Showing posts with label Peripheral Neuropathy. Show all posts
Showing posts with label Peripheral Neuropathy. Show all posts

Wednesday, August 8, 2018

Managing Neurologic Complications of Chronic HCV Infection

In case you missed it
Managing Neurologic Complications of Chronic HCV Infection
Anushka Burde, PharmD; Rebecca Hoover, PharmD, MBA, BCPS
US Pharmacist. 2018;43(1):18-22.

Abstract and Introduction
Chronic hepatitis C virus (HCV) infection can cause a multitude of extrahepatic complications, including neurologic manifestations. These complications can lead to substantial neuropsychiatric deficits, such as fatigue, cognitive impairment, restless legs syndrome, Parkinson's disease, and peripheral neuropathy. In addition to detecting and managing these neurologic complications, pharmacists in community settings can promote HCV screening, improve medication access and adherence, and recommend preventive strategies patients can use to avoid transmission of this widespread infection.

Hepatitis C virus (HCV) infection is widespread, and about one-half of the 3.5 million HCV-infected people in the United States are likely unaware of being infected.1 Community pharmacists, as the most accessible type of healthcare practitioner, are optimally positioned to detect and manage HCV. They can help HCV-infected patients by engaging in appropriate screening, ensuring proper management of the infection, and recognizing extrahepatic symptoms, including neurologic complications.

Pharmacists in community settings should identify those patients most in need of screening. For example, the pharmacist can run a listing of baby-boomer patients (i.e., born between 1945 and 1965) at the pharmacy and can recommend one-time HCV testing irrespective of prior risk factors discussed in the American Association for the Study of Liver Diseases guidelines.1 Factors for the pharmacist to keep in mind are that about 60% of acute HCV infections in the U.S. are a result of injection-drug use and that there is a substantial risk of HCV transmission in HIV-infected men who have unprotected sex with men. The pharmacist can also identify patients for screening by checking medication histories.

The pharmacist should counsel patients to get tested for HCV infection based on the recognition of risk factors, including poor adherence to HIV medications, which can be determined by checking refill history. Patients are more likely to disclose a history of drug use to their pharmacist after developing a sense of trust and confidence. Pharmacists should put patients at ease by assuring them that their information will not be used against them, but rather will be used appropriately to refer them for HCV testing. For example, women with active HCV infection or a history of it should be advised to get their children tested as well. Pharmacists can recommend HCV testing for patients with a history of incarceration by noting that data suggest the presence of anti-HCV antibodies in about 29% of incarcerated persons in North America.1 Other risk factors, such as history of organ transplant, receipt of transfusion, and piercings and tattoos obtained at unregulated settings, should be taken into consideration regarding HCV screening.

Community pharmacies can also engage in screening practices by testing for the presence of HCV antibodies. Multiple diagnostic tests for HCV are available that combine laboratory-based and point-of-care assays. One of these, the OraQuick HCV Rapid Antibody Test, is an FDA-approved Clinical Laboratory Improvement Amendments–waived test.1 This waiver enables patients to be tested at various locations, including community pharmacies. The test is straightforward and efficient, providing results in about 20 minutes. It can test for multiple HCV genotypes, and its accuracy exceeds 98%.2

Patient Education
Pharmacists can educate patients with HCV infection on how to prevent spread of the virus, such as to avoid sharing toothbrushes or shaving equipment. Patients should also be counseled to use barrier precautions to prevent sexual transmission and to stop using illicit drugs. The use of clean needles and syringes should be encouraged, as HCV reinfection is highly likely if the risk of drug use is ongoing.3 Persons infected with HCV should be encouraged to abstain from alcohol and smoking. Patients should be counseled to enter substance-abuse treatment facilities in order to prevent progression of liver disease. The pharmacist should also mention that definitive evidence supporting the use of complementary and alternative supplements is lacking. Other clinical pearls offered by the pharmacist could include possible benefits of coffee consumption, a diet low in fat and sodium, weight loss, and vitamin D testing. The pharmacist should also recommend limiting acetaminophen use to 2 g per day in noncirrhotic HCV-infected patients and 1 g per day in those who are cirrhotic.1 The pharmacist could also recommend a daily multivitamin without iron.

