Clinical Case Summary

Abernethy malformation (AM) is a rare type of congenital extrahepatic portosystemic shunt. Two types are recognised: in type 1 AM, there is complete shunting and absent portal vein, while in type 2 AM there is partial shunting and an hypoplastic portal vein. Multiple congenital anomalies are seen in association with AM and it can present with a broad spectrum of clinical manifestations.

We report the case of a 58-year-old female initially investigated for recurrent episodes of psychomotor lentification, disorientation and elevated ammonia levels. Blood tests and transient elastography excluded advanced chronic liver disease. An abdominal CT scan revealed a portosystemic shunt involving the left portal branch and inferior vena cava (type 2 AM). Although treatment with lactulose was effective at first, the patient ultimately came to develop more frequent episodes. Rifaximin was only partially effective. Thus, interventional Radiology evaluation was requested for eventual treatment. Hepatic hemodynamic studies were significant for a hepatic venous pressure gradient of 14 mmHg, augmented to 24 mmHg during a balloon occlusion test. The decision was made to perform an endovascular single-step occlusion of the shunt. Follow-up CT scan confirmed shunt closure, inferior vena cava patency and reperfusion of intrahepatic portal branches. Subsequent endoscopy was negative for signs of portal hypertension. On 1-year follow-up, the patient is asymptomatic.

No guidelines are currently available to standardise management of AM. The first concern should be to to distinguish AM from intrahepatic shunts and acquired extrahepatic shunts. Liver transplantation is only a valid option for type 1 AM. Conversely, type 2 AM is best managed by obliteration of the shunt, either by surgical ligation or endovascular occlusion. This case highlights the role of minimally invasive techniques in treating this condition without significant morbidity.

References

1. Kraus C, Sheynzon V, Hanna R, Weintraub J. Single Stage Endovascular Treatment of a Type 2 Abernethy Malformation: Successful Nonsurgical Outcome in a Case Report. Case Rep Radiol. 2015;2015:491867.

2. Kwapisz L, Wells MM, AlJudaibi B. Abernethy malformation: congenital absence of the portal vein. Can J Gastroenterol Hepatol. 2014 Dec;28(11):587–8.

3. Lin Y, Li X, Li S, Ba H, Wang H, Zhu L. Treatment Option for Abernethy Malformation-Two Cases Report and Review of the Literature. Front Pediatr. 2020;8:497447.

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.

Clinical Case Summary

The work-up for a liver nodule varies according to the presence or absence of underlying liver disease. In patients with cirrhosis, hepatocellular carcinoma (HCC) is a frequent aetiology. Diagnosis is mainly based on imaging studies, although biopsy is sometimes necessary when diagnosis is unclear.

We report the case of a 61-year-old male with alcohol-related cirrhosis, Child-Pugh B, with a history of a functioning metastasized duodenal neuroendocrine tumour (NET), under treatment with somatostatin analogues. During NET follow-up, a suspicious liver nodule was identified. Abdominal CT scan was significant for a 23mm hypervascular liver nodule (HCC vs. NET metastasis), located in segment VIII/IV, as well as a de novo thoracic hilar adenopathy. Endobronchial ultrasound fine-needle aspiration of the lymph node rendered insufficient material for diagnosis. An 18FDG-PET scan identified multiple other hypermetabolic adenopathy in the upper abdomen and right mediastinum/hilum, compatible with malignant involvement. Upon multidisciplinary image review, HCC was considered a highly likely aetiology, and a hepatic hilar adenopathy was selected for fine-needle aspiration via endoscopic ultrasound. However, histological analysis confirmed a diffuse large B-cell lymphoma, with high mitotic rate. Further liver nodule work-up was suspended, and the patient is now undergoing therapy with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone.

