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Autoimmune, Cholestatic and Biliary Disease
Article first published online: 1 MAY 2013
Copyright © 2013 American Association for the Study of Liver Diseases
Volume 57, Issue 6, pages 2399–2406, June 2013
How to Cite
Ngu, J. H., Gearry, R. B., Frampton, C. M. and Stedman, C. A.M. (2013), Predictors of poor outcome in patients w ith autoimmune hepatitis: A population-based study. Hepatology, 57: 2399–2406. doi: 10.1002/hep.26290
Potential conflict of interest: Nothing to report.
Dr. Ngu's stipend was supported by a Clinical Research Training Fellowship from the Health Research Council of New Zealand, a Ferring/New Zealand Society of Gastroenterology Fellowship, and a Canterbury Medical Research Foundation Fellowship. Research-related expenses were supported by a grant from the Royal Australasia College of Physicians.
- Issue published online: 12 JUN 2013
- Article first published online: 1 MAY 2013
- Accepted manuscript online: 28 JAN 2013 03:55PM EST
- Manuscript Accepted: 16 JAN 2013
- Manuscript Received: 12 OCT 2012
- Clinical Research Training Fellowship
- Health Research Council of New Zealand
- Ferring/New Zealand Society of Gastroenterology Fellowship
- Canterbury Medical Research Foundation Fellowship
- Unknown funding agency
- Royal Australasia College of Physicians
Autoimmune hepatitis (AIH) can lead to cirrhosis, hepatic failure, and death. We aimed to identify predictors of advanced liver fibrosis at presentation, predictors of incomplete response to initial immunosuppression, and predictors of poor liver-related outcomes in the population-based AIH cohort from Canterbury, New Zealand. Cases diagnosed after 1980 that fulfilled standard diagnostic criteria were included. Cases were censored at death or liver transplantation and had a median follow-up of 9 years. Analyses were performed with Cox proportional hazards regression and logistic binary regression. The times to event outcomes were summarized using Kaplan-Meier curves. A total of 133 AIH patients were included. Predictors for advanced liver fibrosis at diagnosis were age at presentation of ≤20 years or >60 years (P = 0.02), serum albumin <36 g/L (P < 0.01), platelet <150 U/L (P < 0.01), and International Normalized Ratio (INR) >1.2 (P < 0.01). The only independent predictor for incomplete normalization of alanine aminotransferase (ALT) at 6 months was age at presentation ≤20 years. Independent predictors of poor liver-related outcomes were incomplete normalization of ALT at 6 months (P < 0.01), serum albumin <36 g/L (P < 0.01), and age at presentation of ≤20 years or >60 years (P = 0.01). Kaplan-Meier estimates showed that 10-year adverse liver event-free survival was 80% for age at presentation ≤20 years and >60 years, and 93% and 100% for age at presentation between 21-40 years and 41-60 years, respectively. Conclusion: Incomplete normalization of ALT at 6 months, low serum albumin concentration at diagnosis, and age at presentation of ≤20 years or >60 years were significant independent predictors of liver-related death or requirement for liver transplantation. Histological cirrhosis at diagnosis was not associated with poor prognosis and did not influence the response to initial immunosuppressive treatment. (HEPATOLOGY 2013;57:2399–2406)
Autoimmune hepatitis (AIH) is a chronic progressive inflammatory liver disease that can lead to cirrhosis, hepatic failure, the need for liver transplantation, and death. Despite the availability of effective treatment, AIH is not a benign condition, with recent long-term studies reporting a 2-fold higher mortality than that of the general population.1, 2 Therefore, it is important to identify patient characteristics that are associated with a poor outcome, so that tailored management strategies can be developed, studied, and implemented to improve prognosis.
A number of clinical and demographic factors have been associated with a poor outcome. The presence of cirrhosis at AIH presentation was a factor associated with higher risk of death or liver transplantation in some3-7 but not all studies.8, 9 Both prolonged International Normalized Ratio (INR) at presentation and nonresponse to initial immunosuppressive treatment have also been reported to predict a worse outcome.3 Lack of improvement in the United Kingdom Endstage Liver Disease (UKELD) score at day 7 was reported to be associated with treatment failure in a selected subgroup of patients who presented with icteric hepatitis.10 Serum aspartate aminotransferase (AST) levels greater than 10 times ULN (upper limit of normal) at presentation were found to be protective against poor outcomes.6 However, to date, studies have been performed in specialist referral units where there is likely to be an overrepresentation of younger patients with more severe disease. Therefore, population-based data are needed to more accurately reflect those in the general population.
