Treatment of primary biliary cirrhosis with low-dose weekly methotrexate

Nine women with symptomatic precirrhotic primary biliary cirrhosis have been treated with oral pulse methotrexate, 15 mg/wk, for 12-34 months. Three women had pruritus, two fatigue, and four pruritus and fatigue. Itching disappeared and fatigue lessened or disappeared in all within 4-11 months after starting methotrexate. All who itched were able to discontinue cholestyramine (five) or antihistamines (two). Biochemical tests of liver function improved in all patients and then worsened in three when methotrexate was discontinued or the dose lowered. Mean serum alkaline phosphatase decreased from 471 to 171 U/L (P less than 0.01), serum bilirubin from 0.99 to 0.59 mg/dL (P less than 0.05), and serum alanine aminotransferase from 132 to 61 U/L (P = 0.02), and serum cholesterol fell from 265 to 213 mg/dL (NS). The decrease in serum cholesterol was significant, P = 0.05, if data were used just from the six women whose baseline serum cholesterol levels were elevated. Serum albumin remained normal in all. The serum bilirubin levels became normal in three of four patients with elevated levels. The serum alkaline phosphatase levels became normal in four patients and the alanine aminotransferase levels in three. Liver histology improved in five patients and was stable in the remaining four based on a quantitative evaluation of coded liver biopsy specimens. The improvement in histology was primarily due to decreased portal inflammation and bile duct injury. The titer of antimitochondrial antibody decreased in seven patients. The data suggest that methotrexate may be effective treatment for precirrhotic primary biliary cirrhosis. Controlled trials are needed to evaluate long-term efficacy and toxicity.     

Efficacy of colchicine in patients with primary biliary cirrhosis poorly responsive to ursodiol and methotrexate

OBJECTIVE: Approximately 20-30% of patients with primary biliary cirrhosis (PBC) respond fully to treatment with ursodeoxycholic acid (UDCA). The rest have progressive disease and eventually develop cirrhosis and liver failure. More effective treatment is needed. Methotrexate improved biochemical tests of liver function and liver histology in patients with PBC who had failed to respond to UDCA in one report and induced sustained biochemical and histological remission in another. The role of colchicine in PBC is unclear. We describe three patients with symptomatic PBC who responded very well to the addition of colchicine after they had failed to respond to UDCA alone and in combination with methotrexate. We suggest that colchicine should be tried in PBC patients who clearly fail to respond to UDCA. METHODS: Three patients with symptomatic biopsy-proven, antimitochondrial antibody-positive PBC failed to respond to UDCA and then to the addition of methotrexate. Colchicine was eventually added to the regimen. Symptoms, biochemical tests of liver function, and percutaneous liver biopsies were done at baseline, after treatment with UDCA, UDCA plus methotrexate, and UDCA plus methotrexate plus colchicine. RESULTS: All three patients responded after colchicine was added to UDCA and methotrexate. Symptoms, biochemical tests of liver function, and liver histology improved in all, and blood tests normalized in two. CONCLUSIONS: Colchicine may be effective treatment in some symptomatic patients with PBC who respond incompletely to UDCA alone or in combination with methotrexate. Colchicine may be tried in such patients.     

Colchicine for primary biliary cirrhosis: a Cochrane Hepato-Biliary Group systematic review of randomized clinical trials

OBJECTIVES: Colchicine is used for patients with primary biliary cirrhosis due to its immunomodulatory and antifibrotic potential. The results from randomized clinical trials have, however, been inconsistent. We conducted a systematical review to evaluate the effect of colchicine for primary biliary cirrhosis. METHODS: We identified randomized clinical trials comparing colchicine with placebo/no intervention. We analyzed effects by fixed and random effects model. We investigated heterogeneity by subgroup and sensitivity analyses. RESULTS: We included 10 trials involving 631 patients, four of which were high-quality trials. No significant differences were detected between colchicine and placebo/no intervention regarding mortality (relative risk (RR), 1.21; 95% confidence interval (CI), 0.71-2.06), mortality or liver transplantation (RR = 1.00; 95% CI, 0.67-1.49), liver complications, liver biochemical variables, liver histology, or adverse events. Regarding mortality, an extreme case analysis favoring colchicine did not demonstrate beneficial effects of colchicine, whereas an extreme case analysis favoring placebo/no intervention demonstrated a detrimental effect of colchicine (RR = 2.28; 95% CI, 1.17-4.44). The number of patients without improvement of pruritus significantly decreased in the colchicine group (RR = 0.75; 95% CI, 0.65-0.87). However, this estimate was based on only 156 patients from three trials. CONCLUSIONS: There is insufficient evidence to support the use of colchicine for patients with primary biliary cirrhosis. As we are unable to exclude a risk of increased mortality, we recommend to use colchicine only in randomized clinical trials.     

