Improving the end point of corticosteroid therapy in type 1 autoimmune hepatitis to reduce the frequency of relapse

OBJECTIVE: Relapse of autoimmune hepatitis may reflect incomplete suppression of disease activity prior to corticosteroid withdrawal, and liver tissue examination prior to the termination of therapy may be insufficient to predict subsequent course. Our goal was to refine treatment end point criteria so as to reduce the frequency of relapse after drug withdrawal. METHODS: One hundred thirty-two patients with definite type 1 autoimmune hepatitis who fulfilled clinical, laboratory, and histological criteria for remission were evaluated. The degree of laboratory improvement at the termination of treatment was correlated with subsequent clinical course in patients who had improved to normal or near-normal histological findings during corticosteroid therapy. RESULTS: Serum aspartate aminotransferase (AST) levels at the end of treatment were higher in patients who subsequently relapsed than in those who sustained remission (32 +/- 2 U/L vs 25 +/- 2 U/L, P= 0.04). Serum gamma-globulin (1.4 +/- 0.1 g/dL vs 1.2 +/- 0.1 g/dL, P=0.03) and immunoglobulin G (IgG) (1,416 +/- 55 mg/dL vs 1,079 +/- 57 mg/dL, P=0.001) levels were also higher in these patients prior to termination of therapy. The frequencies of abnormal serum AST (40%vs 13%, P=0.008), gamma-globulin (25%vs 3%, P=0.009), and IgG levels (36%vs 4%, P=0.001) at treatment withdrawal were also greater in the patients who subsequently relapsed. CONCLUSIONS: Patients who are treated to normal serum AST, gamma-globulin, and IgG levels have a lower frequency of relapse than others despite comparable histological findings.     

Sustained remission after corticosteroid therapy for type 1 autoimmune hepatitis: a retrospective analysis

Autoimmune hepatitis commonly relapses after corticosteroid therapy, and long-term management strategies have been proposed based on the premise that repeated relapses after drug withdrawal are inevitable. Our goal was to determine the frequency that remission can be sustained after its induction and termination of therapy. A total of 107 patients who had entered remission on conventional regimens were assessed for sustained remission after initial treatment and after relapse and re-treatment. Re-treatment strategies included conventional regimens and long-term maintenance schedules. Twenty-two patients (21%) achieved a sustained remission after initial treatment, and 24 of 85 patients who relapsed and were re-treated (28%) had a similar outcome. The probability of a sustained remission was 47% after 10 years of follow-up. Patients who sustained remission after initial therapy were distinguished only by a lower serum gamma-globulin level at entry. Conventional re-treatment schedules after relapse were able to induce a sustained remission more commonly then long-term maintenance schedules (59% vs. 12%, P =.00002). In conclusion, patients who respond to initial corticosteroid therapy can achieve a sustained remission after treatment withdrawal or after relapse and re-treatment. All patients are candidates for this outcome, and withdrawal of medication, even during maintenance schedules, is necessary to assess its likelihood.     

Sustained remission after corticosteroid therapy of severe hepatitis B surface antigen-negative chronic active hepatitis

To determine the frequency of a sustained remission and to assess the long-term prognosis of relapse and retreatment, 66 patients with severe hepatitis B surface antigen-negative chronic active hepatitis and prolonged follow-up after initial corticosteroid withdrawal (mean, 10 +/- 0.4 yr) were evaluated. Selection of patients was made from among 206 cases of severe disease. Twenty-four patients (36%) sustained remission for at least 5 yr (mean, 11 +/- 0.6 yr) after initial therapy, and 42 (64%) relapsed and were retreated. Patients who sustained remission had shorter durations of illness before therapy (8 +/- 1 vs. 14 +/- 2 mo, p less than 0.05) and they had greater laboratory improvements during treatment. The frequencies of cirrhosis and death were not significantly greater in patients who relapsed. Of the 42 patients who relapsed, 9 (21%) ultimately entered a sustained remission after retreatment. Remission for at least 5 yr was possible in 33 of the 66 patients (50%). Major drug complications developed more commonly in those who relapsed and required retreatment (59% vs. 29%, p less than 0.05). We conclude that 50% of patients who enter remission during initial therapy may ultimately achieve a sustained remission, especially if their disease is of short duration and adequately suppressed during treatment. Relapse does not affect long-term prognosis, but retreatment is associated with more side effects.     

