HepB Forum : Unofficial Research Thread (URT) Tx info

[stevenNYer]

I am reposting articles / summaries on the treatment management of chronic HepB.  "cajim" located these articles which are quite informative.  I thought about putting them on a seaprate Health Page but didn't think it was appropriate since we didn't write them.

Let's make this a sort of "Unofficial Research Thread" or "URT" for this type of information.  Let's keep this URT free of comments.  For comments, start a new thread indicating that it's in reference to URT.

We'll see how it goes.

[cajim]

Update on Hepatitis B Management, 2008.

Peginterferon alfa-2a in HBeAg-Negative Chronic Hepatitis B

Patrick Marcellin, MD: With hepatitis B, we have 2 treatment strategies: peginterferon alfa or nucleos(t)ide analogues. The advantage of peginterferon alfa is that when it works, its effects are durable and it is associated with a high rate of hepatitis B surface antigen (HBsAg) suppression. The disadvantages are its subcutaneous administration, adverse effects, and relatively low overall efficacy rate. Advantages of nucleos(t)ide analogues are ease of administration (1 pill daily), a good safety profile, and substantial efficacy with new agents, such as entecavir or tenofovir, with 70% to 90% of patients achieving undetectable HBV DNA.[1-4] The disadvantage of nucleos(t)ide analogues is that treatment must be continued for many years—possibly lifelong—and the rate of HBsAg loss or seroconversion is very low. Let us being the discussion with 2 studies that look at the use of peginterferon alfa-2a inpatients with hepatitis B e antigen (HBeAg)–negative chronic hepatitis B. Worldwide, HBeAg negative infection is the predominant form of hepatitis B and is associated with high relapse rates.[5,6] In a previously published, randomized, controlled trial conducted by a group of which I was a member, the efficacy and safety of 48 weeks of peginterferon alfa-2a, lamivudine, or acombination of the 2 treatments were evaluated in 537 patients with HBeAg-negative chronic hepatitis B.[7] In that analysis, peginterferon alfa-2a was more effective than lamivudine at achieving sustained suppression of HBV DNA to < 400 copies/mL for 6 months after completion of treatment (19% vs 7%, respectively), with the combination of peginterferon alfa-2a plus lamivudine offering no additional benefit compared with peginterferon alfa-2a alone(20% vs 19%, respectively). Loss of HBsAg occurred in 12 patients receiving peginterferonalfa with or without lamivudine vs none receiving lamivudine alone. Forty-two of the original 54 study centers participated in a long-term observational follow-up of patients. In the current analysis presented at the European Association for the Study of the Liver (EASL) in Milan, Italy, we evaluated long-term response and relapse rates 4 years after completion of treatment in 230 patients who received peginterferon alfa-2a with or without lamivudine and 85 patients who received lamivudine alone.[8] Patients entering the long-term study who had received lamivudine only were more likely to have achieved an end-of treatment response at Week 48 than those who received peginterferon alfa-2a with or without lamivudine. However, by a modified intent-to-treat analysis, significantly more patients had HBV DNA < 400 copies/mL at 4 years after end of treatment in the group who received peginterferon alfa-2a with or without lamivudine compared with those treated with lamivudine alone (17% vs 7%, respectively; P = .042). Most interestingly, the rate of HBsAg clearance increased over time after end of treatment, reaching 11% of patients in the peginterferon alfa-2a with or without lamivudine group at 4 years after end of treatment compared with 2% of patients who were treated with lamivudine alone (P = .021).These findings indicate that in 17% of patients who respond well to peginterferon alfa-2a and achieve HBV DNA < 400 copies/mL, the response is usually sustained and a increasing number of those patients (66% at 4 years) achieves HBsAg loss, which is considered to be the clinical cure of hepatitis B. The other three quarters of patients do not respond well to treatment or relapse and, in those cases, should receive alternative treatment such as nucleos(t)ide analogues because previous interferon exposure does not decrease the chance of response to these drugs. This message supports the continued inclusion of peginterferon alfa treatment as a first-line option for some patients, as detailed in many international guidelines. Clinicians must weigh the advantages and disadvantages of peginterferon vs nucleos(t)ide analogues. I do not think there is any conflict between the 2 strategies, but we must learn which strategy is best for individual patients.

