Autoimmune hepatitis and primary sclerosing cholangitis after direct-acting antiviral treatment for hepatitis C virus:A case report

BACKGROUND Chronic hepatitis C virus(HCV)infection is a major global health concern that leads to liver fibrosis,cirrhosis,and cancer.Regimens containing direct-acting antivirals(DAAs)have become the mainstay of HCV treatment,achieving a high sustained virological response(SVR)with minimal adverse events.CASE SUMMARY A 74-year-old woman with chronic HCV infection was treated with the DAAs ledipasvir,and sofosbuvir for 12 wk and achieved SVR.Twenty-four weeks after treatment completion,the liver enzyme and serum IgG levels increased,and antinuclear antibody became positive without HCV viremia,suggesting the development of autoimmune hepatitis(AIH).After liver biopsy indicated AIH,a definite AIH diagnosis was made and prednisolone was initiated.The treatment was effective,and the liver enzyme and serum IgG levels normalized.However,multiple strictures of the intrahepatic and extrahepatic bile ducts with dilatation of the peripheral bile ducts appeared on magnetic resonance cholangiopancreatography after 3 years of achieving SVR,which were consistent with primary sclerosing cholangitis.CONCLUSION The potential risk of developing autoimmune liver diseases after DAA treatment should be considered.

STAT3-Dependent Effects of Polymeric Immunoglobulin Receptor in Regulating Interleukin-17 Signaling and Preventing Autoimmune Hepatitis

One-third of patients with autoimmune hepatitis(AIH)have cirrhosis at the time of diagnosis.The relevance of these variables,although unknown,is believed to be critical in AIH because of suspected interactions between the gut microbiome and genetic factors.Dysbiosis of the gut flora and elevated polymeric immunoglobulin receptor(pIgR)levels have been observed in both patients and mouse models.Moreover,there is a direct relationship between pIgR expression and transaminase levels in patients with AIH.In this study,we aimed to explore how pIgR influences the secretion of regenerating islet-derived 3 beta(Reg3b)and the flora composition in AIH using in vivo experiments involving patients with AIH and a concanavalin A-induced mouse model of AIH.Reg3b expression was reduced in pIgR gene(Pigr)-knockout mice compared to that in wild-type mice,leading to increased microbiota disruption.Conversely,exogenous pIgR supplementation increased Reg3b expression and maintained microbiota homeostasis.RNA sequencing revealed the participation of the interleukin(IL)-17 signaling pathway in the regulation of Reg3b through pIgR.Furthermore,the introduction of external pIgR could not restore the imbalance in gut microbiota in AIH,and the decrease in Reg3b expression was not apparent following the inhibition of signal transducer and activator of transcription 3(STAT3).In this study,pIgR facilitated the upregulation of Reg3b via the STAT3 pathway,which plays a crucial role in preserving the balance of the intestinal microbiota in AIH.Through this research,we discovered new molecular targets that can be used for the diagnosis and treatment of AIH.

Fermented Lentinus edodes extract containingα-glucan ameliorates concanavalin A-induced autoimmune hepatitis in mice

Autoimmune hepatitis(AIH)is a chronic inflammatory liver disease that threatens human health worldwide.The aim of this study was to detect the protective effect of a fermented Lentinus edodes extract containingα-glucan(FLA),in a concanavalin A(Con A)-induced AIH mouse model and to determine the underlying liver-protective mechanism.The results showed that compared with the model group,the level of proinflammatory cytokines in serum of FLA pretreated mice was significantly decreased,and the degree of inflammatory cell infiltration in liver,thymus and spleen was significantly reduced.Quantitative polymerase chain reaction,immunohistochemistry,and Western blotting showed that FLA pre-treatment inhibited the Con A-induced apoptosis of hepatocytes by down-regulating the expression of BAX and up-regulating the expression of BCL-2.Further research found that FLA may improve liver injury in mice by activating NRF2 signaling pathway and inhibiting TRAF6/NF-κB signaling pathway.Thus,FLA may improve liver injury in mice by shifting gut microbial composition to reduce the release of inflammatory cytokines in the serum and prevent the necrosis of hepatocytes.Up-regulation of NRF2 signaling pathway,down-regulation of TRAF6/NF-κB signaling pathway,and an increase in the relative abundance of Lactobacillus_johnsonii and Ligilactobacillus_murinus play a protective role in liver.

