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Gastrointestinal Imaging |
1 From the Departments of Radiology (F.B., W.B.H., H.R., Z.F., R.C.S.), Medicine (R.S.), and Pathology and Laboratory Medicine (J.T.W.), University of North Carolina, CB 7510, 101 Manning Dr, Chapel Hill, NC 27599-7510; and Cardiovascular Disease Program, School of Public Health, University of North Carolina, Chapel Hill, NC (G.V.). Received July 19, 2005; revision requested September 6; revision received November 9; accepted December 23. Address correspondence to R.C.S. (e-mail: richsem{at}med.unc.edu).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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MATERIALS AND METHODS: This study was compliant with the Health Insurance Portability and Accountability Act and approved by the institutional review board. The need for informed consent was waived. Thirty-two patients (29 female and three male patients; mean age, 44 years; age range, 14–69 years) undergoing treatment for AIH underwent unenhanced and gadolinium-enhanced MR imaging. Two radiologists reviewed all cases independently to determine the presence of patchy or heterogeneous liver enhancement, biliary duct changes, lymphadenopathy, and findings of portal hypertension. Fibrosis was graded as mild, moderate, or severe reticular (corresponding to a grading scale of 1–3) or as confluent. Agreement between radiologists was assessed by using 
coefficients. Mean MELD scores were compared across fibrosis categories by using the Kruskal-Wallis analysis of variance.
RESULTS: Of the 32 patients, two (6%) had no imaging findings of cirrhosis. Thirty patients (94%) had reticular fibrosis with a mean grade of 1.8. Six patients had confluent fibrosis, and all six had associated reticular fibrosis. Mild intrahepatic biliary duct dilatation involving the right and left lobes was observed in four patients (12%). Lymphadenopathy was observed in 12% of patients. None of the patients had hepatocellular carcinoma. There was no significant overall association between fibrosis grade and MELD score (P = .36).
CONCLUSION: Although fibrosis is a common feature in AIH and is often moderate to severe, no significant correlation between fibrosis grade and MELD score was found.
© RSNA, 2005
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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A definite diagnosis of AIH is established in patients with elevated autoantibody levels (including antinuclear antibody and smooth muscle antibody), hyperglobulinemia, interface hepatitis without histologic evidence of coexistent disease, and a predominant serum aminotransferase abnormality. Genetic, acute viral, and toxic causes must be excluded (1). Overlap syndromes involving AIH and other immune-mediated causes such as primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and autoimmune cholangitis can occur (3,4). AIH-PSC overlap is the most common overlap syndrome, with a reported overlap of 41%–54% in several series (3). An accurate diagnosis of AIH versus an overlap syndrome has important treatment and prognostic implications (3,4).
The imaging findings of PBC (5) and PSC (6) have previously been described. To our knowledge, however, the imaging findings of AIH have not been previously published. Thus, the purpose of our study was to retrospectively evaluate the morphologic and enhancement features of the liver on MR images obtained in patients with AIH and to determine if there is a correlation between MR imaging findings and the severity of clinical disease as measured with the Mayo end-stage liver disease (MELD) score.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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In all patients, the diagnosis of AIH was made on the basis of the presence of at least three of the following diagnostic criteria defined by the International Hepatitis Group: (a) antinuclear antibodies, anti–smooth muscle antibodies, anti–liver-kidney microsome type I antibodies, or anti–liver cytosol antibodies at substantial titers; (b) a 
-globulin level of more than 20 g/L; (c) coexistence of nonhepatic autoimmune diseases, including autoimmune thyroiditis, rheumatoid arthritis, and systemic lupus erythematosis, and the elimination of other forms of hepatitis such as viral or toxic hepatitis; and (d) histologic examination findings consistent with AIH (1,2).
The MELD score was used to measure the severity of liver cirrhosis. The MELD score is calculated on the basis of the total serum bilirubin level (in milligrams per deciliter), the creatinine level (in milligrams per deciliter), and the international normalized ratio for prothrombin time. One patient did not have all of the serologic data necessary to calculate the MELD score; thus, the MELD score was calculated for 31 patients. Patients were classified into one of three groups according to the MELD score: group 1 had MELD scores lower than 10, group 2 had scores of 10–19, and group 3 had scores higher than 19 (7).
