Lecture of Fulminant Hepatitis

2021-03-23 12:00 AM

The pathogenesis of diffuse hepatic necrosis is associated with lipid redox, the Lysosome proteolytic enzymes, the immunological state, and the autoimmune process.

Define

Malignant viral hepatitis (or the malignant form of viral hepatitis) is the most severe form of acute viral hepatitis. This can be called a complication of acute viral hepatitis (according to Harrison), because liver cells are massively necrotic, leading to severe liver failure. So most cases lead to brain-liver syndrome and death.

Nomenclature

The noun malignant hepatitis is called by many authors with different names such as: Acute liver dystrophy, acute liver necrosis, widespread liver necrosis, liver gangrene. The widely used noun is Hepatodystrophia proposed by Herxheimer G. (1924) to refer to massive hepatic necrosis and degenerative necrosis. Since the disease is usually acute and most often fatal, many authors refer to it as fulminant hepatitis. Nhixevich NI and Utraikin VF (1982) found that all the above nouns do not fully generalize the pathological properties of the disease, but each noun represents only one side of the pathological process. Therefore, the authors have come up with the noun malignant viral hepatitis which is a noun that fully expresses the pathological properties of this form in viral hepatitis.

Mechanism of pathogenesis

The pathogenesis of acute and subacute diffuse hepatic necrosis of the malignant form in viral hepatitis is complex and has not been fully studied. It is divided into the process of destroying liver cells into 2 phases: biochemical stage and the body stage.

The biochemical stage (also known as the pre-body phase)

It is manifested by an increase in cell membrane permeability and thereby introduce into the blood bioactive substances, and first of all enzymes. In patients with viral hepatitis, the increase in membrane permeability is explained by an increase in lipid redox and a sudden decrease in the oxidation of the cell membrane.

Bodybuilding stage

Liver cells are destroyed. An important role in the destruction of liver cells are Lysosome enzymes.

Nhixevich NI said that: The pathogenesis of diffuse liver necrosis is related to lipid redox, Lysosome proteolytic enzymes, the immune state and the autoimmune process.

Many authors have demonstrated that lipid redox plays an important role in viral hepatitis (Forney SR; Lynn WS1964; Raubal WT; Tappel AL1966; Nhixevich NI1982 ...). Cell necrosis is primarily the disruption of the cell membrane, of which the membrane is made up of mainly Lipoprotein. Thus, modifications of Lipoprotein will cause direct damage to the cell membrane. In the acute phase of viral hepatitis a marked increase in lipid redox (oxidation of lipid free radicals) is observed and the degree of lipid redox is related to the severity of the disease. In patients with severe and malignant viral hepatitis, the reoxidation of lipid free radicals is highly increased, due to the effect of the hepatitis virus on the cell membranes to produce free radicals.

The multiplicative lipid redox (redox of lipid free radicals) has resulted in structural changes in the lipid components of the cell membranes due to the formation of hydroperoxide groups and the creation of holes of the biofilm. Therefore, increasing permeability leads to the movement of biologically active substances according to concentration gradien. The released intracellular enzymes, especially those of Lysosomes (Ribonuclease, Desoxyribonuclease, Catepsin ...) together with a decrease in the activity of protein hydrolysis inhibitors ( a 2- Macro globulin, a1- Antitrypsin ...) will damage liver cells. The protein components of necrotic liver cells will act as antigens and the body produces antibodies against it, which will continue to attack other liver cells. Recently, many authors have discussed the role of impaired cellular immunity (decreased T lymphocyte function) and increased autoimmune processes (increased B lymphocytes).

clinical

Divide the clinical form according to progression and prognosis

The clinical manifestations of viral hepatitis malignancy are diverse. The patient may develop pre-coma, coma or not. Coma is a predictive indicator. In patients without pre-coma or coma the prognosis is usually good. Malignant hepatitis in children is mostly comatose, so the prognosis is often worse than that of adults.

As the disease progresses: Malignant viral hepatitis can be very acute (extreme, lightning), acute, subacute, and even chronic:

Lightning strike

Coma occurs very quickly, before the symptoms of jaundice and usually on the 3-4 day of the illness and ends quickly with death.

Acute form

 Coma occurs in the general stage and usually on 5-8 days of jaundice.

Semi-level

Symptoms occur slowly after progression, leading to a coma, usually from 3 weeks to 5 weeks of illness. Especially when it progresses to post-necrotic cirrhosis, the later becomes coma.

Prognosis of malignant viral hepatitis

Depends on whether or not coma has occurred (brain-liver syndrome). In patients without coma, the prognosis usually resolves, whereas in patients with coma it often ends in death.

The main clinical symptoms of malignant viral hepatitis

Mental disorders

As a primary and early onset symptom in patients with malignant viral hepatitis. The first manifestation of psychosis is a state of excitation. The patient feels restless, uncomfortable, and does not lie still. The night was almost awake and could not sleep, even when taking sleeping pills, which was caused by damage to the subcutaneous centers (Gurebich ES1963).