Low-dose corticosteroid therapy after multiple relapses of severe HBsAg-negative chronic active hepatitis

To evaluate the efficacy of low-dose corticosteroid therapy after multiple relapses of severe HBsAg-negative chronic active hepatitis, 22 patients who had relapsed on 3.4 +/- 0.4 occasions (range = two to seven relapses) were treated with the lowest dose of medication necessary to ameliorate symptoms and maintain serum AST activity below five-fold normal. Results were compared with those in 31 patients who had received conventional retreatments after 3.4 +/- 0.3 relapses (range = two to eight relapses). During 44 +/- 7 mo of low-dose therapy (range = 9 to 149 mo), one patient (5%) entered sustained remission, 16 patients (72%) continued treatment, two patients (9%) received liver transplantations, two patients (9%) died of liver-related complications and one patient (5%) died of a nonliver-related cause. Drug-related side effects improved in 11 of 13 patients who had acquired them during conventional therapy (85%). The median dose of prednisone was 7.5 mg daily (range = 1 to 17.5 mg) with and without azathioprine. Thirteen patients received long-term treatment consisting of 10 mg or less of prednisone only. Patients receiving conventional treatment entered remission more frequently than those on low-dose therapy (97% vs. 36%, p less than 0.001) but they relapsed after drug withdrawal (53% vs. 87%, p greater than 0.01), required continuous therapy (55% vs. 72%, p greater than 0.1) and died of liver-related complications (10% vs. 9%) as commonly as those receiving low-dose therapy. We conclude that low-dose corticosteroid therapy in patients who have experienced multiple relapses has similar efficacy and less morbidity than conventional retreatments.     

Risk factors associated with relapse of type 1 autoimmune hepatitis in Japan

Aim: Patients receiving corticosteroid therapy on a tapered schedule occasionally suffer autoimmune hepatitis (AIH) relapses. The aim of this study was to assess the frequency and features of relapses, explore risk factors associated with relapses, and evaluate the effectiveness of azathioprine (AZP) therapy against relapses in Japanese patients with type 1 AIH. Methods: We assessed clinical characteristics and therapeutic processes in 67 patients diagnosed with AIH. Results: Twenty patients (29.9%) suffered from relapses during tapering of corticosteroid therapy. The remaining 47 patients sustained their remission. At the onset of disease, risk factors associated with relapse were: age of 50 years or older; total bilirubin of 1.5 mg/dL or more; aspartate aminotransferase levels of 250 IU/L or more; alanine aminotransferase levels of 250 IU/L or more; prothrombin activity of 80% or more; γ‐globulin levels of 3.4 g/dL or more; and International Autoimmune Hepatitis Group (IAIHG) score of 17 or more in univariate analysis. Grading of histological interface hepatitis is not significantly associated with relapse. Multivariate analysis revealed that IAIHG scores of 17 or more were significantly associated with relapse (odds ratio = 6.57, 95% confidence interval = 1.19–36.33). Seven patients who relapsed were treated with AZP and prednisolone (PSL), and all sustained remission (100%). Of the remaining 13 relapse patients who received only PSL, eight (61.5%) suffered additional relapses. Conclusion: Our results demonstrate the risk factors associated with relapse of AIH. We also show that early administration of AZP after the first relapse may help to prevent additional relapses.     

Hepatitis C virus infection as a determinant of behavior in type 1 autoimmune hepatitis

To determine if hepatitis C virus infection influences the behavior of type 1 autoimmune hepatitis and to assess the performance parameters of third-generation immunoassays for viral infection in this disease, 64 patients with different patterns of disease behavior were assessed retrospectively for antibodies to hepatitis C virus by third-generation enzyme-linked immunosorbent assay and recombinant immunoblot assay and for HCV RNA by polymerase chain reaction. Hepatitis C virus RNA was detected in seven patients (11%) and antibodies to hepatitis C virus were found in five (8%). All patients who had an acute onset of illness or who sustained remission after therapy lacked HCV RNA in serum. In contrast, four of 31 patients who relapsed (13%) and three of 17 patients who failed treatment (18%) had HCV RNA in serum. Patients with HCV RNA were indistinguishable from those without HCV RNA; in three patients, infection was recognized only by testing for HCV RNA. Four of seven patients with HCV RNA responded fully to corticosteroids, although each relapsed after drug withdrawal. Smooth muscle antibodies (43% versus 91%,P=0.006) and concurrent smooth muscle and antinuclear antibodies (0% versus 60%,P=0.003) occurred less frequently in patients with HCV RNA than in counterparts without HCV RNA. The specificity of the third-generation enzyme immunoassay was 98% and its overall predictability was 94%. Its sensitivity, however, was 57% and false positive results occurred in 20%. Hepatitis C virus infection is an uncommon determinant of disease behavior in type 1 autoimmune hepatitis, but it may be present in relapse or treatment failure. Some patients with HCV RNA may respond fully to corticosteroids, although remission is unsustained.     

