Significant advances have been made in recent years in terms of disease-modifying treatment of multiple sclerosis (MS). A large number…
Case Study 1
A 34-year-old, former inter-county Gaelic footballer (six years), was referred to the clinic with a history of persistent, severe pain in the right hip, which has come to affect his daily quality of life (sleeping, driving, any long journeys) for the last six months. At time of initial consultation, he was no longer able to play sports or run due to pain. He suffered from chronic, recurrent groin discomfort during his inter-county career. On examination, there was marked global stiffness and he had lost a significant amount of flexion, all rotation and adduction of the flexed hip. X-rays confirmed significant osteoarthritis. Due to increasing discomfort, limping and inability to perform daily activities, he decided to proceed with total hip replacement 11 months later.
Case Study 2
A 28-year-old male competitive rugby player (playing since he was eight years old) presented with a gradual onset of symptoms for over four years. Imaging of his hip was undertaken three years earlier at another institution, revealing osseous prominences suggestive of early CAM-type morphology.
At time of presentation to our clinic, he complained of a moderate level of pain, slight limp and difficulty putting on shoes/socks. X-rays taken demonstrated that his left hip had signs of established osteoarthritis (OA) and would not benefit from preservation surgery. Magnetic resonance arthrogram (MRA) demonstrated joint space narrowing and thinning of the articular cartilage and the presence of a paralabral cystic degeneration.
During the last decade in particular, the movement-associated clinical disorder known as femoroacetabular impingement (FAI) has become commonly recognised as the source of chronic hip and groin pain. The prevalence is estimated to be 10-to-15 per cent of the general population and is significantly higher among athletes (as much as 72 per cent reported for field-based athletes). As knowledge about this mechanical problem has advanced, its contribution to the premature degeneration of the hip is becoming clearer.
FAI occurs when there is abnormal, repetitive contact between the ball-and-socket structures of the hip joint as it moves. This can begin to occur from as young as 10-to-12 years of age when the naturally spherical femoral head becomes misshapen (known as a CAM deformity) or when the acetabular rim of the socket develops excess bone (known as a Pincer deformity). For the most part, these abnormalities are developmental in nature and become progressively worse over time. A CAM can result in a shearing force on the labrum (whose function is to provide depth and stability to the hip socket), as well as to the protective covering of the hip surface (articular cartilage).
A pincer will also cause destruction to the labrum and articular cartilage. The risk of developing osteoarthritis (OA) as a result of damage to these protective structures then becomes inevitable.
The general consensus is that higher demands placed across the hip joint contribute to FAI-associated deformities becoming symptomatic, consequently leading to accelerated cartilage wear. When considering the requirements being expected from the joint in terms of activity regimes, as a clinician, it is important to know when to act and what management route to take to preserve optimum functioning of the hip joint. In all cases, particularly for the developing athlete, early diagnosis is vital to prevent irreversible damage to the articular cartilage.
Given the limitations of access to x-ray and magnetic resonance arthrogram (MRA) scanning, the physiotherapist or GP attending a symptomatic athlete must have a high index of suspicion to the possibility of an underlying hip pathology. Careful evaluation of potential symptoms coupled with a thorough clinical examination will alert the practitioner to early signs of FAI.
Unfortunately, as we see in our clinic all too often, athletes are referred too late, considering the duration of their symptoms. In the two case studies in this article, all athletes reported a long-standing, identifiable hip/groin issue, which they have struggled to alleviate with conservative management. It is worth mentioning that a period of conservative management towards alleviating acquired hip and groin symptoms should always be trialled initially. However, the question then arises of how long an athlete should persevere with conservative treatment for FAI when a mechanical bony restriction is hindering any observable results.
There are very few studies evaluating outcomes, such as return to sport or duration of any lasting benefits from conservative treatment alone. More focused comparative trials are needed to substantiate this as a viable treatment option for FAI.
In order to determine the impact of a particular treatment course for symptomatic FAI, it is necessary to objectively evaluate outcome. There is an overwhelming international body of evidence that demonstrates the successful results of arthroscopic surgery in the treatment of athletes with symptoms from hip impingement. For the past decade at The Hip and Groin Clinic, outcome measures have been an important component of clinical practice for all patients undergoing surgical treatment for symptomatic FAI.
The premise behind arthroscopic preservation surgery is to prevent the further degradation of the hip and subsequent development of OA by correcting abnormal and destructive hip mechanics and repairing protective structures such as the labrum and stabilising the hip capsule. A specialised technique (labral cuff repair) developed and only performed at UPMC Whitfield has this focus in mind; relieving pain in 97.1 per cent of cases and enabling a return to sports in 94.2 per cent of cases.
