Hepatitis C in patients with ß-thalassemia major. A single-centre experience.

Chronic hepatitis C (CHC) and iron overload are the main causes of liver disease in ß-thalassemia major (ßTM). There is limited data regarding the course of CHC in this population. All patients (n=144) from the thalassemia centre of the University Hospital of Patras were evaluated (January 1981 to June 2012). Patients were classified into group A (n=57), which consisted of patients with CHC, who either had received antiviral treatment (n=49) or not (n=8), and group B which included 87 patients without CHC. Nineteen patients died during follow-up (median: 257.5 months (1-355)). Survival rates were 84.2 % and 88.5 % for group A and B, respectively. The causes of death were heart failure (63.2 %), accident (10.5 %), sepsis (5.3 %), liver failure (5.3 %), hepatocellular carcinoma (HCC) (5.3 %), non-Hodgkin lymphoma (5.3 %) and multiorgan failure (5.3 %). There were no differences in total survival between the two groups (p=0.524). In the multivariate analysis, survival was neither correlated with CHC (p=ns), nor with anti-HCV treatment (p=ns), whereas independent negative predictors were presence of heart failure (p<0.001), presence of malignancy other than HCC (p=0.001) and non-adherence to chelation treatment (p=0.013). Predictive factors for the development of cirrhosis were: CHC (p<0.001), age>35 years (p=0.007), siderosis grade 3/4 (p=0.029) and splenectomy (p=0.001); however, multivariately, only siderosis grade 3/4 was found to be significant (p=0.049). In this study, survival of patients with ßTM was mainly associated with heart failure, presence of malignancy other than HCC and non-adherence to chelation treatment, rather than with liver disease. Multicentre studies need to be designed to define more accurately the indications of antiviral treatment in this population.

Abnormal liver function tests in a patient with myotonic dystrophy type 1.

Myotonic dystrophy type 1, also known as Steinert's disease, is a multisystemic disorder with significant genetic and clinical heterogeneity. Apart from skeletal muscles' myotonia and wasting, a variety of system organs can be affected. We report on a 49 years old female patient with unremarkable medical and family history, who presented with elevated liver enzymes without signs or symptoms of chronic liver disease neither neurological features. Initial assessment, including liver biopsy, did not reveal the cause of these abnormalities. Eight months later, she complained for disequilibrium and eventually electromyography confirmed the diagnosis of Steinert's disease. Steinert's disease should be considered in the differential diagnosis of patients with elevated liver enzymes, as long as abnormal liver tests may be the initial presentation. The pathophysiological mechanism of this abnormality remains unclear.

Fatigue and depressive symptoms associated with chronic viral hepatitis patients. health-related quality of life (HRQOL).

BACKGROUND AND RATIONALE: It is well established that chronic viral hepatitis (CVH) negatively affects patients . health-related quality of life (HRQOL). The aim of the present study was to assess the extent to which fatigue and depressive symptoms are associated with CVH patients. HRQOL. METHODS: Eighty-four adult CVH outpatients [45 with hepatitis B virus (HBV) and 39 with hepatitis C virus (HCV) infection] participated in the study. The Short Form-36 Health Survey (SF-36), the Beck Depression Inventory-II (BDI-II) and the Fatigue subscale of the Functional Assessment of Cancer Therapy-Anemia Scale (FACT-F) were used to assess HRQOL, depression and fatigue, respectively. RESULTS: All aspects of HRQOL perceived by CVH patients were significantly impaired compared to the general population, as a comparison with Greek population-based normative data revealed. HBV patients presented similar HRQOL with HCV patients. Clinical parameters including infection activity, fibrosis stage or inflammation grade, as well as depressive symptoms and fatigue were found to be significantly associated with HRQOL. Multivariate analyses showed that older age (p <0.001) and higher fatigue scores (p <0.001) were the variables most closely associated with the physical HRQOL, whereas higher rates on depressive symptoms (p <0.0005) and fatigue (p <0.020) scales were the variables most closely associated with the mental HRQOL. CONCLUSIONS: In conclusion, CVH is associated with impaired HRQOL. Fatigue and impaired psychological functioning is associated with diminished HRQOL in CHV, independent of the disease etiology. Consequently, management of fatigue and depressive symptoms should be considered a priority, in order to improve HRQOL in CVH patients.