Histological features associated with relapse after corticosteroid withdrawal in type 1 autoimmune hepatitis

Abstract: Relapse of type 1 autoimmune hepatitis after drug withdrawal may relate to incomplete histological improvement during corticosteroid therapy and/or persistence of pathogenic mechanisms. Aim: Determine the histological features prior to drug withdrawal that are associated with relapse in patients satisfying pre‐established clinical, laboratory, and histological criteria for remission and relapsing after corticosteroid withdrawal. Methods: One hundred liver tissue samples obtained immediately prior to corticosteroid withdrawal from 88 patients who had previously satisfied criteria for histological remission were reviewed retrospectively. Results: Histological findings in the patients who relapsed were similar to those in the patients who sustained remission in regard to histological activity index (1.7 ± 0.1 versus 1.6 ± 0.2, P = 0.6), fibrosis score (2.6 ± 0.3 versus 2.3 ± 0.4, P = 0.5), and frequencies of interface hepatitis (36% versus 20%, P = 0.2), cirrhosis (21% versus 17%, P = 0.8), and normal or near normal tissue (9% versus 7%, P > 0.9). Only the presence of portal plasma cells was associated with relapse (31% versus 7%, P = 0.01). The positive predictability of portal plasma cell infiltration for relapse was 92%, but its sensitivity was only 31%. Conclusions: Portal plasma cell infiltration is predictive of relapse after drug withdrawal in tissue specimens already satisfying criteria for remission. Portal plasma cell infiltration may be indicative of an active antibody‐dependent pathogenic mechanism. Its low sensitivity for relapse indicates the need for other complementary predictors of outcome.     

Chloroquine for the maintenance of remission of autoimmune hepatitis: results of a pilot study

BACKGROUND: Due to the risks related to long-term treatment with prednisone and azathioprine, most clinicians try to withdraw these drugs when patients with autoimmune hepatitis are in remission. However, there is a high probability of relapse, and most patients end up receiving maintenance treatment. AIM: To evaluate the safety and efficacy of maintenance treatment with chloroquine in the prevention of autoimmune hepatitis relapses. METHODS: Classical treatment was stopped after achievement of biochemical and histological remission of autoimmune hepatitis. Chloroquine diphosphate, 250 mg daily, was given for at least 12 months or until the occurrence of relapses defined by levels of aminotransferases at least twice the upper normal values. RESULTS: Fourteen patients were consecutively treated and compared with 18 historical controls. There was a 6.49 (1.38-30.30) greater chance of relapse in the historical controls when compared with patients treated with chloroquine (72.2% x 23.5%; 0.031). CONCLUSIONS: The group treated with chloroquine had a lower frequency of relapses. Chloroquine was safe in patients with autoimmune hepatitis and hepatic cirrhosis without decompensation, on 250 mg daily up to 2 years. These preliminary results provide a basis for upcoming controlled studies comparing chloroquine with placebo or for maintenance treatment with prednisone and/or azathioprine for the prevention of autoimmune hepatitis relapses.     

Behavior and significance of autoantibodies in type 1 autoimmune hepatitis

BACKGROUND/AIM: Smooth muscle antibodies and antinuclear antibodies characterize type 1 autoimmune hepatitis. Our aim was to correlate the appearance and disappearance of these autoantibodies with clinical and histological events. METHODS: One hundred and seven patients were evaluated successively over 128+/-9 months. Autoantibodies were determined by indirect immunofluorescence during routine follow-up and at key clinical events. RESULTS: Eighty-one patients (76%) lost one or both of the autoantibodies, and disappearance was associated with improved laboratory and histological features. Autoantibody status, however, was not highly predictive of laboratory (69%) or histological activity (72%). Patients who relapsed were seronegative at the time of drug withdrawal as commonly as patients who sustained remission (29% versus 25%). Only 27 patients (25%) lost their autoantibodies long term. Patients who eventually entered a sustained remission lost their autoantibodies more commonly than those who required retreatment (76% versus 43%, p=0.03). Disappearance of the autoantibodies, however, preceded sustained remission in only 38%. Serum titers at presentation did not distinguish patients with more severe disease or different treatment outcomes. CONCLUSIONS: Smooth muscle antibodies and antinuclear antibodies commonly disappear and reappear. Their loss is associated with improved laboratory tests and biopsy findings, but disappearance does not predict treatment outcome. Autoantibody titer at presentation and autoantibody behavior during therapy are not accurate indices of disease severity or prognosis.     

