Lecture of Chronic Viral Hepatitis

2021-03-23 12:00 AM

Hepatitis B viruses, hepatitis C and hepatitis caused by HBV and HDV are viruses that easily progress to chronic hepatitis, there is no other virus excluded.

Chronic hepatitis is one of the most common forms of liver disease caused by many causes with inflammation and necrosis of the liver lasting at least 6 months. Chronic hepatitis is usually the result of acute hepatitis, but in many cases, the disease progresses silently and manifests itself only in the chronic stage. Progression of chronic hepatitis is reversible, but severe cases often lead to cirrhosis and hepatocellular cancer. Chronic viral hepatitis is also a type of chronic hepatitis, with many similarities to chronic hepatitis in general.

Classification of chronic hepatitis

Sort by cause

Chronic viral hepatitis: The hepatitis B virus (HBV), hepatitis C (HCV) and HBV + HDV hepatitis are viruses that easily progress to chronic hepatitis (no other virus is excluded).

Chronic autoimmune hepatitis: Based on serum diagnosis, people classify types 1, 2, 3.

Chronic drug-induced hepatitis and intoxication (Of particular note is chronic alcoholic hepatitis)

Chronic hepatitis of unknown origin or latent hepatitis.

Sorted by degree

Based on the evaluation of histopathology through liver biopsy ie based on the degree of inflammation and necrosis. The mildest is portal inflammation, more severe inflammation that invades both the liver lobule (infiltrates the inflammatory cells) and the surrounding necrosis (termite necrosis). The most severe is necrosis from the portal space to the central vein forming bridges (bridging necrosis). To be able to evaluate in more detail, people use the Histologic Activity Index (HAI) by Knodell-Ishak by scoring.

Histological Activity Index (HAI)

 (Knodell - Ishak scoring system) for chronic hepatitis

Image of diseased tissue



1. Deaths around the door

- Not at all

- Light termite-type necrosis

- Termites gnaw medium

- Termites chew heavily

- Moderate termites + Bridge-style necrosis

- Severe termites + Bridge

- Necrosis many minor lobes








2. Necrosis in the minor spleen

- Not at all

- Light

- Fit

- Heavy





3. Inflammation of the portal space

- Not at all

- Light

- Fit

- Heavy





4. Fiber

- Not at all

- Extend the doorway

- The fiber bridge around the door

- Clear cirrhosis of the liver





Maximum number of points



Based on TWO one can divide chronic hepatitis into the following levels:



Term used

1 – 3

Chronic hepatitis is very mild

Nonspecific reactive hepatitis, chronic primary spleen hepatitis, and chronic hepatitis exist

4 – 8

Mild chronic hepatitis

Chronic sub-spleen hepatitis, persistent chronic hepatitis, active chronic hepatitis.

9 - 12

Moderate chronic hepatitis

Moderate-acting chronic hepatitis

13- 18

Severe chronic hepatitis

Severe chronic hepatitis with bridge necrosis

Sort by stage

The stage of chronic hepatitis is a reflection of the progression of the disease. This rate of progression is based on the degree of fibrosis.

Score system according to Scheuer PJ

Fibre damage


- No fiber

- Light fibers (wide opening, fibrosis)

- Medium fibers (around door fiber bridges, door-door fibers)

- Severe fibrosis (fibrosis causes slight structural changes but the cirrhosis is unclear)

- Clear cirrhosis of the liver






Classification of chronic hepatitis used in clinical practice

Based on histological lesions and disease progression, chronic hepatitis is divided into the following categories (from mild to severe): persistent chronic hepatitis, chronic small-type hepatitis and active chronic hepatitis.

Chronic persistent hepatitis

Features of histopathological damage: Inflammatory cell infiltrates are only localized in the portal space, not invading the hepatic lobule. There is no rodent necrosis or bridge necrosis, but mild fibrosis around the portal space may be present. Imaging of the regeneration of liver cells is common.