Pharmacists can also ensure that patients who are susceptible to HCV infection receive appropriate, routine CDC-recommended vaccines, including those for hepatitis A and B. Pneumococcal vaccine should be administered to patients with cirrhosis.1

Significant side effects and profound laboratory abnormalities plagued older HCV treatments, making them unfavorable options for patients.4 Interferon-based regimens, historically the standard of care, were associated with substantial side effects, such as flulike symptoms, fatigue, neuropsychiatric symptoms, and hematologic effects. Newer interferon-free, direct-acting antiviral (DAA) oral regimens introduced since 2013 have successfully achieved sustained virologic response (SVR), a marker of virologic cure. A few commonly used DAAs include ledipasvir-sofosbuvir (Harvoni), sofosbuvir-velpatasvir (Epclusa), sofosbuvir (Sovaldi), daclatasvir (Daklinza), elbasvir-grazoprevir (Zepatier), and ombitasvir-paritaprevir-ritonavir plus dasabuvir (Viekira Pak). Glecaprevir-pibrentasvir (Mavyret) and sofosbuvir-velpatasvir-voxilaprevir (Vosevi) were approved in 2017. Epclusa, Mavyret, and Vosevi are pangenotypic and may be used to treat all HCV genotypes (i.e., types 1-6). Treatment with and duration of DAAs depend on HCV genotype, presence of cirrhosis, HCV RNA level, and history of prior treatment.

Reductions in all-cause mortality, liver-related adverse outcomes such as end-stage liver disease, and hepatocellular carcinoma are the goals of treatment in HCV-infected persons. Despite the availability of successful treatments, multiple barriers must be overcome. One such barrier is lack of access to treatment, reasons for which include high medication costs, lack of insurance, geographic distance, and lack of specialist availability. A treatment-naïve genotype 1a patient will require treatment that can cost up to $54,600 to $150,000, on average.3,4 Longer duration of treatment further increases these costs. Community pharmacists can help patients by identifying patient-assistance programs and providing appropriate navigation through insurance plans to alleviate some of the cost burden.

Medication Adherence
Educating patients with HCV on the importance of medication adherence is a critical component of HCV treatment and determines virologic cure. Adherent and immunologically competent treatment-naïve patients with compensated liver disease are 95% more likely to achieve SVR with direct-acting antivirals.1,4 Several methods for checking compliance may be implemented at a community pharmacy, including pharmacy-refill assessment, pill counts, and follow-up phone calls to patients. The pharmacist should advise patients that modification of certain risk factors—such as reducing alcohol intake, weight loss (in obese patients), and cessation of cigarette smoking and marijuana use—can reduce, and may also reverse, progression of liver disease. Pharmacists are also in a key position to identify drug-drug interactions, including prescription medications for comorbidities and OTC products.

Neurologic Extrahepatic Complications
Many community pharmacists go the extra mile for their patients by screening for HCV infection and overseeing therapy upon diagnosis. However, pharmacists should understand that HCV can impact health beyond liver dysfunction. A variety of extrahepatic issues are associated with chronic hepatitis C, including diabetes and dermatologic manifestations such as porphyria cutanea tarda and lichen planus.1 Fatigue, arthralgias, renal disease, and neurologic diseases such as peripheral neuropathy are manifestations of cryoglobulinemia, a lymphoproliferative disorder that causes local deposition of immune complexes.1

An increased prevalence of neuropsychiatric symptoms in HCV-infected patients, independent of any preexisting mental disorders or high-risk behaviors, is being reported in emerging literature. HCV likely has a direct biological effect on the central nervous system. Possible mechanisms include neuroinflammation, as noted on brain imaging, and peripheral inflammation across the blood-brain barrier that is induced by elevation of proinflammatory cytokines.5

Fatigue and Cognitive Impairment: Chronic HCV infection is associated with fatigue and cognitive impairment, which contribute to reduced quality of life. More than 50% of HCV-infected patients report that fatigue is the most common symptom. The occurrence of fatigue may be difficult to predict. HCV RNA, HCV genotype, and liver histology are not associated with fatigue.6 Numerous quality-of-life measures have shown that fatigue impairs the quality of life and activity level of HCV-infected patients. Cure of HCV infection results in a reduction in fatigue, as noted in some studies.1 The community pharmacist should recognize chronic HCV as a potential cause when a patient complains of chronic fatigue, low energy levels, and pain. Abnormal circulating levels of thyroid-stimulating hormone or thyroxine have been noted in HCV-infected patients, which might result in a high prevalence of fatigue.6 Pharmacists could suggest thyroid-function testing in these patients.

