Sandbox JA

Progress

Recommended Treatment of Chronic Hepatitis B

HBeAg	ALT	HBV DNA	Treatment Regimen
+	≤2 x Upper Limit of Normal	>20,000 IU/mL	Low efficacy with present treatment Observe: treatment should be considered as ALT rises Biopsy should be considered in adults >40years, when: Persistence of an elevated ALT: [Normal;<2xUpper Limit of Normal] Family history of hepatocellular carcinoma Treatment should be considered when: HBV DNA > 20,000 IU/mL Signs of inflammation (moderate to severe) or fibrosis on biopsy
+	>2 x Upper Limit of Normal	>20,000 IU/mL	Observation for 3 to 6 months. Treatment should be started if no spontaneous HBeAg loss If compensated, liver biopsy should be considered prior to treatment If patient is jaundiced or decompensated, start immediate treatment Initial therapy may include: IFNα/pegIFNα Lamivudine Adefovir Entecavir Tenefovir Telbivudine Adefovir plays a minor role due to increased resistance rate after 1 year, and weak antiviral activity Lamivudine and telbivudine play a minor role due to increased resistance rate Treatment goal - seroconversion with production of anti-HBe to HBeAg Treatment duration: IFN-α - 16 weeks PegIFN-α - 48 weeks Lamivudine or adefovir or entecavir or telbivudine or tenofovir disoproxil fumarate - >1 year; treatment should be continued >6 months after HBeAg seroconversion Tenofovir disoproxil fumarate or entecavir for: absence of response to IFN-α; or when IFN-α is contraindicated
-	>2 x Upper Limit of Normal	>20,000 IU/mL†	Initial therapy may include: IFN-α/PegIFN-α Lamivudine Adefovir Entecavir Tenofovir disoproxil fumarate Telbivudine Lamivudine and telbivudine play a minor role due to increased resistance rate Adefovir plays a minor role due to increased resistance rate after 1 year, and weak antiviral activity Treatment end-point not defined Treatment duration: IFN-α/PegIFN-α - 1 year Lamivudine or adefovir or entecavir or telbivudine or tenofovir disoproxil fumarate - > 1 year Tenofovir disoproxil fumarate or entecavir for: absence of response to IFN-α; or when IFN-α is contraindicated
-	[1; >2] x Upper Limit of Normal	>2,000 IU/mL	If signs of necroinflammation (moderate to severe) or fibrosis on liver biopsy - consider liver biopsy and treatment
-	≤ Upper Limit of Normal	≤2,000 IU/mL	Observation. Treatment should be started when: ALT or HBV DNA rise
+/-	Cirrhosis	Traceable	If compensated: HBV>2,000 IU/mL - Initial therapy may include Lamivudine Adefovir Entecavir Telbivudine Tenofovir disoproxil fumarate
+/-	Cirrhosis	Untraceable	If compensated - observation If decompensated - indication fro liver transplant

Antiviral Medications

There are three types of treatment groups:

1. Interferon (IFN)
2. Nucleoside analogs
3. Nucleotide analogs

First Line agents

Entecavir (ETV)

• An anti-HBV nucleoside analog
• A 94% clearance rate after 5 years of treatment is observed in HBeAg positive patients.
• A 90% clearance rate after 48 weeks of treatment is observed in HBeAg negative patients.
• A necroinflammation improvement of 96% and fibrosis improvement of 88% is seen after a treatment for 6 years.

Tenofovir (TDF)

• An anti-HBV nucleotide analog
• A 68% clearance rate in HBV DNA after 4 years of treatment is observed in HBeAg positive patients.
• A 84% clearance rate in HBV DNA after 4 years of treatment is observed in HBeAg negative patients.

Interferons

• Antiviral and antiproliferative glycoprotein.
• No antiviral resistance have been noted
• Best results noted with genotype A or B who are HBeAg positive.

Second line agents

Telbivudine (LDT)

• Nucleoside analog
• Worse resistance than first line agents and not indicated if resistance to other nucleoside analogs are noted.

Adefovir (ADV)

• Nucleotide analog
• Worse resistance than first line agents
• Used in cases of nucleotide analog resistance.

Lamivudine

• Nucleoside analog
• Has a high rate of resistance and hence not used currently.

Pathogenesis

Treatment

When listeric meningitis occurs, the overall mortality may reach 70%; from septicemia 50%, from perinatal/neonatal infections greater than 80%. In infections during pregnancy, the mother usually survives. Reports of successful treatment with parenteral penicillin or ampicillin exist. Trimethoprim-sulfamethoxazole has been shown effective in patients allergic to penicillin.

Bacteriophage treatments have been developed by several companies. EBI Food Safety and Intralytix both have products suitable for treatment of the bacteria. The FDA of the United States approved a cocktail of six bacteriophages from Intralytix, and a one type phage product from EBI Food Safety designed to kill the bacteria L. monocytogenes. Uses would potentially include spraying it on fruits and ready-to-eat meat such as sliced ham and turkey.

Table

Disease	Findings
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