Ultimately, the aim is to avoid the need for premature hip replacement, while restoring quality of life and athletic performance. An important point to note is that the potential for lasting benefits of surgery are largely related to the initial integrity of the hip joint, as well as surgeon experience. The emphasis is therefore directed toward the hip in its pre-arthritic state, ideally before the onset of irreversible cartilage damage.
One of the most identifiable radiographic signs and a relative contra-indication for preservation surgery is a significant loss of joint space (generally evidenced by Tonnis Grade >2 or <2mm of joint space). The arrival to this state is progressive and in retrospect all symptomatic athletes will reveal that throughout their sporting career they continued to play with symptoms and ignored warning signs such as stiffness after activity, recurrent groin pain, recurrent hamstring tightness and reduced range of hip movements.
In cases where athletes are presenting with these recognised symptoms, appropriate onward referral should not be delayed.
Screening for FAI
Naturally, there will always be an increased prevalence of OA with increasing age, among athletes in particular but also within the general population as a whole. In a recent screening study undertaken at the Hip and Groin Clinic, a cohort of asymptomatic GAA athletes were assessed for prevalence of signs and symptoms known to be associated with FAI. In this study of 124 athletes, 59.3 per cent reported stiffness in one or both hips; 43.1 per cent experienced pain in the hip/groin; impingement testing (pain on hip flexion, internal rotation and adduction, FADIR) was positive in 27 per cent of hips; flexion was reduced in 10.1 per cent of hips (<114o); and internal rotation was reduced in 23.8 per cent of hips (<27o). The results of this study revealed a high proportion of athletes demonstrated symptoms and signs in keeping with underlying FAI. Further longitudinal screening studies are needed in order to be able to understand the relationship between early warning signs and the progression to symptomatic FAI or OA, with the hope of putting preventative strategies in place before irreversible damage is done.
Outcomes from our clinic show that those who have symptoms for more than two years prior to scheduling surgical intervention, while improving significantly from their pre-operative state, have poorer outcomes compared to those who have initial symptoms for less than two years. Arthroscopic surgery generally yields superior outcomes for those at the younger age spectrum. For the 2,000+ athletic cases undergoing surgical management, one-in-three cases reported symptom duration longer than two years and all had exhausted conservative treatment, with prior attendance to an average of 2.7 HCPs for their symptoms.
Quality-of-life (QoL) and economic toll of FAI
While improved quality of life and symptomatic relief are the objective for any clinician dealing with a case of hip and/or groin issues, the effect of a particular treatment regimen toward achieving these goals must also be scrutinised. One recent study compared the cost-effectiveness of hip arthroscopic surgery against structured rehabilitation alone for the treatment of labral tears in patients without OA. It was found that hip arthroscopy was more cost-effective and the lifetime incidence of symptomatic OA was over twice as high for patients treated with rehabilitation compared to arthroscopic surgery. Timely recognition and diagnosis of related conditions, such as labral tears, are an important source of cost-effectiveness.
It is important that not only the patient, but also GPs and other healthcare practitioners who are collaboratively involved in the treatment of an athlete with hip and groin symptoms are provided with up-to-date outcomes, both surgical and conservative.
Athletes are particularly prone to developing symptomatic FAI due to the twisting/turning, acceleration/deceleration aspects of their sports.
Evidence-based research suggests that FAI causes OA.
Red-flag warning signs of possible FAI:
Recurrent groin pain.
Recurrent hamstring tightness.
Accurate diagnosis requires radiographic-specific imagery, in addition to patient history and clinical examination.
Delay in diagnosis (symptoms >two years) can lead to poorer long-term outcomes.
Preservation surgery can produce excellent outcomes, provided early diagnosis is made.
The most appropriate course of treatment can only be given once all possibilities are explored. Clinical outcomes and structured follow-up are vital to assess the outcome of intervention.
A 30-year-old male inter-county hurler presented to the clinic with bilateral hip pain, with symptom duration of three years. The patient had a history in keeping with femoroacetabular impingement (FAI), and reported pain while twisting and turning and substantial stiffness following activity, although was still engaged in full training and competition. His symptoms had failed to resolve with conservative management.
Upon assessment, the patient had a positive FADIR (flexion, adduction and internal rotation) test and had radiological signs indicative of FAI. The patient was subsequently assessed on all of the functional assessments mentioned above and displayed lower levels of acceleration, agility and range of motion (ROM) compared to the average healthy control group scores.