Knockout of C6orf120 in Rats Alleviates Concanavalin A-induced Autoimmune Hepatitis by Regulating Macrophage Polarization

Objective The effect of the functionally unknown gene C6orf120 on autoimmune hepatitis was investigated on C6orf120 knockout rats(C6orf120^(-/-))and THP-1 cells.Method Six–eight-week-old C6orf120^(-/-)and wild-type(WT)SD rats were injected with Con A(16 mg/kg),and euthanized after 24 h.The sera,livers,and spleens were collected.THP-1 cells and the recombinant protein(rC6ORF120)were used to explore the mechanism in vitro.The frequency of M1 and M2 macrophages was analyzed using flow cytometry.Western blotting and PCR were used to detect macrophage polarization-associated factors.Results C6orf120 knockout attenuated Con A-induced autoimmune hepatitis.Flow cytometry indicated that the proportion of CD68^(+)CD86^(+)M1 macrophages from the liver and spleen in the C6orf120^(-/-)rats decreased.C6orf120 knockout induced downregulation of CD86 protein and the mRNA levels of related inflammatory factors TNF-α,IL-1β,and IL-6 in the liver.C6orf120 knockout did not affect the polarization of THP-1 cells.However,rC6ORF120 promoted the THP-1 cells toward CD68^(+)CD80^(+)M1 macrophages and inhibited the CD68^(+)CD206^(+)M2 phenotype.Conclusion C6orf120 knockout alleviates Con A-induced autoimmune hepatitis by inhibiting macrophage polarization toward M1 macrophages and reducing the expression of related inflammatory factors in C6orf120^(-/-)rats.

Management of autoimmune hepatitis induced by hepatitis delta virus

Approximately 12-72 million people worldwide are co-infected with hepatitis B virus(HBV)and hepatitis delta virus(HDV).This concurrent infection can lead to several severe outcomes with hepatic disease,such as cirrhosis,fulminant hepatitis,and hepatocellular carcinoma,being the most common.Over the past few decades,a correlation between viral hepatitis and autoimmune diseases has been reported.Furthermore,autoantibodies have been detected in the serum of patients co-infected with HBV/HDV,and autoimmune features have been reported.However,to date,very few cases of clinically significant autoimmune hepatitis(AIH)have been reported in patients with HDV infection,mainly in those who have received treatment with pegylated interferon.Interestingly,there are some patients with HBV infection and AIH in whom HDV infection is unearthed after receiving treatment with immunosuppressants.Consequently,several questions remain unanswered with the challenge to distinguish whether it is autoimmune or“autoimmune-like”hepatitis being the most crucial.Second,it remains uncertain whether autoimmunity is induced by HBV or delta virus.Finally,we investigated whether the cause of AIH lies in the previous treatment of HDV with pegylated interferon.These pressing issues should be elucidated to clarify whether new antiviral treatments for HDV,such as Bulevirtide or immu-nosuppressive drugs,are more appropriate for the management of patients with HDV and AIH.

Autoimmune hepatitis-primary biliary cholangitis overlap syndrome complicated by various autoimmune diseases:A case report

BACKGROUND Autoimmune hepatitis(AIH)and primary biliary cholangitis(PBC)are two common clinical autoimmune liver diseases,and some patients have both diseases;this feature is called AIH-PBC overlap syndrome.Autoimmune thyroid disease(AITD)is the most frequently overlapping extrahepatic autoimmune disease.Immunoglobulin(IgG)4-related disease is an autoimmune disease recognized in recent years,characterized by elevated serum IgG4 levels and infiltration of IgG4-positive plasma cells in tissues.CASE SUMMARY A 68-year-old female patient was admitted with a history of right upper quadrant pain,anorexia,and jaundice on physical examination.Laboratory examination revealed elevated liver enzymes,multiple positive autoantibodies associated with liver and thyroid disease,and imaging and biopsy suggestive of pancreatitis,hepatitis,and PBC.A diagnosis was made of a rare and complex overlap syndrome of AIH,PBC,AITD,and IgG4-related disease.Laboratory features improved on treatment with ursodeoxycholic acid,methylprednisolone,and azathioprine.CONCLUSION This case highlights the importance of screening patients with autoimmune diseases for related conditions.

