Esophagogastric varices as a prognostic factor for the determination of clinical stage in patients with primary biliary cirrhosis

Background Primary biliary cirrhosis (PBC) is usually classified as either asymptomatic PBC (a-PBC) or symptomatic PBC (s-PBC). Although the proportion of a-PBC versus s-PBC patients has been consistently increasing, it is not clear whether the present criteria for the staging of PBC are optimal or not. We investigated the clinical stage of PBC patients from the standpoint of esophagogastric varices (EGV).Methods One hundred and nine PBC patients were enrolled in this retrospective study. We investigated the clinical features of PBC based on laboratory data, histological stage, symptoms, and existence of EGV. In addition, the clinical course and prognosis in patients who were periodically followed up were also studied.Results (1) EGV was detected in a-PBC patients, and there was no difference in the grade of EGV between a-PBC and s-PBC patients. (2) a-PBC patients with EGV had more liver damage than those without EGV, and a-PBC patients with EGV had a poorer prognosis than those without EGV. (3) Three of 11 patients who progressed from a-PBC to s-PBC within 3 years had EGV. (4) One of 3 a-PBC patients with EGV had progressed to s-PBC at 3-year follow-up.Conclusions These results indicate that EGV is one of the most important factors for evaluating PBC. Therefore, we would like to propose that a-PBC patients with EGV should either be included in the presently defined s-PBC class, or that new prognostic classes of PBC be created that include EGV as a prognostic factor.     

Natural history of primary biliary cirrhosis.

The natural history of primary biliary cirrhosis (PBC) has improved significantly over the last two decades. Most patients are diagnosed with asymptomatic PBC (a-PBC). The prognosis of a-PBC is usually better than that of symptomatic PBC (s-PBC). Among a-PBC patients, some remain asymptomatic, whereas others progress to s-PBC. The prognosis of s-PBC is still poor and the main cause of death in PBC is liver failure. Other complications, such as esophageal varices and hepatocellular carcinoma, also affect the prognosis of PBC patients. Ursodeoxycholic acid treatment improves the prognosis of PBC patients in the early stage. There seems to be several types of PBC progression.     

Liver/spleen volume ratio as a predictor of prognosis in primary biliary cirrhosis

BACKGROUND: The course of primary biliary cirrhosis (PBC) is determined by clinical symptoms and histological findings. The present study examined the prognostic importance of imaging parameters in PBC. METHODS: The volumes of the liver and spleen of patients with PBC were assessed by computed tomography (CT). The volume ratio of liver to spleen (LV/SV ratio) was evaluated and used for further analyses. RESULTS: The prognosis was significantly poorer in PBC patients with a low, rather than high, LV/SV ratio. The Cox proportional hazard regression model showed that the serum bilirubin level and the LV/SV ratio could predict the prognosis of PBC patients. In addition, the LV/SV ratio was significantly lower in patients who developed symptoms (s-PBC) than in those who remained asymptomatic (a-PBC) during the observation period. CONCLUSIONS: The LV/SV ratio is of prognostic importance in patients with PBC.     

Neuropsychiatric symptoms in hepatitis C patients resemble those of patients with autoimmune liver disease but are different from those in hepatitis B patients

Chronic fatigue, mood alterations and cognitive impairment are frequent accessory symptoms of HCV infection. Fatigue and mood alterations have also been observed in autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC), but not in hepatitis B virus (HBV)‐infection, thus indicating an autoimmune response as possible cause of HCV infection‐associated encephalopathy. Data, however, are sparse. This study aimed to prove that HCV patients feature similar to those with autoimmune liver disease but contrary to HBV patients regarding neuropsychiatric symptoms. A total of 132 noncirrhotic patients (HCV: 46, HBV: 22, AIH: 27, PBC: 29, AIH/PBC: 8) completed questionnaires addressing the domains mentioned above. Eighty‐eight underwent a comprehensive neuropsychological assessment. Patient groups were compared among each other and to 33 healthy controls. Fatigue, anxiety and depression scores were significantly increased, and the SF‐36 mental score significantly decreased in all patient groups compared to controls. Fatigue was significantly more pronounced in HCV than in HBV patients. HCV patients scored significantly worse than HBV patients but not AIH and PBC patients in the SF‐36. HCV, AIH and PBC but not HBV patients did significantly worse than controls in word learning. Recognition of words was impaired in HCV, AIH and PBC patients and recognition of figures in HCV patients, exclusively (P ≤ 0.002). HCV patients did also worse than controls and HBV patients concerning alertness and working memory (P ≤ 0.001). The neuropsychiatric profiles of HCV patients are similar to those of AIH and PBC patients but differ from those of HBV patients, suggesting an autoimmune response as a possible cause for these differences.     

