The hepatitis A virus accounts for 20-25 per cent of all clinical hepatitis worldwide. Therefore, it may be referred to as an infectious hepatitis.
EPIDEMIOLOGY: HAV is spread by the faeco-oral route. Parenteral spread may very rarely follow transfusion of blood from a donor who is in the incubation stage of the disease. Children of school age are most often affected. Adults are usually infected by spread from children.
There are about 7000 cases of HAV per year in the UK:
* Fifteen per cent of cases are associated with foreign travel, of which 50 per cent are associated with travel to the Indian subcontinent
* Three per cent implicate food contamination most commonly shellfish. Epidemics may occur, usually associated with water or food contamination.
CLINICAL FEATURES: Hepatitis A virus infection has a two to six week incubation during which time the virus replicates in the liver and is shed into the faeces. Faecal excretion of the virus declines once the infection becomes asymptomatic.
Typically, there is a prodrome with non-specific symptoms such as mild fever, joint pain, malaise and non-specific gastrointestinal symptoms. This may then be followed by jaundice, pruritus and tender hepatomegaly. The urine may be dark and the stools pale.
The hepatitis is usually mild. In children, it is frequently, sub-clinical. Adults tend to experience a more serious and prolonged disease.
Malaise, tenderness and minor abnormalities of hepatic function may persist during convalescence.
SEROLOGY: There is a rise in serum transaminases 22-40 days after the exposure. Serum antibody to HAV appears as the stool becomes negative for virus:
* Serum IgM anti-HAV implies recent infection; it persists for two to six months, rarely for up to one year, in low titer.
* Serum IgG anti-HAV persists for many years and probably conveys immunity to further infection with HAV.
TREATMENT: The treatment has little effect on altering the course and is mainly supportive. Bed rest is preferable but is less necessary in young, previously fit persons. In acute hepatitis B, gammaglobulin is advocated and this should help limit the disease.
Admission to hospital is recommended if the attack is severe or the patient is unwell and lives alone. A low-fat, high carbohydrate diet may be advised. It is popular primarily because it is highly palatable.
Measures should be taken to prevent transmission, such as careful attention to washing hands and personal hygiene. Patients are infectious for two to three days before and about a week after the development of jaundice.
Alcohol and potentially hepatotoxic drugs should be withdrawn, preferably for up to one year after the attack.
In fulminant acute liver failure, liver transplantation may be indicated; this, however, is a contentious issue. Acute liver failure has a high mortality, but the indications and timing of transplantation have yet to be determined.
PROGNOSIS: The prognosis of HAV hepatitis is excellent:
The illness is self-limiting without chronic sequelae and rarely persists for more than three months (recovery is usual about 10 days of illness).
It accounts for less than one per cent of the cases of fulminant viral hepatitis.
The mortality in large epidemics is less than one per 1000.
Viral carriage in faeces is transient
There is only one subtype of the virus patients develop antibodies and become immune to further infection.
PREVENTION: Prevention by isolation of patients and contacts is rarely effective as the virus is excreted in the faeces for as long as two weeks before the appearance of jaundice. Passive immunization with immune serum globulin is recommended for travellers to highly endemic areas and to close personal contacts of sufferers. Preliminary testing for anti-HAV avoids giving immunoglobulin indiscriminately.
Active immunization with hepatitis A vaccines has now replaced immune globulin in many non-emergency situations and the high incidence of hepatitis A is such that it is the most common infection in travellers that may be prevented by vaccination.
Hepatitis B
Hepatitis B virus is transmitted parenterally, or by intimate, usually sexual, contact. The complete virus particle is known as the Dane particle and has characteristic serological markers. Acute hepatic failure occurs in one to four per cent of the hospitalized patients with HBV. Chronic sequelae are attributed to deficiency in the host immune response rather than to the cytotoxicity of HBV.
Persons at increased risk of infection include:
Parenteral drug abusers shared, unsterile needles.
Recipients of blood transfusions if donor blood is not screened for HBsAg.
Haemodialysis patients.
Sexual partners of chronic HBV carriers.
Persons with multiple sexual partners.
Neonates of HBsAg positive mothers usually at the time of birth or during close contact afterwards, rather than via the umbilical vein.
Family members of infected patients shared toothbrushes, shared razors, sexual contacts.
Health care workers e.g. skin abrasions.
Institutionalized individuals and their attendants e.g. prisoners, mentally handicapped.
TRANSMISSON:
HBV is present in high concentration in the blood and bodily fluids of many hepatitis B virus carriers.
