Introduction

Macrophage activation syndrome (MAS), also known as secondary hemophagocytic lymfohistiocytosis (HLH) is poorly described life-threatening condition. It is caused by excessive activation of immune system with subsequent proinflammatory state resulting in multiorgan involvement. Clinically, MAS is characterized by fever, cytopenia, hepatosplenomegaly and elevated circulating ferritin. MAS can develop into acute liver failure (ALF) with poor prognosis.

Aims & Methods

We retrospectively analysed patients referred to our transplantation centre for ALF in whom the diagnosis of MAS was confirmed by histology. We focused on diagnosis leading to MAS, survival, transplantation outcome and clinical, laboratory and histological findings.

Results

From January 2005 to November 2022, we found eight patients with MAS referred to our centre for ALF. The underlying condition was EBV infection in five cases and adult Still disease in three cases. All eight patients had strongly elevated circulating ferritin (in average 19321 μg/l), leukocytosis and thrombocytopenia. All patients except one had at least one negative bone marrow or lymph node examination prior to definitive diagnosis of MAS. Seven patients were treated with high-dose corticosteroids. Four patients met King's College criteria for urgent liver transplantation. Two of them were transplanted. Despite intensive therapy based on mechanical ventilation, continuous renal replacement therapy and circulation support, their clinical condition further deteriorated and all four patients died on average 34 days after symptom onset of multiorgan failure. At the autopsy, hemophagocytic macrophages have been described in multiple organs. Four patients who responded to corticosteroid therapy are in long-term remission after specialized haematological treatment with etoposide.

Conclusion

Macrophage activation syndrome represents rare cause of acute liver failure with high mortality, it is difficult to diagnose and even harder to treat. Our case series suggests that when the patients meet King's College criteria, they die despite the successful liver transplant. Therefore, it is important to carefully consider liver transplantation in these patients.

Clinical Case Summary

A 58-year-old female patient with a history of repeated colon resections for fistulizing Crohn's disease on biological therapy with vedolizumab, comes in for dark urine and jaundice. Laboratory examination revealed elevated obstructive enzymes and bilirubin. Sonography showed dilated intrahepatic and extrahepatic bile ducts without signs of choledocholithiasis. We perform endoscopic retrograde cholangiopancreatography (ERCP) with papillotomy. Cholangiogram shows irregular dilated left-sided bile ducts and unclear findings in the hilum area. A brush cytology was taken and a stent was inserted into the right-sided bile ducts. Reactive changes of biliary epithelia in inflammatory terrain were found in brush cytology. MRCP shows pathological masses in the hepatic junction, which have a higher signal than bile in T1W, similar changes in a short section of dist. choledochus just above the papilla. We performed a second ERCP with wedge biopsy and brush cytology from both hilum and distal choledochus, which were evaluated as malenoma metastasis. A review of the patient's medical history revealed the removal of malignant melanoma of the skin 7 years ago. The extent of the disease did not allow surgical resection and the patient was referred to a specialized centre for oncological treatment.
Conclusion: Metastasis of melanoma in the common bile duct is an extremely rare cause of jaundice. It should be thought of in patients with obscure masses in the bile ducts with hyperintense signal on T1W MR sequences. Taking a thorough medical history is particularly important.

Introduction

Primary sclerosing cholangitis (PSC) is a chronic liver disease causing inflammation of the bile ducts, forming progressive strictures and stenoses of bile ducts resulting in recurrent cholangitis, liver cirrhosis and death. Liver transplantation (LT) is necessary for most of the patients as the only curative treatment. However, about 30% of patients develop recurrence of PSC (rPSC), which negatively impacts the outcome of liver grafts and patients. The pathogenesis of recurrent disease is multifactorial, but not entirely understood.

Aims & Methods

The aim of this study was to evaluate the risk factors for rPSC and graft failure (GF) in patients after LT for PSC and PSC/AIH overlap syndrome. Furthermore, we evaluated the patient survival, graft survival and the patient survival after post-LT. In this single-centre retrospective study (IKEM, Prague, Czech Republic), we included patients who underwent LT for PSC in our transplant centre between 1996-2019.

