原发性胆汁性肝硬化伴系统性硬化症的临床特点与预后

背景与目的：原发性胆汁性肝硬化（PBC）伴系统性硬化症（SSc）的预后仍不十分清楚，该研究拟对其临床特点及预后进行评估。方法：从一个含580例患者的PBC数据库中选出43例PBC伴SSc患者，同时为每例PBC—SSc患者匹配2例单纯PBC患者作为对照，监测初次就医时的血清胆红素浓度。结果：局限皮肤型SSc者40例（93％）。诊断PBC时的中位年龄为49．7岁，胆红素浓度为17μmol／L，白蛋白水平为40．5g／L。24例（56％）患者于SSc后在中值为4．9年发生PBC。配对患者诊断PBC时的中位年龄为53．2岁、胆红素浓度为12μmol／L、白蛋白水平为41g／L。两组患者中位随访时间相似：PBC—SSc组为3．16年，单纯PBC组为4．8年。PBC—SSc患者南于较少接受移植手术（HR0．068；P：0．006），在校正性别、年龄、胆红素对数及碱性磷酸酶等因素后，其移植术或死亡风险（HR0．116；P=0．01）均明显降低，同时胆红素上升的比例亦较低（P=0．04）。     

Long-term ursodeoxycholic acid therapy for primary biliary cirrhosis: a follow-up to 12 years

BACKGROUND: It is uncertain whether ursodeoxycholic acid therapy slows down the progression of primary biliary cirrhosis, according to two meta-analyses. However, the randomized trials evaluated had only a median of 24 months of follow-up. AIM: To evaluate long-term ursodeoxycholic acid therapy in primary biliary cirrhosis. METHODS: We evaluated 209 consecutive primary biliary cirrhosis patients, 69 compliant with ursodeoxycholic acid and 140 untreated [mean follow-up 5.79 (s.d. = 4.73) and 4.87 (s.d. = 5.21) years, respectively] with onset of all complications documented. Comparison was made following adjustment for baseline differences according to Cox modelling, Mayo and Royal Free prognostic models. RESULTS: Bilirubin and alkaline phosphatase concentrations improved with ursodeoxycholic acid (at 36 months, P = 0.007 and 0.018, respectively). Unadjusted Kaplan-Meier analysis showed benefit (P = 0.028), as 44 (31%) untreated and 15 (22%) ursodeoxycholic acid patients died or had liver transplantation. However, there was no difference when adjusted by Cox modelling (P = 0.267), Mayo (P = 0.698) and Royal Free models (P = 0.559). New pruritus or fatigue or other complications were not different, either before or after adjustment for baseline characteristics. CONCLUSIONS: Long-term ursodeoxycholic acid therapy did not alter disease progression in primary biliary cirrhosis patients despite a significant improvement in serum bilirubin and alkaline phosphatase consistent with, and similar to, those seen in ursodeoxycholic acid cohorts in randomized trials.     

Clinical features and prognosis of primary biliary cirrhosis associated with systemic sclerosis

BACKGROUNDS AND AIMS: To evaluate the prognosis of primary biliary cirrhosis (PBC) together with systemic sclerosis (SSc), as this is unknown. METHODS AND RESULTS: A PBC database of 580 patients identified 43 with PBC and SSc: two patients with PBC alone were matched to each PBC-SSc patient for serum bilirubin concentration at the initial visit. Forty (93%) patients had limited cutaneous SSc. At diagnosis of PBC, median values were: 49.7 years, bilirubin 17 micromol/l, and albumin 40.5 g/l. Liver diagnosis occurred a median 4.9 years after SSc in 24 (56%) patients. In matched patients, median values at diagnosis were: 53.2 years, bilirubin 12 micromol/l, and albumin 41 g/l. Median follow up was similar: 3.16 years (PBC-SSc) and 4.8 years (PBC alone). The risk of transplantation or death from diagnosis, adjusting for sex, age, log bilirubin, and alkaline phosphatase was significantly lower in PBC-SSc (hazard ratio 0.116, p=0.01) due to less transplantation (hazard ratio 0.068, p=0.006). The rate of bilirubin increase was less in PBC-SSc (p=0.04). Overall survival was similar (hazard ratio 1.11, p=0.948); there were nine deaths (21%) in PBC-SSc (six SSc related and two liver related) and nine (11%) in PBC alone (six liver related). CONCLUSIONS: Liver disease has a slower progression in PBC-SSc compared with matched patients with PBC alone.     

Ascertainment of acute liver injury in two European primary care databases

Purpose

The purpose of this study was to ascertain acute liver injury (ALI) in primary care databases using different computer algorithms. The aim of this investigation was to study and compare the incidence of ALI in different primary care databases and using different definitions of ALI.

Methods

The Clinical Practice Research Datalink (CPRD) in UK and the Spanish “Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria” (BIFAP) were used. Both are primary care databases from which we selected individuals of all ages registered between January 2004 and December 2009. We developed two case definitions of idiopathic ALI using computer algorithms: (i) restrictive definition (definite cases) and (ii) broad definition (definite and probable cases). Patients presenting prior liver conditions were excluded. Manual review of potential cases was performed to confirm diagnosis, in a sample in CPRD (21 %) and all potential cases in BIFAP. Incidence rates of ALI by age, sex and calendar year were calculated.

Results

In BIFAP, all cases considered definite after manual review had been detected with the computer algorithm as potential cases, and none came from the non-cases group. The restrictive definition of ALI had a low sensitivity but a very high specificity (95 % in BIFAP) and showed higher rates of agreement between computer search and manual review compared to the broad definition. Higher incidence rates of definite ALI in 2008 were observed in BIFAP (3.01 (95 % confidence interval (CI) 2.13–4.25) per 100,000 person-years than CPRD (1.35 (95 % CI 1.03–1.78)).

Conclusions

This study shows that it is feasible to identify ALI cases if restrictive selection criteria are used and the possibility to review additional information to rule out differential diagnoses. Our results confirm that idiopathic ALI is a very rare disease in the general population. Finally, the construction of a standard definition with predefined criteria facilitates the timely comparison across databases.