Hepatocellular carcinoma in patients with autoimmune liver diseases: two case reports and literature review

Background and aims: Hepatocellular carcinoma has been reported as a rare complication of autoimmune liver diseases. We describe herein two patients with this neoplasia associated with autoimmune hepatitis and primary biliary cirrhosis, and we also review the literature.Cases report: The first case corresponds to a 49-year-old woman presented for evaluation of right upper abdominal pain. She had been diagnosed with autoimmune hepatitis 4 years before. Alpha-fetoprotein was markedly elevated and an abdominal MRI showed a 10 cm × 9.0 cm mass. She received transarterial chemoembolization, and currently the disease has progressed to the lungs and bones, and she is on supportive care. The second case corresponds to a 68-year-old woman presented for evaluation of a liver mass found in a screening ultrasound. She had been diagnosed with primary biliary cirrhosis 5 years previously. At admission alpha-fetoprotein was 1000 ng/mL and an abdominal MRI revealed a 4 cm × 3 cm liver tumor. She was treated with percutaneous radiofrequency ablation getting complete response, and currently she has no evidence of neoplastic disease. These two patients constitute the only cases of hepatocellular carcinoma associated to autoimmune liver diseases that have been attended in our Institute.Conclusion: These cases highlight that hepatocellular carcinoma secondary to autoimmune hepatitis and primary biliary cirrhosis, although rare, can occur in the absence of coexistent viral hepatitis, or excessive alcohol consumption. The utility of screening for hepatocellular carcinoma in autoimmune liver diseases is still not defined.     

Autonatibody against 70 kD heat shock protein in patients with autoimmune liver diseases

Background/Aims: It has recently been suggested that heat shock proteins are implicated in the pathogenesis and the pathophysiology of various immunological disorders, and the presence of antibodies against heat shock proteins has been reported in several autoimmune diseases.Methods: We investigated autoantibodies against the two major human heat shock proteins (hsp70 and hsp90) in sera from patients with primary biliary cirrhosis and autoimmune hepatitis, the two major autoimmune liver diseases. Reactivity with human heat shock proteins obtained from phytohemagglutinin stimulated cells was investigated by immunoblots with sera at 1:20 dilution.Results: Reactivity with human hsp90 was not found in any sera from patients or normal controls. In contrast, reactivity with human hsp70 was found in 16 of 35 (45.7%) primary binary cirrhosis patients and in 9 of 17 (52.9%) autoimmune hepatitis patients, but similar reactivity was found in only 2 of 15 patients with chronic hepatitis B and 1 of 13 patients with chronic hepatitis C. All the normal controls showed a negative reaction. Two-dimensional immunoblots and immunoabsorption experiments established that the autoantibody recognized only human hsc70 (73 kD/pI 5.5), a constitutive form of the hsp70 family.Conclusions: Although the pathological significance of the autoantibody against hsc70 in these autoimmune liver diseases remains unknown, the serum autoantibody detected in primary biliary cirrhosis patients is closely related to clinical variables including serum total bilirubin, alanine aminotransferase, IgG, IgM, titers of antimitochondrial antibodies, and major symptoms (pruritus and/or icterus). These observations may suggest that the anti-hsc70 antibody is an indicator for the disease activity of primary biliary cirrhosis.     

Comparison of simplified score with the revised original score for the diagnosis of autoimmune hepatitis: A new or a complementary diagnostic score?

Background and aims

The International Autoimmune Hepatitis Group developed a simplified score for autoimmune hepatitis. We assessed this “new scoring system” and compared it with the International Autoimmune Hepatitis Group original revised score.

Methods

502 patients were evaluated namely, 428 had liver diseases of various etiology [hepatitis B (n = 109), hepatitis C (n = 100), hepatitis D (n = 4), alcoholic liver disease (n = 28), non-alcoholic fatty liver disease (n = 55), autoimmune cholestatic diseases (n = 77), liver disorders of undefined origin (n = 32) and miscellaneous hepatic disorders (n = 23)], 13 had autoimmune hepatitis/overlap syndromes, 18 had autoimmune hepatitis/concurrent with other liver diseases and 43 had autoimmune hepatitis.