This case highlights the importance of maintaining suspicion for other differential diagnosis during liver nodule work-up, even in high-risk HCC patients, and also underlines the increased risk of other primary cancers after NET diagnosis (7.9%). Initial evaluation of the liver nodule deemed HCC as a likely cause, and would hence attribute adenopathy to secondary involvement. However, enlarged lymph nodes were not associated with HCC metastases, but with a different neoplastic process, namely a diffuse large B-cell lymphoma.

References

1. Zhou J, Sun H, Wang Z, Cong W, Wang J, Zeng M, et al. Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2019 Edition). Liver Cancer. 2020;9(6):682–720.

2. Tsai HJ, Wu CC, Tsai CR, Lin SF, Chen LT, Chang JeffreyS. Second Cancers in Patients with Neuroendocrine Tumors. Scheurer M, editor. PLoS ONE. 2013 Dec 31;8(12):e86414.

3. Sadaps M, Mehta N, Li H, Estfan BN. Incidence and patterns of secondary malignancies in patients with neuroendocrine neoplasms: A SEER database analysis. JCO. 2021 Jan 20;39(3_suppl):374–374.

Clinical Case Summary

A 48-year-old woman was diagnosed with subacute ataxia. One day after a cycle of treatment with Immunoglobulin, she presented with elevated liver enzymes, with alanine aminotransferase(ALT)levels reaching up to 5 times the normal upper limit. An abdominal ultrasound and CT scan revealed no abnormalities. Viral serologies and autoimmune tests were also normal. She was reevaluated a week later and showed improvement in liver function tests. Due to suspicion of hepatic toxicity from immunoglobulin and worsening neurological symptoms, she started methylprednisolone. Four days after, she was admitted in the emergency department with epigastric pain, nausea, and vomiting. On physical examination, she had a soft abdomen that was tender on palpation of the epigastric and right hypochondriac regions. Laboratory tests showed leukocytosis of 17,500(73% neutrophils), aspartate aminotransferase of 145 U/L, and ALT of 373U/L. An abdominal CT scan revealed multiple pericentimeter areas of enhancement in the arterial phase, more evident in the right hepatic lobe, some of which appeared coalescent and became homogeneous relative to the rest of the liver parenchyma in the venous phase, suggestive of hepatic peliosis. The corticosteroid therapy was suspended. The patient remained asymptomatic with improvement in liver function parameters. An MRI was performed three months later, which showed partial regression of the lesions. An abdominal CT scan was performed three months after that and showed complete resolution of the lesions.
Peliosis hepatis can be associated with various conditions, including infectious diseases, neoplasms, and immunosuppressive drugs such as corticosteroids, as in the presented case. Although it can be an incidental finding in asymptomatic patients, in some cases, it can lead to complications such as intraperitoneal hemorrhage, liver failure, and portal hypertension. Once the diagnosis is established, it is important to identify and remove the underlying cause.

Introduction

Congenital portosystemic shunts (CPSS) are associated with an array of clinical signs and symptoms of varying severity in both adults and children. Yet, symptoms are often missed and ascribed to other etiologies. Understanding presenting complaints will increase awareness of this rare disorder. To this end the International Registry of Congenital Portosystemic shunts (IRCPSS) was created. Here we report an up-to-date description of the patients enrolled in the IRPCSS focusing on presenting complaints.

Aims & Methods

Descriptive analysis of the ESPGHAN sponsored IRCPSS described in (1)

Results

256 patients were enrolled - 125 females (49%). Type of CPSS was available for 212: 88 (41.5%) presented with intrahepatic (IHS) and 124 (58.5%) with extrahepatic (EHS) shunts. Clinical data were available for 71 with IHS and 106 with EHS. 51 (72 %) of IHS were asymptomatic. Of the 20 (28%) symptomatic, median age at diagnosis was 0.59 years (14 days-19.9 years). Presenting complaint included liver in 14, cardiopulmonary in 6, neurological in 2, other in 7. Of 56 IHS closed, 21 (37.5%) closed spontaneously before age 1. 29 (52%) were closed using interventional radiology. Among 106 patients with EHS, 72 (68%) were asymptomatic. Among symptomatic patients, median age at diagnosis was 7.49 years (14 days- 24.9 years). Presenting complaints included liver in 15, cardiopulmonary in 13, neurological in 13, and other in 17. 74 patients had closed shunts at last follow-up; they were closed at a median age of 2.7 years (18 days- 25.4 years). Spontaneous closure was reported in 2 patients, otherwise closure was performed by interventional radiology in 25 (34%), or surgery in 40 (54%) and 7 undergoing LT.

