Management of dialysis patients with hepatitis C virus in the era of direct-acting antiviral therapy
Corresponding Author
Hidenori Toyoda
Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
Correspondence
Hidenori Toyoda, Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, Gifu 503-8502, Japan.
Email: [email protected]
Search for more papers by this authorKan Kikuchi
Division of Nephrology, Shimoochiai Clinic, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Hidenori Toyoda
Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
Correspondence
Hidenori Toyoda, Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, Gifu 503-8502, Japan.
Email: [email protected]
Search for more papers by this authorKan Kikuchi
Division of Nephrology, Shimoochiai Clinic, Tokyo, Japan
Search for more papers by this authorAbstract
The clinical use of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection has dramatically changed management of patients with HCV liver disease since 2014; this is also true for patients undergoing dialysis. Due to the high tolerability and antiviral efficacy of anti-HCV therapy, most dialysis patients with HCV infection should currently be candidates for this treatment. Many patients with HCV antibodies no longer have HCV infection, and it is difficult to identify patients with actual HCV infection based only on HCV antibody assays. Despite the high rate of successful HCV eradication, the risk of liver-related events such as hepatocellular carcinoma (HCC), the major complication of HCV infection, persists even after HCV cure, and patients at risk of HCC should undergo continuous HCC surveillance. Finally, the rarity of HCV reinfection and the survival benefit of HCV eradication in dialysis patients should be explored in further studies.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflict of interest on this manuscript.
REFERENCES
- 1Fabrizi F, Takkouche B, Lunghi G, Dixit V, Messa P, Martin P. The impact of hepatitis C virus infection on survival in dialysis patients: meta-analysis of observational studies. J Viral Hepat. 2007; 14: 697–703.
- 2Nitta K, Nakai S, Masakane I, Hanafusa N, Goto S, Taniguchi M, et al. 2018 annual dialysis data report of the JSDT renal data registry: patients with hepatitis. Ren Replace Ther. 2021; 7: 22.
10.1186/s41100-021-00338-8 Google Scholar
- 3Renehen A, Smith U, Kirkman MS. Linking diabetes and cancer: a consensus on complexity. Lancet. 2010; 375: 2201–2.
- 4Roth D, Bloom RD, Molnar MZ, Reese PP, Sawinski D, Sise ME, et al. KDOQI US commentary on the 2018 KDIGO clinical practice guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C. Am J Kidney Dis. 2020; 75: 665–83.
- 5 No authors listed. Guideline 3: preventing HCV transmission in hemodialysis units. Kidney Int. 2008; 73(Suppl 109): S46–52.
- 6Kikuchi K, Akiba T, Nitta K, Masakane I, Ando R, Izumi N, et al. Multicenter study of pegylated interferon α-2a monotherapy for hepatitis C virus-infected patients on hemodialysis: REACH study. Ther Apher Dial. 2014; 18: 603–11.
- 7Liu CH, Huang CF, Liu CJ, Dai CY, Liang CC, Huang JF, et al. Pegylated interferon-α2a with or without low-dose ribavirin for treatment-naive patients with hepatitis C virus genotype 1 receiving hemodialysis: a randomized trial. Ann Intern Med. 2013; 159: 729–38.
- 8 Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO clinical practice guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease. Kidney Int. 2022; 2022(102): S129–205.
- 9Toyoda H, Kumada T, Tada T, Takaguchi K, Ishikawa T, Tsuji K, et al. Safety and efficacy of dual direct-acting antiviral therapy (daclatasvir and asunaprevir) for chronic hepatitis C virus genotype 1 infection in patients on hemodialysis. J Gastroenterol. 2016; 51: 741–7.
- 10Suda G, Furusyo N, Toyoda H, Kawakami Y, Ikeda H, Suzuki M, et al. Daclatasvir and asunaprevir in hemodialysis patients with hepatitis C virus infection: a nationwide retrospective study in Japan. J Gastroenterol. 2018; 53: 119–28.
- 11Kawakami Y, Imamura M, Ikeda H, Suzuki M, Arataki K, Moriishi M, et al. Pharmacokinetics, efficacy and safety of daclatasvir plus asunaprevir in dialysis patients with chronic hepatitis C: pilot study. J Viral Hepat. 2016; 23: 850–6.
- 12Miyazaki R, Miyagi K. Effect and safety of daclatasvir-asunaprevir combination therapy for chronic hepatitis C virus genotype 1b-infected patients on hemodialysis. Ther Apher Dial. 2016; 20: 462–7.
- 13Atsukawa M, Tsubota A, Koushima Y, Ikegami T, Watanabe K, Shimada N, et al. Efficacy and safety of ombitasvir/paritaprevir/ritonavir in dialysis patients with genotype 1b chronic hepatitis C. Hepatol Res. 2017; 47: 1429–37.
- 14Pockros PJ, Reddy KR, Mantry PS, Cohen E, Bennett M, Sulkowski MS, et al. Efficacy of direct-acting antiviral combination for patients with hepatitis C virus genotype 1 infection and severe renal impairment or end-stage renal disease. Gastroenterology. 2016; 150: 1590–8.
- 15Nazario HE, Ndungu M, Modi AA. Sofosbuvir and simeprevir in hepatitis C genotype 1-patients with end-stage renal disease on haemodialysis or GFR <30 ml/min. Liver Int. 2016; 36: 798–801.
- 16Roth D, Nelson DR, Bruchfeld A, Liapakis AM, Silva M, Monsour H Jr, et al. Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease (the C-SURFER study): a combination phase 3 study. Lancet. 2015; 386: 1537–45.
- 17Bruchfeld A, Roth D, Martin P, Nelson DR, Pol S, Londoño MC, et al. Elbasvir plus grazoprevir in patients with hepatitis C virus infection and stage 4-5 chronic kidney disease: clinical, virological, and health-related quality-of-life outcomes from a phase 3, multicentre, randomised, double-blind, placebo-controlled trial. Lancet Gastroenterol Hepatol. 2017; 2: 585–94.
- 18Suda G, Kurosaki M, Itakura J, Izumi N, Uchida Y, Mochida S, et al. Safety and efficacy of elbasvir and grazoprevir in Japanese hemodialysis patients with genotype 1b hepatitis C virus infection. J Gastroenterol. 2019; 54: 78–86.
- 19Gane EJ, Lawitz E, Pugatch D, Papatheodoridis G, Braeu N, Brown AS, et al. EXPEDITION-IV: safety and efficacy of GLE/PIB in adults with renal impairment and chronic hepatitis C virus genotype 1–6 infection. Hepatology. 2016; 64:1125A.
- 20Atsukawa M, Tsubota A, Toyoda H, Takaguchi K, Nakamuta M, Watanabe T, et al. The efficacy and safety of glecaprevir plus pibrentasvir in 141 patients with severe renal impairment: a prospective, multicenter study. Aliment Pharmacol Ther. 2019; 49: 1230–41.
- 21Suda G, Hasebe C, Abe M, Kurosaki M, Itakura J, Izumi N, et al. Safety and efficacy of glecaprevir and pibrentasvir in Japanese hemodialysis patients with genotype 2 hepatitis C virus infection. J Gastroenterol. 2019; 54: 641–9.
- 22Balk EM, Adam GP, Jadoul M, Martin P, Gordon CE. A systematic review of direct-acting antivirals for hepatitis C in advanced CKD. Kidney Int Rep. 2023; 8: 240–53.
- 23 [cited 2023 Apr 20]. https://www.gilead.com/-/media/files/pdfs/medicines/liver-disease/harvoni/harvoni_pi.pdf
- 24 [cited 2023 Feb 7]. https://www.hcvguidelines.org/unique-populations/decompensated-cirrhosis
- 25 European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C: final update of the series. J Hepatol. 2020; 73: 1170–218.
- 26Asahina Y, Drafting Committee for Hepatitis Management Guidelines, the Japan Society of Hepatology. JSH guidelines for the management of hepatitis C virus infection, 2019 Update; protective effect of antiviral therapy against hepatocarcinogenesis. Hepatol Res. 2020; 50: 775–90.
- 27Wong YJ, Tran S, Huang CF, Hsu YC, Preda CM, Toyoda H, et al. Real-world treatment outcome with protease inhibitor (PI) vs non-PI direct acting antivirals (DAAs) in decompensated HCV cirrhosis: a REAL-C study. Gastroenterology. 2022; 162:S-1124.
- 28Taneja S, Duseja A, Mehta M, De A, Verma N, Premkumar M, et al. Sofosbuvir and velpatasvir combination is safe and effective in treating chronic hepatitis C in end-stage renal disease on maintenance haemodialysis. Liver Int. 2021; 41: 705–9.
- 29Liu CH, Chen CY, Su WW, Tseng KC, Lo CC, Liu CJ, et al. Sofosbuvir/velpatasvir with or without low-dose ribavirin for patients with chronic hepatitis C virus infection and severe renal impairment. Gut. 2022; 71: 176–84.
- 30 [cited 2023 Feb 7]. https://www.hcvguidelines.org/unique-populations/renal-impairment
- 31Toyoda H, Yasuda S, Moriya A, Itobayashi E, Uojima H, Watanabe T, et al. Misunderstanding of hepatitis C virus (HCV) infection status by non–specialized medical doctors in patients who achieved sustained virologic response to anti-HCV therapy. J Infect Chemother. 2022; 28: 1231–4.
- 32Hayashi K, Ishigami M, Ishizu Y, Kuzuya T, Honda T, Hirooka Y, et al. Late relapse of hepatitis C virus in patients with sustained virological response after daclatasvir and asunaprevir therapy. J Viral Hepat. 2018; 25: 1446–51.
- 33Toyoda H, Yasuda S, Shiota S, Kumada T, Tanaka J. Lack of hepatitis C virus reinfection in lifetime of Japanese general population with previous hepatitis C virus (HCV) infection successfully treated with anti-HCV therapy. J Infect Chemother. 2021; 27: 1674–5.
- 34Liu CH, Peng CY, Kao WY, Yang SS, Shih YL, Lin CL, et al. Hepatitis C virus reinfection in patients on haemodialysis after achieving sustained virologic response with antiviral treatment. Aliment Pharmacol Ther. 2022; 55: 434–55.
- 35Durand CM, Bowring MG, Brown DM, Chattergoon MA, Massaccesi G, Bair N, et al. Direct-acting antiviral prophylaxis in kidney transplantation from hepatitis C virus-infected donors to noninfected recipients: an open-label nonrandomized trial. Ann Intern Med. 2018; 168: 533–40.
- 36Reese PP, Abt PL, Blumberg EA, van Deerlin VM, Bloom RD, Potluri VS, et al. Twelve-month outcomes after transplant of hepatitis C-infected kidneys into uninfected recipients: a single-group trial. Ann Intern Med. 2018; 169: 273–81.
- 37Molnar MZ, Nair S, Cseprekal O, Yazawa M, Talwar M, Balaraman V, et al. Transplantation of kidneys from hepatitis C-infected donors to hepatitis C-negative recipients: single center experience. Am J Transplant. 2019; 19: 3046–57.
- 38Kanwal F, Kramer J, Asch SM, Chayanupatkul M, Cao Y, el-Serag HB. Risk of hepatocellular cancer in HCV patients treated with direct-acting antiviral agents. Gastroenterology. 2017; 153: 996–1005.
- 39Carrat F, Fontaine H, Dorival C, Simony M, Diallo A, Hezode C, et al. Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment: a prospective cohort study. Lancet. 2019; 393: 1453–64.
- 40Ghany MG, Morgan TR, AASLD-IDSA Hepatitic C Guidance Panel. Hepatitis C Guidance 2019 update: American Association for the Study of Liver Diseases–Infectious Diseases Society of America recommendations for testing, managing, and treating hepatitis C virus infection. Hepatology. 2020; 71: 686–721.
- 41Kanda T, Lau GKK, Wei L, Moriyama M, Yu ML, Chuang WL, et al. APASL HCV guidelines of virus-eradicated patients by DAA on how to monitor HCC occurrence and HBV reactivation. Hepatol Int. 2019; 13: 649–61.
- 42Toyoda H, Hiraoka A, Uojima H, Nozaki A, Shimada N, Takaguchi K, et al. Characteristics and prognosis of de novo hepatocellular carcinoma after sustained virologic response. Hepatol Commun. 2021; 5: 1290–9.
- 43Toyoda H, Tada T, Tsuji K, Hiraoka A, Tachi Y, Itobayashi E, et al. Characteristics and prognosis of hepatocellular carcinoma detected in patients with chronic hepatitis C after the eradication of hepatitis C virus: a multicenter study from Japan. Hepatol Res. 2016; 46: 734–42.
- 44Toyoda H, Hiraoka A, Tada T, Michitaka K, Takaguchi K, Tsuji K, et al. Characteristics and prognosis of hepatocellular carcinoma in Japanese patients undergoing dialysis. Ther Apher Dial. 2017; 21: 465–72.
- 45Rydahl C, Thomsen HS, Marckmann P. High prevalence of nephrogenic systemic fibrosis in chronic renal failure patients exposed to gadodiamide, a gadolinium-containing magnetic resonance contrast agent. Invest Radiol. 2008; 43: 141–4.
- 46Prince MR, Zhang H, Morris M, MacGregor JL, Grossman ME, Silberzweig J, et al. Incidence of nephrogenic systemic fibrosis at two large medical centers. Radiology. 2008; 248: 807–16.
- 47Agarwal R, Brunelli SM, Williams K, Mitchell MD, Feldman HI, Umscheid CA. Gadolinium-based contrast agents and nephrogenic systemic fibrosis: a systematic review and metaanalysis. Nephrol Dial Transplant. 2009; 24: 856–63.
- 48Toyoda H, Kikuchi K, Tsuruta Y, Hiraoka A, Tsuji K, Tanaka J. Utility of serological tumor biomarkers for surveillance of hepatocellular carcinoma in patients undergoing dialysis. Nephrol Dial Transpl. 2021; 36: 1097–103.
- 49Bravo AA, Sheth SG, Chopra S. Liver biopsy. N Engl J Med. 2001; 344: 495–500.
- 50Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003; 38: 518–26.
- 51Vallet-Pichard A, Mallet V, Nalpas B, Verkarre V, Nalpas A, Dhalluin-Venier V, et al. FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. Comparison with liver biopsy and FibroTest. Hepatology. 2007; 46: 32–6.
- 52Guh JY, Lai YH, Yang CY, Chen SC, Chuang WL, Hsu TC, et al. Impact of decreased serum transaminase levels on the evaluation of viral hepatitis patients. Nephron. 1995; 69: 459–65.
- 53Lopes EPA, Gouveia EC, Albuquerque ACC, Sette LHBC, Mello LA, Moreira RC, et al. Determination of the cutoff of serum alanine aminotransferase in patients undergoing hemodialysis, to identify biochemical activity in patients with hepatitis C viremia. J Clin Virol. 2006; 35: 298–302.
- 54Ziol M, Handra-Luca A, Kettaneh A, Christidis C, Mal F, Kazemi F, et al. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology. 2005; 41: 48–54.
- 55Tada T, Kumada T, Toyoda H, Ito T, Sone Y, Okuda S, et al. Utility of real-time shear wave elastography for assessing liver fibrosis in patients with chronic hepatitis C infection without cirrhosis: comparison of liver fibrosis indices. Hepatol Res. 2015; 45: E122–9.
- 56Imajo K, Kessoku T, Honda Y, Tomeno W, Ogawa Y, Mawatari H, et al. Magnetic resonance imaging more accurately classifies steatosis and fibrosis in patients with nonalcoholic fatty liver disease than transient elastography. Gastroenterology. 2016; 150: 626–37.
- 57Kumada T, Toyoda H, Yasuda S, Sone Y, Ogawa S, Takeshima K, et al. Prediction of hepatocellular carcinoma by liver stiffness measurements using magnetic resonance elastography after eradicating hepatitis C virus. Clin Transl Gastroenterol. 2021; 12:e00337.
- 58Kumada T, Toyoda H, Yasuda S, Ogawa S, Gotoh T, Tada T, et al. Combined ultrasound and magnetic resonance elastography predict hepatocellular carcinoma after hepatitis C virus eradication. Hepatol Res. 2022; 52: 957–67.