MR Imaging
All MR images of the abdomen were obtained with a 1.5-T unit (Vision or Sonata; Siemens Solutions, Malvern, Pa) by using a phased-array torso coil. The following MR sequences were used: transverse fat-suppressed and coronal T2-weighted single-shot turbo spin echo (single-shot repetition time, effective echo time of 90 msec), transverse turbo short-inversion-time inversion recovery (5000/81 [repetition time msec/echo time msec]), transverse and coronal T1-weighted in-phase spoiled gradient echo (GRE) (140/4.5, 80° flip angle), and transverse out-of-phase spoiled GRE (140/2.2, 80° flip angle). Serial contrast material–enhanced GRE images were acquired with the spoiled GRE sequence initiated 18 seconds after the start of the gadolinium chelate (gadodiamide [Omniscan]; Amersham, New York, NY) injection. Twenty milliliters of 0.5 mmol/L contrast material was injected at a rate of 2 mL/sec. A second transverse data set was acquired 45 seconds after completion of the contrast material injection by using either a transverse spoiled GRE or three-dimensional volumetric interpolated breath-hold examination (4.7/2.2). A fat-suppressed transverse T1-weighted spoiled GRE sequence (147/4.1, 80° flip angle) was performed 90 seconds after contrast material administration.
Image Interpretation
All MR images were retrospectively reviewed independently by two abdominal radiologists (W.B.H., H.R.). The images were subsequently interpreted in consensus. Both radiologists had MR imaging fellowship training with either 7 years (W.B.H.) or 1 year (H.R.) of experience in the interpretation of MR images of the liver. The two readers evaluated the MR images for (a) the presence and pattern of fibrosis, (b) the enhancement pattern, (c) intrahepatic biliary duct dilatation, and (d) the morphologic features.
The imaging pattern of liver fibrosis was characterized as absent, reticular, confluent, or both reticular and confluent. Reticular fibrosis was defined as fine lines that had low signal intensity at short echo time out-of-phase MR imaging and showed prominent enhancement on the 90-second gadolinium-enhanced MR images. A four-point scoring system was used to evaluate the extent of reticular fibrosis, as follows: 0 for none, 1 for mild, 2 for moderate, and 3 for severe. We defined mild reticular fibrosis as a fine network of linear fibrous tissue with a diameter of less than 2 mm without obvious liver surface nodularity, moderate reticular fibrosis as linear fibrotic strands measuring 2–5 mm with liver surface nodularity caused by intervening bands of fibrosis, and severe reticular fibrosis as thick fibrotic strands measuring more than 5 mm. Confluent fibrosis was defined as a region of amorphous fibrosis, greater than 2 cm in diameter, that showed the same pre- and postcontrast MR characteristics as reticular fibrosis. Confluent fibrosis was defined as being either isolated or associated with reticular fibrosis. The enhancement pattern was characterized as homogeneous or patchy on early contrast-enhanced MR images (8).
Intrahepatic biliary duct dilatation was considered to be present if the diameter of the intrahepatic duct was greater than 3 mm, as determined with half-Fourier rapid acquisition with relaxation enhancement or delayed contrast-enhanced MR imaging. Intrahepatic biliary dilatation was considered to be general when it involved the entire liver and segmental when it involved only a segmental or subsegmental distribution (6).
Morphologic liver findings that were assessed included liver volume, segmental enlargement or atrophy, caudate lobe enlargement, surface nodularity, hepatic steatosis, and presence of hypervascular nodules (9–11). Liver volume was determined by manually tracing the liver boundary on consecutive 8–10-mm-thick sections of a data acquisition encompassing the entire liver. Surface nodularity was assessed subjectively by evaluating the irregularities along the liver surface. Liver steatosis was determined subjectively by observing the signal loss on out-of-phase images as compared with the intensity of the signal on in-phase images. The presence of liver nodules was determined by using previously reported criteria (12).
