Managing hepatitis in primary care
Dr Rajneesh Kumar, a senior consultant at the Department of Gastroenterology and Hepatology, Singapore General Hospital, highlights the high prevalence of hepatitis, and speaks to Roshini Claire Anthony about the transmission, prevention, and treatment of the disease.
About 2.3 billion people in the world are infected with one or more of the hepatitis viruses. It has been reported that 2 billion people are infected with hepatitis B. Approximately 185 million of those are infected with hepatitis C and 20 million infected with hepatitis E. In high endemic regions, more than 90 percent of children are infected with hepatitis A by age 10 years, although few develop complications. [Vaccine 2010;28:6653-6657]
Viral hepatitis results in around 1.4 million deaths each year. Hepatitis B and hepatitis C are responsible for about 90 percent of these fatalities (780,000 hepatitis B-related deaths are documented globally each year), while the remaining 10 percent is caused by other hepatitis viruses. More than 300,000 people are estimated to die each year due to the chronic consequences of hepatitis B, particularly cirrhosis and liver cancer. [Lancet 2015;385:117-171]
Approximately 100 million hepatitis B carriers live in World Health Organization (WHO) South East Asia member countries. Current estimates for hepatitis prevalence in the South East Asian region:
· Hepatitis A: 400,000 cases with 800 deaths annually
· Hepatitis B*:1.38 million cases with 300,000 deaths annually
· Hepatitis C*: 500,000 cases with 120,000 deaths annually
· Hepatitis E: 6.5 million cases with 160,000 deaths and 2,700 stillborns annually
The WHO estimates that there are an estimated 257 million persons with hepatitis B globally and 900,000 hepatitis B-related deaths each year. An estimated 71 million people are infected with hepatitis C globally which results in over 400,000 deaths each year.
Non-A–E hepatitis is uncommon and is caused by viruses that can also affect other parts of a patient’s body. Some viruses do not have a predilection for a patient’s liver and the liver is a bystander. For example, the dengue virus can also cause hepatitis. Similarly, viruses such as the cytomegalovirus (CMV) and the herpes simplex virus (HSV) can also affect the liver causing severe hepatitis, though incidents of these are rare.
Transmission and risk factors
Hepatitis A and hepatitis E are transmitted by infected water via the faecal-oral route. The infection is transmitted though the faeces of the infected person, and the infection spreads when an uninfected person ingests contaminated food or water.
Hepatitis B and hepatitis C are transmitted by blood (eg, through intravenous needles, sexual relations, mother-to-child transmission). It is a misconception that hepatitis B and C can be transmitted by hugging, kissing, and through sharing of utensils.
Risk factors for infection transmission include mother-to-child transmission during childbirth, the use of infected needles (eg, drug abuse, tattoos in unregulated settings), and blood transfusions (especially among people who received blood transfusions before 1992 when hepatitis testing was less stringent than now).
Most cases in Asia are due to mother-to-child transmission as there was no compulsory vaccination before 1985 (ie, children of an infected mother would get infected too). However, the prevalence of hepatitis B has been declining in Singapore.
Symptoms of hepatitis
Common symptoms of hepatitis include:
· Loss of appetite
· Yellowing of the eyes
· “Tea-coloured” urine
It is important to note that chronic hepatitis B and C can remain asymptomatic in most patients.
For hepatitis A and E, diagnosis is based on serology testing and checking for symptoms.
The tests include:
· Anti-hepatitis A virus (HAV) immunoglobulin M (IgM) testing for hepatitis
· Anti-hepatitis E virus (HEV) IgM and HEV RNA testing using polymerase chain reaction (PCR)
Diagnosis of hepatitis B and C is based on serology testing and specific blood tests. Hepatitis C confirmation may require additional RNA testing.
General screening for hepatitis B and C is warranted as it is prevalent in South East Asia. Early diagnosis helps identify asymptomatic patients and can prevent further complications through regular follow up.
Challenges in diagnosing hepatitis
The main challenges would be undiagnosed hepatitis B and C infections as most cases remain asymptomatic and are only diagnosed via screening blood tests. By the time symptoms develop, the patients may have already developed cirrhosis or hepatocellular carcinoma, by which time the condition may be irreversible.
Asymptomatic hepatitis C carriers may act as infection reservoirs and may unknowingly transmit the condition to others.
Misdiagnosis or missed diagnosis is uncommon from blood tests, as blood tests for hepatitis B and C in the general population are quite sensitive and specific. However, in certain populations, such as in immunocompromised patients, the use of antibody testing only can lead to false negative results. As such, testing in this population should be complemented with nucleic acid testing.
Treatment for hepatitis B is either oral (entecavir, tenofovir, lamivudine, or adefovir) or via injections (eg, interferon).
There are few oral drugs available in South East Asia and the ones available include sofosbuvir/velpatasvir and elbasvir/grazoprevir. Both combinations are very efficacious and have minimal side effects.
While current treatment for hepatitis B is effective, long-term (potentially life-long) treatment is necessary. Nucleoside analogues are effective in suppressing the virus, but once treatment is withdrawn, virus rebound can occur in most patients. While on treatment, only 1–7 percent of patients will be able to successfully clear the hepatitis B virus.
For hepatitis B, the long duration of treatment poses the largest challenge. To overcome this, new drugs to reduce treatment duration are currently being investigated. These include RNA inhibitors, capsid inhibitors, therapeutic vaccines, and TLR- agonists, which are all currently in different phases of trials.
Hepatitis A and E are mostly managed symptomatically, while ribavirin can be used in some cases of hepatitis E, especially in patients who are on immunosuppressive medications.
For hepatitis C treatment, the sofosbuvir/velpatasvir combination has 95–98 percent efficacy. The success rate for the treatment of hepatitis C is around 95 percent after a 12-week course of treatment. New oral medications can be effective in 95–98 percent of hepatitis C cases, with treatment durations ranging from 8–12 weeks. However, the cost of medication in some countries can be high, thus restricting their easy access and use.
The main prevention strategies would be vaccination, screening for hepatitis B and C, and regular follow-up for hepatitis B.
Vaccinations for hepatitis A and hepatitis B are safe and effective. Completing the series of booster shots is needed for full protection, though booster shots are not required for individuals not residing in high-risk areas.
We follow the main guidelines of the American Association for the Study of Liver Disease (AASLD), European Association for the Study of the Liver (EASL), and the Asian Pacific Association for the Study of the Liver (APASL), as well as the Clinical Practice Guidelines (CPG) for Singapore.
Long-term complications of hepatitis include liver cirrhosis and liver cancer. Patients would need to consult with specialists who can provide the necessary medications, and they would require constant specialist follow-up.
GPs can provide vaccinations for hepatitis A and hepatitis B and assist with the monitoring of chronic hepatitis B. The GP’s role in the prevention, screening, and monitoring of patients with hepatitis B is crucial for timely diagnosis and linkage to optimal ongoing specialist care.
National Foundation for Digestive Diseases
Mind Your Liver