Although a variety of organs can be involved in SLE, damage to digestive system organs is less common, especially liver damage. Hepatic involvement in SLE can be classified as primary (SLE related) and secondary (non-SLE related). Secondary antiphospholipid syndrome (APS), secondary Sjogren's syndrome, Raynaud's phenomenon or anti-ribosomal P antibodies have been found to be associated with the development of SLE-related liver damage [2-4]. Non-SLE related hepatic involvement in patients with SLE is usually a result of drug-induced liver injury, fatty liver, viral hepatitis, or rarely due to an overlapping autoimmune liver disease. After exclusion of secondary causes, hepatitis due to SLE may be seen in 3%–5% of cases [5]. SLE-related hepatic abnormalities are usually synchronous with disease activity [6]. A recent study by Zheng et al [7] based on their strict discrimination criteria reported a 9.3% incidence of lupus hepatitis among the 504 SLE patients that were evaluated. They also reported that the prevalence of lupus hepatitis in patients with active SLE was higher than those with inactive SLE (11.8% vs 3.2%) [7]. The patients with hepatic involvement due to SLE mostly showed mild to moderate elevations of serum transaminase levels. Large multicenter studies of mortality in SLE have shown that hepatitis was not a major cause of morbidity or mortality [8, 9]. Therefore, even the latest SLE classification criteria published in 2019 by EULAR and the American College of Rheumatology (ACR) [10] did not consider hepatic involvement relevant for establishing a diagnosis of SLE, and none of the measurement tools included any liver criteria to evaluate disease activity. This exclusion was probably due to the rarity of primary hepatic involvement and the benign, transient course of these abnormalities [11].

However, in recent years, there have been some reported cases of severe liver damage due to SLE, such as non-cirrhotic portal hypertension (NCPH), cirrhosis and even liver failure [12]. According to the literature search by Yang QB et al., 22 cases of NCPH associated with SLE were reported from 1994 to 2017 [13]. Pulmonary arterial hypertension (PAH) and pancytopenia (PCP) were also observed in 18.2% (4/22) of patients. Portal thrombosis was not detected in any of the patients. Ten (45.5%) of those patients did not have hepatic dysfunction according to clinical laboratory tests. Furthermore, the majority of patients had nodular regenerative hyperplasia (NRH, 16/22), shown by hepatic histopathology. NRH usually presents with clinical symptoms of NCPH with normal liver function tests, and imaging studies could support a diagnosis, but it is confirmed definitively with a liver biopsy and histopathological findings. HU Rong-rong et al. [14] summarized retrospectively the clinical data of 12 SLE-NCPH patients admitted to Peking Union Medical College Hospital between 1996 to 2013, and they reported no neuropsychiatric complications in the NCPH-SLE group, while thrombocytopenia in the NCPH-SLE group occurred more frequently than in the control group. HU Rong-rong et al. [14] also found that the effects of steroids and immunosuppressive agents had minimal effect in improving portal hypertension (PHT). The prognosis of SLE patients was affected by complications of portal hypertension and PHT management may have been helpful in relieving their symptoms. In 2020, You H et al. [15] conducted a case-control study, and a total of 21 patients with SLE cirrhosis were enrolled. You H et al. [15] found that cirrhosis was a rare and severe subtype of SLE with a poor prognosis, and more attention should be paid to those patients with hematological system involvement and impaired liver function.

The exact pathogenesis of SLE-related liver damage, especially NCPH and cirrhosis remains unclear. The deposition of immune complex and complement in the vascular wall might cause vasculitis in the liver, lumen partial or complete occlusion leading to liver cell necrosis and regeneration, followed by the formation of NRH and NCPH which eventually develops into cirrhosis [16, 17]. Vasospasms caused by Raynaud's phenomenon, microthrombosis caused by coagulation disorders with positive anti-phospholipid antibodies, and some immunosuppressants (cyclophosphamide, azathiopine) might be high risk factors for the development of NCPH [17].

This patient had a short medical history and no history of drug abuse or alcohol addiction. Routine blood tests did not show any abnormalities. There was no increase in blood ammonia or decrease in coagulation function (instead, hypercoagulability was found), and liver function indexes were within the normal range. Sjogren's syndrome, Raynaud's phenomenon and pulmonary hypertension were secondary to SLE. Other hepatic diseases such as viral hepatitis and hepatolenticular degeneration were excluded based on the patient’s laboratory results and medical history. Therefore, the patient was diagnosed with active SLE complicated by SLE related NCPH according to her clinical features and auxiliary investigations [18], despite the lack of liver histopathology due to the patient’s refusal for a liver biopsy. Of note, the diagnosis of NCPH was also supported by the patient’s response to treatment.

The diagnostic criteria for neuropsychiatric systemic lupus erythematosus (NPSLE) was proposed by the ACR in 1999, including 19 neurological syndromes (12 central and 7 peripheral NP) [19]. NPSLE is one of the most serious disorders in SLE and is usually associated with a poor prognosis. It has been reported that an acute confused state, seizures, and cerebrovascular disease in NPSLE were risk factors that affected survival [20]. The incidence of NPSLE ranged from 12.2% to 94.7% for SLE patients [21, 22], and stroke was reported to occur in 3%–30% of patients with SLE, most of which were ischemic strokes [23]. The diversity and heterogeneity of NP presentations suggested that multiple pathogenetic mechanisms such as antibodies, cell-related inflammation, cytokine-related inflammation, complement activity and the presence of secondary APS were involved in NPSLE [24,25]. Previous studies showed that NPSLE usually occurred within 3 years after onset of SLE [25, 26], and high disease activity was likely associated with diffuse NP manifestations of the central nervous system [27]. However, NPSLE may precede lupus or may occur during latent phase in some patients, which may be related to the regional immune inflammation of the nervous system.

Cranial magnetic resonance imaging (MRI) is still the most commonly used imaging technique for detecting and evaluating NPSLE in clinical practice. Abnormal cranial MRI results were divided into inflammatory lesions, small vessel disease (SVD), and large vessel disease (LVD) [25]. The prevalence of inflammatory lesions ranged from 0% to 38.1% in patients who underwent MRI [28, 29]. A previous study showed that inflammatory lesions might be related to cerebral vasculitis in SLE patients, which can be diffuse or have focal distribution, involving both the large and small arteries [30]. According to the standards for reporting vascular changes observed on neuroimaging, SVD was divided into white matter hyperintensity, subcutaneous small infarcts, luminal infarction, microbleeding, and brain atrophy [31]. LVD, defined as cerebral infarction in the great arteries area, was described according to the number of lesions (single/multiple), related arteries, and status (acute/chronic) [25]. Patients with inflammatory lesions and LVD on MRI may have poorer prognoses [25].

In this young woman, NP events caused by other diseases such as cardiogenic thromboembolism, central nervous system infections, metabolic abnormalities, neoplasm, trauma, electrolyte imbalance and toxic exposure were excluded. Active SLE was considered to be the cause of multiple acute cerebral infarctions, and immunosuppressive therapy for NPSLE was effective in improving her brain lesions. Vasculitis, which was suggested by imaging, might be the possible cause of her acute cerebral infarctions. The APS related antibody spectrum was not extensively tested for in this patient, so secondary APS could not be completely excluded.