Deficits in measures of attention, higher executive functions like planning, decision making, judgment, or reasoning skills, verbal learning ability, recall, and working memory have been reported in literature examining HCV-associated cognitive impairment.7 Pharmacists should refer patients to their medical provider for complaints of brain fog or neuropsychiatric symptoms such as difficulty paying attention, concentrating, failing memory, and so on. Patients should be counseled that studies have shown that successful clearance of the virus is associated with improved attention, vigilance, and working memory.

Restless Legs Syndrome (RLS): Beyond cognitive manifestations, patients with HCV may also have motor-neuron problems. HCV infection may place patients at greater risk for RLS. This condition, which is characterized by an impulse to move the legs, typically manifests in the evening and at night. Cirrhosis and use of older agents, such as interferon-alpha, for drug therapy are associated with RLS and are of particular concern.8,9 Patients complaining of sleep difficulties or those using prescription or OTC sleep aids with or without RLS treatment may benefit from further education and evaluation regarding the possible relationship between RLS and HCV infection.

Parkinson’s Disease: Most evidence supports an association between Parkinson’s disease and HCV infection, but the cause is unclear.10-12 Parkinson’s disease could be a direct consequence of HCV infection or perhaps even its treatment. The relationship could also be due to similarities in the mechanisms of the diseases. The extent of the association is unclear as well. A recent analysis of data from Medicare patients failed to find an association between HCV infection and occurrence of Parkinson’s disease.12 However, in the same way that early detection is essential for HCV treatment, early detection of Parkinson’s disease is important for maintaining quality of life. Pharmacists should be alert to complaints of movement disorders in HCV-infected patients. Asking patients about movement problems or tremors is an important first step. Parkinson’s disease may have a gradual onset, and patients may not readily recognize early signs. Community pharmacists can counsel HCV patients to self-monitor parkinsonian symptoms by looking for shaking, slowed movement, or changes in speech. Patients reporting these problems are good candidates for further assessment by a specialist or primary care provider.

Peripheral Neuropathy: Peripheral neuropathy is a common complaint presented at community pharmacies. Although most pharmacists associate neuropathy with diabetes, thyroid disorder, or renal failure, it is important to also consider HCV. Neuropathy is caused by a breakdown of sensory and motor neurons, which prevents proper signals between the central and peripheral nervous systems. Mechanisms for neuropathy in HCV are likely due to indirect factors such as inflammation and cryoglobulinemia, in which immunoglobulins precipitate and clump together.13 About 10% of HCV patients report peripheral neuropathy, which is most likely to occur in those with cryoglobulinemia.14

Patients may complain of motor problems such as weakness or sensory impairment such as numbness, burning or prickling sensation, or intense pain.4 Neuropathy presents in various forms, and it may be hard to determine the cause. Because neuropathy in HCV patients may go unrecognized, it is important to ask patients about their pain status and refer them to their primary care provider as needed. It may be useful for patients to keep a pain journal to detect triggers or determine which therapy works best. Neuropathy can be difficult to alleviate, and it may be necessary to help the prescriber select the medication and titrate as appropriate.

Interrelatedness of Extrahepatic Complications: Beyond traditional neurologic implications, it is necessary for pharmacists to appreciate that extrahepatic manifestations of HCV infection are interrelated. For example, a stroke may be caused by cardiovascular risks related to HCV infection but may result in neurologic impairment. Literature shows that HCV promotes carotid plaque formation, a well-known predictor of cardiovascular disease. Other possible contributory mechanisms are cryoglobulinemia-associated vasculitis and autoimmune antibody development. Patients who have had a cryptogenic stroke should be screened for HCV and cryoglobulins.1 Being vigilant in monitoring a patient’s response and adherence to treatment can help prevent extrahepatic issues. HCV management should be gradually geared toward primary care through collaboration with specialists, and complicated cases should always be referred to HCV specialists.