Kris V. Kowdley, MD, FACP, FACG, FASGE, AGAF: Peginterferon has several unique attributes that warrant consideration of its use as a first-line therapy for chronic hepatitis B. HBeAg-positive patients without cirrhosis who have genotype A infection, especially if associated with relatively low levels of viremia and activenecro inflammation on liver biopsy, may represent ideal candidates for consideration of peginterferon as first-line therapy. I have also found peginterferon an attractive option in women of childbearing age who wish to pursue a finite course of therapy and are concerned about possible teratogenic risks with nucleos(t)ide agents.

Predicting Responses to Peginterferon alfa-2a

Patrick Marcellin, MD: Based on these results, the next important question is how to identify the approximately 25%of patients who will respond well to peginterferon. To investigate this important issue, Brunetto and colleagues[9] evaluated the association between HBsAg decline on treatment and long-term HBsAg clearance in 315 patients from the same cohort (Magnitude of HbsAg Decline on Treatment Predicts Posttreatment HBsAg Clearance Following Peginterferon alfa-2a–Based Therapy). There was a clear association between reductions in serum HbsAg levels during treatment and sustained posttreatment HBsAg clearance. Two predictors of HBsAg loss following peginterferon-based therapy were identified: achieving HBsAg  2 log10 IU/mL during therapy. HBsAg clearance was seen in 42% to 52% of patients achieving these on-treatment reductions in HBsAg.

Kris V. Kowdley, MD, FACP, FACG, FASGE, AGAF: The approximately 50% rate of HBsAg clearance among patients achieving these HbsAg reduction on therapy is very high, and if these results are confirmed, HBsAg decline may become a useful marker. The authors proposed measuring quantitative HBsAg at baseline and during therapy, perhaps at Week 24. At that point, one might consider stopping therapy inpatients not achieving an adequate rate of HBsAg decline. This is based on the concept of the 24-week milestone used for assessing response to several of the oral agents.[10]

[cajim]

His laboratory studies revealed the following:

Glycosylated hemoglobin: 5.8%
HBV DNA: 62,500 IU/mL
HBsAg (+), HBsAb (-), HBeAg (-) and HBeAb (+)
AFP: 6 ng/mL
ALT: 40 IU/L
AST: 35 IU/L
Total bilirubin: 0.9 mg/dL
Creatinine: 0.9 mg/dL
Blood urea nitrogen: 25 mg/dL

Evaluation of 12-month follow-up. The patient was receiving treatment for metabolic syndrome. His HBV DNA became positive after being undetectable for more than 1 year while on lamivudine.

On the basis of these findings, we suspected that the patient had a virologic breakthrough most probably as a result of development of the YMDD mutation and resistance to lamivudine. At this point in management, adefovir 10 mg/day was added to continued lamivudine therapy.

Lamivudine Resistance
Currently available antiviral agents for chronic hepatitis B are either nucleoside (lamivudine, entecavir, telbivudine) or nucleotide (adefovir, tenofovir**) analogs. Using oral antivirals requires long-term therapy (and in most patients, indefinite treatment) to maintain viral suppression. Long duration of therapy increases the risk for antiviral drug resistance. Lamivudine resistance occurs in approximately 20% of patients after 1 year and in up to 65% after 5 years.[6] The characteristic mutations occur in the YMDD motif of the HBV DNA polymerase. When this mutation occurs, the sensitivity to lamivudine decreases greater than 100-fold. Lamivudine-resistant mutations confer cross-resistance to other nucleosides, such as emtricitabine,** telbivudine, and clevudine.** They also decrease susceptibility to entecavir. The main approach to managing lamivudine resistance is to add adefovir or tenofovir (when approved) to ongoing lamivudine therapy.[7]

