Tag Archives: autoimmune hepatitis

Infliximab for Autoimmune Hepatitis

Posted on by

C Efe et al. Hepatology 2025; 81: 1660-1670. Efficacy and safety of infliximab in patients with autoimmune hepatitis

In this multicenter retrospective study, there were two groups of patients with autoimmune hepatitis (AIH) who received infliximab treatment:

  • Group 1 (n=20) had failed standard, second-line (mycophenolate mofetil and 6-mercaptopurine) or third-line (tacrolimus or cyclosporine) therapy.
  • Group 2 (n=22), infliximab was given for treatment of concomitant extrahepatic autoimmune diseases. Only 6 of these patients had active AIH at time of initiation of infliximab therapy

Key findings:

  • Overall, 65% (17/26) of the patients with active AIH achieved complete biochemical remission* (CR) on infliximab.  This included CR in 75% (6/8) of nonresponders to second-line and in 46% (6/13) of failing third-line therapy.
  • *CR defined as normalization of serum transaminases and IgG levels
  • Five patients developed anti-infliximab antibodies, 1 had an allergic reaction and 4 had a lack of control of a concurrent autoimmune disorder, prompting discontinuation of infliximab

My take: While a randomized controlled trial would be better, this study demonstrates that infliximab is an option for AIH, especially in those with concurrent immune-mediated disorders and in those not responding to standard therapy. It is worth noting that infliximab can paradoxically induce an autoimmune hepatitis and stopping infliximab therapy can be curative in these patients (we recently had such a case).

Related blog posts:

Current Practices and Wide Variation in Autoimmune Hepatitis Treatment Across Europe

Posted on by

M Cananzi et al. J Pediatr Gastroenterol Nutr. 2025;80:260–270. Current practice in the management of paediatric autoimmune liver disease in Europe

Methods: Thirty-six centers from 22 European countries responded to the survey that was sent to European Reference Network for Rare Liver Disorders (ERN RARE-LIVER) and members of the Hepatology Interest Group (HIG) of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN)

Key findings:

  • All centers use predniso(lo)ne as first-line therapy, alone (15/36) or with azathioprine (21/36)
  • Azathioprine and mycophenolate are the preferred second-line options in centres using first-line steroid monotherapy (11/15) or combined steroid-azathioprine (19/21)
  • Tacrolimus is used as third-line agent in 15/36 centers
  • Proactive measurement of drug metabolites and target levels vary widely among centers. About 27/36 centers have thiopurine methyltransferase (TPMT) genotyping available, of which 21 (58%) routinely perform this test before prescribing AZA. Among the 12 centres that reported target metabolite levels, 10 aim for levels between 200 and 300 pmol/8 × 108 red blood cells (RBC).
  • About 24/36 centers routinely incorporate PPIs into steroid treatment protocols, seven prescribe PPIs solely when there are risk factors for peptic ulcer disease, and the remainder refrain from using PPIs unless gastrointestinal symptoms occur.

My take: There is a great deal of variation in the management of autoimmune hepatitis indicating the need for more collaborative efforts to advance evidence-based therapeutic strategies.

Related blog posts:

White Temple, Chiang Rai, Thailand

Key Advances in 2024: An Overview from GutsandGrowth (Part 2)

Posted on by

This year I had the opportunity to give a lecture to our group that reviewed much of the important advances that happened in 2024. Here are some of the slides (if you have any trouble reading the slides, you can search for the original blog post using author name).

Teaching an Old Dog a New Trick: Optimizing Thiopurine Therapy in Autoimmune Hepatitis

Posted on by

Key findings:

  • Over 4 years (N = 146), patients with higher average 6TGN levels were associated with those with stable complete biochemical remission (CBR) (260 pmol/0.2 mL) compared to those failing to maintain CBR (181 pmol/0.2 mL; p = 0.0014) or never achieving CBR (153 pmol/0.2 mL; p < 0.0001), with an optimal 6TGN cutoff of ≥223 pmol/0.2 mL
  • Adding allopurinol to thiopurines in difficult-to-treat patients (N = 36) raised 6TGN (168→321 pmol/0.2 mL; p < 0.0001) and lowered 6MMP (2125→184 pmol/0.2 mL; p < 0.0001), resulting in improved transaminases in all patients and long-term CBR in 75%.
  • Limitation: most of the 337 patients did NOT have sequential azathioprine metabolite monitoring. This could indicate that the 146 patients with sequential monitoring could have a selection bias favoring patients with a more aggressive disease course. Thus, the proposed 6-TGN level of 223 may not be applicable for all patients.