Results

The specificity of the simplified score was similar to that of the revised score (97% vs. 97.9%). The sensitivity in unmasking autoimmune hepatitis in autoimmune hepatitis/overlap syndromes was also similar in both systems (53.8% and 61.5%). However, the sensitivity for autoimmune hepatitis diagnosis in autoimmune hepatitis patients with concurrent liver disorders was lower by the new score (p = 0.001). Liver biopsy proved to be the only independent factor for unmasking autoimmune hepatitis component among patients (p = 0.003).

Conclusion

The simplified score is a reliable and simple tool for excluding autoimmune hepatitis. However, both systems cannot unmask autoimmune hepatitis component efficiently in autoimmune hepatitis patients with concurrent autoimmune or non-autoimmune liver diseases. This study also strongly reiterates the importance of liver biopsy in the work-up of patients.     

Waitlist mortality in patients with autoimmune liver diseases

Introduction and ObjectivesAutoimmune liver diseases such as autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis are the primary indication for ～24% of total liver transplants. The liver transplant allocation system is currently based upon the Model for End-Stage Liver Disease and it often underestimates the severity of autoimmune liver diseases. We aim to compare the rate of adverse waitlist removal among patients with all autoimmune liver diseases and other indications for liver transplant in the Model for End-Stage Liver -Na era.Materials and MethodsUsing the United Network for Organ Sharing database, we identified all patients listed for liver transplant from 2016 to 2019. The outcome of interest was waitlist survival defined as the composite outcome of death or removal for clinical deterioration. Competing risk analysis was used to evaluate the waitlist survival.ResultsPatients with autoimmune hepatitis had a higher risk of being removed from the waitlist for death or clinical deterioration (SHR 1.37, 95% CI 1.08–1.72; P<0.007), followed by primary biliary cholangitis (SHR 1.34, 95% CI 1.07–1.68; P<0.011).ConclusionsHigh waitlist death or removal for clinical deterioration was observed in patients with PBC and AIH when compared to other etiologies. It may be useful to reassess the process of awarding MELD exception points to mitigate such disparity.     

Abnormal hepatic biochemistries and clinical liver disease in patients with primary Sjögren's syndrome

Background/Aims: Patients with primary Sjögren’s syndrome may present liver involvement. Our goals were to establish the prevalence of abnormal hepatic biochemistries and clinical liver disease in patients with primary Sjögren’s syndrome and correlate their presence with other clinical and laboratory features. Methods: Ninety-five patients with diagnosis of primary Sjögren’s syndrome were studied. Data on gender, age, clinical features, liver biochemistries, tests of inflammation and autoimmunity, and concomitant diseases were collected. Results: Forty-two patients (44%) had abnormal hepatic biochemistries, and of these 19 patients (20%) had clinical liver disease. Patients with abnormal hepatic biochemistries had higher frequency of autoimmune hypotiroidism, arthritis, vasculitis, Raynaud’s phenomenon, higher sedimentation rate, and higher frequency of antinuclear and antimitochondrial antibodies than patients with normal liver biochemistries (P < 0.05 for each). Patients with clinical liver disease had higher frequency of arthritis, vasculitis, and higher frequency of antimitochondrial antibodies than patients without clinical liver disease (P < 0.05 for each). Twenty-one patients had diagnosis of a specific liver disease, such as hepatitis C virus infection (n = 11), autoimmune hepatitis (n = 2), primary biliary cirrhosis (n = 5), nonalcoholic fatty liver disease (n = 2), and hepatitis B virus infection (n = 1). In half of patients with liver involvement a definitive cause could not be identified. Conclusion: Liver involvement is frequently found in patients with primary Sjögren’s syndrome, and its presence is associated with clinical features of systemic disease, and markers of autoimmunity and inflammation. There may be a subgroup of patients with liver involvement secondary to primary Sjögren’s syndrome.     

