Prevalence and Response to Hepatitis C Infection in Pakistan and Its Association with Hepatocellular Carcinoma-A Review

Viral hepatitis is a major public health concern worldwide, affecting millions of people and contributing to significant morbidity and mortality. Hepatitis C affects approximately 5% of the Pakistani population and remains one of the country's leading causes of chronic liver disease. Hepatocellular carcinoma is the third leading cause of cancer-related mortality worldwide. In Pakistan, the transfusion of unscreened blood, reuse, misuse, and unsafe disposal of syringes are among the leading causes of HCV transmission. Most patients are diagnosed at a chronic stage, resulting in persistent disease progression. The diagnosis of chronic hepatitis C typically involves liver tissue biopsy to assess liver damage and quantitative PCR (qPCR) for viral RNA detection. Sequence analysis has identified chronic HCV infection as a major risk factor for HCC, with genotype 3a (HCV-3a) having a high prevalence (40.96%) in Pakistan, suggesting a strong correlation between HCV-3a and the development of HCC. Early diagnosis, direct-acting antiviral (DAA) therapy, and preventive public health measures should be prioritized to combat HCV infection. Although several vaccine candidates are under investigation, no licensed vaccine is currently available. However, in Pakistan, the high cost of hepatitis treatment poses a significant barrier, making preventive strategies essential to reduce both disease prevalence and economic burden. This review highlights the prevalence of hepatitis C in Pakistan, its association with hepatocellular carcinoma, genotype distribution, current treatment options, and preventive measures to control disease progression in the country.

Hepatitis is a major global health concern, affecting millions of people worldwide, with particularly severe infections reported in certain regions, including Pakistan. Compared to malaria, HIV, and tuberculosis, hepatitis is responsible for over 1.4 million deaths annually [1-3]. The hepatitis epidemic gained significant attention in 2015 when the World Health Organization (WHO) reported that hepatitis B virus (HBV) and hepatitis C virus (HCV) collectively infect 1 in 3 people worldwide, leading to approximately 1.3 million fatalities annually, making hepatitis the seventh leading cause of death globally [4,5].

Currently, six distinct types of hepatitis viruses have been identified: hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), hepatitis E virus (HEV), and hepatitis G virus (HGV). Among these, HBV, HCV, and HDV are responsible for persistent and chronic infections, whereas HAV and HEV typically cause acute, self-limiting infections [6,7]. HBV and HCV alone account for 90% of hepatitis-related fatalities, while the remaining 10% of deaths result from other hepatitis viruses [8,9].

Hepatitis viruses belong to different viral families, each with distinct genetic structures and replication strategies. Their clinical features and disease outcomes vary significantly. HAV and HEV infections are transient and primarily transmitted through the fecal-oral route, with HEV also having zoonotic transmission, mainly from swine. In contrast, HCV, HBV, and HDV are transmitted via the parenteral route, with infections ranging from transient to chronic. Despite these differences, all hepatitis viruses target hepatocytes, where they infect and replicate, usually without inducing cytolysis. However, they differ in host receptor interactions, immune evasion mechanisms, and pathogenesis, leading to varying disease severities and persistence strategies [10].

Pakistan bears one of the highest burdens of hepatitis globally, with increased morbidity from HAV and HEV infections and the highest mortality rates associated with HBV, HCV, and HDV [11]. As an underdeveloped country with a rapidly growing population and limited healthcare resources, Pakistan has the highest global burden of HCV infection, affecting approximately 5% (8 million people) of its population. Hepatitis C, an RNA virus from the Flaviviridae family, causes acute infections, with 50-80% of cases progressing to chronic hepatitis. Many infected individuals remain unaware of their condition, leading to chronic liver damage, cirrhosis, hepatocellular carcinoma (HCC), and, in severe cases, death. Consequently, HCV is a leading cause of liver transplantation in adults [12,13].

