| Research backgroundSystemic lupus erythematosus(SLE) is a diffuse connective tissue disease which can influences multi-system of the body. SLE distributes widely and its incidence changes with different region, race, gender and age. Its incidence in young women and in the colored race was significantly high. The etiology and pathogenesis of SLE is not clear. In recent years, a large number of studies suggest that the pathogenesis of systemic lupus erythematosus is related to polygenic inheritance, metabolic abnormality of sex hormone and somatotropin, EB virus infection and some environmental factors. Through the role of autoimmune mediated, large amounts deposition of antibodies and immune complex in connective tissue caused corresponding organ damage. The majority of SLE patients show an insidious onset. The natural courses of SLE are subacute and chronic and often in the form of alternating from disease exacerbation to remission. Its symptoms are various and complex. In the early stage, only one or two systems are involved in SLE, and its performances are fever, rash, hair loss, mouth and nose mucous membrane ulcer, individual joint inflammation, platelet reduce purpura. With the disease progress, the RBC, WBC and PLT will be reduced. What is more, a plurality of joint swelling and pain, migraine, cognitive impairment, abdominal pain, diarrhea, lung qualitative change, pleural inflammation, hematuria, proteinuria will appear. Only a small number of patients are subclinical lupus or in light state in long-term.Systemic lupus erythematosus can cause multiple systems involvement. About 40% of SLE patients can be merged with digestive system damage, such as common for nausea, vomiting, difficulty swallowing, abdominal pain, diarrhea and others. Some serious patients can present as surgical acute abdomen, such as mesenteric vasculitis, stomach and 12 intestinal ulcer, acute pancreatitis, liver cirrhosis, lupus peritonitis and ascites and so on. Liver has a dual blood supply and plays an important role in the metabolism of protein, carbohydrate and a lot of drugs. In addition, the liver, the role of immune tolerance, is a target organ bound to immune mediated damage. So the liver can be affected in systemic autoimmune disease, such as granuloma disease, rheumatic diseases, malignant tumors and circulatory system diseases. The lupus liver involvement is one of the common digestive system diseases in SLE. And its incidence rate is up to 20%-52%. Two reasons are considered to result in the etiology and pathogenesis of liver involvement in systemic lupus erythematosus. One is the deposition of immune complexes and complement induced by vasculitis, and the liver cell inflammation. The other may be Budd Chiari syndrome which caused by hepatic vein and (or) inferior vena cava occlusion occlusive. The symptoms of liver involvement in systemic lupus erythematosus may only show abnormal liver function, such as elevated transaminase and alkaline phosphatase, or asymptomatic enlargement of the liver, while most of the patients appeared different degree of nausea, vomiting, abdominal pain, tired of greasy, a few appear double lower limbs edema, jaundice, abdominal water. Its clinical symptoms may appear as the first symptom of systemic lupus erythematosus, or appear gradually in the course of the disease.The diagnosis of lupus liver involvement is not difficult according to the clinical manifestations and auxiliary examinations.However, the diagnosis should to exclude other possible causes of liver damage, such as drugs, virus, biliary tract disease, hemolytic, other connective tissue diseases, especially autoimmune hepatitis. Autoimmune hepatitis is an inflammatory liver lesion with hypergammaglobulinemia and autoantibodies. The main identification between lupus liver involvement and autoimmune hepatitis are clinical manifestations, autoantibodies and liver pathologies. Autoimmune hepatitis usually presents not typical butterfly lesions, arthritis, serositis, blood system damage, but it often has hepatitis history, obvious hepatosplenomegaly and higher positive rate of anti-smooth muscle antibody and anti-liver kidney microsome antibody. And the histopathological features of autoimmune hepatitis often shown periportal infiltration of lymphocytes and plasma cells and boundary plate inflammation, but histopathology of lupus hepatitis often have