Intrahepatic IgG/IgM plasma cells ratio helps in classifying autoimmune liver diseases

Background/AimPlasma cells infiltrate in the liver is a prototype lesion of autoimmune liver diseases. The possible role of plasma cells isotyping (IgM and IgG) in the liver in the diagnostic definition of autoimmune liver disease, and particularly in variant syndromes such as autoimmune cholangitis and the primary biliary cirrhosis/autoimmune hepatitis overlap syndrome, is less defined.MethodsWe analysed the clinical, serological and histological features of 83 patients with autoimmune liver disease (40 primary biliary cirrhosis, 20 autoimmune hepatitis, 13 primary sclerosing cholangitis, 4 autoimmune cholangitis and 6 overlap syndrome) compared to 34 patients with chronic hepatitis C and evaluated the expression of IgM and IgG plasma cells in their liver by immunostaining.ResultsBy Spearman's correlation, the mean-counts of IgM plasma cells in portal tracts were significantly correlated with female gender, serum alkaline phosphatase, gamma-glutamyl transferase and IgM values, positivity for anti-mitochondrial antibody-M2 and, on liver biopsy, with bile duct changes, orcein-positive granules and granulomas. Whereas IgG plasma cells resulted more correlated with alanine aminotransferase levels. IgG/IgM ratio lower than 1 was found no only in primary biliary cirrhosis but also in all patients with autoimmune cholangitis. Conversely, all patients with overlap syndrome showed IgG/IgM ratio higher than 1.ConclusionImmunostaining for IgM and IgG plasma cells on liver tissue can be a valuable parameter for better diagnosis of autoimmune liver disease and also for variant or mixed syndromes.     

High prevalence of small duct primary sclerosing cholangitis among patients with overlapping autoimmune hepatitis and primary sclerosing cholangitis

BackgroundOverlap syndrome is a term used for overlapping features of autoimmune hepatitis and primary sclerosing cholangitis or primary biliary cirrhosis and for autoimmune cholangitis. We describe a high prevalence of small duct primary sclerosing cholangitis among patients with overlapping autoimmune hepatitis and primary sclerosing cholangitis.MethodsWe sought to retrieve all patients with overlap syndrome between primary sclerosing cholangitis and autoimmune hepatitis in six university hospitals in Sweden. The revised autoimmune hepatitis scoring system proposed by the International Autoimmune Hepatitis Group was used to establish the diagnosis autoimmune hepatitis. Endoscopic retrograde cholangiography and/or magnetic resonance cholangiography were used to separate the primary sclerosing cholangitis cases diagnosed through liver biopsy into small and large primary sclerosing cholangitis. A histologocial diagnosis compatible with both autoimmune hepatitis and primary sclerosing cholangitis was required for inclusion.Results26 patients fulfilled our criteria for histological overlap of autoimmune hepatitis and primary sclerosing cholangitis, 7 (27%) of which had small duct primary sclerosing cholangitis. The reliability of the diagnosis small duct primary sclerosing cholangitis was supported by a very close similarity between small and large duct primary sclerosing cholangitis patients in clinical and laboratory data, and by a poor response to immunosuppressive therapy in the small duct primary sclerosing cholangitis patients. Patients with large duct overlap syndrome had a good response to immunosuppressive therapy. In both groups, our limited experience from ursodeoxycholic acid was largely poor.ConclusionsSmall duct primary sclerosing cholangitis is prevalent in the overlap syndrome between autoimmune hepatitis and primary sclerosing cholangitis.     

