Clinical management of autoimmune hepatitis Pape, Simon; Schramm, Christoph; Gevers, Tom JG
United European Gastroenterology Journal,
November 2019, Volume:
7, Issue:
9
Book Review, Journal Article
Peer reviewed
Open access
Autoimmune hepatitis is a rare and chronic liver disease that is characterised by increased serum transaminases and immunoglobulin G, inflammatory liver histology and presence of circulating ...autoantibodies. An autoimmune hepatitis diagnosis justifies life-long treatment in most patients in order to prevent development of cirrhosis and end-stage liver disease. The cornerstone of treatment is steroid induction therapy followed by maintenance therapy with azathioprine, which is effective in most cases. For patients who do not respond to standard treatment, second-line treatment with other immunosuppressants can be effective. Treatment should be aimed at biochemical remission of the disease, which is defined as normalization of transaminases and immunoglobulin G. Patients should be monitored intensively during the first months of treatment in order to monitor side-effects, assess symptoms and individualise treatment. Specialist consultation should be sought in difficult-to-treat patients. Future studies and networking initiatives should result in optimization of current treatment strategies in autoimmune hepatitis.
In autoimmune hepatitis (AIH), normal levels of transaminases and IgG define biochemical remission and are considered the best surrogate markers for histological remission. This study assessed ...whether this also applies to patients with AIH cirrhosis.
In this European multicentric study, we included 125 biopsies from 113 patients with AIH and histologically proven cirrhosis; 105 biopsies from 104 patients with AIH without cirrhosis served as controls. Biochemical parameters were available within 4 weeks of biopsy. AIH activity was graded according to the modified Hepatitis Activity Index (mHAI), with mHAI ≥4/18 considered to indicate risk of disease progression.
In total, 47 out of 125 liver biopsies were obtained from patients with AIH cirrhosis and normal ALT levels at time of biopsy. Only 26% (12/47) of those livers showed histological remission (mHAI <4/18), whereas 36% (17/47) showed moderate to high histological activity (mHAI ≥6/18). In patients with noncirrhotic AIH, 88% (46/52 biopsies) of cases with normal ALT levels had histological remission and only 4% (2/52) had an mHAI ≥6/18 (p <0.001). The addition of IgG to define complete biochemical remission only slightly improved the association with histological remission in the limited number of patients with AIH cirrhosis available for analysis 29% (5/17) of biopsies with mHAI <4/18. ALT correlated closely with mHAI in AIH without cirrhosis but poorly in AIH with cirrhosis.
In contrast to patients with noncirrhotic AIH, in patients with AIH cirrhosis, who are at risk of disease progression, normal ALT levels and potentially also complete biochemical remission are poor surrogate markers of histological remission. Thus, new biomarkers are needed to monitor disease activity and progression in patients with AIH cirrhosis.
Autoimmune hepatitis (AIH) is an inflammatory disease of the liver that usually responds to immunosuppressive therapy. Serum transaminases and IgG levels within the normal ranges define complete biochemical remission and are considered as surrogate markers for histological disease activity. Here, we show that those biochemical markers are not sufficient to indicate low disease activity in patients with AIH and already established cirrhosis. Consequently, until better biomarkers for disease activity are found, only liver biopsy can reliably indicate disease activity in the presence of cirrhosis. Additional investigations, such as measurements of liver stiffness, should be undertaken to monitor non-invasively for disease progression in patients with AIH and established cirrhosis.
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•A considerable proportion of patients with AIH cirrhosis show histological disease activity despite normal ALT levels.•Addition of IgG only slightly improves the prediction of low histological activity in patients with AIH and cirrhosis.•ALT and IgG do not correlate sufficiently with histological activity in AIH cirrhosis.•New surrogate markers of histological activity are needed in patients with AIH cirrhosis.
High IgG levels are considered a hallmark of autoimmune hepatitis (AIH). A subgroup of patients with AIH has IgG within the normal range despite evidence of clinical disease activity. The clinical ...significance of this biomarker has not been explored.