An important symptom that has an important meaning in early diagnosis is an unstable, irritable, and disorientation of space and time. It is followed by acute psychosis and delirium accompanied by motor stimulation and then gradually goes into coma, hiccups and convulsions.

Vomit

 In patients with common viral hepatitis there may be vomiting in the early jaundice, but most likely vomiting in the jaundice. In patients with malignant viral hepatitis, vomiting persists throughout all stages of the disease. Initially, vomiting usually occurs when eating, drinking water or drugs, later on spontaneously vomiting and vomiting a coffee-colored discharge (bleeding from blood clotting disorders).

Bleeding syndrome

Bleeding due to decreased Prothrombin, Fibrinogen, vitamin K and damage to blood vessels due to toxicity. Many study authors have demonstrated that in the majority of patients with severe and malignant viral hepatitis, intravascular scattered coagulation syndrome develops. Patients may bleed under the skin, mucous membranes (nosebleeds, bleeding teeth), bleeding viscera (digestion, urinary ...).

Jaundice

Jaundice gradually increases to a point when the patient enters a coma. However, in some cases of early coma, especially lightning strike, very mild jaundice or no jaundice (die before jaundice).

The breath smells of fresh liver

 Many authors believe that this is a characteristic sign of acute liver necrosis. However, there are also many different ways of describing such as: Sweet aroma, the smell of boots, the smell of fresh liver ... In fact, in patients with lightning, acute and subacute malignancies Fresh liver odor, while patients with chronic form and coma due to end-stage cirrhosis have booty breath. In addition to breathing, fresh liver odor can also be found in the vomit, urine of malignant hepatitis patients.

Fever

 In patients with malignant hepatitis, the fever may persist from the onset, but often returns as the liver shrinks. Fever increases gradually to 400 ° C and constant fever. Fever does not decrease even with antipyretics.

Miniature liver size

 One of the hallmarks of patients with malignant viral hepatitis is that the size of the liver rapidly shrinks from 2-3 cm below the ribs to not palpable within 1-2 days with a poor systemic state. gradually. In the subacute form, the liver shrinks more slowly with increasing intoxication.

Pain in the liver

Pain in the right lower ribs is an early symptom seen in patients with malignant hepatitis. Sometimes severe pain such as in patients with gallstones or mistaken for acute appendicitis. The main cause of pain is necrosis and self-dissolution of the liver, but in addition, it is also due to damage to the bile ducts and pancreas.

Changes in the cardiovascular system

Meet in all patients with malignant viral hepatitis. Common symptoms are tachycardia, blood pressure tends to decrease, mainly the minimum blood pressure. During a coma may experience vascular collapse. Electrocardiogram often sees sinus tachycardia, low T waves, long QT interval and sometimes ST elevation. Changes in the cardiovascular system arise from disturbances in the central region.

Changes in the urinary system

The most common sign is oliguria in the early stages, and then progresses to anuria. When anuria occurs, the prognosis is very severe. Conversely, patients with polyuria, that is a sign of good prognosis. Along with the phenomenon of oliguria and anuria often accompanied by urea, blood creatinine increased. The cause of the changes in the kidneys are microcirculation disorders leading to decreased glomerular filtration. Some authors have also found that in patients with malignant hepatitis the amount of blood through the adrenal medulla is increased due to the tubular connection. Nhixevich NI found edema and damage to the renal tubular endothelium causing the renal tubules to narrow lumen and protein pillars. In addition, endocrine changes such as hyperaldosteronism cause water and salt retention.

Sea changes in the respiratory system

A common sign is difficulty breathing due to intoxication. In the coma stage of Kussmaul-style dyspnea, Cheyne-stokes, acute pulmonary edema occurs in rare cases.

Some variation in the test

CBC

Often seen anemia phenomenon. Thrombocytopenia can lead to thrombocytopenic purpura. Peripheral leukocytes tend to increase, especially during coma. The leukocyte formula turns left and the leukocytosis is increased.

Rate of blood sedimentation

A decrease is a threat sign of malignant hepatitis. Blood sedimentation rate is often one of the diagnostic indicators of malignant hepatitis, especially for lightning and acute forms (subacute and chronic may increase blood sedimentation rate due to superinfection process. ).

Bilirubin blood

 Increases rapidly and reaches a peak after 3 to 5 days, with especially free bilirubin (usually the same or sometimes the free bilirubin is higher than the combined bilirubin).

The rate of Prothrombin decreased

In patients with malignant viral hepatitis there is a marked disturbance of the coagulation system. Many authors believe that there is often scattered intravascular coagulation syndrome. As a result, almost all clotting factors are reduced. However, the rate of Prothrombin is the most obvious and early reduction index.

Gros reaction decreased

According to many authors, during biochemical changes the reduced Gros reaction has practical implications for the diagnosis of malignant hepatitis.