Hepatocellular carcinoma (HCC) is a major global healthcare challenge, accounting for 5% of all cancers worldwide and ranking as the third leading cause of cancer-related deaths. However, data on HCC in Pakistan remain limited, mostly derived from single-center studies focusing on HBV and HCV patients. Studies indicate that 60-70% of HCC cases in Pakistan are associated with HCV, whereas HBV is the predominant cause of liver cancer in other Asian countries, highlighting geographical variations in disease occurrence [14,15].

This review discusses the prevalence of hepatitis C in Pakistan, its association with hepatocellular carcinoma, genotype distribution, current treatments, and preventive measures. The findings could be valuable for healthcare professionals and policymakers in formulating effective strategies for disease management and prevention."

Risk Factors of Hepatitis C

Due to the absence of a centralized registry for HCV-infected patients in Pakistan, data is primarily derived from single-center studies or scattered regional reports. The infection spreads predominantly among the rural population, with key contributing factors including illiteracy, transfusion of unscreened blood products, and misuse of injectable medications. Additionally, the use of unsterilized medical equipment for minor surgical procedures and circumcision remains a significant concern in certain regions of Pakistan.

Use of Needles and Syringes

A significant mode of hepatitis C virus (HCV) transmission is the reuse of hypodermic needles and syringes without proper sterilization or safety precautions [16]. According to a World Health Organization (WHO) report, approximately 16 billion medical injections are administered annually in developing countries, many of which are unsterilized.

It has been observed that 71% of Pakistan’s population, from both urban and rural regions, believes that injections provide quicker pain relief compared to oral medications [17]. Consequently, the excessive use of syringes is widespread in Pakistan [18]. A survey-based report also indicated that some individuals were involved in unethical repackaging and resale of non-sterilized hypodermic syringes, making it difficult for people to differentiate between new, reused, and non-sterilized syringes [19].

In Pakistan’s Digri and Mirpurkhas districts, 68% of individuals use injections for drug intake, while only 54% reported using new, sterilized syringes in the past three months [20]. On average, 8 to 14 syringes are used per person annually, and 94.2% of these injections are deemed unnecessary [21]. This overuse of unsterilized syringes significantly increases the risk of HCV transmission [22].

Studies estimate that 57% to 84% of HCV infections in Pakistan are linked to the misuse of injections, with affected individuals receiving more than 10 intramuscular and 5 intravenous injections annually compared to normal individuals [23]. Another study reported that 94% of cases involved the use of unnecessary and unsterilized injections, with HCV prevalence reaching 44% in these individuals [16].

To combat this issue, WHO has recommended the introduction of a nationwide awareness campaign to educate both healthcare providers and patients about the risks associated with injection overuse. Emphasis should be placed on the use of new, sterilized needles and proper disposal of used syringes to prevent further transmission of HCV [23].

Blood Transfusion

Blood transfusions are widely performed in developing countries, but poor storage practices and contamination with hematogenous pathogens can lead to additional complications. WHO reports indicate that 1.2 to 1.5 million blood transfusions are carried out annually in Pakistan due to the high incidence of anemia, injuries, and obstetric complications.

Although proper screening of blood donors significantly reduces the risk of HCV transmission, inadequate screening procedures remain a major concern in Pakistan [24,25]. A study conducted in Karachi found that:

• Only 50% of blood donors were compensated, while 25% were routine donors.
• Only 23% of blood banks were able to screen for HCV due to economic constraints, as proper screening requires trained personnel and expensive equipment.
• 29% of blood storage facilities operated beyond WHO-recommended temperature guidelines, further increasing the risk of viral survival and transmission [24].

HCV can persist at 37°C (body temperature), room temperature, and even at 4°C (refrigerated storage) without losing its pathogenicity. This poses a serious risk to transfusion recipients, especially thalassemia patients, who frequently require blood transfusions. Studies indicate that 34% to 60% of thalassemia patients in Pakistan are infected with HCV, making them 3.6 times more susceptible to infection [26-31].

Use of Contaminated Instruments in Surgery

Surgical procedures and other medical interventions, such as endoscopy and dialysis, are well-documented routes of HCV transmission.

