Clinical Case Summary

A 64-year-old female with no relevant medical or epidemiological history went to the emergency department with a 3-week history of fever, malaise and headache, associated with a 3-day history of jaundice. Due to hypotension unresponsive to fluids, the patient was admitted to the intensive care unit on vasopressors and large spectrum antibiotics.

The lab values revealed pancytopenia (hemoglobin 9.6g/dL, leucocytes 0.85x10⁹/L and platelets 43x10⁹/L), coagulopathy and cholestatic hepatitis (R-Factor 1.7, with alanine transaminase 10 times and alkaline phosphatase 6 times the reference values), with a total bilirubin of 6.6mg/dL (mainly direct bilirubin). The patient had a lactate desidrogenase value of 4900U/L, serum ferritin of 15000U/L and C-reactive protein of 15mg/L. A contrast-enhanced abdominal computerized tomography revealed multiple infracentrimetric liver nodules.

Due to high clinical suspicion of hemophagocytic syndrome the patient underwent transjugular liver biopsy, bone marrow biopsy and started dexamethasone. Liver biopsy revealed infiltration by monoclonal T-cells, associated with erythrophagocytosis, confirmed by bone marrow biopsy. The patient initiated chemotherapy with cyclophosphamide, gemcitabine and vincristine, with progressive clinical improvement with bilirubin normalization, regression of cytolysis and cholestasis, and the patient was referred to outpatient Hematology clinic after discharge.

Hemophagocytic or macrophage activation syndrome results from immunological hyperactivation with macrophage-mediated multiorgan failure. It develops in a genetic context or secondary to infections, autoimmune diseases or malignancies. The presence of predominant liver involvement is rare and liver biopsy is essential in the diagnostic workup. This clinical case demonstrates liver damage mediated by both hemophagocytic syndrome and liver involvement by a T-cell lymphoma, showing the importance of high clinical suspicion for a prompt diagnosis.

References

1. Histopathological sample of the bone marrow biopsy
2. Histopathological sample of the liver biopsy

Clinical Case Summary

A 30-year-old-female presented with a one-week history of jaundice and pedal edema. Initial laboratory investigations revealed elevated liver enzymes and total bilirubin of 37.90 mg/dL. Over the following three months her condition worsened, a transjugular liver biopsy revealed 50% necrosis, indicative of severe liver injury for which she underwent a Liver transplant. On POD 7 she developed severe thrombocytopenia (8000/μL) and neutropenia (858/μL), along with elevated LFTs (AST=473 IU/L, ALT=992 IU/L), challenging the post-operative management. Some differentials were Acute transplant rejection, CMV, infection, drug induced hepatotoxicity etc. CMV PCR testing was ordered which revealed a positive result, prompting antiviral therapy. Due to persistent pancytopenia a bone marrow biopsy was performed confirming the presence of hemophagocytosis, leading to a diagnosis of Hemophagocytic Lymphohistiocytosis. Diagnosis was supported by other Lab values (platlets=8000/μL, neutrophils=858/μL, LFTs; AST=473 IU/L, ALT=992 IU/L, fibrinogen=508 mg/dl and ferritin=2269 Ng/ml).
Appropriate treatment with high-dose steroids and etoposide was initiated promptly adhering to the HLH-2004 protocol [1], however the patients condition continued to worsen. On POD 16 she eventually succumbed to multi-organ failure due to mucormycosis and septic shock.
The incidence of HLH in liver transplant patients is not well documented, only forty-one previous post-LT HLH cases have been reported in present literature, out of which only 5 were initially diagnosed with acute liver failure [2,3] ,This case adds to the existing literature on HLH and highlights the importance of including HLH as a differential diagnosis in immunocompromised patients, especially in post-liver transplant cases, due to its severe outcomes. Integrating novel diagnostic tools like the HScore may enhance the ability to diagnose HLH in complex clinical situations [4], although they cannot replace astute clinical judgment.

References

1. Henter J, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, et al. HLH‐2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007 Feb 25;48(2):124–31.
2. Chesner J, Schiano TD, Fiel MI, Crismale JF. Hemophagocytic lymphohistiocytosis occurring after liver transplantation: A case series and review of the literature. Clin Transplant. 2021 Aug 8;35(8).
3. Iseda N, Yoshizumi T, Toshima T, Morinaga A, Tomiyama T, Takahashi J, et al. Hemophagocytic syndrome after living donor liver transplantation: a case report with a review of the literature. Surg Case Rep. 2018 Dec 29;4(1):101.
4. Fardet L, Galicier L, Lambotte O, Marzac C, Aumont C, Chahwan D, et al. Development and Validation of the HScore, a Score for the Diagnosis of Reactive Hemophagocytic Syndrome. Arthritis & Rheumatology. 2014 Sep 26;66(9):2613–20.

