standard care for chronic hepatitis c ( chc ) has been a combination of pegylated interferon - alpha ( peg - inf ) and ribavirin , although this treatment has suboptimal antiviral efficacy and significant adverse events . even in the latest treatment recommendation using novel direct acting antiviral agents , interferon ( ifn)-based treatments are still optional . the main drawbacks of interferon - based treatment are unsatisfactory response rate and various adverse effects , which often lead to premature termination of treatment followed by treatment failure . myasthenia gravis ( mg ) is an autoimmune neuromuscular junction disorder characterized by muscular weakness and fatigability . mg is occasionally associated with invasive thymoma that needs surgical resection and may progress to severe respiratory failure . development of mg in patients with chc has been rarely reported before or during antiviral treatment with interferon . a total of 12 cases of mg were reported in association with interferon treatment for chc and 6 of them went through myasthenia crisis that require respiratory support . we experienced a rare case of myasthenia crisis during antiviral therapy for chc , in whom mediastinal thymoma was discovered and successfully managed with surgical thymectomy and meticulous medical care . we reviewed the clinical course of this life - threatening complication of ifn treatment along with the already reported myasthenia crisis cases in chc patients . a 47-year - old male patient presented with a complaining of sudden diplopia that developed one week after 11-week of antiviral combination treatment for chronic hepatitis c ( figure 1a ) . he had been on antiviral combination treatment with peg - ifn-2a ( 180  g / wk ) ( pegasys ; roche , basel , switzerland ) and ribavirin ( 1000  mg / d ) ( lg ribavirin ; lg life sciences , seoul , korea ) for the genotype 1b hepatitis c virus ( hcv ) infection . the pretreatment serum hcv rna level was 2.32    10 iu / ml and ast / alt levels were 255/323  u / l . at 6-week of treatment , the dosage of peg - ifn-2a was reduced to 90  g / wk , but wbc count continued decreasing to 2000/mm . five weeks later , the absolute neutrophil count was 500/mm and the serum hcv rna level was below the limit of detection ( < 15  iu / ml ) . consequently , the antiviral treatment was promptly discontinued and the neutropenia improved on serial blood tests . one week after discontinuation of antiviral treatment , the patient complained of sudden diplopia and right eye ptosis was observed . one week later , right eye ptosis and upper extremities weakness ( grade iii ) were noted . he was immediately hospitalized and initial physical examination was normal except facial palsy with the right ptosis , mild dyspnea , and upper extremities weakness . upon admission , he denied any other oral medications and had no history of vascular or thyroid diseases . ptosis and restricted movement on the right upper lid was improved after treatment ( b ) . on further evaluation , the low rate repetitive nerve stimulation test ( jolly test ) and neostigmine test were positive findings for myasthenia gravis ( table 1 ) and serum antiacetylcholine receptor ( anti - achr ) antibody level of 14.95  nmol / l ( normal range : below 0.2 initial symptoms of ocular mg progressed to difficulties in chewing and swallowing , followed by respiratory failure in 3 days . administration of pyridostigmine ( mestinon ) 180  mg / day was started and chest ct scan was performed which revealed anterior mediastinal mass measuring 7  cm in its greatest dimension , whereas brain imaging study was normal ( figure 2 ) . the patient received a surgical thymectomy and a high - grade thymoma invading pericardium and pleura ( figure 3 ) was observed on the pathological examination of the surgical specimen , which confirmed invasive thymoma ( type b3 , who classification ) . the patient 's respiratory failure aggravated after surgery , leading to an increased ventilator dependency . in response to the worsening respiratory condition , pyridostigmine dose was increased up to 600  mg / d and intravenous immunoglobulin and high - dose steroid pulse therapy were started . after 40 days of intensive care , the patient has his ocular symptoms back to normal ( figure 1b ) and was successfully weaned from the mechanical ventilator . results of low rate repetitive nerve stimulation test ( rnst ) and stigmine test chest ct findings . there was 7-cm sized lobulated solid mass with internal low density and calcified portion at anterior mediastinum . ( a ) h&e stain ( 40 ) shows a multilobular growth pattern and infiltration into lung parenchyma . ( b ) h&e stain ( 100 ) shows thymoma b3 findings : sheet - like growth of medium - size round or polygonal cells with slight atypia ( sheet - like growth pattern ) ; epithelial cells are mixed with a minor component of intraepithelial lymphocytes . treatment for chc with combination of peg - inf and ribavirin eradicates hcv rna in 40% to 50% of treatment - naive patients infected with hcv genotype 1 . in early clinical trials , 10% to 14% of treated patients discontinue combination treatment prematurely due to various adverse events and ifn was the major concern in most of them . unsatisfactory response rate and high rate of unbearable side effects have been the major issues of conventional combination therapy . recently , direct acting antiviral agents ( daa ) against hcv were developed and showed markedly improved clinical efficacy than the conventional combination treatment in terms of both potency and safety aspects . new standards of treatments using direct acting antivirals are being established and rapidly replacing the conventional combination therapy . however , the conventional combination treatment is still widely prescribed for chc and ifn is not completely excluded from some of the daa - based new regimens yet . therefore , for the treatment of chc it is still major concern of clinicians to cope with the various side effects of ifn . mg in patients with chc were mostly associated with ifn treatment , but it may develop without ifn administration . two case reports   described development of mg in chc patients who did not receive antiviral treatment . a 35-year - old male patients with established chc for several years without any treatment developed mg and a 59-year - old male with liver cirrhosis as a result of long - standing hcv infection