July 13, 2020
Wilmark N. Gular, MD
Hepatitis C is an insidious disease. Due to its asymptomatic course, screening for high risk individuals is of utmost importance. The primary care physician is provided with the opportunity to identify and manage these patients especially at a time when orally administered direct acting antivirals (DAAs) have been made available.
The World Health Organization (WHO) in 2015 estimated about 615,000 cases of chronic hepatitis C among Filipinos.1 A 2007 study by Yanase, Y. et al. suggested a 1% prevalence rate of hepatitis C in the Philippines.2 Globally, around 170 million people are afflicted by the disease.4
How Huge is the Problem with Hepatitis C?
Hepatitis C is caused by an RNA virus which has several genotypes. The virus is rapidly mutating which makes neutralizing antibodies short-lived. This leads to a possible reinfection even with the same virus isolate.4 Most cases become chronic and have the propensity to cause cirrhosis and hepatocellular carcinoma (HCC).
The Philippines ranked 5th in the Western Pacific Region in terms of mortality from chronic hepatitis in 2015.1 According to the International Agency for Research on Cancer, 9,485 Filipinos died from liver cancer in 2018, the country having the 14th highest mortality rate for liver cancer worldwide.3 In 2016, WHO Global estimates showed that 58.87% of liver cancer are caused by hepatitis B and C.1
Screening and treatment of HCV infection present a significant financial burden since this is not covered by the national health insurance (PhilHealth). In a government hospital, antibody to HCV (anti-HCV) costs about 1,000 Philippine pesos (Php).5 In his 2015 article for Business World, Reiner Gloor noted the price of HCV viral load (HCV RNA) at 6,500 Php and HCV genotyping at 14,350 Php.6
Currently, the average cost of treatment depends on the specific DAA which range from 50,000 to 60,000 Php, covering 3 months. Most treatments are out of pocket expenditures while new medications can be applied for compassionate use or individual medical assistance program from the Philippine Charity Sweepstakes Office (PCSO).
Recognizing the Risk
Individuals born between 1945-1965 contribute to the highest prevalence of hepatitis C.4 Previous and current injection drug users, recipients of blood products prior to 1992 (before blood screening programs), and healthcare professionals who had needle stick injuries, especially from HCV positive patients, are at a significant risk from contracting HCV.
Children born to HCV-positive mothers, those who had unprotected sex with blood to blood contact, household contacts who shared contaminated personal items such as razors, and toothbrushes, those who had their tattoo or body piercing from unsanitary or unregulated means, people exposed to reused and contaminated medical equipment, and long-term hemodialysis patients are also at risk for HCV infection.7
Signs, Symptoms, and Sequelae
Hepatitis C infection has an acute and chronic course. Both are mostly asymptomatic. Acute symptomatic course is divided into three phases. Variable constitutional symptoms such as fever, malaise, arthralgias, myalgias, headache, nausea and vomiting, anorexia, and fatigue appear in the prodromal phase.4
The second or icteric phase is heralded by jaundice. At this time, the patient may also experience mild weight loss, dark-colored urine, clay-colored (acholic) stools, and liver enlargement and tenderness. This is followed by the recovery or posticteric phase when symptoms subside although some degree of liver enlargement may persist.
Acute HCV infection generally lasts for 2 weeks up to 3 to 6 months. Recovery is expected in 3 to 4 months in 75% of uncomplicated cases.4 Only a fifth of patients recover from the acute infection. Progression to the chronic course is the rule in HCV infection.
Chronic infection has a slow and indolent course. Liver injury usually appears after 2 to 3 decades. About 20% to as much as 50% of patients may develop cirrhosis. Patients with cirrhosis have a 1 to 4% annual risk of HCC and a 4% risk of decompensated liver failure.4 Chronic infection may be complicated by its associations to alcoholic liver disease and coinfection with hepatitis B virus (HBV) as well as human immunodeficiency virus (HIV).