Outcome of second allogeneic transplants using reduced-intensity conditioning following relapse of haematological malignancy after an initial allogeneic transplant

Disease relapse following an allogeneic transplant remains a major cause of treatment failure, often with a poor outcome. Second allogeneic transplant procedures have been associated with high TRM, especially with myeloablative conditioning. We hypothesized that the use of reduced-intensity conditioning (RIC) would decrease the TRM. We performed a retrospective national multicentre analysis of 71 patients receiving a second allogeneic transplant using RIC after disease relapse following an initial allogeneic transplant. The majority of patients had leukaemia/myelodysplasia (MDS) (N=57), nine had lymphoproliferative disorders, two had myeloma and three had myeloproliferative diseases. A total of 25% of patients had unrelated donors. The median follow-up was 906 days from the second allograft. The predicted overall survival (OS) and TRM at 2 years were 28 and 27%, respectively. TRM was significantly lower in those who relapsed late (>11 months) following the first transplant (2 years: 17 vs 38% in early relapses; P=0.03). Two factors were significantly associated with a better survival: late relapse (P=0.014) and chronic GVHD following the second transplant (P=0.014). These data support our hypothesis that the second RIC allograft results in a lower TRM than using MA. A proportion of patients achieved a sustained remission even when relapsing after a previous MA transplant.     

Thyroid hypoechogenicity after methimazole withdrawal in Graves' disease: a useful index for predicting recurrence?

OBJECTIVE A characteristic thyroid ultrasonographic picture with diffuse or scattered low echogenicity has been described in Graves' disease (GD). Thyroid hypoechogenicity in GD at onset has been considered a prognostic index of relapse after medical treatment; moreover, thyroid hypoechogenicity is regularly observed in GD at the onset, but not in patients with ‘burned-out’ disease. The aim of this study was to evaluate the usefulness of thyroid hypoechogenicity changes in predicting GD relapse. DESIGN Longitudinal prospective study of previously untreated patients with GD. PATIENTS Thirty-nine consecutive patients aged 10–72 years were treated with methimazole (MMI) for 12–24 months on a titration regimen. Evaluation of patients in remission or with relapse was done 12 and 24 months after MMI withdrawal. MEASUREMENTS Thyroid ultrasonography and TSH receptor antibodies (TRAb) were evaluated in basal conditions and then one month after MMI withdrawal. Thyroid hypoechogenicity score (assessed by the same observer with the same equipment) was graded as: 0 absent; 1 mild; 2 moderate; 3 marked. At the withdrawal evaluation a score < 2 and a TRAb value < 10 U/l were considered as normal. RESULTS Twelve and 24 months after withdrawal, there were 10 (25.6%) and 17 (44.7%) relapses, respectively. Neither thyroid hypoechogenicity score nor TRAb values evaluated in basal conditions, showed significant differences between patients remaining euthyroid and those who became again hyperthyroid. In the whole group, the thyroid hypoechogenicity score was significantly lower at the withdrawal than in basal conditions (1.1±1.1 vs 2±0.8; P < 0.0001); it was significantly lower in patients in remission (P < 0.001), but not in those who relapsed. The thyroid hypoechogenicity score at withdrawal was normal in 23/29 (79.3%) of patients still euthyroid and in 4/10 (40%) of those who relapsed up to the 12th month (P < 0.05); it was normal in 19/21 (90.4%) of patients still euthyroid and in 7/17 (41.2%) of those who relapsed up to the 24th month (P < 0.05). A normal thyroid hypoechogenicity score at withdrawal of MMI had a higher specificity (0.95) and sensitivity (0.59) with respect to TRAb values (0.86 and 0.53, respectively) for the prediction of the relapse of hyperthyroidism at the 24th month. CONCLUSIONS Basal thyroid hypoechogenicity cannot be used as an index of relapse of GD. MMI treatment induces evident changes in thyroid hypoechogenicity, mainly in patients who subsequently go into remission. The absence or a low grade of thyroid hypoechogenicity after MMI treatment seems to be a favourable prognostic index of remission of hyperthyroidism in GD.     