Until now, the recommended approach to managing HBV infection has involved the use of monotherapy, which is associated with a high risk of developing drug resistance. It has been recommended that patients should be closely monitored for virologic and biochemical response every 3-6 months. When viral breakthrough occurs, the mutant virus replicates, and its titer increases; this is then followed by an increase in aminotransferase levels (biochemical breakthrough) and histopathologic changes on liver biopsy.[2,7]

Strategies for the Management of Drug-Resistant HBV Infection Close follow-up allows for early detection of viral breakthrough and implementation of appropriate management strategies (Table 7) before the patient develops biochemical breakthrough and histopathologic deterioration.[1,2,7]

Table 7. Potential Management of HBV Antiviral Drug Resistance[1,2,7]

Resistance to HBV Antivirals Strategy
Lamivudine Add adefovir or tenofovir**or switch to tenofovir/emtricitabine**
Adefovir Add lamivudine or telbivudine or add/switch to entecavir if not prior
lamivudine resistance or switch to tenofovir/emtricitabine**
Telbivudine Add adefovir or tenofovir** or switch to tenofovir/emtricitabine**
Entecavir Switch to or add adefovir or tenofovir** Switch to
emtricitabine/tenofovir**

**Not currently approved by US FDA
Continued Management (2008)
Since mid-2003, the patient has been on lamivudine 100 mg daily in combination with adefovir 10 mg daily. His current laboratory values are as follows:

ALT: 28 IU/L
AST: 32 IU/L
HBV DNA: < 29 IU/mL
HBsAg: positive
HBsAb: negative
HBeAg: negative
HBeAb: positive.
Platelets: 189 x 103/mm3
AFP: 5 ng/mL
Total bilirubin: 1.1 mg/dL
Albumin: 4.8 g/dL.
Cholesterol: 161 mg/dL
Serum triglycerides: 136 mg/dL
High-density lipoprotein: 57 mg/dL
Low-density lipoprotein: 77 mg/dL
Glycosylated hemoglobin: 6.6%

Long-term Management Plan
The patient continues his clinic visits for follow-up of his HBV infection at 6-month intervals, during which time he undergoes laboratory work-up to assess his liver enzyme levels and serum HBV DNA. He undergoes biannual screening for hepatocellular carcinoma mainly with ultrasound examination. Serum AFP as a single test for hepatocellular carcinoma has lost favor, although it is commonly done in conjunction with an ultrasound of the liver.[8-10]

Conclusion
When screening, diagnosing, and managing hepatitis B infection, clinicians should always consider the "rule of 3's":

3 tests to screen: HBcAb, HBsAg, HBsAb


3 tests to diagnose: HBeAg, HBeAb, HBV DNA


3 findings to contemplate therapy:


HBsAg positivity and


HBV DNA ™ 2000 IU/mL (if HBeAg negative) or ™ 20,000 IU/mL (if HBeAg positive), and


Elevated ALT or normal ALT and a liver biopsy showing chronic active hepatitis


3 findings indicating when to stop treatment of oral antivirals: HBV DNA undetectable, HBsAg-negative, and HBsAb-positive (the stopping rules apply for all types of HBV, and they are rarely achievable) Patients with chronic hepatitis B, in any of the various phases of the infection, require close observation and frequent testing to initiate treatment and to monitor response to therapy. Failure to respond after the first 6 months of treatment (primary treatment failure), or virologic breakthrough after achieving initial response (secondary treatment failure), requires adding another agent to the initial therapy or switching therapies. Lamivudine resistance is very common, and patients who continue to use lamivudine should be closely monitored to detect any genotypic mutations. They should be managed by adding either adefovir or tenofovir** before they develop biochemical breakthrough and lose the histopathologic improvement that they gained from previous therapy. Currently, lamivudine is no longer recommended as initial therapy due to the high rate of resistance. The oral antiviral drugs with a high genetic barrier to resistance and/or high potency (eg, entecavir or tenofovir) are generally recommended as initial treatment.[1,2] The current strategy for managing the development of resistance to any monotherapy involves adding a second drug that is not cross-resistant with the first (eg, adding a nucleotide drug when resistance to a nucleoside agent is detected, and vice versa; Table 7).