Additional criteria were based on evaluation of periportal and portocaval lymphadenopathy (short axis greater than 1 cm), portal vein thrombosis, varices, splenomegaly (defined as greater than 13 cm in maximum dimension), and ascites.
Statistical Analysis
The prevalence of MR imaging findings was estimated as a percentage of the patients displaying each abnormality. The agreement between the two radiologists was assessed by using the statistic with associated 95% confidence intervals. For the agreement about the severity of fibrosis, described on an ordinal scale, a weighted coefficient was used to weigh extreme disagreements more heavily than close disagreements. The overall association between MELD score and fibrosis categories was assessed with a contingency table by using the Fisher exact test.
The Kruskal-Wallis analysis of variance (ANOVA) was used to evaluate the differences between MELD scores when compared across fibrosis categories. Because the groups to be compared presented a nonnormal distribution, Kruskal Wallis ANOVA was used as a nonparametric alternative to one-way ANOVA. (Unlike the standard ANOVA, the Kruskal-Wallis ANOVA does not assume normality.) All statistical tests were evaluated at the .05 level of statistical significance. Our sample size was limited to 32 patients. With this sample size, our study had a power of 70% for the detection of an effect size, 
(specified by the difference between the largest mean and the smallest mean, in units of the within-cell standard deviation) of 1.25, and 
level of significance of .05. All statistical analyses were performed by using SAS, version 8.1 (SAS Institute, Cary, NC), statistical software.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Imaging Findings
Of the 32 patients, two (6%) had no imaging findings of cirrhosis. Reticular fibrosis was observed either independently or by consensus in 30 (94%) patients. Mild fibrosis (Fig 1) was diagnosed in 14 patients (44%) by one reader, in 11 patients (34.%) by the other reader, and in 11 patients (34%) by consensus. Moderate fibrosis (Fig 2) was diagnosed in 12 patients (38%) by one reader, in 14 patients (44%) by the other reader, and in 14 patients (44%) by consensus. Severe fibrosis (Fig 3) was diagnosed in four patients (12%) by one reader, in five patients (16%) by the other reader, and in five patients (16%) by consensus. With use of the grading scale for fibrosis described earlier, the mean fibrosis grade was 1.7. Confluent fibrosis was observed most commonly in liver segment eight and was present in this location in four of six patients with confluent fibrosis. Patchy enhancement was observed by both readers in 10 patients (31%).
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Hypervascular nodules were observed in nine patients (28%) by one reader, in seven patients (22%) by the other reader, and in seven patients (22%) by consensus. In those patients in whom hypervascular nodules were observed, the mean nodule diameter was 7 mm (range, 4–9 mm). The mean number of hypervascular nodules was 1.7. No siderosis was seen within these nodules at unenhanced T1-weighted imaging. None of our patients had hepatocellular carcinoma. Large regenerative nodules (>2 cm in diameter) were observed by both readers in two patients (6%). In both cases, the nodules were isointense to liver parenchyma at T1- and T2-weighted imaging without evidence of siderosis, demonstrated a contrast enhancement pattern comparable to that of the surrounding liver parenchyma, and were centrally located in the region of the porta hepatis. Neither of these patients had associated biliary dilatation.
Liver surface irregularity was observed by both readers in 20 patients (62%). With consensus reading, caudate lobe enlargement was observed in three patients (9%), lateral segment enlargement was observed in eight (25%), left medial segmental atrophy was observed in 18 (56%), and right lobe atrophy was observed in eight (25%). With consensus reading, findings of portal hypertension included varices in 29 patients (91%), ascites in 12 (38%), and splenomegaly in 22 (69%).
Lymphadenopathy was observed in four patients (12%), and portal vein thrombosis was observed in two (6%). Calculated liver volumes ranged between 673 and 2086 mL, with a mean volume of 1175 mL.
