Clinical Case Summary

Kamini and other Ayurvedic medications are a part of an ancient Indian medical system "Ayurvedia" that is still widely practised. However, there is a lack of centralised regulation in ayurvedic medications and some formulations have ben found to contain opiates and heavy metals far exceeding the recommended daily exposure rates by factors of up to a thousand. Today we present a case-report of lead and opiate toxicity leading to significant hepatitis and abdominal pain in a patient with regular kamini use. Ayurvedia use is commonplace; a national health statistics report published in 2015 in the United States (US) describe 1 in 1000 people in the US having used ayurvedics and we therefore aim to raise public awareness.

A young Indian man presented with abdominal pain, tachycardia, and constipation. Investigations revealed deranged liver function tests with a bilirubin of 108umol/L, alanine transaminase 165U/L, and gamma-glutamyl transpeptidase of 243U/L. He also had a microcytic anaemia and hyponatraemia with osmolalities consistent with syndrome of inappropriate antidiuretic hormone (SIADH). Various imaging modalities inclusive of a computed tomography urogram (performed given history of renal stones), abdominal ultrasound, and magnetic resonance cholangiopancreatography were non-diagnostic. Careful history taking and literature search indicated lead and opiate toxicity from Kamini as a unifying diagnosis. To substantiate the diagnosis a blood film was performed which confirmed basophilic stippling and clinical examination revealed Burton's line on his gum - both signs of lead toxicity. Eventually serum lead levels returned significantly elevated at 5.6umol/L (normal <0.24umol/L).

He was initiated on Dimercaptosuccinic acid every 8 hours alternating between 400mg and 600mg for 5 days followed by 14 days of 400mg and 600mg alternating doses every 12 hours alongside weaning of opiates with subsequent improvement of clinical symptoms and biochemical markers

References

1. Photo of Burton's Line that was identified on examination of the patient
2. Photo of basophilic stippling identified on blood film examination

References
- Chopra A, Doiphode VV. Ayurvedic medicine. Core concept, therapeutic principles, and current relevance. Med Clin North Am. 2002 Jan;86(1):75–89, vii.
- Gunturu KS, Nagarajan P, McPhedran P, Goodman TR, Hodsdon ME, Strout MP. Ayurvedic herbal medicine and lead poisoning. J Hematol OncolJ Hematol Oncol. 2011 Dec 20;4:51.
- Mikulski MA, Wichman MD, Simmons DL, Pham AN, Clottey V, Fuortes LJ. Toxic metals in ayurvedic preparations from a public health lead poisoning cluster investigation. Int J Occup Environ Health. 2017 Jul;23(3):187–92.
- Clarke TC, Black LI, Stussman BJ, Barnes PM, Nahin RL. Trends in the use of complementary health approaches among adults: United States, 2002-2012. Natl Health Stat Rep. 2015 Feb 10;(79):1–16.
- Pearce JMS. Burton’s line in lead poisoning. Eur Neurol. 2007;57(2):118–9.
- Basophilic stippling of red blood cells: a nonspecific finding of multiple etiology - PubMed [Internet]. [cited 2024 Feb 21]. Available from: https://pubmed.ncbi.nlm.nih.gov/6202140/#
- Beattie AD, Mullin PJ, Baxter RH, Moore MR. Acute lead poisoning: an unusual cause of hepatitis. Scott Med J. 1979 Oct;24(4):318–21.

Introduction

Distal malignant biliary obstruction (DMBO) is a serious diagnosis that often results in significant morbidity and mortality due to development of obstructive jaundice and related complications. Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) has been described as a salvage therapy for patients with DMBO following unsuccessful ERCP and/or EUS-guided biliary drainage [1,2]. EUS-GBD leverages the proximity of the gallbladder to the gastrointestinal lumen to establish a new passage for biliary drainage, which offers a viable and potentially safer alternative to current EUS-BD techniques, particularly when the gallbladder is distended [3]. There is a paucity of data reporting on the outcomes of EUS-GBD for this indication, limited by small cohorts an​d single-centre design. We report a multi-centre study of outcomes for EUS-GBD performed for DMBO in non-surgical candidates.