Community pharmacists serve a vital function in the care of patients infected with HCV. The pharmacist can play an important role in HCV management by identifying patients who should be tested for HCV, providing extensive medication and disease-state counseling, recommending and administering appropriate vaccines, determining and managing extrahepatic complications, and collaborating with providers on care.


1. AASLD/IDSA HCV Guidance Panel. Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015;62:932-954.
2. OraSure Technologies, Inc. OraQuick HCV Rapid Antibody Test product information. Accessed November 3, 2017.
3. CDC. Viral hepatitis surveillance—United States, 2014. Accessed December 5, 2017.
4. Deming P. Viral hepatitis. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill Education; 2017:561-578.
5. Negro F, Forton D, Craxì A, et al. Extrahepatic morbidity and mortality of chronic hepatitis C. Gastroenterology. 2015;149:1345-1360.
6. Poynard T, Cacoub P, Ratziu V, et al. Fatigue in patients with chronic hepatitis C. J Viral Hepat. 2002;9:295-303.
7. Gess M, Forton D. Effect of hepatitis C on the central nervous system of HIV-infected individuals. J Virus Adaptation Treat. 2012;4:93-106.
8. Anderson K, Jones DE, Wilton K, Newton JL. Restless leg syndrome is a treatable cause of sleep disturbance and fatigue in primary biliary cirrhosis. Liver Int. 2013;33:239-243.
9. Tembl JI, Ferrer JM, Sevilla MT, et al. Neurologic complications associated with hepatitis C virus infection. Neurology. 1999;53:861-864.
10. Abushouk AI, El-Husseny MW, Magdy M, et al. Evidence for association between hepatitis C virus and Parkinson’s disease. Neurol Sci. 2017;38:1913-1920.
11. Pakpoor J, Noyce A, Goldacre R, et al. Viral hepatitis and Parkinson disease: a national record-linkage study. Neurology. 2017;88:1630-1633.
12. Golabi P, Otgonsuren M, Sayiner M, et al. The prevalence of Parkinson disease among patients with hepatitis C infection. Ann Hepatol. 2017;16:342-348.
13. Nemni R, Sanvito L, Quattrini A, et al. Peripheral neuropathy in hepatitis C virus infection with and without cryoglobulinaemia. J Neurol Neurosurg Psychiatry. 2003;74:1267-1271.
14. Bonetti B, Scardoni M, Monaco S, et al. Hepatitis C virus infection of peripheral nerves in type II cryoglobulinaemia. Virchows Arch. 1999;434:533.535.

Thursday, March 8, 2018

Neurological manifestation in chronic hepatitis C: Peripheral neuropathy

Research Article
Neurological manifestations in chronic hepatitis C patients receiving care in a reference hospital in sub-Saharan Africa: A cross-sectional study
N. Y. Mapoure , M. N. Budzi, S. A. F. B. Eloumou, A. Malongue, C. Okalla, H. N. Luma

Published: March 7, 2018

Full Text Article
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Abstract Background
Chronic hepatitis C infection is a major public health concern, with a high burden in Sub-Saharan Africa. There is growing evidence that chronic hepatitis C virus (HCV) infection causes neurological complications. This study aimed at assessing the prevalence and factors associated with neurological manifestations in chronic hepatitis C patients.

Through a cross-sectional design, a semi-structured questionnaire was used to collect data from consecutive chronic HCV infected patients attending the outpatient gastroenterology unit of the Douala General Hospital (DGH). Data collection was by interview, patient record review (including HCV RNA quantification, HCV genotyping and the assessment of liver fibrosis and necroinflammatory activity), clinical examination complemented by 3 tools; Neuropathic pain diagnostic questionnaire, Brief peripheral neuropathy screen and mini mental state examination score. Data were analysed using Statistical package for social sciences version 20 for windows.