Advancements in autoimmune hepatitis management:Perspectives for future guidelines

The first-line treatment for autoimmune hepatitis involves the use of prednisone or prednisolone either as monotherapy or in combination with azathioprine(AZA).Budesonide has shown promise in inducing a complete biochemical response(CBR)with fewer adverse effects and is considered an optional first-line treatment,particularly for patients without cirrhosis;however,it is worth noting that the design of that study favored budesonide.A recent real-life study revealed higher CBR rates with prednisone when equivalent initial doses were administered.Current guidelines recommend mycophenolate mofetil(MMF)for patients who are intolerant to AZA.It is important to mention that the evidence supporting this recommendation is weak,primarily consisting of case series.Nevertheless,MMF has demonstrated superiority to AZA in the context of renal transplant.Recent comparative studies have shown higher CBR rates,lower therapeutic failure rates,and reduced intolerance in the MMF group.These findings may influence future guidelines,potentially leading to a significant modification in the first-line treatment of autoimmune hepatitis.Until recently,the only alternative to corticosteroids was lifelong maintenance treatment with AZA,which comes with notable risks,such as skin cancer and lymphoma.Prospective trials are essential for a more comprehensive assessment of treatment suspension strategies,whether relying on histological criteria,strict biochemical criteria,or a combination of both.Single-center studies using chloroquine diphosphate have shown promising results in significantly reducing relapse rates compared to placebo.However,these interesting findings have yet to be replicated by other research groups.Additionally,second-line drugs,such as tacrolimus,rituximab,and infliximab,should be subjected to controlled trials for further evaluation.

Immunological crossroads:The intriguing dance between hepatitis C and autoimmune hepatitis

Delving into the immunological crossroads of liver diseases,this editorial explores the dynamic interplay between hepatitis C virus(HCV)and autoimmune hepatitis(AIH).While HCV primarily manifests as a viral infection impacting the liver,previous studies unveil a captivating connection between HCV and the emergence of AIH.The dance of the immune system in response to HCV appears to set the stage for an intriguing phenomenon-an aberrant autoimmune response leading to the onset of AIH.Evidence suggests a heightened presence of autoimmune markers in individuals with chronic HCV infection,hinting at a potential overlap between viral and autoimmune liver diseases.Navigating the intricate terrain of viral replication,immune response dynamics,and genetic predisposition,this editorial adds a layer of complexity to our understanding of the relationship between HCV and AIH.In this immunological crossroads,we aim to unearth insights into the complex interplay,using a compelling case where AIH and primary sclerosing cholangitis overlapped following HCV treatment with direct-acting antivirals as background.

Research progress on the mechanism of traditional Chinese medicine in the treatment of autoimmune hepatitis

Autoimmune hepatitis is an inflammatory liver disease primarily mediated by T cell.It has not been fully elucidated about the pathogenesis,and it is presently thought to be related to genetic susceptibility,infection and environmental triggers,and abnormal autoimmune regulation.Recent studies have found that traditional Chinese medicine can improve the biochemical indicators and clinical symptoms of patients with autoimmune hepatitis.This article reviews the specific mechanism of traditional Chinese medicine on treating autoimmune hepatitis in order to propose new ideas for its clinical diagnosis and treatment.

Autoimmune hepatitis and liver transplantation:Indications,and recurrent and de novo autoimmune hepatitis

Autoimmune hepatitis is a chronic inflammatory disease of the liver that is characterized by circulating autoantibodies and elevated serum globulin levels.Liver transplantation may be required for patients with acute liver failure,decompensated cirrhosis,and hepatocellular carcinoma.Recurrence is defined as development of the same disease in the allograft following liver transplantation.Autoimmune hepatitis recurs in 36%-68%of the recipients 5 years after liver transplantation.De novo autoimmune hepatitis is the development of autoimmune hepatitis like clinical and laboratory characteristics in patients who had undergone liver transplantation for causes other than autoimmune hepatitis.Diagnostic work up for recurrent and de novo autoimmune hepatitis is similar to the diagnosis of the original disease,and it is usually difficult.Predniso(lo)ne with or without azathioprine is the main treatment for recurrent and de novo autoimmune hepatitis.Early diagnosis and treatment are vital for patient prognosis because de novo autoimmune hepatitis and recurrent autoimmune hepatitis cause graft loss and result in subsequent retransplantation if medical treatment fails.