Methotrexate improves biochemical tests in patients with primary biliary cirrhosis who respond incompletely to ursodiol.

BACKGROUND & AIMS: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of presumed autoimmune etiology. Ursodeoxycholic acid (UDCA), methotrexate, and colchicine each have shown promise in its treatment. The value of combining 2 or 3 of these drugs is uncertain. The aim of this study was to determine whether addition of methotrexate to the treatment regimen improves results of liver biochemical tests in patients with antimitochondrial antibody-positive PBC who responded incompletely to treatment with UDCA and colchicine. METHODS: Methotrexate was added to the treatment regimen of 10 consecutive patients with antimitochondrial antibody-positive PBC who had an incomplete response to therapy with UDCA alone or in combination with colchicine. The primary end point was biochemical response. Symptoms and histological changes were also recorded. RESULTS: Addition of methotrexate to the UDCA plus colchicine regimen was associated with a significant reduction in serum alkaline phosphatase (ALP) levels beyond those found with UDCA and colchicine alone or in combination. Median ALP concentration was 389 IU (range, 247-1013 IU) at baseline, 300 IU (range, 155-467 IU) after treatment with UDCA plus colchicine, and 120 IU (range, 66-351 IU) after treatment with methotrexate. CONCLUSIONS: Addition of methotrexate to a regimen of UDCA and colchicine may be beneficial for patients with PBC who respond incompletely to treatment with UDCA and colchicine.     

A randomized controlled trial of colchicine plus ursodiol versus methotrexate plus ursodiol in primary biliary cirrhosis: ten-year results

Primary biliary cirrhosis frequently progresses despite treatment with ursodeoxycholic acid (UDCA), the only approved therapy. Previous studies suggested that colchicine and methotrexate may improve biochemical tests of liver function, symptoms, and liver histology. The aim of the present study was to determine if the addition of colchicine or methotrexate to UDCA would improve survival free of liver transplantation. Eighty-five patients with histologically confirmed primary biliary cirrhosis whose serum alkaline phosphatase levels were at least twice the normal level and who were not yet candidates for liver transplantation were randomly assigned to receive colchicine or methotrexate in a double-blind study. UDCA was administered to all patients after 2 years. The primary end point was survival free of liver transplantation. Patients were followed up for a total of up to 10 years or until treatment failure. Data were analyzed on an intention-to-treat basis. Transplant-free survival was similar in both groups: 0.57 for colchicine plus UDCA and 0.44 for methotrexate plus UDCA, results that are similar to those predicted by the Mayo prognostic model. Significant improvement in liver biochemical tests and liver histology was observed in a subset of patients in both treatment groups who remained in the study for all 10 years. In conclusion, neither colchcine plus UDCA nor methotrexate plus UDCA improved survival beyond that predicted by the Mayo prognostic model. However, clinical, histologic, and biochemical improvement observed among those who remained in the study for 10 years suggests a possible benefit of these drugs in a subset of patients.     

Pilot Study of Low Dose Oral Methotrexate Treatment for Primary Biliary Cirrhosis

Objective: To assess the efficacy of low doses of oral methotrexate as therapy for primary biliary cirrhosis. Methods: Ten symptomatic patients with this disease were treated with methotrexate at a dose of 15 mg/wk in an open label trial. Results: Eight patients completed 1 yr of treatment and six completed 2. Pruritus and fatigue decreased in all patients treated for at least 1 yr. Mean levels of serum alkaline phosphatase, ALT, and IgM were less at 1 and 2 yr than corresponding baseline means. Total serum bilirubin increased in three patients during treatment. Serum aminotransferases and alkaline phosphatase became normal in one patient with stage I disease. Although liver biopsies at 1 and 2 yr revealed a decrease in the intensity of the Inflammatory infiltrate, they also showed an increase in fibrosis suggestive of disease progression. Methotrexate was discontinued in five patients: for disease progression in four (one at 4 months, one at 1 yr, and two at 2 yr) and for intractable pruritus in one (at 4 months). All patients experienced transient mucositis and intermittent dyspepsia. Conclusions: These findings suggest that methotrexate treatment in patients with primary biliary cirrhosis is not beneficial in patients with advanced disease; in patients with early disease, methotrexate may be associated with amelioration of symptoms, reduction in serum biochemical indices of liver disease, and reduction in hepatic inflammation. However, prospective, randomized, controlled trials will he necessary for definitive evaluation of the effects of methotrexate on the quality of life and survival of patients with primary biliary cirrhosis.     