We therefore aimed to describe: (1) predictors of advanced liver fibrosis and cirrhosis at presentation, (2) predictors of incomplete response to initial immunosuppression, and (3) predictors of liver-related death or requirement for liver transplantation, in the established population-based AIH cohort from Canterbury, New Zealand.11
Patients and Methods
This study was conducted in the geographically defined region of Canterbury, which lies on the east coast of the South Island of New Zealand. It is New Zealand's largest province by area and second largest by population. The estimated population for this region in 2010 was 508,100. Christchurch Hospital is a tertiary teaching hospital without a liver transplant unit and is the only public hospital in this region that provides gastroenterology and hepatology services. Patients who require liver transplantation are referred to the New Zealand Liver Transplant Unit located in Auckland. In addition, there are five private specialist clinics that provide hepatology services to the region.
The population-based AIH cohort was recruited and validated with methods described in detail in our earlier studies.1, 11 In brief, cases were recruited both prospectively and retrospectively using multiple case-finding strategies. All private and public gastroenterology clinic notes, inpatient discharge codes, laboratory, pathology, and radiology reports were searched to identify retrospectively all known cases of AIH in Canterbury diagnosed from January 1, 1980 to December 31, 2006. All gastroenterologists who serve the region also provided a list of their patients with these diseases. From 2007 to 2011, cases were recruited prospectively.
Demographic, clinical data, laboratory, radiology, and histology results were extracted from paper and computer case notes. Cases were included in the study if they had definite or probable AIH as determined using the revised original scoring system.12 All patients were tested for hepatitis C infection. Potential cases with uncertain hepatitis C status were excluded from the study (a total of 12 patients were excluded for this reason). The date of diagnosis was taken as the date that the liver biopsy was performed. Patients who did not undergo a liver biopsy or had follow-up of less than 6 months were excluded from this study. End of follow-up was at death, liver transplantation, last outpatient clinic consultation for those that were lost to follow-up, or the end of study (December 31, 2011). There were minor differences in the characteristics of the study cohort compared to earlier studies, as this study included patients diagnosed in 2011 and had excluded patients without a liver biopsy. This study received ethical approval from the Upper South A Regional Ethics Committee.
Baseline factors that were evaluated in this study include gender, age, serological markers, immunoglobulin G (IgG), bilirubin, liver enzymes, platelet count, albumin, INR at presentation, and histological fibrosis stage at diagnosis. Stages of fibrosis were evaluated using the Metavir scoring system. Advanced liver fibrosis was defined as Metavir stages 3 and 4, and histological cirrhosis was defined as Metavir stage 4. Age at presentation was categorized into four groups: group 1 (ages 0-20 years), group 2 (ages 21-40 years), group 3 (ages 41-60 years), and group 4 (ages over 60 years). The ULN range of our laboratory for alanine aminotransferase (ALT) is 30 U/L. For this study, pretreatment ALT levels were also categorized into four groups: group A (<90 U/L), group B (91-150 U/L), group C (151-300 U/L), and group D (>300 U/L). Response to initial immunosuppression was defined as normal ALT at 6 months from diagnosis, as it had been reported that the majority of AIH patients would respond to treatment within 3-6 months.13 Unfortunately, serum IgG level was not routinely monitored, especially prior to 2008, and repeat liver biopsies were not routinely performed in our cohort; therefore, these values were not used as assessment of treatment response. Liver-related endpoints were defined as death secondary to liver failure or hepatocellular carcinoma (HCC), and requirement for liver transplantation in order to minimize bias towards a poorer outcome in the elderly who were prone to other causes of death.
Comparisons between groups with and without cirrhosis at AIH diagnosis, and between those who did or did not normalize ALT within the first 6 months, were made using binary logistic regression, and summarized as odds ratios (OR) with 95% confidence intervals (CI). The associations of putative risk factors and outcomes were analyzed using Cox proportional hazards regression and are summarized as hazard ratios (HR) with 95% CI. The times to event outcomes were also summarized using Kaplan-Meier curves. All analyses were undertaken using statistical software SPSS v. 20, and a two-tailed P-value <0.05 was taken to indicate statistical significance.
Characteristics of the Study Cohort.