The risk of HCV infection increases by 1.7 to 2.4 times if surgical procedures are performed by untrained individuals, especially in dental clinics. Additionally, the risk of infection triples during major surgeries conducted under non-sterile conditions [29-33].

Barbers & Public Grooming Practices 

In Pakistan, face and armpit shaves at roadside barber shops are a common practice [34]. Unfortunately, many barbers are unaware of the risks of infection transmission through shared razors, scissors, and towels [35].

• Studies show that only 42% of barbers are aware of the risk of HCV transmission through contaminated tools.
• 90% of barbers do not wash their hands between clients.
• 66% of barbers reuse the same towel for multiple customers [36].

Additionally, potash alum (phitkari)-a commonly used antiseptic aftershave-has been identified as a potential source of HCV transmission. Cuts or wounds from infected individuals may contaminate the alum, and reuse on other customers can facilitate HCV transmission [37,38].

Sexual Transmission

In Pakistan, sexual transmission of HCV has not been widely reported. However, data from various studies indicate that 38% of the partners of patients with chronic liver disease tested HCV seropositive [39].

While sexual transmission is considered a less common route, risk factors such as unprotected intercourse, multiple sexual partners, and co-infection with other sexually transmitted infections (STIs) may increase susceptibility.

Prevalence of Hepatitis C in Provinces and Various Groups of Pakistan

HCV affects millions of people worldwide, with infection rates ranging from intermediate to high. Pakistan is among the most severely affected countries, with both acute and chronic infections. Given Pakistan’s size and rapidly growing population, there is a surprising lack of comprehensive data on the prevalence of hepatitis C, although its risk factors are well-documented.

According to Arshad et al., the prevalence of HCV in different provinces of Pakistan was reported as 5.46% in Punjab, 2.55% in Sindh, 6.07% in Khyber Pakhtunkhwa, 25.77% in Balochistan, and 3.37% in the Federally Administered Tribal Areas (FATA). The overall HCV prevalence across all provinces was estimated at 8.64%. The study identified the major transmission routes as the reuse of syringes and needles and unsafe blood transfusions. The prevalence of HCV among different population groups in Pakistan is further discussed in this review [40,41].

General Population

The prevalence of HCV in the general population of Pakistan has been estimated through various studies conducted over the past decade. The majority of these studies were published around 2010, with approximately six major studies contributing to the data. Additionally, two studies were conducted in 2008, two in 2011, two in 2012, and one in 2013. Based on a comprehensive assessment of these reports, the overall prevalence of HCV in the general population was estimated at 11.55% [41].

Children

A study assessing the prevalence of HCV infection in children enrolled 3,533 participants, who were examined for the presence of anti-HCV antibodies [42].

Pregnant Women

Most studies investigating HCV prevalence in pregnant women were conducted between 2008 and 2011. Hepatitis C during pregnancy can lead to serious complications, including maternal and fetal morbidity and, in severe cases, death. Past studies estimated the HCV prevalence in pregnant women at 4.65% [41].

Blood Donor

Blood donation is a noble act that saves lives. However, in Pakistan, HCV transmission through infected blood donations remains a significant concern and a major risk factor that requires strict monitoring [29]. Data on the prevalence of HCV among blood donors was collected from various studies, primarily published in 2009 and 2010. The combined findings indicated that the prevalence of HCV among blood donors in Pakistan was 10.10% [41].

Injection Drug User

The use of injectable drugs in Pakistan has increased significantly, contributing to the rapid spread of blood-borne infections such as HCV. The sharing of contaminated needles and syringes among drug users is a primary mode of transmission [43].

Chronic drug dependency is known to cause neurocognitive impairments, leading to structural and functional changes in the brain, which may result in adverse behavioral outcomes [39]. In recent years, there has been a notable shift from inhaled drug use to injectable drug use, further exacerbating the risk of HCV transmission.

A review of studies conducted between 2005 and 2013 estimated that the overall prevalence of HCV among injectable drug users (IDUs) in Pakistan was 51% [41].

