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.

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

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

Clinical Case Summary

57 year old male with a history of diabetes mellitus and heart ischemic disease that is referred to our department due to an incidental ultrasound finding of liver nodule of 3.8 cm in segment VIII and posterior CT with contrast compatible with hepatocellular carcinoma. Radiologically no data for advanced liver disease and normal fibroscan.
Given these findings, we decided to perform contrast-enhanced ultrasound, appreciating a subcapsular lesion in segment VIII that after contrast administration presents homogeneous early enhancement in the arterial phase, with homogeneous washout at the end of the same, maintaining the enhancement peripherally and later with progressive washing throughout the portal and late phase. This data suggests the diagnosis of intrahepatic cholangiocarcinoma. Hence, we perfomed a liver biopsy twice, as in the first occasion we found material compatible with normality and suspected malignant patology was high. After the histological analysis of the second biopsy ,we established the diagnosis of hepatic PEComa.
The pathogenesis of PEComas is uncertain, the main hypothesis s that it originates from undifferentiated neural crest cells capable of expressing phenotype of melanocytic and smooth muscle cells (1).
Despite their rarity, they should be included in the differential diagnosis of hepatic tumors as they present malignant potential even if it is low (2). Diagnosis may be easy through a histopathological study that proves the presence of marked immunohistochemical melanocytic (melan-A) and muscular (SMA) (2). However, they show a wide spectrum of findings in imaging tests (3), for what its suspected diagnosis and differential diagnosis with hepatocellular carcinoma and cholangiocarcinoma is complex. We have not found a description in the literature of its behavior with ultrasound contrast, hence the relevance of our case.

References

1. Arribas Jurado, Martina; Revollo, Ivia; Rubio Fernández, Alejandro; Galeano Díaz, Francisco; Blanco Fernández, Gerardo (2015). PEComa hepático. Cirugía Española, 93(9), 600–601.
2. Abhirup, Banerjee; Kaushal, Kundalia; Sanket, Mehta; Ganesh, Nagarajan (2015). Malignant hepatic perivascular epithelioid cell tumor (PEComa) – Case report and a brief review. Journal of the Egyptian National Cancer Institute.
3. Yan Tan, En-hua Xiao (2012). Hepatic perivascular epithelioid cell tumor (PEComa): dynamic CT, MRI, ultrasonography, and pathologic features—analysis of 7 cases and review of the literatura. 37(5), 781–787.

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.