Natural history of primary biliary cirrhosis

The natural history of PBC is characterized by slowly progressive cholestasis with liver damage, development of cirrhosis and its complications, and death, unless the patient undergoes liver transplantation. The disease has at least three clinical presentations, each with a different course and prognosis: the silent and usually less aggressive form, the asymptomatic form, and the symptomatic form. There are no identifiable features that distinguish the asymptomatic population who will remain symptom-free from those patients who will develop symptoms. As expected, the survival is longer in asymptomatic than in symptomatic patients. Overall survival of asymptomatic PBC is shorter than for an age- and gender-matched control population, but the patients remaining asymptomatic had a survival equal to that of the general population. Natural history studies have identified several variables associated with survival, particularly age, bilirubin, albumin, prothrombin time, ascites, encephalopathy, and advanced histological stage. Development of esophageal varices and hepatocellular carcinoma can also affect survival. Serum bilirubin level is, however, the most heavily weighted prognostic variable and can be used as a simplistic prognostic index for patients with PBC. In the last two decades, natural history models have been developed that include clinical, biochemical, and histological variables, the most popular being the Mayo model. It has the advantage ofavoiding histological variables, and therefore can be applicable to a broad spectrum of patients with PBC. The models may also be used to evaluate the efficacy of different new treatments. Prognostic models based on serial measurements of the independent predictors of poor prognosis would lead to a more accurate prediction of survival; however, they probably will not replace clinical outlook.     

Asymptomatic primary biliary cirrhosis: clinical features, prognosis, and symptom progression in a large population based cohort

BACKGROUND: Many patients with primary biliary cirrhosis (PBC) are asymptomatic at the time of diagnosis. However, because most studies of asymptomatic PBC have been small and from tertiary centres, asymptomatic PBC remains poorly characterised. AIMS: To describe the features and progression of initially asymptomatic PBC patients. METHODS: Follow up by interview and note review of a large geographically and temporally defined cohort of patients with PBC, collected by multiple methods. RESULTS: Of a total of 770 patients, 469 (61%) were asymptomatic at diagnosis. These patients had biochemically and histologically less advanced disease than initially symptomatic patients. Median survival was similar in both groups (9.6 v 8.0 years, respectively) possibly due to excess of non-liver related deaths in asymptomatic patients (31% v 57% of deaths related to liver disease). Survival in initially asymptomatic patients was not affected by subsequent symptom development. By the end of follow up, 20% of initially asymptomatic patients had died of liver disease or required liver transplantation. The majority of initially asymptomatic patients developed symptoms of liver disease if they were followed up for long enough (Kaplan-Meier estimate of proportion developing symptoms: 50% after five years, 95% after 20 years). However, 45% of patients remained asymptomatic at the time of death. CONCLUSIONS: Although asymptomatic PBC is less severe at diagnosis than symptomatic disease, it is not associated with a better prognosis, possibly due to an increase in non-hepatic deaths. The reasons for this are unclear but may reflect confounding by other risk factors or surveillance bias. These findings have important implications for future treatment strategies.     

Prevalence and associated factors with esophageal varices in early primary biliary cirrhosis

Background and Aims: Recent routine testing for anti‐mitochondrial antibodies has increased the number of patients with early primary biliary cirrhosis (PBC). The prevalence and clinical significance of esophageal varices in those patients remains obscure. Methods: A systematic cohort analysis of 256 PBC patients was performed to clarify the prevalence, characteristics, and prognosis of the patients with early PBC and esophageal varices. Results: Twenty‐two patients had esophageal varices at the time of diagnosis: 5.5% (12/217) with early disease of histological stage 1 or 2, and 25.6% (10/39) with advanced disease of stage 3 or 4. Immediate treatments were required for two patients with early PBC: one for bleeding varices, and the other for large varices. The overall survival of the patients with early PBC and esophageal varices at diagnosis did not significantly differ from that of patients without esophageal varices (P = 0.66). High alkaline phosphatase (ALP) ratios (odds ratio = 2.3) and low platelet counts (odds ratio = 0.77) were significantly associated with the presence of esophageal varices in the patients with early PBC. Significant associations of these two factors with the development of esophageal varices during follow‐up were also revealed (odds ratio = 1.4 and 0.88, respectively). The patients with early PBC and high ALP ratios ≥ 1.9 had significantly high risks of developing esophageal varices during follow‐up (P = 0.022). Conclusions: High ALP ratios and low platelet counts at diagnosis and decreased platelet counts during follow‐up are useful predictors of esophageal varices in patients with early PBC.     