Two Tests for HCV
People at risk for HCV should be screened with anti-HCV. Anti-HCV may be obtained 12 to 24 weeks after a history of needle-stick injury or mucosal exposure.8A positive anti-HCV warrants testing for HCV RNA for confirmation which shows the viral load. HCV RNA is the most sensitive indicator for HCV infection and is considered the gold standard.4
A nonreactive anti-HCV means that there was no previous exposure to HCV. Patients who test positive for anti-HCV but with a negative result for HCV RNA might have acute infection when HCV RNA is on transient clearance. This combination may also represent resolution of infection or a false positive anti-HCV. HCV RNA can be retested 4 to 6 months after the initial test to confirm resolution of HCV.8
Chronic hepatitis C is diagnosed by positive anti-HCV and HCV RNA.8 A positive anti-HCV does not distinguish between recent and past infection. Those who are reactive to anti-HCV with a high viral load have active infection and require treatment.4
Thoughts on Treatment
Before initiation of treatment, the following must be considered: HCV genotype, previous treatment for HCV, comorbidities, and presence of cirrhosis or liver failure.7 History of HBV infection must be checked because of the risk of reactivation of HBV with HCV treatment.9
Coinfection with HIV must be assessed since DAAs can be given before antiretroviral therapy for HIV. Some DAAs should be avoided in patients with severe and end-stage renal failure and this presents a problem for HCV positive patients on long-term hemodialysis. The antiarrhythmic amiodarone should not be given with DAAs due to serious bradyarryhthmia.9
The goal of treatment is viral load clearance.7 Measurement of HCV RNA at the end of treatment is usually compared with the baseline. Undetectable viral load at 12 and 24 weeks following treatment signifies sustained virologic response (SVR). The SVR simply means that the patient has recovered from HCV and a possibility of rebound or viral return is very minimal.
The Dawn of Direct Acting Antivirals (DAAs)
Second generation DAAs are orally administered and are usually given once daily. These make the regimen simpler compared to older drugs used for HCV such as the parenterally-administered interferon. In addition, these DAAs have a more benign safety profile. But more importantly, these are highly efficient medications achieving 95 to 97% cure rate.9
Treatment is recommended in patients with a positive anti-HCV and a high viral load, whether the hepatitis is acute or chronic. DAAs are usually given in combination with each other. Specifically, a polymerase inhibitor is used together with an inhibitor of NS5A, a hepatitis C protein. This combination works for most genotypes including genotype 1, which is the most common genotype among Filipinos.9
The duration of treatment is usually 12 weeks for treatment-naïve patients and even in those with cirrhosis. Treatment may be extended to 24 weeks for those who were previously treated and for those who currently have decompensated liver failure. But the latter must be referred to a liver center for consideration of liver transplant.9
DAAs are generally well-tolerated. Their main adverse effects include fatigue, gastrointestinal symptoms, and headache.7 Special consideration is given to those with renal failure. Newly developed DAAs are recommended for this set of patients. DAAs are currently not recommended for pregnant women.7
Handling Hepatitis C at the Primary Care Level
The primary care physician (PCP) of today can detect and manage uncomplicated HCV infection following different local and international specialty guidelines. This readiness was seen in the ASCEND study where trained PCPs in HCV diagnosis and treatment demonstrated the same level of competence as specialists.7
The responsibility of PCPs in HCV management extends to monitoring, proper and timely referral to specialists, and education and counseling. Due to the transmissibility of the virus, the PCP should counsel patients with HCV regarding risk-minimizing behaviors such as avoidance of sharing personal items like toothbrush, nail clippers, and shaving equipment.
As stewards of health, PCPs must recommend avoidance of drinking alcoholic beverages especially among patients with cirrhosis. Although not a major problem in our country, injection drug users should be advised to stop this habit and avoid needle sharing. HCV positive patients should also be advised against blood and body organ donation.8
Part of the preventive strategy includes vaccination against hepatitis A and B among patients with HCV who have negative anti-HAV IgG, and HBsAg and anti-HBs, respectively.8 Unless presenting with debilitating symptoms or decompensated liver cirrhosis, PCPs can clear patients with HCV infection for employment following a thorough evaluation. The patient must also show compliance to treatment and follow-up.8
In terms of monitoring, HCV RNA for viral load testing is recommended at baseline, at 4 weeks of treatment, and at 12 and 24 weeks after completing therapy. HCV RNA predicts response to therapy with the goal of SVR at 12 and 24 weeks. Timely referral to specialists is needed among patients with cirrhosis especially those who have signs of hepatic encephalopathy and impaired coagulation for possible liver transplantation.7
July 28 is World Hepatitis Day. Hepatitis C contributes as much to this spectrum of diseases. The primary care physician has the duty to identify populations at risk and to treat or refer them appropriately. With the management of HCV infection in the primary level, eradication of the disease is on the horizon.