The patient underwent bilateral arthroscopic hip surgery for the correction of FAI (one week apart): The abnormal, bony deformity was resected using a mechanical burr, restoring the normal contour of the acetabular rim (pincer) and femoral neck (CAM) (), a torn labrum was repaired with suture anchors and a capsular repair was performed to optimise hip stability. No complications were recorded following the procedure and a standardised rehabilitation was given to the patient to complete.
At 12 weeks’ post-surgery, the patient was symptom-free and had completed their post-surgical rehabilitation; functional performance tests were performed and demonstrated statistically significant improvement in measures for agility and hip ROM, with significant reduction in pain during all ambulatory and squatting tests. The patient returned to training and competition 13 weeks’ post-surgery.
At one-year follow-up, the functional performance tests were repeated and the patient had improved on all functional tasks, with greater acceleration, further improvements on the agility measure, increased squatting depth and increased jump height. All improvements in ROM observed at three months’ post-surgery were maintained at one year and the patient reported no pain or stiffness on any of the test measures. Scores were now comparable to a mean matched, healthy control group, demonstrating restoration of athletic performance.
The benefits of regular participation in sports during adolescence and adulthood are numerous and well documented. Yet the increased focus on success with amplified training and competition schedules has the potential to cost young athletes far more than just time and effort. Injuries in sport are inherent and at times unavoidable but the worrying increase of hip-related issues among young athletes is a growing cause for concern. One of the most recognised sources of chronic hip injury in athletes is known as femoroacetabular impingement (FAI).
FAI is a motion-related disorder of the hip caused by excessive bone growth on the femoral head/neck junction (CAM impingement) or the rim of the pelvic acetabulum (pincer impingement). Although these deformities may develop in isolation, patients generally present with a combination of both. During movement, this additional bone leads to repeated abnormal contact between the prominent acetabular rim and the abnormal femoral head/neck junction.
Over time, this will lead to degrading of the underlying soft tissue within the joint, namely the labrum and articular cartilage, and the potential to develop osteoarthritis is a major concern. This issue is extremely common among young athletic populations, especially those involved in sports that require a high level of twisting and turning movements.
What is the cause of FAI?
The aetiology of FAI is still unclear and no doubt multifactorial in nature. Recent literature has shown that not everyone with a bony deformity will progress to symptomatic FAI, therefore contextual factors must be examined in determining why this is the case. Increased sports participation, especially during bone development, may be a risk factor for the development of bony deformities, which progress to symptomatic FAI as the athlete grows older. There is a growing body of evidence which supports this concept; a common theme emerging from the research shows athletes of 12 years of age or younger appear to be particularly at risk of developing abnormal bony hip morphology.
A study conducted at our institution (recently accepted for publication following peer review) compared athletes undergoing arthroscopic FAI surgery to an asymptomatic, matched control group, with regard to the number of weekly training hours carried out between the ages of 10-to-12 and 13-to-15 years. Our results show that the athletic patients reported engaging in more structured training in the 10-to-12 years age category compared to the healthy, athletic control group. This study highlights the potential risk high training volumes could pose for the development of FAI later in the player pathway.
Rather than deter parents from allowing their children to participate in sport, we suggest the need for increased awareness of the potential risk among coaches, physiotherapists, doctors and parents. Early hip screening and consistent monitoring of at-risk adolescent athletes will allow for earlier preventative measures to decrease the risk of developing abnormal bony morphology and later progression to symptomatic FAI.
What to look out for?
Patients will typically present with anterior groin pain and hip stiffness during and following activity, which they describe as insidious in nature and not attributed to a traumatic event. Patients may also report an audible clicking sound emanating from the hip during movement, and upon clinical assessment, will display lower levels of hip range of motion (ROM) and a positive impingement test with pain on flexion, adduction and internal rotation (FADIR).
Radiographic assessment of the patient, which includes plain radiography and magnetic resonance arthrogram (MRA), is used to determine the shape of the femoral head/neck junction, the acetabulum and to determine labral and cartilage pathology.
How to treat FAI?
Treatment options include activity modification and conservative management. Evidence to support successful outcomes using conservative treatment measures for symptomatic FAI is poor and therapy methods commonly employed are largely based on recommendations rather than objective results. However, it is generally accepted that rest, activity modification, NSAIDS and physiotherapy should be undertaken for a period of up to three months before considering surgical options.
Arthroscopic hip surgery that removes the obstructing bone and repairs the underlying tissue has been shown to improve symptoms and allow athletes to return to a pre-injury level of competition. Long-term follow-up studies have shown sustained improvements at 10 years’ post-surgery for patients with no evidence of osteoarthritis at the time of surgery. However, in the presence of established preoperative osteoarthritic changes, a poorer outcome with conversion to total hip arthroplasty is more likely.
