Chinese Consensus on Antiviral Treatment of Chronic Hepatits B Patients with Nucleos(t)ide Analogues

Antiviral treatment is the main method for chronic hepatitis B(CHB).After antiviral treatment,some patients may obtain satisfactory therapeutic effect,but some patients still show primary non-response,suboptimal response,even resistance to nucleos(t)ide analogues or relapse,which are becoming the key problems and confusing the clinical staffs.Thus,in January 2013,editorial department of Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition),Chinese Journal of Liver Diseases(Electronic Edition)

Use of endoscopic ultrasound for diagnosis of cholangiocarcinoma in auto-immune hepatitis

In this report, a patient was exposed to an herbal remedy for hypercholesterolemia. She became acutely jaundiced while taking the remedy and presented for medical care. Endoscopic ultrasound was utilized, and found a distal common bile duct mass. Endoscopic retrograde cholangiopancreatography guided bile duct biopsies revealed that the mass was cholangio-carcinoma (CCA). This case highlights a unique association between autoimmune hepatitis and CCA. It also highlights that EUS can be safely used in patients with cirrhosis to spare invasive evaluation such as exploratory laporotomy for diagnosis and staging of cholangio-carcinoma.

Molecular mechanism of hepatitis B virus X protein function in hepatocarcinogenesis

Many factors are considered to contribute to hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC),including products of HBV,HBV integration and mutation,and host susceptibility. HBV X protein(HBx) can interfere with several signaling pathways associated with cell proliferation and invasion,and HBx C-terminal truncation has been suggested to impact the development of HCC. This review focuses on the pathological functions of HBx in HBV-induced hepatocarcinogenesis. As a transactivator,HBx can affect regulatory non-coding RNAs(nc RNAs),including micro RNAs and long nc RNAs. HBx is also involved in epigenetic modification and DNA repair. HBx interacts with various signal-transduction pathways,such as the p53,Wnt,and nuclear factor-κB pathways. We conclude that HBx hastens the development of hepatoma.

Nonalcoholic fatty liver disease and hepatic cirrhosis: comparison with viral hepatitis-associated steatosis

Nonalcoholic fatty liver disease(NAFLD) including nonalcoholic steatohepatitis(NASH) is globally increasing and has become a world-wide health problem. Chronic infection with hepatitis B virus or hepatitis C virus(HCV) is associated with hepatic steatosis. Viral hepatitis-associated hepatic steatosis is often caused by metabolic syndrome including obesity,type 2 diabetes mellitus and/or dyslipidemia. It has been reported that HCV genotype 3 exerts direct metabolic effects that lead to hepatic steatosis. In this review,the differences between NAFLD/NASH and viral hepatitis-associated steatosis are discussed.

Application of nucleoside analogues to liver transplant recipients with hepatitis B

Hepatitis B is a common yet serious infectious disease of the liver, affecting millions of people worldwide. Liver transplantation is the only possible treatment for those who advance to end-stage liver disease. Donors positive for hepatitis B virus(HBV) core antibody(HBc Ab) have previously been considered unsuitable for transplants. However, those who test negative for the more serious hepatitis B surface antigen can now be used as liver donors, thereby reducing organ shortages. Remarkable improvements have been made in the treatment against HBV, most notably with the development of nucleoside analogues(NAs), which markedly lessen cirrhosis and reduce post-transplantation HBV recurrence. However, HBV recurrence still occurs in many patients following liver transplantation due to the development of drug resistance and poor compliance with therapy. Optimized prophylactic treatment with appropriate NA usage is crucial prior to liver transplantation, and undetectable HBV DNA at the time of transplantation should be achieved. NA-based and hepatitis B immune globulin-based treatment regimens can differ between patients depending on the patients' condition, virus status, and presence of drug resistance. This review focuses on the current progress in applying NAs during the perioperative period of liver transplantation and the prophylactic strategies using NAs to prevent de novo HBV infection in recipients of HBc Ab-positive liver grafts.

