Georgia Papadamou

Mycophenolate for the treatment of autoimmune hepatitis: prospective assessment of its efficacy and safety for induction and maintenance of remission in a large cohort of treatment-naïve patients.

BACKGROUND & AIMS Standard therapy for autoimmune hepatitis (AIH) is corticosteroids with or without azathioprine. However, 20% of patients do not respond or are intolerant to conventional treatment. Therefore, we evaluated prospectively the efficacy and safety of mycophenolate mofetil (MMF) in inducing and/or maintaining remission in treatment-naïve AIH patients. METHODS Fifty-nine treatment-naïve patients with well defined AIH were treated with prednisolone plus 1.5-2g/d of MMF. Patients were candidates for MMF withdrawal after at least 4 years. Treatment outcomes were defined according to the International Autoimmune Hepatitis Group report. RESULTS Treatment duration with MMF was 26months (range 3-92). Eighty-eight percent (52/59) of patients responded initially clinically and biochemically (normalization of transaminases and γ-globulins) most of them within 3months. The remaining 7 patients (12%) had partial response. In total, 59.3% (35/59) of patients had complete response (CR) with 37% (22/59) of them having achieved CR off prednisolone, while 28.8% (17/59) had initial CR with relapses. No patient was non-responder. Prednisolone withdrew in 57.6% (34/59) of patients in 8months. The only independent predictor of treatment outcome, was γ-GT (baseline γ-GT, p=0.008 and γ-GT on month 24, p<0.05). Severe side effects leading to MMF discontinuation occurred in only 3.4% (2/59) of patients. Six patients (2 according to protocol and 4 for personal reasons), stopped treatment with MMF, but 3 relapsed. CONCLUSIONS MMF seems safe and effective as first-line therapy in inducing and maintaining remission in treatment-naive patients with AIH, having a significant and rapid steroid sparing effect as attested by the fact that so far, 37% (22/59) of AIH patients achieved CR off prednisolone.

Increased incidence of anti-LKM autoantibodies in a consecutive cohort of hepatitis C patients from central Greece.

Objectives In Greece, there are insufficient data regarding the presence of non-organ and liver-related autoantibodies in hepatitis C patients. This study in a consecutive cohort of 39 such patients from central Greece investigates (1) the prevalence of non-organ and liver-related autoantibodies, and (2) the reactivity of anti-liver–kidney microsomal type 1 antibodies (in the case of positivity with at least one of the methods used) against their molecularly defined antigens. Design All serum samples were tested by standard and molecular assays for the presence of anti-nuclear antibodies, smooth muscle antibodies, anti-liver–kidney microsomal type 1 antibodies, antibodies against parietal cells, anti-CYP2A6, anti-CYP1A2 and anti-CYP2D6 autoantibodies. Methods Indirect immunofluorescence, competitive enzyme-linked immunosorbent assays, immunoblotting and novel radioligand assays based on immunoprecipitation of [35S]-methionine labelled recombinant CYP2A6, CYP1A2 and CYP2D6 His-taq fusion proteins produced by in vitro transcription/translation were used. Results Seven out of 39 patients (17.9%) tested positive for smooth muscle antibodies, 2/39 (5.1%) tested positive for anti-nuclear antibodies, 1/39 (2.5%) tested positive for parietal cell antibodies, and 4/39 (10.3%) were found to be anti-liver–kidney microsomal positive (with at least one of the methods used). All sera were negative for anti-CYP2A6 and anti-CYP1A2 autoantibodies. Three out of four anti-liver–kidney microsomal positive samples had the typical liver–kidney microsomal staining pattern shown by indirect immunofluorescence. However, none tested positive for anti-CYP2D6 autoantibodies using the competitive CYP2D6 enzyme-linked immunosorbent assay, the specific CYP2D6 radioligand assay, and western blot using either human microsomes or recombinant CYP2D6. The fourth patient tested negative for anti-liver–kidney autoantibodies by either indirect immunofluorescence or the competitive enzyme-linked immunosorbent assay, but was repeatedly positive for anti-CYP2D6 autoantibodies by the sensitive and specific radioligand assay. Western blot experiments using human microsomes in this patient serum revealed two bands of 50 kDa and 55 kDa that documented as anti-CYP2D6 and anti-uridine triphosphate glucuronosyltransferase autoantibodies when recombinant CYP2D6 and recombinant uridine triphosphate glucuronosyltransferase autoantigens were used for immunoblot, respectively. Conclusions A relatively high incidence of anti-liver–kidney microsomal autoantibodies (10.3%) was found in a consecutive sample of Greek patients with hepatitis C. The expanded panel of assays, however, failed to document CYP2D6 as the target autoantigen of anti-liver–kidney microsomal autoantibodies in most patients. We report for the first time the detection of parietal cell antibodies and both anti-CYP2D6 (anti-liver–kidney microsomal type 1) and anti-uridine triphosphate glucuronosyltransferase (anti-liver–kidney microsomal type 3) autoantibodies in patients who were hepatitis C positive/hepatitis D negative. Further studies are needed to confirm our findings and to determine whether these preliminary results have a clinical importance or not.

