Background and Aims
The presence of the hepatitis B virus (HBV)‐eAg in patients with hepatitis B is associated with higher HBV replication and with an increased risk to develop liver‐related clinical ...endpoints defined as liver related death, liver transplantation, development of hepatocellular carcinoma and hepatic decompensation. The aim of this study was to investigate the role of HBeAg in patients co‐infected with the hepatitis D virus (HDV).
Methods
We studied virological markers of HBV and HDV infection and as well as biochemical and clinical features of liver disease in a cohort of 534 anti‐HDV‐positive patients. In addition, we compared the clinical long‐term outcome of HBeAg‐positive HDV‐infected patients with HBeAg‐negative control patients matched for age, gender and baseline‐MELD score.
Results
HBeAg‐positive hepatitis delta was detected in 71 of 534 patients (13.3%). HBeAg positivity was associated with a higher biochemical disease activity and higher HBsAg levels in HDV co‐infected patients. Sixty one per cent of the HBeAg‐positive HDV‐infected patients presented with HBV DNA levels below 2000 IU/ml, at least once during follow‐up. Both HBeAg‐positive and ‐negative patients showed a similar severe clinical long‐term course with about half of the patients developing a liver‐related clinical complication after a median follow‐up period of 51 months (range: 9–193 months).
Conclusions
HBV DNA levels are low in both HBeAg‐negative and HBeAg‐positive patients suggesting suppressive effects of HDV on HBV irrespective of the phase of HBV infection. The clinical long‐term outcome of HBeAg‐positive patients is not different to HBeAg‐negative patients infected with the HDV.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
AIM: To present the characteristics and the course of a series of anti- hepatitis B virus core antibody (HBc) antibody positive patients, who experienced hepatitis B virus (HBV) reactivation after ...immunosuppression. METHODS: We retrospectively evaluated in our tertiary centers the medical records of hepatitis B virus surface antigen (HBsAg) negative patients who suffered from HBV reactivation after chemotherapy or immunosuppression during a 3-year period (2009-2011). Accordingly, the clinical, laboratory and virological characteristics of 10 anti-HBc (+) anti-HBs (-)/HBsAg (-) and 4 anti-HBc (+)/antiHBs (+)/HBsAg (-) patients, who developed HBV reactivation after the initiation of chemotherapy or immunosuppressive treatment were analyzed. Quantitative determination of HBV DNA during reactivation was performed in all cases by a quantitative real time polymerase chain reaction kit (COBAS Taqman HBV Test; cut-off of detection: 6 IU/mL). RESULTS: Twelve out of 14 patients were males; median age 74.5 years. In 71.4% of them the primary diagnosis was hematologic malignancy; 78.6% had received rituximab (R) as part of the immunosuppressive regimen. The median time from last chemotherapy schedule till HBV reactivation for 10 out of 11 patients who received R was 3 (range 2-17) mo. Three patients (21.4%) deteriorated, manifesting ascites and hepatic encephalopathy and 2 (14.3%) of them died due to liver failure. CONCLUSION: HBsAg-negative anti-HBc antibody positive patients can develop HBV reactivation even 2 years after stopping immunosuppression, whereas prompt antiviral treatment on diagnosis of reactivation can be lifesaving.
Hepatitis C virus(HCV)infection is a global health problem that affects more than 170 million people worldwide.It is a major cause of cirrhosis and hepatocellular carcinoma,making the virus the most ...common cause of liver failure and transplantation.The standardof-care treatment for chronic hepatitis C(CHC)has been changed during the last decade and direct acting antiviral drugs have already been used.Besides,understanding of the pathogenesis of CHC has evolved rapidly during the last years and now several host factors are known to affect the natural history and response to treatment.Recent genome-wide association studies have shown the important role of interleukin-28B and inosine triphosphatase in HCV infection.The present review article attempts to summarize the current knowledge on the role of host factors towards individualization of HCV treatment.
