Hepatitis C: From Early Detection to Curative Therapy

Let's start with the relevance of the disease, i.e., its prevalence. Is Hepatitis C a common disease? What is the incidence in Lithuania?

Researchers at Vilnius University Hospital Santaros Klinikos studied the prevalence of this virus in the Lithuanian population. Our staff stood at major shopping centers in cities across the country and offered free Hepatitis C testing. According to the results of this study, about 2.4% of the population in Lithuania is infected. This is quite significant compared with other European countries. We aim to reach the level of countries such as Belgium and France, where the prevalence is below 1%. There are countries with higher prevalence rates, for example, Italy and Romania, where 2.6–3.3% of the population is infected. Our situation is average—not the best, but not the worst either.

Data from blood donor screening programs also follow global trends. The prevalence of this infection among blood donors in Lithuania is around 2%. It is estimated that 50,000–60,000 people are living with Hepatitis C in Lithuania, but only about 10,000–15,000 have been identified.

It is commonly believed that this disease mainly affects antisocial or drug-dependent individuals. But is that really the case? Who should be tested for Hepatitis C?

Cases in which people become infected with Hepatitis C during medical procedures, through blood donation, or after receiving blood or plasma transfusions account for about 60% of all infections. Only 7–10% of patients become infected through intravenous drug use. Therefore, the majority of patients currently diagnosed with chronic Hepatitis C in Lithuania are individuals who received blood or plasma transfusions before 1993 or who were blood or plasma donors at that time. Before 1993, there were no available methods to screen donated blood for this infection.

Patients also include individuals who underwent surgery before 1993 and people with hemophilia. In short, anyone who underwent blood transfusions or other blood-related procedures may have been exposed. There is also an increased risk of Hepatitis C infection among intravenous drug users, prisoners, homeless individuals, immigrants, and people living with HIV. Healthcare workers are also at risk, as are people who received tattoos or piercings using non-sterile instruments and individuals with multiple sexual partners, although sexual transmission of the virus is relatively uncommon.

If a family member is infected with Hepatitis C, all family members should be tested. The virus can also be transmitted during childbirth, so newborns of infected mothers should be tested. Individuals with elevated liver function tests should also undergo testing, as viral hepatitis is one of the first conditions that should be excluded. As we can see, the population at risk for Hepatitis C is quite large. Universal screening is not currently justified, so it is important to carefully identify and test individuals in high-risk groups.

Another important point is that about 10% of Hepatitis C patients cannot identify the source of their infection. They may not have donated blood, undergone surgery, or received blood transfusions, yet the virus is present in their bloodstream. Dentists are sometimes blamed in such cases.

Even today, many Hepatitis C cases are diagnosed incidentally during routine health examinations, screening for other chronic diseases, or blood donation.

What are the main problems caused by this disease?

The main problem is that the disease is usually asymptomatic, allowing people to live for many years without knowing they are infected. By the time symptoms develop, the disease has often progressed significantly and caused substantial liver damage. Liver cirrhosis is frequently diagnosed at this stage, making treatment more complicated. Even when Hepatitis C is diagnosed at an advanced stage, the virus can still be eliminated, but cirrhosis and existing liver damage cannot be reversed. Therefore, early diagnosis and timely identification of patients are perhaps the most important steps.

A study conducted in the United States showed that more than 50% of infected individuals are unaware that they have Hepatitis C. Of these, only half seek medical attention, and only 10% ultimately receive successful treatment. This reflected the situation 2–3 years ago, when treatment consisted of a combination of pegylated interferon (PegIFN) and ribavirin (RBV). Today, infection with genotype 1 can be cured in almost 100% of cases. Effective medications for other HCV genotypes have also been developed and are expected to become available in Lithuania soon. Therefore, the greatest challenge now is identifying infected individuals.

Most patients are unaware that they have HCV. The situation in Lithuania remains poor. For example, in 2015, 1,100 new HCV cases were diagnosed in Lithuania, whereas neighboring Latvia, despite its smaller population, diagnosed 2,000 cases. The diagnosis rate in Lithuania is only about 12%, meaning that only 12% of people living with HCV have been identified. Latvia has achieved much better results, identifying approximately 42% of infected individuals. This exceeds the European average. In countries such as France, Sweden, Finland, and Malta, 88–90% of HCV cases have been diagnosed. Lithuania remains among the countries with the lowest diagnosis rates, alongside Poland and Romania.

When will this problem be addressed? How could family physicians contribute to earlier HCV diagnosis?

People need to be educated about the disease and informed that it often causes no specific symptoms. Today, people routinely check their cholesterol and blood glucose levels, but liver function tests should also receive greater attention.

The role of the family physician is crucial. Family physicians already have the opportunity to prescribe annual liver function tests, including liver transaminases. Unfortunately, this opportunity is often underutilized, resulting in delayed diagnosis.