Aims & Methods

A review of a prospectively collected database of 28 EUS-GBD cases was performed between 2017 and 2024 at two referral centres in New Zealand. At both centres, patients were consented for biliary drainage via ERCP, EUS-BD, and/or EUS-GBD prior to sedation so that drainage could be achieved in a single anaesthetic session. Ethics approval was provided at participating centres before commencement. Included participants were adults diagnosed with DMBO who had unsuccessful ERCP and/or EUS-BD, and a patent hepatocystic junction. A transduodenal approach was universal, using electrocautery-enhanced lumen apposing metal stents (LAMS), and propofol-assisted anaesthesia. Technical success (TS), clinical success (CS), length of hospital stay (LOS), adverse events (AEs), reinterventions, and survival were recorded. CS was defined by improvement in biochemistry and symptoms within 72 hours. AEs were categorised into serious and non-serious events. Re-interventions were categorised into early (<7 days) or delayed (≥7 days) procedures. Follow up duration was from time of intervention until patient death.

Results

Mean age was 74 years with 32.1% females. Pancreatic cancer was the most common diagnosis. Mean Charlson comorbidity index was 9.8 ± 1.4 and mean ASA physical status classification was 3.9 ± 0.5. The 10mm LAMS was most commonly used (78.6%), with co-axial plastic stent placement performed in 25%. TS and CS was achieved in all cases. Pre-procedure bilirubin improved from mean 126 ± 115 umol/L to 63 ± 49 umol/L at 72 hours. There were no intra-procedural complications and no early reinterventions recorded. Mean LOS was 3 ± 3 days. There were 9 non-serious AEs, all infective in aetiology and treated with antibiotics. 5 serious AEs were recorded (cholangitis (n=1), recurrent obstruction (n=3) and LAMS obstruction (n=1)) and only these cases required reintervention. These were treated with ERCP (n=1), percutanous drainage (n=3), and stent removal (n=1) respectively. No repeat procedure was required in 23/28 (82.1%) patients. Median cohort survival was 135 days.

Conclusion

EUS-GBD offers excellent TS and CS as a salvage therapy for DMBO in the second or third-line setting. Furthermore, it is safe with a favourable AE profile, short LOS and low rate of reintervention. This is particularly important in this cohort of patients with advanced malignancy. EUS-GBD offers a durable therapy and can be used as destination platform for other DMBO therapeutics. We have also demonstrated feasibility of sequential deployment within the same interventional session as ERCP and EUS-BD procedures creating a streamlined process for limiting cumulative anaesthetic exposures.

References

1. Imai, H., et al., EUS-guided gallbladder drainage for rescue treatment of malignant distal biliary obstruction after unsuccessful ERCP. Gastrointestinal endoscopy, 2016. 84(1): p. 147-151.
2. Debourdeau, A., et al., Effectiveness of endoscopic ultrasound (EUS)‐guided choledochoduodenostomy vs. EUS‐guided gallbladder drainage for jaundice in patients with malignant distal biliary obstruction after failed endoscopic retrograde cholangiopancreatography: Retrospective, multicenter study (GALLBLADEUS Study). Digestive Endoscopy, 2024.
3. Kamal, F., et al., Efficacy and safety of EUS-guided gallbladder drainage for rescue treatment of malignant biliary obstruction: A systematic review and meta-analysis. Endoscopic ultrasound, 2023. 12(1): p. 8-15.

Introduction

Management of acute cholecystitis in high-risk surgical candidates presents a clinical challenge. Percutaneous drainage via a cholecystostomy tube has been the preferred alternative in this cohort, with high rates of complications and low patient acceptability. Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) using lumen-apposing metal stents (LAMS) has been proposed as an alternative. Although several prospective studies and one randomised control trial have been published, it is not current standard of practice and there remains some concerns regarding its safety and efficacy.

Aims & Methods

This study evaluates the efficacy and safety of EUS-GBD for non-surgical candidates presenting with acute cholecystitis in the largest prospective cohort at a tertiary hospital within Australia and New Zealand. From July 2024, prospectively collected cases who underwent EUS-GBD using LAMS were entered into a secure database at our institution. Patients were followed for up to 180 days after index EUS-GBD procedure. Primary outcomes included technical and clinical success. Secondary outcomes include adverse events (AE), re-intervention rates and mortality.

Results

Twenty four patients (12 females, 12 males; mean age 75.5 years; range: 54–90) were included from July 2024 to April 2025. Patients were comorbid (mean Charlson Comorbidity Index 5.1), frail (mean Clinical Frailty Scale 4), and had high peri-operative risk (mean ASA score 3). EUS-GBD was technically and clinically successful in 100% of cases. Two (8.33%) patients experienced adverse events (stent occlusion requiring reinterventions). One (4.15%) patient developed atrial fibrillation driven by underlying sepsis necessitating admission to the high-dependency unit following EUS-GBD. There was one death occurring 23 days following EUS-GBD, deemed unrelated to the procedure. There were no procedure related mortality during the study period with an average follow up of 155 days.