A total of 138 patients with AIH were identified, but five patients were excluded as they did not undergo a liver biopsy. Of the remaining 133 patients, 74% were female. Mean age at diagnosis was 50 years. Only one patient had type 2 AIH with positive antiliver kidney microsomal antibody. None of the patients had a positive hepatitis C antibody. Total follow-up was 1,282 person years, with median follow-up of 9 years. During the follow-up period, there were 32 deaths and, of these, 13 deaths were liver-related. Liver failure was the cause of death in 11 patients, while HCC was responsible for the other two deaths. Three patients received a liver transplant during the follow-up period. At diagnosis, 45 (34%) patients had histological cirrhosis, and 36 (27%) patients had Metavir stage 3 fibrosis. The characteristics of the study cohort are summarized in Table 1.
|Total number of included cases||133|
|Recruited from public hospital||116 (87%)|
|Recruited from private clinics||17 (13%)|
|NZ Maori||3 (2%)|
|Pacific Islander||1 (1%)|
|Mean age at diagnosis (years)||50|
|Median age at diagnosis (years, range)||53 (14-82)|
|Age at presentation|
|Group 1 (0-20yrs)||12 (9%)|
|Group 2 (21-40yrs)||28 (21%)|
|Group 3 (41-60yrs)||54 (41%)|
|Group 4 (>60yrs)||39 (29%)|
|Total follow up (years)||1282|
|Median follow up (years, range)||9 (1-30)|
|Mean follow up (years)||9.6|
|Total number of deaths||32|
|Total liver transplantation||3|
|Total liver related death||13|
|Fibrosis stages at diagnosis (Metavir)|
|Stage 0||6 (5%)|
|Stage 1||23 (17%)|
|Stage 2||23 (17%)|
|Stage 3||36 (27%)|
|Stage 4||45 (34%)|
Baseline Factors Associated With Cirrhosis at Diagnosis.
The results from single predictor logistic regression evaluating the relationship between baseline patient factors and the presence or absence of cirrhosis at diagnosis are presented in Table 2. Cirrhosis at diagnosis was associated with the age at presentation, although the form of the relationship was not linear (Fig. 1A). Using the oldest age group (>60 years) as the reference group, it is evident that patients who presented between 21 and 60 years old had a significantly lower risk of cirrhosis at diagnosis. However, for those who presented before the age of 20 years the risk of cirrhosis at diagnosis was not significantly different from that of the oldest age group.
|Factors (at Diagnosis)||No. Cases with Cirrhosis (%)||OR||95% CI||P-value|
|Age at presentation||<0.01|
|Group 1 (0-20yrs)||5 (42%)||0.61||0.17-2.27||NS|
|Group 2 (21-40yrs)||3 (11%)||0.10||0.03-0.40||<0.01|
|Group 3 (41-60yrs)||16 (30%)||0.36||0.15-0.85||0.02|
|Group 4 (>60yrs)||21 (54%)||1|
|Anti-SMA (titer ≥1:80)||26 (32%)||0.78||0.38-1.63||NS|
|ANA (titer ≥1:80)||24 (31%)||0.76||0.37-1.56||NS|
|IgG (>14g/L)||41 (35%)||2.00||0.53-7.60||NS|
|Bilirubin (>50μmol/L)||44 (34%)||2.00||0.93-4.28||NS|
|ALP (>150U/L)||27 (34%)||1.03||0.50-2.10||NS|
|Albumin (<36g/L)||25 (51%)||3.33||1.57-7.07||<0.01|
|Platelet (<150U/L)||18 (75%)||9.11||3.28-25.30||<0.01|
|INR (>1.2)||20 (59%)||4.23||1.86-9.60||<0.01|
|Group A (<3x ULN)||10 (40%)||1.25||0.49-3.20||NS|
|Group B (3-5x ULN)||4 (29%)||0.75||0.21-2.64||NS|
|Group C (5-10x ULN)||6 (27%)||0.71||0.25-2.03||NS|
|Group D (>10x ULN)||25 (35%)||1|
We also found that male patients were significantly more likely to have cirrhosis at diagnosis compared to female patients (OR = 2.78, 95% CI: 1.23-6.18, P = 0.01). Factors known to be associated with hepatic synthetic failure and portal hypertension such as low serum albumin concentration, prolonged INR, and low platelet count at presentation were all significantly associated with cirrhosis (P < 0.05).
Baseline Factors Associated With Advanced Liver Fibrosis at Diagnosis.
