Hepatitis 411 And Support: 12/10/13

Fibromyalgia, Hepatitis C Infection,and the Cytokine ConnectionMollie E. Thompson, MD, PhD* and André Barkhuizen, MDAddress*Division of Arthritis and Rheumatic Diseases, Oregon Health & ScienceUniversity, 3181 Sam Jackson Park Road OP-09, Portland, OR 97239, USA.E-mail: thompsmo@ohsu.eduCurrent Pain and Headache Reports 2003, 7:342–347Current Science Inc. ISSN 1531–3433Copyright © 2003 by Current Science Inc.IntroductionFibromyalgia is a syndrome characterized by widespreadmusculoskeletal pain, fatigue, and nonrestorative sleepthat affects approximately 2% of adults in the UnitedStates. Clinically, the symptoms of fibromyalgia arereminiscent of a viral syndrome. This observation hasled investigators to search for underlying chronic viralinfections in patients with fibromyalgia. Fibromyalgiasyndrome has been documented in 10% to 16% ofpatients with chronic hepatitis C virus (HCV) infection, arate significantly higher than in the general population[1,2]. It is unknown why fibromyalgia occurs socommonly in association with this chronic viral infection.One hypothesis is that chronic hepatitis C infection causespersistent upregulation of the cellular immune response,accompanied by abnormal cytokine responses. Alteredproinflammatory cytokine levels could cause perturbationsin the sympathetic nervous system and hypothalamicpituitary-adrenal (HPA) axis and also may directly causesome of the symptoms that are common to fibromyalgia.In this paper, the existing literature on cytokines andtheir possible role in the pathogenesis of fibromyalgia andhepatitis C are discussed.Fibromyalgia and the Immune SystemFibromyalgia is a complex syndrome of widespread pain inmuscles and joints accompanied by tenderness in specificanatomic locations referred to as tender points. Fibromyalgiais estimated to effect approximately 2% ofthe population, with more than 90% of the patientsbeing women diagnosed between the ages of 20 and 40years [3–5]. Patients with fibromyalgia syndrome oftenhave associated symptoms including fatigue, irregular sleeppatterns, cognitive dysfunction, and autonomic symptomssuch as lightheadedness, irritable bowel, and irritable bladder.The pathophysiology of fibromyalgia is not understoodcompletely, but is thought to involve perturbationsin the immune system, the hypothalamic-pituitary axis,and the sympathetic nervous system (SNS). The interactionsbetween these systems are complex and there ismounting evidence that the clinical manifestations of thedisease, including myalgias, fatigue, autonomic dysfunction,and sleep and mood disorders, may result fromabnormalities in any one of these systems [6•,7].The immune system is thought to play a role in thepathogenesis of fibromyalgia through its interactions withthe HPA and SNS, but the precise mechanisms continueto be elucidated. Numerous studies have examined theoverall function of the immune system in patients withfibromyalgia [8]. A subset of patients with fibromyalgiaexhibit low-level autoantibodies (antinuclear antibody) orimmunoglobulins (Ig; rheumatoid factor) and may haveFibromyalgia and chronic hepatitis C infection share manyclinical features including prominent somatic complaintssuch as musculoskeletal pain and fatigue. There is a growingbody of evidence supporting a link between cytokines andsomatic complaints. This review discusses alterations ofcytokines in fibromyalgia, including increased serum levelsof interleukin (IL)-2, IL-2 receptor, IL-8, IL-1 receptor antagonist;increased IL-1 and IL-6 produced by stimulatedperipheral blood mononuclear cell in patients with FM forlonger than 2 years; increased gp130, which is a neutrophilcytokine transducing protein; increased soluble IL-6 receptorand soluble IL-1 receptor antagonist only in patientswith fibromyalgia who are depressed; and IL-1 , IL-6, andTNF-α by reverse transcriptase-polymerase chain reactionin skin biopsies of some patients with fibromyalgia. In addition,this review describes the mechanism by which alterationsin cytokines in fibromyalgia and chronic hepatitis Cinfection can produce hyperalgesia and other neurally mediatedsymptoms through the presence of cytokine