Of the 121 chronic hepatitis C patients (51.2% males) recruited, 54.5% (95% Confidence interval: 46.3%, 62.8%) had at least one neurological manifestation, with peripheral nervous system manifestations being more common (50.4%). Age ≥ 55 years (Adjusted Odds Ratio: 4.82, 95%CI: 1.02–18.81, p = 0.02), longer duration of illness (AOR: 1.012, 95%CI: 1.00–1.02, p = 0.01) and high viral load (AOR: 3.40, 95% CI: 1.20–9.64, p = 0.02) were significantly associated with neurological manifestations. Peripheral neuropathy was the most common neurological manifestation (49.6%), presenting mainly as sensory neuropathy (47.9%). Age ≥ 55 years (AOR: 6.25, 95%CI: 1.33–29.08, p = 0.02) and longer duration of illness (AOR: 1.01, 1.00–1.02, p = 0.01) were significantly associated with peripheral neuropathy.

Over half of the patients with chronic hepatitis C attending the DGH have a neurological manifestation, mainly presenting as sensory peripheral neuropathy. Routine screening of chronic hepatitis C patients for peripheral neuropathy is therefore necessary, with prime focus on those with older age and longer duration of illness.

Continue reading:

Recommended Reading
Extrahepatic Manifestations of Hepatitis C—Peripheral Neuropathy | Alan Franciscus
October 24, 2017
In the past, peripheral neuropathy was believed to be confined to people only infected with hepatitis C-related cryoglobulinemia, but now it is known that peripheral neuropathy may occur even in the absence of cryoglobulinemia.

Of Interest In The Media
Mar 12, 2018
Treating HCV Reduces Risk of Extrahepatic Conditions

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Other Conditions Related To HCV

Tuesday, October 24, 2017

October Series From HCV Advocate - HCV and Peripheral Neuropathy

New Online: HCV-related diseases

In October, HCV Advocate launched a series of patient-friendly articles about the Extrahepatic Manifestations of Hepatitis C, written by Alan Franciscus.

Browse through topics provided below, make sure not to miss new articles published later this month, sign up here to receive updates, follow HCV Advocate on Twitter or connect on Facebook. Find out what's new, here!

Begin with HCV Advocates Extrahepatic Manifestation Glossary and Fact Sheets.

October Blog Special
Extrahepatic Manifestations of Hepatitis C—Peripheral Neuropathy | Alan Franciscus
October 24, 2017
In the past, peripheral neuropathy was believed to be confined to people only infected with hepatitis C-related cryoglobulinemia, but now it is known that peripheral neuropathy may occur even in the absence of cryoglobulinemia.
Continue reading (LINK)

Friday, June 8, 2012

Peripheral neuropathy in Egyptian hepatitis C virus patients: Correlation to some clinical and laboratory parameters

Original Article
Prevalence of peripheral neuropathy in Egyptian hepatitis C virus patients: Correlation to some clinical and laboratory parameters

Manal Aly Abdel Khaleka, Amal Mohamad El-barbarya, Ferial Salah Elkallab,
Salwa Abdel-Moneim Essac a Rheumatology and Rehabilitation Department, Faculty of Medicine, Tanta University, Egypt b Tropical Medicine Department, Faculty of Medicine, Tanta University, Egypt c Clinical Pathology Department, Faculty of Medicine, Tanta University, Egypt

Received 24 January 2012. Accepted 2 April 2012. Available online 19 May 2012., How to Cite or Link Using DOI

Aim of the work

The present study was undertaken to assess prevalence and characteristics of peripheral neuropathy (PN) in Egyptian hepatitisCvirus (HCV) patients.

Patients and methods
Eighty newly diagnosed HCV patients were enrolled, with 20 healthy volunteers. All were subjected to: full clinical examination, neurological examination, laboratory assessment including; routine blood tests, ESR, CRP, RF, ANA, C4, cryoglobulins (CGs), anti-GM1 antibodies, HCV antibodies, Quantitative PCR, abdominal ultrasonography, liver biopsy, and electrophysiological assessment.

