Search

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease in which anti-mitochondrial antibodies (AMA) are the diagnostic hallmark. Whether AMA-negative PBC patients represent a different phenotype of disease is highly debated. The purpose of our study was to compare AMA-positive and AMA-negative PBC patients in a large non-white admixed Brazilian cohort. The Brazilian Cholestasis Study Group multicentre database was reviewed to assess demographics, clinical features and treatment outcomes of Brazilian PBC patients, stratifying data according to AMA status. A total of 464 subjects (95.4% females, mean age 56 ± 5 years) with PBC were included. Three hundred and eighty-four (83%) subjects were AMA-positive, whereas 80 (17%) had AMA-negative PBC. Subjects with AMA-negative PBC were significantly younger (52.2 ± 14 vs. 59.6 ± 11 years, p = 0.001) and had their first symptom at an earlier age (43.2 ± 13 vs. 49.5 ± 12 years, p = 0.005). Frequency of type 2 diabetes was significantly increased in subjects with AMA-negative PBC (22.5% vs. 12.2%, p = 0.03). Lower IgM (272.2 ± 183 vs. 383.2 ± 378 mg/dL, p = 0.01) and triglycerides (107.6 ± 59.8 vs.129.3 ± 75.7 mg/dL, p = 0.025) and higher bilirubin (3.8 ± 13.5 vs. 1.8 ± 3.4 mg/dL, p = 0.02) levels were also observed in this subgroup. Response to ursodeoxycholic acid varied from 40.5 to 63.3% in AMA-positive and 34 to 62.3% in AMA-negative individuals, according to different response criteria. Outcomes such as development of liver-related complications, death and requirement for liver transplantation were similar in both groups. AMA-negative PBC patients are similar to their AMA-positive counterparts with subtle differences observed in clinical and laboratory features.

Watch a video presentation of this article.

Background and Aim Standard treatment for autoimmune hepatitis (AIH) consists of predniso(lo)ne and azathioprine. However, alternative therapy is required for non‐ or partial responders and in cases of side effects. The aim of this study was to evaluate the treatment outcomes associated with chloroquine plus prednisone in AIH patients. Methods Fifty‐seven patients were recruited to receive either azathioprine or chloroquine, both with prednisone, in a randomized trial. The primary end‐point was complete remission, based on normalization of aminotransferase levels in the first 6 months of treatment plus maintenance for at least 18 months, with minimal or no inflammatory activity in the liver biopsy. Secondary end‐points were partial and nonresponse, severe side effects, and treatment withdrawal. Results There were no differences between groups regarding clinical, serological, histological, and treatment characteristics at baseline. There were no significant differences in the biochemical response rate (67.7 vs 53.8%, P = 0.41) or the complete remission rate (32.26 vs 15.38%, P = 0.217). However, despite the long study period, the sample size was smaller than that required for a noninferiority study. The mean prednisone dose was similar in both groups. There was a nonsignificantly higher rate of adverse effects and a tendency toward improvement in glycemic and cholesterol profiles in the chloroquine group (P = 0.09 and P = 0.07, respectively). Conclusions The combination of chloroquine and prednisone exhibited potentially beneficial effects in AIH patients (https://ClinicalTrials.gov: NCT02463331)., The aim of this study was to evaluate the association of chloroquine and prednisone in the treatment of autoimmune hepatitis (AIH). The combination of chloroquine and prednisone exhibited potentially beneficial effects in AIH patients.