Early diagnosis of Hepatitis C largely depends on family physicians. When a patient visits a family physician, the physician should assess the individual's HCV risk by taking an epidemiological history and evaluating potential exposure. Family physicians should consider recommending HCV testing for patients with unexplained fatigue or weakness, particularly if they belong to one of the recognized risk groups. They should also explain that diagnosing the disease early is far more beneficial than waiting until it progresses to liver cirrhosis, which is considerably more difficult and less effective to treat.

When is treatment initiated? Can the new highly effective drugs be prescribed immediately to all patients infected with HCV genotype 1?

Treatment with this combination is prescribed for patients with advanced HCV infection who have genotype 1 (whether treatment-naïve, previously unsuccessfully treated, or experiencing relapse after completing treatment) and have liver fibrosis at stage 2 or higher. Modern treatment is initiated once liver damage has developed. Before treatment, the HCV genotype and viral load (viremia) must be determined. A liver biopsy should also be performed to assess the degree of liver fibrosis.

Fibrosis refers to the formation of connective tissue (scarring) in the liver and is classified into stages 1, 2, 3, and 4. Stage 4 fibrosis represents liver cirrhosis. Stage 2 fibrosis is not yet considered advanced liver fibrosis, so initiating treatment at this stage can completely cure the patient, with regression of the fibrotic process. Incidentally, most patients are diagnosed with stage 2 fibrosis or higher.

Is this sufficient to prescribe the new drugs? Should modern treatment not be started earlier, when fibrosis is at stage 0 or 1?

The new treatment is expensive, making it impossible to prescribe it immediately to all patients. Previously, the effectiveness of treating genotype 1 HCV with pegylated interferon (PegIFN) and ribavirin (RBV) was only about 40%. With the new drug combinations, treatment success reaches approximately 99%.

Today, there is growing international consensus that all patients with genotype 1 HCV should receive treatment with the new drugs regardless of the degree of liver fibrosis, because sooner or later they will require treatment. It is more rational to start therapy as early as possible, since earlier treatment leads to better outcomes. Lithuania is gradually moving toward this strategy. Initially, we had a large number of genotype 1 patients who had undergone two or three unsuccessful treatment courses with various medications. When the new drugs became available in 2015, these patients were prioritized. I believe that their numbers will soon decline. In addition, access to these medications is improving. Therefore, Lithuania is expected to begin treating patients regardless of their fibrosis stage in the near future.

Is treatment with ombitasvir/paritaprevir/ritonavir plus dasabuvir superior?

Previous treatment with PegIFN and RBV was not very effective. It was associated with numerous adverse effects and required a prolonged treatment period. As a result, many patients declined antiviral therapy.

Treatment with direct-acting antiviral agents is significantly more effective, shorter in duration, and better tolerated. The main factor limiting their use is concomitant medication. This regimen is contraindicated with certain drugs, including some cardiovascular and psychotropic medications. Using specialized interaction databases and reference tables, physicians evaluate whether the patient's current medications present contraindications to the new antiviral therapy. Fortunately, relatively few patients fall into this category. It is expected that newer antiviral agents effective against all HCV genotypes will also become available for these patients.

Is it important to diagnose the disease and initiate treatment as early as possible?

The best outcomes are achieved when treatment is started early. Treating advanced HCV infection after liver cirrhosis has developed is much more challenging. Although the virus itself can still be eliminated, the risk of liver cancer remains. Therefore, these patients require annual surveillance for hepatocellular carcinoma.

What are the latest developments in HCV diagnosis and treatment?

As mentioned earlier, pan-genotypic antiviral drugs are expected to become available. Once these therapies are introduced, together with the currently available highly effective treatments, it will be possible to successfully treat patients infected with all HCV genotypes.

Curing an individual with HCV benefits not only the patient but also the healthcare system. Treatment is costly, but it effectively prevents further transmission of the virus. Patients who are cured no longer face the ongoing risk of developing liver cirrhosis, existing liver damage may gradually regress, and fewer patients with cirrhosis will ultimately require liver transplantation.

Have all the problems related to HCV been solved? Could you summarize the key issues?

The most important priority is to diagnose the disease as early as possible and initiate treatment promptly. As mentioned previously, only about 10,000–15,000 HCV cases have been identified in Lithuania, whereas the true number of infected individuals is estimated to be almost three times higher.

One reason for this gap is the absence of a coordinated national strategy and a national HCV patient registry. Such a registry would include all diagnosed patients and create a comprehensive database. Latvia already has a national hepatitis registry, which our colleagues presented to us about a year ago. In my opinion, it would be reasonable to adopt a similar system rather than develop one from scratch. It would simply need to be translated into Lithuanian and implemented.

A registry would provide information on when and how patients were treated and what treatment outcomes were achieved. It would also facilitate monitoring and control of hepatitis, as well as treatment planning. At present, it remains unclear who should be responsible for the long-term management of HCV-infected patients, how screening should be organized, and which tests should be performed. A dedicated national program is needed to define patient monitoring, screening strategies, treatment pathways, and long-term follow-up.

Thank you for the interview.

Interview by Natalija Voronaja.

"Gastroenterology," Supplement to the Journal "Internist", 2017, No. 1 (16).