Thirty-six patients (45%) had clinical neuropathy, 18 patients (22.5%) had subclinical neuropathy. Thirty-eight out of the 54 PN patients (70.3%) showed axonal neuropathy which is mainly sensory affecting lower limbs. Twelve patients showed +ve cryoglobulinemia, all of them had neuropathy (10 clinical, 2 subclinical). Abnormal titers of anti-neuronal antibodies were associated with electrophysiological abnormalities in 50 out of the 54 PN patients. PN correlated with age, disease duration, ESR, CRP, RF, HCV viraemia, CGs, anti-GM1 and hypocomplementinemia.

PN exists in high prevalence among Egyptian HCV patients, and is associated with CG. It is mainly of axonal sensory type more affecting lower limbs. HCV patients should be investigated for the presence of CGs even in the absence of clinical manifestations.

Discussion Only
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The population of Egypt has a heavy burden of liver disease, mostly due to chronic HCV infection. The overall prevalence of antibody to HCV in the general population is around 15–20% [28]. The majority of the literature reporting on the neurological manifestations of HCV patients points to the PNS and describes painful neuropathies [29]. Antibodies against several neural antigens have been associated with a number of chronic immune-mediated neuropathies [30]. Detection of these anti-neuronal antibodies might provide additional prognostic insights and suggest a new scenario of the pathogenesis of the neurological manifestations of HCV related MCG [14].

In the current study, 70% of our patients were over 40 years which agrees with Frank et al. [28] who reported increased prevalence of HCV with age, and they explained it by the possibility of exposure of these groups to schistosomiasis campaigns in Egypt, and the use of contaminated needles or syringes during campaigns.

The majority of our patients was males (60%). Habib et al. [31], revealed that the HCV is more prevalent in males than females in Egypt due to the existence of two common potential HCV exposures for males: (1) shaving by a community barber using the same razor blade and (2) smoking tobacco with a water pipe (Shisha) which can theoretically result in exposure to blood from individuals with gingivitis.

PN was clinically diagnosed in 45% out of our patients, 42.5% showed sensory PN. The predominance of sensory PN among our patients agrees with Sterling and Bralow [32], who demonstrated that sensory deficiencies are more common than motor loss, and that sensory symptoms may persist for months to years before any motor deficit become clinically evident. On the other hand, the high prevalence of clinical PN among our patients is close to that reported by Cacoub et al. [10], which was up to 50%. Meanwhile, it was not consistent with previous Egyptian studies. The highest prevalence of PN among Egyptian HCV patients was 30% reported by Abul Hassan et al. [33], followed by 15.63% in the study of El Ghoneimy et al. [19] and 10% in the study of Abo Al-Soud et al. [34]. In western countries, Gomes et al. [35] reported PN prevalence of 34.6%, while other studies reported prevalence up to 10.6% [7], [13] and [36].

This wide variability of PN prevalence among different studies can be attributed to the model of patient enrollment, which in our study was based on the presence of HCV infection in untreated patients, independently of the signs or symptoms. It also can be attributed to the use of different methods for PN clinical evaluation.

It was mentioned that pure clinical assessment tends to underestimate PNS involvement in the HCV population [13] and that symptoms alone have relatively poor diagnostic accuracy in predicting the presence of PN and stressed on the importance of electrodiagnosis for its diagnosis [37]. We confirmed this statement when electrophysiological examination of our patients disclosed a subclinical PN in 18 additional patients (22.5%). This is in keeping with some authors who diagnosed subclinical PN in their patients [13] and [34], and disagrees with Ripault et al. [36] who reported equal prevalence of clinical and electrophysiological PN, and with Gomes et al. [35] who found clinical PN to be more than electrophysiological PN.

In the current study, a total of 67.5% (54/80) of our patients were diagnosed to have PN by electrophysiological examination. This finding disagrees with many authors where their percentage ranged from 8% to 37% [13], [34], [35], [36], [38] and [39].

Out of the 54 neuropathy patients, 38 patients (70.3%) showed axonal neuropathy which was mainly sensory affecting lower limbs more than upper limbs. While 16 patients (29.7%), showed mixed axonal and demyelinating sensorimotor polyneuropathy; with the same distribution and predominance of sensory affection. This finding is in accordance with some authors who demonstrated axonal type of neuropathy among their HCV patients with distal sensory or sensory-motor affection [7] and [33] or multifocal mononeuropathy. The underlying pathogenetic mechanisms for this complication are systemic CG and vasculitis [11], [12], [34], [36], [40], [41], [42], [43] and [44]. Peripheral demyelinating neuropathy has been rarely described, most often in CG−ve patients and results from the heterogeneity of the pathophysiological mechanisms of neuropathies [11], [42], [45], [46] and [47].