Introduction Routinely, pediatric donor (PD) grafts are allocated to pediatric liver transplantation (LT) recipients; however, occasionally they can be allocated for adult recipients (ARs). Some authors reported decreased patient/graft survival and higher vascular complications, such as hepatic artery thrombosis (HAT), in LT in ARs using PDs. Methods It is a retrospective study enrolling 1202 ARs undergoing LT using whole liver grafts during the period of January 2002 to April 2019. The patients were categorized according to donor age in 2 groups: PDs and adult donors (ADs). The variables were collected from the database including the graft to recipient weight ratio (GWRW) and the incidence of HAT and graft primary nonfunction (PNF). Results The AD group had 1152 patients, and the PD group had 50 patients. PNF occurred in 68 (5.66%) patients, and the distribution between the 2 groups were similar: 65 (5.64%) in the AD group, and 3 (6%) in the PD group (P = .915). HAT was diagnosed in 30 (2.6%) patients in the AD group and in 6 (12%) patients in the PD group. HAT was significantly higher in the PD group (P = .001). In the PD group, the GWRWs among patients diagnosed with HAT were similar (P = .152). Conclusion HAT is higher in PDs, although it is a viable alternative with satisfactory results. Serial Doppler in the first week and early introduction of platelet antiaggregants and/or anticoagulants may be beneficial, albeit it is not clear if it could reduce the incidence of HAT.

Background and Aims Azathioprine (AZA) and prednisone (PD) are the standard treatment (ST) for the onset or relapse of autoimmune hepatitis (AIH). Antimalarials were effective for maintenance of remission of AIH after immunosuppression withdrawal. Our aim is to describe a series of patients who relapsed after antimalarial withdrawal and achieved biochemical remission after reintroduction of chloroquine in monotherapy. Methods Eight patients received chloroquine diphosphate (DCQ) 250mg/d or hydroxichloroquine (HCQ) 400-800mg/d in monotherapy for biochemical remission after relapse. The schedule is described below: histological remission (HR) with ST → ST withdrawal and antimalarial use for maintenance of remission for 1-3y → antimalarial withdrawal → relapse of AIH → reintroduction of antimalarial instead of ST, at the request of patient due to corticosteroids side effects (SE). Four out of 8 patients underwent liver biopsy to evaluate HR after at least 18mo of biochemical remission. Results Mean age at diagnosis of AIH of 36.2 ± 20.4y; 6 type-1, 2 anti-SLA/LP (5 reactive in 7 tested); 3 with cirrhosis at diagnosis. Mean doses of AZA/PD at HR were, respectively, 84.4 ± 18.6 and 9.4 ± 2.2mg/d. Mean interval between antimalarial withdrawal and relapse was 20.5 ± 34.1mo. Mean ALT at relapse was 139.7 ± 54.2 U/L. Three patients received DCQ and 5 HCQ. During HCQ intake 1 patient needed further adjustment of drug to 800 mg/d for 15 days due to worsening of ALT from 130 to 246 U/L, with subsequent reduction to the initial dose. Seven patients achieved biochemical remission, in a mean time of 14.2 ± 19.9mo; 3/4 had histological remission. The drug was well tolerated and there were no serious SE. Conclusions CQ monotherapy was safe and effective for induction of remission in this subgroup of AIH. This finding raises arguments to include this drug as an option for treatment of AIH, not necessarily in monotherapy.

Background and Aims: Hepatocellular carcinoma (HCC) occurrence is rare in autoimmune hepatitis (AIH) and data about its characteristics are still scarce. The aims of this study were to describe HCC prevalence and risks factors in AIH patients in a tertiary referral hospital. Methods: Retrospective cohort of AIH patients followed from 2003 to 2019. The hazard ratios (HR) and their respective 95% confidence intervals (95%CI) were estimated using simple Cox regression. A multivariate regression model was fitted using relevant covariates for HCC occurrence. Results: Among 355 AIH patients, 84.5% were female, 85% AIH-1, 65% with cirrhosis and mean age at AIH diagnosis of 27±18yr. Sixteen cases of HCC were diagnosed (4.5%), all of them in cirrhotic patients, 81.3% female, mean age of 49±20yr, 83% overweight (BMI 34±5kg/m2) and 3 with associated steatohepatitis. The pooled incidence rate for HCC was 3.2 per 100 patient-years. The pooled incidence of HCC in patients with cirrhosis at AIH diagnosis was 4.5 per 100 patient-years. The median time between AIH diagnosis and HCC was 9 years (1-42). At univariate analysis the factors associated with HCC risk were age at diagnosis of AIH (HR,1.05; 95%CI,1.02-1.08; p

