Hepatitis D does not announce itself loudly. The virus can remain hidden for years, quietly accelerating liver damage in people already infected with Hepatitis B, before cirrhosis, liver failure or liver cancer finally brings the disease to medical attention. For thousands of Pakistanis, the danger may not simply be the virus itself but the gaps that allow it to remain undiagnosed.
Unlike other forms of viral hepatitis, Hepatitis D virus (HDV) cannot infect a person independently. It requires the presence of Hepatitis B virus (HBV) to survive and reproduce. A person can acquire both viruses at the same time, known as coinfection, or develop HDV after already having chronic HBV, known as superinfection. The latter can follow a particularly aggressive course.
The World Health Organisation (WHO) describes chronic Hepatitis D as the most severe form of chronic viral hepatitis because HDV infection can accelerate liver damage and substantially increase the risk of cirrhosis, liver failure and liver cancer.
Yet Pakistan does not currently have a reliable, up-to-date nationwide estimate of the prevalence of HDV. Available studies have produced widely varying figures because they have generally been conducted among selected hospital or HBV-positive populations rather than through representative national surveys.
A recent WHO-supported survey in Sindh found that 32.8 per cent of HBsAg-positive participants were also positive for anti-HDV antibodies, highlighting the substantial burden in parts of the country. Earlier studies have also reported high rates in Sindh and Balochistan, while lower but still significant levels have been reported in Punjab and Khyber-Pakhtunkhwa (K-P).
For experts, the absence of reliable nationwide surveillance is itself part of the problem.
Dr Yasar Yousafzai, Professor of Haematology at the Institute of Pathology and Diagnostic Medicine at Khyber Medical University, said HDV was certainly present in Khyber-Pakhtunkhwa but its current provincial burden could not be determined because no province-wide survey had been conducted.
“Older studies from K-P have generally found HDV in approximately 10 to 15 per cent of hepatitis-B-positive patients, while one molecular study found HBV-HDV coinfection in around 14 to 15 per cent of patients,” he said.
However, he cautioned that these figures were based on older studies and selected patient groups and could not be used to establish the current prevalence across the province.
“The important issue is that we are not routinely monitoring HDV because testing is not widely available in government or local private-sector facilities,” Dr Yousafzai said.
The missing diagnosis
The problem begins even before HDV testing. A large proportion of people living with Hepatitis B in Pakistan remain undiagnosed, while many of those who are diagnosed do not enter or remain in long-term care. Patients may discover they are infected incidentally during blood donation screening, pre-surgical testing or investigations for another illness, but detection does not always lead to registration, specialist assessment or continued follow-up.
“Many of these patients are identified accidentally, but they are not properly registered or followed up,” Dr Yousafzai said. “They may be lost from the system without confirmation, HDV detection or registration under the provincial programme.”
This creates a critical gap between finding Hepatitis B and completing the diagnostic pathway needed to determine whether a patient also has Hepatitis D.
Both infections can remain silent for years. By the time symptoms such as worsening liver function or other complications become apparent, significant damage may already have occurred.
“By the time obvious symptoms develop, significant liver damage may already have occurred,” Dr Yousafzai said.
He added that tertiary-care hospitals and private gastroenterologists frequently encounter patients with advanced liver disease who were previously unaware that they had HBV or HDV.
Without a provincial patient registry, he said, authorities also cannot determine what proportion of HDV patients eventually develop cirrhosis, liver failure or liver cancer.
Although specialised HDV testing is technically available in Pakistan, access remains limited.
Current clinical recommendations support screening people who are HBsAg-positive for anti-HDV antibodies at least once. Where antibodies are detected, an HDV RNA PCR test can confirm active infection and determine whether the virus is replicating.
But these tests are not routinely accessible to every Hepatitis B patient, particularly outside major cities.
Dr Yousafzai said some specialised private laboratories could perform HDV RNA testing, while the Public Health Reference Laboratory in K-P did not currently offer Hepatitis D testing.
“The biggest problem is the gap between detecting hepatitis B and completing the HBV-HDV diagnostic pathway,” he said.
The problem is not only availability but affordability. Patients in remote districts may have to travel to larger cities or specialised centres for molecular testing, while the cost of PCR and other investigations can place diagnosis beyond the reach of low-income families.
A recent survey of Pakistani liver specialists similarly highlighted the financial barrier. Around 83 per cent of experts surveyed said HDV diagnostic tests were available but unaffordable for many patients. Only about half reported routinely ordering the specific PCR test for HDV among their Hepatitis B patients.
For patients already struggling with the cost of repeated consultations, liver-function tests, imaging and antiviral medicines, an additional molecular test can become a significant burden.
The silent progression
The problem is particularly visible in Khyber-Pakhtunkhwa, where the provincial hepatitis programme provides services for Hepatitis B and C but HDV has not been systematically incorporated into routine surveillance and diagnostic systems.
Dr Tariq Mehmood, Director of Khyber-Pakhtunkhwa's Integrated Programme on HIV, Hepatitis and Thalassaemia, confirmed that the programme's current mandate primarily covers Hepatitis B and Hepatitis C.
“Under our programme, our mandate is focused on hepatitis B and hepatitis C,” he said.
For specialists, this omission is significant because the consequences of missing HDV can be severe.
Dr Mushtaq Ahmad, Assistant Professor of Gastroenterology and Hepatology at KMU Hospital and Research Centre, described HDV as an aggressive infection that can significantly increase the risk of severe liver damage, cirrhosis, liver failure and liver cancer.
