中医药防治重型肝炎探析

在回顾中医药对重型肝炎认识的基础上,总结了重型肝炎的临床特点,提出对重型肝炎的防治思路,认为应首先处理好中西医协作及中医理论与中药的关系,以卫气营血辨证为辨证方法,分黄疸期、内毒素血症期、脏腑功能衰竭期3期治疗,并强调解毒排毒、调畅气机、养阴生津是其中的共性原则和关键环节。

Immunogenicity and reactogenicity of a recombinant hepatitis B vaccine in subjects over age of forty years and response of a booster dose among nonresponders

AIM:The study was initiated to evaluate the reactogenicity and immunogenicity of a recombinant hepatitis B vaccine in age group >40 years and to study the response of a single booster dose in primary non-responders to the hepatitis B vaccination. METHODS:A total of 102 volunteers without markers of hepatitis B infection (negative for HBsAg,anti-HBc antibody, HBeAg and anti-HBs antibody) received 20μg of recombinant HB vaccine intramuscularly at 0,1,and 6 months.Anti HBs titers were evaluated by a quantitative Elisa kit at 90 and 210 days.A booster dose of 20μg HB vaccine was given after 6 months of the 3^(rd) vaccine dose to the 15 non- responders and anti-HBs titers were measured after i month. RESULTS:Seroprotection (anti-HBs GMT^3 10 IU/L) was achieved in 85.3 % (87/102) volunteers.The mean GMT titers of the vaccine responders was 136.1 IU/L.Of the seroprotected individuals,there were 32.4% (33/102) hyporesponders (anti- HBs titers <10-99 mIU/ml) and 52.9% (54/102) were responders (anti-HBs titers >100 IU/L).All the non-responders (15/15) responded to a single dose of the booster dose of recombinant HB vaccine and their mean anti-HBs antibody titers were more than 100.5 mIU/ml after the booster dose. CONCLUSION:Recombinant hepatitis B vaccine offers good seroprotection in the age group >40 years and has a good safety profile.A single booster dose after 6 months in primary non-responders leads to good seroprotective anti-HBs antibody titers.However,larger population based studies are needed to evaluate the role of a booster dose in selected group of non-responders and whether such an approach will be cost effective.

Analysis of prognosis on patients with severe viral hepatitis using the model for end-stage liver disease

AIM: To study the practical use of the model for endstage liver disease (MELD) on clinic and assess its validity by the concordance (C)-statistic in predicting the prognosis of the patient with severe viral hepatitis.METHODS: One hundred and twenty-one patients were divided into plasma exchange group and non-plasma exchange group, and were graded with MELD formula.The death rate was observed within 3 mo.RESULTS: Eighty-one patients died within 3 mo (35 cases in PE group, 46 cases in non-PE group). The mortality of patients in PE group whose MELD score between 20-30and 30-40 were 31.6% and 57.7%, respectively, but in non-PE cases they were 67.6%, 81.3% respectively.There was significant difference between PE group and non-PE group (P＜0.05). However, the mortality of patients whose MELD score higher than 40 were 93.3% in PE group and 100% in non-PE group and there was no significant difference between the two groups (P= 0.65＞0.05). The optimal cut-off values of MELD to predict the prognosis of patients were 30 in PE group whose sensitivity, specificity and C-statistic were 80.0%, 52.0% and 0.777, but in non-PE group they were 25, 82.6%, 86.7% and 0.869, respectively.CONCLUSION: The MELD score can act as a disease severity index for patients with severe viral hepatitis, and the mortality of the patient increases with the increase of the MELD score. The MELD can accurately predict the short-term prognosis of patients with severe viral hepatitis.