Methotrexate therapy for primary biliary cirrhosis

OBJECTIVE: Preliminary data suggested possible benefits of methotrexate in primary biliary cirrhosis. We assessed the effectiveness of methotrexate use in primary biliary cirrhosis and its tolerance in patients with this disease. METHODS: A total of 110 primary biliary cirrhosis patients began methotrexate 15 mg/wk; for most, ursodeoxycholic acid was added during the study. We analyzed data from patients completing 5 yr of treatment with methotrexate to assess its effect on biochemical and histologic parameters after 5 yr of therapy. Based on an intent to treat analysis, we also compared survival of our patients (n = 110) with that of patients in a previously published, placebo-controlled trial of ursodeoxycholic acid (n = 180). RESULTS: Only half of the study group completed 5 yr of methotrexate therapy. Therapy did not prevent progression of disease, as indicated by a rising Mayo risk score. Portal fibrosis tended to remain the same. Methotrexate did not diminish the risk of death or liver transplantation when compared with ursodeoxycholic acid or placebo; however, ursodeoxycholic acid use decreased the risk of death or transplant (p = 0.006). CONCLUSIONS: Methotrexate is not well tolerated in primary biliary cirrhosis. The toxicity of methotrexate and its inability to prevent complications of progressive liver disease or improve survival and the need for liver transplantation limits its utility. The benefits of ursodeoxycholic acid were again confirmed.     

熊去氧胆酸治疗原发性胆汁性胆管炎患者疗效及对血清Nrf2和HO-1水平的影响

目的 探讨熊去氧胆酸(UDCA)治疗原发性胆汁性胆管炎和肝硬化(PBC)患者疗效及对血清核因子相关因子2(Nrf2)和血红素加氧酶-1(HO-1)水平的影响.方法 2017年1月～2020年1月我院诊治的原发性胆汁性胆管炎患者31例和原发性胆汁性肝硬化患者34例(Child A级15例,Child B级12例,Chil...     

A controlled trial of colchicine in primary biliary cirrhosis. Trial design and preliminary report

Colchicine (1 mg/day), or an identical placebo, was given to 64 patients with primary biliary cirrhosis in a double-blind controlled trial. Due to a novel, pair-matched trial design, the two groups were exceptionally well matched at entry. In comparison with placebo, colchicine produced a beneficial effect on serum albumin and bilirubin levels at 3 months in patients who had abnormal liver function (bilirubin greater than 20 mumol/l) at entry: (albumin, P = 0.047; bilirubin, P = 0.022). In patients with normal liver function at entry (bilirubin less than 20 mumol/l), beneficial effects were noted on total globulin levels at 3 months (P = 0.013) and on immunoglobulin G levels at 3 and 6 months (P = 0.044 and 0.001, respectively). At 18 months, survival estimate in the colchicine and placebo groups were 84% and 69%, respectively. The difference did not reach significance. Colchicine produced an early improvement in liver function and immunoglobulin levels. Few serious side effects were encountered, and colchicine clearly merits long-term study in the treatment of primary biliary cirrhosis.     