receptorson glial cells and opiate receptors on lymphocytes andthe influence of cytokines on the hypothalamus-pituitaryadrenalaxis such as IL-1, IL-6, and TNF-α activating and IL-2and IFN-α down-regulating the HPA axis, respectively.The association between chronic hepatitis C infection andfibromyalgia is discussed, including a description of keycytokine changes in chronic hepatitis C infection. Futurestudies are encouraged to further characterize theseimmunologic alterations with potential pathophysiologicand therapeutic implications. Fibromyalgia, Hepatitis C Infection, and the Cytokine Connection • Thompson and Barkhuizen 343evidence of low-level systemic inflammation [8]. However,most patients with fibromyalgia exhibit relatively normalimmune function, which is measured by lymphocytesubsets, IgG subclasses, and circulating immune complexes[9]. Recent research has focused on the possible role ofabnormal cytokine regulation in producing the symptomsof fibromyalgia. The rationale for these studies is derivedfrom the observation that cytokines are important inorchestrating the interactions of the immune system withthe SNS and HPA. In addition, abnormalities in cytokinelevels have been shown to be associated with some ofthe most common symptoms of fibromyalgia such asdepression, sleep disorders, and pain [6•,10–12].Evidence supporting the hypothesis that cytokines areimportant in fibromyalgia is derived from human andanimal models. Glial cells in the central nervous systempossess cytokine receptors, an observation indicating thatcytokines may help regulate pain responses from the SNS.Experiments with rats exposed to intraperitoneal tumornecrosis factor (TNF)-α demonstrate cytokine-inducedhyperalgesia that can be blocked by vagotomy [12]. Thisobservation suggests that cytokines cause hyperalgesiaby binding to paraganglia associated with afferent vagalfibers [12]. Furthermore, lymphocytes have been foundto express opiate receptors that respond to substance P, aprimary modulator of pain in the central nervous system[10,11]. Investigators observed that patients with cancerwho underwent therapy with the cytokine interleukin (IL)-2 experienced myalgias, fatigue, malaise, and sleep disturbancesymptoms similar to what is experienced in patientswith fibromyalgia [13].In animal and human studies, proinflammatorycytokines such as interleukin 1 (IL-1), TNF-α, and IL-6have been shown to produce hyperalgesia by directlyinfluencing nociceptive neurons and to cause fatigue, sleepdisorders, and depressive symptoms [12,14,15]. Cytokinessuch as IL-6 can activate the SNS and IL-8 is known to playa role in sympathetic pain [16]. It also is known that IL-1and TNF-α are somnogenic and that interferon α (IFN-α)can produce disorientation and fatigue [9,17]. Cytokinesalso influence the function of the HPA axis. IL-1, IL-6and TNF- activate and IL-2 and IFN-α down-regulate theHPA axis [18].Efforts have been made to determine whether patientswith fibromyalgia exhibit systematic abnormalities inthe levels of serum cytokines or cytokines produced bycirculating immune cells. Patients with fibromyalgiawere reported to have elevated levels of serum IL-2 andincreased production of IL-2 by T lymphocytes whencompared with control subjects [13]. Serum levels of IL-1,IL-6, IL-8 and soluble IL-2 receptor (IL-2r) were measuredin 113 patients with fibromyalgia and 32 healthy subjects[19]. IL-1 and IL-6 levels did not differ between diseaseand control groups, but the patients with fibromyalgiahad statistically significantly increased levels of IL-8 andIL-2r. Furthermore, higher serum levels of IL-8 wereobserved to be associated with an increase in self-reportedpain intensity [19].Serum cytokine levels (IL-1β, IL-2, IL-6, IL-8, IL-10, IL-2r,IL-1 receptor antagonist [IL-1ra], IFN-γ , and TNF-α) andcytokines derived from resting and stimulated peripheralblood mononuclear cells (PBMC) were measured in 56patients with fibromyalgia [20]. These cytokine levels werecompared with levels measured in gender- and age-matchedhealthy control subjects. Investigators observed increasedserum levels of IL-8 and IL-1ra in patients with fibromyalgia.Furthermore, patients with a