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Little is known about autoantibody pattern in liver transplantation (LT). The aim of the study was to examine autoantibodies (AAB) and immunoglobulins in patients with end-stage liver disease before and after LT. Patients with LT who underwent post-LT biopsies between 10/2008 and 8/2011 were enrolled. AAB were assessed at the time of LT and liver biopsy. Demographics, serum immunoglobulins, AAB, and liver histology (explant, post-LT biopsies) were analyzed. Two hundred and twenty patients (M/F 143/77; age at LT 54 (19-73)) were included; AAB and immunoglobulins were evaluated in 76 patients. Length of follow-up from LT was 285 (30-1462) days. Sixty-one percent of patients had hepatitis C (HCV); 83% developed recurrent HCV. A significant decrease in IgG, IgA, IgM (p < 0.001 each), anticardiolipin antibodies IgG and IgM (p = 0.02), and beta-2 microglobulin (p = 0.004) was observed post-LT. HCV patients had higher IgG (p = 0.005), rheumatoid factor (p = 0.044) before LT; elevated IgM was associated with increased inflammation in the explant (p = 0.007). Lower IgG levels and antismooth muscle antibodies were present before LT in a higher percentage in patients who would develop recurrent HCV (p = 0.004, p = 0.077, respectively). In conclusion, AAB change significantly after LT and have a different pattern in HCV. Some immunological markers are associated with HCV recurrence and advanced inflammation on explant., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Interferon use for post liver transplantation (LT) recurrent hepatitis C (HCV) has not consistently been associated with acute cellular rejection (ACR). We examined the incidence of chronic ductopenic rejection (CR) in patients receiving pegylated interferon alfa-2a and ribavirin (PEG) to treat recurrent HCV., Methods: A chart review of 12 patients developing CR while receiving an escalating dose regimen of PEG with protocol liver biopsies every 6 months was conducted. Values are shown as median (range)., Results: Twelve of the 70 patients treated with PEG developed CR. Median age at LT was 53 (37-63) years; immunosuppression consisted of tacrolimus or cyclosporine with prednisone. PEG was started at 3.6 (0.2-13.5) years after LT. Two patients had one episode of ACR before PEG. Four patients had first ACR while receiving PEG. CR was diagnosed after 12 (4-17) months of PEG; by then 8 patients had undetectable HCV-RNA. Tacrolimus and cyclosporine levels (ng/mL) were 7.9 (3.2-18.9) and 76 (71-93) before PEG, and 6.9 (3.7-9.7) and 130 (81-153) at CR. Six patients were treated more than 1 year with PEG; three had undetectable HCV-RNA when CR was diagnosed. Five patients are being treated for CR; one has been listed for LT; two patients were retransplanted. Five patients died as a result of sepsis partially related to CR., Conclusions: Treatment with pegylated-interferon alpha-2a and ribavirin may trigger rapidly progressive CR in patients with therapeutic immunosuppressive trough levels, with or without first inducing ACR.

Aim: This long-term study aimed to evaluate recurrence and evolution of primary biliary cirrhosis (PBC) after orthotopic liver transplantation (OLT). Methods: We reviewed “blindly” allograft biopsy specimens of women who underwent transplantation for PBC ( n = 84), and women who received a transplant for chronic hepatitis C virus infection (CHCV ) ( n = 108). All needle liver biopsy specimens obtained more than 6 months post-OLT were examined, including 83 specimens from 44 PBC patients and 152 specimens from 58 CHCV patients. Results: Granulomatous destructive cholangitis was found in five biopsies from four PBC patients ( P = 0.0048). Non-necrotizing epithelioid cell granulomas were present in four biopsies from four PBC patients, and in two biopsies from one CHCV patient. Piecemeal necrosis ( P = 0.0002), lobular necroinflammatory activity ( P < 0.0001), steatosis ( P < 0.0001) and fibrosis ( P < 0.0001) were more prevalent in CHCV patients than PBC patients. Four PBC patients developed histologic evidence of autoimmune hepatitis (AIH), at a mean time of 3.66 years post-OLT. One of these patients had histologic features of AIH/PBC overlap syndrome. All four patients developed bridging fibrosis ( n = 2) or cirrhosis ( n = 2). No other PBC patient had evidence of cirrhosis after OLT. Conclusions: Histologic findings indicative of recurrent PBC were present in 15.9% of the PBC patients undergoing biopsy in this series. However, this group of patients did not suffer significant bile duct loss or fibrosis, as compared to the control group, suggesting that recurrent PBC is a mild or slowly progressive disease. Histologic evidence of AIH was observed in allograft biopsies of some PBC patients. [ABSTRACT FROM AUTHOR]

Immune-mediated liver diseases contribute significantly to morbidity and mortality due to liver failure and the need for liver transplantation. The pathogenesis of the immune-mediated chronic liver diseases, primary sclerosing cholangitis, autoimmune hepatitis, and primary biliary cirrhosis, is poorly understood. Genetic susceptibility factors may play a role, but increasing attention is being given to the association between environmental factors and these diseases. The existence of such a relationship is supported by epidemiologic surveys, animal models, and geographic clustering analyses. Unearthing the cause of this association may provide insight into the pathogenesis of immune-mediated chronic liver diseases and autoimmunity. [ABSTRACT FROM AUTHOR]