Bone mineral density measurements, bone markers and serum vitamin D concentrations in men with chronic non-cirrhotic untreated hepatitis C.

INTRODUCTION: The high prevalence of chronic hepatitis C (CHC) and its consequent cirrhosis has been associated with bone fragility. Whether CHC may cause bone and mineral abnormalities in the absence of hepatocellular dysfunction is still unknown. In this study we aimed to determine the prevalence of osteoporotic vertebral fractures and low BMD measurements in men with non-cirrhotic CHC. Risk factors for low BMD and fractures were also investigated. METHODS: Morphometric vertebral fractures and BMD measurements were performed in 60 non-cirrhotic untreated men with CHC and 59 healthy controls, matched for age and gender, weight and current smoking. Serum CTx, calcium, phosphate, intact PTH, alkaline phosphatase and vitamin D (25OHD) concentrations were measured in all participants. Clinical risk factors for low BMD and fractures were evaluated by a structured questionnaire as well as details regarding HCV infection. RESULTS: Trochanter and total femur BMD were significantly lower in CHC patients as compared to healthy men (p = 0.04). In men 50 years and older, the prevalence of osteoporosis was significantly higher among CHC patients (p = 0.01). Lower levels of physical activities and more often report of prolonged immobilization were observed among CHC patients (p<0.05). Liver inflammation and fibrosis, viral load and genotype did not correlate with BMD measurements. Bone markers and 25OHD concentrations were similar in both groups. Only a few vertebral fractures were observed. CONCLUSIONS: Our results demonstrate that non-cirrhotic untreated CHC patients have lower BMD at the femur as compared to healthy men in spite of the absence of significant bone and mineral abnormalities.

Unexpected distribution of hepatitis B genotypes in patients with kidney disease: comparison with immunocompetent subjects.

Hepatitis B virus (HBV) infection has a high prevalence among hemodialysis and renal transplant patients. Data regarding genotype distribution in these populations are scarce and are still under investigation. The aim of this study was to evaluate the distribution of HBV genotypes in end-stage renal disease (ESRD)-patients and renal transplant patients and to compare with the distribution observed in immunocompetent patients from the same geographic region. From a population of 213 patients evaluated initially, 120 patients with detectable HBV-DNA were included in the study and submitted to genotype determination by amplification of S gene by nested PCR followed by sequencing method. Among 41 hemodialysis patients the most frequent genotype was D (83%), followed by genotype A (10%), C (5%), and F (2%). Genotype D was also the most prevalent (73%) among 33 renal transplant patients, followed by genotype A (18%), F (6%), and B (3%). This distribution was similar in these two groups of patients and for the comparative analysis they were considered in the kidney disease group. Compared to immunocompetents, patients with kidney disease (ESRD and renal transplant patients) showed a distinct distribution, with a higher prevalence of genotype D (78% vs. 17%, P < 0.001) whereas genotype A was the most prevalent among immunocompetent patients (70% vs. 14%, P < 0.001). In conclusion, the higher frequency of genotype A in immunocompetent patients and of genotype D in patients with renal disease suggest a higher capacity of environmental transmission or a better adaptability of this genotype in patients with a different pattern of immunologic response.

Steatosis in chronic hepatitis C: relationship to the virus and host risk factors.

BACKGROUND: Steatosis occurs frequently in hepatitis C. However, the mechanisms leading to this lesion are still unknown, and the role of steatosis in the progression of the disease remains controversial. The aim of the present paper was to determine the prevalence of steatosis in hepatitis C and its association with hepatitis C virus (HCV) genotype, viral load and the presence of risk factors for steatosis, and to analyze the association between steatosis and the intensity of liver disease. METHODS: Patients infected with HCV who underwent liver biopsy were included. Patients coinfected with hepatitis B virus and/or human immunodeficiency virus and those previously treated for hepatitis C were excluded. The following risk factors for steatosis were investigated: obesity (body mass index [BMI] > 25 kg/m(2)), diabetes mellitus, hyperlipidemia, alcoholism, and use of potential steatosis-inducing drugs. Histological analysis evaluated the presence of steatosis, the degree of periportal activity and staging. Patients with and without steatosis were compared regarding demographic, epidemiological, laboratory and histological characteristics. Logistic regression analysis was applied to identify variables that were independently associated with the presence of steatosis. RESULTS: Ninety patients (55 men, 35 women) with a mean age of 45 +/- 13 years were included. The prevalence of steatosis was 67%. Variables that remained independently associated with steatosis were age, female gender, obesity and genotype 3. CONCLUSIONS: The prevalence of steatosis in hepatitis C was high. Risk factors usually related to steatosis such as age, female gender and obesity, as well as genotype 3, were independently associated with the presence of steatosis. Steatosis was not independently associated with the intensity of histological liver disease.