Evaluation of immunogenicity and reactogenicity of recombinant DNA hepatitis B vaccine produced in India

AIM： （1） To gain information on immune responses to an accelerated schedule of 0, 1, and 2 mo in paramedical staff and BDS students who are at an increased risk of getting hepatitis B infection and come under high risk groups. （2） To assess the efficacy and safety of En/vac- HB in different age groups, using genetically modified yeast strain Pichia pastoris, a new recombinant hepatitis B accine developed and manufactured in India. METHODS： A prospective, comparative, and single blinded trial of rapid （0, 1, and 2 mo） hepatitis B immunization schedulewas reported. A total of three hundred and seven （212 females and 95 males） healthy volunteers divided into three age groups （18-29, 30-39, and 40-49） were enrolled after screening for markers of hepatitis B. All the volunteers received 20 mg of the vaccine intramuscularly at 0, 1, and 2 mo. RESULTS： Geometric mean titers were calculated pre and post vaccination. Before immunization the GMT was 0.0124 mIU/mL. One month after the administration of the third dose of recombinant vaccine 296/307 （96.5%） subjects achieved seroprotective levels of anti-HBs. The geometric mean anti-HBs titers achieved after one month of the third dose was 2 560.0 mIU/mL. The geometric mean anti-HBs titer of males was 2 029.0 mIU/mL, while that of the females was 2 759.0 mIU/mL. In the age group of 18-29 years, anti-HBs titer was 3 025.0 mIU/ mL, while that in the age group of 30-39 years was 2 096.0 mlU/mL. In third age group of 40-49 years, anti- HBs titer was 1 592.0 mIU/mL. Hyper-responses （anti-HBs≥100 mIU/mL） were shown in 88.0% （271/307） of subjects. Eleven （3.5%） subjects responded poorly to the vaccine in the age group of 40-49 years. There was only mild pain at the site of injection otherwise there were no other adverse drug reactions （ADRs）. CONCLUSION： This vaccine （Enivac-HB） is safe and efficacious, providing significant protection after the third dose and rapid hepatitis B immunization schedule of 0, 1, and 2 mo can be recommended whenever rapid protection is the goal.

Study progress on mechanism of severe acute pancreatitis complicated with hepatic injury

Study on the action mechanism of inflammatory mediators generated by the severe acute pancreatitis （SAP） in multiple organ injury is a hotspot in the surgical field. In clinical practice, the main complicated organ dysfunctions are shock, respiratory failure, renal failure, encephalopathy, with the rate of hepatic diseases being closely next to them. The hepatic injury caused by SAP cannot only aggravate the state of pancreatitis, but also develop into hepatic failure and cause patient death, lts complicated pathogenic mechanism is an obstacle in clinical treatment. Among many pathogenic factors, the changes of vasoactive substances, participation of inflammatory mediators as well as OFR （oxygen free radical）, endotoxin, etc. may play important roles in its progression.

An overlap syndrome involving autoimmune hepatitis and systemic lupus erythematosus in childhood

We report a 12 years old female patient with an overlap syndrome involving autoimmune hepatitis （AIH） and systemic lupus erythematosus （SLE）. The patient presented with jaundice, hepatosplenomegaly, malaise, polyarthralgia, arthritis and butterfly rash on the face. Laboratory tests revealed severe liver dysfunction, Coombs positive hemolytic anemia and a positive ANA/ anti-dsDNA test. Renal biopsy showed class IIA kidney disease, while liver biopsy showed chronic hepatitis with severe inflammatory activity. The patient satisfied the international criteria for both SLE and AIH. Clinical symptoms and laboratory findings of SLE improved with high dose treatment with corticosteroids and azathioprine, however, remission of the liver disease could not be achieved. Repeat biopsy of the liver after three years of therapy revealed ongoing chronic hepatitis with high level of inflammatory activity. The present case indicates that children with liver dysfunction and SLE should be investigated for AIH. There is much diagnostic and therapeutic dilemma in patients with AIH-SLE overlap syndrome.

Immunogenicity of recombinant hepatitis B vaccine in treatment-nave and treatment-experienced chronic hepatitis C patients: The effect of pegylated interferon plus ribavirin treatment