[cajim]

Patients chronically infected with HBV do not always remain in the same phase of infection. The interaction between the virus and the immune system of the patient affect viral replication, the extent of liver injury, and the patient's symptomatology. Over the lifetime of the infection, patients who perinatally acquired HBV can present with one of 4 main phases of infection (Table 4).[3] Early in the course of infection, when the patient is still an infant, the immune system does not mount a reaction against the viral infection. During that time, the patient is considered to be in the immune-tolerant phase, which can last for decades. However, some patients develop fluctuations in their serum aminotransferases, usually associated with active inflammation on liver biopsy. This phase is considered the HBeAg-positive phase and is characterized by HBeAg positivity. Although HBV DNA levels fluctuate, they remain significantly elevated and is associated with elevated aminotransferases. In this phase, there is immune-mediated lysis of the HBV-infected hepatocytes. In most patients this phase precedes another phase in which HBeAg loss occurs and HBeAb develops (seroconversion). As patients move out of this phase, they may progress to the inactive carrier state or the HBeAg-negative state. The inactive carrier state is characterized by HBeAg negativity, low viral titer or HBV DNA negativity, normal aminotransferases, and the absence of active inflammation on liver biopsy. The HBeAg-negative state is characterized by HBeAg loss, but viral replication continues, albeit at a lower level than it was in the HBeAg-positive phase of infection. This phase is also associated with elevated aminotransferases and active inflammation on liver biopsy. Although patients may remain in one phase for the life of the infection, movement across phases is more common. It is rare that a patient spontaneously loses HBsAg (seroclearance) and develops HBsAb. These patients have undetectable HBV DNA, normal liver enzymes, and no active inflammation on liver biopsy.[3]

Table 4. Phases of Chronic Hepatitis B[3]

Phases Laboratory Findings
Immune tolerant HBsAg (+); HBeAg (+);HBV DNA> 20,000 IU/mL; normal ALT
HBeAg-positive HBsAg (+); HBeAg (+); HBV DNA> 20,000 IU/mL; elevated ALT
Inactive carrier HBsAg (+); HBeAg (-); HBV DNA (-) or  2000 IU/mL; elevated ALT


Diagnosis
The patient was diagnosed with chronic active hepatitis B infection (HBsAg positive> 6 months); phase: HBeAg negative with high viral replication (HBV DNA> 2000 IU/mL and elevated ALT [130 IU/L]).

Treatment
In some patients, chronic HBV infection can lead to chronic progressive hepatitis, fibrosis, and cirrhosis. Patients who develop cirrhosis are at high risk for liver decompensation and death. In addition, chronic HBV infection is the main cause of liver cancer worldwide.[4] Chronically infected patients could develop hepatocellular carcinoma even in the absence of liver fibrosis or cirrhosis. Treatment of HBV infection is essential and involves either boosting the immune system through the use of immune modulators or using oral antiviral agents to suppress viral replication and allow the immune system to control further viral replication when therapy ends. The more commonly applied therapeutic approach is oral antiviral therapy to suppress viral replication and decrease or eliminate the chronic inflammatory process in the liver. This normalizes aminotransferases, regresses fibrosis, and possibly decreases the risk of developing hepatocellular carcinoma. Some patients require long-term treatment with the oral antiviral agents.[4] The FDA has approved a number of medications for patients with chronic actively replicating hepatitis B virus who present with increased aminotransferase levels and/or histopathologic hepatitis (Table 5). These include interferon alfa-2b, pegylated interferon alfa-2a, and the oral antiviral agents lamivudine (nucleoside analog), adefovir (nucleotide analog), entecavir (nucleoside analog), and telbivudine (nucleoside analog).