Drug-induced autoimmune hepatitis:A minireview

Drug-induced autoimmune hepatitis(DIAIH)is a specific phenotype of druginduced liver injury that may lead to the devastating outcome of acute liver failure requiring liver transplantation.Drugs implicated in DIAIH include antimicrobials such as nitrofurantoin and minocycline,non-steroidal anti-inflammatory drugs,statins as well as anti-tumor necrosis agents.The clinical features of druginduced liver injury are indistinguishable from idiopathic autoimmune hepatitis(AIH)as both may have positive AIH-related autoantibodies,elevated immunoglobulin G,as well as similar histopathological findings.In patients who show no clinical improvement,or there is progressive liver injury despite cessation of the suspected drug,a liver biopsy should be considered,whereby the presence of advance fibrosis on histology favors the diagnosis of idiopathic AIH.Empirical treatment with corticosteroids may be required in patients with non-resolving liver injury.A typical clinical scenario supportive of DIAIH includes a history of drug exposure with spontaneous resolution of liver injury after drug withdrawal and the absence of relapse after rapid steroid taper.In this article we report two cases of DIAIH secondary to Sorafenib and Atorvastatin along with a review of currently available literature.Early identification and treatment often lead to a favorable outcome in DIAIH.

CD4+Foxp3+CD25+/-Tregs characterize liver tissue specimens of patients suffering from drug-induced autoimmune hepatitis:A clinical-pathological study

Background: The diagnosis of drug-induced autoimmune hepatitis(DIAIH) and its differentiation from idiopathic autoimmune hepatitis(AIH) is challenging. This study aimed to differentiate DIAIH from AIH by comparing the biochemical changes, histological features, and frequencies of CD4~+Foxp3~+CD25+/-regulatory T cells(Tregs) in liver tissues or peripheral blood lymphocytes.Methods: A total of 15 DIAIH patients and 24 AIH patients who underwent liver biopsies at initial presentation were enrolled in this study. The liver histological changes were assessed by HE staining. The phenotypic recognition and distribution of CD4~+Foxp3~+CD25+/-Tregs in liver tissues were evaluated by single/double immunostains in serial sections. The CD4~+Foxp3~+CD25+/-Tregs in peripheral blood were analyzed by flow cytometry.Results: The median values of ALT and AST were 404.50 U/L and 454.10 U/L in DIAIH patients and309.50 U/L and 315.00 U/L in AIH patients, respectively. More importantly, for the first time we found that patients with DIAIH had higher levels of serum ALT and AST, more severe degree of lobular inflammation,higher frequencies of zone 3 necrosis and higher number of lobular CD4~+Foxp3~+CD25~-Tregs compared with AIH(P < 0.05). Furthermore, there were positive correlations in DIAIH between the degree of lobular inflammation and either the AST/ALT level or the number of lobular CD4~+Foxp3~+CD25~-Tregs(P < 0.05).However, the frequency of peripheral blood CD4~+Foxp3~+CD25+/-Tregs were not significantly different between DIAIH and AIH.Conclusions: The differences of ALT, AST and the number of lobular CD4~+Foxp3~+CD25~-Tregs between patients with DIAIH and those with AIH are clinically helpful in differentiating these two diseases in their early stage.

Genetic distinctions between autoimmune hepatitis in Italy and North America

AIM: Our goals were to analyze the known genetic predispositions for autoimmune hepatitis (AIH) in AIH Italian population and to compare them with North American counterparts. METHODS: Human leukocyte antigens (HLA) B8, C7, DR3, DR4, DR7, DR11, DR13, DQ2 and the B8-DR3-DQ2 phenotype were determined by microlymphocytotoxicity and polymerase chain reaction in 74 Italian patients (57 with type 1 and 17 with type 2 AIH) and 149 North American patients with type 1 AIH, and in adequate controls. RESULTS: B8-DR3-DQ2 occurred more frequently in Italian patients with type 1 AIH than in Italian controls (30% vs 7%, P<0.0001), but less frequently than in North American counterparts (30% vs 48%, P= 0.02). DR4 occurred less frequently in Italian patients with type 1 AIH (23% vs 43%, P= 0.01) and in controls (16% vs 34%, P= 0.0003) than in North American counterparts. No differences were found in alleles' frequency between type 1 and type 2 Italian AIH patients. DR11 had a frequency lower in type 1 Italian AIH patients than controls (17% vs 35%, P= 0.01). CONCLUSION: HLA DR4 is not associated with AIH in Italy. The known HLA risk factors for AIH occur similarly in Italian patients with type 1 and type 2 AIH, and they are less frequent than in North American patients. B8-DR3-DQ2 is the predominant phenotype of type 1 AIH also in Italy, and HLA DR11 may be a regionally distinctive protective factor against type 1 AIH.