Reader Agreement and MELD Scores
The agreement between the two radiologists was highest with regard to the severity of fibrosis, with a linear weighted coefficient of 0.79 (95% confidence interval: 0.61, 0.97). Fair agreement was observed for hypervascular nodules ( = 0.51; 95% confidence interval: 0.16, 0.84). There was no significant overall association between fibrosis grade and MELD score (P = .36, two-sided Fisher exact test). The mean MELD scores in the patients with low, moderate, and severe fibrosis were 12.23, 12.36, and 10.50, respectively. There were no significant differences between the mean MELD scores across these fibrosis groups (P = .76).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Another interesting feature of AIH is that it commonly occurs in combination with other liver diseases such as PSC, PBC, and viral hepatitis. We excluded six patients from our study owing to overlap syndrome because our intention was to determine the MR imaging findings of AIH specifically. Although overlapping, AIH-PBC is characterized by the serologic findings of PBC—that is, antimitochondrial antibody positivity—and the histologic findings of chronic AIH. Overlap syndrome occurs in 5% of patients with AIH and in 19% of those with PBC (3). Overlapping AIH-PSC is characterized by the clinical features of AIH, but cholestatic clinical and/or laboratory features, antimitochondrial antibody negativity, coexistent chronic ulcerative colitis, and an abnormal cholangiogram are compatible with PSC. To our knowledge, the frequency of AIH-PSC has not been established (3). Overlapping AIH–viral hepatitis should be suspected in patients with a highly elevated antimitochondrial antibody level and/or antinuclear antibody and hypergammaglobulinemia (3).
The role of MR imaging in the evaluation of cirrhosis has been previously reported (9–11). Fibrosis is a consistent feature in liver cirrhosis and a major factor in the distortion of liver architecture that is observed on imaging studies. Histologic findings show that fibrosis is present in all types of AIH and may progress or regress depending on therapeutic response (4,13). Although the presence of fibrosis has been previously described in MR imaging studies (8,11), in the current study we attempted to grade the severity of fibrosis and correlate the MR imaging grade with the MELD score. Diffuse reticular fibrosis was the most common pattern of fibrosis; it was observed in 94% of patients. AIH has been described as resulting in extensive fibrosis at histopathologic examination (13); this description is consistent with our findings. Biliary duct dilatation is a typical finding in PSC and has been observed in 80% of patients with this disease (6). In our study, we observed biliary duct dilatation in 12% of patients with AIH. Because of the common occurrence of AIH-PSC overlap syndrome, the observation that biliary duct dilatation occurs in AIH alone may be important to recognize.
Surface nodularity was observed in 62% of our patients and was associated with moderate to severe reticular fibrosis in all cases, with small regenerative nodules occurring between fibrotic strands. Regions of increased enhancement on immediate contrast-enhanced spoiled GRE images were observed in 31% of our patients. This likely represented acute inflammation superimposed on chronic hepatitis. Patchy early enhancement after the administration of contrast material has been described as reflecting recent hepatocellular damage (8). It should be noted that all of our patients were receiving treatment at the time of their examinations and that treatment may have ameliorated the findings of early enhancement. Early patchy enhancement may be a dominant finding in patients with AIH before treatment because of the intense inflammatory infiltrates found in these patients at histopathologic examination (13). This would need to be ascertained in future investigations evaluating the appearance of AIH at initial presentation.
None of our patients had hepatocellular carcinoma. Although hypervascular nodules that likely represented dysplastic nodules were observed in 22% of patients, they remained stable during the entire follow-up period. Our observation supports the findings described previously: that hepatocellular carcinoma is rare in AIH (14).
Lymphadenopathy is a prominent feature in other forms of cirrhosis such as viral hepatitis, PSC, and PBC (6,15,16). However, in our study it was observed in only 12% of the patients and was neither a prominent nor a consistent finding in the patients with AIH.
Liver volume was calculated in all patients, and global atrophy was the most common finding. Caudate lobe enlargement, which has been described as a prominent feature in other forms of cirrhosis, especially PSC (6), was observed in only 9% of the patients, and left lateral segment enlargement was observed in 25% of the patients.