Early intervention for symptomatic FAI is associated with more substantial and sustainable improvements; early diagnosis and appropriate treatment, therefore, are paramount to improved outcomes.
Implications for athletic performance
FAI by nature does not require immediate cessation of sports participation and athletes may continue to compete, albeit at a disadvantage compared to their competitors. The effect of FAI on athletic performance had not been examined previously until a prospective research study was undertaken at Waterford Institute of Technology and UMPC Whitfield. Athletes with FAI (average age 25 years) were examined prior to arthroscopic treatment on a number of performance measures and compared to matched healthy athletes (for age, height, weight, sporting type and sporting level). All participants were assessed first for acceleration and agility capacity; both of which are essential attributes needed to perform well during field sports. Squatting depth was assessed, and a single-leg drop jump (dropping from a height of 30cm) was used to indicate lower limb power. Finally, hip ROM was assessed for flexion, abduction and internal rotation.
Three-quarters of the athletic patient group were still engaged in full training and competition schedules at the time of testing. Results indicated that the patient group was 3 per cent slower to accelerate and 8 per cent slower on the agility measure. Athletic patients also reported anterior groin pain both during the acceleration (54 per cent) and agility (62 per cent) assessments. We did not find any differences between the groups for squatting depth or in the generation of lower-limb power, however 56 per cent of patients reported groin pain while squatting. The patient group also had lower levels of ROM in all three planes compared to the healthy athletes.
These deficits in performance, as well as pain, place athletes with FAI at a considerable disadvantage compared to other competitors, which can ultimately affect team performance. Coaches should also note that discrepancies in performance are not fitness related and considerations should be made to cater for athletes with FAI in fitness programming if the athlete wishes to continue with competition. Recognition of the symptoms by coaching and medical staff working with athletes will mean implementation of treatment earlier and better outcomes.
The role of surgery in improving athletic performance
Arthroscopic surgery has been reported throughout the literature to improve symptoms among athletic patients and an overall return-to-play rate of 74 per cent. Risk factors for poorer outcomes include patients who are older at the time of surgery, those who have evidence of osteoarthritis and those who have more severe symptoms or longer symptom duration. In relation to athletic performance, there is very little research currently published which chronicles athletic performance following intervention. Preliminary results from the prospective study mentioned above, which were presented at the International Society for Hip Arthroscopy conference proceedings in 2017, indicate that hip ROM and agility improved as early as 12 weeks, with some reductions in pain. At one year, the patient group showed improvements in agility, squatting depth, lower-limb power and sustained the improvements in hip ROM.
The high-intensity, multi-directional nature of hurling places significant demands on the hip joint (Picture Source: Donall Farmer/INPHO)
FAI — key symptoms to remember
Young, otherwise healthy athlete with no prior history of hip problems during childhood.
Progressive hip stiffness and increase in general inflexibility.
Groin pain during or following activity, especially twisting and turning sports.
Tight hamstrings, gluteal discomfort.
Clicking sound within the hip.
Reduced range of hip motion.
Symptomatic FAI will affect athletic performance.
Trial three months conservative treatment.
Arthroscopic surgery may resolve symptoms and restore athletic function.
For further information, please contact firstname.lastname@example.org, or visit the websites www.sportship.com or www.hipandgroinclinic.ie.
A 72-year-old man attended his GP complaining of a painless gradual fall in vision over the preceding 12 months, with the right eye becoming significantly worse in the past two weeks. The man had no past ophthalmic history apart from hyperopia (farsightedness). His medical history was significant for hypertension, which was controlled with a calcium channel blocker and he had a 40 pack-year smoking history. His GP referred him to his local ophthalmic emergency department.
On examination his Snellen visual acuity was 6/48 in the right eye and 6/18 in the left. Central vision was reduced, causing considerable difficulty with reading, however, peripheral vision was maintained. The man did not have visually significant cataract. Testing with an Amsler grid revealed marked metamorphopsia in the right eye. (See below). Dilated fundal exam revealed a haemorrhage at the right macula and atrophic changes at the left macula. Fundus fluorescein angiography (FFA) confirmed a diagnosis of neovascular (wet) AMD in the right eye and non-neovascular (dry) AMD in the left.
The man was commenced on monthly intravitreal injections of anti-VEGF agent bevacizumab into the right eye and reviewed in the medical retina clinic after his third injection. Visual acuity in the right eye improved to 6/18 with a marked reduction of intra-retinal fluid and the patient was commenced on maintenance of six- to eight-weekly injections to preserve his central vision.