Autoimmune hepatitis: standard treatment and systematic review of alternative treatments

Autoimmune hepatitis is a rare chronic inflammatory liver disease,affecting all ages,characterised by elevated transaminase and immunoglobulin G levels,positive autoantibodies,interface hepatitis at liver histology and good response to immunosuppressive treatment. If untreated,it has a poor prognosis. The aim of this review is to summarize the evidence for standard treatment and to provide a systematic review on alternative treatments for adults and children. Standard treatment is based on steroids and azathioprine,and leads to disease remission in 80%-90% of patients. Alternative first line treatment has been attempted with budesonide or cyclosporine,but their superiority compared to standard treatment remains to be demonstrated. Second-line treatments are needed for patients not responding or intolerant to standard treatment. No randomized controlled trials have been performed for second-line options. Mycophenolate mofetil is the most widely used second-line drug,and has good efficacy particularly for patients intolerant to azathioprine,but has the major disadvantage of being teratogenic. Only few and heterogeneous data on cyclosporine,tacrolimus,everolimus and sirolimus are available. More recently,experience with the anti-tumour necrosis factoralpha infliximab and the anti-CD20 rituximab has been published,with ambivalent results; these agents may have severe side-effects and their use should be restricted to specialized centres. Clinical trials with new therapeutic options are ongoing.

Immune mechanisms of Concanavalin A model of autoimmune hepatitis

As a chronic inflammatory disease of the liver,the pathogenic mechanisms of autoimmune hepatitis (AIH) have not yet been elucidated,with prognosis and diagnosis remaining unsatisfied.Currently the only viable treatments of AIH are immunosuppressant application and liver transplantation.It is considered that lack of good animal AIH models is the main reason for the shortage of a simple and efficient cure.The Concanavalin A (Con A) model is a typical and well established model for investigating T-cell and macrophage dependent liver injury in mice,which closely mimics the pathogenesis mechanisms and pathological changes of patients,and is regarded as the best experimental model for AIH research so far.In this paper we eluci-dated the pathogenic mechanisms of AIH and the evolution of relative animal models.We go on to further focus on Con A-induced liver injury from the point of immunological mechanisms and the change of cytokine levels.Finally,we manifested the clinical significance of the AIH animal models and the challenges they would meet during their future development.

Update on autoimmune hepatitis

Autoimmune hepatitis (AIH) is a necroinflammatory liver disease of unknown etiology that occurs in children and adults of all ages. Characteristics are its autoimmune features,hyperglobulinemia (IgG),and the presence of circulating autoantibodies,as well as a response to immunosuppressant drugs. Current treatment consists of prednisone and azathioprine and in most patients this disease has become very treatable. Over the past 2 years,a couple of new insights into the genetic aspects,clinical course and treatment of AIH have been reported,which will be the focus of this review. In particular,we concentrate on genome-wide microsatellite analysis,a novel mouse model of AIH,the evaluation of a large AIH cohort for overlap syndromes,suggested novel criteria for the diagnosis of AIH,and the latest studies on treatment of AIH with budenoside and mycophenolate mofetil.

Factoring the intestinal microbiome into the pathogenesis of autoimmune hepatitis

The intestinal microbiome is a reservoir of microbial antigens and activated immune cells. The aims of this review were to describe the role of the intestinal microbiome in generating innate and adaptive immune responses, indicate how these responses contribute to the development of systemic immune-mediated diseases, and encourage investigations that improve the understanding and management of autoimmune hepatitis. Alterations in the composition of the intestinal microflora(dysbiosis) can disrupt intestinal and systemic immune tolerances for commensal bacteria. Toll-like receptors within the intestine can recognize microbe-associated molecular patterns and shape subsets of T helper lymphocytes that may cross-react with host antigens(molecular mimicry). Activated gutderived lymphocytes can migrate to lymph nodes, and gut-derived microbial antigens can translocate to extra-intestinal sites. Inflammasomes can form within hepatocytes and hepatic stellate cells, and they can drive the pro-inflammatory, immune-mediated, and fibrotic responses. Diet, designer probiotics, vitamin supplements, re-colonization methods, antibiotics, drugs that decrease intestinal permeability, and molecular interventions that block signaling pathways may emerge as adjunctive regimens that complement conventional immunosuppressive management. In conclusion, investigations of the intestinal microbiome are warranted in autoimmune hepatitis and promise to clarify pathogenic mechanisms and suggest alternative management strategies.

