According to J Gastroenterol Hepatol [1999, 14(Suppl):A230] in the U.S. Hollinger reported that the hepatitis B virus is distributed globally, and according to statistics, there are about 350 million chronic carriers of HBV in the world.
The goals of effective treatment are to (i) inhibit viral replication and clear the virus; (ii) reduce symptoms; (iii) reduce inflammation and improve liver function; (iv) prevent progression to cirrhosis and hepatocellular carcinoma; and (v) improve patient survival. There are many treatments available for chronic hepatitis B, including antivirals, immunomodulation, cytokines, antifibrosis, antisense oligonucleotides, and nucleases. Effective treatment is defined as durable clearance of HBV DNA from the blood, negative HBeAg, appearance of anti-HBe, and reduction of ALT values to normal, as detected by non-PCR techniques. When an infection moves from the replicative to the integrative phase, the usual outcome is remission rather than cure. In the United States, interferon and lamivudine are the only drugs currently approved for the treatment of hepatitis B.
Interferon A recent meta-analysis of 15 studies evaluated the efficacy of interferon. Compared with untreated controls, the HBsAg negative rate was 6% higher and the HBeAg negative rate was 21% higher. the HBV DNA negative rate was 20% (detection threshold of 1.5-30.0 pg/ml or 500-1 million copies/ml). The HBV DNA negative conversion rate will be lower if PCR is used. Interferon 5MU or 10MU daily 3 times a week or every other day is the preferred treatment regimen. Predictors of treatment effectiveness are low pretreatment viral load (HBV DNA <100pg/ml or <33 million copies/ml), high ALT (greater than 3 times the upper limit of normal), active necrotizing inflammation of the liver (including cytoplasmic HBcAg positivity), and HIV negativity.
High-dose interferon is more effective than smaller doses, but side effects are increased. Treatment for 6 months was no more effective than 3 months, although interferon treatment for 4 or 6 months resulted in significantly higher HBsAg-negative rates. Women have better outcomes than men, and Chinese patients have lower rates of effectiveness. Among cirrhotic patients, those with more severe disease (Child-Pugh class B or C) had poorer outcomes.
Nucleoside and nucleotide analogs include lamivudine, famciclovir, adefovir, dipivoxil, and lopukavir. They inhibit HBV DNA replication. In large-scale, randomized, controlled clinical trials, patients taking lamivudine 100 mg/day orally for 12 months*** had HBeAg negativity and reduction of HBV DNA to <1.5pg/ml or <500,000 copies/ml in 16% to 32% of patients, compared with an effectiveness rate of only 6% in the control group. Hepatic histology improved in the majority of patients. durable efficacy rate of >80% at 6 to 18 months. If lamivudine treatment is prolonged (>6 months), mutations in the HBV YMDD locus occur in 15% to 30% of patients, which leads to a decrease in lamivudine efficacy. The best predictor of lamivudine efficacy was a baseline ALT level greater than twice the upper limit of normal, and patients with normal ALTs did not fare better than controls.HBV DNA levels were not a predictor of HBeAg negativity, and those patients whose HBV DNA fell to less than 10,000 copies/ml within 20 weeks of treatment had a greater likelihood of being effective. The optimal dose is 100 mg/day, and although higher doses (300 mg/day) result in a more rapid decline in HBV DNA, HBV DNA clearance and HBeAg negativity are similar after 3 to 6 months of treatment. An Asian study showed that extending the course of lamivudine to 3 years increased the HBeAg-negative rate to 65%.
Combination therapy In some recent studies, interferon (10 MU) 3 times weekly for ****16 weeks plus lamivudine 100 mg daily for 24 weeks resulted in a 29% efficiency rate; this compared with 18% to 19% for one drug alone, but the difference was not statistically significant.
Antisense oligodeoxyribonucleotides and ribozymes Antisense oligodeoxyribonucleotides block gene expression by forming hybridization between the positive and negative strands of HBV DNA. In a recent study, antisense oligodeoxyribonucleotides resulted in long-term inhibition of Pekin duck DHBV replication and gene expression. Nucleases represent another molecular mechanism for inhibiting viral replication; they are antisense oligodeoxynucleotide catalysts that cleave RNA at specific sites.
Immune regulation Clinical regression of acute HBV infection is dependent on the quality and strength of the host's antiviral response, and, precisely, the HBV in infected hepatocytes is probably cleared by cytotoxic T-lymphocytes (CTLs) by the following possible mechanisms The possible mechanisms are: (i) antigen-activated CTL kill HBV directly and lead to the destruction of infected hepatocytes; (ii) CTL secrete cytokines (IFN-γ and TNF-α) to remove HBV by non-cytolytic means leading to viral destruction (without destroying the hepatocytes), and to remove a large number of intracellular hepatocytes by inhibiting viral replication and gene expression. . tolerance is virus-specific rather than generalized immunosuppression. Many experimental studies have suggested that CD8+, MHC type I CTLs can clear the virus from infected cells. Therefore, T-cell HBeAg antigen-determining cluster vaccines can be used to treat chronically HBV-infected individuals.