From editorial:

  • “In this issue of Hepatology, “Weltzsch et al1 conducted a multicenter study on the metabolic monitoring of thiopurines in AIH. The authors defined an optimal cutoff of ≥223 pmol/0.2 mL average 6TG level to maintain long-term biochemical remission (BR). Notably, 66% of patients with 6TG levels above this cutoff sustained BR rates. 
  • Allopurinol shifts the thiopurine metabolism toward 6TG production, allowing thiopurine dose reduction to 25%–30%, which improves efficacy and tolerability. (The 100 mg dose of allopurinol had more favorable 6MMP/6TG ratio).
  • However, they note that in a prior study (J Hepatol 2021; 75: 324-32), “patients with subtherapeutic 6TG levels (75–225) achieved similar BR rates (75% vs. 81%, p = 0.589) to those with therapeutic levels (225–450), while experiencing significantly fewer adverse drug reactions (44% vs. 86%, p = 0.0002).”
Proposed Algorithm

My take: This study shows in patients who have not achieved a biochemical remission, optimization of azathioprine dosing with metabolite monitoring improves biochemical remission. In those with low 6TG and low 6MMP, increasing the azathioprine should be considered. In those with low 6TG and high 6MMP, reducing azathioprine and adding allopurinol should be considered.

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Metabolite Spectroscopy As a Diagnostic Tool for Autoimmune Hepatitis

Posted on by

A Dimou et al. Hepatology 2024; 80: 266-277. NMR-based metabolomic signature: An important tool for the diagnosis and study of pathogenesis of autoimmune hepatitis

Methods: The authors examined treatment-naive patients with well-established AIH and compared them to healthy controls and those with other liver diseases.

Key Finding:

  • Fifteen metabolites (out of a total of 52 analyzed) differentiated AIH from disease controls (PBC+chronic viral hepatitis+metabolic dysfunction–associated liver disease) (95% sensitivity and 92% specificity)

In their discussion, the authors review the metabolism of the various metabolites and why they may be altered in AIH. “Our study found that cirrhosis did not seem to affect our results.” In ongoing studies, the authors are trying to determine how these metabolites change with treatment and whether they could be a predictive marker.

My take: Metabolite measurement could be helpful in the diagnosis of AIH as “NMR technology dose not need much sample handling, is highly reproducible, and with low costs.

Related blog posts:

Is First Line Therapy for Autoimmune Hepatitis Changing? CAMARO Study Results

Posted on by

RJ Snijders et al. J Hepatol 2024; 80: 576-585. Open Access! An open-label randomised-controlled trial of azathioprine vs. mycophenolate mofetil for the induction of remission in treatment-naive autoimmune hepatitis

Methods: In this 24-week, prospective, randomised, open-label, multicentre superiority trial, 70 patients (mean age 57.9 years) with treatment-naive AIH received either MMF or azathioprine, both in combination with prednisolone. The primary endpoint was biochemical remission (BR) defined as normalisation of serum levels of alanine aminotransferase and IgG after 24 weeks of treatment.

Treatment dosing in study (Table S2):

Key findings:

  • 56.4% of the MMF group and 29.0% of the azathioprine group achieved BR
  • No serious adverse events occurred in patients who received MMF (0%) but serious adverse events were reported in four patients who received azathioprine (12.9%) (p = 0.034)

Excerpts from the discussion:

  • “The evidence for the current standard induction therapy in AIH with azathioprine and prednisolone is limited and stems from the early seventies of the last century.”
  • “Patients assigned to azathioprine were significantly more prone to discontinuing treatment because of intolerance or SAEs, with nausea and vomiting as the main reasons for cessation of treatment.”
  • “MMF exhibits high teratogenicity. MMF should not be used during pregnancy and may only be used with strict contraceptive measures in women of childbearing age and men planning to father a child, as its use is absolutely contraindicated during pregnancy.”
  • “In addition, MMF must be administered twice daily, while azathioprine is given as a single dose daily…relevant for a disease that requires lifelong treatment.”

My take: This study needs to be replicated in the pediatric age group. Though many patients have some frequent side effects with MMF, the overall safety (and possibly effectiveness) appears improved with MMF compared with azathioprine.

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Autoimmune Hepatitis, Horseshoes and Hand Grenades

Posted on by

“Close don’t count in baseball. Close only counts in horseshoes and hand grenades.” –Frank Robinson 1973.

This study used the the International Autoimmune Hepatitis Group retrospective registry (IAIHG-RR), a web-based platform. This retrospective, observational, multicenter study analyzed 2559 patients; however, only 1700 had adequate follow-up. A complete biologic response (CBR) was defined as normalization of aminotransferases and serum IgG within 6 months; only 706 had serial results of these parameters to assess for a CBR.

Key findings:

  • Among the 706 with adequate data, 68.5% achieved a CBR.
  • Non-White ethnicity (HR 4), cirrhosis (HR 3.5), variant syndrome with primary sclerosing cholangitis (PSC) (HR 3.1), and lack of complete biochemical response within 6 months (HR 5.7) were independent prognostic factors.
  • Patients with a CBR had a greater actuarial survival over a 20-year period (91%) compared to those without a CBR (61%). Lack of a CBR at 6 months conferred a 3.6-fold higher risk of progression to cirrhosis.
  • Even in patients with cirrhosis, a CBR increased long-term survival: 82% versus 34%.