熊去氧胆酸及其联合激素和免疫抑制剂治疗原发性胆汁性肝硬化的临床观察

目的 观察熊去氧胆酸(UDCA)、UDCA联合泼尼松龙、UDCA联合硫唑嘌呤3种方案治疗对原发性胆汁性肝硬化(PBC)的疗效,并评价影响疗效的危险因素.方法 82例初诊PBC患者随机分为单用UDCA(U组,28例)、UDCA联合泼尼松龙(UP组,27例)、UDCA联合硫唑嘌呤(UA组,27例)3个治疗组,在治疗第0、3、6、12个月采集临床、实验室资料及药物不良反应.主要采用重复测量的方差分析和COX回归进行统计学处理.结果 UP组患者较U组及UA组在乏力和瘙痒程度上有明显改善(P=0.015和P=0.037),U组、UA组无改善.3组患者治疗后丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)、谷氨酰转肽酶(GGT)、总胆红素、直接胆红素(DBIL)和IgM均下降,组内比较差异有统计学意义(P＜0.05),3组间比较差异无统计学意义(P＞0.05).发生疾病进展的患者Mayo危险性评分高(P=0.018)、凝血酶原时间(PT)延长(P=0.042).UP组血糖升高2例、满月脸5例、多毛1例;UA组白细胞下降2例,胆绞痛1例,U组未出现药物不良反应.ALP、GGT、总胆固醇基线水平高是生化缓解的危险因素(P=0.015).总胆红素、DBIL、总胆汁酸增高、PT延长不利于肝生化缓解(P=0.075).结论 3种方案对PBC患者肝脏生化指标、IgM的改善作用相近,UDCA联合泼尼松龙方案可减轻乏力、瘙痒症状,单用UDCA方案不良反应发生率最低.Mayo危险性评分高、PT延长的患者疾病易进展;高水平的ALP、GGT、总胆固醇是生化缓解的危险因素;高水平的总胆红素、DBIL、总胆汁酸、PT不利于生化缓解.

Abstract：

Objective The aims of this study were to compare the clinical and laboratory responses to ursodeoxycholic acid (UDCA) monotherapy with the combination therapy of UDCA plus prednisolone/azathioprine in primary biliary cirrhosis(PBC),and to investigate the risk factors affecting the therapeutic responses.Methods Eighty-two patients with untreated PBC were divided randomly into three groups.Group U (28 patients) received UDCA alone,group UP(27 patients) received UDCA and pr ednisolone,while group UA (27 patients ) received UDCA and azathioprine.The clinical and laboratory data were recorded after treated for 3,6 and 12 months.Repeated measures ANOVA and COX regression model were used for statistical analysis.Results Fatigue and pruritus were improved only in group UP(P=0.015 and P=0.037 respectively).Alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),gamma-glutamyl transferase (GGT),total bilirubin (TBIL),direct bilirubin (DBIL) and IgM in the 3 groups were decreased (P＜0.05),while there was no statistical significant difference between the three groups (P＞0.05).The patients with disease progression had higher Mayo risk score (MRS) (P=0.018) and prolonged prothrombin time (PT)(P=0.042).In group UP,side-effect associated with glucocorticosteroids occurred in eight patients while there was no side-effect in group U.High baseline levels of ALP、GGT and CHO were risk factors for biochemical remission(P=0.015).The increase of DBIL,TBIL,total bile acid(TBA) and PT did not contribute to the prediction of biochemical remission ( P=0.075 ).Conclusion There are no differences among the three groups in the improvement of hepatic biochemical data and IgM.The combination therapy of UDCA with prednisolone could relieve fatigue and itching.The disease of patients with higher Mayo risk score and prolonged PT tend to progress.High baseline levels of ALP,GGT and CHO are risk factors for biochemical remission.High baseline levels of TBIL,DBIL,TBA and PT could not predict biochemical remission.The incidence of adverse effect is lowest when treated with UDCA alone.     

Colchicine reduces procollagen Ⅲ and increases pseudocholinesterase in chronic liver disease

AIM:To test whether colchicine would be an effective antif ibrotic agent for treatment of chronic liver diseases in patients who could not be treated with α-interferon.METHODS:Seventy-four patients(46 males,28 females) aged 40-66 years(mean 53±13 years) participated in the study.The patients were affected by chronic liver diseases with cirrhosis which was proven histologically(n=58);by chronic active hepatitis C(n=4),chronic active hepatitis B(n=2),and chronic persistent hepatitis C(n=6).In the four patient...     