longer duration of disease(> 2 years) had the highest levels of IL-8. The other serumcytokine levels did not appear to differ between patientswith fibromyalgia and control subjects. Levels of IL-1raand IL-6 from resting PBMC were found to be elevated infibromyalgia patients, with a longer duration of diseasecompared with control subjects, but no differences werefound in those levels between fibromyalgia patients whohad the disease for less than 2 years and control subjects[20]. In vitro stimulation of PBMC produced increasedlevels of IL-1 and IL-6 in fibromyalgia patients with longerdisease duration compared with control subjects. Theauthors hypothesize that the increase in IL-6 and IL-8is caused by the increased central sensitization and releaseof substance P and that the elevated level of IL-1ra is acompensatory anti-inflammatory response. The elevation ofthese proinflammatory cytokines may explain some ofthe symptoms of fibromyalgia such as hyperalgesia, fatigue,and depression.In comparing 21 patients with fibromyalgia with 33healthy subjects, investigators found that soluble levels ofgp130, a common signal transducer protein for neutrophiliccytokines, were significantly increased in fibromyalgiapatients [21]. In contrast, serum levels of IL-6did not differ and levels of soluble IL-6 receptor (sIL-6r)and soluble IL-1 receptor antagonist (sIL-1a) were elevatedonly in the subpopulation of fibromyalgia patientswith more severe depression [21]. Serum soluble gp130competes with its membrane-bound counterpart; therefore,it potentially could interfere with signaling fromproinflammatory cytokines such as IL-6. The authorsinterpret the results to indicate that patients with fibromyalgiahave a suppressed rather than an overactiveimmune response.Levels of cytokines were measured by reverse transcriptasepolymerase chain reaction (RT-PCR) in skinbiopsies of 53 patients with longstanding fibromyalgiaand were compared with those from 10 healthy controlsubjects [22]. IL-1β was detectable in skin biopsies from38% of the patients with fibromyalgia, IL-6 was detectablein 27%, and TNF-α was detectable in 32%. In contrast,none of these cytokines could be detected in skin biopsiesfrom the control subjects. In the skin biopsies from thepatients with fibromyalgia, immunohistochemistry localizedexpression of these cytokines to mononuclear c344 FibromyalgiaInvestigations of cytokines in fibromyalgia have beenconflicting and have failed to demonstrate a clear patternof cytokine abnormalities common to patients with fibromyalgia.Some of the disparate results may reflect physiologicdifferences between subsets of fibromyalgia patientsand variations in cytokine patterns with disease duration.Furthermore, it is unclear whether pathophysiologicprocesses are better reflected in levels of serum cytokines,tissue-specific cytokines, or cytokines derived fromcirculating immune cells. Nonetheless, it is well substantiatedthat cytokines play a key role in helping to regulatethe immune system and its interactions with the SNS andHPA axis. Additionally, that fibromyalgia-like symptomscan be induced in patients exposed to elevated levels ofproinflammatory cytokines makes for an intriguinghypothesis regarding the pathogenesis of fibromyalgiawith regard to altered cytokine regulation.Fibromyalgia and Hepatitis CThe initial event or events that precipitate the developmentof fibromyalgia syndrome are unknown. Patients withfibromyalgia often describe a “flu-like” illness precedingthe development of their symptoms of chronic musculoskeletalpain and fatigue. In one study [23], a flu-likeillness was reported in 50% of the patients. This observationhas led some investigators to look for evidence ofunderlying chronic infections in patients with fibromyalgiaand associations have been noted with HCV, Lyme disease,HIV, Coxsackie virus, and parvovirus [24–26].Hepatitis C virus is a single-stranded RNA virus thatcauses chronic hepatitis in most of the patients whobecome infected. In chronic HCV infection, the hostimmune response acts to control viral replication. If theimmune system is unable to eradicate the virus, activatedlymphocytes are recruited to the liver and may