Carbapenem-resistant Gram-negative bacteria are a public health threat that requires urgent action. The fact that these pathogens commonly also harbor resistance mechanisms for several other ...antimicrobial classes further reduces patient treatment options. The present study aimed to provide information regarding the multidrug resistance genetic background of carbapenem-resistant Gram-negative bacteria in Central Greece. Strains from a tertiary care hospital, collected during routine practice, were characterized using a DNA microarray-based assay. Various different resistance determinants for carbapenems, other beta-lactams, aminoglycosides, quinolones, trimethoprim, sulfonamides and macrolides were detected among isolates of the same sequence type. Eighteen different multidrug resistance genomic profiles were identified among the twenty-four
ST258, seven different profiles among the eight
ST11, four profiles among the six
ST409 and two among the three
. This report describes the multidrug resistance genomic background of carbapenem-resistant Gram-negative bacteria from a tertiary care hospital in Central Greece, providing evidence of their continuous genetic evolution.
AbstractWe retrospectively investigated the characteristics, patterns of disease progression, outcome and difficulties in the management in 11 patients with concurrent autoimmune hepatitis (AIH) and ...HBV or HCV infections (5 HCV and 6 HBV including 2 with HDV co-infection) since there are scarce data on this issue. HCV or HBV diagnosis preceded that of AIH in all patients by many years. At initial clinical and histological assessment almost half of patients had cirrhosis (45.5%) with the group of AIH and HCV carrying the highest frequency (4/5; 80%). In two thirds of patients, mostly with HCV and HBV/HDV, AIH was assumed to be IFNalpha-induced and experienced difficulties in achieving sustained virological response. On the contrary, the outcome of patients with HBV and AIH was better compared to those with AIH and HCV or HDV. In conclusion, chronic viral hepatitis infections concomitant with AIH are often very difficult to recognize and therefore, a significant delay in AIH diagnosis in this specific group of patients is usual. HBV patients with concomitant AIH seem to carry the most favorable outcome compared to those with HCV probably because of the use of nucleos(t)ide analogues which contrary to IFN-alpha can control HBV replication with no adjacent effect, related to exacerbation of autoimmune phenomena.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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 ± 11.2vs 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% vs33.3% 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.
Sjögren's syndrome (SjS) and primary biliary cholangitis (PBC) can be classified as a model of generalized autoimmune epithelitis based on their frequent coexistence in clinical practice and the ...highly specific immune mediated injury of target epithelial cells. Both of these autoimmune diseases are characterized by female predominance, highly specific circulating autoantibodies, and immune-mediated destruction of the salivary and lachrymal glands and the biliary epithelial cells, respectively. Although the genetic predisposition has been well described for both diseases, genetic studies have failed to completely elucidate their pathogenesis. The recent integration of epigenetic data, analyzing the different cellular partners, opens new perspectives and allows for better understanding of these complex and still incurable diseases. Epigenetic studies on SjS have elucidated the role of DNA methylation alterations in disease pathogenesis, while epigenetic changes that influence expression of genes on the X chromosome have been implicated in the geo-variability and occurrence of PBC. The aim of this review is to describe the advances in epigenetics in the field of autoimmune epithelitis as well as to highlight how epigenetic changes could contribute to better understanding of disease pathogenesis and progression. These advances could yield insights on novel therapeutic interventions.