Structure and Pathogenesis of Hepatitis C Virus

Hepatitis C virus (HCV) is a single-stranded, positive-sense RNA virus belonging to the Flaviviridae family, genus Hepacivirus [44,45]. The virion has a diameter of 45-65 nm. Its genome consists of approximately 9.6 kb, containing a single open reading frame (ORF) that encodes a polyprotein of ~3,000 amino acids. This polyprotein is encapsulated in a nucleocapsid, which is non-icosahedral in structure and composed of multiple small core proteins. The nucleocapsid is further surrounded by a lipid bilayer envelope, embedded with two envelope glycoproteins (E1 and E2).

The ORF is organized into two main sections: The N-terminal region, which encodes structural proteins (core, E1, and E2), and the C-terminal region, which encodes non-structural proteins (p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B). In an infected host, viral particles associate with low-density lipoproteins (LDLs) and very-low-density lipoproteins (VLDLs), forming lipoviroparticles (LVPs) containing apolipoproteins B, C, and E [46,47].

Viral Entry and Replication

HCV attachment to host cells involves E1 and E2 envelope glycoproteins, apolipoproteins, and several host cell receptors. Initial binding occurs via glycosaminoglycans and LDL receptors, followed by interactions with CD81 and scavenger receptors. Entry is further facilitated by claudin-1, -6, or -9, occludin, and epidermal growth factor receptor (EGFR), forming a tight HCV-host receptor complex that promotes viral transmission. The virus enters the host cell via clathrin-mediated endocytosis, where E1 acts as a fusogen, enabling fusion of viral and endosomal membranes, leading to nucleocapsid release into the cytoplasm. Meanwhile, E2 glycoprotein contains hypervariable regions, allowing HCV to evade host immune responses [48,49].

Once inside the host cell, HCV undergoes uncoating, releasing its genome into the cytosol, where it serves as both a template for replication and mRNA for polyprotein synthesis. Polyprotein synthesis occurs in the endoplasmic reticulum (ER) and requires host-derived enzymes (signalase and signal peptidase) and viral proteases (NS2 and NS3/4A) for cleavage. Host peptidases facilitate the synthesis of structural proteins, while viral proteases process non-structural proteins.

For replication, the positive-sense RNA strand serves as a template for negative-strand RNA synthesis, which then generates additional positive-strand RNAs. This process is mediated by the RNA-dependent RNA polymerase (NS5B), while NS5A and NS3 (helicase-NTPase) regulate replication. NS5A facilitates RNA binding, whereas NS3 separates newly synthesized strands. At later stages, viral assembly occurs via VLDL pathways, leading to the release of new virions that infect additional host cells [48-55].

Immune Evasion and Chronic Infection

HCV employs multiple mechanisms to evade host immune responses, leading to persistent infection. The virus triggers innate and adaptive immune responses, with natural killer (NK) cells playing a key role in innate immunity and CD4+ and CD8+ T cells contributing to adaptive immunity. However, HCV-specific antibodies are often ineffective due to genetic and structural variability in the viral genome.

During the progression from acute to chronic infection, T-cell subpopulations decline, leading to immune dysfunction. Experimental studies on chimpanzees have shown that the absence of CD8+ T cells results in persistent infection until the T-cell response is restored. HCV interferes with the interferon (IFN) signaling pathway through NS3/4A proteins, suppressing antiviral responses. As chronic infection advances, immune exhaustion increases, leading to functional impairments in mucosal invariant T cells, NK cells, and intrahepatic T cells. At later stages, programmed cell death markers (apoptosis) are upregulated, facilitating viral persistence. Inefficient viral clearance results in persistent hepatocyte damage, contributing to fibrogenesis, cirrhosis, and hepatocellular carcinoma (HCC) [13,56].

HCV-Induced Fibrogenesis and Hepatocellular Carcinoma (HCC)

Chronic HCV infection is a leading cause of liver fibrosis, cirrhosis, and HCC. Fibrogenesis is triggered by host inflammatory responses, including oxidative stress, cytokine release, and immune cell infiltration. Overproduction of chemokines, cytokines, and growth factors activates hepatic stellate cells (HSCs), which differentiate into myofibroblasts, promoting fibrosis.