Thymosin α-1 increases endogenous IFN-α and γ levels, as well as IL-2, and it also increases IL-2 receptor expression and enhances the proliferation and activity of CD3, CD4, CD8 and NK cells. In HBV-infected duck hepatocytes, thymosin alpha-1 appears to reduce viral replication, especially at the level of viral protein expression. Its safety profile is excellent, but it requires subcutaneous injection. Combining the results of four studies showed that after 6 months of treatment (1.6 mg twice weekly) in 183 patients 36% of patients had HBeAg and HBV DNA turned negative and ALT decreased to normal. In contrast, 111 untreated control patients were effective in only 19% of patients.
Careful medical selection
Currently, domestic and foreign treatment of hepatitis, in terms of drug selection, the book includes three aspects, (1) anti-viral aspects of the drug; (2) immunomodulators: (3) to promote the repair of liver cell regeneration of drugs.
There is a wide variety of drug types for the treatment of viral hepatitis, and it is estimated that the drugs used for the treatment of hepatitis (including liver-protecting drugs, antiviral drugs, and drugs to regulate immune function) in the whole country can be up to more than seven hundred kinds of drugs. In the protection of liver function, to prevent further necrosis of liver cells in the treatment of drugs, progress is still relatively significant. For example, the mortality rate of severe hepatitis was as high as 80% in the 60s and 70s, but in the 80s and 90s, the mortality rate has been reduced to about 40%, which indicates that the measures to prevent hepatocyte necrosis and to promote hepatocyte regeneration have taken a big step forward, but so far, there is not a special drug that can cure viral hepatitis. However, a variety of media on hepatitis treatment publicity overstatement, said what "hepatitis can be cured", "** drugs on hepatitis efficacy of the best" and other violations of the laws of science, the language of the absurd advertising campaigns are common, such as claiming to be the "king of the conversion", "hepatitis nemesis", "Hepatitis B has been a breakthrough", "triple yang all turn negative", "to solve the hundreds of millions of patients with hepatitis in our country's urgent need" and so on.
Recently, a number of hepatitis experts have called for proper media publicity and not to mislead patients to be deceived. And pointed out that the purpose of the treatment of hepatitis B is not a variety of viral markers negative, but to prevent hepatitis to chronic and fibrosis development. At present, there is not a "miracle drug" to eliminate the transmission of hepatitis B virus, and there is no provision for hepatitis B virus markers negative as a standard of efficacy. As mentioned above, although there are many drugs for the treatment of viral hepatitis, especially chronic hepatitis, there is no drug that can cure the hepatitis B virus. For this reason, the author believes that all hepatitis B "triple positive", "small triple positive", "1.5 positive" or some with mild transaminase elevation, as well as hepatitis C transaminase mildly elevated patients, do not go around looking for those who "turn negative king" and other characters. Our countermeasure is to focus on basic treatment, i.e., proper rest, optimism, reasonable diet, adequate nutrition, and choosing appropriate health food, which is very good for protecting liver function and preventing chronicity and fibrosis of hepatitis. For those patients with severe hepatitis, it is better to be hospitalized for systematic treatment.
Scientific use of hepatoprotective drugs Zhang Shige (1999.10.20)
The etiology or pathogenesis of many liver diseases has not yet been fully understood, and therefore there are no specific drugs at present. Most of the drugs used in liver diseases have only an adjunctive therapeutic effect and are still symptomatic, and the efficacy of some of these drugs has yet to be evaluated. On the one hand, the treatment focuses on protecting and nourishing liver cells in order to restore their vitality and function as much as possible, and on the other hand, it is hoped to reduce the proliferation of connective tissues and prevent cirrhosis from occurring.
There are more than a hundred kinds of medicines for treating liver diseases, which can be categorized according to their pharmacological effects: (1) anti-hepatitis virus medicines, which mainly inhibit the replication of the hepatitis B virus. (2) Hepatoprotective drugs, including anti-hepatocellular necrosis drugs, liver cell repair drugs, immunomodulators, detoxification and liver protection drugs. (3) Anti-fatty liver drugs: promote fat decomposition, accelerate fat transfer and metabolism, and prevent fat accumulation in the liver.
The auxiliary drugs for liver disease in the national non-prescription drug list are: inosine, oleanolic acid, glucuronolactone.
Because the causes and pathologies of liver diseases are diverse, even among the same disease, there are differences in the severity of the disease, the course of the disease and the individual patient. Therefore, in the treatment of different conditions, we should grasp the main contradiction, take into account the secondary contradiction, and comprehensively integrate. To prevent fatty liver, inosine can be taken orally, 200-500 mg per time, three times a day. Vitamins and trace elements should also be supplemented. Patients with liver disease often have different degrees of nutritional deficiencies, which can be corrected through dietary therapy and generally do not need medication. For patients with severe malnutrition, vitamin deficiencies, low intake of food, or prolonged intravenous fluid replacement, additional vitamins, minerals, and trace elements should be added.