Clinical course and prognosis of primary biliary cirrhosis--multivariant analysis on cases of national survey

In order to predict prognosis and clinical course of BPC, theory quantification was applied and the discriminated rate was calculated concerning the cases of PBC national survey in Japan. We examined the prediction of three and five year's survival about all cases, the prediction of appearance of symptoms about asymptomatic PBC and that of jaundice about asymptomatic PBC and symptomatic PBC alone with pruritus. The useful items for the prediction of prognosis were serum bilirubin, albumin and the presence of esophageal varices at first medical examination. Fairly good discriminated rate was obtained on the prediction of three and five year's survival. However poor results were obtained concerning the prediction of appearance of symptoms. In conclusion we can predict the prognosis of PBC based on clinical features.     

Is primary biliary cirrhosis a different disease in the elderly?

We examined the presenting features, clinical course and prognosis in relation to age in 121 patients with primary biliary cirrhosis (PBC) for a mean follow-up of 4.6 years. 35 patients (29%) were over age 65 years at presentation/detection. There was a higher proportion of patients asymptomatic of liver disease in the older (over 65 years old) than younger (under 65 years old) group. The clinical features of PBC were less marked in the older patients both in number of symptoms (p less than 0.05) and in progression of serum bilirubin, a marker of prognosis (p less than 0.001). There was no difference in liver-related mortality between old and young patients during the follow-up period. Overall mortality in patients with PBC presenting over age 65 was no different from age- and sex-matched controls.     

Long-term outcomes in antimitochondrial antibody negative primary biliary cirrhosis

Objectives Antimitochondrial antibodies (AMA) are a sensitive and specific marker for primary biliary cirrhosis (PBC). AMAs are present in 95% of patients with PBC. However, 5% do not have AMAs and data on these patients is scarce. We aim to evaluate the long-term outcomes of patients with AMA negative PBC. Methods A retrospective chart review of 71 AMA negative PBC patients. Disease presentation, laboratory results, and clinical endpoints were recorded. AMA negative patients were matched on year of diagnosis to a control group of 71 AMA positive patients. Results Ninety-six percent of the AMA negative patients were of female gender with a median age at diagnosis of 55 years and a length of follow-up of 7.5 years vs. 86% females, a median age of 56 and a follow-up of 8.3 years in the control group. Mean total bilirubin and alkaline phosphatase levels were 0.7?mg/dL vs. 0.6 and 570?U/L vs 341, in AMA negative vs. AMA positive patients at presentation, respectively (p?=?NS). AMA negative patients did not differ in terms of age, serum IgM levels, ANA status, or length of follow-up. Notably, AMA negative patients had a significantly reduced survival free of liver-related complications including transplantation and death compared to AMA positive patients (p?=?0.0182). Conclusion In this large experience, AMA negative PBC patients had a significantly worse prognosis compared to AMA positive PBC patients. The reason for the difference in prognosis is unclear, as it may be true difference or reflect delays in case detection among AMA negative patients.     

Quality of life in Dutch patients with primary biliary cholangitis: Discrepancies between patients’ perspectives and objective disease parameters

Aim

This study aims to assess the health-related quality of life (HRQoL) in a Dutch population of patients with primary biliary cholangitis (PBC) in relation to the prognosis and need for second line-therapy, based on both objective disease parameters and patients’ perspectives.

Methods

In this cross-sectional multicenter study, HRQoL was assessed by using the Dutch PBC-40 according to objective clinical parameters and patients’ perspectives on treatment and prognosis.

Results

In total, 178/269 (66%) patients responded; mean age 61.2 (SD 9.9) years and 165 (92.7%) women. The PBC-40 domain scores did not differ according to the GLOBE score response (p > 0.05 for all) or according to the POISE criteria (p > 0.05), except for the domain itch (p = 0.031). Patients who considered their survival to be impaired scored higher on all domains as compared to those expecting a normal prognosis (p < 0.05). Similarly, PBC-40 domain scores were higher among patients who considered that they were in need of additional therapy compared to those who did not (p < 0.05 for all, except for domain itch [p = 0.056]). However, 45/62 (72.6%) patients with a self-expected impaired prognosis had a GLOBE score indicative of a normal prognosis. Twenty-five of the 40 (62.5%) patients who believed they needed additional therapy were below POISE criteria.