Table 5. Therapies for Hepatitis B

Therapy Comments
Interferon alfa-2b
(daily or 3-times-weekly injection) Immune modulator
Pegylated interferon alfa-2a
(once-weekly injection) Immune modulator
Lamivudine First nucleoside analog used in the treatment of HBV; not
recommended as initial therapy due to high risk for resistance
Adefovir, entecavir, telbivudine* First-line viral suppressors
Tenofovir** Under FDA review for likely approval in 2008; first-line therapy
following licensure (will likely replace adefovir)
Emtricitabine**, clevudine** In clinical trials

*Alternative option
**The US Food and Drug Administration has not approved this medication for
this use.
Our patient had 3 of the major criteria for therapy (Table 6). He is
HBsAg-positive and HBeAg-negative, with high viral replication and elevated
serum ALT. Therefore, he was a candidate for antiviral therapy.

Table 6. Whom to Treat (3 Criteria)

HBsAg positive
HBV DNA> 2000 IU/mL
Elevated serum ALT or normal ALT and chronic active hepatitis on liver biopsy

The patient was started on lamivudine 100 mg/day (standard treatment in 2002)[5] and was encouraged to stop smoking and to minimize his alcohol intake. He was advised to adhere to a diabetic diet and continued treatment for his diabetes (glipizide).

3-Month Follow-up Visit
At 3 months, the patient had no complaints, was feeling well, and reported that his energy had improved. His HBV DNA level was < 50 IU/mL and his serum ALT and AST levels were 34 IU/L and 23 IU/L, respectively.

6-Month Follow-up Visit
At 6 months, the patient returned for evaluation. He continued to feel well and had no symptoms. His HBV DNA level was still < 50 IU/mL, and he was HBeAg-negative and HBeAb-positive. His serum ALT and AST were 18 IU/L and 20 IU/L, respectively.

12-Month Follow-up Visit
At 12 months, the patient was doing well, but was diagnosed with the metabolic syndrome (hypertension, hyperlipidemia, and diabetes mellitus). His primary care provider started him on lisinopril, ezetimibe, and gemfibrozil.

[cajim]

Notes on “Strategies in the Management of Chronic Hepatitis B  CME,” Deanna L. Oliver, BS   Tarek Hassanein, MD, FACP, FACG, Hepatitis B: Advances in Screening, Diagnosis, and Clinical Management -- Volume 2, 2008.

History of Present Illness

A 32-year-old Korean-American man who worked as a software engineer came to the clinic in July 2002 complaining of fatigue, low energy, and right upper quadrant discomfort. The discomfort was dull in character and radiated to the back. He denied nausea, vomiting, and diarrhea. He reported weight loss of 30 pounds in 8 months. He also complained of polyuria, polydipsia, and dry mouth. The patient was diagnosed 1 year ago with non-insulin-dependent diabetes mellitus and was being treated with glipizide. However, he was not adherent to his therapy. He admitted to smoking a pack of cigarettes per day and to regularly drinking alcoholic beverages. His family history was significant for hepatitis B infection in one brother and diabetes mellitus in both parents. His physical examination showed no peripheral signs of chronic liver disease and no hepatomegaly, splenomegaly, or ascites.

Hepatitis B virus (HBV) is highly endemic in areas such as Southeast Asia and Africa, and individuals from regions with high or intermediate prevalence of HBV should be offered screening.[1] Other populations who would benefit from screening include individuals of Asian descent and close contacts of HBV-infected individuals.[1]

This patient was an Asian American who had a family history of hepatitis B. Accordingly, he should be screened for HBV infection. The standard serologic markers used to screen for HBV include hepatitis B core antibody (anti-HBc), hepatitis B surface antigen (HBsAg), and hepatitis B surface antibody (HBsAb). See Table 1.[1,2] HBcAb positivity indicates prior exposure and infection with HBV; HBcAb-IgG class indicates previous exposure, whereas the HBcAb-IgM class defines acute infection or viral reactivation and should be screened for in patients with jaundice and signs of acute hepatitis. The presence of HBsAg positivity for more than 6 months defines chronic infection, whereas HBsAb indicates immunity.