To protect the liver's storage function. Patients with liver disease should protect the remaining reserve function of the diseased liver as much as possible, so that it will not be further weakened. On the one hand, use drugs to protect liver cells, promote liver cell regeneration, or improve intrahepatic microcirculation to reduce fibrosis. On the other hand, it is necessary to avoid aggravating the burden on the liver to prevent further liver damage. Oleanolic acid and glucuronolactone can be taken orally.
It is also necessary to prevent the toxic side effects of drugs on the liver. All kinds of drugs into the human body, are metabolized by the liver and detoxification, too much to take the drug is to increase the burden on the liver; secondly, some drugs have hepatotoxicity, will damage liver cells. Therefore, you should choose your medication carefully and take less or no unnecessary medication.
Currently, there are hundreds of proprietary Chinese medicines in China for treating liver diseases, the main effects of which include clearing heat from the internal organs and relieving depression, etc., which can be taken under the guidance of a doctor by choosing the varieties with precise therapeutic effects. In the process of treatment and recuperation, we should avoid the abuse of drugs, and prohibit alcohol, quit smoking, and prevent secondary infections.
Hepatoprotective and enzyme-lowering: need to re-evaluate
Lou Yuyao
In recent years, scholars at home and abroad generally believe that most of the efficacy of hepatoprotective drugs is unproven, and some may have a pro-fibrotic effect, even as an adjunct to the drugs need to be reevaluated. Then there are enzyme-lowering drugs, such as schizandra, biphenyl biphenyl, pituitary grass, etc., although there is a definite enzyme-lowering effect, which can make the ALT quickly return to normal, but the inflammation of the liver still exists and develops, so this kind of drug should not be used as the main means of treatment.
What are the current effective drugs for hepatitis B
What are the current effective anti-hepatitis B virus drugs? How to choose the medication?
New progress in the treatment of chronic hepatitis B
1. Treatment goal: to stop the development of liver lesions by inhibiting the replication of hepatitis B virus or eliminating the infection, which is specifically shown as: ① serum hbvdna negative; ② serum hbeag negative, anti-hbe positive (i.e., the "major triple positive" turned to "minor triple positive"); ③ normal serum alt; ④ improved liver histology.
2. Indications for antiviral therapy: serum hbvdna or/and hbeag positivity lasting for more than 6 months; recurrent elevation of serum alt level; histologic examination of liver suggesting chronic hepatitis B virus infection with more than moderate degree of inflammation.
3. Effective anti-hepatitis B virus drugs:
3.1a-interferon:
In 1992, the U.S. Food and Drug Administration (fda) approved the use of a-interferon for the treatment of chronic hepatitis B patients, both inhibitory viral replication and immune-enhancing function, the recommended dose of each subcutaneous injection of 5 million units, three times a week, the course of treatment at least 6 months. Currently, there are imported drugs such as "Interferon", "Robitussin", "Huifuren", and domestic drugs such as "Seroquel" and "Yunjin".
Better indicators of therapeutic efficacy include: pretreatment serum hbvdna levels below 200pg/ml, serum alt above 100u/l, liver histology suggesting significant inflammatory activity, female, history of acute hepatitis, shorter duration of persistent viral infection, non-maternal-to-child transmission, and non-viral mutation.
Possible adverse reactions include: flu-like symptoms, bone marrow suppression (manifested by a decrease in the number of peripheral blood white blood cells, platelet counts), loss of appetite, emaciation, hair loss , mental depression.
3.2 Lamivudine:
Lamivudine (China's trade name "Herceptin") is another drug approved by the U.S. FDA in December 1998 for the treatment of hepatitis B virus, which can only inhibit viral replication, and is recommended to be taken orally at 100mg per dose once a day for at least one year. The course of treatment is at least 1 year.
Possible adverse reactions: No significant adverse reactions have been identified.
Precautions: After 9 months of treatment, it is necessary to check for viral mutation to prevent drug resistance
3.3 Famciclovir:
Famciclovir (the trade name of "Lizufeng") is another class of nucleoside analogs with a mechanism of action similar to that of lamivudine, and the recommended regimen is to take 0.5g of the drug orally three times a day for a period of at least 4 months. The recommended regimen is 0.5g orally 3 times a day for at least 4 months.
3.4 Immunomodulators:
Thymotropin a1 (trade name "Nidaxan") is an immune enhancer, which plays an antiviral role by enhancing the immune effect against hepatitis B virus, and is usually used in combination with a-interferon or lamivudine, and the recommended regimen is to administer 1.6mg subcutaneously once daily for 4 consecutive days and then switch to lamivudine. 1 time, after 4 consecutive days to 2 times a week, the course of treatment 4-6 months.
4. Precautions: monitor serum alt, hbvdna, hbeag/anti-hbe during the treatment, and treat under the guidance of specialized physicians
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