Age-related macular degeneration (AMD) is the most common cause of vision loss in people over 50 in the Western world. The two main forms of AMD are neovascular and non-neovascular, or ‘wet’ and ‘dry’ AMD as they are more commonly referred to. AMD affects a patient’s central vision and therefore has a significant impact on that person’s ability to function independently, as reading and writing can become difficult to impossible.
Increasing age – 0.2 per cent of women and 0.3 per cent of men have AMD at ages 50-54 years compared with 1.5 per cent of women and 2.0 per cent of men aged 70-74 years. Many prevalence studies show a higher prevalence in women however this is generally attributed to increased longevity in females.
Race – AMD is more common in Caucasian individuals than in those of other races.
Tobacco smoking – Current smokers have a two-to-three-fold increased risk of developing AMD and there is a dose-response relationship with pack-years of smoking. This is the main modifiable risk factor and can affect the patient’s response to treatment.
Cardiovascular disease – Hypertension has been associated with AMD in some but not in all studies.
Hypermetropia – positive findings in cross-sectional studies have not been confirmed by the results of larger population-based prospective studies.
A healthy diet – High fat intake and obesity may promote AMD, with antioxidant intake having a protective effect in some groups. Green leafy vegetables when consumed regularly confer a lower risk of AMD.
Heredity – The risk of AMD is up to three times higher if a first-degree relative has the disease.
The dry, non-neovascular form accounts for 90 per cent of AMD and is characterised by a gradual loss of retinal pigment epithelial (RPE) cells and photoreceptors at the macula causing a gradual worsening of central vision. The diagnosis is made by examining the macula for soft drusen, focal hyperpigmentation or geographic atrophy in the late stages and confirming a lack of fluid with the use of optical coherence tomography (OCT).
Fundus fluorescein angiography (FFA) is usually performed if there is doubt about the presence of a choroidal neovascular membrane. Unfortunately, there is no treatment available that reverses the damage caused by dry AMD. However, patients are counselled, supported with low-vision aids, advised regarding lifestyle changes such as smoking cessation and vitamin supplementation, and given an Amsler grid to allow home-monitoring for new distortion.
Patients with late AMD in one eye have a 50 per cent chance of developing advanced AMD in the fellow eye within five years. The Age-Related Eye Disease Studies (AREDS I and II) provided substantial evidence that taking high-dose antioxidant vitamins on a regular basis can decrease the risk of development of advanced AMD. Experimental surgeries such as the implantation of miniature intraocular telescopes are being trialled and may be of use in selected cases.
Wet (neovascular) AMD makes up 10-15 per cent of AMD cases and tends to develop at a faster pace. This form of AMD is characterised by the ingrowth of permeable, fragile new blood vessels from the choroid into the retinal pigment epithelial and subretinal spaces.
These new vessels, known as choroidal neovascular membranes (CNV), are thought to be stimulated by the pathological secretion of vascular endothelial growth factor (VEGF). Untreated, these new vessels bleed and eventually cause scarring of the macula and a profound loss of central visual function occurs. In the UK, CNV causes severe visual impairment or blindness in 3.5 per cent of people aged 75 years or over. Wet AMD presents with a much more acute onset of worsening central vision, metamorphopsia, and/or central scotoma.
A yellow-green plaque-like membrane or haemorrhage (as well as ipsilateral and/or contralateral drusen) is seen on dilated fundal exam. These patients should be evaluated promptly, usually with FFA, which would confirm choroidal neovascularisation. Non-invasive OCT (see Figure 3) is performed to quantify sub- and intra-retinal fluid and to monitor progress and response to treatment.
Treatment of neovascular AMD has been revolutionised in the past 15 years by the introduction of intravitreal anti-VEGF medications. The most frequently used anti-VEGF agent is the monoclonal antibody bevacizumab, which was licenced for systemic use in colorectal cancers and remains off-label for ophthalmic use. Others include ranibizumab, a humanised monoclonal antibody fragment developed specifically for ophthalmic use, and aflibercept, a recombinant fusion protein that binds to VEGF-A, VEGF-B and PlGF). Bevacizumab was shown to be equally as effective as ranibizumab for the treatment of neovascular AMD at two years in the CATT study.
Older treatments such as photodynamic therapy (PDT) are now rarely used for neovascular disease, but may be useful in cases where there is refusal of intravitreal therapy.
The UK NICE guidelines recommend: “For eyes with confirmed active wet AMD for which anti-angiogenic treatment is recommended, offer treatment as soon as possible (within 14 days of referral to the macula service).” This is a guideline supported and endorsed by the UK Royal College of Ophthalmologists.
