Propylthiouracil Treatment Research Articles

Thyroid and pregnancy.

Thyroid and pregnancy.

Chronic Effects of Propylthiouracil on Metabolism and Secretion of Adrenocorticotropin and Corticosterone in Male Rats

Background: Propylthiouracil (PTU) is a thioamide drug for treating hyperthyroidism. We have already found that chronic administration of PTU decreases the level of plasma corticosterone and attenuates both the activities of 11β- hydroxylase and the generation of cyclic adenosine monophosphate (cyclic AMP) in rat zona fasciculata-reticularis (ZFR) cells. The present study aimed to investigate the chronic effects of PTU on metabolism, adrenocorticotropic hormone (ACTH) and corticosterone secretion. Methods: Male rats were randomly divided into four groups and injected subcutaneously with saline, PTU, thyroxine (T4) or PTU plus T4 once daily for 2 weeks. For metabolism studies, the body weight, food intake, water intake, urine volume, and feces weight of every rat were recorded daily. The rats were sacrificed after treatment, and the plasma thyroid stimulating hormone (TSH), ACTH, and corticosterone were measured. ZFR cells were separated from adrenal glands and then stimulated by forskolin (an activator of adenylyl cyclase, 10^(-5) M), 8-bromo-cAMP (8-Br-cAMP, a permeable analogue of cAMP, 10^(-5) M), ACTH (a stimulator to increase corticosterone secretion, 10^(-9) M), and deoxycorticosterone (DOC, a steroidogenic precursor of corticosterone, 10^(-5) M) in order to investigate the alternation of corticosterone secretion and enzyme activity. Results: Chronic administration of PTU decreased food intake and feces weight but increased urine volume. The concentration of plasma TSH increased after chronic PTU treatment. PTU also suppressed release of ACTH and decreased production of corticosterone. After the isolation of ZFR cells from PTU and PTU plus T4-treated rats, both basal and evoked levels of corticosterone release were enhanced. Conclusion: Chronic administration of PTU inhibited pituitary gland from releasing ACTH, and this reaction led to decrease in corticosterone production in vivo. PTU treatment might upregulate downstream messengers of ACTH signal pathway in ZFR cells, thus enhancing release of corticosterone in vitro.

PP-217. Early managing of a newborn with caudal regression syndrome

male infants and 2 women to female. Of these women no one gave birth with ichthyosis. Five patients had isolated very low estriol levels (<0.01 MoM). Of these women one had umbilical cord knot, one was on corticosteroid treatment due to Crohn's disease and 3 were on Propylthiouracil treatment due to severe thyroid dysfunction. Our congenital ichthyosis rate was 1/10,806 during a 3 year period (2007– 2009). Six cases of congenital ichthyosis were identified during a 3 year period. Of these six babies, five were male and one was female and all of them survived. We could reach the triple screen results of three, which were within normal range. Two of these mothers were on Propylthiouracil treatment due to thyroid dysfunction. The other woman used insulin due to gestational diabetes mellitus and anti-Rh immunoglobulin to prevent rhesus disease. So in 50% of ichthyosis cases there was history of maternal drug intake.

Stimulatory Effects of Propylthiouracil on Pregnenolone Production through Upregulation of Steroidogenic Acute Regulatory Protein Expression in Rat Granulosa Cells

Propylthiouracil (PTU) is a common and effective clinical medicine for the treatment of hyperthyroidism. Our previous study demonstrated that short-term treatment with PTU inhibits progesterone production in rat granulosa cells. However, our present results indicate that a 16-h treatment with PTU was able to stimulate pregnenolone production in rat granulosa cells, although progesterone production was diminished by PTU through inhibition of 3β-hydroxysteroid dehydrogenase. Notably, we found that PTU treatment enhanced the conversion of cholesterol into pregnenolone, whereas the protein level of the cytochrome P450 side-chain cleavage enzyme (P450scc, which is the enzyme responding to this conversion) was not affected. Interestingly, the levels of steroidogenic acute regulatory protein (StAR) in both total cell lysate and the mitochondrial fraction were significantly increased by PTU treatment. Furthermore, the binding of steroidogenic factor-1 (SF-1) to the StAR promoter region was also enhanced by PTU treatment, which suggests that PTU could upregulate StAR gene expression. In addition to SF-1 regulation, we found that mitogen-activated protein (MAP) kinase kinase activation is an important regulator of PTU-stimulated StAR protein expression, based on the effects of the MEK inhibitor PD98059. In conclusion, these results indicate that PTU plays opposite roles in the production of progesterone and its precursor, pregnenolone. The regulation of negative feedback on speeding the cholesterol transportation and pregnenolone conversion after a 16-h PTU treatment may be the mechanism explaining PTU's inhibition of progesterone production in rat granulosa cells.