Celiac disease markers in patients with liver diseases: A single center large scale screening study

AIM:To study the coincidence of celiac disease, we tested its serological markers in patients with various liver diseases.METHODS:Large-scale screening of serum antibodies against tissue transglutaminase (tTG), and deamidated gliadin using enzyme-linked immunosorbent assay and serum antibodies against endomysium using immunohistochemistry, in patients with various liver diseases (n = 962) and patients who underwent liver transplantation (OLTx, n = 523) was performed. The expression of tTG in liver tissue samples of patients simultaneously suffering from celiac disease and from various liver diseases using immunohistochemistry was carried out. The final diagnosis of celiac disease was confirmed by histological analysis of small-intestinal biopsy. RESULTS:We found that 29 of 962 patients (3%) with liver diseases and 5 of 523 patients (0.8%) who underwent OLTx were seropositive for IgA and IgG anti-tTG antibodies. However, celiac disease was biopsy-diagnosed in 16 patients:4 with autoimmune hepatitis type Ⅰ, 3 with Wilson's disease, 3 with celiac hepatitis, 2 with primary sclerosing cholangitis, 1 with primary biliary cirrhosis, 1 with Budd-Chiari syndrome, 1 with toxic hepatitis, and 1 with non-alcoholic steatohepatitis. Unexpectedly, the highest prevalence of celiac disease was found in patients with Wilson's disease (9.7%), with which it is only rarely associated. On the other hand, no OLTx patients were diagnosed with celiac disease in our study. A pilot study of the expression of tTG in liver tissue using immunohistochemistry documented the overexpression of this molecule in endothelial cells and periportal hepatocytes of patients simultaneously suffering from celiac disease and toxic hepatitis, primary sclerosing cholangitis or autoimmune hepatitis type Ⅰ. CONCLUSION:We suggest that screening for celiac disease may be beneficial not only in patients with associated liver diseases, but also in patients with Wilson's disease.     

Liver transplantation in autoimmune liver diseases

Liver transplantation is indicated for terminal phases of autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis. Indications for transplantation in autoimmune liver diseases are similar to those used in other acute or chronic liver diseases. Therapeutic advances have reduced the need for transplantation for autoimmune hepatitis and primary biliary cirrhosis but not for primary sclerosing cholangitis. Overall, outcomes of transplantation for autoimmune liver diseases are excellent. However, recurrence of autoimmune liver diseases in the allograft has variable impacts on graft and patient survivals. Treatment of recurrent diseases requires changes in immunosuppression or addition of ursodeoxycholic acid. Among autoimmune liver diseases, only autoimmune hepatitis occurs de novo in recipients transplanted for other diseases. Patients transplanted for autoimmune hepatitis or primary sclerosing cholangitis are at risk for reactivation or de novo onset of ulcerative colitis. Better understanding of the pathogenesis of recurrent autoimmune liver diseases is needed to devise effective means of prevention and treatment.     

Autoimmune hepatitis with giant-cell transformation

Background/Aims: Giant-cell hepatitis (GCH), also known as postinfantile or syncytial giant cell hepatitis, is a frequent pattern of liver injury in the neonate, primarily seen in the first three months of life. Few cases in adults have been reported, some of them associated to autoimmune diseases such as autoimmune hepatitis.Methods: We present a case of autoimmune hepatitis with giant cell transformation in a 39 year old male with polyarthritis. We discuss his clinical presentation and course. We made a review of the literature of agents associated to this diagnosis, the mechanisms involved in the formation of giant hepatocytes, the histological findings, clinical course, treatment options and prognosis of this rare entity.Results and conclusions: In conclusion, the clinical course varies from normalization of hepatic histology to progression to cirrhosis and liver failure. The prognosis is dictated by the underlying liver disease and in the setting of autoimmune hepatitis the clinical course is usually severe with most of the patients progressing to cirrhosis. Prolonged treatment with corticosteroids and immunosuppressants is usually effective in rendering the cirrhosis inactive.     

