Clinical Case Summary

Neurological manifestations in Hepatitis E Virus (HEV) infection are rare. Even so, they constitute the most frequent extrahepatic involvement (55%). The most frequent neurological presentations are amyotrophic neuralgia, Guillain-Barré Syndrome (GBS) and meningoencephalitis.
A 58-year-old presents 2 week's progressive weakness of the lower limbs and jaundice. Blood tests show elevated liver enzymes and hyperbilirubinemia; with no signs of liver insufficiency. Serologies show positivity for HEV IgG and IgM. The patient confesses game meat (deer) consume in the prior 5 weeks.
The neurological examination reveals a general decrease in symmetrical strength, with abolished musculoskeletal reflexes. After normal CT, cerebrospinal fluid discloses albumin-cytological dissociation. The electromyogram is compatible with motor radiculopathy. Diagnosis of GBS is stablished and so, immediate iv immunoglobulins 0.4g/kg are administered for 5 days, with progressive analytical and clinical improvement.
HEV is the main cause of acute viral hepatitis in humans. Infection in endemic areas is generally related to the consumption of contaminated water. In contrast, in developed countries, sporadic cases are frequently described and linked to the consumption of animal meat (pigs, wild boars and deer). Thus, HEV is currently considered an emerging zoonosis.
Most cases are asymptomatic, with spontaneous clearance in most healthy subjects. As with any hepatitis, it frequently presents as painless jaundice and asthenia.
The association with GBS is well established. An immune-mediated mechanism has been postulated as the immediate cause. Supportive treatment with immunoglobulins, plasmapheresis, steroids and physical therapy are generally used. The use of ribavirin is reserved for acute fulminant hepatitis or chronic hepatitis cases.
The course is usually satisfactory with complete recovery around 60% of patients.

Clinical Case Summary

A 40-year-old male came to our emergency department referring worsening jaundice, mental status deterioration, epigastric pain and anorexia over the past week. Four weeks earlier he presented odynophagia, myalgias, and hand pruritus but didn’t seek medical attention.
Patient’s clinical background included cognitive impairment due to peripartum anoxia and type 2 Diabetes Mellitus. At admission, he had elevated liver enzymes (R value=2,7), coagulopathy (INR 1.3), pancreatic enzymes >3 times the upper normal level and hyperbilirubinemia (mostly conjugated).
The CT-scan revealed pancreatic tail globosity, diffuse abdominal and retroperitoneal peri-centimetric lymph nodes and excluded biliary lithiasis.
After common causes of acute hepatitis and pancreatitis were ruled out, and since patient was at risk of acute liver failure despite supportive treatment, a liver biopsy was performed. Autoimmune hepatitis, drug-induced liver injury or lymphoproliferative disease were held as potential differentials. Hepatitis E Virus (HEV) RNA was then found and genotyped in the serum (genotype 3). HEV infection was assumed as the cause for both hepatitis and pancreatitis. Histological pattern was inconclusive and epidemiological source wasn’t found.

HEV infection paradigm has changed and is now considered an endemic zoonotic infection in most high-income countries (Portuguese seroprevalence is 16.3%)¹. Infection occurs due to ingestion of undercooked pig or boar meat and should be suspected in every acute hepatitis, mostly with a cholestatic pattern.
The setting of acute HEV hepatitis complicated with acute pancreatitis (AP) is uncommon². AP usually starts after a median of 10 days of jaundice onset³. Literature only reports association between AP and HEV caused by genotype 1 from Southeast Asia^{3 4}, and genotype 3 was only related to gallstone-related pancreatitis, according to current knowledge⁵. This might be the first form of HEV genotype 3 infection with hepatitis and pancreatitis.