AIM： To retrospectively evaluate the vaccinationinduced anti-HBs seroconversion rates in treatmentnaive and treatment-experienced chronic hepatitis C （CHC） patients. Also to prospectively evaluate the seroconversion rates in CHC patients during pegylated interferon （PEG） plus ribavirin （RIB） treatment. METHODS： Seventy treatment-naive CHC patients （group A）, 22 sustained virological responders-SVR following interferon （IFN） plus RIB treatment CHC patients （group B） and 121 healthy subjects （group C） had been participated in the same HBV vaccination schedule （20 μg, 0-1-6 mo）. Seroconversion was considered if anti-HBs levels were above 10 mIU/mL within 3 mo following the third dose of the vaccine. Moreover, we prospectively selected 30 non-cirrhotic CHC patients and evaluated them for the efficacy of the same vaccine schedule randomizing them in two groups： Group-1, 15 CHC patients received the first dose of the vaccine in parallel with the initiation of PEG plus RIB treatment and Group-2, 15 patients received the same vaccination schedule without concomitant treatment. Determination of anti-HBs was performed at mo 1, 2, and 7. Statistical analysis of data was based on ANOVA student＇s t-test and chi-square analysis （P 〈 0.05）. RESULTS： Fifty-eight of 70 group A patients （82.85%）, 20/22 group B （90.9%） and 112/121 healthy subjects （92.56%） had been seroconverted. The seroconversion rates were significantly higher in the control group than in treatment-naive CHC patients （P = 0.04）. The corresponding rates were comparable between group A and group B CHC patients （P = 0.38）. The vast majority of non-responders （10/14, 71.43%） had been infected by genotype-1 of HCV. The seroconversion rates were comparable between group 1 and 2 CHC patients at mo 1 （20% versus 26.7%, P = 0.67）, mo 2 （46.7% vs 60%, P = 0.46） and mo 7 （86.7% versus 93.3%, P = 0.54） of follow-up. CONCLUSION： The immunogenicity of HBV vaccine seems to be lower in CHC patients compared to healthy subjects. SVR following IFN plus RIB treatment does not affect the antibody response to HBV vaccine. Infection by genotype-1 seems to negatively influence the seroconversion rates. Vaccination against HBV during PEG plus RIB combination treatment is not beneficial in terms of anti-HBs seroconversion rates.

Changes in intestinal microflora in patients with chronic severe hepatitis

Objective To investigate changes in intestinal microflora in patients with chronic severe hepatitis (CSH), and their role in this life-threatening disease.Methods We classified nineteen patients with chronic severe hepatitis as the CSH group, thirty patients with chronic hepatitis (CH) as the CH group and thirty-one healthy volunteer as the control group. Fecal flora from all subjects were analyzed. Concentrations of plasma endotoxin, serum cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) and liver function were assessed.Results The number of fecal bifidobacterium (P<0.001, P<0.05 respectively), as well as bacteroidaceae (P<0.001, P<0.01 respectively) were significantly deceased in patients with chronic severe hepatitis compared with the CH and control groups, while the number of enterobacteriaceae (P<0.001, P<0.05 respectively) and yeasts (P<0.01, P<0.05 respectively) were significantly increased. Levels of plasma endotoxin, serum TNF-α, IL-1β and total bilirubin (TBiL) were significantly increased in the CSH group. The concentration of endotoxin positively correlated with levels of both TNF-α, IL-1β and TBiL (P<0.001, respectively). Levels of plasma endotoxin were positively correlated with the number of fecal enterobacteriaceae and negatively correlated with bifidobacterium (P<0.05, P<0.001, respectively).Conclusion Intestinal flora in patients with chronic severe hepatitis were severely disturbed and gut mircobiological colonization resistance was impaired. Changes in intestinal flora may have a pivotal role in both the elevation of plasma endotoxin and further hepatic lesions resulting in liver failure.

Gender disparity in hepatocellular carcinoma(HCC):multiple underlying mechanisms

On the global scale, hepatitis B virus(HBV) infection is the main cause of hepatocellular carcinoma(HCC) especially in regions of Asia where HBV infection is endemic. Epidemiological studies show that the incidence of inflammation-driven HCC in males is three times as high as in females. Recent studies suggest that sex hormones have a crucial role in the pathogenesis and development of HBV-induced HCC. We found that the estrogen/androgen signaling pathway is associated with decreased/increased transcription and replication of HBV genes and can promote the development of HBV infections by up/downregulating HBV RNA transcription and inflammatory cytokines levels, which in turn slow down the progression of HBV-induced HCC. Additionally, sex hormones can also affect HBV-related HCC by inducing epigenetic changes. The evidence that both morphology and function of the human liver are affected by sex hormones was found over 60 years ago. However,the underlying molecular mechanism largely remains to be elucidated. This review focuses mainly on the molecular mechanisms behind the sex difference in HCC associated with HBV and other factors. In addition, several potential treatment and therapeutic strategies for inflammation-driven HCC will be introduced in this review.