Interest and Limits of Systematic Liver Fibrosis Screening in Psychiatric Hospital using Free Biologic Marker FIB4: 26 Months Period Results

Introduction

FIB-4 (Fibrosis-4 index) is a biomarker of the risk of severe hepatic fibrosis (i.e., F3 or F4 fibrosis). The FIB-4 is based on a simple, free algorithm, available on the internet, which is calculated thanks to the patient’s age, platelet rate and transaminases. The frequency of conducting biological tests on the same day (transaminases and platelets) and the free use of the algorithm make it a useful and easy screening tool in the general population. FIB-4 is a simple and free biomarker for diagnosing advanced liver fibrosis. The calculation of the FIB-4 index requires knowledge of age, ALT and AST transaminases and platelet rate. It is simple and free to diagnose advanced liver fibrosis, using the following thresholds [1]:

a) FIB-4 < 1.30 excludes clinically significant hepatic fibrosis.

b) >1.3 and < 2.67 (<65years) intermediate risk.

c) >2 and <2.67 (>65years) intermediate risk.

d) FIB-4 > 1.45/1.3 indicates additional explorations, for example impulse elastometry (FIBROSCAN).

e) 67 high risk of significant fibrosis.

f) >3.25 advanced hepatic fibrosis and requires full hepatological assessment.

Actually, FIB4 can correctly identify patients with severe fibrosis (F3-F4). FIB4 1.45 has a negative predictive value of 93.7%. FIB4 > 4 has a positive predictive value of 66%

Why Screen for Hepatic Fibrosis in a Psychiatric Hospital?

We have many data in FIB4 screening in general population but not in psychiatric patients. However, liver diseases are common in psychiatric patients who combine risk factors: alcohol, overweight and metabolic syndrome, hepatitis C and/ or B, hepatotoxic drugs [2-6].

Current Use of the FIB4

In the case of metabolic liver diseases, the most common situation in psychiatric settings, the French Association for the Study of the Liver made the following recommendations in 2020 [1]:

a) Hepatic fibrosis should be assessed in all patients with one or more metabolic risk factors, particularly in patients with type 2 diabetes (B1).

b) Assessment of hepatic fibrosis should use a single blood marker (FIB-4, NAFLD Fibrosis Score, eLIFT, Forns Score) as the first line (B2).

c) The NAFLD Fibrosis Score should not be used in the specific situation of screening for hepatic fibrosis in the diabetic population (B1).

d) A specialized blood marker (Fibrometer®, Fibrotest®, ELF®) or liver elasticity measurement should be performed as a second line if the simple blood marker suggests the presence of advanced chronic hepatopathy (B1).

e) A specialized consultation should be requested if the specialized eel marker or liver elasticity measurement confirms a possible advanced chronic liver disease (B1).

The psychiatric hospital (CHP) of Thuir serves a basin of nearly 500,000 inhabitants in the department of Pyrénées-Orientales. It is sometimes a place of life but also a potential place of screening. It has 382beds and the 2022 annual active queue is 1434 hospitalized patients (average length of stay 29days). A bimonthly nursing permanence of the Mobile Hepatitis Team of the Hospital Center (general) de Perpignan was set up in 2018 to carry out FIBROSCAN according to a validated protocol of task delegation and a partnership established with the biology laboratory of the CHP for the monitoring of viral serologies B or C positive. A bimonthly hepatology consultation on site completed the device. It appeared to us after internal discussion that screening for hepatic fibrosis could be useful on a large scale. We have described our actions in drugs users and psychiatric patients in previous articles and detailed in Table 1 for HCV patient linkage to care (Table 1) [7,8].

Table 1: HCV Patients linkage to care.

Patients and Methods

An (almost) systematic biological assessment is carried out at the CHP including the biological parameters necessary for the calculation of FIB-4. After informing psychiatrists and general practitioners of the CHP, it was established on October 1, 2020, the automated calculation of the FIB-index4 on all biologics including the determination of transaminases and blood platelets to detect advanced liver fibrosis in hospitalized patients. There was no need for any changes in prescriptions or additional examinations. We chose the threshold of 1.45 validated in the literature as pathological threshold. Patients with FIB-4>1.45 were referred for a FIBROSCAN performed by a nurse from the general hospital, as part of a validated protocol of interprofessional cooperation. If an equivalent F3F4 fibrosis was detected in FIBROSCAN, they were referred to hepatology consultation on site (Figure 1).

Figure 1: FIB4 calculator.

Results

In 26 months, 2251 FIB4 measurements were performed in hospitalized patients with an average value of 0.88 (extreme 0.09-10.23) and an average age of 57.2 years, 60% of men, average BMI of 27.1. In 268 patients (11.9%) had a value greater than 1.45 of which 129 (48%) had a FIBROSCAN. The other people got out of hospital too fast to have this exam (Tables 2,3).

Table 2: General Results.

Table 3: CPK values.

Eighty-seven 87 patients (67%) were classified F0F1, including 7 with excessive alcohol consumption (OH), 1 diabetic, 16 steatosis, 1 hemochromatosis, 3 carriers of hepatitis C (HCV) and 60 with rhabdomyolysis (average CPK 2081); 27 patients were classified F2 (21%) including 4 OH, 5 diabetics, 4 steatosis, 1 hemochromatosis and 13 with rhabdomyolysis (mean CPK 1185); 6 patients were classified F3 including 4 OH, 4 diabetics and 1 steatosis; 9 patients were classified F4, that is to say at the stage of cirrhosis including 7 OH, 3 diabetics, 5 steatosis, 1 HBV and 5 HCV. None of the F3 or F4 patients had rhabdomyolysis. All patients with rhabdomyolysis had multiple intramuscular injections in the previous 3 days. In addition, 105 patients with fatty liver had a CAP probe measurement: 60 patients had a value <240dB/m, 19 between 240 and 280dB/m and 26>280dB/m. All patients with fibrosis estimated to be greater than or equal to F3 or severe steatosis were seen in specialized consultation at the psychiatric hospital site.

Discussion

There are no major studies on the use of FIB4 as a method of systematic screening for hepatic fibrosis in psychiatric hospitals in France. In our study, severe hepatic fibrosis is more common in psychiatric patients than in the general population. The prevalence of patients with significant fibrosis (greater than F2) after FIBROSCAN was 1.9%, severe fibrosis F3F4 0.7%. In a general population study in the Alpes Maritimes (2), the prevalence of a high FIB4 was 1.7%. and that of a significant fibrosis on FIBROSCAN of 13 out of 62 patients (21%). In a study conducted by Bordeaux University Hospital, the prevalence of pathological FIB4 was 7.3%; 45% of these patients had FIBROSCAN, with significant fibrosis in 40% of patients. Consideration of the confounding factor rhabdomyolysis by increasing transaminases for a non-hepatic cause is not reported in the literature.

Conclusions

Biological screening for hepatic fibrosis in psychiatric hospitals is feasible and useful for individualizing patients with moderate or severe fibrosis. The FIB4 allows to select patients to have a FIBROSCAN. The place of the CAP probe remains to be specified in this population at high risk of NASH. Rhabdomyolysis induced by intramuscular injections is an overestimation factor that requires a second measure before affirming the existence of chronic hepatopathy. After FIBROSCAN realization, follow up of these patients will be done according to the EASL/AASLD and BAVENO recommendations [9-11].

Sources of Funding

No specific credit has been dedicated to this study carried out with the operating funds of the Hospitals of Perpignan and Thuir.

Acknowledgement

None.

Conflict of Interest

None.

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