The relationship between patient baseline factors and the presence of advanced liver fibrosis at diagnosis was also assessed, and these results are presented in Table 3. The results are consistent with those of patients with cirrhosis, and show that the age at presentation was also associated with advanced liver fibrosis (Metavir stages ≥3). The form of the relationship was again not linear and demonstrated a U-shaped curve (Fig. 1B). Almost all patients who presented with a diagnosis of AIH at an age of ≤20 years old (92%) had advanced liver fibrosis. This was significantly higher than patients who presented between ages 21-60 years (age groups 2 and 3) (P < 0.05). The oldest age group (>60 years) was also more likely to have advanced liver fibrosis at diagnosis compared with patients who presented at ages 21-60 years old (P < 0.05). Low serum albumin concentration, prolonged INR, and low platelet count at presentation were again significantly associated with advanced liver fibrosis (P < 0.05).
|Factors (at Diagnosis)||No. Cases with Advanced Fibrosis (%)||OR||95% CI||P-value|
|Age at presentation||0.02|
|Group 1 (0-20yrs)||11 (92%)||4.32||0.50-37.57||NS|
|Group 2 (21-40yrs)||13 (46%)||0.34||0.12-0.94||0.04|
|Group 3 (41-60yrs)||27 (50%)||0.40||0.16-0.95||0.04|
|Group 4 (>60yrs)||28 (72%)||1|
|Anti-SMA (titer ≥1:80)||51 (62%)||1.35||0.67-2.75||NS|
|ANA (titer ≥1:80)||41 (53%)||0.54||0.26-1.11||NS|
|IgG (>14g/L)||71 (61%)||2.10||0.69-6.46||NS|
|Bilirubin (>50μmol/L)||49 (65%)||1.89||0.93-3.82||NS|
|ALP (>150U/L)||47 (60%)||1.03||0.50-2.10||NS|
|Albumin (<36g/L)||42 (86%)||7.62||3.07-18.91||<0.01|
|Platelet (<150U/L)||23 (96%)||21.77||2.84-166.91||<0.01|
|INR (>1.2)||29 (85%)||5.68||2.03-15.88||<0.01|
|Group A (<3x ULN)||13 (52%)||0.65||0.26-1.63||NS|
|Group B (3-5x ULN)||12 (86%)||3.6||0.75-17.32||NS|
|Group C (5-10x ULN)||9 (41%)||0.42||0.16-1.10||NS|
|Group D (>10x ULN)||45 (63%)||1|
Baseline Factors Associated With Incomplete Normalization of ALT at 6 Months.
Six months after diagnosis, 65% of the cohort had complete normalization of ALT to less than 30 U/L. Our usual management strategy for AIH patients is to induce remission with prednisone 40 mg per day and to maintain remission with azathioprine up to 2 mg per kg. Table 4 shows that the only factor that was found to be significantly associated with incomplete normalization of ALT at 6 months was age of ≤20 years at presentation compared to those who presented at >60 years. Compared with adult patients who were diagnosed with AIH after 20 years of age (combining groups 2 to 4), younger patients (diagnosed ≤20 years of age) were 4 times more likely to have a persistently raised ALT 6 months after diagnosis (OR 4.21, 95% CI: 1.19-14.82, P = 0.03). None of the other predefined variables which included gender, pretreatment ALT levels, and histological fibrosis stages had a statistically significant association with incomplete normalization of ALT at 6 months.
|Factors (at Diagnosis)||No. Cases with Abnormal ALT (%)||OR||95% CI||P-value|
|Age at presentation||NS|
|Group 1 (0-20yrs)||8 (67%)||5.8||1.43-23.50||0.01|
|Group 2 (21-40yrs)||8 (29%)||1.16||0.39-3.45||NS|
|Group 3 (41-60yrs)||21 (39%)||1.85||0.75-4.56||NS|
|Group 4 (>60yrs)||10 (26%)||1|
|Anti-SMA (titer ≥1:80)||25 (31%)||0.58||0.28-1.20||NS|
|ANA (titer ≥1:80)||29 (38%)||1.28||0.62-2.64||NS|
|IgG (>14g/L)||42 (36%)||1.42||0.42-2.00||NS|
|Bilirubin (>50μmol/L)||23 (31%)||0.59||0.29-1.21||NS|
|ALP (>150U/L)||33 (42%)||1.90||0.89-4.06||NS|
|Albumin (<36g/L)||17 (35%)||0.96||0.46-2.00||NS|
|Platelet (<150U/L)||12 (50%)||2.11||0.86-5.12||NS|
|INR (>1.2)||15 (44%)||1.65||0.75-3.67||NS|
|Group A (<3x ULN)||8 (32%)||0.89||0.34-2.34||NS|
|Group B (3-5x ULN)||4 (29%)||0.75||0.21-2.64||NS|
|Group C (5-10x ULN)||10 (46%)||1.57||0.59-4.13||NS|
|Group D (>10x ULN)||25 (35%)||1|
|Histological stage ≥ 3||31 (39%)||1.53||0.73-3.21||NS|
Factors Associated With Liver-Related Death or Requirement for Liver Transplantation.