不同方案治疗原发性胆汁性肝硬化合并干燥综合征的临床研究

 目的 观察不同方案治疗原发性胆汁性肝硬化（PBC）合并干燥综合征（SS）的疗效。方法 选PBC合并SS患者79例,分为3组:单用熊去氧胆酸组（U组,29例）、熊去氧胆酸+泼尼松龙组（UP组,37例）、熊去氧胆酸+硫唑嘌呤组（UA组,13例）,观察不同治疗方案的疗效。 结果3种方案对PBC合并SS患者的乏力、瘙痒均有明显改善,但组间比较差异无统计学意义（P值均＞0.05）;3种方案治疗后ALT、AST、碱性磷酸酶（ALP）、γ-谷氨酰转移酶、TBil、DBil、IgG、IgM均有明显下降,组内比较差异有统计学意义（P值均＜0.05）,但组间比较差异无统计学意义（P值均＞0.05）。结论 PBC合并SS以肝脏受累为主要表现时应以治疗PBC为主,熊去氧胆酸联合糖皮质激素或硫唑嘌呤治疗未发现优于单用熊去氧胆酸。     

Long-term follow-up of patients with primary biliary cirrhosis on colchicine therapy

We followed up a group of patients with primary biliary cirrhosis who participated in a 4-yr prospective, double-blind controlled trial of colchicine therapy for 4 additional years. All were placed on open label colchicine (0.6 mg twice daily) after the trial was concluded. Of the original group of 28 patients treated with colchicine, 8 died and 5 received transplants (3 of the 5 died). Of the original placebo control group eight patients died and six received transplants (1 of the 6 died). Surviving patients on long-term colchicine therapy (mean period = 8.1 yr, range = 5.3 to 9.1) showed reduction of mean serum alkaline phosphatase from 5.1 times the upper limit of normal values to 1.9 times (p less than 0.01). Mean ALT fell from 1.8 to 1.2 times the upper limit of normal (p = 0.05), and mean serum total bilirubin remained stable (1.6 mg/dl vs. 1.5 mg/dl). Major complications of cirrhosis developed in four patients in the colchicine group and five patients in the original control group. The only side effect of colchicine was diarrhea, which was noted in three patients. The diarrhea resolved with reduction in the dose of colchicine. Colchicine is a safe and inexpensive drug for the long-term treatment of primary biliary cirrhosis. The biochemical parameters of disease activity (alkaline phosphatase and ALT) remain improved after long-term follow-up, and bilirubin values remain stable. However, complications of cirrhosis, deaths and transplantations were not prevented. The clinical usefulness of colchicine in the treatment of primary biliary cirrhosis seems to be limited.     

A novel treatment for refractory primary biliary cirrhosis?

BACKGROUND/AIMS: Bezafibrate is naturally used for hyperlipidemia worldwide. In 1992 Day et al reported that the value of ALP and gamma-GTP in hyperlipidemia declined after administering bezafibrate orally. We conducted a study to investigate whether or not ALP and gamma-GTP in primary biliary cirrhosis which is characterized by the elevation of these enzymes improved after taking bezafibrate. METHODOLOGY: We administered bezafibrate additionally for 6 months to 13 patients with primary biliary cirrhosis (refractory PBC) whose liver enzymes (ALP or gamma-GTP) did not remain within normal range out of 21 patients treated by monotherapy of ursodeoxycholic acid for 18 months. RESULTS: At 2, 4, and 6 months, gamma-GTP level significantly decreased compared with that prior to the initiation of bezafibrate. At 4 and 6 months, ALP level significantly decreased compared with that prior to the initiation. At 2, 4 and 6 months, ALT level significantly decreased compared with that prior to the initiation. The value of IgG and IgM was also reduced significantly 6 months after the initiation. CONCLUSIONS: If the effectiveness of bezafibrate for primary biliary cirrhosis is confirmed histologically and by a randomized trial, a combination therapy of bezafibrate and ursodeoxycholic acid appear to be the medical treatment of choice for primary biliary cirrhosis in the future.     