causepersistent inflammation and hepatocyte damage [27•,28]. The immune response to HCV also is responsible forsome of the extrahepatic manifestations of hepatitis Cinfection [29,30]. Symptoms referable to the musculoskeletalsystem, including arthralgias, myalgias, vasculitis,polyarticular arthritis, and fibromyalgia syndromehave been documented to occur in patients with chronicHCV infection.Several recent studies have examined the epidemiologyof fibromyalgia and chronic HCV infection. These studiessuggest that fibromyalgia is more common among patientswith chronic HCV infection than would be expected basedon the chance occurrence of the two syndromes together.Musculoskeletal pain was reported in 70% of 239 patientswith a variety of hepatic disorders who attended a hepatologyclinic. Musculoskeletal pain was significantly morecommon in the subset of patients with HCV infection(81%) than in HCV-negative patients (56%) [29,30].Fatigue also was more common in the subset of patientswith isolated hepatitis C infection. The likelihood ofreporting myalgia as an extrahepatic manifestationof chronic HCV infection was not related to the severity ofliver disease from hepatitis. In a French cohort of 1202patients with chronic hepatitis C infection, self-reportedarthralgia was present in 23% and myalgia in 15% ofpatients [31]. Female gender and higher body mass indexwere associated independently with those reportingmyalgias in that cohort. In another study, investigatorsdocumented fibromyalgia in 16% of 90 patients withHCV infection and in 3% of patients with non-hepatitis Ccirrhosis, but in none of the healthy control subjects [2].In a study from Spain, HCV infection was documentedin 15% of 112 fibromyalgia patients compared with 5.3%of the control subjects with rheumatoid arthritis. In thesame report, 53% of the patients with hepatitis C infectionreported diffuse musculoskeletal pain, but only 10% metdiagnostic criteria for fibromyalgia [1]. This is comparedwith a control group of surgery clinic patients in which22% reported widespread pain and 1.7% met criteriafor fibromyalgia. The risk of developing fibromyalgia inthe setting of chronic HCV infection was not associatedwith the level of liver damage, which was measured bytransaminase elevation or autoimmune markers, becausetransaminase levels were normal in approximately 50% ofthe patients with fibromyalgia [1].Studies have documented decreased pain thresholds inpatients with fibromyalgia at the fibromyalgia tenderpoints and at the control points [3,32–34]. Levels ofpain perception after repetitive thermal stimulation werehigher in patients with fibromyalgia indicating increasedtemporal summation, supporting the hypothesis thatmodulation of pain in these patients is abnormal [35].Fibromyalgia patients with chronic hepatitis C infectionalso have been found to exhibit reduced pain thresholdswhen measured by dolorimetry compared with healthycontrol subjects. Ninety patients with chronic HCV infectionwere examined for tender points and pain thresholds[36]. The tender point count was significantly higher andthe pain thresholds were significantly lower in the subsetof patients with fibromyalgia compared with patients withchronic HCV who did not have fibromyalgia.Numerous authors have hypothesized that a viralinfection may be the triggering event that results in thedevelopment of fibromyalgia. The epidemiologic studiesoutlined previously support the contention that fibromyalgiaoccurs more commonly in HCV-infected patientsthan in healthy control subjects or in patients with non-HCV chronic liver disease. Furthermore, HCV is foundmore commonly amongst patients with fibromyalgia thanin healthy age- and gender-matched control subjects. Themechanism by which chronic HCV infection may cause thedevelopment of fibromyalgia syndrome is unknown.Investigators have proposed that anxiety caused by theknowledge of a chronic infectious diagnosis may resultin the stress-related development of fibromyalgia [37].However, in some studies, more than 50% of the patientsFibromyalgia, Hepatitis C Infection, and the Cytokine Connection • Thompson and Barkhuizen 345with fibromyalgia who were examined had no