核苷(酸)类似物抗乙型肝炎病毒达到治疗终点标准停药后复发的相关因素分析

目的 探讨影响核苷(酸)类似物(NA)治疗慢性乙型肝炎(CHB)患者达到治疗终点标准(达标)停药后复发的相关因素.方法 CHB患者81例,接受NA抗病毒治疗.拉米夫定(LAM)治疗38例,阿德福韦酯(ADV)25例,恩替卡韦(ETV)12例,LAM+ADV 6例.HBeAg阳性40例,NA初治患者67例,耐药复治14例.达标停药或延长疗程后停药,分别于基线、病毒学应答前每个月、病毒学应答后每3个月、停药后半年内每个月、半年后每2个月检测HBV DNA、HBV血清学标志物和ALT.将性别、年龄、乙型肝炎家族史、基线HBV DNA、基线HBeAg、基线ALT、病毒学应答时间、总疗程(月)、延长疗程(月)、初治或耐药复治、停药时HBsAg水平、药物种类共12个可能影响复发的因素进行单因素、多因素Cox比例风险模型和分层分析,累计复发率采用Kaplan-Meier法计算.结果 81例患者达标停药后,36例患者在1年内复发,占44.4%.初治或耐药复治、乙型肝炎家族史、病毒学应答时间、停药时HBsAg水平分别是影响停药后复发的独立危险因素.耐药复治者复发率高于初治患者(78.6%比37.3%,χ2=7.983,P=0.005),有乙型肝炎家族史的患者复发率高于无乙型肝炎家族史者(64.5%比15.0%,χ2=12.096,P=0.002),病毒学应答发生在3个月内的患者复发率低于发生在3个月后的患者(34.0%比64.3%,χ2=6.823,P=0.009),停药时HBsAg≤150μg/L的患者复发率低于>150μg/L者(27.6%比53.8%,χ2=5.199,P=0.023).结论 耐药复治、有乙型肝炎家族史、病毒学应答时间晚、停药时高水平HBsAg是导致NA治疗停药后复发的主要因素.对此类患者治疗达标后应适当延长疗程,巩固疗效.

Abstract：

Objective To explore the influence factors on hepatitis B virus (HBV) relapse after nucleos(t)ide analogues (NA) withdrawal in the chronic hepatitis B (CHB) patients who met NA cessation criteria. Methods Eighty-one consecutive CHB patients were treated with NA, 38 with lamivudine (LAM), 25 with adefovir dipivoxil (ADV), 12 with entecavir (ETV), 6 with LAM +ADV. Among recruited patients, 40 were hepatitis B virus e antigen (HBeAg) positive, 41 were HBeAg negative, 67 of them were initial treatment, 14 were retreatment due to resistance to NA at baseline. The treatment was discontinued after meeting China therapeutic end-point criteria. HBV DNA, HBV serological markers, alanine aminotransferase (ALT) were measured respectively at baseline, every month before virological response, every 3 months after virological response, every month within first 6 months and every 2 months over 6 months after drugs withdrawal. Twelve probable influence factors on relapse which were sex, age, HBV family history, baseline HBV DNA,baseline HBeAg status, baseline ALT, virological response time, total duration of treatment, duration of additional treatment, the level of hepatitis B virus surface antigen (HBsAg) at cessation therapy,initial treatment or retreatment, drug category were analyzed with univariate, multivariate Cox regression modle and stratified analysis. The cumulative relapse was calculated by the Kaplan-Meier method. Results A total of 36 patients (44. 4%) relapsed within 1 year. Initial treatment or retreatment, HBV family history, virological response time, the level of HBsAg at cessation therapy were independent risk factors. The relapse rate of retreatment was higher than that of initial treatment (78.6% vs 37. 3% , χ2 = 7. 983, P = 0. 005) , those of patients with HBV family history higher than without family history (64. 5% vs 15.0%, χ2 =12. 096,P = 0.002), those of patients obtained virological response within 3 months lower than after 3 months(34. 0% vs 64. 3% , χ2 =6. 823,P=0. 009) , those of patients with HBsAg≤150 μg/L at cessation therapy lower than >150 μg/L(27. 6% vs 53. 8%, χ2=5. 199,P=0. 023). Conclusions Retreatment, HBV family history, later virological response and higher HBsAg level at cessation therapy are risk factors of relapse after NA withdrawal. Such patients should be treated with prolonged duration after meeting end-point criteria to strengthen the efficacy.     