Conclusion

The HRQoL of patients with PBC was impaired in terms of nonfavorable disease status according to the expectations of patients, but not according to objective disease parameters. Substantial discrepancies between patients’ perspectives and objective parameters were observed, which highlights the need for better patient guidance among patient with PBC.     

Sex differences in clinical presentation and prognosis in patients with primary biliary cholangitis

Abstract

Objectives: Primary biliary cholangitis (PBC) is a chronic inflammatory disease of the small intrahepatic bile ducts disproportionally affecting women. Timely diagnosis and treatment can often prevent progression to liver cirrhosis. We hypothesized PBC diagnosis in male patients is delayed and prognosis impaired. We, therefore, conducted a case–control study and compared clinical and prognostic features among male and female patients with PBC.

Materials and methods: 49 male patients with PBC treated at a German tertiary care center between 2006 and 2017 were identified and compared to 98 age-matched female controls. Prospectively collected clinical/biochemical data were analyzed retrospectively. Liver biopsies were scored in a blinded fashion. Prognostic parameters were calculated using established prognostic scores (GLOBE, PBC-UKE). Statistical analysis was performed using Mann-Whitney test and Fisher´s exact test.

Results: At PBC diagnosis, male patients reported significantly less PBC-associated symptoms as compared to female controls (34 versus 71%, p?<?.01). Compared to female patients, median time from onset of PBC-related symptoms and/or first reported elevated cholestatic biochemical parameters to PBC diagnosis was significantly increased in men (36 versus 12?months, p?=?.02). In addition, male patients underwent liver biopsy to establish PBC diagnosis more frequently, tended to show more advanced fibrosis and showed significantly poorer prognostic PBC score results. Hepatocellular carcinoma was only observed in male patients (n?=?3).

Conclusions: When compared to women, men with PBC suffer from less PBC-related symptoms, receive PBC diagnosis delayed and have a worse prognosis. Despite its rarity, the diagnosis of PBC should be considered in men with elevated cholestatic parameters.     

Body mass index in Japanese patients with autoimmune liver disease: overweight patients with primary biliary cirrhosis tend to be asymptomatic

BACKGROUND/AIMS: The aim of this study was to investigate the effects of being overweight on autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) patients. METHODOLOGY/RESULTS: 44 AIH and 95 PBC patients were enrolled in this study. Body weight and body mass index (BMI) of AIH (57.6 +/- 10.4 kg and 23.8 +/- 2.9 kgm(-2), respectively) were higher than those of PBC (51.6 +/- 7.0 kg and 22.0 +/- 2.6 kgm(-2), respectively) (P < 0.001). The prevalence of overweight patients in AIH was also higher than those in PBC (P < 0.005). Being overweight and having 25 < or = BMI < 30 did not affect the progression of hepatic fibrosis in AIH and PBC. In comparison with the non-overweight with PBC, overweight patients with PBC tended not to be symptomatic, such as having itching or fatigue (P = 0.027). CONCLUSIONS: Clinicians should be aware that not only non-alcoholic fatty liver disease but also PBC patients might be included among the overweight hepatic disease patients with unknown etiology.     

自身免疫性肝炎、原发性胆汁性胆管炎及其重叠综合征患者临床特征比较*

目的 比较自身免疫性肝炎(AIH)、原发性胆汁性胆管炎(PBC)和AIH/PBC重叠综合征(AIH/PBC OS)患者临床特征的异同。方法 2017年12月～2019年2月南通市第三人民医院收治的92例自身免疫性肝病患者中包括AIH 35例、PBC 30例和AIH/PBC OS 27例,记录临床表现和血液化验资料并比较三组的异同。结果 AIH、PBC和AIH/PBC OS患者年龄、性别、体质指数和病程比较,无显著性差异(P>0.05);三组乏力、腹胀、纳差、发热和皮肤瘙痒发生率无显著性差异(P>0.05);PBC和AIH/PBC OS患者黄疸更深,血清ALP和GGT水平更高,而AIH患者血清ALT和AST水平更高 (P<0.05);AIH患者凝血功能指标TT显著长于其他两组(P<0.05);AIH患者外周血Hb水平显著低于其他两组(P<0.05);AIH患者血清ASMA阳性率为14.3%,显著高于其他两组的0.0%和0.0%(P<0.05),PBC和AIH/PBC OS患者血清AMA/AMA-M2阳性率分别为93.3%和92.6%,而AIH患者为0.0%(P<0.05);三组血清免疫球蛋白水平差异无统计学意义(P>0.05),三组合并甲状腺功能亢进、系统性红斑狼疮、干燥综合征、类风湿性关节炎、2型糖尿病和慢性肾小球肾炎方面差异,也无统计学意义(P>0.05)。结论 AIH、PBC和AIH/PBC OS患者具有相似的临床症状和体征,但血生化指标、自身抗体表现各有特征,了解这些特征对临床提高诊断和治疗水平将有很大的帮助。     