Additionally, HCV directly acts as a fibrogenic agent, accelerating liver fibrosis through interactions between viral proteins and host cell cycle regulators. Oxidative stress-induced DNA damage disrupts cell cycle checkpoints, further promoting hepatocyte transformation and oncogenesis. Over time, fibrosis progresses to cirrhosis, with 4-5% of cirrhotic patients developing HCC, making it a key determinant of liver cancer. This suggests that HCV contributes to carcinogenesis by overriding cell cycle regulation, inducing genomic instability, and facilitating hepatocyte transformation [13,56]."

Association between Hepatitis C and Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. It is a heterogeneous group of tumors that vary in risk factors as well as genetic and epigenetic alterations. The molecular progression of HCC depends on diverse factors involving multiple pathways. A few important pathways associated with HCC progression are discussed here. HCC is a multistep process that can take up to 20 to 40 years to develop. It requires the establishment of chronic HCV infection with persistent liver inflammation, which progresses into fibrogenesis, followed by the formation of a chronic neoplastic condition with irreversible genetic/epigenetic alterations and the progression of malignant clones into a functioning carcinogenic tissue microenvironment [57].

Chronic HCV infection with well-established inflammation can lead to HCC. This malignant transformation of hepatocytes is due to a continuous and recurring process of necrosis and regeneration, inducing mutations and DNA damage in hepatocytes, which are then passed on to daughter cells. The accumulation of mutations in individual cells over time results in uncontrolled liver cell growth and malignant transformation [58]. HCV-induced reprogramming of metabolic processes, such as lipid metabolism dysregulation, mitochondrial dysfunction, and oxidative stress, contributes to HCC development. Dysfunctional lipid metabolism is triggered by impairment of β-oxidation, leading to mitochondrial damage. As a result, oxidative stress is activated, further driving HCC progression. The production of reactive oxygen species (ROS) has also been associated with genomic mutations, which are critical markers for cancer cells.

In addition, increased activity and mutations in the telomerase (TERT) promoter are considered hallmarks of HCC development in HCV-infected individuals. Enhanced TERT expression has been identified as one of the earliest and most prevalent neoplastic events in HCC. The Fas system allows HCV to escape T-cell-mediated immunity, enabling persistent HCV infection. Moreover, the effect of viral proteins on the epithelial-mesenchymal transition (EMT) pathway promotes fibrogenesis, tumor development, and metastasis, leading to the generation of chemokines, cytokines, and other inflammatory markers associated with HCC progression [59].

Idrees et al. conducted a study on a small group of HCV-infected individuals (n=145) to determine the association between HCV and disease progression to HCC in Pakistan. HCV identification in patient samples was performed using qPCR, and genotypic analysis of positive samples was conducted using the non-coding region of the viral genome through sequence analysis. The study found that 63% of patients had HCV as the major risk factor for HCC development, with HCV genotype 3a (40.9%) being the most predominant, followed by genotype 3b (15.66%), genotype 1a (9.63%), and genotype 1b (2.40%). These findings suggest a strong association between chronic HCV infection, genotype 3a, and HCC in Pakistan [60].

Hepatitis C Genotypes and Their Prevalence in Pakistan

According to phylogenetic and clinical analyses, HCV is classified into six major genotypes and more than 100 subtypes, designated as a, b, c, etc. These genotypes differ based on their biological properties, clinical outcomes, and response to antiviral treatment. The genetic variability of HCV provides important insights into the prevalence of the disease in specific regions, transmission modes, and pathogenesis [61-63].