Conclusion

Most shunts were asymptomatic at diagnosis. Among symptomatic patients, the median age at diagnosis was higher in EHS than IHS. IHS and EHS were equally likely to be closed, with IHS more likely to close
spontaneously within the first year of life.

References

(1) Korff S, Mostaguir K, Beghetti M, D'Antiga L, Debray D, Franchi-Abella S, Gonzales E, Guerin F, Hachulla AL, Lambert V, Makrythanasis P, Roduit N, Savale L, Senat MV, Spaltenstein J, van Steenbeek F, Wildhaber BE, Zwahlen M, McLin VA. International registry of congenital porto-systemic shunts: a multi-centre, retrospective and prospective registry of neonates, children and adults with congenital porto-systemic shunts.Orphanet J Rare Dis. 2022 Jul 19;17(1):284.

Disclosure

V McLin consults for Mirum and Ipsen. L Savale consults for MSD, Janssen, and GSK. Neither

Introduction

Advanced chronic liver disease (ACLD) may present in different stages with distinct prognoses. Child-Pugh and MELD scores are commonly used models for predicting liver-related mortality and decompensation, but they have several limitations. An alternative or complementary tool that is simple and cost-effective would be invaluable. Recently, some studies identified a potential role of ammonia in predicting liver-related outcomes.

Aims & Methods

Our primary objective was to explore the predictive role of plasma ammonia levels regarding liver-related complications and mortality. Our secondary aim was to validate a new measure that corrects baseline ammonia levels to the upper limit of normal (AMM-ULN) and test a cut-off which was proposed in the literature to define patients at higher risk of such outcomes (AMM-ULN ≥ 1.4).
This retrospective study included 278 patients with ACLD who had an ammonia measurement in our hospital between 2018 and 2022. ACLD patients were divided into compensated and decompensated stages, with the latter being subdivided into three stages, according to the type of decompensation. Outcomes of liver-related decompensation and mortality were assessed in each group. AMM-ULN was evaluated as a predictor of these outcomes both in compensated and decompensated patients. The predictive accuracy of AMM-ULN was then determined by identifying the best cut-off.

Results

Plasma ammonia levels and AMM-ULN were predictors of hepatic decompensation (HR = 1.453, 95%CI 1.085 – 1.945, p = 0.012) and mortality (HR = 1.010, 95%CI 1.003 – 1.017, p < 0.001) at 12 months, in the compensated patient group. The AUROC for AMM-ULN was 67.4% in 1-year decompensations and 69.5% in 1-year mortality, with similar results for ammonia levels. AMM-ULN ≥ 1.4 identified patients at higher risk of liver-related decompensation and mortality at 12 months (p = 0.009 and p = 0.020, respectively).

Conclusion

Both ammonia levels and AMM-ULN were predictors of hepatic decompensation and liver-related mortality in compensated patients, at 12 months of follow-up. AMM-ULN ≥ 1.4 identified patients at higher risk of liver-related decompensation and mortality at 12 months.

