In Vivo Suppression of Precore mRNA Synthesis Is Associated with Mutations in the Hepatitis B Virus Core Promoter

AbstractWe have examined the in vivo effect of hepatitis B virus (HBV) core promoter mutations on the expression of precore mRNA and pregenomic RNA transcripts in the liver of 24 patients with chronic HBV infection, applying a novel transcript-specific RT-PCR assay. The double A1762T/G1764A mutation in the basic core promoter was detected in 11 cases. This mutation was in all cases associated with absence or low levels of precore mRNA transcripts without significantly affecting the levels of total core promoter-directed transcription in the liver of infected patients. Precore mRNA synthesis was suppressed by the A1762T/G1764A mutation regardless of the presence of the precore stop codon mutation G1896A, suggesting that in addition to downregulating an immunomodulatory protein this double basic core promoter mutation may also confer a replication advantage to the virus. Additional mutations detected in the core promoter may also contribute to the observed changes in precore mRNA levels. Our in vivo study shows therefore that the double A1762T/G1764A mutation is associated with the specific suppression of precore mRNA synthesis directed by the HBV core promoter

Speed of sound index for liver steatosis estimation: a reliability study in normal subjects

PURPOSENon-alcoholic fatty liver disease (NAFLD) is the most widespread type of chronic liver disease in the Western countries. Ultrasound (US) is widely used for NAFLD staging. The Resona 7 US system (Mindray Bio-Medical Electronics Co., Ltd.) includes an image optimization and speed of ultrasound-related feature, Sound Speed Index (SSI). SSI is applied in a region of interest (ROI) that could potentially aid in tissue characterization. The purpose of this study is to evaluate the reliability of SSI on various examination parameters on normal subjects.METHODSTwenty normal subjects were examined by two radiologists performing SSI measurements in the liver in different ROI depths and sizes. Intraclass correlation coefficient (ICC) was calculated to measure intra- and inter-observer variability and inter-ROI variability.RESULTSFor all ROIs and both radiologists, the mean inter-observer ICC was 0.62 and the mean intraobserver ICC was 0.52 and 0.79. The mean SSI values for all ROIs and examiners were in the range 1528.79-1540.16 m/s.CONCLUSIONThe results indicate that SSI can lead to reliable measurements on normal subjects, independent of ROI size but dependent on ROI placement. More studies processing NAFLD patients, utilizing reference methods of liver fat quantification either for reliability or correlation with SSI, should be performed to further investigate the relevance of the SSI as a potential biomarker in clinical practice for liver steatosis grading

Hepatocellular carcinoma in transfusion dependent thalassemia patients: a review from a clinical perspective

Survival in patients with transfusion-dependent thalassemias (TDT) has increased, and complications such as hepatocellular carcinoma (HCC) are emerging. Risk factors include viral infection, mainly hepatitis C virus (HCV), iron overload, the presence of cirrhosis, and immune dysregulation. Median survival after HCC occurrence has been estimated at 12 months, while data regarding the incidence of HCC in this population are minimal. Implementing effective hepatitis B virus (HBV)/HCV antiviral treatment and universal HBV vaccination programs is expected to decrease the risk for hepatocarcinogenesis substantially. Significant hemosiderosis and hepatic fibrosis are common in patients with TDT despite chelation therapy and have been correlated with HCC development. Thus, iron overload should be monitored with liver iron concentration and ferritin levels, and effective chelation therapy should be applied. In addition, all TDT patients, particularly those with cirrhosis, should be under surveillance every six months with abdominal ultrasound ± alpha-fetoprotein levels, as this combination seems to provide better sensitivity for early HCC detection

Adaptive immunity in hepatocellular carcinoma: prognostic and therapeutic implications

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and has a poor prognosis. Host immunity can either protect or promote tumor growth by the predominance and activation of certain subsets of immune cells. It has been established that antigens such as AFP, MAGE, glypican 3 and NY-ESO, which are highly expressed in HCC, are potential targets for T-cell responses. Several studies have come to the conclusion that cytotoxic T-cell infiltration of the tumors is indicative of a better survival, whereas the predominance of suppressor cells is associated with a worse outcome and lower survival rates. Finally, certain therapeutic strategies, including radiofrequency ablation and chemoembolization, can enhance the release and exposure of tumor antigens, which might help to overcome the immune tolerance towards the tumor. Therefore, such immune-stimulating therapeutic interventions in combination with immunotherapy strategies represent a promising future approach for HCC treatment

Clinical characteristics, spontaneous clearance and treatment outcome of acute hepatitis C: A single tertiary center experience

Background and Aims: Acute hepatitis C is rarely diagnosed due to its predominantly asymptomatic course. However, early treatment results in viral eradication in a high number of patients thus, preventing chronicity. The aim of our study was to describe our experience with patients with acute hepatitis C virus (HCV) infection who presented and followed-up in our liver unit, pointing on treatment strategy, and outcome. Patients and Methods: Retrospective, descriptive study of 30 patients with acute HCV infection (26 males and 4 females) with a mean age of 32 years. Results: The source of infection was mainly injection drug use in 17/30 (56.7) and medical procedures 6/30 (20%). Twenty patients (66.6%) were symptomatic. HCV-ribonucleic acid (RNA) was detectable at presentation in 26 (86.7%) patients. The genotype distribution was: 13/26 (50%) genotype 1, 3/26 (11.5%) genotype 2, 8/26 (30.8%) genotype 3 and 2/26 (7.7%) genotype 4. Totally, 9 patients (30%) experienced spontaneous viral eradication. No significant differences could be documented between patients who spontaneously cleared the virus and those who had viral persistence. Thirteen patients (44%) were treated with peginterferon-based regimen. All patients (100%) achieved non-detectable HCV-RNA and had normal serum alanine aminotransferase levels at the end of the treatment. Eleven patients achieved sustained virologic response (SVR), one relapsed and one was lost to follow-up. The overall SVR rate was 84.6%. None of the patients required dose reduction or stopped the treatment due to side effects. Conclusion: In conclusion, early initiation of anti-viral treatment in patients with acute hepatitis C results in high-SVR rates (independently of genotype) and is well-tolerated