Liver disease complicating Familial Mediterranean Fever: a study on 66 patients out of 533 adult from the JIR cohort

First author: M. DELPLANQUE et al,

Journal: Liver International

Link to the article: https://doi.org/10.1111/liv.16232

Abstract:

Background: Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease, associated with MEFV mutations. FMF patients can experience liver involvement, potentially leading to cirrhosis.

Objectives: This study aimed to evaluate liver involvement in FMF patients at a French tertiary center for adult FMF.

Methods: We conducted an observational study with FMF patients displaying 2 pathogenic MEFV mutations at the Adult National Reference Centre for Autoinflammatory Diseases and Inflammatory Amyloidosis (CEREMAIA) in Paris and included in the JIR cohort. MEFV heterozygous patients and those with other liver disease causes were excluded.

Results: Among 533 FMF patients 12.4% had chronic liver abnormalities, with 30% who developed cirrhosis 54 years [36-57] in median after disease onset. Forty-seven percent were colchicine resistant, and 41% received interleukin-1 inhibitors. Cirrhotic patients experienced delayed hepatopathy diagnosis, prolonged FMF diagnosis delay, and late-onset treatment initiation compared to those with only liver function test abnormalities. Colchicine resistance and interleukin-1 inhibitor use were more common in cirrhotic patients. Body mass index and AA amyloidosis rates did not differ significantly between groups. Twenty-one patients undergone liver biopsies including 14 cirrhotic patients revealing steatohepatitis in 12 cases and probable steatohepatitis in 4. Other lesions, like iron overload and sinusoidal dilatation, were sporadically observed.

Conclusion: FMF patients are at risk of chronic liver disease. Regular liver function monitoring is crucial, particularly in case of persistent inflammation, due to the risk of progression to cirrhosis and its associated morbidity and mortality.

Lay Summary

More than, 10% of FMF patients develop chronic liver abnomalities over time and 4% cirrhosis. High-risk includes those with 2 MEFV mutations and colchicine resistance and chronic liver disease often begins after age 55 in FMF patients. In FMF patient with impaired liver function optimizing treatment targeting chronic inflammation is a key point in their care.

Liver biopsy of FMF patient

a. Liver biopsy with cirrhosis (sirius red staining)

b. Same liver biopsy with steatohepatitis associating steatosis, hepatocellular ballooning and inflammation (H&E staining)

Biopsie du foie d'un patient atteint de FMF

Complications of cirrhosis in FMF patients

(A) Esophageal varices visualized by upper gastrointestinal endoscopy

(B) Hepatomegaly and ascite of a cirrhotic FMF patient detected in an abdominal CT scan

(C) Hepatomegaly and ascite of a cirrhotic FMF patient detected in an abdominal CT scan

Complications de la cirrhose chez les patients atteints de FMF

Table 1. Demographic and clinical characteristics of the enrolled cohort.

Data are presented as median [Q1-Q3]. N= number of patients

††CRP C protein reactive, BMI Body Mass Index, FMF Familial Mediterranean fever, W women, M men

Table 4. Complication and Child Pugh Score of FMF patients with cirrhosis (n=20)

Transjugular intrahepatic portosystemic shunts (TIPS)

(% among cirrhotic patients)

Liver Disease Complicating Familial Mediterranean Fever.

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Efficacy and safety of targeted therapies in VEXAS syndrome: retrospective study from the FRENVEX

First author: Hadjadj et al.

Link to article: DOI: 10.1136/ard-2024-225640

Summary:

Study Objective:

To assess the efficacy and safety of targeted therapies in VEXAS syndrome, an adult-onset autoinflammatory disease associated with somatic mutations in the UBA1 gene.

Methodology:

A multicenter retrospective study including 110 patients who received at least one targeted therapy. Complete response (CR) and partial response (PR) were defined based on specific clinical and biological criteria.

Results:

A total of 110 patients received 194 targeted therapies: 78 (40%) JAK inhibitors (JAKi), 51 (26%) IL-6 inhibitors, 33 (17%) IL-1 inhibitors, 20 (10%) TNFα blockers, and 12 (6%) other targeted therapies.

At 3 months, the overall response rate (CR and PR) was 24% with JAKi, 32% with IL-6 inhibitors, 9% with IL-1 inhibitors, and 0% with TNFα blockers or other targeted therapies.

At 6 months, the overall response rate was 30% with JAKi and 26% with IL-6 inhibitors.

Treatment-free survival was significantly longer with JAKi compared to other targeted therapies.

Among patients who discontinued treatment, reasons included primary failure, secondary failure, serious adverse events, or death, with varying rates depending on the therapy.

Conclusions:

JAK and IL-6 inhibitors show clinical benefits, while other therapies demonstrate lower efficacy. These findings require confirmation in prospective trials.

Genetic and clinical features of Familial Mediterranean Fever in a cohort of patients with kidney failure

First author: Ahmed Sheyyab

Journal: Journal of Nephrology

Link to the article: doi.org/10.1007/s40620-025-02272-y

Author of the abstract: Rim BOURGUIBA

Introduction

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease worldwide. In its classic form, it is mainly associated with mutations in exon 10 of the MEFV gene. AA amyloidosis is the most severe complication of FMF.

The aim of this study was to compare the frequency of MEFV variants in hemodialysis patients versus healthy controls in a Mediterranean country, Jordan.

Methods

This was a cross‑sectional study including 78 patients with end‑stage kidney disease on hemodialysis and 201 healthy controls in Jordan. All patients underwent Sanger sequencing for the main MEFV variants. The following variants were tested: p.E148Q, p.P369S, p.F479L, p.M680I (G/C), p.M680I (G/A), p.I692del, p.M694V, p.M694I, p.K695R, p.V726A, p.A744S, and p.R761H.

Patients carrying a variant were then clinically assessed according to the Tel‑Hashomer criteria. Five underwent rectal biopsy to detect amyloidosis.

Results

Among dialysis patients, 16% had at least one MEFV variant versus 12.9% in the control group (not significant). The two most frequent mutations in the hemodialysis group were M694V (p = 0.035) and V726A (p = 0.009). The variants detected in both groups are summarized in Table 1. In the control group without renal failure, 22 individuals were heterozygous for the E148Q variant. Three patients met diagnostic criteria for FMF, and one case of AA amyloidosis was confirmed by biopsy.

Conclusion

FMF is the most common autoinflammatory disease in Mediterranean countries, yet it remains underdiagnosed even in high‑risk populations. This diagnostic delay leads to complications, notably AA amyloidosis. This study shows that 4% of hemodialysis patients were diagnosed with FMF. It also confirms the non‑pathogenic nature of the E148Q variant, which was detected in 22 healthy, asymptomatic individuals.

Overall, these findings underscore the importance of testing for MEFV mutations in patients with AA amyloidosis in countries where FMF is highly prevalent, in order to offer appropriate treatment to prevent AA amyloidosis and progression to renal failure.

Genetic and clinical features of familial Mediterranean fever in a cohort of patients with.

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