Clinical Case Summary

A 56-year-old woman was referred to tertial hospital for decompensated liver cirrhosis of unknown origin. She was slightly overweight (BMI 25.3) and denied alcohol consumption or any history of liver disease. Since childhood, she had been diagnosed with congenital ichthyosis, strabismus, and myopia, had a history of bilateral neurosensory hearing loss, arterial hypertension, and cataracts. Since 2016, she had been experiencing progressive muscle weakness, and intermittent speech impairment. The patient complained of eyes dryness, episodic joint and muscle pain, muscle weakness, general malaise, dizziness, dry and scaling skin. Physical examination revealed diffuse skin dryness, scaling and an enlarged abdomen. Radiological examination revealed a cirrhotic liver, splenomegaly and moderate ascites. The MELD score was 18 and the Child-Pugh - 9. Laboratory tests excluded Wilson's disease, autoimmune liver diseases, hemochromatosis, α-1 antitrypsin deficiency. Liver biopsy showed macro and microvesicular steatosis (>50% of hepatocytes with lipid vacuoles), hepatocytes ballooning and inflammation compatible with MAFLD related liver cirrhosis. In peripheral blood smear was detected multiple lipid vacuoles in the leukocytes cytoplasm, known as Jordan‘s anomaly, confirming Chanarin–Dorfman syndrome (CDS) - a rare autosomal recessive neutral lipid storage disease. Genetic testing confirm diagnosis and revealed a potentially pathogenic homozygous c.133+3A>C mutation in the ABHD5 gene. Due to progression of liver failure patient was referred for liver transplantation (LT) and liver was successfully transplanted in 2024.
The case showed that LT is a realistic option if liver function deteriorates in CDS. LT does not affect neurological, dermatological and other extrahepatic symptoms of the syndrome. In early post-transplant period attention should be paid to possible temporary worsening of heart failure due to cardiomyopathy associated with CDS.

Clinical Case Summary

Hematopoietic stem cell transplantation (HPSCT) is associated with multiple complications, such as hepatic sinusoidal obstruction syndrome (SOS) (hepatomegaly, ascites, jaundice, and thrombocytopenia) and graft-versus-host disease (GVHD) (skin, gastrointestinal tract and liver are the main targets). These entities may present overlapping clinical findings, being considered differential diagnoses. Coexistence is rare.
A 29-year-old man undergoes HPSCT for acute myeloid leukemia. On day(D)+20, he presents with hyperbilirubinemia (HBR), pleural effusion, ascites, painful hepatomegaly. Ultrasound is suggestive of SOS – Defibrotide was initiated. On D+44, acute cutaneous, intestinal and hepatic GVHD develops. He started methylprednisolone, with analytical improvement. On D+132, worsening cholestasis and abdominal pain. MRCP revealed caliber compromise in several segments of the intrahepatic bile ducts and wall irregularity of the main bile duct. Due to clinical and analytical worsening, he was admitted to the ICU. As he maintained total HBR (30mg/dL) and thrombocytopenia (30,000cell/uL), he underwent an hepatic hemodynamic study (hepatic venous pressure gradient of 10 mmHg) and a transjugular liver biopsy that showed canalicular hepatic cholestasis, bile duct injury and focal hepatocellular necrosis - probable GVHD – and injury to centrilobular veins and centrilobular necrosis - possible SOS. Mycophenolate mofetil was started, but on D+195 the patient died.
This case is notable for its complexity and for demonstrating the rare co-existence of histological aspects of SOS (several weeks after its diagnosis and clinical resolution) and GVHD. Although the clinical and analytical findings may be sufficient for the diagnosis, it is important to highlight the importance of transjugular liver biopsy in patients with severe thrombocytopenia for the characterization and histological confirmation of cholestatic hepatitis, especially when the etiology may be multifactorial.

References

- Ramachandran V, Kolli SS, Strowd LC. Review of Graft-Versus-Host Disease. Dermatol Clin. 2019 Oct;37(4):569-582. doi: 10.1016/j.det.2019.05.014.
- Fan C, Crawford J. Sinusoidal obstruction syndrome (hepatic veno-occlusive disease). J Clin Exp Hepatol. 2014 Dec;4(4):332-46. doi: 10.1016/j.jceh.2014.10.002.
- Matsukuma K, Wei D, Sun K, Ramsamooj R, Chen M. Diagnosis and differential diagnosis of hepatic graft versus host disease (GVHD). J Gastrointest Oncol. 2016 Apr;7(Suppl 1):S21-31. doi: 10.3978/j.issn.2078-6891.2015.036.
- Tuncer H, Rana N, Milani C, Darko A, Al-Homsi S. Gastrointestinal and hepatic complications of hematopoietic stem cell transplantation. World J Gastroenterol. 2012 Apr 28;18(16):1851-60. doi: 10.3748/wjg.v18.i16.1851.
- Corbacioglu S, Jabbour EJ, Mohty M. Risk Factors for Development of and Progression of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome. Biol Blood Marrow Transplant. 2019 Jul;25(7):1271-1280. doi: 10.1016/j.bbmt.2019.02.018.