Four-year follow up of hepatitis C patients vaccinated against hepatitis B virus

AIM: Patients with chronic hepatitis C have been recommended to receive vaccinations against hepatitis B. Our study aimed at evaluating the hepatitis B immunogenicity and efficacy against hepatitis B virus infection 4 years after primary immunization series in a group of patients with chronic hepatitis C.METHODS: We recruited 36 out of 48 hepatitis C virus (HCV) infected individuals who were vaccinated against hepatitis B virus (20 μg of recombinant HBsAg at 0-1-6mo schedule) in 1998. Here we measured anti-HBs titers and anti-HBc 4 years after delivery of the third dose of primary immunization series.RESULTS: After 4 years a total of 13/36 (36%) HCV infected patients had seroprotective titers of anti-HBs compared with 9/10 (90%) in the control group, (P＜0.05).Similarly the mean concentration of anti-HBs found in hepatitis C patients was significantly lower than that found in healthy subjects (18.3 and 156.0 mIU/mL respectively (P＜0.05). None of the HCV infected patients or controls became infected with HBV during the study period as confirmed by anti-HBc negativity.CONCLUSION: We demonstrated that 4 years after HBV immunizations' more than 60% of vaccinated HCV patients did not maintain seroprotective levels of anti-HBs, which might put them at risk of clinically significant breakthrough infections. Further follow-up studies are required to clarify whether memory B and T lymphocytes can provideprotection in chronic hepatitis C patients in the absence or inadequate titers of anti-HBs.

Efficacy of pegylated interferon-alpha-2a plus ribavirin for patients aged at least 60 years with chronic hepatitis C

Background In China, patients with hepatitis C virus （HCV）-associated liver disease are getting older, and thus the number of deaths due to such disease is increasing. The efficacy of combination therapy with ribavirin and interferon for chronic HCV infection in elderly patients has not been fully clarified. The aim of the present study was to evaluate the efficacy and tolerability of the combination therapy in the elderly patients. Methods Sixty-eight chronic hepatitis C patients, who received the combination therapy, were classified into two age groups： elderly group （〉60 years, n=25） and non-elderly group （〈60 years, n=43）. Rapid virological response, complete early virological response, sustained virological response, relapse, non-response rate, and safety were compared between the elderly group and non-elderly group. Results Overall sustained virological response was lower in the elderly group than non-elderly group （44% vs. 75%, P=0.012, OR=0.270, and 95% CI 0.095-0.768）. Among patients with HCV genotype 1, sustained virological response was lower in the elderly group than non-elderly group （45% vs. 77%, P=0.015, OR=0.247, 95% CI 0.078-0.781）. The proportions of dose reduction due to laboratory abnormalities were significantly higher in the elderly group than non-elderly group （60.0% vs. 32.6%, P=0.027）. Multiple binary Logistic regression analysis confirmed that patient age was an associated factor for sustained virological response. Conclusion Among patients with HCV genotype 1, the elderly patients had lower sustained virological response than non-elderly patients during pegylated interferon-alpha-2a plus ribavirin combination therapy.

Clinical Observation on Effect of Ruangan Granule (软肝颗粒剂) in Treating Chronic Hepatitic Liver Fibrosis

Objective: To observe the clinical effect of Ruangan granule (RGG) in treating liver fibrosis.Methods: One hundred and twenty patients of chronic viral hepatitis B were randomly divided into two groups, 60 patients in the treated group and 60 patients in the control group. They were treated with RGG or composite Biejia Ruangan tablet (复方鳖甲软肝片) respectively for three months. The changes of liver function, liver fibrosis indices, including fibronectin (FN), laminin (LN) and hyaluronic acid (HA), as well as liver morphology by B ultrasonic examination were observed after treatment. A three month follow up study was also conducted. Results: In the treated group, the markedly effective rate was 50.0% and effective rate was 41.7%, while in the control group, the corresponding rates were 26.7% and 55.0% respectively. Comparison of the markedly effective rate between the two groups showed significant difference ( P <0.01). The serum levels of FN, LN, HA as well as splenomegaly and portal vein widening in the treated group after treatment were significantly improved ( P <0.05), as compared with those in the control group after treatment; significant difference was shown in comparison of serum FN, LN and HA. Conclusion: RGG could improve effectively serum liver fibrosis indices and liver function in patients of chronic hepatitic fibrosis. It is helpful in alleviating and inhibiting the genesis and development of liver fibrosis so as to block the progression of liver cirrhosis.