Hugo Tanno

Viral hepatitis

This disease is an example in medicine of what can be classified as biological variability, since its clinical forms of presentation are the most diverse, from an absolutely asymptomatic modality, only detectable by serological studies, to an over-acute and fulminant one that leads to death with the most florid symptoms of liver failure. Between these two clinical forms there is a wide range of intermediate possibilities that have been characterized by various names, many of them in disuse.

Pathophysiology . In order to expose the most important pathophysiological aspects of this disease, it is convenient to review the etiological agents that produce it. At present, different viral agents capable of causing liver damage are known; the most common are viruses A, B, C, D and E. Viruses C and E correspond to the formerly called non-A non-B forms.

Other etiological agents have been recognized as causes of acute viral hepatitis: Epstein-Barr viruses (infectious mononucleosis), herpes simplex type I, congenital rubella, Coxsackie, yellow fever and Argentine hemorrhagic fever, etc.

Certain important characteristics of the four most common agents will be described very briefly.

Virus . Isolated in the past decade, it is made up of a 227 nm diameter particle, with a fairly homogeneous structure, made up of two RNA chains. The replication of the virus takes place in the hepatocyte, and it is excreted through the biliary tree to the intestine, making the fecal matter its vehicle of infection. The period of viremia is short, and for this reason blood and other fluids are not very infectious. The excreta that contaminate food makes the oral route the main route of infection.

The incubation period is relatively short (4 weeks) and its excretion by fecal matter quite limited (2 weeks). This means that the danger of contagion exists only at the end of the incubation period and at the beginning of the state period. In man the cotagium occurs from person to person.

Virus B . Chronologically it was the first to be discovered in the mid-1960s. It is composed of a double structure. The superficial, lipoprotein, is known as the B virus surface antigen (HbsAG) and it is the one that for years served as a humoral marker of the virus ("Australian antigen"). The central structure, made up of DNA, is called the core and is known by the acronym HbcAG. It constitutes a different antigenic system and it is the one that conditions viral infectivity.

The replication of virus B is done in the hepatocyte, synthesizing the capsule in the cytoplasm and the core in the nucleus. There is a third antigenic system known by the acronym HbeAG / Beca that seems to correspond to a core metabolite. The presence of HbeAg is related to the synthesis of DNA polymerase of viral origin and is the expression of the infective capacity of the virus.

The determination of the virus DNA has recently been incorporated into the laboratory routine. The presence of DNA in serum is recognized as the marker with the highest fidelity of viral replication and its detection is important in chronic patients to define possible therapies. The RPC (polymerase chain reaction) technique is the most sensitive for its search.

Blood and all organic fluids are contaminated, constituting the main vehicle of contagion, either orally or parenterally.
Its incubation period is usually between 2 and 3 months.

C Virus . This virus not yet isolated has been synthesized by genetic engineering and from its synthesis techniques have been produced that allow to identify the patients carrying the antibody (IgG); More recently, the development of RPC techniques has made it possible to identify the viral antigen, the virus was classified as a flavivirus (RNA). It is transmitted by blood or blood derivatives and its sexual transmission is highly debated. Vertical transmission does not seem to have the importance it has in form B. The mechanism of injury would be direct cototoxic, although the possibility of some indirect immune mechanism is not ruled out.

Delta virus . It needs the presence of virus B for its multiplication. It can be transmitted simultaneously with the B virus or as an over-aggregated infection to a chronic carrier of the B virus. It is the causative agent of a significant number of severe forms (chronic and fulminant).

E virus . It was recently described and belongs to the Calcividirae (RNA) family. It is a virus of short incubation (3 to 4 weeks) and is spread orally (contaminated water). At the moment, there is no clinical diffusion test that allows its investigation. However, the antibody in IgM that detects patients with acute disease is studied. Unlike the hepatitis viruses B, C and D that does not go to chronicity. Its mechanism of action appears to be cytopathogenic.

The most studied by the monitoring of its humoral markers is the virus B. Although the mechanism of damage is different, it would seem that the three viral types do not exert a direct cytopathogenic action against the liver cell, but that the effector of this damage would be the immune system in its response. In B virus infection, the T lymphocyte is the producer of cell damage. The deficiency of the immune system explains the presence of healthy carriers of the B virus, as well as variations in this immunological deficit can explain the transition to chronicity in hepatitis B.

The core of the virus (HbcAG) is the target for the immune response. In this way, the cells that present HbcAG are marked for the action of the T lymphocyte. In the natural history of this disease, HbcAG disappears, leaving only the replication of HbsAG. This is not a cellular marker for the immune response, in such a way that the disease enters remission due to a cessation of the mechanism of injury mediated by the immune system.

In hepatitis A there is evidence that the type of damage is mediated by the immune system, since on the one hand there is no evidence of lesion in tissue cultures, and on the other the transaminases rise as an expression of necrosis quite parallel to the appearance of specific IgM antibodies against virus A.