Background. Primary sclerosing cholangitis (PSC) is associated with a broad phenotypic spectrum in different populations from diverse ethnic and racial backgrounds. This study aimed to describe the clinical characteristics and outcomes of PSC in a multicenter cohort of patients from Brazil. Methods. Data from the Brazilian Cholestasis Study Group were retrospectively reviewed to assess demographic information and clinical characteristics of PSC, as well as the outcomes, such as transplantation-free survival. Results. This cohort included 210 patients. After excluding 33 (15.7%) patients with PSC and overlap syndrome of autoimmune hepatitis, 177 (97 males, median age 33 (21–42) years) with clear-cut PSC were eligible for this study. Most of the patients (n = 139, 78.5%) were symptomatic, and 104 (58.7%) had advanced PSC at the time of diagnosis. Concurrent inflammatory bowel disease was observed in 78 (58.6%) of the investigated patients (n = 133), and most of them had ulcerative colitis (n = 61, 78.2%). The 1- and 5-year survival free of liver transplantation or death were 92.3 ± 2.1% and 66.9 ± 4.2%, respectively, and baseline advanced PSC, pruritus, and elevated bilirubin levels were independent risk factors for the composite adverse outcome. Females were significantly older and had lower bilirubin levels than males at baseline, but survival was not associated with sex. Approximately 12.4% (n = 22) of patients with PSC died, and 32.8% (n = 58) underwent liver transplantation at a median follow-up time of 5.3 and 3.2 years. Conclusion. Multiethnic Brazilian PSC patients exhibited a less pronounced male predominance and a lower frequency of inflammatory bowel disease than Caucasians. Adverse outcomes were more frequent, probably due to advanced disease at baseline.

New data concerning the management of autoimmune liver diseases have emerged since the last single-topic meeting sponsored by the Brazilian Society of Hepatology to draw recommendations about the diagnosis and treatment of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), overlap syndromes of AIH, PBC and PSC and specific complications and topics concerning AIH and cholestatic liver diseases. This manuscript updates those previous recommendations according to the best evidence available in the literature up to now. The same panel of experts that took part in the first consensus document reviewed all recommendations, which were subsequently scrutinized by all members of the Brazilian Society of Hepatology using a web-based approach. The new recommendations are presented herein.

Context Coronavirus disease 2019 (COVID-19) is a proinflammatory and prothrombotic condition, but its impact on adrenal function has not been adequately evaluated. Case report A 46-year-old woman presented with abdominal pain, hypotension, and skin hyperpigmentation after COVID-19 infection. The patient had hyponatremia, serum cortisol Discussion We identified 9 articles, including case reports, of new-onset adrenal insufficiency and/or adrenal hemorrhage/infarction on CT in COVID-19. Adrenal insufficiency was hormonally diagnosed in 5 cases, but ACTH levels were measured in only 3 cases (high in 1 case and normal/low in other 2 cases). Bilateral adrenal nonhemorrhagic or hemorrhagic infarction was identified in 5 reports (2 had adrenal insufficiency, 2 had normal cortisol levels, and 1 case had no data). Interestingly, the only case with well-characterized new-onset acute primary adrenal insufficiency after COVID-19 had a previous diagnosis of antiphospholipid syndrome. In our case, antiphospholipid syndrome diagnosis was established only after the adrenal infarction triggered by COVID-19. Conclusion Our findings support the association between bilateral adrenal infarction and antiphospholipid syndrome triggered by COVID-19. Therefore, patients with positive antiphospholipid antibodies should be closely monitored for symptoms or signs of acute adrenal insufficiency during COVID-19.