Immunological features of patients with primary biliary cirrhosis (PBC) overlapping systemic sclerosis: A comparison with patients with PBC alone

To characterize the immunological features of patients with primary biliary cirrhosis (PBC) overlapping systemic sclerosis (SSc), 26 patients with PBC were classified according to the presence of scleroderma-related features (Raynaud's phenomenon, sclerodactyly etc.). The patients were classified into 10 patients with PBC overlapping SSc (PBC-SSc), four patients with some scleroderma-related features although not meeting the criteria of SSc (PBC-SSc spectrum) and 12 patients with PBC alone. Sera from PBC-SSc showed a significantly higher positivity to anti-centromere antibody (P < 0.01) and to E1β of pyruvate dehydrogenase complex (P < 0.005) than those from patients with PBC alone. The same tendency was observed in PBC-SSc spectrum patients. Patients with PBC exhibiting scleroderma-related features, in both the PBC-SSc and PBC-SSc spectrum, may comprise a subset in PBC, not only clinically, but also immunologically.     

Pulmonary hypertension in primary biliary cirrhosis: A prospective study in 178 patients

Objective. To analyze the incidence, clinical features, and prognosis of patients with primary biliary cirrhosis (PBC) complicated by pulmonary hypertension (PH). Material and methods. A total of 178 consecutive PBC patients, who were admitted to Peking Union Medical College Hospital from January 2001 to March 2007, were included in this prospective study. A structured interview, systemic rheumatological examination, laboratory tests (including autoantibodies), and Doppler echocardiography were conducted for each patient and compared between patients with and without PH. Results. Twenty-one PBC patients (11.8%) had PH. Among them, four patients (19.0%) had moderate to severe PH, and one patient died of right heart failure instead of liver failure. The incidences of Raynaud's phenomenon, interstitial lung disease, Sjögren's syndrome, and portal hypertension, the proportion of patients with a positive anti-SSA, the level of serum IgA, as well as the Mayo risk score in the PH–PBC patients were significantly higher than in the non-PH-PBC group (p = 0.02, 0.001, 0.02, 0.03, 0.006, 0.04 and 0.02, respectively). Conclusions. PH, including moderate to severe PH, is not a rare complication of PBC. This complication is closely associated with portal hypertension and immunological dysregulation and indicates a poor prognosis.     

Antibodies to E1 and E2/Protein X components of pyruvate dehydrogenase complex in sera of patients with primary biliary cirrhosis

Aims/Methods: Using purified E1 component of pyruvate dehydrogenase complex (PDC) from bovine heart, we measured the levels of anti-E1 anti-bodies in PBC sera using ELISA and determined the degree of inhibition that these antibodies exerted on E1 enzyme activity. We also estimated levels of anti-E2/Protein X (Pro-X) antibodies in PBC sera using purified E2 and Pro-X of PDC which were copurified with E1.Results/Conclusions: Anti-E1 antibodies were detected in 87.5% (35/40) of PBC sera. Some of these sera inhibited E1 enzyme antivity but inhibition did not correlate with levels of anti-E1 antibodies.A high positive correlation (r=0.918) was found between levels of anti-E1 and anti-E2/Pro-X antibodies, suggesting that anti-PDC antibody production was stimulated by PDC itself. Levels of IgG class anti-E2/Pro-X antibodies were significantly higher in sera of symptomatic PBC patients than in those of asymtomatic PBC patients. It was also found that patients who were positive for only IgM class anti-E2/Pro-X antibodies had early-stage PBC.     