Cardiac myosin heavy chain gene regulation by thyroid hormone involves altered histone modifications

The antithetical regulation of cardiac α- and β-myosin heavy chain (MHC) genes by thyroid hormone (T(3)) is not well understood but appears to involve thyroid hormone interaction with its nuclear receptor and MHC promoters as well as cis-acting noncoding regulatory RNA (ncRNA). Both of these phenomena involve epigenetic regulations. This study investigated the extent that altered thyroid state induces histone modifications in the chromatin associated with the cardiac MHC genes. We hypothesized that specific epigenetic events could be identified and linked to cardiac MHC gene switching in response to a hypothyroid or hyperthyroid state. A hypothyroid state was induced in rats by propylthiouracil treatment (PTU), whereas a hyperthyroid (T(3)) was induced by T(3) treatment. The left ventricle was analyzed after 7 days for MHC pre-mRNA expression, and the chromatin was assessed for enrichment in specific histone modifications using chromatin immunoprecipitation quantitative PCR assays. At both the α-MHC promoter and the intergenic region, the enrichment in acetyl histone H3 at K9/14 (H3K9/14ac) and trimethyl histone H3 at K4 (H3K4me3) changed in a similar fashion. They were both decreased with PTU treatment but did not change under T(3), except at a location situated 5' to the antisense intergenic transcription start site. These same marks varied differently on the β-MHC promoter. For example, H3K4me3 enrichment correlated with the β-promoter activity in PTU and T(3) groups, whereas H3K9/14ac was repressed in the T(3) group but did not change under PTU. Histone H3K9me was enriched in chromatin of both the intergenic and α-MHC promoters in the PTU group, whereas histone H4K20me1 was enriched in chromatin of β-MHC promoter in the normal control and T(3) groups. Collectively, these findings provide evidence that specific epigenetic phenomena modulate MHC gene expression in altered thyroid states.

Up-regulation of type 2 iodothyronine deiodinase in dilated cardiomyopathy

Thyroid hormone (TH) has prominent effects on the heart, and hyperthyroidism is occasionally found to be a cause of dilated cardiomyopathy (DCM). We aim to explore the potential role of TH in the pathogenesis of DCM. The pathophysiological role of TH in the heart was investigated using a knock-in mouse model of inherited DCM with a deletion mutation DeltaK210 in the cardiac troponin T gene. Serum tri-iodothyronine (T(3)) levels showed no significant difference between wild-type (WT) and DCM mice, whereas cardiac T(3) levels in DCM mice were significantly higher than those in WT mice. Type 2 iodothyronine deiodinase (Dio2), which produces T(3) from thyroxin, was up-regulated in the DCM mice hearts. The cAMP levels were increased in DCM mice hearts, suggesting that transcriptional up-regulation of Dio2 gene is mediated through the evolutionarily conserved cAMP-response element site in its promoter. Propylthiouracil (PTU), an anti-thyroid drug, prevented the hypertrophic remodelling of the heart in DCM mice and improved their cardiac function and life expectancy. Akt and p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation increased in the DCM mice hearts and PTU treatment significantly reduced the phosphorylation levels, strongly suggesting that Dio2 up-regulation is involved in cardiac remodelling in DCM through activating the TH-signalling pathways involving Akt and p38 MAPK. Dio2 gene expression was also markedly up-regulated in the mice hearts developing similar eccentric hypertrophy after myocardial infarction. Local hyperthyroidism via transcriptional up-regulation of the Dio2 gene may be an important underlying mechanism for the hypertrophic cardiac remodelling in DCM.