AIM：To determine the prevalence and significance of primary biliary cirrhosis （PBC）-specific autoantibodies in firstdegree relatives （FDRs） of Greek PBC patients. METHODS：The presence of ...antimitochondrial antibodies （AMA） and PBCspecific antinuclear antibodies （ANA） were determined using indirect immunofluores-cence assays, dot-blot assays, and molecularly based enzyme-linked immunosorbent assays in 101 asymp-tomatic for liver-related symptoms FDRs of 44 PBCpatients. In order to specify our results, the same investigation was performed in 40 healthy controls and in a disease control group consisting of 40 asymptomatic for liver-related symptoms FDRs of patients with other autoimmune liver diseases namely, autoimmune hepati-tis-1 or primary sclerosing cholangitis （AIH-1/PSC）. RESULTS： AMA positivity was observed in 19 （only 4 with abnormal liver function tests） FDRs of PBC patients and none of the healthy controls. The preva-lence of AMA was significantly higher in FDRs of PBC patients than in AIH-1/PSC FDRs and healthy controls 18.8%, 95% confidence interval （CI）：12%-28.1% vs 2.5%, 95% CI：0.1%-14.7%, P = 0.01; 18.8%, 95% CI：12%-28.1% vs 0%, 95% CI： 0%-10.9%, P = 0.003, respectively. PBC-specific ANA positivity was observed in only one FDR from a PSC patient. Multivariate analysis showed that having a proband with PBC independently associated with AMA positivity （odds ratio： 11.24, 95% CI：1.27-25.34, P = 0.03） whereas among the investigated comorbidities and risk factors, a positive past history for urinary tract infections （UTI） was also independently associated with AMA detection in FDRs of PBC patients （odds ratio：3.92, 95% CI：1.25-12.35,P = 0.02）. CONCLUSION：In FDRs of Greek PBC patients, AMA prevalence is significantly increased and independently associated with past UTI. PBC-specific ANA were not detected in anyone of PBC FDRs.
Giant cell hepatitis (GCH) is commonly reported in neonatal and infantile liver diseases but rarely in adults where the term postinfantile GCH (PIGCH) is used. PIGCH is associated with many diseases, ...including drugs toxicity, viruses, and autoimmune liver diseases, with autoimmune hepatitis (AIH) being the most prevalent. We present a case of PIGCH in a 76-year-old female without known history of liver disease who suffered from an acute severe episode of hepatitis. After careful exclusion of other hepatitis causes by imaging, virological, immunological, and microbiological investigations, a diagnosis of acute severe AIH (AS-AIH) was established. The patient was started on corticosteroids but she did not respond and died 3 days later because of advanced acute liver failure. Postmortem liver biopsy showed typical PIGCH lesions. Physicians must keep this catastrophic entity in mind in cases of unexplained acute liver injury as, contrary to our case, prompt rescue therapy with corticosteroids may be life-saving.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Background & objectives: In the past, patients with haemoglobinopathies were at high risk for acquiring hepatitis C virus (HCV) due to multiple transfusions before HCV screening. In these patients ...the coexistence of haemochromatosis and chronic hepatitis C (CHC) often leads to more severe liver disease. We assessed the HCV prevalence, clinical characteristics and outcome in this setting with particular attention to the response to treatment including therapies with the new direct acting antivirals (DAAs).Methods: The medical records of 81 consecutive patients followed the last 15 years were reviewed retrospectively.Results: 43/81 (53%) patients were anti-HCV positive including 31/43 (72.1%) with CHC (HCV-RNA positive; age 25±7 years; 45.2% with genotype 1b; 19.4% cirrhotics; baseline ferritin 887 ng/ml; range: 81-10.820). Thirty patients received IFN-based therapy with or without ribavirin with sustained virological response (SVR) in 14/30 (46.7%). Eleven patients (9 non-responders to IFN-based therapies, 1 relapser and 1 naïve) received treatment with DAAs (SVR: 100%). 3/11 patients increased their transfusion needs while 1/11 reported mild arthralgias. No drug-drug interactions between DAAs and chelation agents were observed as attested by the stability of ferritin levels during treatment. Conclusions: More than 1/3 of patients with haemoglobinopathies suffered from CHC. Response rates to antiviral treatment seem to be similar to other patients with CHC, while treatment with DAAs was very effective and safe even in difficult to treat patients (most null responders with severe fibrosis) suggesting that this group of HCV patients should no longer be regarded as a difficult to treat.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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