Aetiopathogenesis of autoimmune hepatitis

The histological hallmark of autoimmune hepatitis（AIH） is a dense portal mononuclear cell infiltrate that invades the surrounding parenchyma and comprises T and B lymphocytes,macrophages,and plasma cells.An unknown but powerful stimulus must be promoting the formation of this massive inflammatory cellular reaction that is likely to initiate and perpetuate liver damage.An autoimmune attack can follow different pathways to inflict damage on hepatocytes.Liver damage is likely to be orchestrated by CD4^＋ T lymphocytes recognizing an autoantigenic liver peptide.To trigger an autoimmune response,the peptide must be embraced by an HLA class Ⅱ molecule and presented to naive CD4^＋ T helper（Th0） cells by professional antigen presenting cells,with the co-stimulation of ligand-ligand fostering interaction between the two cells.Th0 cells become activated,differentiate into functional phenotypes according to the cytokines prevailing in the microenvironment and the nature of the antigen,and initiate a cascade of immune reactions determined by the cytokines produced by the activated T cells.Th1 cells,arising in the presence of the macrophage-derived interleukin（IL） -12,secrete mainly IL-2 and interferon-gamma（IFN-γ）,which activate macrophages,enhance expression of HLA classⅠ（increasing liver cell vulnerability to a CD8^＋ T cell cytotoxic attack）,and induce expression of HLA class Ⅱ molecules on hepatocytes.Th2 cells,which differentiate from Th0 if the microenvironment is rich in IL-4,produce mainly IL-4,IL-10,and IL-13 which favour autoantibody production by B lymphocytes.Physiologically,Th1 and Th2 antagonize each other.Th17 cells,a recently described population,arise in the presence of transforming growth factor beta（TGF-β） and IL-6 and appear to have an important effector role in inflammation and autoimmunity.Theprocess of autoantigen recognition is strictly controlled by regulatory mechanisms,such as those exerted by CD4^＋CD25^＋ regulatory T cells,which derive from Th0 in the presence of TGF-β,but in the absence of IL-6.If regulatory mechanisms fail,the autoimmune attack is perpetuated.Over the past three decades different aspects of the above pathogenic scenario have been investigated.In particular,a defect in immunoregulation affecting CD4^＋CD25^＋ regulatory T cells（T-regs） has been demonstrated in AIH,particularly at diagnosis or during relapse.Advances in the study of autoreactive T cells have occurred mostly in AIH type 2,since the knowledge that CYP2D6 is the main autoantigen has enabled the characterization of both CD4 and CD8 T cells targeting this cytochrome.CD4 T cells from patients with type 2 AIH positive for the predisposing HLA allele DRB10701 recognize seven regions of CYP2D6,five of which are also recognized by CD8 T cells.High numbers of IFN-γ producing CD4 T cells and CD8 T cells are associated with biochemical evidence of liver damage,suggesting a combined cellular immune attack.

Low-dose tacrolimus ameliorates liver inflammation and fibrosis in steroid refractory autoimmune hepatitis

AIM: To determine the eff icacy of tacrolimus on clinical status, histopathological status and biochemical markers in patients with steroid refractory autoimmune hepatitis (AIH). METHODS: Retrospectively, clinical parameters, biochemistry and histology were obtained from patient records. RESULTS: Nine patients [8 females/1 male, median age 32 (range 16-64) years] were identified to have received tacrolimus for a median duration of 18 (12-37) mo. Before initiation of tacrolimus treatment the patients were maintained on a prednisolone dose of 20 mg daily (range 20-80 mg/d), which was tapered to 7.5 (5-12.5) mg/d (P = 0.004). Alanine aminotransferase and immunoglobulin-G concentrations decreased from 154 (100-475) to 47(22-61) U/L (P = 0.007), and from 16 (10-30.2) to 14.5 (8.4-20) g/L (P = 0.032), respectively. All patients showed improvement of the liver inflammatory activity, as determined by the Ishak score (P = 0.016), while the degree of f ibrosis tended to decrease (P = 0.049). CONCLUSION: The use of low dose tacrolimus can lead to biochemical and histologic improvement of inflammation with no progression of the stage of f ibrosis in patients with steroid refractory AIH. Low dose tacrolimus therapy also allows substantial reduction of prednisone dose.

Clinical features and management of autoimmune hepatitis

Autoimmune hepatitis(AIH) is a chronic hepatitis of unknown etiology which can progress to cirrhosis.Its clinical manifestations are highly variable and some-times follow a fluctuating course.Diagnosis is based on characteristic histologic,clinical,biochemical and sero-logical findings.Anti-inflammatory/immunosuppressive treatment frequently induces remission but long-term maintenance therapy is often required.Liver transplan-tation is generally successful in patients with decompen-sated cirrhosis unresponsive to or intolerant of medical therapy.