Using Cox proportional hazards regression analysis, three factors were identified as showing a statistically significant association (P < 0.05) with liver-related death or requirement for liver transplantation (Table 5). These were: incomplete normalization of ALT at 6 months from diagnosis, low serum albumin concentration at diagnosis, and age at presentation ≤20 years and >60 years.
|Age at presentation||0.02|
|Group 1 (0-20yrs)||1.24||0.25-6.09||NS|
|Group 2 (21-40yrs)||0.10||0.01-0.85||0.04|
|Group 3 (41-60yrs)||0.15||0.04-0.62||0.01|
|Group 4 (>60yrs)||1|
|Anti-SMA (titer ≥1:80)||0.89||0.29-2.72||NS|
|ANA (titer ≥1:80)||1.03||0.35-3.08||NS|
|Abnormal ALT at 6 months||4.82||1.48-15.72||<0.01|
|Histological stage ≥ 3||4.03||0.89-18.19||NS|
Patients who did not achieve complete normalization of ALT at 6 months had almost a 5-fold increase in risk of having a liver-related adverse outcome. Patients with a low serum albumin concentration at diagnosis, a sign of liver decompensation, had an increased risk of a poor outcome. It is interesting to note that age at presentation was associated with poor outcome. Using the oldest age group (>60 years) as the reference, patients who presented between ages 21-60 years (age groups 2 and 3) had a significantly better prognosis. Patients who presented at a very young age (≤20 years), however, did not have a significantly different prognosis than those in the oldest age group. The prognosis of the youngest age group was significantly poorer than age range 21-60 years (P < 0.05). Figure 2 shows the cumulative Kaplan-Meier survival estimate for liver-related death or liver transplantation for each age group. This shows that at 10 years, 93% of those in the age range 21-40 years and 100% of those in the age range 41-60 years had not died from a liver-related cause and had not had a liver transplant. However, for those in the youngest and oldest age groups the 10-year estimates were 80% (P < 0.01, Log Rank). In short, it is clear that ages at presentation with AIH of ≤20 years and >60 years are associated with poorer liver-related outcome.
Multivariate Cox proportional hazards regression using both forward and backward stepwise analysis confirmed that incomplete normalization of ALT at 6 months from diagnosis, low serum albumin concentration at diagnosis, and age at presentation ≤20 years and >60 years were all independent predictors of liver-related death or requirement for liver transplantation (Table 6). It is important to note that neither advanced liver fibrosis nor cirrhosis at diagnosis was associated with poor outcome in this population-based cohort.
|Age at presentation||0.01|
|Group 1 (0-20yrs)||0.414||0.08-2.12||NS|
|Group 2 (21-40yrs)||0.08||0.01-0.78||0.03|
|Group 3 (41-60yrs)||0.08||0.02-0.40||<0.01|
|Group 4 (>60yrs)||1|
|Abnormal ALT at 6 months||7.79||2.12-28.68||<0.01|
Despite the availability of effective treatment, AIH is not a benign condition. Our earlier study had shown that AIH patients have a 2-fold higher mortality than that of the general population1 and this finding has been confirmed by another long-term study.2 Therefore, it is important to identify patient characteristics that are associated with a poor outcome. We have systematically examined the population-based Canterbury AIH cohort and found that incomplete normalization of ALT at 6 months, low serum albumin concentration at diagnosis, and age at presentation of ≤20 years or >60 years were significant independent predictors of liver-related death or requirement for liver transplantation.
Surprisingly, neither histological advanced liver fibrosis nor cirrhosis at diagnosis was associated with poor liver-related adverse outcomes in this population-based cohort. Instead, we showed that low serum albumin concentration at diagnosis (a sign of liver decompensation) was a more significant determinant of poor outcomes. It is important to note that patients with cirrhosis were equally likely to achieve complete normalization of ALT as patients with mild fibrosis. These results suggest that patients with cirrhosis should be offered prompt treatment to avoid hepatic decompensation. Our finding that incomplete normalization of ALT at 6 months independently predicts poor outcome provides evidence to further support recent reports and guideline recommendations that complete normalization of ALT should be the goal of treatment in patients with AIH.14-16 However, as IgG levels were not analyzed during therapy in this study, their role as surrogate markers for treatment response could not be validated.