There is a 30-40 per cent chance of transmitting the infection to a susceptible contact via a needlestick injury
Perinatal transmission up to 90 per cent of babies infected with the virus will become chronic carriers. Most babies get infected at delivery rather than in utero. This emphasises the importance of active and passive immunisation at delivery to attempt to interrupt transmission.
Sexual transmission associated with heterosexual and homosexual intercourse.
Intravenous drug users account for over 20 per cent of identified UK acute cases.
Less frequent transmission routes include body piercing, tattooing and blood transfusion. In developing countries, invasive dental and medical procedures are a route of transmission. Such cases are now very rare in the UK. There is a definite but small risk of transmission to household contacts e.g. shared razors, toothbrushes, clinical features.
Hepatitis B virus infection has a two to six month incubation. There is a prodrome of non-specific symptoms such as fever, joint pain, urticarial or maculopapular rashes, malaise and non-specific gastrointestinal symptoms such as nausea.
The acute episode may be similar to that seen in HAV or HAC but more severe. Jaundice rarely persists for more than four weeks and usually, is not severe.
In many patients, the disease is subclinical. Non-jaundiced patients are more likely to develop chronic disease than icteric ones.
A fulminant course may indicate superimposed infection in a symptomless HBV carrier with a new agent such as HDV or HAV.
Treatment has little effect on altering the course and is mainly supportive. Bed rest is preferable but is less necessary in young, previously fit persons.
In acute hepatitis B, gammaglobulin is advocated and this should help limit the disease.
Admission to hospital is recommended if the attack is severe or the patient is unwell and lives alone.
A low-fat, high carbohydrate diet may be advised. It is popular primarily because it is highly palatable.
Measures should be taken to prevent transmission, such as careful attention to hand washing and personal hygiene. Patients are infectious for two to three days before and about a week after the development of jaundice.
Alcohol and potentially hepatotoxic drugs should be withdrawn, preferably for up to one year after the attack.
In fulminant acute liver failure, liver transplantation may be indicated, this, however, is a contentious issue. Acute liver failure has a high mortality, but the indications and timing of transplantation have yet to be determined.
PROGNOSIS: Exposure to HBV can produce a variety of different states (the percentages quoted are for adults):
Sixty to 65 per cent show subclinical disease and recover fully i.e., no resultant liver damage.
Twenty to 25 per cent develop acute hepatitis.
Ninety-nine per cent of the patients recover.
One per cent develop fulminant hepatitis with a case mortality of about 80 per cent.
Five to 10 per cent become healthy carriers i.e. HBsAg +ve after six months less than five per cent show changes on liver biopsy that range from non-specific minimal abnormalities to chronic active hepatitis and cirrhosis. Infectivity and ongoing disease is indicated by a positive serum HBV DNA, IgM anti-HBc and HBeAg.
Five to 10 per cent develop chronic hepatitis which may be:
Chronic persistent.
Chronic active which may progress to cirrhosis and hepatocellular carcinoma.
The likelihood of chronic disease following HBV exposure is more likely in:
Males than females a six fold increased risk.
In those with immunological incompetence, such as:
The very young and the very old more than 90 per cent of the exposed neonates develop chronic disease.
Homosexuals.
AIDS sufferers.
Patients with underlying malignancy e.g. leukaemia.
Patients on immunosuppressive therapy.
The risk of hepatocellular carcinoma is increased 10-390 fold in patients with chronic HBV disease.
Concomitant infection with hepatitis D virus is generally associated with a poorer prognosis than infection with HBV alone.
Immunoprophylaxis may be:
Passive hepatitis B immunoglobulin.
Active hepatitis B vaccine.
There has been some concern that variants of the hepatitis B virus might prevent their control by vaccination, particularly since these variants develop in a large proportion of chronic carriers. Initial indications, however, suggest that these viral escape mutants do not alter substantially the effectiveness of vaccination programmes aimed at large populations.
Hepatitis C
The hepatitis C accounts for most cases of viral hepatitis previously designated as non-A, non-B viral hepatitis.
The HCV is a single stranded, an enveloped RNA virus. It is structurally similar to the flaviviruses and is 30-38nm in size, having a genome of 9379-9481 base pairs.
HCV has an incubation period of 15-150 days which is broadly comparable to that of HBV. The patient may be asymptomatic. About 10 per cent develop jaundice. Fulminant hepatitis is rare. Patients who are HIV positive may have a rapidly progressive course.