Necrotizing vasculitis in a patient affected by autoimmune hyperthyroidism treated with propylthiouracil

Necrotizing vasculitis is a complex phenomenon because of an inflammation of small and larger vessels with polymorph infiltration within the vessel walls and leukocytoclasis, occurring in several autoimmune diseases. Propylthiouracil (PTU) is a medication commonly used to treat hyperthyroidism, but it is associated with various rare side effects, such as antineutrophil cytoplasm antibody-positive vasculitis. In the last decades, multiple cases of PTU causing antineutrophilic cytoplasmic antibody have been reported, some of them fatal. The present authors report the case of a 34-year-old Caucasian female affected by autoimmune hyperthyroidism treated with PTU, presenting an antineutrophil cytoplasm antibody-positive necrotizing vasculitis, with high levels of anticardiolipin antibodies that involved the upper arms and buttocks. The clinical manifestations improved after discontinuing of PTU and immunosuppressant treatment.

Hyperthyroidism Caused by a Germline Activating Mutation of the Thyrotropin Receptor Gene: Difficulties in Diagnosis and Therapy

Germline activating mutations of the thyrotropin receptor (TSHR) gene have been considered as the only known cause of sporadic nonautoimmune hyperthyroidism in the pediatric population. Here we describe the long-term follow-up and evaluation of a patient with sporadic nonautoimmune primary hyperthyroidism who was found to have a de novo germline activating mutation of the TSHR gene. The patient was an infant who presented at the age of 10 months in an unconscious state with exsiccation, wet skin, fever, and tachycardia. Nonautoimmune primary hyperthyroidism was diagnosed, and brain magnetic resonance imaging and computed tomography showed also Arnold-Chiari malformation type I. Continuous propylthiouracil treatment resulted in a prolonged clinical cure lasting for 10 years. At the age of 11 years and 5 months the patient underwent subtotal thyroidectomy because of symptoms of trachea compression caused by a progressive multinodular goiter. However, 2 months after surgery, hormonal evaluation indicated recurrent hyperthyroidism and the patient was treated with propylthiouracil during the next 4 years. At the age of 15 years the patient again developed symptoms of trachea compression. Radioiodine treatment resulted in a regression of the recurrent goiter and a permanent cure of hyperthyroidism without relapse during the last 3 years of his follow-up. Sequencing of exon 10 of the TSHR gene showed a de novo heterozygous germline I630L mutation, which has been previously described as activating mutation at somatic level in toxic thyroid nodules. The I630L mutation of the TSHR gene occurs not only at somatic level in toxic thyroid nodules, but also its presence in germline is associated with nonautoimmune primary hyperthyroidism. Our case report demonstrates that in this disorder a continuous growth of the thyroid occurs without any evidence of elevated TSH due to antithyroid drug overdosing. This may justify previous recommendations for early treatment of affected patients with removal of as much thyroid tissue as possible.

Developmental Iodine Deficiency and Hypothyroidism Reduce Phosphorylation of Calcium/Calmodulin-Dependent Kinase II in the Rat Entorhinal Cortex

Iodine is essential for the synthesis of triiodothyronine (T₃) and thyroxine (T₄). Iodine deficiency leads to inadequate thyroid hormone. Hypothyroidism induced by iodine deficiency during gestation and postnatal period leads to cognitive deficits in learning and memory. However, the mechanism underlying these deficits is unclear. Calcium-dependent calmodulin kinase II (CaMKII) known as a potential memory molecule regulates important neuronal functions including learning and memory. Recent studies have shown that hypothyroidism alters phosphorylation of CaMKII in hippocampus or even in sympathetic ganglia of rats. Though the entorhinal cortex (EC) is an important functional structure within the neuronal network responsible for learning and memory, little is known about the effect of hypothyroidism on phosphorylation of CaMKII in the EC. Here, we report that iodine deficiency and propylthiouracil treatment through gestation and lactation reduce phosphorylation of CaMKII in the EC of pups. The increase of calcineurin, as well as reduction of neurogranin and calmodulin, may account for the reduced phosphorylation of CaMKII induced by developmental iodine deficiency and hypothyroidism. These findings in the EC may contribute to understanding the mechanisms that underlie impairment of learning and memory induced by developmental iodine deficiency and hypothyroidism.