The impact of coronavirus disease‐19 (COVID‐19) in liver recipients remains largely unknown. Most data derive from small retrospective series of patients transplanted years ago. We aimed to report a single‐center case series of five consecutive patients in the early postoperative period of deceased‐donor liver transplantation who developed nosocomial COVID‐19. Two patients presented important respiratory discomfort and eventually died. One was 69 years old and had severe coronary disease. She rapidly worsened after COVID‐19 diagnosis on 9th postoperative day. The other was 67 years old with non‐alcoholic steatohepatitis, who experienced prolonged postoperative course, complicated with cytomegalovirus infection and kidney failure. He was diagnosed on 36th postoperative day and remained on mechanical ventilation for 20 days, ultimately succumbing of secondary bacterial infection. The third, fourth, and fifth patients were diagnosed on 10th, 11th, and 18th postoperative day, respectively, and presented satisfactory clinical evolution. These last two patients were severely immunosuppressed, since one underwent steroid bolus for acute cellular rejection and another also used anti‐thymocyte globulin for treating steroid‐resistant rejection. Our novel experience highlights that COVID‐19 may negatively impact the postoperative course, especially in elder and obese patients with comorbidities, and draws attention to COVID‐19 nosocomial spread in the early postoperative period.

Despite the great number of cases of COVID‐19 around the world, data in liver transplant (LT) recipients are still settling down. We share our experience after the first four cases of long‐term LT recipients admitted for hospitalization and the measures for suspicion and diagnostic investigation adopted after these cases. The mean time of initial symptoms at hospitalization was 8 days; only one case had the classical respiratory symptoms.

Late-Onset Hepatitis with Yellow Fever Brazil has had 2585 confirmed cases of yellow fever during the past 2 years. In this report, investigators from Sao Paulo describe cases of hepatitis occurrin...

The rapid spread of the coronavirus pandemic worldwide warrants a huge transformation in the health assistance system and patient care. Most countries affected by coronavirus disease (COVID-19) are in lockdown, with restrictions on the movement of people and in services to prevent rapid transmission that may consequently lead to a health system collapse. The disease is known to cause severe acute respiratory syndrome (SARS), especially in the elderly population and in patients with comorbidities. Patients with chronic liver diseases can [...]

Introduction and objectives: Little is known about primary biliary cholangitis (PBC) in non-whites. The purpose of this study was to evaluate clinical features and outcomes of PBC in a highly admixed population. Material and methods: The Brazilian Cholestasis Study Group multicentre database was reviewed to assess demographics, clinical features and treatment outcomes of Brazilian patients with PBC. Results: 562 patients (95% females, mean age 51 ± 11 years) with PBC were included. Concurrent autoimmune diseases and overlap with autoimmune hepatitis (AIH) occurred, respectively, in 18.9% and 14%. After a mean follow-up was 6.2 ± 5.3 years, 32% had cirrhosis, 7% underwent liver transplantation and 3% died of liver-related causes. 96% were treated with ursodeoxycholic acid (UDCA) and 12% required add-on therapy with fibrates, either bezafibrate, fenofibrate or ciprofibrate. Response to UDCA and to UDCA/fibrates therapy varied from 39%-67% and 42-61%, respectively, according to different validated criteria. Advanced histological stages and non-adherence to treatment were associated with primary non-response to UDCA, while lower baseline alkaline phosphatase (ALP) and aspartate aminotransferase (AST) levels correlated with better responses to both UDCA and UDCA/fibrates.Conclusions: Clinical features of PBC in highly admixed Brazilians were similar to those reported in Caucasians and Asians, but with inferior rates of overlap syndrome with AIH. Response to UDCA was lower than expected and inversely associated with histological stage and baseline AST and ALP levels. Most of patients benefited from add-on fibrates, including ciprofibrate. A huge heterogeneity in response to UDCA therapy according to available international criteria was observed and reinforces the need of global standardization.