In a European multicentre study we compared biochemical, clinical and histological features from patients with AIH and normal IgG-values at diagnosis to an age- and sex-matched control group of patients with typical AIH presenting with elevated IgG. Data were assessed at diagnosis, after 12 months of therapy and at last follow-up.
Out of 1,318 patients with AIH, 130 (10%) had normal IgG at presentation. Histological and biochemical parameters at diagnosis, as well as treatment response, showed no difference between groups. Stable remission off treatment was achieved more commonly in the normal IgG group than in the typical AIH group (24 vs. 8%; p = 0.0012). Patients of the control group not only had higher IgG levels (29.5 ± 5.8 vs. 12.5 ± 3.2 g/L; p <0.0001), but also a higher IgG/IgA ratio (9.3 ± 6.9 vs. 5.4 ± 2.4; p <0.0001) at diagnosis. The IgG/IgA ratio only declined in patients with typical AIH and was no longer different between groups after 12 months (6.3 ± 4.3 vs. 5.5 ± 2.2; p = 0.1), indicating a selective increase of IgG in typical AIH and its suppression by immunosuppression. Autoantibody titres were higher in the typical AIH group, but not when controlled for IgG levels.
Compared to AIH with typical biochemical features, patients with normal IgG levels at diagnosis (i) show similar biochemical, serological and histological features and comparable treatment response, (ii) appear to lack the selective elevation of serum IgG levels observed in typical active AIH disease, (iii) may represent a subgroup with a higher chance of successful drug withdrawal.
A characteristic feature of autoimmune hepatitis (AIH) is an elevation of immunoglobulin G (IgG), which is therefore used as a major diagnostic criterion, as well as to monitor treatment response. Nevertheless, normal IgG does not preclude the diagnosis of AIH. Therefore, we herein assessed the features of patients with AIH and normal IgG in a large multicentre study. This study demonstrates that about 10% of all patients with AIH have normal IgG; these patients are indistinguishable from other patients with AIH with respect to biochemical markers, liver histology, disease severity and treatment response, but might represent a subgroup with a higher chance of remission after drug withdrawal.
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•Patients with AIH and normal IgG comprise around 10% of all patients with AIH.•These patients are indistinguishable from patients with typical AIH by biochemical markers or liver histology.•They have no selective IgG elevation, with lower IgG and IgA levels than patients with typical AIH.•These patients might represent a subgroup in whom there is a high chance of successful drug withdrawal.
New porous materials based on covalently connected monomers are presented. The key step of the synthesis is an acetalisation reaction. In previous years we used acetalisation reactions extensively to ...build up various molecular rods. Based on this approach, investigations towards porous polymeric materials were conducted by us. Here we wish to present the results of these studies in the synthesis of 1D polyacetals and porous 3D polyacetals. By scrambling experiments with 1D acetals we could prove that exchange reactions occur between different building blocks (evidenced by MALDI-TOF mass spectrometry). Based on these results we synthesized porous 3D polyacetals under the same mild conditions.
Recently we introduced iron trichloride as an environmentally benign and cost-efficient reagent for the synthesis of N-benzoylguanidines. This highly attractive synthetic approach grants access to a ...broad spectrum of N-benzoylguanidines under mild conditions in short reaction times. In this work we present an extended scope of our methodology along with the results obtained from mechanistic studies via in situ IR spectroscopy in combination with LC (liquid chromatography)-MS analyses. On the basis of these new mechanistic insights we were able to optimize the synthetic protocol and to develop an alternative mechanistic proposal. In this context the symbiotic roles of iron trichloride and oxygen in the guanylation process are highlighted.
In situ generated palladium on aluminum oxide provides an active catalytic system for Matsuda-Heck reactions in gram-scale. The novel catalyst proceeded through a significantly higher catalytic ...activity compared to the classical Pd/C system. Based on the high catalytic activity the first α,β,β-triarylation of methyl acrylate in good yields could be provided in one-step.
A new synthetic approach for the guanylation of aroylthioureas using iron trichloride is presented. Our synthetic method distinguishes itself by benign reaction conditions, low costs and a broad ...product spectrum. The scope of the reaction and calorimetric studies are described.
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