Prevalence of anti-HAV antibodies in multitransfused patients with beta-thalassemia.

AIM: To detect the prevalence of anti-HAV IgG antibodies in adult multitransfused beta-thalassemic patients. METHODS: We studied 182 adult beta-thalassemic patients and 209 controls matched for age and sex from the same geographic area, at the same time. Anti-HAV IgG antibodies, viral markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were evaluated. RESULTS: Anti-HAV IgG antibodies were detected more frequently in thalassemic patients (133/182; 73.1%) than in healthy controls (38/209; 18.2%, P < 0.0005). When we retrospectively evaluated the prevalence of anti-HAV IgG antibodies in 176/182 (96.7%) thalassemic patients, whose medical history was available for the previous ten years, it was found that 83 (47.2%) of them were continuously anti-HAV IgG positive, 16 (9.1%) acquired anti-HAV IgG antibody during the previous ten years, 49 (27.8%) presented anti-HAV positivity intermittently and 28 (15.9%) were anti-HAV negative continuously. CONCLUSION: Multitransfused adult beta-thalassemic patients present higher frequency of anti-HAV IgG antibodies than normal population of the same geographic area. This difference is difficult to explain, but it can be attributed to the higher vulnerability of thalassemics to HAV infection and to passive transfer of anti-HAV antibodies by blood transfusions.

Prevalence of liver steatosis in patients with chronic hepatitis B: a study of associated factors and of relationship with fibrosis.

OBJECTIVES: The clinical significance of hepatic steatosis in chronic hepatitis B virus patients is poorly understood. The purpose of this study was to determine risk factors for liver steatosis in chronic hepatitis B patients and its relationship with fibrosis. METHODS: We retrospectively evaluated liver biopsies from patients with chronic hepatitis B treated in our department. Patients co-infected with other viruses (hepatitis C virus, HIV) or suffering from liver disease of any other cause were excluded from the study, as well as patients consuming alcohol above 30 g/day for males or 20 g/day for females. Liver steatosis, necroinflammation and fibrosis were assessed. RESULTS: A total of 233 patients with chronic hepatitis B were included in the study. The mean age was 44.7+/-16.2 years. There were 164 men (70.4%) and 69 women (29.6%). The majority of patients were HbeAg-negative, 196/233 (84.1%). Thirty-seven patients had cirrhosis (15.9%). Steatosis was present in 42 patients (18%). Steatosis was independently associated with fasting glucose level (P=0.019) and being overweight (body mass index >or=25; P=0.021). No correlation was found with stage of fibrosis, grade of inflammation, alcohol use or other parameters. Ninety-four out of 233 patients (40.3%) had advanced fibrosis. Patients with advanced fibrosis were older than those with minimal or no fibrosis (47.6+/-17 versus 42.3+/-15.2 years, P=0.024) and more frequently had a higher grade of necroinflammation activity (57/94 (60.6%) versus 26/139 (18.7%), P<0.0001). There was no significant association between advanced fibrosis and the presence of steatosis or mild alcohol consumption. CONCLUSION: Hepatic steatosis is present in 18% of our patients with biopsy-proven chronic hepatitis B. Steatosis is independently associated only with body mass index and fasting glucose level, risk factors for metabolic steatohepatitis, and was not correlated with the degree of fibrosis.

Occult hepatitis B virus infection in hemodialysis patients with chronic HCV infection.

BACKGROUND: The aim of this study was to determine the prevalence of occult hepatitis B infection in hemodialysis patients with chronic HCV infection and to compare it with that of HCV-infected patients with normal renal function. METHODS: Forty-nine patients on maintenance hemodialysis and 48 HCV-infected but otherwise normal patients, both groups HCV RNA-positive and HBsAg-negative and matched for age and sex, were evaluated for the presence of HBV DNA in serum by polymerase chain reaction (PCR). A proportion of patients (11/49 and 39/48, respectively) were also examined for HBV antigens in hepatocytes by immunohistochemistry. RESULTS: HBV DNA was detected by PCR in 10/49 (20.4%) hemodialysis patients and in 3/48 (6.3%) patients with normal renal function (p=0.041). HBV DNA concentrations were low (<10 3 copies/mL) in both groups. HBV DNA-positive hemodialysis patients had a significantly lower prevalence of past HBV vaccination and lower anti-HBs titers in serum than HBV DNA-negative patients of the same group. No positive staining for HBsAg or HbcAg was observed in the liver biopsies of either group. CONCLUSIONS: Occult HBV infection is more frequent in HCV-infected hemodialysis patients than otherwise normal patients with chronic HCV infection, probably because of impaired immune function in uremic patients and high risk of parenteral exposure to HBV. The clinical significance of this finding is unknown, but HBV vaccination of hemodialysis patients and staff could be an effective way of limiting the risk of transmission of HBV infection within dialysis units.