Iron overload in patients with chronic hepatitis C virus infection: clinical and histological study.

BACKGROUND: Recently it has been found that iron is an important element in the natural history of hepatitis C. Serum markers of iron stores are frequently increased in chronic hepatitis C virus (HCV)-infected carriers but the real impact of the hepatic iron overload is poorly understood. The purpose of the present paper was to determine the prevalence of iron overload and to study the relationship between hepatic iron concentration (HIC) and clinical, biochemical and histological characteristics in chronic HCV-infected carriers. METHODS: Patients presenting with anti-HCV and HCV-RNA were included. Hepatic iron concentration was determined in liver tissue by atomic absorption spectrophotometry. The association between HIC and age, gender, risk factor of transmission, duration of infection, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, iron and serum ferritin, transferrin saturation, HCV-RNA level, grading of inflammatory activity, staging of fibrosis, hepatic steatosis, and stainable iron was analyzed. Statistical analysis included the Mann-Whitney test and a multiple linear regression model. RESULTS: Ninety-six patients (58% male) with a mean age of 44 +/- 10 years were studied. Serum iron, ferritin and transferrin saturation were elevated in 28%, 27% and 12.5% of patients, respectively. Stainable iron was detected in few patients (15.6%). Higher grades of stainable iron (2 and 3) were observed in only 7%. The HIC (>30 mmol/g dry weight) was elevated in five patients (5%). Neither grading nor staging were related to HIC. Higher HIC were observed in male patients (P < 0.001), in patients with elevated serum ferritin (P = 0.001) and in patients with stainable iron (grades 2 and 3; P = 0.001). Multiple linear regression analysis showed that only stainable iron was independently correlated with HIC (P = 0.003). CONCLUSIONS: Iron overload in chronically HCV-infected patients was uncommon and hepatic iron content seemed not to be related to the liver damage process. In the eventuality of iron overload, histochemical liver iron is a useful marker to estimate HIC.

Role of gamma-glutamyl transferase activity in patients with chronic hepatitis C virus infection.

BACKGROUND: Increased serum gamma-glutamyl transferase (GGT) levels are frequently observed in chronic hepatitis C virus (HCV) infection. However, the significance of this finding remains unclear. The purpose of the present paper was to assess the relationship between GGT levels and clinical, biochemical and histological features in chronic HCV-infected carriers. METHODS: Patients with a liver biopsy presenting anti-HCV and HCV-RNA were evaluated. Age, gender, risk factors of transmission, serum alanine aminotransferase (ALT), GGT and alkaline phosphatase (ALP) levels and histological features were assessed in all. Data were analyzed statistically by the chi2 test and multivariate logistic regression analysis. RESULTS: Among 201 patients studied, elevated GGT levels and bile duct damage were observed in 48% and 35% of them, respectively. No association was seen between GGT level and bile duct damage or between GGT level and hepatic steatosis. Initially, age >40 years (P=0.007), elevated ALT (P=0.01), grading of inflammatory activity (P=0.004) and staging of fibrosis (P<0.001) were found to be associated with elevated GGT levels. After multivariate regression analysis, histology grading 3 and 4 inflammation activity (P=0.01) and staging 3 and 4 fibrosis (P=0.01) remained independently associated with elevated GGT level. CONCLUSIONS: A significant number of patients with chronic HCV infection had elevated serum GGT levels. Furthermore, this enzyme seemed to be useful as an indirect marker of more advanced liver disease in chronic hepatitis C.