no specificity, mainly showing fatty infiltration.Autoantibody in blood is another important feature of systemic lupus erythematosus. According to the present studies, there is a close correlation between antibodies and systemic lupus erythematosus. Some antibodies have important reference values and guiding significance. For example, the specificity of anti-ds-DNA antibody in the diagnosis of lupus was as high as 90%, and the level of anti-ds-DNA antibody is in parallel with the degree of disease activity, which can be used to detect the change of the disease and observe the curative effect of the drugs. The routine screening of anticardiolipin antibody, anti- β 2-GPI and lupus anticoagulant can significantly help to the diagnosis of antiphospholipid syndrome in the onset SLE patients. Anti Ro/SSA and anti La/SSB antibodies can cause neonatal lupus and atrioventricular block, such as congenital heart disease. Patients with positive anti Ro/SSA and anti La/SSB antibodies may show light allergies, vasculitis, purpura, lymph node enlargement and other clinical manifestations. In conclusion, the detection of antibodies provides an effective hint for the diagnosis of SLE and its various systems symptoms. The correlation between positive rate of each antibody and clinical manifestations is very valuable for clinical diagnosis and treatment. The correlation of lupus liver damage and antibodies is still not clear. Present studies suggest that lupus liver damage is related to anti-ribosomal P protein strongly. It is extremely rare to find high titers of anti-smooth muscle antibody and anti-mitochondrial antibody. But there are also studies suggest that anti-ribosomal P antibodies is extremely high specific in systemic lupus erythematosus. What is more, it is related to lupus nephritis, nervous system damage in systemic lupus erythematosus, and lupus liver involvement. But only exclusion of lupus nephritis and lupus nerve nervous system damage, the diagnosis diagnostic value of antibody for lupus liver involvement is important. In addition, it is also reported that there is a correlation between anti-Ul-nRNP antibodies and lupus liver damage.The rate of lupus liver involvement is lower. In clinical works, the majority of physicians think lupus liver damage is not SLE major comorbidities.The liver function abnormal in SLE patients did not cause enough attention. Misdiagnosis or delay diagnosis in SLE patients may happen, when liver damage was the initial presentation of SLE.ObjectiveAccording to the observations of systemic lupus erythematosus (SLE) patients with or without liver damage, their general conditions, the clinical manifestations, laboratory findings, image characteristics have been studied, we analysised the risk factors for the occurrence of SLE liver damage. To observe the clinical effects of drug treatment of SLE liver damage, we analyzed the factors that may be related to the prognosis, and try to provide objective basis and new ideas for the diagnosis and prevention for the disease.Subjects and MethodsFor the study,422 systemic lupus erythematosus patients were selected retrospectively from the Department of Rheumatology of Nanfang Hospital from January 2010 to May 2015.All the patients were consistent with the 1997 American College of Rheumatology (ACR) SLE classification standard revision. Among the 422 cases, there were 84 liver damage cases, but 33 cases were excluded for other causes (drug induced liver damage, and Sjogren syndrome scleroderma, myositis causing liver damage of connective tissue disease, biliary disease cause liver damage, viral hepatitis, fatty liver, heart failure secondary to hepatic congestion, hemolytic anemia, schistosomiasis liver damage). The remaining 51 systemic lupus erythematosus patients with liver involvement were grouped into case group, and the other 338 SLE patients without liver damage were grouped into control group. The gender, age, course of disease, primary and general conditions of two groups patients was recorded. What is more, the clinical manifestations of all the patients were observed such as Raynaud’s phenomenon, oral ulcer, photosensitivity, neurological damage, kidney damage, heart damage, lungs damage, blood system damage, gastrointestinal damage. The clinical manifestations of the case group patients were observed such as fatigue, anorexia, nausea, vomiting, abdominal