It has been hypothesized that SRAR can be used for the detection of early axonal loss; because the sural SNAP amplitude will decrease first, thereby also decreasing the SRAR value [48]. Our study showed that sensitivity of H-reflex and SRAR HCV patients was the same (55.5%) but combination of both tests increased sensitivity to 94.4%. This agrees with the study by Kim et al. [49] Moreover, Rutkove et al. [50] reported that an SRAR of less than 0.40 was a strong predictor of axonal polyneuropathy, with 90% sensitivity and 90% specificity, as compared to absolute sural amplitude which had sensitivity of only 66%.

The big variation of PN prevalence in HCV patients among different studies may be due to the fact that, it is a multifactorial disease process. Ripault et al. [36] suggested that the most important factor is the viral factors such as, viral genotypes as there is wide difference between the viral genotypes in Egypt and western countries.

15% of our patients showed positive CGs, which is very close to the findings of Gad et al. [51], who reported CGs prevalence of 14% among HCV genotype 4 Egyptian patients. While, this finding disagrees with many authors who reported CG prevalence ranging from 19% up to 54% among their HCV patients [7], [52], [53], [54] and [55], and with Persico et al. [56] and Verbaan et al. [57], who demonstrated 0.8% and 0% prevalences of CG in their patients consecutively.

The low prevalence of CGs among our HCV population can be attributed to: (a) HCV genotype 4 which is the common type among Egyptian patients is associated with low prevalence of CG compared to high prevalence in Japanese patients infected with genotype 1b [51], and to HCV genotype 2a infected patients. (b) The relatively short disease duration, as Lunel et al. [52] showed that the duration of the disease in HCV patients with MCG was almost twice as long than in patients without MCG and (c) relatively younger age of our patients, which agrees with some studies where it was noted that patients with MCG were of older age while sex was not a risk factor [58] and [59].
All of our CG+ patients had PN (10 clinical, 2 subclinical). None of them showed clinical manifestations of MCG. This agrees with the authors stating that HCV related PN is usually associated with CG [10], [11], [19], [36] and [39] and that the presence of serum CGs is predictive of more severe and widespread neuropathic involvement [12] and [60] and also with those who clarified that the only 13–30% of patients with CG are symptomatic [61].

Our patients showed significantly higher levels of anti-neuronal antibodies which were associated with electrophysiological abnormalities in 50 out of the 54 neuropathic patients. This finding is in keeping with Alpa et al. [62] who reported high plasma IgM and IgG anti-GM1 titers in MCG patients, and 61% of patients having abnormal titers were associated with clinical or subclinical evidence of neuropathy. Moreover, Ortiz et al. [63] concluded that high IgM anti ganglioside titers are involved in the etiopathogenesis of demyelinating neuropathies.

Statistical analysis showed a strong correlation between the presence of PN and age of patients, disease duration, load of viraemia, ESR, CRP, RF, IgM & IgG anti-GM1 and the presence of CGs. In addition; there was significant negative correlation between PN and C4 levels. On the other hand, no significant correlation could be found between PN and ANA, staging of liver fibrosis either by ultrasound scoring system or modified Knodells score.

These results are in keeping with Zaltron et al. [39] who reported a strong correlation between old age and PN although it was unrelated to cryocrit levels or type of CG, and with higher RF and reduced C4 activity, and with Santoro et al. [13] who demonstrated that electrophysiological evidence of PN was significantly associated with older age and virus load, but not with disease duration or CG. Also with Nemni et al. [12] who found that HCV-related neuropathy was significantly associated with diminished serum C4 levels. Nevertheless, Lidove et al. [60], reported that RF was always negative and C4 complement level was always normal among their HCV patients.