Clinical manifestations of chronic hepatitis exist: Very faint, with few symptoms and usually mild symptoms (fatigue, anorexia, nausea). The condition of chronic hepatitis is almost normal. Examination shows only enlarged liver, but rarely shows other symptoms of chronic hepatitis. The transaminase enzyme increased slightly.

Progression of chronic hepatitis exists: Usually progresses slowly, decreases gradually and can be cured. rarely, persistent chronic hepatitis progresses to active chronic hepatitis or cirrhosis (except for chronic hepatitis that exists due to the hepatitis virus).

In terms of degree: Chronic hepatitis is the mildest chronic hepatitis.

Chronic lobular hepatitis

It can also be said that chronic lobe hepatitis is a form of chronic hepatitis that exists. Previously, the authors divided chronic hepatitis into two types (persistent chronic hepatitis and attacking chronic hepatitis). That means that chronic sub-lobe hepatitis is classified as existing chronic hepatitis.

In terms of histological damage: In addition to inflammatory infiltrates in the portal space, inflammation also spreads into the liver lobules. In the liver lobules can see necrosis near mild hepatitis. Limit intact lobules. There may be slight fibrosis around the portal space.

Clinically: Chronic lobe hepatitis shows more symptoms than persistent chronic hepatitis, sometimes with an outbreak resembling acute hepatitis. Transaminase enzyme increased moderately. In general, the clinical and subclinical manifestations are similar.

Progression of chronic lobular hepatitis: Similar to chronic hepatitis, that translates to active chronic hepatitis and cirrhosis is rare (except due to viral causes).

Grade: Chronic lobe hepatitis is a mild or moderate chronic hepatitis.

Chronic active hepatitis

Histological damage characteristics of active chronic hepatitis: A dense infiltration of portal mononuclear cells and invasion of the hepatic lobule (in chronic, free-radical hepatitis there are many invasive plasmocytes). Termite necrosis and bridging necrosis and the regeneration of clusters of cells that form false lobules or invert the lobules as the fibrous organization thrives. Regarding the histological criteria of active chronic hepatitis at least there must be termite necrosis. Bridging necrosis can be seen in acute hepatitis but in active chronic streptococcal necrosis is a manifestation of progression to cirrhosis because the bridging necrosis areas develop into fibrous bridges that separate the lobules. the liver forms neoplastic clots (nodules) and develops to cirrhosis of the liver.

Clinically: Most tend to have symptoms (although there is also a certain proportion of asymptomatic). Common symptoms are fatigue, increased transaminase enzyme levels, jaundice.

Regarding the progression of active chronic hepatitis: in cases where only termite necrosis is involved, the likelihood of leading to cirrhosis is difficult to determine, but in cases of bridging necrosis, most lead to cirrhosis.

Chronic viral hepatitis

It is almost only the hepatitis B virus (HBV), the hepatitis C virus (HCV) and the hepatitis D virus (HDV) that causes chronic hepatitis.

Chronic hepatitis B virus (HBV)

The likelihood of progression to chronic hepatitis B following hepatitis B virus infection varies with age. Babies infected with hepatitis B virus after birth usually have no symptoms, but 90-95% will become chronic carriers. Adults and adults infected with hepatitis B virus often have obvious clinical manifestations of acute hepatitis, but the risk of chronic wall is only about 10%. However, chronic hepatitis B can develop in patients who do not have acute hepatitis B.

Levels of chronic hepatitis B: Vary from mild to severe. Evaluation of chronic hepatitis B is also based on histopathology, but more importantly, by the degree of hepatitis B virus (HBV) replication. During the strong replication phase of HBV (HBeAg +, HBV- DNA +, HBcAg + in hepatocytes) the severity is more severe. In contrast, during the non-replicating phase of HBV (HBeAg -, anti-HBe +, HBcAg- in hepatocytes), there is mild chronic hepatitis B or just asymptomatic HBV carrier.

Progression: Chronic HBV infection, especially from birth, increases the risk of hepatocellular cancer. Active chronic hepatitis B is more likely to progress to cirrhosis and hepatocellular cancer (HCC).  