Impact on quality-of-life
AMD is the leading cause of sight loss in people aged over 50 years in Ireland, affecting more than 60,000 individuals (approximately 7,000 with neovascular AMD and 60,000 with non-neovascular AMD).
A recent audit of national waiting times across Irish ophthalmology departments revealed that, on average, patients are waiting 52 days from diagnosis in the clinic to first intravitreal injection. The audit also revealed that average waiting times across different ophthalmology departments ranges from 14 to 92 days. Our national ophthalmology services are under great pressure to cope with current demands for intravitreal injections for neovascular AMD and patient waiting times are stretching as a result. The number of people over the age of 65 years is predicted to increase by 4 per cent (275,000) within the next 12 years and our healthcare system will have to undergo massive investment in infrastructure and personnel to provide a safe standard of care for our patients. A decentralisation of our ophthalmic healthcare service with the delivery of care taking place in community-based settings may be beneficial to our growing number of patients.
What non-ophthalmologists need to know
A significant proportion of your older patients will develop AMD, and while GPs regularly test distance visual acuity, the addition of Amsler grid testing in the community setting will increase the number of patients diagnosed at an earlier stage of disease progression allowing ophthalmologists to better preserve visual function and help patients to maintain an independent lifestyle for longer.
Treatment with anti-VEGF intravitreal injections in primary eye care settings by community ophthalmic physicians or advanced nurse practitioners should be considered to enhance the delivery of sight-saving treatment in a timely manner.
References on request
A 45-year-old man who has sex with men (MSM) presented to a sexual health service requesting a sexual health screening; he had never been screened before. He did not remember if he had been vaccinated against hepatitis A or B in the past. As is currently routine practice, he gave a urine sample and had a rectal and pharyngeal swab testing for gonorrhoea and chlamydia. He had blood drawn for HIV, syphilis, hepatitis A, hepatitis B and hepatitis C.
Two weeks later, he presented for his results. There was no evidence of gonorrhoea or chlamydia, hepatitis B (HBV), hepatitis C, syphilis or HIV. His hepatitis A tested positive. This would not be unusual in this cohort and most likely represented past asymptomatic infection, maybe in childhood. As he was an MSM, he fell into the high-risk category for HBV, and vaccination was proactively encouraged. As per protocol from the most recent immunisation guidelines for Ireland, available on the RCPI website, he was started with a HBV vaccine. Follow-up vaccines were arranged one month later and six months after the first. Two months after the last vaccine, he returned to have a HBV antibody titre blood. This showed that he did not respond to the initial schedule, as his titre level was less than 10mIU/ml of blood.
This man was a HBV vaccination ‘non-responder’. As such, he had no protection against HBV. He was offered a further course of vaccines, this time a double dose, one in each arm at the elected date, one month later and at six months. This time, he had a HBV titre blood drawn and his anti-HBV antibody was greater than 100mIU/ml blood. He had an adequate response to vaccination and needs no further intervention.
According to the World Health Organisation (WHO), in July 2017 there were more than 257 million people chronically infected worldwide with the hepatitis B virus (HBV).
HBV is a potentially life-threatening cause of hepatitis and is a major global health problem causing chronic infection, which can result in cirrhosis and liver cancer. Areas of high prevalence (>8 per cent of the population) include sub-Saharan Africa, South-East Asia, the Pacific islands and the Caribbean. HBV is moderately common (2-7 per cent) in South Central and South West Asia, Russia and Central and South America. In Australia, New Zealand, North America and Western Europe, the prevalence of chronic HBV is <2 per cent. In Ireland, the seroprevalence of HBV infection is <1 per cent.
HBV is a notifiable disease in Ireland and as such, all medical practitioners, including clinical directors of diagnostic laboratories, are required to notify the Medical Officer of Health (MOH)/Director of Public Health (DPH) of new cases of HBV. These notifications are analysed by the Health Protection Surveillance Centre (HPSC) and annual reports are published on the website www.hpsc.ie. In 2016, 488 cases of HBV were notified to the HPSC. That was down on the 2015 figure (548 cases), but according to the HPSC epidemiologists, this represents a levelling-out of annual notifications, not a true decreasing trend. A total of 7 per cent of the notified cases in 2016 were acute hepatitis, where 93 per cent were chronic HBV infection. The high notification of chronic cases reflects people migrating from countries where HBV is endemic.