Empiric therapy of autoimmune hepatitis with mycophenolate mofetil: comparison with conventional treatment for refractory disease

GOAL: To assess the outcomes of empiric therapy with mycophenolate mofetil in patients with autoimmune hepatitis. BACKGROUND: Mycophenolate mofetil is a purine antagonist that selectively inhibits immunocyte proliferation, and its empiric use in autoimmune hepatitis has been stimulated by small clinical experiences. STUDY: Eight patients received mycophenolate mofetil (0.5-3 g daily) for 19 +/- 7 months as frontline therapy or after adverse responses to conventional corticosteroid treatment. Seventeen patients who had been treated with high-dose corticosteroid regimens after treatment failure constituted a historical comparison population. RESULTS: Five of the 8 patients receiving mycophenolate mofetil and all 17 patients who had been treated with the conventional corticosteroid regimens for treatment failure responded to therapy. The frequency of response (62% vs. 100%, P = 0.02) was lower during longer intervals of treatment (19 +/- 7 months vs. 6 +/- 1 months, P = 0.02) in the patients receiving mycophenolate mofetil. None receiving mycophenolate mofetil resolved their laboratory abnormalities, whereas 6 patients in the comparison group improved to normal tests (0% vs. 35%, P = 0.1). Histologic resolution did not occur in 4 patients sampled during treatment, and successive specimens in 2 patients showed progressive fibrosis. Corticosteroids could not be withdrawn in the patients treated with mycophenolate mofetil, whereas discontinuation was possible in 7 patients in the comparison group (0% vs. 41%, P = 0.06). CONCLUSIONS: Mycophenolate mofetil did not induce laboratory resolution, prevent progressive fibrosis, or allow corticosteroid withdrawal. Clinical trials are needed to evaluate its role and target population.     

Can calprotectin predict relapse risk in inflammatory bowel disease?

OBJECTIVE:  Assessing the clinical course of inflammatory bowel disease (IBD) patients consists of periodical clinical evaluations and laboratory tests. We aimed to assess the role of calprotectin tests in predicting clinical relapse in IBD patients.
METHODS:  Ninety-seven patients with ulcerative colitis (UC) and 65 with Crohn's disease (CD) in clinical remission were prospectively included in the study. A 10-g stool sample was collected for calprotectin assay. The cutoff level was set at 130 mg/kg of feces. Patients were followed up for 1 yr after the test or until relapse. The cumulative proportion of relapses was estimated by the Kaplan-Meier analysis. Statistics for equality of survival distribution were tested using the log-rank test.
RESULTS:  The calprotectin test was positive in 44 UC patients and 26 of them relapsed within a year, while 11 of 53 UC patients with a negative calprotectin test relapsed within the same time frame. Thirty CD patients had a positive calprotectin test and 13 of them relapsed within a year, as did 7 of the 35 with a negative test result. A significant correlation emerged between a positive calprotectin test and the probability of relapse in UC patients ( P = 0.000). In CD patients, only cases of colonic CD showed a significant correlation between a positive calprotectin test and the probability of relapse, i.e ., 6 colonic CD patients were positive for the calprotectin test and 4 relapsed ( P = 0.02).
CONCLUSIONS:  Measuring calprotectin may help to identify UC and colonic CD patients at higher risk of clinical relapse.     

Emergency department return visits in chronic obstructive pulmonary disease: the importance of psychosocial factors

STUDY OBJECTIVES: Relapses are common after treatment of decompensated chronic obstructive pulmonary disease (COPD) in the emergency department. The purpose of this study was to identify psychosocial and pulmonary function variables that distinguish patients who relapse from those who do not. DESIGN: Retrospective case analysis. A relapse was defined as an unscheduled return to the ED within two weeks of treatment. SETTING: 475-bed Veterans Administration Medical Center. TYPE OF PARTICIPANTS: 33 male veterans with COPD who used the ED. MEASUREMENTS: Demographic profile, a Likert-scaled questionnaire about illness beliefs, and physiologic data obtained by chart review. MAIN RESULTS: Patients who relapsed at least once (R patients) were more likely to be widowed, separated, or divorced than patients who did not relapse at any time (N patients) (52.4% vs 8.3%; P = .011). R patients were more likely to have lost a first-order relative within three years (57.1% vs 8.3% P = .006). Stepwise logistic regression showed that the loss of a first-order relative, a negative attitude about prognosis, and a higher forced vital capacity distinguished R from N patients. Stepwise linear regression showed that six specific illness beliefs, distance of the home from the hospital, and baseline bronchodilator response correlated with the number of relapses (multiple r2 = 0.82; P less than .001). CONCLUSION: Social and psychological parameters are closely correlated with relapse in patients with decompensated COPD.     