Multidetector computed tomography versus platelet/spleen diameter ratio as methods for the detection of gastroesophageal varices.

BACKGROUND: All patients with liver cirrhosis should undergo screening endoscopy, but there are limitations and this approach places a heavy burden upon endoscopy units. The aim of this study was to compare multidetector computed tomography (MDCT) and the platelet/spleen diameter ratio as non-invasive methods for the detection of gastroesophageal varices. METHODS: The study included 38 cirrhotics who underwent upper gastrointestinal (GI) endoscopy and MDCT within one month. Two radiologists reviewed the scans, in order to determine the presence and the size of varices. Blood tests and measurement of the spleen maximum diameter were also carried out and the platelet/spleen diameter ratio was calculated. Endoscopy was considered the gold standard and the results of the two methods were compared to it. RESULTS: Varices were detected by upper GI endoscopy in 24 of 38 patients. The mean sensitivity and specificity of MDCT for the two observers was 86.1% and 57.1% respectively. In patients with large varices (>5 mm), the sensitivity was 100% (4/4). Using 909 as a cut-off value of the platelet/spleen diameter ratio this method yielded a sensitivity of 56.5% and a specificity of 35.7%. The difference in sensitivity and specificity between the two methods was statistically significant P<0.05. CONCLUSION: MDCT was accurate for the detection of gastroesophageal varices, especially those with clinically significant size (>5 mm), and superior to platelet/spleen diameter ratio. MDCT could replace, in selected patients, upper GI endoscopy as a method for detecting gastroesophageal varices in cirrhotic patients.

Viraemia, cryoglobulins and autoantibodies in haemodialysis patients infected with hepatitis C virus.

OBJECTIVES: The clinical features of hepatitis C virus (HCV) infection depend on the immune and autoimmune reactions induced by the virus. Chronic renal failure might alter the pattern of these reactions. The aim of this study was to determine the prevalence of cryoglobulinaemia, the frequency of autoantibodies and HCV viral load in HCV infected Greek patients on chronic haemodialysis. METHODS: Seventy-three HCV Ab(+) patients on maintenance haemodialysis and 87 otherwise normal patients with chronic HCV infection were evaluated for the presence of cryoglobulins, autoantibodies and viral markers. RESULTS: Cryoglobulins were detected in 22/73 (30.1%) haemodialysis patients and in 23/87 (26.4%) patients with normal renal function (NS). The mean cryocrit value was significantly lower in the haemodialysis group ( = 0.002). Haemodialysis patients had significantly higher levels of C4 component of complement and lower incidence of rheumatoid factor than those of patients with normal renal function. Serum HCV RNA levels were found significantly lower in the haemodialysis group (median, 2.20 Meq/ml; range, 119.9 Meq/ml) than in the group with normal renal function (median, 4.50 Meq/ml; range, 114.9 Meq/ml; = 0.046). The distribution of genotypes was not different between the two groups. CONCLUSIONS: There are subtle differences in autoimmune features of HCV infection if the patients are also haemodialysed for renal failure. HCV viral load is lower in haemodialysis patients, with no difference in the HCV genotype prevalence. The clinical significance of these findings is unknown.

Cryoglobulinemia and progression of fibrosis in chronic HCV infection: cause or effect?