References

1. Nascimento MSJ, Pereira SS, Teixeira J, et al. A nationwide serosurvey of hepatitis E virus antibodies in the general population of Portugal. Eur J Public Health 2018;28(4):720-24. doi: 10.1093/eurpub/ckx213 [published Online First: 2017/12/14]
2. Debnath P, Datta AK, Chakraborty U, et al. Acute viral hepatitis E complicated with acute pancreatitis in an immunocompetent adult. BMJ Case Rep 2021;14(2) doi: 10.1136/bcr-2020-239684 [published Online First: 2021/02/06]
3. Haffar S, Bazerbachi F, Garg S, et al. Frequency and prognosis of acute pancreatitis associated with acute hepatitis E: A systematic review. Pancreatology 2015;15(4):321-6. doi: 10.1016/j.pan.2015.05.460 [published Online First: 2015/06/08]
4. European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL Clinical Practice Guidelines on hepatitis E virus infection. J Hepatol 2018;68(6):1256-71. doi: 10.1016/j.jhep.2018.03.005 [published Online First: 2018/04/04]
5. Karlsson M, Norder H, Bergstrom M, et al. Hepatitis E virus genotype 3 is associated with gallstone-related disease. Scand J Gastroenterol 2019;54(10):1269-73. doi: 10.1080/00365521.2019.1666163 [published Online First: 20190925]

Introduction

Acute variceal bleeding (AVB) is a medical emergency that requires urgent evaluation. It is a complication of portal hypertension and, despite the improvements in the management of these patients, mortality is still high. According to the best available data, all patients should be risk stratified according to the validated clinical scores MELD and Child-Pugh.

Aims & Methods

To access the predictive capacity of PALBI and CLIF-C AD scores and to compare them with the currently recommended MELD and Child-Pugh scores for the following outcomes: in-hospital mortality, mortality at 6 weeks and rebleeding.
Retrospective review of all cirrhotic patients admitted for AVB between January 2016 and December 2022 in a Gastroenterology department in Portugal. The area under the receiver operating characteristics curve (AUROC) was calculated for all scores and compared with DeLong test.

Results

100 patients included, average age 61.87±14.68years, 77% male. Alcohol was the most frequent aetiology (n=56).
All patients were hemodynamically resuscitated and more than 90% underwent endoscopic evalutation within 12hours from admission. 30% of patients had active bleeding at the time of upper GI endoscopy. 90% of patients had esophageal varices (GOV-1) bleeding treated with endoscopic band ligation. 10% of patients had acute gastric (cardiofundal) variceal (GOV2, IGV1) bleeding treated with cyanoacrylate injection. 5% of patients had persistent bleeding and thus a Sengstaken-Blakemore tube was placed. Rebleeding occurred in 11% of patients.
Median time of admission was 6 days (1-30 days). In-hospital mortality was 28% and mortality at 6 weeks was 19%.
The average scores were MELD: 15.98 ± 6.89 points; Child-Pugh 8.65 ± 2.10 points; PALBI -1.71 ± 0.47 points; CLIF-C AD 58.48 ± 11.42 points.
The AUROC of PALBI for in-hospital mortality (AUROC=0.742) and for mortality at 6 weeks (AUROC=0.616) was similar to the traditional scores MELD (AUROC=0.747 and AUROC=0.698) and Child-Pugh (AUROC=0.794 and AUROC=0.673). PALBI was also a good predictor for rebleeding (AUROC=0.795), superior to MELD (AUROC=0.726) and inferior to Child-Pugh (AUROC=0.801). Comparison of the AUROCs of the three scores showed no statistically significant differences.
Regarding CLIF-C AD, it was a good predictor for in-hospital mortality (AUROC=0.708) and mortality at 6 weeks (AUROC=0.706), with no statistically significant differences compared to MELD and Child-Pugh scores. The predictive capacity for CLIF-C AD for rebleeding was not satisfactory (AUROC=0.552).