pain, abdominal distension, skin and sclera yellow dye, skin itching, spider angioma, ascites. Laboratory data were collected including liver function (alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), glutamyltranspetidase (gamma GT), total bilirubin (Tb), the ratio of serum albumin and globulin (A/G)), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), triglyceride (TG), total cholesterol (TC), the determination of autoantibodies including anti-nuclear antibody (ANA), anti-double stranded DNA antibody (ds-DNA), anti Jo-1 antibody (Jo-1), anti SSB, anti Ul-nRNP antibody (SSB) (U1-nRNP) antibody and anti-ribosomal P protein antibody (ARPA/Rib-P) and proliferating cell nuclear antigen (PCNA) antibody, anti-mitochondrial antibody (AMAM2), anti-centromere antibody (CENP-B), anti PM-scl antibody (PM-scl), anti Scl-70 antibody and anti SSA antibody (Scl-70) (SSA), anti-nucleosome antibody (Anua), ant- histone antibody (AHA), anti-recombinant antibody Ro-52 Ro-52 and humoral immunity in six including complement 3 (C3), complement 4 (C4), immunoglobulin protein A (IGA), immunoglobulin M protein (IgM), immunoglobulin protein G (IgG), total compensation activity of 50 (CH50). According to the liver ultrasound or CT results, We told whether the patients had abnormal echo and structural abnormalities, portal hypertension, merger of biliary calculi, inflammation and other diseases or not. The liver pathologic biopsies were observed. In addition, all the patients were assessed by SLEDAI (Lupus Erythematosus Disease Activity Index Systemic) score, as a standard to assess the severity of the disease. For all the data, variance homogeneity test was conducted for the measurement data, if there were homogeneity, two sample t test was conducted. Their results was showed by x±s. If there were non-homogeneity, two independent samples nonparametric test (Mann Whitney U test) was conducted. Their results were showed by number and percentage; count data for chi square test. Logistic regression analysis was conducted for the case group and control group. P values and 95% confidence intervals were used to explore the risk factors for the occurrence of liver damage. Among the 51 cases of lupus patients with liver damage, there were 37 cases accepted regular treatment. Among the 37 cases, drugs of treatment, the time when the patient’s liver function improved or returned to normal were recorded. Independent sample of non-parametric test was used to analysis the relationship between glucocorticoid dosage and treatment effects of liver function, and the relationship between the different course of disease and the treatment effects of liver function. All the data were processed by software SPSS19.0.Results1 Clinical features of systemic lupus erythematosus with liver damage1.1 General characteristics of systemic lupus erythematosus liver damage:a total of 51 cases, including 3 males and 48 females, aged 13-64 years old, aged 13-64 years old, mean age (30.57+13.81) years old. The average SLEDAI score was (10.4 +6.38) points, there are 24 cases (47.1%) scored more than 10 points.1.2 Clinical manifestation of Liver damage in patients with systemic lupus erythematosus:there were 422 patients with systemic lupus erythematosus,84 patients with liver damage (19.9%), of which 51 cases (12.1%) were caused by systemic lupus erythematosus. In the case group of 51 patients, there are 30 cases (58.8%) patients with no obvious symptoms and signs,14 cases (27.4%) patients had fatigue, anorexia and nausea and vomiting,10 cases (19.6%) patients appeared pain, bloating or liver area unwell,5 cases patients (9.8%) appeared skin and sclera yellow dye, skin itching,1 case (2%) patients presented with ascites,1 case (2%) patients appeared portal hypertension. Only one patient underwent liver biopsy, its pathological examinations showed that diffuse hepatocytes hydropic degeneration and periportal fibrous tissue hyperplasia and a large number of lymphocytes and a few plasma cells infiltration. There were 4 case were diagnosed of liver cirrhosis in our hospital by B ultrasound or CT examination.1.3 The treatment and the prognosis of systemic lupus erythematosus with liver damage:In the case group of 51 patients,, there were 37 cases hospitalized and timely given Hugan Lidan, non-steroid anti-inflammatory drugs, glucocorticoids and (or) immunosuppressive. The liver function