Co-infection with other blood-borne viruses, such as hepatitis C and HIV, can lead to more severe liver disease and an increased risk of liver cancer in people with HBV infection. Four HBV cases notified in 2016 were co-infected with hepatitis C and 13 additional cases were co-infected with HIV. Other sexually-transmitted infections were also reported for some of the cases of HBV notified in 2016. Five had recently been diagnosed with chlamydia, three with syphilis (two HIV positive), one with gonorrhoea and one with genital herpes simplex (HIV positive).
HBV is a double-stranded DNA virus belonging to the hepadnaviridae viral family. The whole virus consists of an inner core and an outer surface coat. The inner core contains genetic material (DNA), DNA polymerase, an enzyme essential for reproduction, the core antigen and the e antigen. The whole genome is 32kb long. This genome is very small and HBV uses overlapping reading frames that encode four different proteins that make up the intact virus. During viral replication, viral proteins are combined to form intact viruses. Some of the viral proteins are synthesised in excess of the amount used to form infectious virions. These are empty viral particles that do not contain the genetic material of HBV.
These empty particles form the basis of the laboratory assay HBV surface antigen (HBsAg) and HBV infection is diagnosed by testing for these empty viral particles.
Transmission of HBV occurs mainly by sexual contact, particularly anal and vaginal intercourse. Having another sexually-transmitted disease resulting in a breach of the genital mucosa at the time facilitates infection with HBV. Perinatal transmission occurs in 70-to-90 per cent of cases where the mother is infectious. HBV can live outside the body for a week or more, so percutaneous exposure, such as sharing needles in the setting of intravenous drug use is a key infection risk. Sharing toothbrushes and razors, piercing and tattooing can also result in HBV infection. Occupational and non-occupational needle-stick injury with blood from a source that has infectious HBV will result in infection without intervention in 30 per cent of cases. Transfusion-related HBV infection is rare in the developed world.
Once infected with HBV, there are three possible outcomes: Recovery (90-to-95 per cent); fulminant liver disease with a rapid decline in liver function and death (1 per cent); and chronic infection.
Serological markers of HBV are available to diagnose HBV. Testing determines whether the person is infected with HBV; if so infected, whether the infection is acute or chronic; and if not infected, whether protective antibodies exist.
There are three antigenic determinants associated with HBV infection, hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBcAg) and hepatitis B e antigen (HBeAg) and three corresponding antibodies — anti-HBs, anti-HBc and anti-HBe.
Chronic infection is defined as detectable HBsAg in the blood for more than six months.
HBsAg appears in the blood from about six weeks after an acute infection, usually before jaundice is clinically evident. Its presence indicates current infection or a chronic infection, as well as a carrier state. The presence of HBsAg in the serum indicates HBV infection and all HBsAg-positive persons should be considered infectious. A carrier is defined as someone who is HBsAg-positive on at least two occasions, at least six months apart. In persons who recover from HBV infection, HBsAg disappears from the blood and anti-HBs develop. Its presence in the serum indicates immunity from HBV infection following natural infection or vaccination.
HBcAg does not circulate in blood and does not appear on the laboratory results.
Its corresponding antibody, HBcAb, appears at the onset of liver test abnormalities and persists for life. Acute or recently-acquired infection can be distinguished by the presence of immunoglobulin M (IgM) class of anti-HBc and can persist for up to six months if the disease resolves.
The HBeAg may be detected in the serum of patients with acute or chronic infection. It is a measure of viral replication and infectivity. Its persistence correlates with the development of chronic liver disease and its loss correlates with low levels of viral replication. Certain HBeAg-negative individuals have high measurable HBV DNA levels (viral genetic material) suggesting high viral turnover. This is due to a mutation in the precore region of the HBV genome and results in failure to produce HBeAg, even in the presence of active viral replication. This is known as the ‘precore mutant’ HBV. Anti-HBe appears in the blood after the disappearance of HBeAg and correlates with low infectivity.
When screening for HBV infection, one needs to know three things: Has the person been vaccinated in the past, or has the person been infected with HBV, and if so, has the person cleared the virus or not? Anti-HBc (anti-hepatitis B core antibody) and HBsAg should be requested, unless the person has been vaccinated already. If the anti-HBc is positive, it means that the patient has had past exposure to HBV and may or may not have active infection at the time of phlebotomy. If the HBsAg is positive, it indicates that the patient is actively infectious and the infection may be acute or chronic. Patients have an approximately 90 per cent chance of clearing the virus and in this case, the HBsAg will be negative. The anti-HBc will, however, remain positive, indicating past infection and that vaccination is not warranted. If the anti-HBc IgM is positive, it will distinguish between acute and chronic HBV infection. A positive anti-HBc IgM indicates acute infection.