Alterations and mutations in the viral genome can drive the progression of chronic HCV infection into hepatocellular carcinoma in patients with established cirrhosis [64-67]. These mutations vary across different regions of the HCV genome. A high mutation rate has been observed in two hypervariable regions of the E2 envelope glycoprotein [68] and in the 5' untranslated region of the open reading frame [69,70]. Due to its genetic diversity, HCV exhibits significant genetic heterogeneity, with a nucleotide substitution rate of up to 1.92 × 10³ per site [71]. Based on this variability, HCV isolates are categorized into types, subtypes, isolates, and quasispecies [69].

Three distinct genotypic distribution patterns of HCV strains have been identified, including genetic diversity across different geographical regions, subtype distribution among specific risk groups [72,73], and the circulation of a single subtype within particular populations. Recently, a shift in genotype distribution has been observed, with genotypes 3a and 1a becoming more prevalent, while the prevalence of other genotypes is declining in many countries [74-77].

In Pakistan, approximately 10 million people are affected by HCV, with genotype 3a being the most prevalent, followed by genotypes 3b and 1a [18,78]. However, due to limited data and available literature, an exact evaluation of infection routes and their correlation with genotypes remains challenging [79].

Ijaz et al. conducted a study on a small population group in Lahore, Pakistan, to assess the prevalence of HCV genotypes. The study reported that 51.6% of individuals were infected with genotype 3a, 27.7% with genotype 3b, 13.5% with genotype 1b, 3.2% with untypable genotypes, 2.5% with mixed genotypes 3a/1b, and 10.6% with mixed genotypes 3a/1a and 3b/1a. However, the mode of infection transmission was not determined in this study group [80].

Etiology and Clinical Presentation of Hepatocellular Carcinoma

There are various contributing factors in the etiology of hepatocellular carcinoma (HCC), which vary with geographical distribution. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are recognized as the major causes of HCC worldwide. More than half of HCC cases are linked to HBV and HCV infections. Liver cirrhosis, regardless of its cause, leads to HCC progression in the majority of cases, with an estimated 93% of HCC patients having underlying cirrhosis. Other established risk factors associated with hepatocarcinogenesis include alcoholic liver disease, nonalcoholic steatohepatitis (NASH), consumption of aflatoxin-contaminated food, diabetes, and obesity. The development of HCC is a complex process involving multiple alterations in several pathways and genetic transformations of hepatocytes [81-85].

HCC remains asymptomatic in most patients and may progress to critical conditions. Approximately 90-95% of HCC patients present with right upper quadrant pain, a palpable mass, and weight loss [86]. Common symptoms associated with HCC include jaundice, hepatic encephalopathy, anasarca, ascites, variceal bleeding, diarrhea, paraneoplastic symptoms, skin manifestations, and abnormal laboratory findings. However, certain rare clinical presentations have been reported in metastatic HCC, including nasal alae involvement, parotid gland metastasis, and spinal cord compression [87].

Diagnosis of Hepatitis C and Hepatocellular Carcinoma

The diagnosis of hepatitis C is based on serological and molecular assays, which are essential not only for detecting the infection but also for guiding therapeutic decisions and evaluating the response to antiviral treatments [88]. Various immunoassays have been developed to detect anti-HCV IgG in patient serum.

In the past, third-generation enzyme immunoassays (EIAs) were commonly used for the detection of anti-HCV antibodies. However, more recently, fourth-generation immunoassays have been developed, which can simultaneously detect HCV capsid antigens, including core, NS3, NS4, and NS5, as well as anti-HCV antibodies [89]. Nucleic acid testing (NAT) is a highly sensitive method used to detect HCV RNA in blood. Quantification of HCV RNA can be achieved through quantitative real-time PCR (qRT-PCR) and branched DNA (bDNA) technology. In addition, standard RT-PCR is available as a qualitative method for detecting HCV RNA [90]. Different HCV genotypes exhibit variable responses to antiviral therapy; therefore, genotyping assays are crucial for treatment planning. These assays are based on sequencing highly conserved genomic regions such as NS5, core, E1, and the 5' untranslated region (5’UTR) [91].