of 20 patients (54%) returned to normal in 2 weeks,9 cases (24%) patients returned to normal from 3 weeks to 2 months. For 8 cases (22%) patients, multiple indicators of liver function were still higher than normal when discharged from the hospital referral, or more than half a year. There was no difference between the duration of disease and the treatment effect. Statistical results showed that there was no significant difference in patients with different course of disease(x2=1.445, v= 3, P=0.695). In glucocorticoid therapy,5 patients were given small doses,13 patients were given moderate doses,13 patients were treated with large doses,6 patients were treated with steroid pulse therapy (0.5g/d) for 3 days. To compare the effects of different steroid dosages on the recovery time of liver function, the results showed that there was no significant difference in the therapeutic effects of patients with different course of disease(x2=0.589, v=3, P=0.899).21 cases were treated by immunosuppressive, of which 9 patients given cyclophosphamide (intravenous drip,0.4g/2 weeks). For 4 patients, liver function returned to normal within 2 weeks,2 patients returned to normal within 3 weeks to 2 months,3 cases of liver function in patients with no obvious improvement or aggravation.2. The comparison between the case group (systemic lupus erythematosus with liver damage group) and the control group (non-liver damage group)2.1 The comparison of the general characteristics of the two groups:Compared with patients without liver damage, there was no significant difference of gender, age, but duration≤3 months (62.8%/35.2%, P<0.05), onset (51%/37.3%, P<0.05), SLEDAI score high (10.4 ± 6.38/7.5 ± 5.37, P<0.05) were significantly different.2.2 The clinical manifestations between the two groups:a comparison was made between the case group and control group, neuropsychiatric lupus system involvement with the proportion of 21.6%vs 5.9%(P< 0.05), infection with the proportion of 19.6%vs 8.3%(P< 0.05), lupus blood system damage with the proportion of 72.5%vs 48.5%(P< 0.05). There were no significant difference of the other clinical manifestations such as Raynaud’s phenomenon, oral ulcer, photosensitivity, hair loss, arthritis, lupus and nervous system damage, lupus nephritis, lupus cardiac involvement, Lupous pulmonary damage, lupus gastrointestinal damage, between the case group and the control group.2.3 The comparison of serologic results:serological results were statistically analyzed between the case group and control group. We found that the proportion of ESR≥20mm/1h was 84.3% vs 71.2%(P< 0.05), the proportion of complement C3 ≤0.4 g/L was 52.9%vs.25.1%(P< 0.05), the proportion of complement C40.1 g/ L was 54.9%vs 38.2%(P< 0.05), the proportion of CH50≤23U/ml was 41.2%vs 26.2%(P< 0.05),and the proportion of triglyceride≥1.7mmol/L was 45.1%vs 24.9% (P< 0.05). They were all statistically significant. There were no significant difference of fourteen autoantibodies including anti-ds DNA antibody, anti-Sm antibody, anti-Ul-nRNP antibody, ARP/Rib-P antibody, ANA M2 antibody and AnuA antibody, anti-SSB antibody, anti-SSA antibody, anti-PCNA antibody and anti-ScL-70 antibody, anti-PM-scl antibodies to, CENP-B antibody, anti-AHA antibody, anti-ro-52 antibody positive rate (P> 0.05).2.4 Risk factors analysis of cases:logistic regression analysis results showed that, the duration≤3 months, lupus neuropsychiatric involvement, lupus blood system involvement, positive anti-Ul-nRNP antibody and decreased complement C3, were independent risk factors for SLE liver damage (P< 0.05, exp (b)> 1).Conclusions(1) The lupus liver involvement patients often showed elevated liver enzymes, a few of which may develop cirrhosis. (2) More attention should be paid to the oneset intensive SLE patients who had a higher risk of liver damage. The lupus liver involvement patients have higher degree activity of SLE and are often accompanied with lupus neuropsychiatric involvement and blood system involvement. (3) The positive rate of anti U1-nRNP antibody was higher in the patients with lupus liver damage, and may be related to the occurrence of liver damage. (4) If the lupus liver involvement patients were given standardized treatment, liver function can return to normal within two months and the prognosis would be relatively good. |
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