Introduction: Little is known about primary biliary cholangitis (PBC) in Latin America, where this disease is thought to be rare. Objectives: To analyze clinical and biochemical features of Brazilian PBC patients. Methods: The Brazilian Cholestasis Study Group multicentre database was reviewed to assess demographics, clinical and laboratory features from PBC patients. Results: 562 patients with PBC were included; 80 (14.2%) had overlapping syndrome with autoimmune hepatitis and were excluded. Most subjects were middle-aged women (95%; mean age 51 ± 11 years) with classical symptoms of pruritus and/or fatigue (65%) and jaundice (22%). Mean time to diagnosis was 2.5 years. Prevalence of antimitochondrial (AMA) and antinuclear antibodies was 82.8% and 72.1%, respectively. Concurrent autoimmune diseases occurred in 18.9%, mainly Hashimoto's thyroiditis and Sjogren syndrome. Celiac disease was diagnosed in 1:80 (1.2%). Osteopenia and osteoporosis were demonstrated in 42% and 26%, respectively. Liver pathology at diagnosis was available for 326 patients (67.6%). One third of them had advanced PBC. After a mean follow-up of 6.2 ± 5.3 years, 32% of the subjects had clinical, laboratory or imaging evidence of cirrhosis. Requirement for liver transplantation and liver-related deaths were reported in 6.6% and 3.2% of the patients, respectively. Hepatocarcinoma was diagnosed in 1.9% of the subjects. Conclusion: A higher predominance of PBC among females, compared to other populations, was observed, while AMA positivity was lower. Concurrent autoimmune, celiac and bone diseases are common and should be adequately screened. Prolonged time to diagnosis and high prevalence of advanced liver disease might reflect difficulties in health care access in Brazil.

Introduction Low Phospholipid-Associated Cholelithiasis (LPAC) is a clinical spectrum of Progressive Familial Intrahepatic Cholestasis type 3 (PFIC3), with mutations in the ABCB4 gene, reduced levels of phosphatidylcholine in bile, formation of cholesterol gallstones, damage of bile ducts epithelium and cholestasis. Ursodeoxycholic acid (UDCA) is effective and fibrates may also be used to activate PPAR-α receptor, inducing bile secretion of phosphatidylcholine. Aim Retrospectively evaluate efficacy and safety of ciprofibrate in LPAC/PFIC3. Method Diagnosis of PFIC3 was confirmed by detection of mutations of ABCB4 gene. LPAC diagnosis was suggested by 2 out of 5 criteria: biliary symptoms before 40 years; recurrence after cholecystectomy; intrahepatic lithiasis; cholelithiasis in first‐degree relatives; intrahepatic cholestasis of pregnancy or contraceptive‐induced cholestasis. Enzymes, liver function and pruritus were analyzed after 3, 6 and 12 months of UDCA and after ciprofibrate 100mg/day using the Wilcoxon test. Results 27(93%) patients with clinical diagnosis of LPAC and 2 of PFIC3. 23 (79%) female with mean age at onset of symptoms of 26.7±13.6 years. 23(80%) had family history of biliary disease; 22(76%) cholelithiasis before 40 years; 7(24%) intrahepatic lithiasis. 22/29 (78%) received ciprofibrate after 4.5±4.9 months of UDCA use, in a mean dose of 13.1±2.2mg/kg/day. During UDCA there was a significant decrease in aminotransferases, alkaline phosphatase(AP) and gamma-glutamyltransferase(GGT) levels, without significant improvement in the liver function. After addition of fibrate, pruritus disappeared in all 7 patients, with significant improvement of AP, GGT and albumin in the third month. There was no significant renal dysfunction. Fibrate was discontinued in 8: 1 liver transplantation, 2 irregular use, 5 side effects. 27 patients are still in follow up. Conclusion Ciprofibrate was beneficial to improve pruritus and laboratory tests in LPAC/PFIC3 after partial response with UDCA. Fibrate therapy was safe and well tolerated.

Hepatitis E Virus (HEV) is an infection known worldwide for its asymptomatic and self-limited course in most cases. Some cases progressing to chronicity have been described in immunosuppressed patients, especially in recipients of solid organ transplants. We evaluated laboratory parameters of HEV infection (HEV RNA, anti-HEV IgM and anti-HEV IgG) through enzyme-linked immunosorbent assay (Elisa), confirmed by immunoblotting, in a cohort of 294 patients who received liver transplants at the HCFMUSP (Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo). Laboratory and demographic data were collected from the entirety of the transplanted population. Hepatic biopsies of 122 patients transplanted due liver failure secondary to hepatitis C (HCV), with or without serological or molecular markers of HEV, were analyzed according to METAVIR score. Out of 24 (8.2%) patients tested positive for anti-HEV IgG, six (2%) were positive for anti-HEV IgM and 17 (5.8%) for HEV RNA. Of the patients transplanted because of HCV infection, 95 (77.8%) had received treatment including ribavirin for at least six months before blood sample collection. Among patients transplanted due to HCV cirrhosis who tested positive for anti-HEV IgG, only three (37.5%) showed fibrosis beyond stage 2, while five (41.7%) of the HEV RNA-positive patients had liver fibrosis beyond stage 2. Overall, the prevalence of HEV in the post-hepatic transplant scenario appears to be low, and, at least histologically, seemingly not harmful. We conclude that, although some studies reported a risk of HEV chronification, patients who had their livers transplanted due to HCV and showed serological or molecular markers of HEV did not have higher levels of fibrosis compared to patients who showed no indications of HEV infection at the time of the analysis.