Regulation of arteriolar density in adult myocardium during low thyroid conditions

Low thyroid function induced by either propylthiouracil (PTU) treatment or thyroidectomy surgery led to a reduction of arteriolar density in adult rat myocardium, which can be prevented by treatment with thyroxine or the thyroid hormone analogue 3,5-diiodothyropropionic acid (DITPA). However, many questions related to pathophysiological changes and the regulation of arteriolar density in the heart due to hypothyroidism remain unanswered. Sprague–Dawley rats were treated with PTU in drinking water for 1, 3, and 6 weeks, or co-treated with the vasodilator dipyridamole and PTU for 6 weeks, or treated with PTU for 6 weeks and treatment discontinued for 2 or 4 weeks. Heart mass, body mass, cardiac function and myocardial arteriolar density were determined. Arteriolar loss in hypothyroidism induced by PTU treatment progressed gradually with a 22% reduction after 3 weeks treatment and 34% by 6 weeks which was largely reversed after discontinuing PTU treatment for only 2 weeks. Combined treatment with the vasodilator dipyridamole during the 6-week PTU treatment period prevented vessel loss indicating the mechanism of arteriolar loss from hypothyroidism may result from vasoconstriction. These results suggest that thyroid hormone is a powerful regulator of vasculature in adult myocardium, particularly in low thyroid states.

Effect of transient postpubertal hypo- and hyperthyroidism on reproductive parameters of Iranian broiler breeder hens

One hundred and thirty two 26-week-old broiler breeder hens were randomly assigned into one of three treatments as control, hypothyroid (HYPO; propylthiouracil (PTU)-treated) or hyperthyroid (HYPER; thyroxine (T4)-treated) group. PTU and T4 were administered between weeks 30 and 33 of age. Blood sampling was started at week 29, and repeated every week until week 35, coinciding with weekly body weighing. Using ELISA, plasma levels of T3, T4 and estradiol were assayed. Egg number, fertility, hatchability, grading of day-old chicks and embryonic developmental stage of unhatched eggs were determined for individual artificially inseminated hen. Effects of PTU and T4 treatment on plasma T4 levels were significant (P 0.05). In conclusion, among the different reproductive parameters in this study, hatchability and weekly egg production were the most responsive parameters to decreased or increased plasma thyroid hormone levels, respectively.

NADPH-d/NOS reactivity in the lumbar dorsal horn of congenitally hypothyroid pups before and after formalin pain induction

We have previously demonstrated that congenitally hypothyroid rat pups exhibit altered behavioral response to formalin pain induction during postnatal period. In the present study, using NADPH-diaphorase histochemistry and NOS immunostaining, we investigated the effect of congenital hypothyroidism on the NOS expression in spinal cord of intact neonates at postnatal days of 15 and 21. We also examined the effect of thyroid dysfunction on the NADPH-d/NOS expression in response to formalin nociception. Congenital hypothyroidism induced by propylthiouracil (PTU) treatment started from gestational day 16 and continued to postnatal day 15 or 21. Congenitally hypothyroid pups exhibited marked reduction in NADPH-d reactive cells (84% and 66% in P15 and P21, respectively; P<0.001) and NOS-ir cells (52% and 91% in P15 and P21, respectively; P<0.001) in superficial lumbar dorsal horn laminae (I–II) as compared to that of normal pups. Moreover, in congenitally hypothyroid pups the NADPH-d/NOS expression following hindpaw formalin injection did not change significantly. Our results demonstrate that congenital hypothyroidism affect developmental expression of NOS in spinal dorsal horn, which may in part explain the altered behavioral pain response as we previously reported in hypothyroid pups.

Differential effects of propylthiouracil, methimazole and thyroidectomy on liver ferritin.

Different groups of rats were made hypothyroid by thyroidectomy (Tx) or treatment with propylthiouracil (PTU) or methimazole (MMI). Some of the hypothyroid rats from each group were simultaneously treated with thyroxine (T4). Liver ferritin concentration and 14C-glycine incorporation into liver ferritin in these rats were studied. Only in MMI-treated rats the ferritin concentration was elevated, which was reduced by simultaneous T4 treatment. PTU treatment resulted in 36-42% reduction in ferritin synthesis, which was not responsive to T4. Thyroidectomy induced 23% enhancement in ferritin synthesis, which was normal in T4-treated Tx rats. The possible causes for these differential effects in hypothyroid rats have been discussed.