priorknowledge of their hepatitis C status, making it difficult toimplicate a psychologic response to their HCV status as acausative mechanism [1].Alternatively, active viral replication or the release ofinflammatory modulators in response to viral infectionmay result in symptoms of fibromyalgia. The next sectionexamines the existing evidence regarding inflammatorycytokines and their role in acute and chronic HCV infection.Cytokines and Hepatitis CMost patients exposed to HCV will develop chronicinfection. The host defense against HCV is complex andappears to involve components of the humoral andcellular immune systems. The relative contributions of theinnate immune system, B cells, and CD4+ and CD8+ Tcells in eradicating the virus are unclear. Most patientsexposed to the virus develop an HCV-directed antibodyresponse, but many are unable to clear the virus. This isthought to be a result of the quasispecies nature of thevirus that enables selection of strains that are able to avoidthe immune system.In addition to an antibody response, the host exhibitsCD4+ and CD8+ cellular immune responses to HCVinfection. Type-I (Th1) CD8+ T-cell immune responsesare characterized by the release of certain cytokines (IL-2,IFN-γ , TNF-α) that are important in host defense againstintracellular pathogens such as viruses. However, the host’shumoral response to pathogens is based on a Type-II (Th2)CD4+ T-cell response and is characterized by the productionof a different set of cytokines (IL-4, IL-5, IL-10) [38].The Chimpanzee model has been studied extensivelywith regard to the cellular immune response to HCV. Inthis animal model, the Chimpanzee’s ability to eradicatethe virus depends on an early, Th1 cytotoxic lymphocyteresponse. Animals in which the response is directed toonarrowly or that do not develop a CD8+ HCV-specificresponse are more likely to develop chronic infection.Similar observations have been made in humans suggestingthat clearing of the virus requires an early, broad CD8+cytotoxic lymphocyte response (ThI response).Studies comparing patients with chronic HCV infectionwith those who are able to clear the HCV infection showthat patients who mount a strong Th1 response without adetectable Th2 response are more likely to clear the virus.In contrast, patients who develop chronic infection withactive liver damage are more likely to exhibit a milder Th1response along with a Th2 response to HCV infection[27•]. Cytotoxic lymphocytes specific for HCV are abundantin liver tissue in patients with chronic hepatitis Cinfection and, in vitro, these cells are capable of producinga Th1 cytokine response [38,39]. Therefore, it does notappear to be a complete absence of appropriate cellularimmune response, but qualitative differences in immuneresponse that account for persistence of HCV infection.Cytokine release plays an important role in theinflammatory cascade that results in fibrosis in patientswith chronic HCV. T cells isolated from hepatic tissuefrom patients with chronic HCV are CD8+ Th1 cells thatproduce IFN-γ , TNF-α, IL-8, GM-CSF, and IL-10 in responseto stimulation with hepatitis C-specific antigens [40].These cytokines would be expected to be important in hosteradication of a viral infection. TNF-α is known to havedirect antiviral activity against HCV while also enhancingproliferation of lymphocytes, IFN-γ inhibits viral replication,and IL-2 has antiviral effects against hepatitis B withunknown effects against hepatitis C.However, with a chronic HCV infection, persistent T-cellactivation and the release of these cytokines leads toongoing recruitment of inflammatory cells and cancontribute to hepatocyte damage and liver fibrosis. TNF-αand IFN-γ can contribute to hepatocyte necrosis, apoptosis,and fibrosis. The Th2 cytokines Il-4 and IL-10 act to downregulatethe Th1 cytokine response and to control fibroticand necrotic effects of the proinflammatory cytokines. Thisis supported by the observation that the amount of liverdamage on biopsy is proportional to the level of Th1 cytokinesin patients with chronic hepatitis C [41]. Furthermore,patients with chronic hepatitis C with elevated Th1 cytokinesare less likely to respond to