My take: A CBR is associated with the best long-term outcomes. My suspicion is that a biochemical response is actually similar to horseshoes. Improvement with treatment is likely beneficial but not as good as hitting the stake (the target).

Related blog posts:

What to Do with Refractory Autoimmune Hepatitis: Case Report

Posted on by

N Hadzic et al. NEJM 2024; 390: 284-286.JAK Inhibition in STAT1 Gain-of-Function–Mediated Treatment-Resistant Autoimmune Hepatitis

In this case report, the authors describe a 21 month old who presented with jaundice and abnormal liver tests. Diagnostic evaluation identified high titers of LKM antibodies (1:10,520) along with liver biopsy findings consistent with type 2 autoimmune hepatitis (AIH). After 6 months of treatment with steroids and subsequently azathioprine, the patient continued with severe biochemical relapses and a liver biopsy showed only a partial response.

Subsequently, “genetic testing found the patient had a heterozygous c.821G→A p.(Arg274Gln) pathogenic variant in the gene encoding signal transducer and activator of transcription 1 (STAT1)… Functional assays in the patient repeatedly showed abnormally high STAT1 phosphorylation as compared with healthy controls; this confirmed an autosomal dominant STAT1 gain-of-function defect.”

Treatment with “baricitinib, an inhibitor of Janus kinase 1 (JAK1) and 2 (JAK2), was started. Within weeks, the patient’s aminotransferase levels normalized. ..A liver-biopsy sample that was obtained 4 months after the initiation of baricitinib therapy showed an absence of appreciable inflammation with residual mild fibrosis…She was weaned off mycophenolate and is continuing to receive daily baricitinib (8 mg) and prednisolone (2.5 mg) along with fluconazole and azithromycin for infection prophylaxis.”

My take: In children with refractory autoimmune hepatitis, genetic testing is worthwhile and may allow targeted therapy.

Related blog posts:

Tyre Palm on St. John

Immune Mediated Disorders Associated with TNF Inhibitors Can Involve the Liver Too

Posted on by

Yesterday’s post highlighted immune-mediated disorders likely caused by anti-TNF therapy; this includes rheumatoid arthritis, psoriasis, hidradenitis suppurativa, and chronic recurrent multifocal osteomyelitis. Anti-TNF inhibitors can be the reason for drug-induced liver disease (DILI) including autoimmune hepatitis (AIH) as well. 

  • In one study, 8% of children receiving anti-TNF therapy developed a new elevation in ALT.
  • Most often liver enzyme elevation is mild and transient
  • Differential diagnosis for persistent elevation can be due to DILI, autoimmune liver disease (eg. PSC, AIH), or rarely due to a combination (autoimmune drug-induced liver disease). The latter can improve with drug cessation and with corticosteroid treatment.

Some slides on this topic (courtesy of William. Balistreri):

My take: Serious liver injury related to anti-TNF therapy is rare. When liver enzymes are persistently elevated, consider DILI including anti-TNF agents.

Related blog posts:

Is It a Mistake to Use Budesonide for Autoimmune Hepatitis?

Posted on by

A Diaz-Gonzalez et al. Hepatology 2023; 77: 1095-1105. Open Access! Budesonide as first-line treatment in patients with autoimmune hepatitis seems inferior to standard predniso(lo)ne administration

Background: AASLD guidelines also suggest the use of budesonide with azathioprine as an alternative agent (to prednisone with azathioprine) in patients without cirrhosis or a severe acute presentation.1–3 However, particularly in pediatrics, there is concern that it is not as effective.

Methods: This was a retrospective, multicenter study of 105 naive AIH patients treated with budesonide as the first-line drug. The control group included 276 patients treated with prednisone.

Key findings:

  • The biochemical response (BR) rate was significantly higher in patients treated with prednisone (87% vs. 49% of patients with budesonide, p < 0.001). BR was defined as normalization of both serum transaminases and IgG.
  • The probability of achieving BR was significantly lower in the budesonide group (OR = 0.20) at any time during follow-up, and at 6 (OR = 0.51) and 12 months after starting treatment (0.41)
  • Prednisone treatment was significantly associated with a higher risk of adverse events (24.2% vs. 15.9%). These differences vanished when patients with cirrhosis were excluded from the analysis, showing a similar incidence of AEs in both groups (p = 0.119). Of the specific adverse effects, only the presence of osteoporosis was significantly higher in the prednisone group (mainly in those older than 60 years)
  • The authors note that budesonide was “only indicated in 5.4% of patients newly diagnosed with AIH… Budesonide was mainly employed in patients with low baseline transaminases, suggesting that this drug is preferred in patients with less severe disease.”

My take: “The use of budesonide in the real-life setting was low and was associated with a lower probability of achieving BR with respect to prednisone.” It likely needs to be restricted to those with mild disease, and those with adverse events with prednisone. Cost is less of an issue as budesonide can be obtained as a generic (Mark Cuban Costplus pharmacy: Budesonide).

Related blog posts: