Thrombocytopenia in Patients with Chronic Hepatitis C Virus Infection

Sumit Dahal1, Smrity Upadhyay2, Rashmi Banjade3, Prajwal Dhakal4, Nabin Khanal2 and Vijaya Raj Bhatt5

1 Interfaith Hospital, Department of Medicine, New York, USA
2 Creighton University Medical Center, Department of Internal Medicine, Omaha, Nebraska, USA
3 Montefiore New Rochelle Hospital, Department of Medicine, New York, USA
4 Michigan State University, Department of Medicine, East Lansing, Michigan, USA
5 University of Nebraska Medical Center, Department of Internal Medicine, Division of Hematology-Oncology, Omaha, Nebraska, USA

Corresponding author: Prajwal Dhakal, MBBS. Department of Medicine, Michigan State University. East Lansing, MI, 48824 Tel:. (W): 517-353-5100. E-mail: prazwal@gmail.com  

Published: March 1, 2017
Received: November 21, 2016
Accepted: February 7, 2017
Mediterr J Hematol Infect Dis 2017, 9(1): e2017019 DOI 10.4084/MJHID.2017.019
This article is available on PDF format at: 

This is an Open Access article distributed under the terms of the Creative Commons Attribution License
https://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Thrombocytopenia in patients with chronic hepatitis C virus (HCV) infection is a major problem. The pathophysiology is multifactorial, with auto-immunogenicity, direct bone marrow suppression, hypersplenism, decreased production of thrombopoietin and therapeutic adverse effect all contributing to thrombocytopenia in different measures.  The greatest challenge in the care of chronic HCV patients with thrombocytopenia is the difficulty in initiating or maintaining IFN containing anti-viral therapy. Although at present, it is possible to avoid this challenge with the use of the sole Direct Antiviral Agents (DAAs) as the primary treatment modality, thrombocytopenia remains of particular interest, especially in cases of advanced liver disease.
The increased risk of bleeding with thrombocytopenia may also impede the initiation and maintenance of different invasive diagnostic and therapeutic procedures. While eradication of HCV infection itself is the most practical strategy for the remission of thrombocytopenia, various pharmacological and non-pharmacological therapeutic options, which vary in their effectiveness and adverse effect profiles, are available. Sustained increase in platelet count is seen with splenectomy and splenic artery embolization, in contrast to only transient rise with platelet transfusion. However, their routine use is limited by complications. Different thrombopoietin analogues have been tried. The use of synthetic thrombopoietins, such as recombinant human TPO and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMDGF), has been hampered by the development of neutralizing antibodies. Thrombopoietin-mimetic agents, in particular, eltrombopag and romiplostim, have been shown to be safe and effective for HCV-related thrombocytopenia in various studies, and they increase platelet count without eliciting any immunogenicity Other treatment modalities including newer TPO analogues- AMG-51, PEG-TPOmp and AKR-501, recombinant human IL-11 (rhIL-11, Oprelvekin), recombinant human erythropoietin (rhEPO), danazol and L-carnitine have shown promising early result with improving thrombocytopenia. Thrombocytopenia in chronic HCV infection remain a major problem, however the recent change in DAAs without IFN,  as the frontline therapy for HCV, permit to avoid the dilemmas associated with initiating or maintaining IFN based anti-viral therapy.


Chronic hepatitis C virus (HCV) infection affects 3% of the world’s population and 1.3% of the United States’ population.[1,2] It is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma, and is one of the most common causes of liver transplants in the United States.[2] Besides hepatic complications, chronic HCV infection is also associated with several extra-hepatic manifestations including thrombocytopenia. Thrombocytopenia in chronic HCV infection is a major problem, particularly in patients with advanced liver disease. The risk of serious bleeding with severe thrombocytopenia can prevent invasive procedures including biopsies for staging.[3] Thrombocytopenia can also complicate bleeding manifestations such as variceal bleeding. It may impede the initiation and continuation of antiviral therapy, potentially decreasing the probability of successful HCV treatment.[4] Recent studies have evaluated the underlying mechanism of thrombocytopenia in chronic HCV infection and assessed the usefulness of several therapeutic options.


The prevalence and degree of thrombocytopenia increase with the severity of liver disease and correlates to hepatocellular damage and hepatic fibrosis. [5] However, use of varying definition for thrombocytopenia and insufficient data on study characteristics such as age, gender, HCV treatment rates and disease severity preclude a more accurate estimate of the overall prevalence.[6] A systematic review estimated the average prevalence of thrombocytopenia in chronic HCV infection to be nearly 24% (Table 1).[6]

Table 1 Table 1. Prevalence of thrombocytopenia in chronic hepatitis C infection.


The pathophysiology of thrombocytopenia in patients with HCV infection is thought to be multifactorial. Besides inducing an autoimmune reaction with production of anti-platelet antibodies, the virus also causes direct bone marrow suppression with resulting thrombocytopenia.[7-10] Chronic HCV infection induced liver fibrosis and cirrhosis leads to portal hypertension with subsequent hypersplenism and sequestration of platelets, decreased the production of thrombopoeitin, and endothelial dysfunction, all of which can contribute to thrombocytopenia.[11-14] Although uncommonly used in developed countries, interferon (IFN) and ribavirin used as part of anti-HCV therapy can also contribute to low platelet count.[15]

Impact on Clinical Management

Although thrombocytopenia in chronic HCV infection is typically low grade and not life-threatening, it represents an obstacle to different diagnostic or therapeutic modalities and may preclude the use of anti-viral treatment.
The greatest challenge in the care of chronic HCV patients with thrombocytopenia is the difficulty in initiating or maintaining IFN containing anti-viral therapy. Although this challenge can be avoided with the use of sole DAAs as the primary treatment modality, thrombocytopenia remains of particular interest, especially in cases of advanced liver disease. In a study by Wang et al., baseline thrombocytopenia increased the risk of drug cessation. Patients with baseline thrombocytopenia actually exhibited compromised sustained virologic response (SVR) rates while those with acquired thrombocytopenia did not. Thus, use of growth factors to maintain SVR rate would be beneficial in those with baseline thrombocytopenia rather than in those who acquire it during therapy as dose reduction doesn’t decrease SVR in such cases.[16]
Thrombocytopenia in HCV may also be a problem for patients with baseline platelet count of <50.000/mm
3, particularly in the presence of previous bleeding even when they are treated with DAAs. However, patients with thrombocytopenia and fibrosis have attained >90% SVR with DAAs even if in a proportion lower in respect to patients with a normal platelet count. Thus, DAAs may be continued most of the times without interruption and thrombopoietin mimetics would be helpful only with severe thrombocytopenia (such as a platelet count of <25,000/mm3).[17-19]
Directly-acting antivirals (DAAs): Recently updated World Health Organization guidelines recommend that DAA regimens (including simeprivir, grazoprevir, daclatasvir, ledipasvir, and sofosbuvir) be used for the treatment of persons with hepatitis C infection rather than regimens with pegylated interferon and ribavirin.[16] Combinations of 2 or 3 DAAs have been shown to be highly effective and safe in both cirrhotic and non-cirrhotic patients in different phase III clinical trials and large real life cohorts with providing SVR rates of >95%. While headache, diarrhea, fatigue, and nausea have frequently been observed, hematologic abnormalities including thrombocytopenia were reported in no more than 1% of cases.[17,18] Lee et al. reported that DAA therapy in one patient precipitated ITP refractory to various treatment modalities and it required several weeks of therapy with multiple platelet transfusions, intravenous immunoglobulin, steroids and romiplostim to achieve a stable platelet count of 40,000/mm
3 with no signs of bleeding.[19] However, this is only one case describing any relation of DAA with thrombocytopenia. A study by Forns et al. showed that HCV genotype 1a-infected patients with surrogate markers of portal hypertension or impaired liver function such as thrombocytopenia and hypoalbuminemia at baseline achieved high SVR rates with ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin and treatment was well tolerated.[20] Additionally, reduction in liver fibrosis markers such as fibrosis-4 score and aspartate transaminase platelet ratio along with regression of transient elastography have been reported with use of DAAs in chronic hepatitis C.[21] In any case, by the time, thrombocytopenia improves following SVR obtained with any antiviral therapy among   chronic  HCV infected patients with advanced hepatic fibrosis.[21,22]
INF based antiviral therapy: Although IFN based antiviral therapy is uncommonly used in developed countries nowadays, the prohibitive cost of DAA may require the use of INF based therapy along with the addition of thrombopoietin mimetics, if required, in economically disadvantaged areas.  Additionally, in chronic hepatitis C cases treated with pegylated INF plus ribavirin, single nucleotide polymorphisms at or near the IL-28B gene have been shown to be a predictor of SVR.[23,24] The American Gastroenterological Association recommends dose reduction of INF with a platelet count between 25,000-50,000 and withdrawal of INF-based treatment with a count below 25,000.[25] This is important because the antiviral therapy itself may cause a further drop in platelet count.[26] Studies have shown IFN-based therapy to cause severe thrombocytopenia in up to 13% of patients, with the incidence higher in patients with lower baseline platelet count.[27,28] The modifications in IFN-based therapy have potential to lower the chances of attaining SVR. The increased risk of bleeding may also impede the initiation and maintenance of different invasive diagnostic and therapeutic procedures such as liver biopsy, variceal banding, paracentesis and thoracentesis, central line insertion, endoscopy and elective surgery.


Various pharmacological and non-pharmacological therapeutic options are available for the management of thrombocytopenia in chronic HCV infection (Table 2). These treatment modalities vary in their effectiveness and adverse effect profiles. The most practical strategy in treating HCV-related thrombocytopenia is based on the principle that eradication of HCV infection may result in remission of thrombocytopenia. By eradicating  HC virus, DAAs are supposed to improve thrombocytopenia related to hepatitis C infection but may not ameliorate  thrombocytopenia related to cirrhosis or portal hypertension.  In cases of IFN based antiviral therapy, the usual approach is to continue with the therapy, reducing the dose if platelet count drops below 50,000 cells/μL or discontinuing it for a platelet count of below 25,000 cells/μL.[25] The measures described below are mostly supportive. As expected, there is a lot of published data on how these measures might be necessary to IFN-based therapy but not to them with DAAs. 

Table  2 Table 2. Management of hepatitis C-related thrombocytopenia

Platelet transfusion: Though widely used for the management of thrombocytopenia, platelet transfusion has several limitations, especially in patients with chronic liver disease. The increase in platelet count is transient, and hence useful only for procedures or during bleeding. Patients are also at risk for transfusion-related complications, which can occur in up to 30% of the recipients and include viral or bacterial infection, febrile non-hemolytic reactions, and iron overload.[29] Nearly half of all patients undergoing multiple platelet transfusions can develop platelet refractoriness secondary to human leukocyte antigen (HLA) alloimmunization.[30,31] It may not always ensure maintenance of homeostatic platelet levels.[32] Besides, the requirement of hospitalization and high cost may be prohibitive in a resource-poor setting.
Splenectomy and splenic artery embolization: Splenectomy and splenic artery embolization have been used to correct thrombocytopenia in patients with hypersplenism, producing significant and persistent increases in platelet count.[33,34] Akahoshi et al. studied the effect of splenectomy in patients with HCV-associated thrombocytopenia and found above 200% rise in mean platelet count at 1 month after splenectomy.[35] In cases of IFN-based antiviral therapy, the positive effect is known to persist even after the initiation of antiviral therapy, with the mean platelet count nearly 80% above baseline after 12 months of the therapy. Splenectomy, however, is an invasive procedure with high risk of bleeding, sepsis and portal vein thrombosis. Asplenic patients are susceptible to overwhelming post-splenectomy infection. Splenic artery embolization may be an alternative option. In a study by Barcena et al., the mean platelet count increased by 342% from the baseline after 12 weeks of partial splenic artery embolization.[36] Splenic artery embolization, though associated with lower morbidity and mortality than splenectomy, is not free of complications.
Pharmacotherapy: Steroids: With HCV reported to play a pathogenic role in some cases of immune thrombocytopenic purpura, there have been case reports of significant improvement in HCV-related thrombocytopenia with the use of corticosteroid.[37] As described earlier, Lee et al. described a case of resistant ITP which developed after DAA therapy and did not respond to high dose prednisone.[20] Lebano et al. reported a case where the platelet count increased by 175% from baseline six months after steroid therapy and improved further (360% above baseline) after another six months of IFN and ribavirin.[37] Despite similar reports of steroids causing a variable rise in platelet counts, they are not routinely considered in the management of thrombocytopenia in HCV infection because of the possible risk of worsening viral loads and liver damage.[38,39]
Thrombopoietin analogue: Thrombopoietin (TPO) is a cytokine predominantly synthesized by the hepatocytes in the liver and plays a central role in thrombopoiesis. It binds to TPO receptors (mpl) expressed on the surface of megakaryocyte precursor cells and megakaryocytes, activating signal transduction cascades that result in proliferation and maturation of megakaryocytes.[40] A better understanding of TPO and its role in platelet production and function has led to newer treatment modalities. Synthetic thrombopoietins such as recombinant human TPO and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMDGF) cause an increase in platelet count.[41,42] However, their use has been hampered by the appearance of neutralizing antibodies that cross-reacts with both recombinant and endogenous TPO.[43] In a study using PEG-rHuMDGF injection by Li et al., an initial rise in platelet count was followed by the development of an antibody against TPO, detected as early as 56 days after the initial injection.[44] This was associated with corresponding fall in platelet count and a marked decrease in bone marrow megakaryocytes, with an average nadir platelet count of 6% to 8% of baseline.
Thrombopoietin-mimetic agents, in particular, eltrombopag and romiplostim, have been shown to increase platelet count without eliciting any immunogenicity.[45-47] Romiplostin is a peptibody composed of four TPO mimetic peptides attached by glycine bridges to the heavy chain portion of immunoglobulin G. It acts by dimerizing the TPO receptor via its paired peptides, which stimulates platelet production.[48] It is given by weekly subcutaneous injections. Various clinical trials in patients with chronic immune thrombocytopenic purpura have shown romiplostin to cause a dose dependent increase in platelet count, resulting in lower rates of treatment failure, decreased the need for splenectomy and improved quality of life.[49-51]  Lee et al. described romiplostim use in a case of resistant ITP after DAA therapy.[20] A study by Moussa et al. in 35 patients with chronic liver disease and thrombocytopenia secondary to HCV infection showed more than three-fold increase in mean platelet count from the baseline after 3 weeks of therapy.[52] And the mean platelet count remained 1.5 times above the baseline even after 2 months of stopping the drug. Similarly, Voican et al. reported two cases where romiplostin was used to control severe thrombocytopenia; this allowed anti-HCV treatment with pegylated-IFN and ribavirin to be completed successfully without any dose reduction or discontinuation.[53]
Eltrombopag, an orally active TPO agonist, interacts with the trans-membrane domain of the thrombopoietin receptor, activating JAK2/STAT signaling pathways and increasing proliferation and differentiation of human bone marrow progenitor cells into megakaryocytes.[54] Preclinical studies have shown the binding site on the receptor and the signal transduction mechanism to be different for eltrombopag as compared to thrombopoeitin, causing the two to have an additive effect on platelet production.[55] Eltrombopag has been found to be safe and effective in the management of HCV-related thrombocytopenia.[56,57] In a phase II trial,[56] 71-91% of the patients receiving eltrombopag had a dose dependent increase in their platelet counts to levels which allowed initiation of antiviral therapy. 36-65% of patients in the eltrombopag group completed first 12 weeks of antiviral therapy compared to 6% in the placebo group. Though platelet counts decreased during the antiviral treatment phase despite the use of eltrombopag, the count consistently remained above baseline as well as above the level at which a reduction in the pegylated-IFN dose is recommended (<50,000 per cubic millimeter). Another phase III trial, Eltrombopag to Initiate and Maintain Interferon Antiviral Treatment to Benefit Subjects with Hepatitis C-Related Liver Disease (ENABLE-1 and ENABLE-2), showed a higher rate of sustained virological response with the use of eltrombopag than placebo (23% vs. 14%, p=0.0064 in ENABLE-1 and 19% vs. 13%, p=0.0202 in ENABLE-2).[57] Pegylated-IFN was administered at higher doses, with fewer dose reductions in the eltrombopag group. Throughout the antiviral treatment, a platelet count of 50,0000 per cubic millimeter or higher was maintained in more patients receiving eltrombopag than placebo (69% vs. 15% in ENABLE-1 and 81% vs. 23% in ENABLE-2).
The most common side effect with these thrombopoietin-mimetic agents is a headache, with the reported incidence in clinical trials ranging from 7% to 21%.[49-51,56,57] Eltrombopag also commonly causes dry mouth, abdominal pain, and nausea, and may be associated with hepatic decompensation like ascites and hepatic encephalopathy.[56,57] Romiplostin may be associated with increased deposition of reticulin in the bone marrow, and possibly marrow fibrosis.[58] The risk of thromboembolic events like portal vein thrombosis is seen with all these agents.[57,58]
Other newer drugs currently under investigation include the peptidic compounds like AMG-531 and PEG-TPOmp, non-peptidic compound like AKR-501, and monoclonal antibodies. AMG-531, a TPO agonist, has been designed with no sequence homology to human TPO to reduce the likelihood of an anti-TPO immune response. Phase II and III studies in ITP patients have shown promising early results with a dose-dependent increase in platelet count with no serious adverse events.[59,60] PEG-TPOmp is a pegylated TPO peptide agonist and has shown to be effective in animal studies. Similarly, AKR-501 is an orally active TPO agonist and has been shown to be effective in clinical studies involving healthy volunteers.[60] In vitro studies have shown engineered monoclonal antibodies to bind mpl and activate TPO-expressing cell lines.[61] However, all these compounds and drugs need further clinical studies, including in patients with HCV and chronic liver disease before they can be considered for routine use.
Cytokines with thrombopoietic potential: Cytokine such as interleukin-11 (IL-11) has thrombopoietic activity. Recombinant human IL-11 (rhIL-11, Oprelvekin), approved for the management of chemotherapy-related thrombocytopenia, has also been shown to increase platelet count in chronic HCV infection.[62-64] In a study by Lawitz et al., use of rhIL-11 (Oprelvekin) in patients with advanced liver disease associated with chronic HCV infection caused a 38% increase in mean platelet count from baseline after 12 weeks of therapy, along with an improvement in the mean Knodell Histology Activity Index from 7.3 to 5.9 (p= 0.006).[65] However, the platelet level tends to fall back on discontinuing the drug.[62] It also causes fluid retention in most patients, and this can be a significant management problem in patients with decompensated cirrhosis.[64]
Erythropoietin: The amino-terminal domain on TPO, which binds to thrombopoietin receptor shares significant homology with erythropoietin. Recombinant human erythropoietin (rhEPO) has shown promising results in improving thrombocytopenia in cirrhotic patients.[66,67] Pirisi et al. studied the effect of rhEPO on the platelet count in 19 patients with thrombocytopenia related to chronic liver disease, and found an increase in mean platelet count by 45% from the baseline in the treatment group as compared to 0% in the placebo group (p < 0.02).[67] As rhEPO has also been suggested for the treatment of ribavirin-induced anemia in patients with HCV, this provides the possibility of using a single drug for the treatment of both thrombocytopenia and anemia related to the INF-based antiviral therapy. However, further studies are needed to confirm this.
Danazol: Danazole used in immune thrombocytopenic purpura may have a role in HCV-related thrombocytopenia. In a study by Alvarez et al., the use of danazol along with the anti-HCV treatment resulted in a 75% increase in the mean platelet count from the baseline and allowed 90% of the patients to complete their antiviral treatment.[68] Anemia, headache, arthralgia and myalgia were some of the common adverse effects of the combination therapy reported in the study.
L-carnitine: L-carnitine is a nutrient synthesized from amino acids lysine and methionine. In a study, the addition of L-carnitine  to pegylated-IFN-α plus ribavirin resulted in a decrease in the incidence of thrombocytopenia during antiviral therapy.[69]


Thrombocytopenia in chronic HCV infection has a multifactorial pathophysiology and remains a major problem.  The recent change in DAAs without IFN, as the frontline therapy for HCV, permit to avoid the dilemmas associated with initiating or maintaining IFN based anti-viral therapy.
DAAs, with high SVR and less than 1% of hematological adverse effects, have been shown to improve thrombocytopenia associated with HCV infection as well as advanced hepatic disease. While eradication of HCV infection itself is the most practical strategy for the remission of thrombocytopenia, various pharmacological and non-pharmacological therapeutic options, which vary in their effectiveness and adverse effect profiles, are available. Thrombopoietin-mimetic agents like eltrombopag and romiplostim have been shown to be safe and effective for HCV-related thrombocytopenia in various studies.
Studies of the long-term effects of DAA on extrahepatic consequences of HCV infection are in progress..


Vijaya Bhatt is supported by the 2016-2017 Physician-Scientist Training Program Grant from the College of Medicine, University of Nebraska Medical Center.


  1. Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ: The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med 2006;144(10): 705-714. https://doi.org/10.7326/0003-4819-144-10-200605160-00004 PMid:16702586     
  2. Verna EC, Brown Jr RS: Hepatitis C and liver transplantation: enhancing outcomes and should patients be retransplanted. Clinics in liver disease 2008;12(3): 637-659. https://doi.org/10.1016/j.cld.2008.03.010 PMid:18625432     
  3. Seeff LB, Everson GT, Morgan TR, Curto TM, Lee WM, Ghany MG, Shiffman ML, Fontana RJ, Di Bisceglie AM, Bonkovsky HL: Complication rate of percutaneous liver biopsies among persons with advanced chronic liver disease in the HALT-C trial. Clinical Gastroenterology and Hepatology 2010;8(10): 877-883. https://doi.org/10.1016/j.cgh.2010.03.025 PMid:20362695 PMCid:PMC3771318   
  4. Karasu Z, Tekin F, Ersoz G, Gunsar F, Batur Y, Ilter T, Akarca US: Liver fibrosis is associated with decreased peripheral platelet count in patients with chronic hepatitis B and C. Digestive diseases and sciences 2007;52(6): 1535-1539. https://doi.org/10.1007/s10620-006-9144-y PMid:17464564     
  5. Wang C-S, Yao W-J, Wang S-T, Chang T-T, Chou P: Strong association of hepatitis C virus (HCV) infection and thrombocytopenia: implications from a survey of a community with hyperendemic HCV infection. Clinical infectious diseases 2004;39(6): 790-796. https://doi.org/10.1086/423384 PMid:15472809     
  6. Louie KS, Micallef JM, Pimenta JM, Forssen UM: Prevalence of thrombocytopenia among patients with chronic hepatitis C: a systematic review. J Viral Hepat 2011;18(1): 1-7. https://doi.org/10.1111/j.1365-2893.2010.01366.x PMid:20796208     
  7. Aref S, Sleem T, El Menshawy N, Ebrahiem L, Abdella D, Fouda M, Abou Samara N, Menessy A, Abdel-Ghaffar H, Bassam A: Antiplatelet antibodies contribute to thrombocytopenia associated with chronic hepatitis C virus infection. Hematology 2009;14(5): 277-281. https://doi.org/10.1179/102453309X439818 PMid:19843383     
  8. Linares M, Pastor E, Hernandez F, Montagud M, Blanquer A: Autoimmune thrombocytopenia and hepatitis C virus infection. American journal of hematology 1996;53(4): 284-284. https://doi.org/10.1002/(SICI)1096-8652(199612)53:4<284::AID-AJH20>3.0.CO;2-B   
  9. Bordin G, Ballare M, Zigrossi P, Bertoncelli MC, Paccagnino L, Baroli A, Brambilla M, Monteverde A, Inglese E: A laboratory and thrombokinetic study of HCV-associated thrombocytopenia: a direct role of HCV in bone marrow exhaustion? Clin Exp Rheumatol 1995;13 Suppl 13: S39-43. PMid:8730475     
  10. Weksler BB: Review article: the pathophysiology of thrombocytopenia in hepatitis C virus infection and chronic liver disease. Aliment Pharmacol Ther 2007;26 Suppl 1: 13-19. https://doi.org/10.1111/j.1365-2036.2007.03512.x PMid:17958515     
  11. Kedia S, Goyal R, Mangla V, Kumar A, S S, Das P, Pal S, Sahni P, Acharya SK: Splenectomy in cirrhosis with hypersplenism: improvement in cytopenias, Child's status and institution of specific treatment for hepatitis C with success. Ann Hepatol 2012;11(6): 921-929. PMid:23109457     
  12. Adinolfi LE, Giordano MG, Andreana A, Tripodi MF, Utili R, Cesaro G, Ragone E, Mangoni ED, Ruggiero G: Hepatic fibrosis plays a central role in the pathogenesis of thrombocytopenia in patients with chronic viral hepatitis. British journal of haematology 2001;113(3): 590-595. https://doi.org/10.1046/j.1365-2141.2001.02824.x   
  13. Giannini E, Borro P, Botta F, Fumagalli A, Malfatti F, Podestà E, Romagnoli P, Testa E, Chiarbonello B, Polegato S: Serum thrombopoietin levels are linked to liver function in untreated patients with hepatitis C virus-related chronic hepatitis. Journal of hepatology 2002;37(5): 572-577. https://doi.org/10.1016/S0168-8278(02)00274-X   
  14. Osada M, Kaneko M, Sakamoto M, Endoh M, Takigawa K, Suzuki-Inoue K, Inoue O, Satoh K, Enomoto N, Yatomi Y: Causes of thrombocytopenia in chronic hepatitis C viral infection. Clinical and Applied Thrombosis/Hemostasis 2012;18(3): 272-280. https://doi.org/10.1177/1076029611429124 PMid:22327815     
  15. Sulkowski MS: Management of the hematologic complications of hepatitis C therapy. Clinics in liver disease 2005;9(4): 601-616. https://doi.org/10.1016/j.cld.2005.07.007 PMid:16207566     
  16. Wang H, Innes H, Hutchinson SJ, Goldberg DJ, Allen S, Barclay ST, Bramley P, Fox R, Fraser A, Hayes PC, Kennedy N, Mills PR, Dillon JF: The prevalence and impact of thrombocytopenia, anaemia and leucopenia on sustained virological response in patients receiving hepatitis C therapy: evidence from a large 'real world' cohort. Eur J Gastroenterol Hepatol 2016;28(4): 398-404. PMid:26695428     
  17. Feld JJ, Jacobson IM, Hezode C, Asselah T, Ruane PJ, Gruener N, Abergel A, Mangia A, Lai CL, Chan HL, Mazzotta F, Moreno C, Yoshida E, Shafran SD, Towner WJ, Tran TT, McNally J, Osinusi A, Svarovskaia E, Zhu Y, Brainard DM, McHutchison JG, Agarwal K, Zeuzem S: Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N Engl J Med 2015;373(27): 2599-2607. https://doi.org/10.1056/NEJMoa1512610 PMid:26571066   
  18. Foster GR, Afdhal N, Roberts SK, Brau N, Gane EJ, Pianko S, Lawitz E, Thompson A, Shiffman ML, Cooper C, Towner WJ, Conway B, Ruane P, Bourliere M, Asselah T, Berg T, Zeuzem S, Rosenberg W, Agarwal K, Stedman CA, Mo H, Dvory-Sobol H, Han L, Wang J, McNally J, Osinusi A, Brainard DM, McHutchison JG, Mazzotta F, Tran TT, Gordon SC, Patel K, Reau N, Mangia A, Sulkowski M: Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N Engl J Med 2015;373(27): 2608-2617. https://doi.org/10.1056/NEJMoa1512612 PMid:26575258   
  19. Lee LM, Johansen ME, Jy W, Horstman LL, Ahn Y-S: Second Generation Direct-Acting Antiviral Agents Eradicate Hepatitis C Virus (HCV) but Exacerbate Thrombocytopenia in a Patient with HCV-Associated Immune Thrombocytopenic Purpura (ITP): Case Report. Blood 2014;124(21): 5022.   
  20. Forns X, Poordad F, Pedrosa M, Berenguer M, Wedemeyer H, Ferenci P, Shiffman ML, Fried MW, Lovell S, Trinh R, Lopez-Talavera JC, Everson G: Ombitasvir/paritaprevir/r, dasabuvir and ribavirin for cirrhotic HCV patients with thrombocytopenia and hypoalbuminaemia. Liver International 2015;35(11): 2358-2362. https://doi.org/10.1111/liv.12931      
  21. Bachofner JA, Valli PV, Kröger A, Bergamin I, Künzler P, Baserga A, Braun D, Seifert B, Moncsek A, Fehr J, Semela D, Magenta L, Müllhaupt B, Terziroli Beretta-Piccoli B, Mertens JC: Direct antiviral agent treatment of chronic hepatitis C results in rapid regression of transient elastography and fibrosis markers fibrosis-4 score and aspartate aminotransferase-platelet ratio index. Liver International: 2016 Sep 28. doi: 10.1111/liv.13256. [Epub ahead of print] https://doi.org/10.1111/liv.13256   
  22. van der Meer AJ, Maan R, Veldt BJ, Feld JJ, Wedemeyer H, Dufour JF, Lammert F, Duarte-Rojo A, Manns MP, Zeuzem S, Hofmann WP, de Knegt RJ, Hansen BE, Janssen HL: Improvement of platelets after SVR among patients with chronic HCV infection and advanced hepatic fibrosis. J Gastroenterol Hepatol 2016;31(6): 1168-1176. https://doi.org/10.1111/jgh.13252 PMid:26647353     
  23. Afzal MS: Predictive potential of IL-28B genetic testing for interferon based hepatitis C virus therapy in Pakistan: Current scenario and future perspective. World J Hepatol 2016;8(26): 1116-1118. https://doi.org/10.4254/wjh.v8.i26.1116 PMid:27660680 PMCid:PMC5026995   
  24. Gonzalez SA, Keeffe EB: IL-28B As a Predictor of Sustained Virologic Response in Patients with Chronic Hepatitis C Virus Infection. Gastroenterology & Hepatology 2011;7(6): 366-373   .
  25. Dienstag JL, McHutchison JG: American Gastroenterological Association technical review on the management of hepatitis C. Gastroenterology 2006;130(1): 231-264. https://doi.org/10.1053/j.gastro.2005.11.010 PMid:16401486     
  26. McHutchison JG, Manns M, Patel K, Poynard T, Lindsay KL, Trepo C, Dienstag J, Lee WM, Mak C, Garaud JJ: Adherence to combination therapy enhances sustained response in genotype-1–infected patients with chronic hepatitis C. Gastroenterology 2002;123(4): 1061-1069. https://doi.org/10.1053/gast.2002.35950 PMid:12360468     
  27. Hermos JA, Quach L, Gagnon DR, Weber HC, Altincatal A, Cho K, Lawler EV, Grotzinger KM: Incident severe thrombocytopenia in veterans treated with pegylated interferon plus ribavirin for chronic hepatitis C infection. Pharmacoepidemiol Drug Saf 2014;23(5): 480-488. https://doi.org/10.1002/pds.3585 PMid:24677630     
  28. Lin KH, Hsu PI, Yu HC, Lin CK, Tsai WL, Chen WC, Chan HH, Lai KH: Factors linked to severe thrombocytopenia during antiviral therapy in patients with chronic hepatitis c and pretreatment low platelet counts. BMC Gastroenterol 2012;12: 7. https://doi.org/10.1186/1471-230X-12-7 PMid:22257364 PMCid:PMC3275508   
  29. Kaushansky K: Thrombopoietin. The New England journal of medicine 1998;339(11): 746-754. https://doi.org/10.1056/NEJM199809103391107 PMid:9731092    
  30. Murphy M, Waters A: Clinical aspects of platelet transfusions. Blood Coagulation & Fibrinolysis 1991;2(2): 389-396. https://doi.org/10.1097/00001721-199104000-00026 PMid:1893071    
  31. Afdhal N, McHutchison J, Brown R, Jacobson I, Manns M, Poordad F, Weksler B, Esteban R: Thrombocytopenia associated with chronic liver disease. J Hepatol 2008;48(6): 1000-1007. https://doi.org/10.1016/j.jhep.2008.03.009 PMid:18433919     
  32. Schiffer CA, Anderson KC, Bennett CL, Bernstein S, Elting LS, Goldsmith M, Goldstein M, Hume H, McCullough JJ, McIntyre RE: Platelet transfusion for patients with cancer: clinical practice guidelines of the American Society of Clinical Oncology. Journal of Clinical Oncology 2001;19(5): 1519-1538. PMid:11230498     
  33. McCormick PA, Murphy KM: Splenomegaly, hypersplenism and coagulation abnormalities in liver disease. Best Practice & Research Clinical Gastroenterology 2000;14(6): 1009-1031. https://doi.org/10.1053/bega.2000.0144 PMid:11139352     
  34. Shah R, Mahour GH, Ford E, Stanley P: Partial splenic embolization. An effective alternative to splenectomy for hypersplenism. The American surgeon 1990;56(12): 774-777. PMid:2268105     
  35. Akahoshi T, Tomikawa M, Kawanaka H, Furusyo N, Kinjo N, Tsutsumi N, Nagao Y, Hayashi J, Hashizume M, Maehara Y: Laparoscopic splenectomy with interferon therapy in 100 hepatitis-C-virus-cirrhotic patients with hypersplenism and thrombocytopenia. J Gastroenterol Hepatol 2012;27(2): 286-290. https://doi.org/10.1111/j.1440-1746.2011.06870.x PMid:21793908     
  36. Barcena R, Gil-Grande L, Moreno J, Foruny JR, Oton E, Garcia M, Blazquez J, Sanchez J, Moreno A, Moreno A: Partial splenic embolization for the treatment of hypersplenism in liver transplanted patients with hepatitis C virus recurrence before peg-interferon plus ribavirin. Transplantation 2005;79(11): 1634-1635. https://doi.org/10.1097/01.TP.0000155424.52939.3D PMid:15940057     
  37. Lebano R, Rosato V, Masarone M, Romano M, Persico M: The effect of antiviral therapy on hepatitis C virus-related thrombocytopenia: a case report. BMC Res Notes 2014;7: 59. https://doi.org/10.1186/1756-0500-7-59 PMid:24457056 PMCid:PMC3915622   
  38. Hernandez F, Blanquer A, Linares M, Lopez A, Tarin F, Cervero A: Autoimmune thrombocytopenia associated with hepatitis C virus infection. Acta haematologica 1998;99(4): 217-220. https://doi.org/10.1159/000040842 PMid:9644300     
  39. Rajan S, Liebman HA: Treatment of hepatitis C related thrombocytopenia with interferon alpha. American journal of hematology 2001;68(3): 202-209. https://doi.org/10.1002/ajh.1180 PMid:11754404   
  40. Afdhal NH, McHutchison JG: Review article: pharmacological approaches for the treatment of thrombocytopenia in patients with chronic liver disease and hepatitis C infection. Aliment Pharmacol Ther 2007;26 Suppl 1: 29-39. https://doi.org/10.1111/j.1365-2036.2007.03511.x PMid:17958517     
  41. Vadhan-Raj S, Murray LJ, Bueso-Ramos C, Patel S, Reddy SP, Hoots WK, Johnston T, Papadopolous NE, Hittelman WN, Johnston DA, Yang TA, Paton VE, Cohen RL, Hellmann SD, Benjamin RS, Broxmeyer HE: Stimulation of megakaryocyte and platelet production by a single dose of recombinant human thrombopoietin in patients with cancer. Ann Intern Med 1997;126(9): 673-681. https://doi.org/10.7326/0003-4819-126-9-199705010-00001 PMid:9139552     
  42. Harker LA, Roskos LK, Marzec UM, Carter RA, Cherry JK, Sundell B, Cheung EN, Terry D, Sheridan W: Effects of megakaryocyte growth and development factor on platelet production, platelet life span, and platelet function in healthy human volunteers. Blood 2000;95(8): 2514-2522. PMid:10753829     
  43. Basser R. The impact of thrombopoietin on clinical practice. Curr Pharm Des. 2002;8(5):369-77. Review. PubMed PMID: 12069375   .
  44. Li J, Yang C, Xia Y, Bertino A, Glaspy J, Roberts M, Kuter DJ: Thrombocytopenia caused by the development of antibodies to thrombopoietin. Blood 2001;98(12): 3241-3248. https://doi.org/10.1182/blood.V98.12.3241 PMid:11719360     
  45. De Serres M, Ellis B, Dillberger JE, Rudolph SK, Hutchins JT, Boytos CM, Weigl DL, DePrince RB: Immunogenicity of thrombopoietin mimetic peptide GW395058 in BALB/c mice and New Zealand white rabbits: evaluation of the potential for thrombopoietin neutralizing antibody production in man. Stem Cells 1999;17(4): 203-209. https://doi.org/10.1002/stem.170203 PMid:10437983     
  46. Dower WJ, Cwirla SE, Balasubramanian P, Schatz PJ, Barrett RW, Baccanari DP: Peptide agonists of the thrombopoietin receptor. Stem Cells 1998;16(S1): 21-29. https://doi.org/10.1002/stem.5530160705 PMid:11012174     
  47. Kaushansky K: Hematopoietic growth factor mimetics. Annals of the New York Academy of Sciences 2001;938(1): 131-138. https://doi.org/10.1111/j.1749-6632.2001.tb03582.x PMid:11458500     
  48. Broudy VC, Lin NL: AMG531 stimulates megakaryopoiesis in vitro by binding to Mpl. Cytokine 2004;25(2): 52-60. https://doi.org/10.1016/j.cyto.2003.05.001 PMid:14693160     
  49. Bussel JB, Kuter DJ, George JN, McMillan R, Aledort LM, Conklin GT, Lichtin AE, Lyons RM, Nieva J, Wasser JS: AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. New England Journal of Medicine 2006;355(16): 1672-1681. https://doi.org/10.1056/NEJMoa054626 PMid:17050891     
  50. Kuter DJ, Bussel JB, Lyons RM, Pullarkat V, Gernsheimer TB, Senecal FM, Aledort LM, George JN, Kessler CM, Sanz MA: Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. The Lancet 2008;371(9610): 395-403. https://doi.org/10.1016/S0140-6736(08)60203-2   
  51. Kuter DJ, Rummel M, Boccia R, Macik BG, Pabinger I, Selleslag D, Rodeghiero F, Chong BH, Wang X, Berger DP: Romiplostim or standard of care in patients with immune thrombocytopenia. New England Journal of Medicine 2010;363(20): 1889-1899. https://doi.org/10.1056/NEJMoa1002625 PMid:21067381     
  52. Moussa MM, Mowafy N: Preoperative use of romiplostim in thrombocytopenic patients with chronic hepatitis C and liver cirrhosis. J Gastroenterol Hepatol 2013;28(2): 335-341. https://doi.org/10.1111/j.1440-1746.2012.07246.x PMid:22849409     
  53. Voican CS, Naveau S, Perlemuter G: Successful antiviral therapy for hepatitis C virus-induced cirrhosis after an increase in the platelet count with romiplostim: two case reports. Eur J Gastroenterol Hepatol 2012;24(12): 1455-1458. https://doi.org/10.1097/MEG.0b013e328357d5f2 PMid:22890208     
  54. Erickson-Miller C, Delorme E, Giampa L, Hopson C, Valoret E, Tian S-S, Miller SG, Keenan R, Rosen J, Dillon S: Biological activity and selectivity for Tpo receptor of the orally bioavailable, small molecule Tpo receptor agonist, SB-497115. Blood 2004;104(11): 2912-2912   .
  55. Erickson-Miller CL, Delorme E, Tian SS, Hopson CB, Landis AJ, Valoret EI, Sellers TS, Rosen J, Miller SG, Luengo JI: Preclinical Activity of Eltrombopag (SB-497115), an Oral, Nonpeptide Thrombopoietin Receptor Agonist. Stem Cells 2009;27(2): 424-430. https://doi.org/10.1634/stemcells.2008-0366 PMid:19038790 PMCid:PMC2729672   
  56. McHutchison JG, Dusheiko G, Shiffman ML, Rodriguez-Torres M, Sigal S, Bourliere M, Berg T, Gordon SC, Campbell FM, Theodore D: Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. New England Journal of Medicine 2007;357(22): 2227-2236. https://doi.org/10.1056/NEJMoa073255 PMid:18046027    
  57. Afdhal NH, Dusheiko GM, Giannini EG, Chen PJ, Han KH, Mohsin A, Rodriguez-Torres M, Rugina S, Bakulin I, Lawitz E, Shiffman ML, Tayyab GU, Poordad F, Kamel YM, Brainsky A, Geib J, Vasey SY, Patwardhan R, Campbell FM, Theodore D: Eltrombopag increases platelet numbers in thrombocytopenic patients with HCV infection and cirrhosis, allowing for effective antiviral therapy. Gastroenterology 2014;146(2): 442-452 e441.   
  58. Bussel JB, Kuter DJ, Pullarkat V, Lyons RM, Guo M, Nichol JL: Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP. Blood 2009;113(10): 2161-2171. https://doi.org/10.1182/blood-2008-04-150078 PMid:18981291     
  59. Kuter D, Bussel J, George J, Aledort L, Lichtin A, Lyons R, Nieva J, Wasser J, Bourgeois E, Kappers-Klunne M. Long-Term Dosing of AMG 531 in Thrombocytopenic Patients with Immune Thrombocytopenic Purpura: 48-Week Update. ASH Annual Meeting Abstracts. 2006: 476.   
  60. Desjardins RE, Tempel DL, Lucek R, Kuter DJ: Single and multiple oral doses of AKR-501 (YM477) increase the platelet count in healthy volunteers. Blood 2006;108: 477a.   
  61. Orita T, Tsunoda H, Yabuta N, Nakano K, Yoshino T, Hirata Y, Ohtomo T, Nezu J, Sakumoto H, Ono K, Saito M, Kumagai E, Nanami M, Kaneko A, Yoshikubo T, Tsuchiya M: A novel therapeutic approach for thrombocytopenia by minibody agonist of the thrombopoietin receptor. Blood 2005;105(2): 562-566. https://doi.org/10.1182/blood-2004-04-1482 PMid:15374889     
  62. Lawitz EJ, Hepburn MJ, Casey TJ: A pilot study of interleukin-11 in subjects with chronic hepatitis C and advanced liver disease nonresponsive to antiviral therapy. The American journal of gastroenterology 2004;99(12): 2359-2364. https://doi.org/10.1111/j.1572-0241.2004.40047.x PMid:15571583     
  63. Ong JP, Younossi ZM: Managing the hematologic side effects of antiviral therapy for chronic hepatitis C: anemia, neutropenia, and thrombocytopenia. Cleveland Clinic journal of medicine 2004;71(Suppl 3): S17. https://doi.org/10.3949/ccjm.71.Suppl_3.S17 PMid:15468613     
  64. Mendenhall CL, Shakir AR, Zoiss EA, Reese C, Bui H, Goldberg S, Roselle GA: Thrombocytopenia (T) in patients with chronic hepatitis C: Management with interleukin 11. Gastroenterology 2003;124(4): A770. https://doi.org/10.1016/S0016-5085(03)83891-X   
  65. Lawitz EJ, Hepburn MJ, Casey TJ: A pilot study of interleukin-11 in subjects with chronic hepatitis C and advanced liver disease nonresponsive to antiviral therapy. Am J Gastroenterol 2004;99(12): 2359-2364. https://doi.org/10.1111/j.1572-0241.2004.40047.x PMid:15571583     
  66. Homoncik M, Jilma-Stohlawetz P, Schmid M, Ferlitsch A, Peck-Radosavljevic M: Erythropoietin increases platelet reactivity and platelet counts in patients with alcoholic liver cirrhosis: a randomized, double-blind, placebo-controlled study. Alimentary pharmacology & therapeutics 2004;20(4): 437-443. https://doi.org/10.1111/j.1365-2036.2004.02088.x PMid:15298638     
  67. Pirisi M, Fabris C, Soardo G, Cecchin E, Toniutto P, Bartoli E: Thrombocytopenia of chronic liver disease corrected by erythropoietin treatment. Journal of hepatology 1994;21(3): 376-380. https://doi.org/10.1016/S0168-8278(05)80316-2   
  68. Álvarez GC, Gómez-Galicia D, Rodríguez-Fragoso L, Marina VM, Dorantes LC, Sánchez-Alemán M, Méndez-Sánchez N, Esparza JR: Danazol improves thrombocytopenia in HCV patients treated with peginterferon and ribavirin. Ann Hepatol 2011;10(4): 458-468. PMid:21911886     
  69. Malaguarnera M, Vacante M, Giordano M, Motta M, Bertino G, Pennisi M, Neri S, Malaguarnera M, Volti GL, Galvano F: L-carnitine supplementation improves hematological pattern in patients affected by HCV treated with Peg interferon-a 2b plus ribavirin. World journal of gastroenterology: WJG 2011;17(39): 4414. https://doi.org/10.3748/wjg.v17.i39.4414 PMid:22110268 PMCid:PMC3218156   
  70. Ikeda M, Fujiyama S, Tanaka M, Sata M, Ide T, Yatsuhashi H, Watanabe H: Risk factors for development of hepatocellular carcinoma in patients with chronic hepatitis C after sustained response to interferon. J Gastroenterol 2005;40(2): 148-156. https://doi.org/10.1007/s00535-004-1519-2 PMid:15770398     
  71. Moriyama M, Matsumura H, Aoki H, Shimizu T, Nakai K, Saito T, Yamagami H, Shioda A, Kaneko M, Goto I, Tanaka N, Arakawa Y: Long-term outcome, with monitoring of platelet counts, in patients with chronic hepatitis C and liver cirrhosis after interferon therapy. Intervirology 2003;46(5): 296-307. https://doi.org/10.1159/000073209 PMid:14555850     
  72. Nagamine T, Ohtuka T, Takehara K, Arai T, Takagi H, Mori M: Thrombocytopenia associated with hepatitis C viral infection. J Hepatol 1996;24(2): 135-140. https://doi.org/10.1016/S0168-8278(96)80021-3  
  73. Ordi-Ros J, Villarreal J, Monegal F, Sauleda S, Esteban I, Vilardell M: Anticardiolipin antibodies in patients with chronic hepatitis C virus infection: characterization in relation to antiphospholipid syndrome. Clin Diagn Lab Immunol 2000;7(2): 241-244. https://doi.org/10.1128/cdli.7.2.241-244.2000   
  74. Poynard T, Schiff E, Terg R, Moreno-Otero R, Flamm SL, Schmidt WN, Berg T, Goncales Jr FL, Heathcote J, Diago M: S1000 Results from the Epic3 Program: Platelet Counts Are Strong Predictors of Sustained Viral Response (SVR) in the RE-Treatment of Previous Interferon/Ribavirin Non-Responders (Nr). Gastroenterology 2008;134(4): A-772. https://doi.org/10.1016/S0016-5085(08)63605-7   