Chronic hepatitis C virus

It is a silent chronic hepatitis, in many cases there are no symptoms and even the enzyme transaminase is normal. Diagnosis of these cases is mainly based on liver biopsy. The progression of HCV infection is shown in the following diagram:

Clinical manifestations: Chronic hepatitis C is similar to that of chronic hepatitis B, but in general the symptoms are faint, jaundice is rare, there is less damage to the liver, and the enzyme transaminase is lower and fluctuating. The most common symptom is fatigue. Serological tests in some cases can show the presence of Anti-LKM-1 antibodies as in Type 2 autoimmune hepatitis patients.

Progression: 50-80% of cases of chronic hepatitis C develop after acute hepatitis C, progress to cirrhosis after 10 years is 15-20%. Approximately 50% of patients with chronic hepatitis C will develop cirrhosis of the liver including patients with asymptomatic chronic hepatitis C and without an elevated transaminase enzyme. But it is worth noting that patients with high concentrations of HCV-RNA and long duration of HCV infection. Chronic hepatitis C progresses to cirrhosis and hepatocellular cancer, but usually very slowly after a few decades.

Chronic Hepatitis D (Delta Virus Chronic Hepatitis)

Both the hepatitis D virus (HDV) co-infection with hepatitis B virus (HBV) or HDV superinfection in HBV patients can lead to chronic hepatitis. But when co-infection often aggravates acute hepatitis and easily turns into malignant hepatitis, HDV superinfection in chronic HBsAg carriers increases the likelihood of progression to chronic hepatitis.

The clinical manifestations of chronic hepatitis D or chronic hepatitis B are indistinguishable or otherwise, that chronic hepatitis D also has the same clinical manifestations as chronic hepatitis B.

The serological feature of chronic hepatitis D is the presence of anti-LKM antibodies (Liver Kidney Microsomes - anti-microsome antibodies of liver and kidney) circulating in the blood. Anti-LKM-3 anti-LKM-3 in chronic hepatitis D is different from anti-LKM-1 found in patients with autoimmune chronic hepatitis and chronic hepatitis C.

Treatment of chronic viral hepatitis

For persistent hepatitis and chronic minor hepatitis: If you are properly rested and with proper nutrition, most often come to a complete cure (except for a viral cause).

Therefore, when it comes to drugs to treat chronic hepatitis, it is primarily for aggressive chronic hepatitis.

The main classes of drugs used in the treatment of chronic hepatitis are:

Drugs affect the immune status

Immunosuppressants: Corticoids.

Immunomodulatory drugs: Levamisole.

Immunostimulant drugs: Thymogen, Thymodulin (Thymocom) ...

Antiviral drugs

Lamivudin, Adefovir, Entecavir, Ribavirin...

Interferon-alpha (IFN α) and stimulant to produce IFN α

Medicines of plant origin (herbal)

Treatment of chronic hepatitis caused by HBV

The highest target in the treatment of chronic hepatitis caused by HBV

Eliminate the virus from the body (HBsAg and HBV-DNA negative in the blood).

Repair liver damage.

Clinical symptoms and tests returned to normal.

However, up to now, treatment for chronic viral hepatitis in general and HBV, in particular, is still a problem. Interferon and antiviral drugs have brought positive results, but their effectiveness is not more than 50%. Most studies have found that the longer the time to take the drug, the higher the cure rate will be. If using the drug for a short time, the cure rate is low and recurrence after stopping the drug increases.

Goals to achieve in treatment

Reduces or stops the development and multiplication of HBV. With this goal, after treatment, the HBsAg and HBV-DNA levels decrease in the blood, seroconversion (HBeAg from positive to negative and Anti HBe appears) ... is evaluated as progressive. Good treatment development.

All clinical symptoms, biochemical tests were normal.

Reduce inflammatory processes in the liver, prevent liver cell necrosis, prevent progression to fibrosis and cancer.