Symptoms and signs . In its onset, acute viral hepatitis is asymptomatic in most cases. Only at the end of this stage can it manifest itself with symptoms that are generally nonspecific, such as asthenia, anorexia, muscle pain, arthralgia and fever. The non-specificity of the manifestations means that this disease is not always early identifed.

Living with a person affected by hepatitis A, or with a history of injections or transfusions in hepatitis B and C, prioritizes these data in the interrogation. The presence of a urticarial rash and joint pain, especially in the small joints, is common in form B hepatitis. High fever, accompanied by certain gastrointestinal disorders (vomiting, constipation, or diarrhea) is more common in hepatitis A. The C forms are generally not very symptomatic.

The identification of the disease is made from the serum elevation of transaminases. At this time the patient may or may not have jaundice, although the urine is usually choluric. The symptoms already described are accentuated here and abdominal palpation reveals a hepatomegaly of different hierarchy, sometimes painful and with a slight increase in consistency. Hepatomegaly is a frequent finding in children (> 75%), and to a lesser extent in adults; together with general symptoms and dark urine it can define the diagnosis of acute hepatitis.

The intensity of jaundice is variable. Form C is the one that causes jaundice in a smaller number of cases, the B form causes jaundice more frequently; in hepatitis A, jaundice is common in adults, whereas in children the anticteric forms predominate.

The improvement is evidenced by a decrease in decay, the disappearance of certain alterations such as the rejection of certain smells (eg, cigarette), and an increase in appetite.

Hepatic and spenic palpation change with the improvement of the patient. The persistence of splenomegaly, as well as the increase in liver size and consistency, are indicators of disease progression, and they are almost strictly observed in the prolonged and chronic forms.

The appearance of exaggerated sleep, neuropsychiatric disorders (behavior disorders, inconsistencies) and extrapyramidal tremor lead to thinking of liver failure. A typical sign in these patients is asterixis; It consists of the impossibility of maintaining the dorsiflexion of the hand and is due to the compromise of the extrapyramidal pathway. Usually the patient is jaundiced and coagulation alterations are added (intestinal hemorrhage, epistaxis, hemorrhage at the puncture sites, etc.). Sweet and foul smelling breath is characteristic, known as liver breath (hepatic fetus).

Study methodology. The laboratory is the essential complement to confirm acute hepatitis. In most cases, the elevation of transaminases exceeds normal values ​​by 20 times, which, together with the aforementioned symptoms and signs, constitutes the most significant element for the diagnosis. The hemogram is usually normal, with slight leukopenia and lymphocytosis; erythrosesimentation is low or not very high, while bilirubin levels depend on the degree of jaundice. Humoral markers of virus A (IgM) and virus B (HBsAGG) are essential for a correct diagnostic differentiation, and also for prognosis. In this sense, it should be taken into account that hepatitis A is generally benign and that it is not associated with forms of chronic evolution. In contrast, both forms B and C are more severe,

The monitoring of the patient with acute hepatitis is carried out on the basis of the symptoms and signs already mentioned, and the evolution of bilirubin and transaminases. Protein variations, especially the decrease in albumin and the polyclonal increase in immunoglobulins, are signs of chronic evolution.

In fulminant forms, the decrease in the prothrombin rate, the drop in coagulation factors, and the decrease in serum cholinesterase are the humoral signs that most aid in the diagnosis.

The recovery of the patient is manifested by the regression of clinical symptoms, the normalization of liver and splenic palpation and the disappearance of laboratory abnormalities, especially serum transaminases. In hepatitis B, negative HbsAG must be added.

Some hepatitis, due to their own characteristics, receive a special name.

Cholestatic hepatitis

Signs of cholestasis and pruritus predominate; This form can be cholestasic from the beginning or present an outbreak of cholestasis at some point in evolution.

Recurrent hepatitis

It is that hepatitis that seems cured, with disappearance of symptoms and laboratory values ​​that are normal or close to normal, that evolves by pushing and returns to present coluria and / or jaundice with an increase in transaminate levels. Although any of the three types of hepatitis can develop this clinical picture, it has been seen that this double peak in transaminases is more common in the C forms.

Anicteric hepatitis

It is that hepatitis without jaundice that is suspected from its symptoms and confirmed in the laboratory. It is common in form A of the child, but it is found with some frequency in hepatitis B of the immunosuppressed adult and more often in form C at any age of life. It is important to take this form into account, since it has been seen that in hepatitis C and C there is a higher incidence of progression to chronicity.

Fulminant hepatitis

This name is reserved for the very severe forms of acute hepatitis, which present with manifest liver failure, most of the time with neuropsychiatric symptoms. Its reversibility depends not only on the intensity of necrosis, but also on the regenerative capacity of the liver. Lately the determination of alpha-fetoprotein has been used as an expression of liver regeneration.