Geoepidemiology, clinical manifestations and outcome of primary biliary cholangitis in Greece

BACKGROUND & AIMS Primary biliary cholangitis (PBC) is a disease with rising prevalence and considerable geographical variation. To describe the prevalence, spatial and time distribution, baseline characteristics, response to treatment, outcome and the validity of GLOBE score in a large cohort of Greek PBC patients as an independent validation of this score has not been done so far. METHODS The last 16years, 482 PBC patients (86.5% females) were evaluated and analysed retrospectively, using a prospectively collected database. Special attention was paid to the assessment of treatment response according to GLOBE score. RESULTS Age at initial evaluation was 56.3±13.7years. Among 432 Thessaly residents, prevalence was 582/million (non-homogeneous distribution). Nineteen districts showed a prevalence >800/million. Symptomatic disease onset could be identified in 91 patients, with a significant peak during spring (P=0.03). At diagnosis, 43.6% were asymptomatic and 16.2% cirrhotic. Male sex (P=0.02), older age (P<0.001), alcohol consumption (P<0.01) and concomitant liver disease (P<0.001) were negative prognostic factors for cirrhosis. During a median [interquartile range, range] follow-up of 5.1 (7.8, 15.7) years, 62 patients died or underwent liver transplantation. Patients with GLOBE score>0.30 had significantly worse prognosis (P<0.001) with 5-, 10-, and 15-year survival rates of 84%, 50% and 42%. CONCLUSIONS There is increased PBC prevalence in Thessaly with remarkable geographic clustering and seasonal variability. PBC is diagnosed at early stages although males had a more advanced disease. GLOBE score applies perfectly in Greek patients and this will likely help detecting patients that may benefit from new therapies.

Primary biliary cirrhosis in HBV and HCV patients: Clinical characteristics and outcome.

AIM To present the characteristics, management and outcome of patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infections concurrent with primary biliary cirrhosis (PBC). METHODS Since January 2001 to September 2009, we retrospectively evaluated the medical records of all HBV (n = 1493) and HCV patients (n = 526) who are followed in our center for the presence of concurrent PBC. Seventeen patients identified with concurrent viral hepatitis and PBC (8 HCV and PBC; follow-up: 61 ± 37 mo and 9 HBV and PBC; follow-up: 57 ± 38 mo). PBC diagnosis was established if the patients met at least two of the following criteria: positivity for antimitochondrial antibody, elevated cholestatic enzymes and histological lesions of PBC. RESULTS HCV or HBV diagnosis preceded that of PBC in most patients by many years. PBC diagnosis was based on the presence of antimitochondrial antibody and elevated cholestatic enzymes in all 17 patients, while one third (5/17; 29.4%) experienced severe pruritus many years before diagnosis. Patients with PBC and HBV were significantly younger at diagnosis of PBC compared to patients with PBC and HCV (56.1 ± 11.2 vs 68.5 ± 10.3, respectively, P < 0.05). At initial clinical and histological assessment the majority of patients were cirrhotics (10/17; 58.8%) with the group of PBC and HCV carrying the highest frequency (87.5% vs 33.3% in PBC and HBV; P < 0.05). The patients with HBV and concomitant PBC seem to have better outcome compared to those with HCV and PBC since none of the 6 non-cirrhotics with HBV and PBC developed cirrhosis during follow-up. CONCLUSION PBC diagnosis in HBV or HCV patients is very difficult and usually delayed. Therefore, in any case, cholestasis should alert physicians to further search for PBC.

Ascites in a patient with episodic angio-oedema and eosinophilia: thinking outside the box

Episodic angio-oedema with eosinophilia (EAE) or Gleich’s syndrome is a rare condition characterised by recurrent episodes of oedema and eosinophilia, accompanied by urticaria, fever and weight gain. The presence of ascites has not been reported so far. We report a 21-year-old Caucasian woman who presented with marked ocular oedema and ascites. Laboratory evaluation revealed marked eosinophilia. During the last 3 months, three episodes of facial and neck oedema were reported, which resolved spontaneously over a period of 3–5 days. The diagnosis of EAE was established after exclusion of secondary causes (infections, allergic reactions, collagen diseases, neoplasms) and clonal disorders associated with marked eosinophilia. Low-dose steroids resulted in eosinophil decrease and complete resolution of symptoms, including ascites. This case highlights that ascites can be a very rare manifestation of EAE particularly if other more frequent causes of ascites have been excluded and the clinical and laboratory findings are supportive of EAE.

Spontaneous bacterial peritonitis: an unusual manifestation of brucellosis in a previous healthy male patient.

Brucellosis is a common zoonotic disease with worldwide distribution and protean clinical manifestations. Therefore, its prompt and timely diagnosis is still challenging. Among several complications of brucellosis, spontaneous bacterial peritonitis (SBP) in previously healthy participants is rarely recognised, although this condition can be fatal if misdiagnosed and untreated. We present a case of a 69-year-old previously healthy stockbreeder who suffered from back pain along with abdominal pain and distension because of ascites of 6–8 weeks duration. Cultures of ascitic fluid and peripheral blood specimens revealed Brucella spp as the causative agent of ascites and spondylodiscitis, which was then confirmed by MRI findings. After appropriate treatment for 4.5 months (streptomycin 1 g/day for 3 weeks intramuscularly, doxycycline 100 mg twice a day orally and rifampicin 900 mg/day orally), the patient fully recovered. Conclusively, in the appropriate epidemiological and clinical setting, the consideration of brucellosis in the differential diagnosis of SBP could be rational as well as life-saving.

HEPATOCELLULAR CARCINOMA: CLINICAL CHARACTERISTICS OF THE DISEASE IN CENTRAL GREECE

and need for adrenaline, atropine and intubation were associated with poor outcomes. Witnessed arrests had favorable immediate outcome (p<0.01). In cases with primary respiratory arrests successful resuscitation was achieved in 90% and 1-year survival was 76%. There was no statistically significant difference in survival with increasing age. Conclusions: The initial, 1-month and 1-year survival following CPR were 37.9%, 24% and 16% respectively. Early recognition of critically ill patients, nursing in monitored areas and effective advanced life support training may be improving outcomes in our hospital.