Prognostic features and role of liver transplantation in severe corticosteroid-treated autoimmune chronic active hepatitis.

To identify prognostic features and to define the role of liver transplantation in severe autoimmune chronic active hepatitis, findings before and after corticosteroid therapy in 111 patients were correlated with outcome and compared with the findings in 24 patients who had been selected independently for liver transplantation. Patients whose condition deteriorated during corticosteroid treatment were younger (32 +/- 3 yr vs. 43 +/- 2 yr; p less than 0.02) than those who experienced remission, but no individual features predicted outcome. Patients in whom therapy failed required longer durations of continuous treatment than did those who experienced remission (60 +/- 14 mo vs. 20 +/- 12 mo; p = 0.001). Of 13 patients who did not experience remission within 4 yr, 9 (69%) ultimately deteriorated. Ascites developed more often in those patients whose therapy failed and who died of liver failure than in counterparts who survived (86% vs. 33%). Patients undergoing transplantation were similar to those whose treatment failed, but they died less frequently (8% vs. 56%, p less than 0.01). Indeed, the 5-yr survival rate after transplantation was comparable to that of patients who had entered remission (92% vs. 100%). Successive biopsy samples failed to disclose recurrent autoimmune hepatitis after transplantation. Human leukocyte antigens A1, B8 occurred more commonly in patients in whom treatment failed or who underwent transplantation (70% vs. 41%, p less than 0.05). We conclude that failure to achieve remission within 4 yr and the human leukocyte antigen A1, B8 phenotype are associated with poor prognosis. Manifestations of liver decompensation, such as ascites, in patients who have been unable to experience remission justify consideration of transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)     

HBeAg血清学转换对核苷（酸）类似物治疗慢性乙型肝炎患者停药后复发的影响

目的探讨HBeAg血清学转换对核苷（酸）类似物治疗慢性乙型肝炎（CHB）患者停药后复发的影响。方法回顾性分析60例HBeAg阳性接受核苷（酸）类似物治疗的CHB患者,疗程至少1年的停药患者,于基线、治疗后每个月、HBV DNA转阴后每3个月检测ALT,HBV DNA,HBeAg和抗-HBe。停药后继续随访至少6个月,观察停药后复发情况。分析停药时是否发生HBeAg消失/转换对复发的影响;比较发生HBeAg/抗HBe血清转换后巩固治疗≤12个月、12～24个月、〉24个月三组患者的复发率。结果 60例患者中,60%（36例）的患者在停药后6个月内复发。8例患者未发生HBeAg消失（A组）,停药后4个月内100%复发;6例患者发生HBeAg消失,但无抗-HBe（B组）,停药后6个月内83.3%（5例）复发;46例发生HBeAg血清学转换（C组）,停药后6个月内50%（23例）复发,χ2=11.585,P=0.003,A组与C组相比,χ2=6.84,P=0.015,差异有统计学意义;B组与A组、C组相比,χ2=1.333,P=0.248,χ2=2.327,P=0.199,差异无统计学意义;HBeAg/抗-HBe血清转换后继续用药≤12个月（11例）、12～24个月（23例）、〉24个月（C组12例）,停药后6个月内复发率分别为100%（11例）、47.8%（11例）、8.3%（1例）,χ2=19.377,P=0.000,A组与B组、C组相比,χ2=8.609,P=0.003,χ2=19.326,P=0.000,B组与C组相比,χ2=5.303,P=0.027,均有统计学意义。结论 HBeAg血清学转换是HBeAg阳性CHB患者治疗终点的基本指标,HBeAg/抗-HBe血清转换后治疗≤12个月仍有较高的复发率,HBeAg/抗-HBe血清转换继续治疗〉24个月有望获得持久的病毒学应答,但对停药患者6个月内应密切随访观察。     

Sustained virological response in a predominantly hepatitis C virus genotype 4 infected population