References

D’Amico, G., Garcia-Tsao, G., & Pagliaro, L. (2006). Natural history and prognostic indicators of survival in cirrhosis: A systematic review of 118 studies. Journal of Hepatology, 44(1), 217–231. https://doi.org/10.1016/j.jhep.2005.10.013
Haj, M., & Rockey, D. C. (2018). Predictors of clinical outcomes in cirrhosis patients. Current Opinion in Gastroenterology, 34(4), 266–271. https://doi.org/10.1097/MOG.0000000000000450
De Franchis, R. et al (2022). Baveno VII – Renewing consensus in portal hypertension. Journal of Hepatology, 76(4), 959–974. https://doi.org/10.1016/j.jhep.2021.12.022
Shalimar, Sheikh, M. F. et al (2019). Prognostic Role of Ammonia in Patients With Cirrhosis. Hepatology, 70(3), 982–994. https://doi.org/10.1002/hep.30534
Tranah, T. H. et al (2022). Plasma ammonia levels predict hospitalisation with liver-related complications and mortality in clinically stable outpatients with cirrhosis. Journal of Hepatology, 77(6), 1554–1563. https://doi.org/10.1016/j.jhep.2022.07.014
Balcar, L. et al (2023). Impact of ammonia levels on outcome in clinically stable outpatients with advanced chronic liver disease. JHEP Reports, 5(4), 100682. https://doi.org/10.1016/j.jhepr.2023.100682
Elzeftawy, A. et al (2018). Evaluation of the blood ammonia level as a non-invasive predictor for the presence of esophageal varices and the risk of bleeding. The Turkish Journal of Gastroenterology. https://doi.org/10.5152/tjg.2018.17894

Introduction

Hepatic encephalopathy (HE) after Transjugular Intrahepatic Portosystemic Shunt (TIPS) affect 35-50% of patients. The use of prophylactic agents (Lactulose and Rifaximin) to prevent post-TIPS HE remains controversial and currently not recommended by professional guidelines. Our aim was to assess real world practice and identify potential predictors for post-TIPS HE and benefit from post-TIPS prophylaxis.

Aims & Methods

Retrospective cohort study of patients undergoing TIPS at the Tel-Aviv Medical Center (2016-2024). The primary outcome was overt HE, with secondary outcomes of liver transplantation (LT) and mortality.

Results

Seventy-nine patients underwent TIPS, median age was 60 years and 52% were male. Primary liver disease was metabolic dysfunction-associated steatohepatitis (MASH) in 34%, viral (20%), and alcohol-related liver disease (ALD) (16.5%). Indications for TIPS were variceal bleeding (52%) and refractory ascites (38%). Prior to the procedure 31% had ≥ 1 episodes of HE, 21.5% were treated with Lactulose and/or Rifaximin, and 58% were on betablocker treatment. At the time of the procedure, the patient's Child-Pugh score was A/B/C in 19%/66%/11% respectively, with a median MELD-Na of 10.9. Median follow up was 22.75 months. Overall, 22 patients died during follow-up and 8 underwent liver transplantation. 45 patients (57%) developed post-TIPS HE, 60% of them during the first three months. Early post-TIPS HE treatment was given to 49%: 10% Lactulose, 5% Rifaximin, and 34% both. Among those patients, 44% were previously (pre-TIPS) on HE treatment. Development of HE was not predicted by pre-or post-TIPS MELD-Na or Child-Pugh score, TIPS diameter, postTIPS gradient, or post-procedure ammonia levels. Rates of HE also did not differ according to initial prophylaxis treatment (59% with treatment, 56% without, p=1). Pre-TIPS AST and albumin were associated with post-TIPS HE (36.6U/L vs. 60.44 U/L, p=0.03; 34.6g/dl vs. 31.8g/dl, p = 0.05). Prior beta-blocker treatment was associated with post-TIPS HE (14% vs 32%, p = 0.01) but not varices as the indication for TIPS. Mortality rate was not affected by the occurrence of post-TIPS HE (28% among those who developed HE vs. 26% among those who didn't, p = 1).

Conclusion

Early post-TIPS preventive treatment was mostly given to patients previously treated with Lactulose/Rifaximin, however it did not affect the rate of post-TIPS HE. Development of HE did not increase mortality.

References

1. Wolfgang el al. ASSLD practice Guidance, Hepatology (2024)
2. Yao el al.J Gastrointestin Liver Dis (2015)