Table 1. Screening for Hepatitis B Infection

3 tests:
   Hepatitis B core antibody (IgG HBcAb)
   Hepatitis B surface antigen (HBsAg)
   Hepatitis B surface antibody (HBsAb)


Initial Evaluation
The patient underwent the following laboratory investigations:

Complete blood count (CBC) with differential and coagulation parameters

Comprehensive metabolic panel, gamma-glutamyl transferase (GGT), total protein, uric acid, iron, iron binding capacity, ferritin, lipid panel, thyroid-stimulating hormone (TSH), alpha-fetoprotein (AFP), and glycosylated hemoglobin

Viral serologies

Hepatitis B virus (HBcAb, HBsAg, HBsAb)

Others: hepatitis A virus antibody (HAV Ab), hepatitis C virus antibody (HCV Ab), HIV Ab

Autoantibodies: Antinuclear antibodies (ANA), and anti-smooth muscle antibody (ASMA)
The patient also underwent ultrasound examination of the abdomen and liver.

Results of key initial laboratory investigations are shown in Table 2.

Table 2. Results of Initial Laboratory Investigations

Test Comment
Serologies
HBcAb: positive
HBsAg: positive
HBsAb: negative Indicates patient has chronic hepatitis B infection
CBC
WBC: 5.8 103/mm3
Hemoglobin: 14.5 g/dL
Platelets: 154 x 103/mm3 Low platelet count

Chemistries
Alanine aminotransferase (ALT): 154 IU/L
Aspartate aminotransferase (AST): 261 IU/L
Alkaline phosphatase: 85 IU/L
Glucose: 198 mg/dL
AFP: 11 ng/mL
Total bilirubin: 1.1 mg/dL
Creatinine: 0.8 mg/dL
Total protein: 7.0 g/dL
Albumin 4.7 g/dL
Globulin: 2.3
ANA: negative
ASMA: negative Indicates active liver inflammation (ALT/AST high), normal synthetic liver functions (albumin, total bilirubin normal), diabetes (fasting glucose), no renal dysfunction (normal creatinine), and no autoimmune hepatitis (negative ANA and ASMA)
Ultrasound
Liver measured 14.4 cm by long axis; echogenicity was within normal limits; spleen was normal in size; no ascites Indicates no signs of portal hypertension

Follow-up Visit
The patient returned for his first follow-up visit 4 weeks later. At this time, he was diagnosed with chronic hepatitis B infection in addition to his diabetes mellitus type 2.

Additional serologic and virologic work-up was ordered to fully characterize the status/type of chronic active hepatitis B. Specifically, the patient was tested for hepatitis B e antigen (HBeAg), hepatitis B e antibody (HBeAb), and antibody to hepatitis D virus (HDV Ab), and viral load (HBV DNA) was determined. In addition, glycosylated hemoglobin was measured. See Table 3.

Table 3. Additional Tests for Characterizing Status of Chronic Hepatitis B Infection

3 tests:
   HBeAg
   HBeAb
   HBV DNA

Patients with chronic hepatitis B infection (HBsAg -positive) present in different immune stages. The presence of HBeAg and HBeAb, while the virus is replicating at high levels (HBV-DNA> 104 or 105 IU/mL) in the presence of elevated ALT due to viral-induced hepatitis, are the benchmarks for considering antiviral therapy. Accordingly, any patient with HBsAg positivity should be further classified according to their HBeAg, HBeAb, and HBV DNA titer (Table 4).[3] In addition, any patient with chronic hepatitis B infection should be screened for HDV infection as well, as it might modify the therapy of an HBV-infected patient.