Between 50% and 86% of patients with autoimmune hepatitis (AIH) relapse after immunosuppression withdrawal; long-term immunosuppression is associated with increased risk of neoplasias and infections. Chloroquine diphosphate (CQ) is an immunomodulatory drug that reduces the risk of flares in rheumatologic diseases. Our aims were to investigate the efficacy and safety of CQ for maintenance of biochemical remission of AIH in a double-blind randomized trial and to define a subgroup that obtained a greater benefit from its use. A total of 61 patients with AIH in histologic remission (90.1% AIH type 1 [AIH-1]) were randomized to receive CQ 250 mg/day or placebo for 36 months. Of the 61 patients, 31 received CQ and 30 placebo. At baseline, clinical, laboratory, histologic findings, and human leukocyte antigen (HLA) profile were similar between the two groups. Relapse-free survival was significantly higher in the CQ group compared to the placebo group (59.3% and 19.9%, respectively P = 0.039). For those patients completing 3-year treatment, relapse rates were 41.6% and 0% after CQ and placebo withdrawal, respectively. Factors associated with a higher risk of relapse in multiple Cox regression were placebo use (hazard ratio, 2.4; 95% confidence interval [CI], 1.055.5; P = 0.039) and anti-soluble liver antigen/liver-pancreas (anti-SLA/LP) seropositivity (hazard ratio, 5.4; 95% CI, 1.91-15.3; P = 0.002). Although it was not possible to define a subgroup that obtained a greater benefit from CQ according to anti-SLA/LP reactivity or HLA profile, 100% of patients who were anti-SLA/LP-positive (+) relapsed with placebo compared to 50% with CQ (P = 0.055). In the CQ group, 54.8% had side effects and 19.3% interrupted the drug regimen. Conclusion: CQ safely reduced the risk of relapse of AIH, but it was not possible to define a subgroup that obtained a greater benefit with CQ use, probably because of sample size.

Cardiovascular disease is a major contributing factor to long-term mortality after liver transplantation (LT).This study evaluated the evolution of atherogenic risk in liver transplant recipients (LTRs). Thirty-six subjects were prospectively enrolled at 12 months and followed for 48 months after liver transplantation. Serum biomarkers of endothelial dysfunction (sICAM-1 and sVCAM-1), chronic inflammation (serum amyloid A), and oxidative stress (myeloperoxidase) were measured at 12 and 48 months after LT. Additionally, at 12 months all patients underwent a cardiac computed tomography (CT) scan and a coronary artery calcium score (CACS).The prevalence of risk factors of metabolic syndrome (MS) increased over the course of the study. The patients' sVCAM-1 and sICAM-1 increased from 1.82 ± 0.44 ng/mL to 9.10 ± 5.82 ng/mL (P .001) and 0.23 ± 0.09 ng/mL to 2.7 ± 3.3 ng/mL, respectively from month 12 to 48. Serum myeloperoxidase increased from 0.09 ± 0.07 ng/mL to 3.46 ± 3.92 ng/mL (P .001) over the course of the study. Serum amyloid A also increased from 21.4 ± 40.7 ng/mL at entry to 91.5 ± 143.6 ng/mL at end of study (P .001).No association between these biomarkers and MS was noted. The cardiac CT revealed mild and moderate disease in 19% and 25% of the cohort, respectively. No association between serum biomarkers and CACS was noted. Serum biomarkers of atherogenic risk increase rapidly in LTRs and precede coronary plaques.