Effects of postnatal thyroid hormone deficiency on neurogenesis in the juvenile and adult rat

This study addressed the influence of propylthiouracil (PTU)-induced hypothyroidism on postnatal and adult neurogenesis. PTU was administered from birth to postnatal day 10 (P10) or P21, leading to decreased neural stem cell/progenitor proliferation in the dentate gyrus, as well as significantly fewer granule cells and reduced hippocampal volume. Upon P22 PTU withdrawal, plasma thyroid hormone levels were normal by P90, there was no difference in the number of dentate gyrus or subventricular proliferating cells, but brain weight was smaller. In addition, dentate gyrus density of surviving BrdU-labeled cells increased, with no changes to the olfactory bulb. Quantitative PCR revealed decreased FGF-2, NGF, Wnt3a, and VEGF-A hippocampal expression during PTU treatment, with recovery in adulthood. Pro-apoptotic Bax was up-regulated, and anti-apoptotic Bcl-2 was down-regulated, during PTU treatment, both of which were normalized in the adult brain. In contrast, apoptosis-inducing factor ( AIF) was down-regulated in the adult. These results suggest that mechanisms in the adult brain attempt to compensate for decreased neurogenesis due to postnatal hypothyroidism.

Churg-Strauss Syndrome following PTU Treatment

Propylthiouracil (PTU) is a frequently prescribed drug in the treatment of hyperthyroidism. The use of PTU is, however, accompanied by numerous potentially serious side effects including vasculitis. PTU-related vasculitides can present as haematuria, pulmonary haemorrhage, or cutaneous lesion together with aspecific symptoms such as fever, myalgia, arthralgia, and fatigue. Cerebral involvement is seldom observed. We present a 49-year-old female with Graves' disease and asthma, who developed paresis of the proximal extremities, eosinophilia, pulmonary, and cutaneous lesions following treatment with PTU. A cerebral vasculitis consistent with Churg-Strauss syndrome (CSS) was suspected. Although cerebral involvement is seldom observed with PTU treatment, cerebral vasculitis should be considered in patients developing CNS symptoms.

Perinatal exposure to PTU decreases expression of Arc, Homer 1, Egr 1 and Kcna 1 in the rat cerebral cortex and hippocampus

Environmental chemicals have a potential impact on neuronal development and children's health. The current developmental neurotoxicity (DNT) guideline studies to assess their underlying risk are costly and time-consuming; therefore the more efficient protocol for DNT test is needed. Hypothyroidism in rats induced by perinatal exposure to propylthiouracil (PTU), a thyroid hormone synthesis inhibitor, offers an advantageous model of developmental neurotoxicity (DNT). Understanding the associated alterations in gene expression in brain is a key to elucidate mechanisms and find appropriate molecular markers. The purpose of the present study was to identify PTU treatment-affected transcriptomes in the rat cerebral cortex and the hippocampus using DNA microarrays, and to specify candidate genes linked to DNT. We used an approximately 9000 probe microarray to examine differentially expressed genes between PTU-dosed and vehicle-dosed rats at postnatal days 4, 14, 22 and 70. Expression of immediate early genes (IEGs) such as activity-regulated cytoskeleton-associated protein ( Arc), Homer 1, early growth response 1 ( Egr 1), myelin-associated genes such as myelin-associated oligodendrocytic basic protein (MOBP), myelin basic protein (MBP) and proteolipid protein (PLP) and Kcna1 was apparently affected by perinatal administration of PTU. The results suggest that the alterations may be responsible for the detrimental effects caused by PTU treatment on the nervous system.

Propylthiouracil, independent of its antithyroid effect, decreases VSMC collagen expression

Propylthiouracil (PTU), in addition to its antithyroid effect, is recently found to have a potent antiatherosclerotic effect. Because collagen accumulation is the major contributor to the growth of atherosclerotic lesions and the neointimal formation after arterial injury, the aim of this study is to investigate the impact of PTU on collagen regulation. In the rat carotid injury model, PTU administration reversed the up-regulation of collagen in the neointima induced by balloon injury. In vitro, vascular smooth muscle cells (VSMCs), the main origin of arterial collagen, were treated with PTU. Propylthiouracil caused a concentration-dependent decrease in collagen I and III steady-state protein and mRNA levels, as determined by immuno-cytochemistry, Western, and/or Northern blot analyses. Transient transfection experiments using rat type I collagen promoter construct showed that PTU failed to affect collagen gene transcription in VSMCs. Actinomycin D studies demonstrated that the half-life of collagens mRNA decreased with PTU treatment, suggesting that PTU down-regulates collagen expression predominantly at the post-transcriptional level. Taken together, these data suggest that PTU inhibits VSMC collagen production via destabilization of collagen mRNA that contributes to its beneficial effect on atherogenesis and neointimal formation after arterial injury. However, whether the destabilization of collagen may induce plaque rupture in PTU-treated arteries merits further investigation.