The significant relation between PN and virus load supports the mechanism which denotes that HCV may have a direct role in the pathogenesis of neuropathy. Furthermore, it support the immune hypothesis for the pathogenesis of PN as evidenced by the correlation between electrophysiological study and RF & diminished C4, which is in accordance with Sterling and Bralow [32], who found that RF is often positive in chronic HCV.

In conclusion, our findings demonstrate that PN exists in high prevalence among Egyptian HCV patients, and is commonly associated with CG. It is mainly of axonal sensory type with more affection of lower limbs. PN was found to correlate with the age of the patients, disease duration, ESR, CRP, RF, HCV viraemia, IgM and IgG anti-GM1 and hypocomplementinemia. It is recommended that HCV patients should be investigated for the presence of CGs even in the absence of clinical manifestations suggestive of MCG. HCV patients with no clinical evidence of neuropathy should be evaluated by electrodiagnosis, especially if they are CG+ve.

Sunday, October 10, 2010

Peripheral Neuropathy & Liver Disease

Over half of the patients with chronic hepatitis C attending the DGH have a neurological manifestation, mainly presenting as sensory peripheral neuropathy. Routine screening of chronic hepatitis C patients for peripheral neuropathy is therefore necessary, with prime focus on those with older age and longer duration of illness.

Mahim Mittal, Pavan Kumar Singh, Sonu Kurian
Peripheral neuropathy is present in more than half of cirrhosis patients and is unrelated to etiology and nutritional status but related to the severity of cirrhosis.
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Peripheral neuropathy is any nerve disorder affecting nerves outside of the spinal cord and brain, including those carrying messages to and from the organs of the torso and pelvis.The liver plays a key role in all body functions
Liver disease, or hepatic insufficiency, compromises the nervous system and can ultimately lead to death.

The liver is the body's largest gland. It is responsible for making proteins and enzymes that control blood volume and clotting. It stores carbohydrates for conversion to glucose, and produces bile that extracts vitamins A, E, D and K from fat while removing potentially harmful metabolic byproducts from the blood.All blood flows through the liver. You cannot survive without a liver
While alcoholism is associated with cirrhosis, any condition that causes fat to build up in the liver will cause cirrhosis. Obesity, diabetes, hereditary disorders, infections and medications can cause fatty liver, or cirrhosis, in the absence of alcoholism. The secondary problem of peripheral neuropathy will develop with the changes in the liver.

According to the UCLA Department of Medicine, peripheral neuropathy can develop when hepatitis C infects the liver. As the body fights the infection, immune proteins, called cryoglobulins, circulate in the blood. Theory holds that the chronic hepatitis C induces overproduction of infection-fighting proteins. These proteins may lodge in capillary walls, causing inflammation and pain

According to Merck Medical Library, impaired liver function associated with cirrhosis or alcoholism decreases the absorption of vital nutrients, such as vitamin B12. Vitamin B12 deficiencies disrupt the formation of the myelin sheaths that insulate nerve fibers.Without proper sheathing tingling, pain, muscle spasms and loss of sensation can develop as messages from one exposed nerve influence messages from adjacent exposed nerves

Impaired liver function prevents effective albumin production, which regulates fluid levels in the body. Fluids initially build up in the abdomen. This condition, called ascites, causes the belly to bulge. Swelling can also develop in the limbs and joints. This condition, called peripheral edema, can put abnormal pressure on the peripheral nerves and cause pain, tingling and numbness

If you develop unexplained peripheral neuropathy with symptoms of liver disease such as vomiting, yellowing skin and eyes, fatigue and unexplained weight loss, the doctor may order blood tests to check the liver, called a hepatic function panel. If your liver's albumin, bilirubin and enzymes are higher or lower than normal, the doctor must assess the cause of liver impairment to determine a management plan for the peripheral neuropathy

Your doctor may prescribe vitamin B12 supplements when liver disease has triggered a B12 deficiency. Diuretics and salt restrictions may be implemented to control swelling, due to fluid retention, which can relieve some of the pain associated with nerve compression.Your doctor may also prescribe antidepressants, non-steroidal anti-inflammatory drugs or anticonvulsant medications for pain management. Transcutaneous electrical nerve stimulation, or TENS, may be used to ease pain without medication. Long-acting morphine might be prescribed when hepatitis C is present.