interferon therapy [42].Cacciarelli et al. [43] measured Th1 and Th2 cytokinelevels in 11 patients with chronic hepatitis C and comparedthem with levels in control subjects who did not have liverdisease. At baseline, the patients infected with HCV hadsignificantly elevated levels of IL-2, IL-4, IL-10, and IFN-γcompared with control subjects. Levels of IL-4 and IL-10were noted to drop after interferon therapy and levelsparalleled a decreased in HCV RNA. The authors concludedthat the HCV infection results in an activated T-cellresponse and that interferon treatment may workpartly through a diminution of Th2 cytokine response.In another study, serum cytokine levels were measuredin 134 patients infected with HCV and in 54 uninfectedcontrol subjects [44]. The chronic HCV-infected patientsexhibited significantly elevated Th1 cytokines, IL-2, IL-2R,and IFN-γ levels; however, the levels of Th2 cytokines IL-4and IL-6 were significantly lower than they were in thecontrol subjects [44].These studies illustrate the complexity of the immunesystem response to the HCV infection. Patients with chronicHCV infection and patients being treated with interferon forHCV infection experience many symptoms that overlap withthe symptom complex typically seen in patients with fibromyalgia.It remains unclear whether the fatigue, myalgias,sleep disorders, and depression commonly experienced bypatients with HCV may be the result of perturbations incytokine levels that develop from the immune response tothe virus. It also is unclear whether subsets of patients withHCV infection may be more prone to develop fibromyalgiaas a result of cytokine abnormalities. Further studies shouldhelp elucidate these relationships.346 FibromyalgiaConclusionsFibromyalgia and chronic hepatitis C infection share manyclinical features. This review demonstrates that theimmunologic abnormalities identified in both conditionsmay be the reason for some of the clinical similarities.However, much work remains to identify the origins ofimmunologic perturbations in fibromyalgia, particularlythe subset in which no clear initiating or chronic infectionis evident. Similarly, the somatic complaints identifiedfrequently in patients with chronic hepatitis C infectionmay share immune-mediated pathophysiologic changesidentified in fibromyalgia. However, more studies areneeded to identify mechanisms whereby immunologicalterations produce central nervous perturbations, whichare thought to be involved centrally in the fibromyalgiasymptom generation.References and Recommended ReadingPapers of particular interest, published recently, have beenhighlighted as:• Of importance•• Of major importance1. Rivera J, de Diego A, Trinchet M, Garcia Monforte A: Fibromyalgia-associated hepatitis C virus infection. Br J Rheumatol1997, 36:981–985.2. Buskila D, Shnaider A, Neumann L, et al.: Musculoskeletalmanifestations and autoantibody profile in 90 hepatitis Cvirus infected Israeli patients. Semin Arthritis Rheum 1998,28:107–113.3. Wolfe F, Simons DG, Fricton J, et al.: The fibromyalgia andmyofascial pain syndromes: a preliminary study of tenderpoints and trigger points in persons with fibromyalgia,myofascial pain syndrome and no disease. J Rheumatol 1992,19:944–951.4. 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Source Fibromyalgia, Hepatitis C Infection, and the Cytokine Connection Mollie E. Thompson, MD, PhD* and André Barkhuizen, MD

Summary Statistics Reports of FIBROMYALGIA in patients taking INCIVEK: 2 Reports of any side effect developing while on INCIVEK : 5938 Percentage of INCIVEK patients where FIBROMYALGIA is a reported side effect: 0.033681374200067% FDA reports of any drug causing FIBROMYALGIA : 6425 Average percentage for all medicated patients where FIBROMYALGIA is reported as a complication: 0.040268107251675%	Physician opinion on INCIVEK as adverse event culprit: ( global)*