The correlation between the MELD score and the extent of fibrosis as measured with MR imaging was not significant. This may have reflected several factors, including the following: (a) Macroscopic bands of fibrosis that are detectable with MR imaging do not correlate well with severity of liver disease, (b) the responsiveness of AIH to corticosteroids and the fact that all patients were receiving treatment may result in a complex picture of clinical status, and (c) we did not incorporate abnormal early enhancement into the grading system of fibrosis. Inclusion of enhancement may be essential because histopathologic grading of cirrhosis also includes assessment for the presence of cellular infiltrates (13). Early work in MR imaging revealed that early patchy enhancement corresponds to cellular infiltrates and hepatocellular necrosis (8). An additional factor may be the use of fibrotic band thickness alone as the criterion for the assessment of severity of fibrosis. In a reticular network of fibrosis, both band thickness and band density are necessary to quantify the total volume of reticular fibrosis visualized at MR imaging. Volume segmentation of a reticular network, however, would be a difficult quantitative problem, and this was not attempted in this study.
Our study had several limitations. Although we defined three levels of fibrosis severity, we did not have histopathologic confirmation. Because the diagnostic criteria for AIH do not necessarily require biopsy material, pathologic liver core-needle biopsy material was acquired in only 72% of our patients. In addition, a single core-needle biopsy might result in substantial sampling error in terms of the severity of fibrosis if the severity was not uniform. For example, confluent regions of fibrosis in the dome of the liver would not typically be detected. Instead, we attempted to correlate these MR imaging findings with the MELD score. We also did not incorporate early patchy enhancement into the assessment of severity. None of the patients underwent imaging at initial presentation, and we did not attempt to correlate the imaging findings with treatment response as determined by using the clinical findings.
Although we excluded patients with a clinical diagnosis of overlap syndrome, it is conceivable that there were additional patients with overlap syndrome because not all patients underwent biopsy. For example, among the four patients with intrahepatic biliary dilatation, only one had biopsy-proved AIH; an undiagnosed overlap syndrome with PSC could have existed in the remaining three patients. Because central macroregenerative nodules are also correlated with end-stage liver disease due to PSC (6), it is worth noting that the four patients with intrahepatic biliary dilatation were distinct from the two patients with central macroregenerative nodules. In a recent review of AIH and its variant syndromes (3), the coexistence of PBC in patients with AIH was estimated at 5%; however, no estimate was given for AIH-PSC overlap. In our study, five of 40 patients were excluded owing to a diagnosis of overlap syndrome.
Future studies should be conducted to determine whether the extent of fibrosis in AIH, as measured with MR imaging, might exhibit progression or diminution in response to corticosteroid therapy. It might be interesting to correlate the extent of fibrosis with the MELD score in other patient populations. In one previous study (6), MR features were correlated with MELD score in patients with PSC. The authors did not find good correlation. This suggests that morphologic changes and fibrosis visualized with MR imaging may not enable an adequate characterization of the severity of liver compromise.
In summary, we have described the MR imaging appearance of AIH. The majority of patients were female. Extensive reticular and/or confluent fibrosis is a common finding, and the presence of either form may help to establish the diagnosis. Global atrophy of the liver without enlargement of the caudate lobe and/or the left lateral segment, as was a lack of prominent lymphadenopathy, also was observed in a high percentage of the patients. The fact that hepatocellular carcinoma was not observed in any of our patients reflects its rarity in these patients. Despite the common imaging finding of fibrosis in the patients with AIH, no significant correlation was found between the extent of fibrosis and the MELD score.
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FOOTNOTES |
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Abbreviations: AIH = autoimmune hepatitis • ANOVA = analysis of variance • GRE = gradient echo • MELD = Mayo end-stage liver disease • PBC = primary biliary cirrhosis • PSC = primary sclerosing cholangitis
Authors stated no financial relationship to disclose.
Author contributions: Guarantors of integrity of entire study, W.B.H., R.C.S.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, F.B., W.B.H., H.R.; clinical studies, F.B., W.B.H., R.S., J.T.W., R.C.S.; statistical analysis, F.B., W.B.H., H.R., V.G.; and manuscript editing, F.B., W.B.H., H.R., Z.F., R.C.S.
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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  J. Q. Knowlton, A. J. Taylor, M. Reichelderfer, and J. Stang Imaging of Biliary Tract Inflammation: An Update Am. J. Roentgenol., April 1, 2008; 190(4): 984 - 992. [Abstract] [Full Text] [PDF]
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