Conclusion

In addition to liver-specific scores, the predictive performance and clinical utility of PALBI and CLIF-AD C scores for identifying patients with AVB at higher risk for in-hospital mortality, mortality at 6 weeks and rebleeding is very good.
PALBI score deserves recognition, not only because of it is very good predictive capacity for all outcomes, but also because it does not take into account variables whose evaluation has some degree of subjectivity, like hepatic encephalopathy and ascites.

Introduction

Necrotizing pancreatitis with walled-off necrosis (WON) is associated with severe morbidity and substantial mortality. Vascular complications such as pseudoaneurysm, arterial erosion, and especially thrombosis of the splanchnic veins are all associated with acute pancreatitis (AP). However, the occurrence and clinical outcome of vascular manifestations in patients developing WON are poorly described. We aimed to describe vascular complications in a well-defined cohort of consecutive patients endoscopically treated for symptomatic WON.

Aims & Methods

Four hundred and nine patients treated endoscopically for their pancreatic fluid collection during a 10-year period were assessed for inclusion. Patients with pseudocysts, < 18 years, concomitant malignant disease and/or procedure-related bleeding were excluded. A total of 290 patients were eligible for analysis.
Vascular complications included bleeding and thromboembolic events. Thromboembolic complications were defined as confirmation of thrombus in one of the splanchnic veins on contrast-enhanced computed tomography scan (CECT). Bleeding complications were defined as clinical bleeding necessitating intervention, including embolization, surgery or transfusion.

Results

The median age was 59 years (range 18-84), and 57% were males. Gallstones were the etiology in 47%, alcohol in 20%, and post-ERCP pancreatitis in 14%. In 14% of the cases, the etiology was unknown. Infection was the main indication for intervention (92%), followed by gastric outlet obstruction (6%) and pain (2%). The average time from debut of symptoms to index procedure was 35 days (range 6-89). The average duration of hospital admission was 89 days (range 21-286). The overall in-hospital mortality was 14%, and need for admission to intensive care unit (ICU) was 35%.
In total, 87 (30%) patients developed vascular complications of which 53 (18%) were thromboembolic, 34 (12%) bleeding, and nine patients (3%) developed both thromboembolic and bleeding complications.
The portal vein was most affected (34%), followed by the splenic vein (28%) and the superior mesenteric vein (23%). Two or all three splanchnic veins were affected in 15%. The majority (81%) of thromboembolic complications occurred before the index procedure. Development of splanchnic venous thrombosis was not associated with in-hospital mortality (13% vs. 14%, p=1.0) or need for ICU admission (38% vs. 34%, p=0.64). None of the patients with splanchnic vein thrombosis developed variceal bleeding during follow-up.
The splenic artery was the most common cause of bleeding (32%), followed by the gastroduodenal artery (24%) and the left gastric artery (12%). In five cases, the source of the bleeding could not be identified. All patients received blood products, 23 patients were treated with arterial embolization and 4 patients with surgery. Seventy seven percent of the bleeding complications occurred after the index procedure. The need for ICU (59% vs. 32%, p=0.003) and in-hospital mortality (38% vs. 11%, p<0.0001) were significantly higher in patients with arterial bleedings as compared to patients without.

Conclusion

Vascular complications are common in WON patients. The timing of occurrence seems distinct, as the vast majority of thromboembolic complications occur before index endoscopic intervention, while bleeding complications mainly occur after. While arterial bleedings are linked to increased morbidity and in-hospital mortality, thromboembolic complications are not associated with a poor short- or long-term clinical outcome.

Introduction

IgG4-related disease of the liver, pancreas, and bile ducts (IgG4-HPB) can lead to fibrosis and organ damage. Liver stiffness measurement (LSM) by vibration-controlled transient elastography and Enhanced liver fibrosis (ELF) score are validated, non-invasive methods for measuring liver fibrosis in other chronic liver diseases, but little is known about their utility in IgG4-HPB.