二次自体骨髓干细胞移植治疗失代偿期肝硬化与首次移植对比研究

目的 比较失代偿期肝硬化患者行自体骨髓干细胞二次移植与首次移植对肝功能的影响。方法2007年5月至2009年12月在沈阳军区总医院住院治疗的45例失代偿期肝硬化患者,分为首次移植组和二次移植组。首次移植组23例患者均经内科治疗,症状平稳后行经股动脉自体骨髓干细胞移植术。二次移植组的22例患者则在首次移植后4～12个月行第二次干细胞移植。所有患者均于每次自体干细胞移植后第4、8周复查血常规、凝血指标及肝功能生物化学指标。结果 二次自体骨髓干细胞移植8周后,肝功能多项指标明显改善,血浆白蛋白(Alb)由移植前的(37.26±5.90) g/L升至(42.49±4.80) g/L(P＜0.01),丙氨酸转氨酶(ALT)由（57.05±45.51）U/L降至（44.86±29.19）U/L(P＜0.05),天冬氨酸转氨酶(AST)由（53.73±24.98）U/L降至(39.14±15.07) U/L(P＞0.05);凝血功能各项指标明显好转,凝血酶原时间由（16.15±3.01）s降至(14.63±2.32) s(P＜0.01),纤维蛋白原(Fib)由(2.44±0.61) g/L升至（3.00±0.81）g/L(P＜0.01)。与首次移植组患者同期相比,二次移植组移植8周后血浆Alb水平进一步升高,由（38.00±6.33）g/L升至(42.49±4.80) g/L(P＜0.05),AST、ALT也明显改善,两组间差异有统计学意义,同时Child-Pugh B级患者的评分由(7.22±0.67)分降至（6.67±0.71）分(P＜0.05)。二次干细胞移植后,部分凝血指标及胆红素与首次移植组相比差异无统计学意义,但与干细胞移植前相比仍有改善。结论失代偿期肝硬化患者行二次自体骨髓干细胞移植可进一步改善肝功能,维持肝硬化症状的缓解期。     

The AST/ALT ratio as an indicator of cirrhosis in patients with PBC.

OBJECTIVES: A non-invasive, simple and non-expensive test to predict cirrhosis would be highly desirable. The aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio has been proven to be such an indicator of cirrhosis in alcoholic liver disease, hepatitis C. AIM: To test whether the AST/ALT ratio is a marker of cirrhosis also in patients with primary biliary cirrhosis (PBC). METHODS: The study consisted of 160 patients. In 126 patients, we had clinical and laboratory data at the time of diagnosis and follow-up with outcome: liver-related death, liver transplantation and survival. In 121 patients, we had laboratory data and liver histology. RESULTS: We found that the AST/ALT ratio was significantly higher in cirrhotic patients than in non-cirrhotic patients. A high AST/ALT ratio was significantly associated with esophageal varices and ascites. In a multivariate analysis, bilirubin and ALP were predictors of poor prognosis. CONCLUSION: The AST/ALT ratio seems to be of clinical value as a hint to the diagnosis of cirrhosis in patients with PBC but not as a prognostic factor.     

原发性胆汁性胆管炎与肝硬化患者临床指标差异分析

目的 探讨原发性胆汁性胆管炎(PBC)与原发性胆汁性肝硬化患者临床指标的差异。方法 2015年5月～2021年9月我院诊治的PBC患者164例,其中胆管炎组70例,肝硬化组94例。收集临床指标,应用Logistic回归分析影响PBC患者疾病进展的相关危险因素。结果 本组肝硬化患者年龄为(58.6±13.0)岁,显著大于胆管炎组【(53.4±11.1)岁,P<0.05】;血清谷丙转氨酶、谷草转氨酶、碱性磷酸酶、总胆红素分别为49.7(27.5,80.2) U/L、62.6(44.9,114.7) U/L、156.8(126.5,230.5) U/L和31.5(17.6,88.4)μmol/L,显著高于胆管炎组【分别为39.3(23.9,66.0) U/L、36.4(26.8,63.4) U/L、126.5(94.8,187.3) U/L和14.6(10.0,24.3)μmol/L,P<0.05】;肝硬化组血清抗核抗体和抗gp210抗体阳性率分别为91.5%和43.6%,显著高于胆管炎组的80.0%和25.7%(P<0.05);肝硬化组血清IgG、IgA和IgM水平分别为...     

22例原发性胆汁性肝硬化的临床分析

目的 研究原发性胆汁性肝硬化（PBC）的临床特点、实验室检查、治疗转归，提高对PBC的认识。方法 分析22例PBC的临床表现、实验室检查及治疗转归。结果 22例PBC中女性20例，发病平均年龄51岁，主要症状包括皮肤瘙痒、乏力、纳差、腹痛，主要体征包括黄疸、肝大、脾大、腹水，实验室检查以ALP、高GGT、高胆红素血症、高球蛋白血症、存在多种自身抗体如抗线粒体抗体（AMA）、AMA－M2及抗核抗体（ANA）等，多数患者血ALT、AST升高，所有患者血清AST高于ALT。出现症状至临床确诊时间为2月－5年，平均8个月。治疗采用以熊去氧胆酸（UCDA）为主的综合方法，治疗3个月后ALP及TBil下降达50％以上者有12例，72．7％症状改善，死亡2例。结论 PBC以中年女性多，以肝脾肿大、黄疸、瘙痒、乏力为主要临床表现，肝功能异常以胆汁淤积为主，伴有高球蛋白血症及自身抗体；UCDA能够改善患者的症状和部分肝功能异常。     