The standard therapy for some autoimmune diseases consists of a combination of corticosteroids and thiopurines. In non-responders to thiopurine drugs, the measurement of the metabolites of azathioprine, 6-thioguanine, and 6-methylmercaptopurine, can be a useful tool. The measurement has been used during the treatment of inflammatory bowel diseases and, less commonly, in autoimmune hepatitis. Many patients preferentially metabolize thiopurines to 6-methylmercaptopurine (6-MMP), which is potentially hepatotoxic, instead of 6-thioguanine, the active immunosuppressive metabolite. The addition of allopurinol shifts the metabolism of thiopurine towards 6-thioguanine, improving the immunosuppressive effect. We present the case of a 51-year-old female with autoimmune hepatitis who had a biochemical response after azathioprine and prednisone treatment without histological remission, and who preferentially shunted to 6-MMP. After the addition of allopurinol, the patient’s 6-thioguanine levels increased, and she reached histological remission with a reduction of 67% of the original dose of azathioprine. The patient did not develop clinical manifestations as a consequence of her increased immunosuppressive state. We also review the relevant literature related to this issue. In conclusion, the addition of allopurinol to thiopurine seems to be an option for those patients who do not reach histological remission and who have a skewed thiopurine metabolite profile.

In order to draw evidence-based recommendations concerning the management of autoimmune diseases of the liver, the Brazilian Society of Hepatology has sponsored a single-topic meeting in October 18th, 2014 at São Paulo. An organizing committee comprised of seven investigators was previously elected by the Governing Board to organize the scientific agenda as well as to select twenty panelists to make a systematic review of the literature and to present topics related to the diagnosis and treatment of autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis and their overlap syndromes. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript organized in topics, followed by the recommendations of the Brazilian Society of Hepatology. RESUMO Para definir as recomendações baseadas em evidências científicas sobre o diagnóstico e tratamento das doenças autoimnus do fígado, a Sociedade Brasileira de Hepatologia organizou em Outubro de 2014, encontro monotemático em São Paulo. Um Comitê organizador de sete investigadores foi selecionado pela Diretoria da Sociedade para organizar a agenda científica, assim como para selecionar vinte debatedores para fazer uma revisão sistemática e apresentar tópicos relacionados à hepatite autoimune, colangite esclerosante primária, cirrose biliar primária e suas síndromes de superposição (overlap). O texto inicial do submetidoo a apreciação e aprovação da Sociedade Brasileira de Hepatologia através de consulta a todos associados através da home page da Sociedade, O trabalho apresentado representa a versão final do trabalho original, devidamente revisado e organizado em tópicos, segundo as recomendações da Sociedade Brasileira de Hepatologia.