AIM： To assess sustained virological response （SVR） rates in a predominantly hepatitis C virus （HCV） genotype 4 infected population. METHODS： Between 2003-2007, 240 patients who were treated for chronic hepatitis C infection at our center were included. Epidemiological data, viral genotypes, and treatment outcomes were evaluated in all treated patients. Patients with chronic renal failure, previous non-responders, and those who relapsed after previous treatment were excluded from the study. Among all patients, 57% were treated with PEG- interferon （IFN） α-2a and 43% patients were treated with PEG-IFN α-2b; both groups received a standard dose of ribavirin. RESULTS： 89.6% of patients completed the treatment with an overall SVR rate of 58%. The SVR rate was 54% in genotype 1, 44% in genotype 2, 73% in genotype 3, and 59% in genotype 4 patients. There was no statistical difference in the SVR rate between patients treated with PEG-IFN α-2a and PEG-IFN α-2b （61.5% vs 53%）. Patients younger than 40 years had higher SVR rates than older patients （75% vs 51%, P = 0.001）. SVR was also statistically significantly higher when the HCV RNA load （pretreatment） was below 800.000 （64% vs 50%, P = 0.023）, in patients with a body mass index （BMI） less than 28 （65% vs 49%, P = 0.01）, and in patients who completed the treatment duration （64% vs 8%, P ≤ 0.00001）.CONCLUSION： The SVR rate in our study is higher than in previous studies. Compliance with the standard duration of treatment, higher ribavirin dose, younger age, lower BMI, and low pretreatment RNA levels were associated with a higher virological response.     

Induction of remission in active anti-neutrophil cytoplasmic antibody-associated vasculitis with mycophenolate mofetil in patients who cannot be treated with cyclophosphamide

BACKGROUND: Active anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is commonly treated with cyclophosphamide, a drug with serious side effects, and with corticosteroids. OBJECTIVE: To determine the efficacy of a possible alternative drug for cyclophosphamide, oral mycophenolate mofetil (MMF) 1000 mg twice daily and oral prednisolone 1 mg/kg once daily as remission induction treatment. METHODS: 32 consecutive patients with 34 episodes of active vasculitis who could not be treated with cyclophosphamide were diagnosed for a median (range) of 6.0 (0.3-22) years and experienced 4 (0-14) relapses prior to the current episode. Treatment response and relapse-free survival were analysed. RESULTS: Complete remission (CR) was obtained in 25 (78%) patients, partial remission (PR) in 6 (19%), whereas 1 (3%) patient did not respond. 19 patients relapsed, 13 (52%) after CR, 14 (3-58) months after starting the treatment and 6 (100%) after PR, 6 (2-10) months after starting the treatment. The median relapse-free survival was 16 months, comparable with the interval between the previous relapse and the current MMF-treated relapse (17 (3-134) months). Relapse-free survival at 1, 3, and 5 years was 63%, 38% and 27%, respectively. Patients who had been treated successfully with cyclophosphamide before responded better (CR 84%, relapse 50%) than those who had not (CR 50%, relapse 100%). Minor gastrointestinal side effects and infections occurred frequently. MMF was prematurely discontinued due to adverse effects in two patients. CONCLUSION: MMF, in combination with prednisolone, can induce remission in patients with relapses of AAV intolerant to cyclophosphamide.     

Retreatment for 24 vs 48 weeks with interferon-alpha2b plus ribavirin of chronic hepatitis C patients who relapsed or did not respond to interferon alone

We assessed the efficacy of interferon (IFN) plus ribavirin over 24 or 48 weeks for the retreatment of patients with chronic hepatitis C who had relapsed or did not respond to a previous course of IFN. One-hundred and twenty patients (69 non-responders and 51 relapsers) were randomly assigned to receive IFN-alpha2b (3 million units thrice weekly) plus ribavirin (1,000-1,200 mg per day) for 24 weeks (group A: 58 patients) or 48 weeks (group B: 62 patients). Treatment was discontinued at week 12 if the alanine aminotransferase (ALT) level remained elevated. The rate of sustained response was 15.5% in group A and 37.1% in group B (P = 0.013). Relapsers treated for 48 weeks had a sustained response rate of 66.6% compared with a sustained response rate of only 25% in those treated for 24 weeks (P = 0.004). Moreover, a sustained response was seen in 14.3% of non-responders treated for 48 weeks and in 8.8% of those treated for 24 weeks (P = 0.71). Fifty-three per cent of patients with a normal ALT level and undetectable hepatitis C virus (HCV) RNA at week 12 had a sustained response compared with 14% of those who were HCV RNA positive at week 12 (P < 0.001). Independent predictive factors of sustained response were: therapy for 48 weeks (P = 0.0026), relapse after IFN treatment (P = 0.0006), loss of HCV RNA at week 12 (P = 0.0008) and HCV genotype non-1 (P = 0.024). Hence, in patients with chronic hepatitis C who failed to respond to a previous course of IFN monotherapy, combination therapy with IFN plus ribavirin for 48 weeks seems to be more effective than IFN plus ribavirin for 24 weeks.