不同类型自身免疫性肝病患者肝组织炎症因子表达的变化

目的 探讨不同类型自身免疫性肝病(AILD)患者肝组织炎症因子表达的变化。方法 2016年12月～2018年12月我院肝病科收治的AILD患者74例,其中自身免疫性肝炎(AIH)患者19例,原发性胆汁性肝硬化(PBC)患者42例,自身免疫性肝炎/原发性胆汁性肝硬化重叠综合症(AIH/PBC OS)患者13例。采用免疫组化法检测肝穿组织白介素-12(IL-12)、IL-17和干扰素-γ(IFN-γ)表达情况。结果 AIH、PBC和AIH-PBC OS患者血清ALT水平分别为(132.5±12.5)U/L、(40.1±8.4)U/L和(166.2±16.3)U/L,AST水平分别为(120.3±11.7)U/L、(52.8±5.6)U/L和(194.7±18.3)U/L,差异显著(P<0.05);血清ALP水平分别为(98.0±9.2)U/L、(323.5±30.9)U/L和(257.1±24.1)U/L,血清GGT水平分别为(49.1±4.7)U/L、(236.8±22.6)U/L和(376.7±35.5)U/L,差异显著(P<0.05);AIH、PBC和AIH-PBC OS组患者肝组织IL-12表达阳性率无统计学差异(分别为15.8%、7.1%和15.4%,P>0.05),肝组织IL-17阳性表达率无统计学差异(分别为73.7%、76.2%和76.9%,P<0.05),肝组织IFN-γ阳性表达率无统计学差异(分别为68.4%、85.7%和76.9%,P<0.05);AIH患者血清抗肝肾微粒体I型抗体(LKM-1)、抗可溶性肝抗原/肝胰抗原抗体(SLA/LP)阳性率分别为21.1%和10.8%,均显著高于PBC组或AIH-PBC OS患者(分别为0.0%和0.0%,和0.0%和0.0%,P<0.05);PBC患者血清抗sp100抗体阳性率为19.0%,显著高于AIH组(0.0%)或AIH-PBC OS患者(7.7%,P<0.05);AIH-PBC OS组血清抗gp210抗体阳性率为38.5%,显著高于AIH组(0.0%,P<0.05),AIH-PBC OS组患者血清抗线粒体M2抗体(AMA-M2)阳性率为100.0%,显著高于AIH组(0.0%)或PBC组(73.8%,P<0.05);AIH患者血清ANA和SMA阳性率分别为94.7%和78.9%,显著高于PBC患者(分别为19.0%和19.0%,P<0.05)。结论 不同类型AILD患者血清自身抗体呈交叉阳性现象,肝组织炎性因子检测对鉴别诊断没有意义,常规肝功能指标仍对诊断起关键作用。     

70例原发性胆汁性肝硬化患者的临床特点分析

目的 探讨原发性胆汁性肝硬化（PBC）患者的临床特点.方法 回顾性分析2008年1月至2013年3月诊断为PBC的住院患者70例,记录患者的首诊症状、肝功能情况、AMA 亚型抗体（M2、M4、M9）以及3例病理结果,并对ALT、AST、ALP、GGT增高的程度进行秩和检验,采用Wilcoxon法.结果 84.3%为女性患者,平均年龄（59.2±8.7）岁.主要的临床表现为乏力25.7%,皮肤瘙痒24.3%,右胁不适18.6%,腹胀18.6%.生化学异常以GGT[（324.5±250.4）U/L]、ALP[（381.1±259.0）U/L]增高最明显.GGT增高5倍以上的患者较多,与ALT、AST、ALP相比差异有统计学意义（u值分别为-5.861、-4.036、-4.445,P均为0 000）,AST、ALP增高2倍以上的患者亦较ALT多（u值分别为-4.405、-3.625,P均为0.000）.87.1%的患者AM2A阳性; AM4A阳性占31.4%,AM9A阳性占11.4%.结论 PBC是女性多见的以GGT、ALP增高为明显的慢性肝功能损害,AMA抗体亚型（M2、M4、M9）的阳性是诊断该病的重要依据.