OBJECTIVES: Mixed cryoglobulinemia (MC) is the most common extrahepatic manifestation of HCV infection. The aim of this study is to determine the prevalence of MC in HCV infected Greek patients and to identify if it is associated with liver histology or the mode of HCV transmission. METHODS: One hundred and twenty-six patients with chronic HCV infection were evaluated for the presence of serum cryoglobulins, autoantibodies and viral markers. One hundred and eighteen of them underwent liver biopsy and each specimen was evaluated according to the grading and staging system described by Ishak et al. RESULTS: Cryoglobulins were detected in 37/126 (29.4%) HCV patients and cryocrit values ranged between 0.5 and 6.5%. Only two patients presented clear clinical manifestations of MC. In patients with MC, a higher grading (6.40+/-2.06 vs. 5.27+/-2.55, p=0.013) and staging score (3.71+/-1.45 vs. 2.83+/-1.84, p=0.007) was noted in liver biopsy compared to those without MC. Logistic regression analysis identified staging score (OR, 1.33; CI, 1.06-1.66, p=0.015) as the only independent variable associated with cryoglobulinemia. Correlation between the presence of cryoglobulins and the mode of HCV transmission was not found. CONCLUSIONS: Greek patients with chronic HCV infection have high prevalence of cryoglobulinemia. A clear association between the presence of serum cryoglobulins and staging score of chronic hepatitis was found, with no difference in patients' age or the duration of infection. It is possible that cryoglobulinemia results in more rapid hepatic fibrosis in HCV infected patients.

Acceptance of hepatitis B vaccination among health care workers in Western Greece.

Health care personnel are at high risk for hepatitis B virus (HBV) transmission. The aim of the present study was to investigate hepatitis B (HB) knowledge and vaccination acceptance among health care personnel in southwestern Greece, using the Hepatitis B Vaccine Knowledge and Acceptance Questionnaire. One hundred eighty-three employees participated (71 males). Occupation (p < .001), higher education (p < .001), and vaccination (p = .007) were significantly related to HB knowledge. The rate of HBV vaccination coverage was 70.9%. Participants considering themselves at high risk for HBV infection did not report significantly increased vaccination rates. In the multivariate analysis, university personnel (p = .002), occupational category (p < .001), and HB knowledge (p = .049) were significantly associated with vaccination. In conclusion, 29% of hospital personnel were not vaccinated mainly due to negligence. Occupation, education, and knowledge about HB seem to be associated with HBV vaccination.

Higher free serum cortisol is associated with worse survival in acute variceal bleeding because of cirrhosis: a prospective study.

BACKGROUND AND AIMS: Critical illness-related corticosteroid insufficiency has been reported in acute variceal bleeding (AVB). In cirrhosis, free serum cortisol (FC) is considered optimal to assess adrenal function. Salivary cortisol (SC) is considered a surrogate for FC. We evaluated FC and its prognostic role in AVB. METHODS: Total serum cortisol, SC, cortisol-binding globulin, and FC (Coolens' formula) were evaluated in AVB (n=38) and in stable cirrhosis (CC) (n=31). A Cox proportional hazards model was evaluated for 6-week survival. RESULTS: In AVB, the median FC and SC levels were higher with worse liver dysfunction [Child-Pugh (CP) A/B/C: 1.59/2.62/3.26 µg/dl, P=0.019; CPA/B/C: 0.48/0.897/1.81 µg/ml, P<0.001, respectively]. In AVB compared with CC, median total serum cortisol: 24.3 versus 11.6 µg/dl (P<0.001), SC: 0.86 versus 0.407 µg/ml (P<0.001); FC 2.4 versus 0.57 µg/dl (P<0.001). In AVB, 5-day rebleeding was 10.5%, and 6-week and total mortality were 21.1 and 23.7%, respectively. Independent associations with 6-week mortality in AVB were FC at least 3.2 µg/dl (P<0.001), hepatocellular carcinoma (P<0.001), CPC (P<0.001), and early rebleeding (P<0.001). Among patients with normal cortisol-binding globulin (n=14) and albumin (n=31), the factors were hepatocellular carcinoma (P=0.003), CP (P=0.003), and FC (P=0.036). SC was also found to be an independent predictor of 6-week mortality (P<0.001). Area under the curve of FC for predicting 6-week mortality was 0.79. CONCLUSION: Higher FC is present in cirrhosis with AVB compared with CC and is associated independently with bleeding-related mortality. However, whether high FC solely indicates the severity of illness or whether there is significant adrenal insufficiency cannot be discerned.