Active yeast

The activity of amino-converting enzymes (SGOT, SGPT) in the early stages increases, but in the pre-coma and coma stage, when the liver has shrunk, the activity of amino-converting enzymes suddenly decreases sharply. The rapid increase in serum bilirubin levels and a sudden decrease in amino-converting enzyme activity are important and almost always present in acute and subacute malignant hepatitis. Particularly for lightning type of malignant hepatitis, the patient died very soon before jaundice.

Electrolytes and acid-base equilibrium

In patients with malignant hepatitis often seen a decrease in blood Na +. K + can be decreased or increased, but in the red blood cells K + is always decreased. The composition of electrolytes in urine decreased. Blood pH changes to acidosis and the patient is in metabolic acidosis. However, in a deep coma, the metabolic acidosis can turn into metabolic alkalosis.

Lipid metabolism

Decreased composition b -Lipoprotein, Triglycerides, Cholesterol free and esters.

Implementing the quadrants

clinical

Except for the lightning strike that takes place very quickly, with no clinical manifestations, the patient dies before jaundice, while other forms are manifested in the following symptoms: Constant high fever, increasingly dark jaundice. and rapidly increasing, the patient is very tired, helpless, agitated, delirious and eventually lethargic. Continual hiccups, oliguria and anuria, rapidly shrinking liver, fresh liver odour, haemorrhage, bloating ...

Test

Often HBsAg (+), SGOT, SGPT decrease rapidly when entering coma; Bilirubin increased rapidly, the rate of Prothrombin decreased sharply. NH3 in patients with malignant hepatitis is often increased, but does not reflect the mild severity of the disease as in cirrhotic coma.

Differential diagnosis

Coma due to end-stage decompensated cirrhosis

The disease progresses slowly in patients with a long history of hepatobiliary disease or in patients with long-term alcohol abuse, exposure to toxic chemicals ... Coma but the liver is still large, blood bilirubin tests increase. but not maximized, ketone-smelling breath (booties), no fresh liver odor. NH3 is high in the blood, ultrasound of the liver will reveal ultrasound images.

Liver coma caused by end-stage liver cancer

 Disease progression also gradually. Liver is large, painful, lumpy to palpation, liver ultrasound is easy to detect.

Treatment

Treatment of malignant viral hepatitis, especially in comatose patients, is so far difficult and sometimes there are conflicting opinions because the mechanism of hepatic encephalopathy is still many points. It is very clear that more research is needed. It is also important to emphasize that the mechanism of encephalopathy in patients with malignant hepatitis and in patients with end-stage cirrhosis is different. Therefore, the treatment is not entirely the same.

Some of the treatments that apply to patients with malignant hepatitis are:

Correction of disturbances in water metabolism, electrolytes and acid base balance.

Inhibits protein breakdown.

Corticoid therapy.

Usage: Corticosteroids only work in the first 3-5 days in patients with malignant hepatitis. Therefore, the longest use is 7 days and with high doses (Depersolon 120-150 mg / 24 hours intravenous infusion).

The drug reduces free NH3

Ornicetil and L-Ornithine vials 2g and 5g.

Hepa-merz (L-Ornithine + L-Aspartate): ống 10ml = 5g.

L-DOPA (Desoxyphenylalanin).

L-Glutamine.

Intestinal antibiotics

Several other methods have been reported

Change blood.

Blood adsorption.

Cross-cycle.

Connected through liver congeners or heterotypes.

Hemodialysis and peritoneal dialysis.

Liver transplantation.

Summary: The above are the main directions that have been studied and applied to treat patients with malignant hepatitis. In fact, before a patient with malignant hepatitis, the physician needs to perform the following tasks:

Central venous catheterization (especially for children) to monitor fluid volume.

Infusion of Reopolyglukin or polymeric solutions, 5-10% glucose and ringerlactate at the rate of 3/1 and 100 ml / kg / 24 h.

Corticoid therapy: Depersolon 30 mg x 3 to 5 IV ampoules.

Put the stomach and anus sond. Enema and gastric lavage when bleeding occurs. Do not eat protein foods.

Antibiotics that kill intestinal bacteria: Take Ampicilin, Monomycin, Polymycin, or Biseptol.

Protein breakdown inhibitor infusion if available: Traxilol or Gordoc at a dose of 50-100000 UI / day or Contrical at a dose of 1/2 Traxilol.

Carboxylase infusion (50-100 mg), ATP, Ascorbic acid.

When there is bleeding: Vitamin K, Vicasol, Calcium gluconate ... If there are manifestations of scattered intravascular coagulation syndrome, causing bleeding, use Heparin 1-2 times / 24 hours.

TranmissionPlasma, Albumin, Gamma globulin.

Anti-acidosis by infusion of 4.5% sodium bicarbonate and adjustment of electrolyte disturbances according to the electrolyte.

Use diuretics: Lasix, Manitol ..., ensure urine output of 1.5-2 liters / 24 hours.

Sedation, cardiovascular support and other symptomatic treatment.