Results of these additional laboratory investigations revealed the following:

HBeAg: negative; HBeAb: positive; HBV DNA: positive; 7.5 million copies/mL (1.5 million IU/mL)

HDV Ab: negative

Glycosylated hemoglobin: 5.3%

ALT: 130 IU/L; AST: 199 IU/L

[cajim]

Notes on “The case for combination antiviral therapy for chronic hepatitis B virus infection,” Kathryn L Nash, THE LANCET INFECTIOUS DISEASES, Volume 8, Issue 7, July 2008, Pages 444-448

Summary:  The treatment of hepatitis B virus (HBV) infection has been revolutionised in the past decade by the increased availability of effective antiviral agents. Many studies have shown the benefits of single agent therapy, but there is an alarming and rising rate of viral resistance, and clear evidence that viruses that harbour resistant mutations can cause liver disease and death. Current national guidelines for the treatment of HBV recommend a programme that starts with monotherapy, followed by sequential monotherapy or add-on therapy for those infections in which mutations have arisen. Very few studies starting with combination therapy have been undertaken, so there is little evidence of the clinical benefit of this approach to treatment. The studies that have been done have been short term and have concentrated on clinical parameters rather than virological resistance, which is likely to be the key determinant in the longer term. We argue that we should not wait for the evidence to use combination therapy for the treatment of HBV, since such trials may never be done and it would take several years for a benefit to become apparent. In the meantime, multidrug-resistant strains continue to hinder HBV control.

[cajim]

Notes on “Hepatitis B Patients Face Broad Discrimination in China. Ostracized and unable to secure jobs, victims turn to a support web site, now banned by the communist regime.” Wu Xue'er, Epoch Times Staff Jul 04, 2008

Yirenping Center General Coordinator Lu Jun speaks in Hong Kong on the government's interference with the forum. (Wu Xue'Er/The Epoch Times)  HONG KONG—Having passed a civil service exam, a Zhejiang University graduate was subsequently rejected when he was found to have hepatitis B. In a fury, he killed the recruiting official.  It was 2003, and he had graduated from one of China's finest schools. The court found him guilty of murder and handed down the death penalty. He tore the court document stating his sentence into pieces.  A Ph.D. from Xiamen University was unable to secure a job when he was found to be a carrier of hepatitis B. He ended his life by hanging himself in a bathroom.  Many such tragedies occur in China every year, according to Lu Jun, coordinator of the Yirenping Center in Beijing and host of the "Liver and Gallbladder Care" Web site.  Hepatitis B patients face serious discrimination in China. Lu says that such discrimination leads directly to hatred, social exclusion, and tragedies such as these. People with hepatitis B have difficulty finding employment or attending school.  Eighty percent of foreign companies with branches in China also refuse to hire people with hepatitis B.  It is estimated that approximately 100 million people in China carry the hepatitis B virus. Since 2003, many have connected through the "Liver and Gallbladder Care Forum" (bbs.hbvhbv.com).  The forum has become a home for hepatitis B patients who seek information and basic human rights. It enables them to fight discrimination, including organizing anti-discrimination lawsuits against government agencies.  Instead of supporting the forum, however, Lu says that the Chinese communist regime has responded by suppressing and banning it. This has led to much anger and disappointment among those affected.  Lu identifies three factors that have contributed to the widespread discrimination against hepatitis B patients.  First, a lack of government regulation of advertising practices used by pharmaceutical companies resulted in exaggerated claims of the infectious nature of hepatitis B. Though their intention was to increase sales, their tactics led the public to fear and misunderstand the disease.  Second, the government process for hiring civil service employees included screening for hepatitis B beginning in 1997. Many private enterprises followed suit, rejecting hepatitis B patients from employment.  Third, laws have been passed banning hepatitis patients in China from holding certain jobs, including janitor, elevator operator, cashier, schoolteacher, and all jobs in the food industry. These laws, over 20 in number, have deprived hepatitis B patients of their basic rights.