AIH patients who present at a young age (≤20 years) had a higher risk of advanced liver fibrosis at diagnosis and poorer prognosis when compared to patients who presented between ages 21-60 years old. Almost all of them (11 out of 12) had advanced liver fibrosis at diagnosis. The only patient with Metavir stage 2 fibrosis at diagnosis also progressed to cirrhosis on repeat liver biopsy within 4 years despite appropriate treatment. Interestingly, a high incidence of cirrhosis at diagnosis in children with AIH has been reported in a number of case series.17-20 We found that, of those who had not progressed to cirrhosis, most had already developed severe fibrosis. Even more worryingly, when compared to patients who developed AIH in adulthood, these young patients were more resistant to treatment or less likely to achieve complete normalization of ALT at 6 months. These observations suggest that children and adolescents with AIH may have an aggressive phenotype, and may require a more aggressive management strategy.
Although AIH was classically described as a disease of young women, several studies have indicated that this is not the case and may reflect selection biases in studies from referral centers.21-23 In fact, the incidence of AIH in the elderly is probably much higher than we used to believe. Our earlier population-based epidemiology study confirmed that AIH presents predominantly in older women, with a peak in the sixth decade.11 In our cohort, a sizable proportion of AIH patients (29%) presented at >60 years old. These patients had a higher frequency of cirrhosis at diagnosis as well as poorer liver-related adverse outcomes when compared to patients who presented between 21-60 years of age.
There have been conflicting results from various case series on these matters,14, 17, 18, 20, 21 with many reporting no difference in outcomes or the incidence of cirrhosis in older patients compared to younger patients.18, 21, 22, 24, 25 However, some of these discrepancies could be explained by the way in which patients were grouped. For example, grouping patients aged <3024 or <6022 years at diagnosis together would have included those who developed AIH at age ≤20 years. As we have shown, the relationship between cirrhosis and outcomes with age at presentation is not linear, and patients who developed AIH at age ≤20 years had a high incidence of cirrhosis at diagnosis and poorer liver-related adverse outcomes. Therefore, inclusion of patients who developed AIH at age ≤20 years into the younger group would lead to observations concerning differential outcomes being missed. In addition, as previous case series were performed in specialist liver units, they may be subjected to referral bias that could have attracted younger patients with more severe disease and potentially skewing the severity of disease in younger patients.
The relationship between cirrhosis and age at presentation was not linear and had a U-curve pattern with higher incidence seen in ages ≤20 years and >60 years. In addition, a significantly higher incidence of cirrhosis at diagnosis was also seen in male patients. These observations suggest that such patients may either have a more aggressive disease phenotype or, conversely, a more indolent disease with delay in diagnosis.24 These findings may also reflect differences of immune responses in different age groups. Alternatively, one could also hypothesize that these observations raise the possibility of a role in hormonal influence on the disease phenotypic expression, as more severe stages of disease were seen in younger (pubertal), postmenopausal (>60 years old), and male patients. A hormonal influence on AIH pathophysiology is conceivable, as disease behavior is known to be altered by pregnancy.26-28 In addition, it has been shown that estrogen may modify immune responses in other autoimmune diseases.29-32 However, if female sex hormones do play a role in AIH disease manifestation, their mechanism and interaction with the immune system is likely to be complex. Further studies are needed to investigate whether hormones such as estrogen and progesterone had any direct effect on AIH.
In conclusion, incomplete normalization of ALT at 6 months, low serum albumin concentration at diagnosis, and age at presentation of ≤20 years or >60 years were significant independent predictors of liver-related death or requirement for liver transplantation. Patients who developed AIH as a child or adolescent had a very high incidence of advanced fibrosis at diagnosis, and there is an unmet medical need for better treatment of these patients. Higher frequencies of cirrhosis at diagnosis were seen in male and older patients, although histological cirrhosis at diagnosis was not associated with poor prognosis and did not influence the response to initial immunosuppressive treatment.
- 21Autoimmune hepatitis in the elderly. Am J Gastroenterol 2001; 96: 1587-1591., , , , .Direct Link:
- 28Improvement of autoimmune hepatitis during pregnancy followed by flare-up after delivery. Am J Gastroenterol 2002; 97: 3160-3165., , , .Direct Link: