Hepatitis Monthly
Volume:11 Issue: 2, Feb 2011

Patients with chronic hepatitis B infection should be followed up to identify possible changes in disease status, such as HBsAg seronversion. There are little data on the outcome of such cases, and the response rate to HBV vaccine has not been discussed extensively.

Dental health care providers are at risk of infection with hepatitis B virus (HBV). Dentists can occupationally become infected with HBV through needle sticks or exposure to blood and other body fluids. To evaluate anti-HBs antibody titer in students, professors, clinical assistants and non-clinical staff of Faculty of Dentistry, Tehran University of Medical Sciences (TUMS), and to investigate the probable correlation between the level of immunity and a number of associated factors. Patients and 230 participants who had a history of previous HBV vaccination (receiving at least two doses of HBV vaccine) and a negative history of being infected with HBV were studied. Participants'' data were recorded using a checklist, and the level of antibody was measured by enzyme-linked immunosorbent assay (ELISA). While there existed statistically significant correlations between age, occupation, smoking, complete and scheduled vaccination and time of the last vaccination with the level of anti-HBs antibody, the correlation between gender and level of the antibody was not significant. Multiple regression analysis revealed significant association between immune response and age and time of the last vaccination. Due to the significant correlation between younger age and anti-HBs antibody titer in our study, it makes sense to establish a mandatory complete and scheduled vaccination program for all members of dental society younger than 40 years.

Hepatitis C virus (HCV) is a hepatotropic and lymphotropic virus that causes hepatic and extrahepatic disease. Emerging clinical data suggest that chronic HCV infection can lead to many direct and indirect effects on the lung. This article discusses evidence on the relationship between HCV infection and pulmonary fibrosis to increase knowledge on this topic among clinicians and scientists and highlights the need for further study. We searched the MEDLINE، ISI WEB OF KNOWLEDGE، OVID، ELSEVIER، and MDCONSULT databases and top respiratory journals، such as the American Journal of Respiratory and Critical Care، Chest، and Thorax for articles in English using the following keywords: hepatitis C، HCV infection، IPF، pulmonary fibrosis، and interstitial pneumonitis. We reviewed the reference lists of all identified studies. The evidence for a pathogenetic link between pulmonary fibrosis and HCV is: the higher frequency of HCV markers in IPF patients، an increase in lymphocyte and neutrophil numbers in bronchoalveolar lavage of chronic HCV infection patients، and the development of IPF in HCV-related chronic hepatitis that is treated with interferon. There is a discrepancy between studies on the frequency of HCV in IPF patients، which might be attributed to geographical differences of in the prevalence of HCV infection، selection bias in choosing the control group، and the HCV genome. BAL studies in HCV infection are associated with increased counts of lymphocytes and neutrophils in BAL fluid. These studies show that HCV infection is associated with nonspecific pulmonary inflammatory reactions that are not compatible with IPF but that it can lead to pulmonary fibrosis. The other factor is interferon therapy. Interstitial pneumonia and sarcoidosis are well-documented complications of IFN therapy. More extensive cohort studies should be conducted to confirm an actual causal relationship between HCV infection and pulmonary fibrosis.

Non-alcoholic steatohepatitis (NASH), first described by Ludwig et al, in 1980, is a stage in the wide spectrum of non-alcoholic fatty liver diseases (NAFLDs) and one of the leading causes of chronic liver disease. Several scientists have tried to more distinctly discover and describe different aspects of NASH. In contrast with its counterpart in the NAFLDs-the NAFL-NASH consists of inflammation as well as necrosis in the liver tissue resulting in a poor outcome. NASH is also a known etiology for cryptogenic liver cirrhosis. Evidence suggests that cirrhosis developing due to NASH have a relatively worse outcome compared to that of hepatitis C-related cirrhosis. In this review article, we try to review and present all relevant articles about NASH.

Chronic infection with hepatitis B virus (HBV) is the major risk factor for hepatocellular carcinoma (HCC) worldwide. Ten HBV genotypes (A-J) have been discovered so far. Genotypes B and C are endemic in East and Southeast Asia. Genotype C HBV is associated with increased risks of cirrhosis and HCC. Genotype B (B2) is associated with the development of HCC in non-cirrhotic patients younger than 50 years and with relapse of HCC after surgical treatment. It is also associated with earlier hepatitis B e antigen seroconversion than genotype C. High HBV load is independently associated with the occurrence and post-treatment recurrence of HCC. Different genotypes have distinct patterns of mutations. Viral mutations in the core promoter region and in the preS region are frequently found to be significantly associated with an increased risk of HCC. These mutations often occur before the onset of HCC and accumulate during the progression of chronic HBV infection. Multiple such mutations are more frequent in patients with HCC and are specific for HCC. HBV subgenotypes, viral mutations, and viral load can be used for the prediction of HCC. Early identification of HBV-infected individuals who will eventually develop HCC will help to develop active prophylactic protocols to reduce or delay the occurrence of HCC.

Nonalcoholic fatty liver disease develops in patients with chronic hepatitis C. Interferon and ribavirin combination therapy is the standard treatment for chronic hepatitis C، but if present، NAFLD can reduce the virological response to anti-HCV therapies. We determined whether the addition of rosuvastatin to interferon and ribavirin improves the sustained virological response (SVR) and reduces steatosis. Patients and This study was a prospective، randomized، open-label trial. Between January 2004 and December 2007، 65 patients with chronic hepatitis (27 women and 38 men، mean age 48 years) aged 32-63 years (median 46 years) were consecutively enrolled. Patients were randomly assigned to receive leukocyte interferon alpha (3 MIU 3 times per week) plus ribavirin (1200 mg per day) for 12 months or interferon alpha and ribavirin at the same dosages plus rosuvastatin (5 mg per day). The primary endpoints were measurements in SVR، liver enzyme، cholesterol، triglyceride، CRP، glucose، and insulin levels; and Homa-IR، fibrosis، and steatosis scores. After 12 months of treatment، we observed a significant improvement in SVR in 51% of patients who received interferon plus ribavirin plus rosuvastatin compared with 18% of relapsers (OR 1. 52; 95% CI= 0. 41-5. 64; RR 1. 13). There were 23 responders (69%) and 10 nonresponders (30%) (OR 1. 38; 95% CI= 0. 49-16. 5; RR 1. 11). When comparing interferon plus ribavirin group vs interferon plus ribavirin and rosuvastatin group after 12 months، we observed a significant difference in AST (85. 70 vs. 106. 5. 00 IU/ml) (OR 1. 2; 95% CI= 0. 29-4. 94; RR 1. 04; p<0. 001)، ALT (81. 80 vs. 126. 2 IU/ml) (OR 1. 2; 95% CI= 0. 29-4. 94; RR 1. 04; p<0. 001)، LDL-cholesterol (0. 01 vs. 0. 60 mmol/l) (OR 14; 95% CI= 3. 98-49. 16; p RR 2. 96; <0. 001)، triglycerides (0. 17 vs. 0. 2 mmol/l) (OR 20; 95% CI= 4. 94-80. 89; RR 5. 38; p<0. 05)، and Viremia (1. 8 vs. 2. 48 UI/ml، p<0. 05). Mean fibrosis score decreased 0. 10 vs. 0. 50 (OR 4. 5; 95% CI= 0. 89-22. 66; RR 1. 5; p<0. 05)، and mean steatosis score declined 0. 30 vs. 0. 50 (OR 11. 2; CI= 2. 88-43. 53; RR 2. 75; p<0. 001). In HCV patients with NAFLD، the addition of rosuvastatin to interferon and ribavirin significantly reduces viremia، steatosis، and fibrosis without causing side effects.

Dental health care providers are at risk of infection with hepatitis B virus (HBV). Dentists can occupationally become infected with HBV through needle sticks or exposure to blood and other body fluids. To evaluate anti-HBs antibody titer in students, professors, clinical assistants and non-clinical staff of Faculty of Dentistry, Tehran University of Medical Sciences (TUMS), and to investigate the probable correlation between the level of immunity and a number of associated factors. Patients and 230 participants who had a history of previous HBV vaccination (receiving at least two doses of HBV vaccine) and a negative history of being infected with HBV were studied. Participants'' data were recorded using a checklist, and the level of antibody was measured by enzyme-linked immunosorbent assay (ELISA). While there existed statistically significant correlations between age, occupation, smoking, complete and scheduled vaccination and time of the last vaccination with the level of anti-HBs antibody, the correlation between gender and level of the antibody was not significant. Multiple regression analysis revealed significant association between immune response and age and time of the last vaccination. Due to the significant correlation between younger age and anti-HBs antibody titer in our study, it makes sense to establish a mandatory complete and scheduled vaccination program for all members of dental society younger than 40 years.

The aspartate aminotransferases (AST) to platelet ratio index (APRI) may serve as a noninvasive marker to assess liver fibrosis. To assess the diagnostic ability of the APRI for prediction of fibrosis in patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC), and non-alcoholic fatty liver disease (NAFLD).Patients and This retrospective study included 207 patients with CHB, 108 with CHC, and 140 patients with NAFLD. The APRI was calculated as (AST level/upper normal limit for AST)/platelet counts (109/L) × 100. The stage of liver fibrosis in patients with chronic viral hepatitis was graded using the METAVIR scale. The Kleiner system for grading fibrosis was used in patients with NAFLD. Bivariate correlation analyses showed that the APRI was significantly associated with fibrosis scores in patients with CHC (p = 0.2634, p = 0.0059) and NAFLD (p = 0.2273, p = 0.0069), but not in those with CHB (p = 0.1005, p = 0.1495). Receiver operating characteristic (ROC) curves were used for assessing the ability of the APRI as a predictor of the absence or presence of liver fibrosis (fibrosis score of 0 vs fibrosis scores of 1-4). In patients with CHC, the APRI showed a sensitivity of 72.7% and a specificity of 62.4% for detection of fibrosis (p<0.01). In the NAFLD group, the APRI showed a sensitivity of 60.0% and specificity of 73.3% for detection of fibrosis (p<0.01). In patients with CHB, the APRI showed a sensitivity of 55.0% and a specificity of 75.4% for fibrosis (p=NS). The APRI shows an acceptable accuracy for the assessment of liver fibrosis in patients with CHC and NAFLD, but not in those with CHB.

Hepatitis B virus (HBV) infection is an important health problem worldwide with critical outcomes. The nucleoside analog lamivudine (LMV) is a potent inhibitor of HBV polymerase and impedes HBV replication in patients with chronic hepatitis B. Treatment with LMV for long periods causes the appearance and reproduction of drug-resistant strains, rising to more than 40% after 2 years and to over 50% and 70% after 3 and 4 years, respectively. Artificial neural networks (ANNs) were used to make predictions with regard to resistance phenotypes using biochemical and biophysical features of the YMDD sequence.Patients and The study population comprised patients who were intended for surgery in various hospitals in Tehran-Iran. An ACRS-PCR method was performed to distinguish mutations in the YMDD motif of HBV polymerase. In the training and testing stages, these parameters were used to identify the most promising optimal network. The ideal values of RMSE and MAE are zero, and a value near zero indicates better performance. The selection was performed using statistical accuracy measures, such as root mean square error (RMSE), coefficient of determination (R2), and mean absolute error (MAE). The main purpose of this paper was to develop a new method based on ANNs to simulate HBV drug resistance using the physiochemical properties of the YMDD motif and compare its results with multiple regression models. The results of the MLP in the training stage were 0.8834, 0.07, and 0.09 and 0.8465, 0.160.04 in the testing stage; for the total data, the values were 0.8549, 0.115, and 0.065, respectively. The MLP model predicts lamivudine resistance in HBV better than the MLR model. The ANN model can be used as an alternative method of predicting the outcome of HBV therapy. In a case study, the proposed model showed vigorous clusterization of predicted and observed drug responses. The current study was designed to develop an algorithm for predicting drug resistance using chemiophysical data with artificially created neural networks. To this end, an intelligent and multidisciplinary program should be developed on the basis of the information to be gained on the essentials of different applications by similar investigations. This program will help design expert neural network architectures for each application automatically.

The first clinical sign of chronic hepatitis C virus (HCV) infection can be one of the various extrahepatic manifestations. During antiviral treatment, symptoms of HCV-associated neuropathies usually improve, but can also worsen and lead to discontinuation of anti-HCV therapy. Recently, we have reported autonomic dysfunction in patients with HCV infection. In the present prospective study, we analyzed the changes of autonomic function during anti-HCV treatment.Patients and Cardiovagal autonomic function was assessed in 22 HCV RNA-positive, treatment-naive patients by determining heart rate variability (HRV) and baroreflex sensitivity (BRS), at the beginning of treatment and 12, 24 and 48 weeks of antiviral therapy. interferon alfa-2 and ribavirin were given according to the guidelines. Both HRV and BRS time and frequency domain indices decreased after 12 weeks of therapy compared to the pre-treatment values; then the mean±SD values increased significantly by week 24 and continued to improve by week 48 of therapy-253.0±156.1 ms before therapy vs 111.6±81.9 at week 12, and 183.4±169.6 at week 24 vs 211.6±149.1 ms at week 48 for low-frequency HRV index; p<0.05 for all comparisons). These changes were independent from the presence of cryoglobulins and from virologic response. The first rise followed by reversible autonomic dysfunction during antiviral therapy may be caused by the immunomodulatory actions of interferon alfa-2.

The level of HBsAg in some chronic hepatitis B virus (HBV)-infected individuals may decline over time so that it is not detectable in serum. To assess the efficacy of HBV vaccine in those who lost their HBsAg without seroconverssion to anti-HBs antibody.Patients and From April 1993 to December 2008, of 1603 chronic HBV-infected individuals, 34 (22 men and 12 women) became HBsAg-negative in follow-up visits, with no detectable anti-HBs antibody and HBV DNA in their sera. They received HBV vaccination at 0, 1 and 6 months (case group). Fifty-two subjects (30 men and 22 women) who were negative for HBsAg, anti-HBs and anti-HBc antibody, received HBV vaccination according to the said schedule (control group). Anti-HBs antibody was assessed one month after the last dose of vaccination in the both groups. The mean±SD age of the case and control groups was 38±12.7 and 33.4±8.6 years, respectively (p=0.07). The sex distribution between these two groups were similar (p=0.652). The mean±SD years of follow-up for the case group was 7.6±4.5 years. Anti-HBs antibody level ≥10 IU/L was found in 8 (24%) subjects in the case group and in 45 (87%) in the control group (p<0.001). The mean±SD anti-HBs antibody level in the case group was 68±32.66 and in the control group 344.6±38.9 IU/L (p<0.001). We found that nearly 24% of chronic HBsAg-positive subjects who lost their HBsAg responded to HBV and the remaining cases need to be followed for occult HBV infection.

Herein, we report on two cases of hypereosinophilic syndrome presenting as liver mass. One patient was a 22-year-old woman presented with fever, upper abdominal pain, nausea/vomiting and a mass in the right liver lobe. The second patient was a 54-year-old man who presented with nausea and abdominal pain with significant weight loss. He had multiple lesions in both liver lobes. Both patients had eosinophilia that was not attributed to other causes such as allergy or parasites. The patients were treated with glucocorticosteroid and improved clinically. Imaging and laboratory abnormalities resolved.