Effect of Low Thyroid Function on Cardiac Structure and Function in Spontaneously Hypertensive Heart Failure Rats

Background Although low thyroid function is known to have detrimental effects on the cardiovascular system, including microvascular impairment, little is known about the pathophysiologic consequences of hypothyroidism in the background of hypertension. Methods and Results Hypothyroidism was induced in female spontaneously hypertensive heart failure (SHHF) rats by treatment with propylthiouracil (PTU) for 6 months. Untreated SHHF and normotensive Wistar Furth (WF) rats served as controls. In terminal experiments, heart weight, echocardiographic measurements, hemodynamics, and arteriolar morphometry were performed. Left ventricular internal diameter in systole and diastole were increased and wall thickness, ejection fraction, heart rate, systolic blood pressure, and ±dP/dt were significantly decreased in the treatment group. Surprisingly, there were no observed differences in arteriolar density among the 3 groups. Conclusions As expected, PTU treatment of SHHF rats led to systolic dysfunction and chamber dilation. However, PTU treatment did not lead to arteriolar loss as previously observed in normotensive rats treated with PTU. These finding suggest that induced hypothyroidism leads to detrimental changes in SHHF rats, but the overall effects were no worse than those previously observed in normotensive rats treated with PTU.

Clinical importance of antineutrophil cytoplasmic antibody positivity during propylthiouracil treatment

Propylthiouracil (PTU) is the mainstay of antithyroid drug therapy. Previous studies reported antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis in patients treated for Graves' disease. ANCA has been associated with either PTU or to the disease itself. However, this issue has not been investigated in toxic multinodular goitre (TMNG). The aim of this study was to evaluate the frequency of ANCA positivity in both TMNG and Graves' disease patients treated with PTU, and to investigate the clinical importance of this issue. We studied the presence of ANCA in 46 patients treated with PTU (30 Graves' disease, 16 TMNG). Two years after the discontinuation of PTU, ANCA was re-evaluated in 29 patients (18 Graves' disease, 11 TMNG). By indirect immunofluorescence, 19 of the 46 patients (41.3%) on PTU treatment were ANCA positive [13 of the 30 patients in Graves disease (43.3%), six of the 16 patients in TMNG (37.5%)]. There was no statistically significant difference between Graves' disease and TMNG patients for ANCA positivity (p = 0.362). ANCA positivity was not related to gender, thyroid autoantibodies, alanine aminotransferase, aspartate aminotransferase, neutrophil count and PTU dose. Two years after withdrawal of PTU treatment, 10.3% of patients continued to have positive ANCA (p < 0.0001). Signs and symptoms of vasculitis could not be detected in any of the ANCA-positive patients. Our study suggests that PTU but not Graves' disease itself is the most important factor for ANCA development. The frequency of ANCA positivity is 41.3% in our country which was not different in Graves' disease and TMNG patients. The dose of PTU and ethnic factors are not associated with ANCA positivity. After cessation of PTU, vasculitis did not develop during the 2 years of follow-up despite positive ANCA.

Recurrence of hepatitis C virus during leucocytopenia and spontaneous clearance after recovery from cytopenia: a case report

IntroductionThere is little information about the risk of HCV recurrence in immunosuppressed patients. Although the presence of antibodies to HCV and the absence of HCV-RNA is usually considered to indicate viral elimination, the virus may not be completely eliminated but may be under control of an effective immune response.Case presentationA 69 year old man presented with jaundice, elevated ALT, AST, lipase and concomitant abdominal pain. He was found to be positive for HCV-RNA (genotype 3a) and was diagnosed with acute hepatitis C. Six weeks later no HCV-RNA was detected, and the patient was diagnosed with hyperthyreosis and started on propylthiouracil. After 4 weeks of propylthiouracil treatment, the patient developed leucocytopenia, followed by liver function deterioration and reappearance of HCV-RNA. Propylthiouracil was discontinued and his leukocyte counts increased. Twenty-eight weeks after onset of acute hepatitis C, no HCV-RNA was detected.ConclusionThis case history shows the risk of recurrence of HCV during leucocytopenia. These findings indicate that patients who are anti-HCV positive but HCV-RNA negative may be at risk of cytopenia-induced HCV reactivation.