Conclusion

Our study demonstrates that EUS-GBD is an effective and safe management option for gallbladder drainage in non-surgical candidates with acute cholecystitis. The high technical and clinical success rates, coupled with few procedure-related complications, support its use as the preferred option for drainage in otherwise poor surgical candidates due to significant medical comorbidities. However, larger studies are needed to validate these findings.

Disclosure

Drs Weilert, Chin and Prof. Fockens - consultants for Boston Scientific

Clinical Case Summary

Vanishing bile duct syndrome (VBD) is a rare entity characterised by cholestasis and ductopenia. The prognosis is variable depending on the aetiology. A 60-year-old woman with a history of lymphoplasmacytic lymphoma under surveillance and autoimmune haemolytic anaemia was admitted in August 2023 for a haemolytic crisis requiring transfusion support and high-dose steroids (60 mg/day). She was medicated with Trimethropim-Sulfamethoxazole for Pneumocystis Jiroveci prophylaxis on 30 august 2023. Suspended due to thrombocytopenia and replaced by Atovaquone 2 weeks later. On 19th november, she went to the emergency department due to jaundice, choluria and acholia, which had been going on for 4 days. Analyses showed cytocholestasis with a mixed pattern and hyperbilirubinaemia (total bilirubin (BT) 23.17 mg/dl, direct bilirubin 16.85 mg/dl). No bile duct dilatation. The autoimmune study and viral serologies were negative. An echoendoscopy was performed to rule out bile duct lithiasis, during which a liver biopsy was carried out, which revealed atrophy of the bile ducts, intrahepatic cholestasis with the presence of intracanalicular bile thrombi and some foci of necrosis inside the hepatic lobules. She had progressive analytical deterioration, with a maximum BT of 47.5 g/dl, without ascites or hepatic encephalopathy. It was decided to start corticotherapy (1 mg/Kg) and ursodeoxycholic acid (13 mg/Kg). She showed analytical improvement with a sustained drop in cytocholestasis and hyperbilirubinaemia (BT 27.04 mg/dl), but eventually died of an infectious complication. VBD can be associated with various factors, particularly drugs, with cases described with Trimethropim-Sulfamethoxazole and Atovaquone. It generally has a poor prognosis, with progression to terminal liver disease in approximately 50% of cases. As this is a rare entity, there is no consensus on the best therapeutic option, but the use of ursodeoxycholic acid and corticosteroid therapy appear to be beneficial.

Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health concern, with projections indicating that over half of the global population could be affected by 2040. MASLD is strongly linked to cardiometabolic risk factors and can progress to advanced liver diseases such as fibrosis, cirrhosis, and hepatocellular carcinoma. It is characterized by lipid accumulation within hepatocytes, leading to oxidative stress and inflammation. Gilbert’s syndrome (GS), a benign hereditary condition marked by elevated unconjugated bilirubin, is known for its antioxidant and anti-inflammatory properties. These properties have been associated with a reduced risk of several cardiometabolic conditions, raising the question of whether GS may influence the progression or severity of liver disease in MASLD.

Aims & Methods

This study aimed to investigate the potential relationship between GS and MASLD, focusing specifically on the impact of bilirubin’s effects on liver fibrosis and disease severity. A retrospective cohort study was conducted at Nawaloka Hospital, Colombo, Sri Lanka. Medical records from January 2022 to December 2024 were reviewed to extract sociodemographic, anthropometric, and biochemical data. Liver fibrosis was assessed using Fibro Scan® 502. Data analysis was performed using SPSS version 28, employing univariate analyses including t-tests, chi-square tests, and simple linear regression. A P-value <0.05 was considered statistically significant.

Results

A total of 180 patients with MASLD were included, of whom 36 were identified as having GS (defined by total bilirubin >1 mg/dL with elevated unconjugated bilirubin) and 144 without. No statistically significant difference in liver stiffness measurements (LSM) was observed between patients with and without GS (P = 0.8919). GS was not significantly associated with the presence or severity of liver fibrosis. Increasing age (P = 0.0278), body mass index (BMI) (P = 0.0330), and blood sugar levels (P = 0.0257) were positively associated with liver fibrosis. Demographic and clinical characteristics of the participants are summarized in Table 1.

Conclusion

There was no difference in the presence of fibrosis in MASLD patients with GS without GS in our population. This is in keeping with the view that GS is a benign condition. The significant associations of age, BMI, and blood sugar with increased fibrosis are well documented.