Granulomas Formation in Lymph Nodes, Liver and Spleen in Adult-Onset Still's Disease: A Case Report.

Tissue granulomas formation in adult-onset Still's disease (AOSD) is extremely rare. We describe a case of AOSD associated with formation of granulomatous lesions in lymph nodes, liver and presumably spleen. The high dose steroid-dependent nature of our patient's illness, characterized by disease relapses when methylprednisolone dose was reduced below 10 mg/d, was overwhelmed with institution of anakinra (100 mg/d). The histologic finding of granulomas formation in lymph nodes, liver or spleen should not deter the consideration of AOSD as a potential diagnosis in a compatible clinical context; however, other more common etiologies of tissue granulomas formation should be first excluded.

Suppurative necrotizing granulomatous lymphadenitis in adult-onset Still's disease: a case report.

INTRODUCTION: Lymphadenopathy is found in about 65% of patients with adult-onset Still's disease and is histologically characterized by an intense, paracortical immunoblastic hyperplasia. Adult-onset Still's disease has not been previously described as an etiology of suppurative necrotizing granulomatous lymphadenitis. CASE PRESENTATION: We describe a 27-year-old Greek man who manifested prolonged fever, abdominal pain, increased inflammatory markers, episodic skin rash and mesenteric lymphadenopathy histologically characterized by necrotizing granulomatous adenitis with central suppuration. Disease flares were characterized by systemic inflammatory response syndrome with immediate clinico-laboratory response to corticosteroids but the patient required prolonged administration of methylprednisolone at a dose of above 12mg/day for disease control. After an extensive diagnostic work-up, which ruled out any infectious, malignant, rheumatic or autoinflammatory disease the patient was diagnosed as having adult-onset Still's disease. The patient is currently treated with 4mg of methylprednisolone, 100mg of anakinra daily and methotrexate 7.5mg for two consecutive days per week and exerts full disease remission for six months. CONCLUSION: To the best of our knowledge this is the first report of suppurative necrotizing granulomatous lymphadenitis attributed to adult-onset Still's disease. This case indicates that the finding of a suppurative necrotizing granulomatous lymphadenitis should not deter the consideration of adult-onset Still's disease as a potential diagnosis in a compatible clinical context; however, the exclusion of other diagnoses is a prerequisite.

Lapatinib-induced hepatitis: a case report.

Lapatinib is an inhibitor of the tyrosine kinases of human epidermal growth factor receptor type 2 (HER2) and epidermal growth factor receptor type 1, with clinical activity in HER2-positive metastatic breast cancer. We present here a 60 year-old patient with metastatic breast cancer who presented with jaundice and increased serum aminotransferase levels and who had been treated with lapatinib for the previous 14 days. Laboratory tests excluded other causes of acute liver injury. Liver biopsy revealed lesions compatible with drug-induced hepatotoxicity. Bilirubin and liver enzymes returned to normal within three months of lapatinib discontinuation. Lapatinib should be included among the causes of drug-induced hepatitis.

Neuropsychological function in Greek patients with chronic hepatitis C.

BACKGROUND: Research has shown that hepatitis C virus (HCV) infection is associated with subclinical neuropsychological deficits in the absence of hepatic encephalopathy. METHODS: The current study assessed 32 Greek HCV patients without hepatic encephalopathy using standardized neuropsychological measures and compared them with 20 healthy controls and 29 hepatitis B virus (HBV)-infected patients. Patients and controls did not differ on age, educational level, depression or fatigue severity. Moreover, strict criteria were used to exclude any risk factor for cognitive impairment. RESULTS: Chronic HCV patients performed significantly worse than healthy controls on verbal learning and memory (P=0.029). However, hepatitis C and hepatitis B patients were similarly impaired in cognitive function, suggesting that the observed abnormalities are not HCV specific. HCV patients' cognitive capacity was further associated with liver disease severity as indicated by fibrosis stage (r=-0.602, P=0.011). In contrast, cognitive decline did not correlate with patients' psychological distress, indicating that biological mechanisms might be implicated in its pathogenesis. Finally, after controlling for age and educational level, cirrhotic and non-cirrhotic patients appeared to be equally impaired. CONCLUSIONS: In conclusion, this study confirmed previous findings and added further to the existing literature concerning the negative influence of HCV infection on cognition.