- 59Abe K, Wakabayashi H, Nakayama H, Suzuki T, Kuroda M, Yoshida N, et al. Factors associated with hepatocellular carcinoma occurrence after HCV eradication in patients without cirrhosis or with compensated cirrhosis. PLoS One. 2020; 15:e0243473.
- 60Alonso López S, Manzano ML, Gea F, Gutiérrez ML, Ahumada AM, Devesa MJ, et al. A model based on non-invasive markers predicts very low hepatocellular carcinoma risk after viral response in hepatitis C virus-advanced fibrosis. Hepatology. 2020; 72: 1924–34.
- 61Chun HS, Kim BK, Park JY, Kim DY, Ahn SH, Han KH, et al. Design and validation of risk prediction model for hepatocellular carcinoma development after sustained virological response in patients with chronic hepatitis C. Eur J Gastroenterol Hepatol. 2020; 32: 378–85.
- 62Fan R, Papatheodoridis G, Sun J, Innes H, Toyoda H, Xie Q, et al. aMAP risk score predicts hepatocellular carcinoma development in patients with chronic hepatitis. J Hepatol. 2020; 73: 1368–78.
- 63Hiraoka A, Kumada T, Ogawa C, Kariyama K, Morita M, Nouso K, et al. Proposed a simple score for recommendation of scheduled ultrasonography surveillance for hepatocellular carcinoma after direct acting antivirals: multicenter analysis. J Gastroenterol Hepatol. 2019; 34: 436–41.
- 64Hu CC, Weng CH, Hua MC, Chang PH, Lin CL, Chen YT, et al. New scoring method to predict risk of hepatocellular carcinoma in patients with chronic hepatitis C after pegylated interferon and ribavirin therapy. J Interferon Cytokine Res. 2020; 40: 82–91.
- 65Sharma SA, Kowgier M, Hansen BE, Brouwer WP, Maan R, Wong D, et al. Toronto HCC risk index: a validated scoring system to predict 10-year risk of HCC in patients with cirrhosis. J Hepatol. 2018; 68: 92–9.
- 66Shiha G, Waked I, Soliman R, Elbasiony M, Gomaa A, Mikhail NNH, et al. GES: a validated simple score to predict risk of HCC in patients with HCV-GT4 associated advanced liver fibrosis after oral antivirals. Liver Int. 2020; 40: 2828–33.
- 67Tahata Y, Sakamori R, Yamada R, Kodama T, Hikita H, Hagiwara H, et al. Prediction model for hepatocellular carcinoma occurrence in patients with hepatitis C in the era of direct-acting anti-virals. Aliment Pharmacol Ther. 2021; 54: 1340–9.
- 68Tamaki N, Kurosaki M, Yasui Y, Mori N, Tsuji K, Hasebe C, et al. Hepatocellular carcinoma risk assessment for patients with advanced fibrosis after eradication of hepatitis C virus. Hepatol Commun. 2022; 6: 461–72.
- 69Tani J, Morishita A, Sakamoto T, Takuma K, Nakahara M, Fujita K, et al. Simple scoring system for prediction of hepatocellular carcinoma occurrence after hepatitis C virus eradication by directacting antiviral treatment: all Kagawa Liver Disease Group Study. Oncol Lett. 2020; 19: 2205–12.
- 70Watanabe T, Tokumoto Y, Joko K, Michitaka K, Horiike N, Tanaka Y, et al. Predictors of hepatocellular carcinoma occurrence after direct-acting antiviral therapy in patients with hepatitis C virus infection. Hepatol Res. 2019; 49: 136–46.
- 71Hu TH, Su WW, Yang CC, Yang CC, Kuo WH, Chen YY, et al. Elimination of hepatitis C virus in a dialysis population: a collaborative care model in Taiwan. Am J Kidney Dis. 2021; 78: 511–9.
- 72Fabrizi F, Dixit V, Messa P. Hepatitis C virus and mortality among patients on dialysis: a systematic review and meta-analysis. Clin Res Hepatol Gastroenterol. 2019; 43: 244–54.
- 73Nakayama E, Akiba T, Marumo F, Sato C. Prognosis of anti-hepatitis C virus antibody-positive patients on regular hemodialysis therapy. J Am Soc Nephrol. 2000; 11: 1896–902.