Overlap syndrome of primary biliary cirrhosis and autoimmune hepatitis with unusual initial presentation as fulminant hepatic failure

Autoimmune hepatitis and primary biliary cirrhosis are generally easy to discriminate on the basis of clinical, laboratory, and histological findings. The presence of anti-mitocondrial antibodies seropositivity and cholestatic clinical, laboratory, and/or histological features in patients with autoimmune hepatitis indicates the overlap syndrome of autoimmune hepatitis and primary biliary cirrhosis. Fulminant hepatic failure is an unusual initial form of presentation of autoimmune hepatitis and primary biliary cirrhosis overlap syndrome. We report the case of a 50-year-old woman with autoimmune hepatitis and primary biliary cirrhosis overlap syndrome who presented with fulminant hepatic failure. Fulminant hepatic failure has a high mortality rate and may require liver transplant. Our patient revealed a good response to corticosteroid and ursodeoxycholic acid therapy. It is important to identify and distinguish autoimmune hepatitis and variant syndromes from other forms of liver disease because of response to corticosteroid therapy.     

Overlap Syndromes of Autoimmune Hepatitis: An Open Question

The headword “overlap syndromes” of liver diseases includes the coexistence of autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis. These syndromes often represent a diagnostic and therapeutic challenge for hepatologists; it remains unclear whether these overlap syndromes form distinct entities or they are only variants of the major autoimmune liver diseases. The most frequent reported association occurs between autoimmune hepatitis and primary biliary cirrhosis, whereas the overlap between autoimmune hepatitis and primary sclerosing cholangitis is less frequent, typically at young age and often attendant with an inflammatory bowel disease. The choice therapy is based on ursodeoxycholic acid and immunosuppressive drugs, used at the same time or consecutively, according to the course of disease. The diagnostic scores for autoimmune hepatitis can help for diagnosis, even though their definitive soundness is lacking.     

Phenotypical analysis and cytokine release of liver-infiltrating and peripheral blood T lymphocytes from patients with chronic hepatitis of different etiology

Cytokines released by infiltrating T cells may contribute to the hepatic injury in chronic hepatitis. Therefore, we characterized peripheral blood- and liver-infiltrating T cells from patients with chronic hepatitis of different etiology and determined the T cell phenotypes and the cytokine release. Liver tissue and peripheral blood-derived T cells from patients with autoimmune hepatitis and primary biliary cirrhosis predominantly expressed CD4-molecules and the α- and β-chains of the T cell receptor (TCR). In chronic viral hepatitis B and C, liver- and blood-derived T cells were preferentially CD8+ T cells expressing the αβ TCR. Mitogenic stimulation with irradiated Daudi lymphoma cells and phytohemagglutinin led to a strong release of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and interleukin-2 (IL-2) by T cells in patients with chronic hepatitis and in healthy controls. T cells from patients with primary biliary cirrhosis and some patients with autoimmune hepatitis showed a significantly higher secretion of interleukin-4 (IL-4) and interleukin-10 (IL-10) than T cells from patients with chronic viral hepatitis or healthy controls. Histologic inflammatory activity did not correlate with the amount of cytokines released after mitogenic activation. In conclusion, liver tissue and peripheral blood T cells of patients with autoimmune hepatitis and primary biliary cirrhosis were dominated by CD4+ TCR αβ+ T helper/inducer cells, whereas in chronic viral hepatitis an enrichment of CD8+ TCR αβ+ cytotoxic/suppressor T cells was observed. In addition, analysis of the cytokine release showed that T cells in autoimmune and chronic viral liver diseases secreted high amounts of IFN-γ and TNF-α, cytokines predominantly secreted by T_hl-like cells. The secretion of the T_h2 cytokines. IL-4 and IL-10, however, was increased in autoimmune hepatitis and primary biliary cirrhosis. These data show that in autoimmune and chronic viral liver diseases different functional T cell subsets are activated.     