Aims & Methods

The aim of this study is to assess LSM using Fibroscan® and ELF in patients with IgG4-HPB. This is a retrospective observational cohort of patients meeting the ACR/EULAR classification criteria for IgG4-Related Disease at Oxford University Hospitals. Clinical data collected included demographics, organ involvement, clinical flares, serum biomarkers and organ damage. LSM was recorded in 55 IgG4-HPB patients, and sequential LSM was recorded in 32 patients. Serum ELF was measured in 23 patients. Wilcoxon rank, Mann-Whitney U, and Fisher’s exact tests were performed.

Results

Ninety-seven patients with IgG4-HPB were included; median age was 68 years ±19, and 79% were male. Among the entire cohort, 69% had established organ dysfunction and/or damage and, when subdivided by organ involvement, damage was present in 72% of those with liver and biliary disease (IgG4-HB) and 65% of those with pancreatic disease only (IgG4-AIP) (Table 1).

	Overall cohort (n = 97)	HPB cohort (n = 57)	AIP cohort (n = 40)	p-value
Median age (IQR)	67.5 (19)	68.5 (19)	65.5 (18)	0.91
Men	77 (79%)	44 (77%)	33 (82%)	0.61
Established organ damage	67 (69%)	41 (72%)	26 (65%)	>0.99
Diabetes	33 (34%)	26 (46%)	12 (29%)	0.14
Cardiometabolic disease	41 (42%)	22 (39%)	20 (49%)	0.11
MASLD	19 (20%)	13 (23%)	6 (15%)	0.59
Mean cumulative steroid dose (SD)	7326 (17468)	9012 (21263)	4260 (3074)	0.32
Median number of flares (IQR)	1 (2)	1 (2)	0 (1)	0.25

LSM was recorded in 55 patients: IgG4-HB (n = 38) had a higher mean LSM compared with IgG4-AIP (n = 17) (6.1 kPa vs 5 kPa, p = 0.04). IgG4-HB were risk-stratified by LSM: 66% had LSM <8kPa, 21% had LSM ≥8 but <12kPa, and 13% had LSM ≥12kPa. There was a higher prevalence of metabolic associated steatotic liver disease (MASLD) and its metabolic factors (diabetes, hypertension, hypercholesterolemia, and ischaemic heart disease) in those with more advanced liver fibrosis (LSM≥12 kPa). Furthermore, survival analysis showed that patients with LSM ≥ 8kPa develop organ damage faster than those with LSM < 8kPa (p=0.0086).

In longitudinal analysis, 32 patients with IgG4-HPB had serial LSMs. Of those with IgG4-HB (n = 22), 23% showed an increase in LSM over a median of 2 years (IQR 1-4). The proportion of patients meeting criteria for MASLD increased from 20% to 25% over a median of two years. In those with paired readings during active disease and remission (n = 8), there was no discernible variation in LSM.

Twenty-three patients with IgG4-HPB had an ELF test and were stratified by the score: 13/23 (56%) <9.8 and 10/23 (43%) ≥9.8. ELF accurately identified patients with more significant liver fibrosis; no patient with LSM ≥ 8kPA was seen in the <9.8 group (p = 0.0021). There was no association of ELF with disease activity or serum biomarkers.

Conclusion

This is the first study assessing the role of LSM by Fibroscan® and of ELF score in patients with IgG4-HPB. An increased LSM over time was associated with the accumulation of cardiometabolic risk factors, evidence of MASLD, and end-organ damage, while ELF score ruled out advanced fibrosis in this cohort concurrently.

Disclosure

EC: Speaking Fees: Horizon Therapeutics, Advanz (Intercept), Albireo, Dr Falk Pharma, Gilead, GSK; Consulting Fees: Advanz (Intercept), Horizon Therapeutics, Ipsen, Mirum, Moderna, Sanofi, Zenus Pharma; Grant Support: Jansen, Innovate UK, PSC Support, Wellcome Trust; Institutional Funding Support: BRC Oxford NIHR (UK), Oxford Charitable Fund, Research Capability Fund.
SK, RM and CM have nothing to declare.