Liver Disease Staging

The type and duration of HCV treatment depend on the stage of liver damage. Various methods are used to assess the extent of liver damage; however, while non-invasive tests are not as precise as liver biopsies, they are safer and easier to perform. These tests include ultrasonography, CT scan, MRI, and ERCP [92].

Histological Examination

HCC is primarily diagnosed through imaging; however, histological examination, such as tissue biopsy, is an invasive procedure. It is recommended for cirrhotic patients when imaging characteristics suggest HCC. Percutaneous DNA biopsy techniques are used in patients with advanced malignancies; however, biopsy is not indicated in patients with focal lesions in a cirrhotic liver or those with decompensated cirrhosis [92]. In such cases, an alternative approach to tissue biopsy in HCC patients is the investigation of circulating tumor cells (CTCs), which are considered the seeds of tumors [93]. Alpha-fetoprotein (AFP) is a widely recognized tumor marker for the detection of hepatocellular carcinoma [94].

Microscopic Findings of Liver Tumors

The histomorphologic appearance of HCC varies significantly. Its characteristics include well-vascularized tumors with broad trabeculae, prominent acinar patterns, atypical squamous cells, absence of macrophages, and a reduction in the reticulin network. Additionally, the presence of Mallory bodies, pale bodies, and increased bile production in tumor cells are commonly observed features [95].

Treatment and Preventive Measures for Hepatitis C

The treatment of HCV is based on medications that control the symptoms of infection and the use of antiviral drugs that directly target and eliminate the virus. The interferon-free combination of ritonavir, ombitasvir, and ribavirin has shown efficacy against genotype 1 infection [96]. Available drugs include inhibitors of RNA-dependent RNA polymerase, NS3/4A protease inhibitors, NS5A protein inhibitors, and ribavirin; however, the effectiveness of antiviral drugs varies depending on the HCV genotype. The treatment of HCV has been revolutionized by the introduction of direct-acting antiviral agents (DAAs) [97]. These interferon-free regimens are relatively safe, highly effective, and result in sustained viral suppression [98]. Previously, pegylated interferon alpha and ribavirin were the standard of care for HCV genotype 3 infections, achieving a sustained virologic response in approximately 65% of infected patients [99].

Currently, there are no approved vaccines for HCV. The high heterogeneity and mutagenicity of the HCV genome present significant barriers to vaccine development. There are two major approaches to HCV vaccine development: prophylactic and therapeutic. DNA- and vector-based vaccines are currently under development, while peptide and recombinant protein vaccines are in phase I/II clinical trials [100].

The World Health Organization (WHO), in collaboration with health authorities worldwide, has developed strategies to effectively control HCV by reducing its incidence and associated mortality by 2030. However, Pakistan faces several challenges in HCV control and prevention, including lack of awareness, limited diagnostic facilities, an insufficient number of healthcare professionals, and a lack of robust epidemiological data [5]. Increasing public awareness about HCV transmission and prevention can significantly reduce the risk of exposure. Strengthening blood screening protocols, improving patient follow-up studies, and enhancing documentation of cases and risk factors will contribute to better disease prevention and management [101].

Hepatitis C infection is a liver disease that ranges from acute to chronic conditions, with severe liver damage potentially leading to the development of hepatocellular carcinoma (HCC). It is more prevalent in regions with inadequate infection control practices, such as the World Health Organization's Eastern Mediterranean region. Multiple strains of HCV exist, and their distribution varies by geographic location.

HCV is a bloodborne pathogen that is primarily transmitted through the sharing and misuse of syringes, inadequate sterilization of medical equipment, and the transfusion of unscreened blood and blood products. Chronic HCV infection often progresses to cirrhosis, which is triggered by cellular transformation and leads to HCC.

Diagnostic procedures for HCV infection rely on anti-HCV immunoassays and nucleic acid amplification techniques. The degree of liver damage is assessed through liver biopsies or various noninvasive techniques. Since no vaccine is currently available for HCV infection, prevention depends on minimizing the risk of exposure to the virus in healthcare settings and among high-risk populations.

Conflict of Interest

Declared None. 

Acknowledgements

Declared None.