Clinical significance of anti-neutrophil cytoplasmic antibodies (ANCA) in autoimmune liver diseases

BACKGROUND/AIMS: The clinical relevance of anti-neutrophil cytoplasmic antibodies (ANCA) in autoimmune liver disease is unclear. Defining the antigenic specificities of ANCA in these diseases may improve their clinical significance. METHODS: We studied the target antigens of ANCA in 88 patients with autoimmune hepatitis, 53 patients with primary biliary cirrhosis, and 55 patients with primary sclerosing cholangitis by indirect immunofluorescence, antigen-specific enzyme-linked immunosorbent assays, and immunodetection on Western blot, using an extract of whole neutrophils as a substrate. We related the data to clinical symptoms of autoimmune liver disease. RESULTS: By indirect immunofluorescence, ANCA were present in 74% of patients with autoimmune hepatitis, 26% of patients with primary biliary cirrhosis, and 60% of patients with primary sclerosing cholangitis. Major antigens were catalase, alpha-enolase, and lactoferrin. The presence of ANCA as detected by indirect immunofluorescence was associated with the occurrence of relapses in autoimmune hepatitis, with decreased liver synthesis function in primary biliary cirrhosis and in primary sclerosing cholangitis, and with increased cholestasis in primary sclerosing cholangitis. ANCA of defined specificities had only limited clinical relevance. CONCLUSIONS: ANCA as detected by indirect immunofluorescence seem associated with a more severe course of autoimmune liver disease. The target antigens for ANCA in these diseases include catalase, alpha-enolase, and lactoferrin. Assessment of the antigenic specificities of ANCA in autoimmune liver disease does not significantly contribute to their clinical significance.     

Resolution of cirrhosis in autoimmune hepatitis with corticosteroid therapy

Successful therapy for liver diseases, including autoimmune hepatitis, primary biliary cirrhosis, and hepatitis C, has been associated with a reduction in hepatic fibrosis. Recently, a study of needle liver biopsy specimens documented resolution of cirrhosis in a small group of patients with autoimmune hepatitis who responded to corticosteroid therapy. We describe a woman with autoimmune hepatitis who had cirrhosis on a wedge biopsy of the liver in 1985 and who attained a biochemical response with immunosuppressive therapy. A repeat wedge liver biopsy performed 14 years later was normal, providing unequivocal evidence that cirrhosis can reverse completely in autoimmune hepatitis.     

Type II Autoimmune Hepatitis and Small Duct Sclerosing Cholangitis in a Seven Years Old Child: An Overlap Syndrome?

Introduction

Autoimmune hepatitis is an inflammatory disease with multifactorial ethiopatogenesis, characterized by lympho-monocytic infiltration of liver, presence of serum autoantibodies (ANA, SMA, LKM-1) and high levels of immunoglobulins. Overlap syndromes are defined as the association of autoimmune hepatitis with cholestatic diseases such as primary biliary cirrhosis and primary sclerosing cholangitis. The boundaries of these syndromes as distinct pathological entities are still matter of debate and they could be part of a major liver autoimmune disease. Furthermore, cholestatic diseases may present even with atypical features (AMA-negative primary cirrohosis, primary sclerosing cholangitis with normal cholangiography).

Case Presentation

We herein describe a case of a 7 year-old child affected by an overlap syndrome between type 2 autoimmune hepatitis and small duct primary sclerosing cholangitis. Although characterized by a severe onset, the disease showed a good response to treatment with prednisone and azathioprine.

Conclusions

The association of type 2 autoimmune hepatitis and small duct primary cholangitis has been rarely reported in literature and this report adds new data on this still unclear entity.     