developed typical mg symptoms and died due to myasthenia crisis . the authors suggested the cross - reactivity between hcv epitopes and the acetylcholine receptor as the underlying mechanism . the etiologic roles of various viral infections including hcv were suggested for the development of mg , but the exact significance of hcv infection per se is not clear . though mg was not reported in large - scale analyses of chc patients who received ifn treatment , literatures suggesting the association between mg and ifn administration have been published in the form of case reports . there were 12 cases of mg by ifn for chc including 6 myasthenia crisis cases ( table 2 ) . in case reports of myasthenia crisis that developed during ifn - based antiviral treatment for chc , male patients > 44 were most commonly affected and the mean age of patients was 57 years and mean interval between starting ifn administration and diagnosis of mg was 4.57 months ( 6 weeks to 15 months ) . the mean duration of ifn treatment was 4.96 months ( 6 weeks to 15 months ) . the mean level of anti - achr antibody was high as 16.3  nmol / l . in most patients , respiratory distress followed advanced progression of mg symptoms and a case of severe respiratory failure was reported at 6 months after ifn discontinuation . the clinical courses of mg cases by ifn for chc were either mild or severe enough to suffer myasthenia crisis , but most of the patients were recovered eventually with medical care after discontinuing ifn treatment . list of cases of myasthenia crisis by interferon treatment for chronic hepatitis c to our knowledge , this is the second case of thymoma - associated mg during ifn treatment for chc . a case of mg that progressed to myasthenic crisis was reported at 1996 in japanese patient who had thymomectomy for known thymoma - associated mg , 19 years before starting antiviral treatment . thymomas are responsible for 21% of mg cases and 30% of patients with thymoma have symptoms of mg . myasthenic crisis is the most serious complication of mg and thymoma is one of the risk factors attributed to it . the mechanism of mg development by ifn therapy is not completely understood , but some of the complex immunological actions of ifn such as enhanced lymphocyte cytotoxicity , production of pro - inflammatory cytokines , inhibition of t suppressor cell function , activation of t helper lymphocytes by autoantigens , and differentiation of antigen - presenting cell might contribute to the development of ifn - induced autoimmune diseases . the thymus plays a primary role in early - onset mg mediated by anti - achr antibodies . ifn - beta could play a central role in thymic events leading to mg by triggering the overexpression of a - achr probably leading to thymic dendritic cells autosensitization , the abnormal recruitment of peripheral cells , and germinal center formation . the epithelial neoplastic cells of thymoma are capable of presenting epitopes , which cross - reacts with different neuromuscular antigens . in addition to achr antibodies , antibodies against striated muscle titin and ryr antigens are found in most of mg thymoma patients . on the other , it has also been suggested that some infectious viruses and hcv itself may lead to mg via mechanism of cross - reactivity between viral epitopes and the acetylcholine receptor . it is not known whether the patients who experienced mg during ifn treatment for chc had subclinical mg before initiating treatment because pretreatment screening for mg is not routinely recommended . in some patients , pre - existing subclinical mg that might be associated with hcv infection itself , progress to overt mg during ifn treatment , whereas , in others , de novo mg might be induced by ifn administration . in our patient , relatively large thymoma so it seems that thymoma - associated subclinical mg were unrecognized before treatment , which was provoked by ifn administration to progress to life - threatening myasthenic crisis . for the better understanding of clinical implication of ifn - induced mg in chc treatment , screening for mg in chc patient might be considered before starting treatment or at least , during treatment when the patient complained of fatigue , muscle weakness . screening for mg with serum anti - achr antibody test is simple and helpful in many patients , but it needs further investigation in this clinical condition because some of mg patients have serum anti - achr antibody levels within normal range . in patients with chc who is going to receive ifn - based antiviral treatment , whether screening for thymoma or subclinical mg should be included in basal evaluation is not clear but physicians need to keep in mind the potential life - threatening manifestations of mg before and during antiviral treatment especially when patients complain of muscular weakness and easy fatigability .
abstractmyasthenia gravis is occasionally associated with thymoma that needs surgical resection and may progress to severe respiratory failure . 
 we experienced a rare case of myasthenia crisis during antiviral therapy for chronic hepatitis c , in whom mediastinal thymoma was discovered and successfully managed with surgical thymectomy and meticulous medical care.a 47-year - old - male patient complained of sudden diplopia 1 week after stopping 11-week administration of pegylated - interferon and ribavirin for chronic hepatitis c. ophthalmologic examinations revealed ptosis on the right eyelid and restricted right eye movement . 
 myasthenia gravis was confirmed by positive repetitive nerve stimulation test and positive serum antiacetylcholine receptor antibody test , and mediastinal thymoma was found on chest ct scan . 
 the ocular myasthenia gravis progressed to respiratory failure even after discontinuing antiviral treatment but eventually recovered with thymectomy , anticholinesterase administration , steroid pulse therapy , and prolonged ventilator care . 
 we describe the clinical features of this life - threatening complication of interferon treatment along with previous myasthenia crisis cases by interferon for chronic hepatitis c.in patients with chronic hepatitis c who is going to receive interferon - based antiviral treatment , physicians need to keep in mind the potential life - threatening manifestations of myasthenia gravis before and during antiviral treatment especially when patients complain of muscular weakness and easy fatigability .