Validation of a fatigue impact score in primary biliary cirrhosis: towards a standard for clinical and trial use

BACKGROUND/AIMS: Fatigue is the commonest symptom of the chronic liver disease primary biliary cirrhosis (PBC). PBC is increasingly being diagnosed earlier in its natural history at a stage when concerns about progression to liver failure may be less prominent than current symptoms. The importance of symptomatic treatment is therefore increasingly being recognised. Research into the aetiology and treatment of fatigue in PBC has been hampered by the lack of relevant, reproducible measures of fatigue severity. The aim of this study was to validate the Fisk Fatigue Severity Score (FFSS), a measure of the impact of fatigue on daily living, for use in PBC and to use the FFSS to study the severity and correlates of fatigue in this condition. METHODS: Fifty-eight patients with PBC and 31 matched control patients attending hospital for nonhepatic disease were studied. The reproducibility of FFSS was assessed over periods from 1 hour to 1 month. Fatigue, as measured by FFSS, was compared in PBC patients and controls. The severity of fatigue in the patients with PBC was correlated with other symptoms and with established biochemical and histological markers of severity. RESULTS: The FFSS questionnaire was acceptable to patients and had reasonable intra-observer variation (coefficient of reproducibility 13% of mean value at 1 hour). The FFSS was more reproducible than a visual analogue scale. FFSSs varied over 4 weeks by up to 36%. Median FFSS's were 2.3 times higher in PBC patients than controls (p<0.005). There were no associations between FFSS and patient age, disease duration, or histological or biochemical markers of severity. CONCLUSIONS: The FFSS is a highly acceptable, internally consistent and reproducible measure of fatigue severity in PBC. We advocate its use in clinical assessment of patients, in studies of the aetiology of fatigue in PBC and, most importantly, in therapeutic trials of symptomatic treatment.     

熊去氧胆酸治疗老年原发性胆汁性肝硬化的临床研究

目的探讨老年原发性胆汁肝硬化（PBC）的临床特征、诊断和治疗效果。方法将66例诊断为PBC的病人分为老年组40例,中年组26例,比较两组的临床表现、生化免疫指标（碱性磷酸酶：ALP、谷氨酰转肽酶：GGT、抗线粒体抗体：AMA）。两组病例均给予口服熊去氧胆酸（UDCA：优思弗）治疗,服药8W后比较疗效。结果90％病人因体检发现ALP、GGT升高就诊,治疗前两组患者的ALP、GGT升高程度差异无统计学意义（P〉0．05）。非特异性皮肤瘙痒是老年PBC患者的主要表现,中年组患者中88．5％无症状,明显高于老年组的37．5％;口服优思弗8W后,两组ALP、GGT均较治疗前明显程度降低（P〈0．05）。老年组中3例肝硬化患者服用优思弗后,其症状、体征及ALP、GGT均无改善,2例死亡。服药后两组患者乏力、皮肤瘙痒症状均无改善,影像学也无变化。结论：（1）PBC早期缺乏特异症状;（2）AMA对PBC诊断有重要意义,ALP、GGT的升高早于黄疸、肝肿大出现。（3）应重视体检中无法解释的ALP、GGT异常升高。（4）UDCA对早期原发性胆汁肝硬化疗效满意。（5）老龄可能是影响PBC患者预后的因素之一。     

Primary biliary cirrhosis. Subclinical inflammatory alveolitis in patients with normal chest roentgenograms

To determine whether a subclinical inflammatory alveolitis is associated with primary biliary cirrhosis (PBC), we compared the numbers and types of cells recovered by bronchoalveolar lavage from 12 patients with PBC, ten healthy control subjects, and nine patients with alcoholic cirrhosis (AC). All were free of clinical pulmonary symptoms and had normal findings on chest roentgenograms. Total BAL cell count did not differ among patients with PBC (mean 9.6 X 10(4) cells/ml), patients with AC (mean 14.8 X 10(4) cells/ml), and control subjects (mean 9.9 X 10(4) cells/ml). Patients with PBC but not patients with AC had an increased proportion of lymphocytes in bronchoalveolar lavage fluid (respectively 22.4 percent +/- 5.2 and 11.6 percent +/- 2.52 compared with the normal value of 9.9 percent +/- 1.5 p less than 0.05). In the same way, alveolar lymphocytosis of the lower respiratory tract from PBC patients predominantly comprised T4+ (helper/inducer) T-lymphocyte subset in patients showing an increased alveolar lymphocytosis. Alveolar macrophages from PBC patients showed a dramatic increased chemiluminescence response before and after stimulation by phorbol-myristate-acetate, regardless of the intensity of alveolar lymphocytosis. Thus, our data demonstrated that subclinical alveolar inflammation comprising T-lymphocytes and activated alveolar macrophages mimicking sarcoid alveolitis is present in a high proportion of patients with PBC.