Results

A total of 160 patients after LT for PSC and PSC/AIH overlap syndrome were included in the study. Biliary strictures after LT developed in 67 (41.88%) patients, of which 16 (23.88%) were anastomotic. rPSC was confirmed in totally 51 (31.87%) patients. The mean time to diagnosis of rPSC was 6.2 (CI 95% +- 1.04) years. In multivariant analysis of risk factors for rPSC: Cytomegalovirus (CMV) infection (HR 3.21; 95% CI 1.43-7.19), at least one episode of acute cellular rejection (ACR) (HR 3.00; 95%CI 1.00-9.03) and length of hospitalization after LT (HR 1.03; 95% CI 1.01-1.05) were statistically significant predictors of rPSC.
Liver retransplatation (reLT) due to GF was performed in 23 patients (15.22%). The cause of GF was as follows: rPSC in 18 patients (78.26%), hepatic artery thrombosis in 2 patients (8.69%), primary graft dysfunction in 2 patients (8.69%) and persistent biliary leak in 1 patient (4.35%). The median time to reLT due to rePSC was 8.59 (IQR 6.84,13.81) years. Furthermore, 3 patients required 2nd reLT and 1 patient 3rd reLT. In multivariant survival analysis, CMV infection after LT (HR 5.00; 95%CI 1.22-20.5), PSC/AIH overlap syndrome (HR 6.4; 95% CI 1.13-36.4) and length of hospitalization after LT (HR 1.04; 95%CI 1.01-1.07) were significant predictors for GF. Overall survival of patients in 5 years after LT was 89.5%.

Conclusion

Based on our results, ACR, CMV infection and length of hospitalization post-LT were significant risk factors for rPSC. PSC/AIH overlap syndrome, length of hospitalisation post-LT and CMV infection were associated with worse liver graft outcome.

Introduction

Recurrence of primary sclerosing cholangitis (rPSC) is a common long-term complication after liver transplantation (LT), which affect graft survival and overall patient survival. There are several lines of evidence indicating that dysregulation of the microbiome and intestinal barrier dysfunction are key etiologic factors in the pathogenesis of PSC.

Aims & Methods

The aim of this cross-sectional study was to evaluate serological markers of intestinal barrier permeability in patients with PSC after LT and in control group, to determine potential biomarkers for rPSC. The control group consisted of LT recipients for alcohol-related liver disease and/or hepatocellular carcinoma. The rPSC was assessed by MRCP and/or biopsies, all patients underwent colonoscopy. Serum levels of iFABP, Zonulin and Reg3a were evaluated. Non-parametric tests were used to for initial assessment. We further built generalized linear models for the prediction of PSC diagnosis independent of recurrence (Model_1), for the prediction of non-rPSC (Model_2) and for the prediction of rPSC (Model_3) using all three permeability markers, BMI and faecal calprotectin as predictors.

Results

A total of 113 patients were included in the study after LT for PSC and 69 controls. The clinical characteristics of the study participants are listed in Table 1. No significant difference in median of concentrations of Reg3a was found between the PSC group and control group (p=0.01). Interestingly, medians of concentrations of iFABP (p<0.01) and (p<0.0001) Zonulin were significantly higher in the control group in comparison with PSC group. The ROC AUC for Model_1 for prediction of PSC diagnosis per se was 0.79. The increased probability of PSC occurrence was associated with higher Reg3a serum concentration, while a negative relationship was found between the probability of PSC occurrence and BMI, zonulin and iFABP. Model_2, prediction of PSC without recurrence (non-rPSC), achieved slightly better performance, ROC AUC = 0.83, but the predictors and their coefficients and OR were close to Model_1. The ROC AUC for Model_3 predicting rPSC was 0.73. In contrast to previous models, BMI, Reg3A and iFABP were not significantly associated with rPSC, while both higher serum concentrations of zonulin and calprotectin increased the probability of PSC recurrence.

Table 1. - Cohort characteristics

Conclusion

Recurrence of PSC was positively associated with the intestinal permeability marker zonulin and the inflammatory marker calprotectin, while it was independent of BMI, iFABP and Reg3a.

Clinical Case Summary

​Introduction: With approximately 100 cases annually, leptospirosis is among the rarest zoonotic infectious diseases in Germany. It is caused by Leptospira bacteria, which are transmitted through contact with contaminated water or soil. While most infections are self-limiting, some progress to sepsis and multiorgan failure.
Case report: We report the case of a previously healthy 44-year-old man who presented to the emergency department with fever and diarrhoea. Laboratory tests revealed liver failure with hyperbilirubinemia, coagulopathy, and renal dysfunction. Due to his deteriorating condition and unexplained organ failure, he was admitted to the intensive care unit. His clinical status worsened further, requiring endotracheal intubation due to respiratory insufficiency. CT imaging showed bilateral pneumonia and thickened colonic walls. To improve oxygenation, prone positioning was applied. Microbiological testing detected Leptospira in both blood and urine. Treatment with meropenem led to clinical improvement, and the patient was extubated after seven days. Interestingly post-extubation the patient presented tetraplegia and aphasia, which gradually improved. Brain MRI and lumbal puncture did not show any relevant abnormalities.
Conclusion: Icteric leptospirosis affects approximately 5–10% of symptomatic cases and can progress rapidly, with a mortality rate between 5–15%. In cases of moderate to high clinical suspicion, empiric treatment should be initiated promptly, even before laboratory confirmation. This case illustrates a rare and severe presentation of leptospirosis with multiple organ involvement and transient neurological deficits. Clinicians should consider leptospirosis in the differential diagnosis of acute liver failure and refer severe cases promptly to specialised intensive care centers.