in the rapid steatohepatitis deterioration in the adult cases reported by Miura et al[11], and Sim et al[12].

Furthermore, micronutrient and vitamin deficiencies may also contribute to rapid progression. Existing research highlights the critical role of various vitamin and trace element deficiencies in pathogenesis of malnutrition-associated steatotic liver disease[16]. Our patient exhibited markedly low serum zinc and copper levels. Although other vitamins and trace elements were not assayed, severe deficiencies are presumed. Zinc is a cofactor for antioxidant enzymes; its deficiency increases oxidative stress and hepatocyte injury[17]. Copper deficiency impairs free radical scavenging, leading to reactive oxygen species accumulation and oxidative damage to lipids, proteins, and DNA, thereby exacerbating hepatic inflammation and fibrosis[18].

Recent studies underscore the critical role of adequate PERT in managing PD-related PEI and potentially mitigating the risk of post-PD malnutrition-associated steatotic liver disease[19,20]. However, successful PERT requires careful, individualized dosing and strict timing (typically before meals) to be effective. This necessity for precise, long-term administration poses a particular challenge in adolescent patients, in whom adherence can be problematic[21].

Current guidelines recommend at least 40000 USP units of lipase per meal for adults, and for patients aged 4 years and older, an initial dose of 500 lipase units/kg per meal with subsequent titration[22,23]. United Kingdom practical guidelines also recommend starting with at least 50000 units of lipase with meals and 25000 units with snacks[4]. In this case, the documented PERT regimen evolved over time. Possibly due to the unavailability of high-potency lipase in local hospitals, the earliest postoperative regimen was a compound digestive enzyme capsule containing 412 USP units of lipase per capsule, taken three times daily before meals, a dose far below current recommendations. Although the PERT was changed to compound pancreatin tablets six months later and further escalated after the diagnosis of cirrhosis in 2023, the records documented these tablets in mass units (e.g., milligrams) without standardized lipase activity, precluding guideline based comparison. Nevertheless, the persistence of refractory steatorrhea, malnutrition, and trace element deficiencies indicates clinically inadequate enzyme replacement.

Additionally, the present patient exhibited poor adherence to PERT due to the complexity of taking multiple capsules per meal, and gastrointestinal side effects (e.g., bloating, nausea) as reported by the patient and his mother; however, other factors such as insufficient patient education may also have played a role.

We therefore consider non-standardized and likely insufficient PERT, along with poor adherence, as important and potentially modifiable contributors to the adverse hepatic course. Alternative interventions that might have changed the outcome include stepwise dose optimization guided by objective parameters (e.g., FE-1 or coefficient of fat absorption), the use of high-potency lipase formulations, and the involvement of a multidisciplinary team (dietitian, pharmacist, hepatologist) to reinforce adherence to the treatment strategies.

Several limitations exist in this case report. First, FE-1 testing was not performed, so PEI severity could not be objectively quantified; diagnosis relied on clinical features (post-surgical state, steatorrhea, nutritional decline). Second, micronutrient testing was incomplete: Only serum zinc and copper were measured. Fat-soluble vitamins (A, D, E, and K), selenium, and magnesium were not assayed, precluding assessment of their contribution to disease progression. Third, adherence was based on patient/mother self-report rather than objective methods (e.g., pill counts, electronic monitoring, serial FE-1). Thus, the role of poor adherence, though strongly suspected, cannot be definitively quantified.

CONCLUSION

This report describes a rare case of an adolescent patient experiencing a rapid and fatal progression to cirrhosis and liver failure driven by malnutrition-associated steatohepatitis following PD. The confluence of severe PEI-induced malabsorption, the exceptionally high metabolic demands of adolescent growth, likely insufficient PERT, and challenges with therapeutic adherence created a lethal synergy. This case powerfully illustrates that adolescent patients undergoing PD represent a distinct, high-risk population requiring a paradigm shift in postoperative management. An approach centered on aggressive, proactive PEI treatment, intensive multidisciplinary nutritional support, and vigilant, lifelong surveillance of hepatic health is imperative to prevent such catastrophic outcomes in the future. Further prospective research is urgently needed to define the true incidence of hepatic complications and to establish evidence-based management guidelines for this uniquely vulnerable patient group.