The laboratory, in the event of a positive HBsAg result, will perform further serological tests, ie, the HBeAg and the anti-HBe. These tests indicate the degree of infectivity or active viral replication. If the HBeAg is positive and the anti-HBe is negative, it suggests that there is active viral replication and that the patient is highly infectious and the likelihood of viral clearance is small. Similarly, if the HBeAg is negative and the anti-HBe is positive, it indicates that the active infection will most likely have a chronic low-level viraemia.
The gold standard for staging of liver disease is a liver biopsy. Patients with acute hepatitis are rarely biopsied. Microscopic appearance of the liver of a patient with active cirrhosis shows portal tract inflammation and interface hepatitis, normal bile ducts, lobular inflammation with ground glass hepatocytes present and negative special stains for iron, alpha-1 antitrypsin antibodies and copper-associated proteins. Transient elastography is also used to assess the degree of liver elasticity — which decreases as HBV infection progresses — fibrosis, cirrhosis and hepatocellular carcinoma.
The most common laboratory tests performed on patients in whom there is a clinical suspicion of viral infection aside from serology are liver enzymes. Serum ALT (alanine transferase) alone, or in combination with other liver enzymes, is not sufficient to detect chronic viral hepatitis in patients with risk factors for the disease. Furthermore, the correlation between the magnitude of enzyme elevations and the degree of liver injury is poor. Elevated liver enzymes may indicate the presence of the disease, but not the degree of liver damage. Other liver function tests available are the prothrombin time and serum albumin, both of which are an indicator of the liver’s synthetic capacity and the serum bilirubin, a measure of the liver’s functional capacity. Unfortunately, these tests may only become abnormal only after severe liver damage has occurred. Patients with chronic HBV are screened regularly for hepatocellular carcinoma in the setting of chronic HBV and cirrhosis with ultrasonography and alpha-fetoprotein measurement.
The incubation period of HBV ranges from 45-to-180 days, on average 90 days. Most infections are sub-clinical or patients may present with malaise, fatigue, anorexia, abdominal discomfort, nausea or vomiting. Patients may present with arthralgia or rash and 30-to-50 per cent of adults will have jaundice.
Diagnosis and treatment
For many, a diagnosis of HBV is made on routine screening.
There is no specific treatment apart from supportive measures for patients with acute HBV.
Chronic HBV can be treated with oral antiviral agents. In 2015, the WHO recommended tenofovir or entecavir as first-line agents for the treatment of HBV. Antiviral agents reduce viral replication in the liver, can reduce or slow the progression of cirrhosis and reduce the incidence of liver cancer. In the majority, treatment does not cure HBV, but only suppresses the viral replication.
A vaccine against HBV has been available since 1982 and is 95 per cent effective. The vaccine contains recombinant HBsAg. It does not contain live organisms and is not infectious.
In Ireland, it has been recommended by the National Immunisation Committee of the RCPI that certain groups should receive HBV vaccine if non- immune. These include doctors, nurses, dentists, midwives, laboratory staff, cleaning staff, general assistants and anyone who is at particular risk through contact with blood or body fluids. Others who should be vaccinated include the sexual and household contacts of acute cases of HBV; families adopting children from countries with a high prevalence of HBV; babies born to mothers with chronic HBV; people with haemophilia and others requiring regular blood transfusions; patients with chronic renal failure with poor immunity and who may require dialysis; and patients with chronic hepatitis. It is also recommended that security and emergency personnel, intravenous drug users, MSM, tattoo artists, and immigrants from and travellers to an area with a high seroprevalence of HBV are vaccinated too.
The standard vaccine schedule is three vaccines — one at the elected date, one a month later and the third at six months. Accelerated schedules are used in certain circumstances. It is recommended that two months after the last vaccine, a post-vaccination anti-HBs titre be checked. The level is reported in mIU/ml blood. A level greater than 100 is an adequate response and in an immunocompetent cohort, should last for life. A level of 10-to-99, a poor responder, warrants a booster dose and no further action, while those with a level of less than 10 are non-responders. Factors that might suggest that a person will be a non-responder include male sex, age over 40 years, increased body mass index, immunodeficiency and smoking. A further course of a double-dose vaccine, one injection in each arm, is recommended at zero, one, and six months for non-responders. This revaccination schedule is highly effective in inducing seroconversion. Failing seroconversion, patients need to know that despite vaccination, they have no defence against HBV and would need immunoglobulin in the event of a future exposure.
To confirm, the vaccine does not contain infectious HBV but only HBsAg. It does not contain HBcAg, so one does not make antibodies to HBcAg with vaccination. HBcAb are only positive following natural infection.
References on request
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