Familial occurrence of autoimmune liver disease with overlapping features of primary biliary cholangitis and autoimmune hepatitis in a mother and her daughter

We encountered two patients with overlapping features of primary biliary cholangitis and autoimmune hepatitis within the same family. A 68-year-old woman presented at our hospital from a previous medical institution because of the diagnosis of primary biliary cholangitis. Her 49-year-old daughter was admitted with liver dysfunction 4 years later. When compared, these two related patients were found to have overlapping features of primary biliary cholangitis and autoimmune hepatitis. Their human leukocyte antigen haplotype was DRB1*04:05/DRB1*15:02. The clinical and biochemical findings of these two patients immediately improved following treatment with a combination of prednisolone and ursodeoxycholic acid, in accordance with the Japanese guidelines. It is extremely important to identify such pathological conditions as quickly as possible, particularly with the appearance of severe liver dysfunction due to liver cirrhosis, as observed in our case. The Japanese guidelines are considered to be a realistic and useful clinical policy for the swift and efficient treatment of patients with overlapping features of primary biliary cholangitis and autoimmune hepatitis. We suggest that our two patients presented with a genetic predisposition to autoimmune liver disease with overlapping features of primary biliary cholangitis and autoimmune hepatitis within the same family.     

Overlap syndrome of autoimmune hepatitis and primary biliary cirrhosis triggered by fluvastatin

Although statins are generally well-tolerated drugs, recent cases of autoimmune hepatitis (AIH) associated with their use have been reported. A 59-year-old Japanese man reported with liver damage, which appeared one month after beginning treatment with fluvastatin and continued after discontinuation of the drug. Although drug-induced liver injury was possible, positive autoantibody tests (antinuclear antibodies >1/1280, anti-mitochondrial M2 antibodies 21 index value) also suggested autoimmune liver disease. Liver biopsy findings were consistent with an overlap of autoimmune hepatitis and primary biliary cirrhosis. Treatment with prednisone and ursodeoxycholic acid led to a good response. In this patient, manifestation of AIH and primary biliary cirrhosis overlap syndrome was possibly triggered by statin use. Autoimmune liver disease should be considered as a possible diagnosis in patients with evidence of prolonged liver damage after discontinuation of statins.     

Overlap syndrome between autoimmune hepatitis and primary biliary cirrhosis complicated by hepatocellular carcinoma

The risk of hepatocellular carcinoma superimposed in the evolution of autoimmune hepatitis or primary biliary cirrhosis is low, even in patients with long-standing cirrhosis. We report a case of hepatocellular carcinoma occurring in a 46 year old woman with liver cirrhosis following overlap syndrome between autoimmune hepatitis and primary biliary cirrhosis, routinely followed while on the waiting list for liver transplantation. The patient had combined biochemical (elevated aminotransferases, alkaline phosphatase and gamma-glutamyl-transpeptidase in the range of 2-3 times above the upper limit of the normal) and serological (anti-smooth muscle antibody > 1/80 and anti-mitochondrial antibody anti-M2 > 1/40) criteria of autoimmune hepatitis and primary biliary cirrhosis. Hepatocellular carcinoma was diagnosed in the setting of chronic liver disease by the combination of two concordant imaging technics (Doppler ultrasound and magnetic resonance imaging) showing a hepatic nodule with arterial hypervascularization and elevated serum levels of alpha-fetoprotein up to 950 ng/ml. Liver transplantation is the best treatment both for the solitary nodule less than 5 cm and underlying autoimmune cirrhosis. Using the new Model for End-Stage Liver Disease allocation system our patient was placed in a prior position for liver transplantation (MELD 29). Unfortunately, a sudden fulminant liver failure complicated with intravascular disseminated coagulopathy was fatal for our patient while awaiting liver transplantation.     

Spectrum of liver pathology in immune mediated liver diseases

Abstract   Immune mechanisms are involved in a wide range of parenchymal liver diseases and are of particular importance in conditions where the pathogenesis appears to be related to loss of tolerance to self antigens. In the liver there are two classical 'autoimmune' conditions: primary biliary cirrhosis and autoimmune hepatitis. It is increasingly apparent however that these may represent ends of a spectrum and overlap syndromes are well recognised. Furthermore there is evidence that primary sclerosing cholangitis may be a further example of autoimmune liver disease and overlpa conditions between this and autoimmune hepatitis are described. Histopathological assessment remains an important diagnostic tool in the investigation of autoimmune liver disease, particularly in the context of outlier and overlap conditions.