Most common side effects (or coexisting conditions) for patients taking INCIVEK: NAUSEA & INCIVEK ( 927 patients) FATIGUE & INCIVEK ( 785 patients) RASH & INCIVEK ( 679 patients) ANAEMIA & INCIVEK ( 678 patients) VOMITING & INCIVEK ( 523 patients) PRURITUS & INCIVEK ( 522 patients) DIARRHOEA & INCIVEK ( 518 patients) ANORECTAL DISCOMFORT & INCIVEK ( 466 patients) HEADACHE & INCIVEK ( 384 patients) DYSPNOEA & INCIVEK ( 332 patients) PYREXIA & INCIVEK ( 314 patients) RASH GENERALISED & INCIVEK ( 289 patients) ASTHENIA & INCIVEK ( 282 patients) HAEMORRHOIDS & INCIVEK ( 275 patients) RASH PRURITIC & INCIVEK ( 266 patients) ANAL PRURITUS & INCIVEK ( 251 patients) DIZZINESS & INCIVEK ( 248 patients) WHITE BLOOD CELL COUNT DECREASED & INCIVEK ( 238 patients) DECREASED APPETITE & INCIVEK ( 229 patients) CHILLS & INCIVEK ( 224 patients) INSOMNIA & INCIVEK ( 209 patients) DRUG DOSE OMISSION & INCIVEK ( 191 patients) PAIN & INCIVEK ( 189 patients) INFLUENZA LIKE ILLNESS & INCIVEK ( 182 patients) DEHYDRATION & INCIVEK ( 178 patients) HAEMOGLOBIN DECREASED & INCIVEK ( 161 patients) PLATELET COUNT DECREASED & INCIVEK ( 160 patients) WEIGHT DECREASED & INCIVEK ( 154 patients) DYSGEUSIA & INCIVEK ( 134 patients) PROCTALGIA & INCIVEK ( 129 patients) PRURITUS GENERALISED & INCIVEK ( 122 patients) DEPRESSION & INCIVEK ( 112 patients) DRUG RASH WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS & INCIVEK ( 107 patients) INAPPROPRIATE SCHEDULE OF DRUG ADMINISTRATION & INCIVEK ( 105 patients) OEDEMA PERIPHERAL & INCIVEK ( 103 patients) FEELING ABNORMAL & INCIVEK ( 99 patients) ANXIETY & INCIVEK ( 94 patients) COUGH & INCIVEK ( 94 patients) MALAISE & INCIVEK ( 93 patients) CONSTIPATION & INCIVEK ( 92 patients) ARTHRALGIA & INCIVEK ( 86 patients) CONFUSIONAL STATE & INCIVEK ( 83 patients) RECTAL HAEMORRHAGE & INCIVEK ( 80 patients) PNEUMONIA & INCIVEK ( 79 patients) LOSS OF CONSCIOUSNESS & INCIVEK ( 76 patients) BLISTER & INCIVEK ( 75 patients) DEATH & INCIVEK ( 75 patients) HAEMATOCHEZIA & INCIVEK ( 74 patients) RASH ERYTHEMATOUS & INCIVEK ( 74 patients)	User posts:
Most frequent diagnoses/indications for prescribing INCIVEK:HEPATITIS C ( 3939 patients ) PRODUCT USED FOR UNKNOWN INDICATION ( 25 patients ) HEPATITIS ( 4 patients ) DEPRESSION ( 1 patients ) HIV INFECTION ( 1 patients ) DISEASE RECURRENCE ( 1 patients ) ( 0 patients )	Drugs with high rate of report for adverse event FIBROMYALGIA: FOSAMAX & FIBROMYALGIA (1848 patients) VIOXX & FIBROMYALGIA (1685 patients) LYRICA & FIBROMYALGIA (1127 patients) NEURONTIN & FIBROMYALGIA (531 patients) CYMBALTA & FIBROMYALGIA (529 patients) LIPITOR & FIBROMYALGIA (494 patients) NEXIUM & FIBROMYALGIA (493 patients) SEROQUEL & FIBROMYALGIA (488 patients) ASPIRIN & FIBROMYALGIA (452 patients) CELEBREX & FIBROMYALGIA (438 patients) XANAX & FIBROMYALGIA (412 patients) ZOLOFT & FIBROMYALGIA (395 patients) ENBREL & FIBROMYALGIA (394 patients) SYNTHROID & FIBROMYALGIA (337 patients) PREDNISONE & FIBROMYALGIA (326 patients) AVONEX & FIBROMYALGIA (315 patients) PRILOSEC & FIBROMYALGIA (300 patients) VICODIN & FIBROMYALGIA (288 patients) ACCUTANE & FIBROMYALGIA (281 patients) HUMIRA & FIBROMYALGIA (274 patients) FOSAMAX PLUS D & FIBROMYALGIA (273 patients) METHOTREXATE & FIBROMYALGIA (264 patients) AMBIEN & FIBROMYALGIA (262 patients) TOPROL-XL & FIBROMYALGIA (260 patients) PREMARIN & FIBROMYALGIA (259 patients) PREVACID & FIBROMYALGIA (255 patients) LISINOPRIL & FIBROMYALGIA (253 patients) KLONOPIN & FIBROMYALGIA (250 patients) FOLIC ACID & FIBROMYALGIA (248 patients) PERCOCET & FIBROMYALGIA (247 patients) ZOCOR & FIBROMYALGIA (229 patients) EFFEXOR & FIBROMYALGIA (228 patients) OXYCONTIN & FIBROMYALGIA (227 patients) PROZAC & FIBROMYALGIA (226 patients) ELAVIL & FIBROMYALGIA (224 patients) FLEXERIL & FIBROMYALGIA (224 patients) VITAMIN D & FIBROMYALGIA (224 patients) DURAGESIC-100 & FIBROMYALGIA (220 patients) REMICADE & FIBROMYALGIA (219 patients)

Hepatitis 411 And Support

Tuesday, December 10, 2013

MedsFacts.com

MEDSFACTS META-ANALYSIS COVERING ADVERSE SIDE EFFECT REPORTS OF INCIVEK PATIENTS WHO DEVELOPED FIBROMYALGIA.

DASHBOARD VIEW OF OUR RESEARCH LITERATURE CONCERNING INCIVEK :

Hepatitis 411 And Support: Fibromyalgia, Hepatitis C Infection, and the Cytokine Connection Mollie E. Thompson, MD, PhD* and André Barkhuizen, MD

Fibromyalgia, Hepatitis C Infection, and the Cytokine Connection Mollie E. Thompson, MD, PhD* and André Barkhuizen, MD

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