Background: Autoantibodies to ribosomal P proteins (anti-rib P) are specificserological markers for systemic lupus erythematosus (SLE) and are associ-ated with liver involvement in this disease. The similarity in autoimmunebackground between autoimmune hepatitis (AIH) and SLE-associated hepa-titis raises the possibility that anti-rib P antibodies might also have relevancein AIH. Aims: To evaluate the frequency and clinical significance of anti-ribP antibodies in a large AIH cohort. Methods: Sera obtained at diagnosis of96 AIH patients and of 82 healthy controls were tested for IgG anti-ribo-somal P protein by ELISA. All of the sera were also screened for other lupus-specific autoantibodies, three patients with the presence of anti-dsDNA(n = 1) and anti-Sm (n = 2) were excluded. Results: Moderate to high titres(>40 U) of anti-rib P antibody were found in 9.7% (9/93) of the AIHpatients and none of the controls (P = 0.003). At presentation, AIH patientswith and without anti-rib P antibodies had similar demographic/clinical fea-tures, including the frequency of cirrhosis (44.4 vs. 28.5%, P = 0.44), hepaticlaboratorial findings (P > 0.05). Importantly, at the final observation (fol-low-up period 10.2 ± 4.9 years), the AIH patients with anti-rib P had asignificantly higher frequency of cirrhosis compared with the negative group(100 vs. 60%, P = 0.04). Conclusion: The novel demonstration of anti-rib Pin AIH patients without clinical or laboratory evidence of SLE suggests acommon underlying mechanism targeting the liver in these two diseases. Inaddition, this antibody appears to predict the patients with worse AIHprognoses.According to the International Autoimmune HepatitisGroup, autoantibodies are important parameters fordiagnosing autoimmune hepatitis (AIH) (1, 2). Antinu-clear antibodies (ANA) and antibodies to smooth mus-cle (SMA) and liver kidney microsome type 1 antigen(anti-LKM1) are the most frequently detected autoanti-bodies with diagnostic and classification relevance,but they are devoid of prognostic value (3). The gold-standard technique used to detect these antibodies isindirect immunofluorescence, which is operator depen-dent and thus has a reduced level of accuracy (4). Theseobservations explain the continuing search for newautoantibodies that can be assessed by standardizedmethods and that could be potential AIH serologicalmarkers with prognostic value (5, 6).In this regard, anti-ribosomal P proteins antibodies(anti-rib P), which are highly specific markers forsystemic lupus erythematosus (SLE) (7–11), have beenreported to occur in a higher prevalence in lupuspatients with liver involvement than in patients withoutthis complication (12, 13). The potential pathogenicrole of anti-rib P antibodies in liver disease wassupported by the ability of these antibodies to penetrateinto live hepatocytes, causing cellular dysfunction (14).The similarities between AIH- and SLE-associatedhepatitis, such as the presence of ANA, hypergamma-globulinemia and arthritis, have raised the possibilitythat anti-rib P antibodies might also be present inAIH and could have a role in the severity of liverinjury (15). However, the only available study in theliterature reported that this antibody was not detectedin 20 AIH patients (16). The limited number ofpatients and the absence of information regardingsera being tested before treatment have precluded adefinitive conclusion about their findings becauseanti-rib P levels are known to fluctuate during flares(8, 17).Therefore, we retrospectively evaluated the frequency,phenotypic manifestation and prognostic implicationsof anti-rib P antibodies in a large, well-characterized

To assess maternal and fetal outcomes and clinical management of pregnancy in patients with autoimmune hepatitis (AIH).There is a paucity of information about maternal and fetal outcomes, and AIH activity during pregnancy and in the postpartum period. There is no consensus about the administration of azathioprine during pregnancy and breastfeeding.Retrospective analysis of 54 pregnancies (3 still in progress) in 39 AIH patients.The median age at conception was 24 years, and 68.4% of women had liver cirrhosis. Before conception and in early pregnancy, azathioprine and prednisone were administered in 48.1%, but treatment regimen was usually changed further to 20 mg/d prednisone; and 20.4% were off treatment. There were 36 livebirths, and fetal loss rates were 29.4% (13 miscarriages, 1 stillbirth, and 1 ectopic pregnancy). Preterm birth rate was 11.8%. In 2 cases, there was acute fetal distress; and in 2 others congenital malformations (3.9%). The rate of serious maternal complication was 7.8%, with no deaths. There were no flares in 41.2% pregnancies, but aminotransferase elevations occurred in 54.9%, 31.4% of which were true AIH relapses, only registered in the postpartum period.Despite the high fetal miscarriage rate, pregnancy in AIH was safe. Patients needed careful monitoring, especially in the postpartum period because of relapses. There was no evidence of a cause and effect relationship among azathioprine administration and premature births and congenital abnormalities, but more studies are necessary. Higher doses of prednisone may be an alternative option for those who prefer azathioprine withdrawal during pregnancy.

P359 SERUM b-DEFENSIN 2 IS INCREASED IN PRIMARY SCLEROSING CHOLANGITIS AND CORRELATES WITH DEFB4 GENE COPY NUMBER C. Chang, A. Lleo, P. Invernizzi, A. Kananurak, C. Bevins, C.L. Bowlus. Gastroenterology and Hepatology, University of California Davis, Sacramento, CA, United States; Liver Unit and Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Milan, Italy; Microbiology and Immunology, University of California Davis, Davis, CA, United States E-mail: clbowlus@ucdavis.edu