Interferon (IFN) alpha

Interferon a of America (Schering Plow, trade name Intron A) is IFN a 2b, 3 million vials and 5 million UI.

Interferon an of France (company Roche, trade name Roferon) is IFN a 2a, a bottle of 3 million and 4.5 million UI.

Indications for the treatment of patients with chronic aggressive hepatitis with elevated transaminases, low HBV-DNA and short duration of illness (<1.5 years). These cases often give better treatment results.

Dose and duration of treatment: Minimum 3 million UI / day to 10 million UI / day, intramuscular or subcutaneous daily or 3 times / week (every other day). Duration of treatment is at least 4 months.

Undesirable effects (side effects): Fever, "fake flu" syndrome, bone marrow suppression (mild), hair loss, rash, pruritus, diarrhea, possibly autoimmune thyroiditis (rare). .. Side effects disappear rapidly after stopping the drug. The drug must be stored regularly at a temperature of 2-80C and the current price is very expensive. Currently, in order to limit the side effects of IFN, slow-release IFNs (Pegintron A, Pegasis) and endogenous IFN-inducers (Cyclferon - produced by Russia) have been produced.


The main ingredients are Acridon acetic acid and N-Methylglucamin.

After 4 hours of Cycloferon treatment, the concentration of IFN (mainly IFNa and IFNb) increased in serum, peaked after 18 hours and ceased effect after 48 hours. The high concentration of IFN concentrates in the spleen, lung, liver, muscle, and bone.

Well tolerated, safe, and equivalent in effect to IFNa treatment


Lamivudine is a nucleoside analogue with antiviral activity due to inhibition of reverse transcription enzymes, thus inhibiting HBV-DNA synthesis. Lamivudine is used in the treatment of chronic hepatitis caused by HBV and in the treatment of HIV / AIDS infection. The drug is rapidly absorbed, well-tolerated and has few side effects. The drug quickly reduces the concentration of HBV-DNA, causing HBeAg, enzyme transaminase to return to normal. In cases where there is a Polymerase gene mutation of HBV (called YMDD mutation), treatment with Lamivudine continues to be effective.

Dosage: 100 mg tablet, 1 tablet/day, daily for at least 1 year. There have been studies showing that longer treatment (two, three years) works better. Some patients have been treated for 4 years, the drug is still well tolerated.

Adefovir, Entecavir

Is a nucleoside analogue, good for patients with chronic hepatitis B already resistant to lamivudine.    

Medicines of plant origin

Currently, there are many drugs of plant origin being used in the treatment of acute and chronic hepatitis caused by HBV. However, to prove that these drugs are effective in the treatment of chronic HBV hepatitis need to be seriously studied, with a larger number of patients. Some of the drugs used by Chinese and Vietnamese authors are:

Phyllantus (Phyllantin ...): Extracted from bitter Diệp Hạ Châu or Serrated Dog (scientific name: Phyllantus amarus schum).

Haina: Derived from the cucumber plant (Solanum Hainanese).

Combination therapy

IFN (or Cycloferon) + Lamivudine (dosage and usage for each drug as above).

IFN + Cycloferon.

IFN (as above) + Immunostimulating drugs (Thymocom, Thymomodulin ...) 80 mg x 1-2 tablets / day x 6-12 months.

Corticoid for 6 weeks (Prednisolon: 60 mg/day x 2 weeks, then reduce to 40 mg/day x 2 weeks and then 20 mg/day x last 2 weeks), followed by IFN (dosage and usage as above): results of the IFN increase.

Treatment of chronic hepatitis caused by HDV

High dose IFN: 9 million UI / day x 3 times/week. Less effective and easy to relapse when stopping the drug.

Treatment of chronic hepatitis caused by HCV

IFN is more effective, dose 2-5 million UI / day x 3 times / week x 6 months.

IFN (or Cycloferon) + Antiviral drugs (Ribavirin, 200mg tablet x 5-6 tablets / day x 1 year).