“Superinfection can follow an especially aggressive course,” he said, explaining that it can lead to rapid progression of liver fibrosis and cirrhosis, hepatic decompensation and liver failure, while also increasing the risk of hepatocellular carcinoma.
HDV is primarily transmitted through exposure to infected blood and body fluids. Unsafe injections, contaminated needles, inadequately sterilised medical or dental equipment, unsafe blood transfusions and contaminated sharp instruments can all create a risk. Sharing razors and other objects contaminated with blood can also transmit the virus, while sexual transmission is possible.
The virus does not spread through food or water or through ordinary social contact. Shaking hands, hugging, sharing meals or sitting with someone infected with HDV does not transmit the disease.
Dr Imran Ali Syed, consultant gastroenterologist and hepatologist, said the presence of HBV was fundamental to HDV infection.
“Hepatitis D is a viral liver infection that can only occur in people who have Hepatitis B,” he said, adding that HDV can make HBV infection more severe and accelerate progression to cirrhosis and liver cancer.
He said HDV had been reported particularly in Balochistan and Sindh, followed by Punjab, but stressed that there was no reliable current nationwide estimate.
Punjab has established a network of hepatitis clinics through its provincial programme, providing services including registration, testing, vaccination and treatment for Hepatitis B and C. District and tehsil-level hospitals are also part of the system.
However, the situation is less clear when it comes to Hepatitis D. Available government information does not indicate a comparable province-wide programme specifically providing free and routine HDV screening and treatment. This creates a potential gap for patients who have already tested positive for HBV.
Dr Salman Kazmi, a Lahore-based internal medicine specialist, believed that expensive diagnostic tests, limited availability, low public awareness and the absence of a clear national screening policy remained important obstacles.
The issue is particularly important because Hepatitis B patients can require long-term monitoring even when they have few or no symptoms. If HDV is not considered during this follow-up, a potentially serious additional infection can remain undetected.
A costly battle
Managing HDV is considerably more challenging than preventing it.
The objectives of treatment are to suppress HDV replication, reduce liver inflammation and prevent progression to cirrhosis, liver failure and liver cancer.
Pegylated interferon-alpha remains an option for carefully selected patients under specialist supervision. Newer treatments, including bulevirtide, have emerged internationally but remain of limited availability in Pakistan.
Medicines such as tenofovir and entecavir may be prescribed to control Hepatitis B when clinically indicated, but they do not directly suppress HDV replication.
For patients, this can mean prolonged specialist follow-up, repeated blood tests and monitoring for liver complications.
The burden extends beyond medicine. Patients may need to travel repeatedly to tertiary-care hospitals, while families face transport, accommodation and lost-income costs.
In Punjab, patients interviewed for an investigation described being referred to major centres such as the Pakistan Kidney and Liver Institute in Lahore, sometimes after first seeking treatment closer to home. Their experiences highlighted the financial and logistical difficulties of repeated testing and hospital visits.
The medical principle, however, is that not every hepatitis patient necessarily requires referral to a specialised liver centre. Patients with uncomplicated disease can often be managed through appropriate district-level services, while those with advanced cirrhosis, liver failure, complex procedures or transplantation needs require specialised care.
The key question, therefore, is whether referrals are being made because of genuine clinical need or because appropriate diagnostic and treatment facilities are unavailable closer to patients' homes.
Because HDV depends on HBV, preventing Hepatitis B is also the most effective way to prevent Hepatitis D.
Dr Imran Ali Syed said vaccination against Hepatitis B was the most important preventive measure. Safe injections, screened blood, sterile medical and dental equipment, safe sexual practices and testing of people living with HBV were also essential.
This makes strengthening HBV diagnosis and vaccination a central part of any national HDV strategy.
Experts also believe that people already diagnosed with Hepatitis B should not be lost from the healthcare system. They should receive appropriate follow-up, and HDV screening should become part of their clinical assessment.
A recent survey of Pakistani specialists found strong support for formally incorporating HDV into national hepatitis programmes. More than 83 per cent of experts supported treating HDV as a distinct component of the national response, alongside clearer screening guidelines, awareness campaigns and improved access to treatment.
For a country already carrying a substantial Hepatitis B burden, the failure to identify how many patients are also living with HDV creates a dangerous blind spot.
The absence of reliable nationwide data does not mean the disease is absent. Instead, it means Pakistan cannot accurately determine where the burden is highest, how many patients require treatment or how many are progressing towards cirrhosis, liver failure and liver cancer.
Experts believe the response should begin with routine anti-HDV screening for people diagnosed with Hepatitis B, followed by HDV RNA PCR confirmation where appropriate. Testing should be made affordable and available beyond major tertiary-care hospitals.
A stronger response would also require a patient registry, integration of HDV into provincial hepatitis programmes, continuous availability of medicines, decentralised diagnostic services and clear referral pathways for complicated cases.
Public awareness is equally important. Patients need to know that a Hepatitis B diagnosis is not the end of the diagnostic process and that Hepatitis D can significantly alter the course of their illness.
Most importantly, prevention must remain at the centre of the strategy. Every Hepatitis B infection prevented through vaccination is also an HDV infection that cannot occur.
For Pakistan, the challenge is therefore not simply treating Hepatitis D after it appears. It is closing the gaps that allow Hepatitis B and HDV to remain undiagnosed, unmonitored and untreated until irreversible liver damage has already begun.
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