Clinical Case Summary

Post-procedural haemorrhage following percutaneous liver biopsy is a rare yet potentially life-threatening complication, with fistulisation of a hepatic haematoma into the gastrointestinal tract being an exceedingly rare event.
A 75-year-old lady with suspected autoimmune liver disease underwent an ultrasound-guided percutaneous liver biopsy with a 16G needle, performed in a single pass and no immediate complications. Two hours later, the patient developed haemorrhagic shock and was transferred to the ICU, where a contrast-enhanced CT scan revealed a 10 × 9 cm hepatic haematoma in the right lobe with active arterial extravasation and haemoperitoneum (Figure 1). Angiography confirmed active bleeding from a segmental branch of the right hepatic artery (Figure 2), which was successfully embolised with microcoils (Figure 3).
Follow-up CT scan 45 days later showed persistent encapsulated haematoma with fistulisation to duodenal bulb (Figure 4). Gastroscopy showed no haemorrhagic content through the fistula (Figure 5). Given the patient's stable condition and reviewed by a multidisciplinary team, surgery was not required. Radiological control after three months, shows near-complete haematoma resolution and fistula closure (Figure 6). Autoimmune hepatitis was confirmed, and immunosuppressive therapy deferred until resolution of the acute complication.
Percutaneous liver biopsy is safe, with ultrasound guidance reducing complication risk. The most common adverse event is pain, in up to 25% of cases. Haemorrhagic complications, including haemoperitoneum, hepatic haematoma, or haemobilia, occur in 0.01–0.5% of cases. Haemobilia, the rarest complication (~0.006%), presents with abdominal pain, jaundice, and melaena. In cases of active bleeding, selective arterial embolisation is preferred. Fistulisation into the gastrointestinal tract is rare and usually associated with large haematomas. Early diagnosis and intervention were key to preventing a fatal outcome in this case.

References

Tian G, Kong D, Jiang T, Li L. Complications After Percutaneous Ultrasound‐Guided Liver Biopsy. Journal of Ultrasound in Medicine. 2020 Jan 30;39(7):1355–65.

Clinical Case Summary

A 34 year old female attended electively for liver biopsy for investigation of deranged liver function tests (LFTs).
Ultrasound guided percutaneous liver biospy was complicated by immediate abdominal pain with computed tomography (CT) abdomen revealing right subphrenic intracapsular fluid contained within the liver capsule in keeping with post biopsy haemorrhage. This was managed conservatively with overnight admission for observation.
The patient represented within 48h hours with worsening jaundice and severe abdominal pain. LFTs had significantly worsened with a hyperbilirubinaemia of 153 umol/L with a cholestatic pattern. Repeat CT abdomen showed new intrahepatic and extrahepatic bile duct dilation with common bile duct (CBD) measuring up to 16 mm in diameter. In the lower CBD, there was an obstructing opacity measuring approximately 7 mm in diameters by 24 mm longitudinal and given the clinical history, a blood clot was to be the most felt likely be the underlying aetiology.
Urgent endoscopic retrograde cholangiopancreatography (ERCP) was performed. An initial cholangiogram revealed a dilated biliary system with ill-defined opacity distally. Following sphincterotomy a large clot was extracted with a 12 millimetre balloon. Final cholangiogram showed clearance of bile ducts with no post procedural complications. The next day updated imaging with CT abdomen showed complete resolution of the biliary duct dilatation and LFTs had improved to pre-liver biopsy baseline. The patient was discharged with no further complications.
Discussion: Haemobilia is recognised as a rare complication from percutaneous liver biopsy with incidence rate of less than 1% (1). The management of haemobilia may be conservative in minor cases with transcatheter arterial embolization usually recommended as first line intervention and ERCP used for biliary drainage (2). In this case we demonstrated a successful outcome in biliary decompression following clot extraction with ERCP.

References

(1) Thomaides-Brears, H.B., Alkhouri, N., Allende, D. et al. Incidence of Complications from Percutaneous Biopsy in Chronic Liver Disease: A Systematic Review and Meta-Analysis. Dig Dis Sci 67, 3366–3394 (2022).
(2) Yilmaz N: Hemobilia Causing Acute Cholecystitis and Pancreatitis after Percutaneous Liver Biopsy: A Case Report and Review of the Literature. Visc Med 2020;36:246-250.