  75. Sylvestre DL, Clements BJ: The utility of indirect predictors of hepatitis C viremia. Drug Alcohol Depend 2004;74(1): 15-19. https://doi.org/10.1016/j.drugalcdep.2003.11.006 PMid:15072803     
  76. Shanmuganathan G, Palaniappan S, Khor B, Radhakrishnan A, Raj M: The clinico-epidemiological pattern of hepatitis C in a tertiary care hospital in Malaysia: the Kuala Lumpur Hospital experience. 6th Asian Pacific Digestive Week (ADPW 2006). Cebu, Philippines 2006.   
  77. Taliani G, Duca F, Clementi C, De Bac C: Platelet-associated immunoglobulin G, thrombocytopenia and response to interferon treatment in chronic hepatitis C. J Hepatol 1996;25(6): 999. https://doi.org/10.1016/S0168-8278(96)80309-6   
  78. Borroni G, Ceriani R, Cazzaniga M, Tommasini M, Roncalli M, Maltempo C, Felline C, Salerno F: Comparison of simple tests for the non-invasive diagnosis of clinically silent cirrhosis in chronic hepatitis C. Aliment Pharmacol Ther 2006;24(5): 797-804. https://doi.org/10.1111/j.1365-2036.2006.03034.x PMid:16918883     
  79. Dalekos GN, Kistis KG, Boumba DS, Voulgari P, Zervou EK, Drosos AA, Tsianos EV: Increased incidence of anti-cardiolipin antibodies in patients with hepatitis C is not associated with aetiopathogenetic link to anti-phospholipid syndrome. Eur J Gastroenterol Hepatol 2000;12(1): 67-74. https://doi.org/10.1097/00042737-200012010-00013 PMid:10656213     
  80. Kaul V, Friedenberg FK, Braitman LE, Anis U, Zaeri N, Fazili J, Herrine SK, Rothstein KD: Development and validation of a model to diagnose cirrhosis in patients with hepatitis C. Am J Gastroenterol 2002;97(10): 2623-2628. https://doi.org/10.1111/j.1572-0241.2002.06040.x PMid:12385450     
  81. Luo JC, Hwang SJ, Chang FY, Chu CW, Lai CR, Wang YJ, Lee PC, Tsay SH, Lee SD: Simple blood tests can predict compensated liver cirrhosis in patients with chronic hepatitis C. Hepatogastroenterology 2002;49(44): 478-481. PMid:11995477     
  82. Prieto J, Yuste JR, Beloqui O, Civeira MP, Riezu JI, Aguirre B, Sangro B: Anticardiolipin antibodies in chronic hepatitis C: implication of hepatitis C virus as the cause of the antiphospholipid syndrome. Hepatology 1996;23(2): 199-204. https://doi.org/10.1002/hep.510230201 PMid:8591841     
  83. Romagnuolo J, Jhangri GS, Jewell LD, Bain VG: Predicting the liver histology in chronic hepatitis C: how good is the clinician? Am J Gastroenterol 2001;96(11): 3165-3174. https://doi.org/10.1111/j.1572-0241.2001.05275.x PMid:11721766     
  84. Zachou K, Liaskos C, Christodoulou DK, Kardasi M, Papadamou G, Gatselis N, Georgiadou SP, Tsianos EV, Dalekos GN: Anti-cardiolipin antibodies in patients with chronic viral hepatitis are independent of beta2-glycoprotein I cofactor or features of antiphospholipid syndrome. Eur J Clin Invest 2003;33(2): 161-168. https://doi.org/10.1046/j.1365-2362.2003.01110.x PMid:12588291     
  85. Hu KQ, Tong MJ: The long-term outcomes of patients with compensated hepatitis C virus-related cirrhosis and history of parenteral exposure in the United States. Hepatology 1999;29(4): 1311-1316. https://doi.org/10.1002/hep.510290424 PMid:10094980     
  86. Kim YS, Lee HS, Ahn YO: Factors associated with positive predictability of the anti-HCV ELISA method with confirmatory RT-PCR. J Korean Med Sci 1999;14(6): 629-634. https://doi.org/10.3346/jkms.1999.14.6.629 PMid:10642940 PMCid:PMC3054447   
  87. Renou C, Muller P, Jouve E, Bertrand JJ, Raoult A, Benderriter T, Halfon P: Revelance of moderate isolated thrombopenia as a strong predictive marker of cirrhosis in patients with chronic hepatitis C virus. Am J Gastroenterol 2001;96(5): 1657-1659. https://doi.org/10.1111/j.1572-0241.2001.03830.x PMid:11374731     
  88. Cicardi M, Cesana B, Del Ninno E, Pappalardo E, Silini E, Agostoni A, Colombo M: Prevalence and risk factors for the presence of serum cryoglobulins in patients with chronic hepatitis C. J Viral Hepat 2000;7(2): 138-143. https://doi.org/10.1046/j.1365-2893.2000.00204.x PMid:10760044     
  89. Nahon P, Ganne-Carrie N, Degos F, Nahon K, Paries J, Grando V, Chaffaut C, Njapoum C, Christidis C, Trinchet JC, Chevret S, Beaugrand M: Serum albumin and platelet count but not portal pressure are predictive of death in patients with Child-Pugh A hepatitis C virus-related cirrhosis. Gastroenterol Clin Biol 2005;29(4): 347-352. https://doi.org/10.1016/S0399-8320(05)80779-1   
  90. Wang CS, Yao WJ, Wang ST, Chang TT, Chou P: Strong association of hepatitis C virus (HCV) infection and thrombocytopenia: implications from a survey of a community with hyperendemic HCV infection. Clin Infect Dis 2004;39(6): 790-796. https://doi.org/10.1086/423384 PMid:15472809     
  91. Alvarez GC, Gomez-Galicia D, Rodriguez-Fragoso L, Marina VM, Dorantes LC, Sanchez-Aleman M, Mendez-Sanchez N, Esparza JR: Danazol improves thrombocytopenia in HCV patients treated with peginterferon and ribavirin. Ann Hepatol 2011;10(4): 458-468. PMid:21911886     
  92. Malaguarnera M, Vacante M, Giordano M, Motta M, Bertino G, Pennisi M, Neri S, Malaguarnera M, Li Volti G, Galvano F: L-carnitine supplementation improves hematological pattern in patients affected by HCV treated with Peg interferon-alpha 2b plus ribavirin. World J Gastroenterol 2011;17(39): 4414-4420. https://doi.org/10.3748/wjg.v17.i39.4414 PMid:22110268 PMCid:PMC3218156   


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