Serum diagnosis is usually by detecting anti-HCV. HCV RNA may be detected by PCR one to two weeks after infection. PCR is a supersensitive technique but is not routinely available.
Hepatitis C virus is a highly variable agent and there are now six recognized genotypes with numerous subtypes. These genotypes and subtypes are distributed geographically.
Type 4 has a high subtype diversity in Africa, and type 3 in South east Asia. There is very little of the subtype diversity in Europe and North America suggesting that the virus has only been recently introduced to these areas.
Genotype I, especially subtype Ib, has been associated with a poor response to interferon therapy (and combination therapy of alpha interferon and ribavirin) and severe chronic liver disease.
EPIDEMIOLOGY: Hepatitis C virus is a highly variable agent and there are now six recognized genotypes with numerous subtypes. These genotypes and subtypes are distributed geographically. Type 4 has a high subtype diversity in Africa, and type 3 in South east Asia. There is very little subtype diversity in Europe and North America suggesting that the virus has only been recently introduced to these areas as well.
Estimated prevalence in England and Wales varies from 200,000 to 400,000 (1).
There is a variation in prevalence between different subgroups (1).
Up to 50 per cent of IV drug abusers.
0.04 per cent of homosexuals.
One per cent of the attenders in genito-urinary medicine clinics.
0.4 per cent of attenders to antenatal clinics (in London).
TRANSMISSION: It does not occur from casual contact and appears to require transfer of predominantly either blood or sexual transmission. Sexual transmission is rare compared to that seen with HBV and other sexually transmitted agents but may be increased five-fold in patients co-infected with HIV. Vertical transmission from mother to foetus may occur very rarely but is questionable.
Up to 85 per cent of patients exposed to hepatitis C virus progress to develop chronic hepatitis C virus infection.
CLINICAL FEATURES: After exposure to hepatitis C virus, about 20 per cent of the patients will develop acute hepatitis.
Symptoms, when present, are generally mild and only 10 per cent, become jaundiced. Rare cases of fulminant hepatitis associated with non-A non-B hepatitis have been found not to be related to HCV.
Up to 85 per cent of the patients exposed to the virus, progress to chronic infection. Chronic hepatitis is usually asymptomatic in the early stages and so patients present with advanced liver damage.
Twenty to thirty per cent of the chronically infected patients develop cirrhosis of the liver within 20 years. Cirrhosis is a risk factor for hepatocellular carcinoma.
TREATMENT: Being supportive of an acute attack is the best treatment. Measures include abstinence from alcohol, bed-rest, and a low fat, high carbohydrate diet.
Options for treating chronic HCV liver disease include:
Alpha-interferon until recently this was the only licensed treatment for hepatitis C infection
Ribavirin this has recently been licensed for use as a combination therapy with alpha-interferon. The combination of alpha interferon and ribivirin shows greater efficacy than alpha-interferon alone. The use of combination therapy (interferon alpha and ribivirin) has been recommended by the National Institute for Clinical Excellence for the treatment of moderate to severe hepatitis C.
LIVER TRANSPLANTATION:
considered for patients with decompensated cirrhosis; also for those who develop hepatocellular carcinoma.
Surveillance for hepatocellular carcinoma this is achieved by ultrasound and measurement of the alpha-feto protein this is undertaken every three to four months and is part of the care of patients with cirrhosis associated with chronic hepatitis C virus infection.
The best treatment is prevention by screening donor blood for anti-HCV. A vaccine is unlikely to be forthcoming in the near future.
PROGNOSIS: Infection with HCV stimulates no, or very little, immunity. A large proportion, perhaps greater than 75 per cent, of the patients with acute HCV hepatitis develop chronic hepatitis, which may present up to 25 years after blood transfusion. Of these:
Twenty-five per cent progress to liver failure.
Twenty per cent develop cirrhosis.
Three per cent develop hepatocellular carcinoma.
Thirty-three per cent of the patients with HCV infection may never progress to cirrhosis or will not progress for 50 years or more.
Acute HCV hepatitis may also cause:
Aplastic anaemia usually within three to six months of the infection.
Agranulocytosis.
Peripheral neuropathy.
Cure rates (sustained elimination of the viraemia and arrest of the liver disease) may be as high as 40-50 per cent for genotype1 and up to 80 per cent for genotypes 2 and 3. The best responders to treatment are young females recently infected with genotypes 2 or 3 with no co-infections who have low viral loads and do not over-indulge in alcohol.