Recent studies show that hepatitis C has a different prognosis in the fulminant forms compared to forms A and B. The proportion of survivors in C barely exceeds 10%; this poor prognosis is linked, precisely, to a failure in liver regeneration.

Toxic hepatitis

Different chemicals cause liver damage. In the past, liver disease caused by direct toxins was frequently reported; more recently, with the use of multiple drugs in medicine, the spectrum of hepatoxicity has widened.

With a practical criterion, today two types of drug-induced liver injuries are known:

a) drugs of predictable toxicity . They are those in which the damage they cause is related to the administered dose. Usually the type of lesion is necrosis, or steatosis; the lactation period between administration of the drug and the effect is short and depends on the dose. All of them have a model in experimental animals (C1C4, antimetabolites, phosphorus, etc.)

b) drugs of unpredictable toxicity . The lesions are not related to the administered dose and usually respond to hypersensitivity or idiosyncratic mechanisms. Other times the damage is caused by certain toxic metobolites. The latency time and the type of lesion are variable, and include the aforementioned cholestatic forms.

Examples of idiosyncratic injury are those caused by chlorpromazine and sulfonamides; the typical example and the action of toxic killers is that of isoniazid.

Symptoms and signs

The diagnosis is essential in a thorough and exhaustive interrogation especially oriented to the use of drugs or to contact with potentially toxic substances. Extrahepatica of such substances.

The patient with toxic liver disease may present with or without jaundice. Jaundice is related to the type of injury (cholestasis) and also to the hierarchy of damage. Usually the liver is enlarged, with increased sensitivity and consistency. The spleen is normal, but increases in size in cases that progress to chronicity. If liver failure occurs, the manifestations are the same as those already indicated for viral hepatitis.

Study methodology

Laboratory data depend on the type of damage and the degree of neocrosis, cholestasis, steatosis, etc., which are related to the toxin involved.

Liver biopsy is often used for diagnostic purposes in these patients, since the histology allows us to recognize the type of lesion linked to the supposed poison and to rule out other causal noxes. Another recuerso to take into account is the re-exposure to the drug, in special cases and with due precautions (strict control, patient authorization).

Liver damage from alcohol

Liver damage caused by alcohol is related to the amount and time of the alcohol habit, without considering other variables inherent to the patient (race, sex, nutritional status, genetic factors, etc.) that influence the quality and hierarchy of the alcohol. alcoholic injury. Alcoholic hepatitis is produced by chronic toxic exposure, however its presentation and state period allow it to be classified as an acute disease.

Signs and symptoms . The anamnesis of the alcoholic history is the most important data. The frequency with which the alcoholic denies this information means that the information (type, amount, time) is often provided by relatives.

In the general examination of the patient it is important to consider their nutritional status as well as the daily caloric intake. The muscle mass taken in the pectorals or in the eltriceps can be a good repair to evaluate.

The signs and symptoms of alcoholic hepatitis can be very varied. Consciousness is good in mild and moderate forms, but may be compromised in severe ones (drowsiness, coma). It is sometimes difficult to assess, since neurological signs of alcohol withdrawal are often added; in these circumstances the tremor is thicker, the delirium more evident, there is no liver breath and the pupils are not mydriatic. Fever is frequent, sometimes in peaks.

Jaundice is related to the seriousness of the damage, although in some patients it is related more to the intensity of the cholestasis than to the severity of the necrosis; in such cases there is evident itching and the prognosis is better. Stigmascutaneous liver disease (hepatic palm, stellar nevi) and parotid hypertrophy are common. The liver is enlarged in almost all patients, with increased consistency and tenderness on palpation. In most cases there is splenomegaly, with a frank increase in the consistency of the organ. In many patients, extrahepatic symptoms associated with the toxic action of alcohol are added (diarrhea, paresthesia, pain in lower limbs, epigastric pain due to pancreatopathy, etc.)

Study methodology

The clinical presumption of alcoholic hepatitis is confirmed by humoral findings. The most characteristic is the elevation of the GOT above the GPT in values ​​that do not exceed 400 mIU. This is accompanied by significant elevations in gamma-glutamyl transpeptidase and alkaline phosphatase. The hematic formula usually shows macrocytic anemia with variable leukocytosis, and erythrocytic sedimentation is elevated. The increase in bilirubin can be done at the expense of both fractions. It is common to find dysproteinemia, characterized by hypoalbuminemia with a polyclonal increase in immunoglobulins. Compromise of the coagulation system is common in severe cases and constitutes, together with cholinesterase values, a prognostic marker.

Liver biopsy with or without laparoscopy is the best resource to confirm the diagnosis, provided that the patient's coagulation status makes it possible, since the histological patent in this entity is unmistakable.