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The Direct-Acting Antivirals for Hepatitis C Virus and the Risk for Hepatocellular Carcinoma
Paulina Chinchilla-López*, Xingshun Qi**, Eric M. Yoshida***, Nahum Méndez-Sánchez
,
Corresponding author
nmendez@medicasur.org.mx

Correspondence and reprint request:
* Liver Research Unit. Medica Sur Clinic & Foundation, Mexico City, Mexico
** Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, China
*** University of British Columbia & Division of Gastroenterology Vancouver General Hospital, Canada
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="p0010" class="elsevierStylePara elsevierViewall">Cirrhosis is the end stage of every chronic liver disease&#46; The most common causes of hepatic fibrosis are the viral infection &#40;hepatitis B and C&#41;&#46; Furthermore obesity rates have increased the risk of liver injury through nonalcoholic fatty liver disease &#40;NAFLD&#41; and nonalcoholic st-eatohepatitis &#40;NASH&#41;&#44; as well as consumption of alcohol and autoimmune diseases&#46; At the stage of liver cirrhosis&#44; patients are at elevated risk of liver failure and hepatocel-lular carcinoma &#40;HCC&#41;&#44; two complications that shorten their life expectancy&#46;</p><p id="p0015" class="elsevierStylePara elsevierViewall">Interestingly&#44; Davis&#44; <span class="elsevierStyleItalic">et al</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">1</span></a> in 2003 conducted an elegant study projecting the complications of HCV in the United States&#46; Those investigators predicted that&#44; according to their model&#44; the projected total number of patients with HCV to decline gradually over the next three decades &#40;2020&#44; 2030 and 2040&#41;&#46; However&#44; the number of cases with cirrhosis increased to 25&#37; in 2010&#44; 32&#37; in 2020&#44; 36&#37; in 2030&#44; and 38&#37; in 2040&#46; In the same way&#44; the number of cases of HCC were projected to increase over the next 2 decades&#44; nearly doubling before stabilizing&#46; Our group<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">2</span></a> observed the projected trends in liver disease prevalence in Mexico from 2005 to 2050&#44; and we predicted that the prevalence of chronic liver diseases will become high and HCC will continue increase over the time&#46;</p><p id="p0020" class="elsevierStylePara elsevierViewall">The treatments about this topic have been evaluated over the years&#44; and today we have to be aware of the advantages and disadvantages of each of them&#46; On the one hand interferon-based regimens with the combination of Pegylated interferon and ribavirin result in sustained vi-rologic response &#40;SVR&#41; in approximately half of treated cases&#46; Several studies have confirmed the benefits of this treatment by reducing the risk of HCC&#46; Unfortunately&#44; the achievement of SVR did not eliminate this risk&#46; For example&#44; Yamashita&#44; <span class="elsevierStyleItalic">et al</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">3</span></a> reported that patients who had a SVR after the treatment with Pegylated interferon and ribavirin developed a HCC in 26&#37; &#40;the cumulative rates of HCC were 3&#46;1&#44; 10&#46;1&#44; and 15&#46;9&#37; at 5&#44; 10&#44; and 15 years&#44; respectively&#41;&#46; Similarly&#44; Innes&#44; <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">4</span></a> identified individuals who achieved SVR with interferon-based antiviral therapy in Scotland between 1996-2011 using a national database&#44; then followed them 5&#46;2 years after SVR&#46; The investigators calculated standardized mortality ratios to compare the frequency of mortality in SVR patients to the general population and reported a higher mortality rate &#40;HR 1&#46;9&#41;&#46; The main causes &#40;66&#37;&#41; of the death was due to drug-related causes and death from liver cancer&#46; On the other hand&#44; in a multicenter cohort study&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">5</span></a> the researchers observed the low risk for all cause-mortality in patients with chronic hepatitis C who achieved SVR with interferon-based treatment&#46; The risk was almost 4-fold lower compared without SVR&#46; In Canada&#44; Janjua&#44; <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">6</span></a> reported on a provincial British Columbia database of 8147 patient treated with interferon-based therapy and found that SVR was associated with a lower risk of HCC &#40;subdistribution HR &#61; 0&#46;20&#44; 95&#37; CI&#58; 0&#46;13-0&#46;3&#41;&#46; They emphasized that SVR with interferon-based therapy reduced the risk but that a significant risk of HCC still remained&#46;</p><p id="p0025" class="elsevierStylePara elsevierViewall">Nowadays with the introduction of direct-acting antiviral &#40;DAA&#41; for the treatment of HCV the viral eradication in most if not all patients who undergo treatment&#46; The question arise if those patients treated with the DAA have a lower risk to develop HCC than those patients treated with pegylated interferon and ribavirin&#46; Interesting there are some publications that to suggest an increasing risk for HCC in patients treated with DAA&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">7</span></a> But other publications did not support this finding&#46;</p><p id="p0030" class="elsevierStylePara elsevierViewall">From a treatment perspective&#44; it appears that HCC itself diminishes the likelihood of virus eradication&#46; In Prenner&#39;s study published recently&#44;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">8</span></a> the aim of that study was to assess the efficacy of all oral-DAA regimens in HCV &#43; cirrhotic patients who have or had HCC compared to those without HCC&#46; The investigators studied 421 patients HCV with cirrhosis of whom 33&#37; had active&#44; or a history of&#44; HCC&#46; The most frequent genotype was type 1 &#40;86&#37;&#41; and 60&#37; had been previously been treated for HCV&#46; The results of this study showed that the presence of active HCC tumor at the time of HCV treatment initiation was associated with treatment failure using all-oral DAA regimen &#40;p &#61; 0&#46;04&#41; but that successfully treated HCC was associated with a high likelihood of achieving SVR&#46;</p><p id="p0035" class="elsevierStylePara elsevierViewall">In addition&#44; some studies report surprisingly high rates of recurrence HCC in patients treated successfully with DAA regimens after their tumors had been treated&#44; presumably successfully&#44; by various therapies other than liver transplant&#46; This suggests that DAA associated SVR does not protect against HCC recurrence post HCC treatment&#46; For example Conti&#44; <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">9</span></a> confirmed in patients previously treated for HCC that there is still a high risk of tumor recurrence&#44; despite successful DAA treatment&#46; They analyzed 344 patients&#8217; cirrhotic patients&#44; 285 without HCC and 59 with previous HCC with follow up for 24 weeks&#46; The development of recurrent HCC was found in 17 patients of 59 &#40;with previous HCC&#41; compared to 9 of 285 without&#46; Advanced cirrhosis represented a predictor of recurrent HCC&#46;</p><p id="p0040" class="elsevierStylePara elsevierViewall">At the same time Reig&#44; <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">10</span></a> observed HCC in patients with a complete response after HCC treatment by resection&#44; ablation&#44; or chemoembolization and after antiviral therapy using DAAs&#46; The patients who achieved a SVR had an unexpectedly high rate of HCC recurrence &#40;28&#37;&#41;&#46;</p><p id="p0045" class="elsevierStylePara elsevierViewall">If the previously mentioned projections are accurate&#44; we can expect increases in the complications of cirrhosis in the future&#46; Therefore the long-term non-virologic effects of antiviral treatment must continue to be evaluated&#46; Some authors hypothesize that the type of therapeutic option employed to treat the HCC may condition its reappearance and this may influence the apparent oncologic DAA failure &#40;i&#46;e&#46; HCC recurrence&#41;&#46; Although the early studies reporting HCC post-DAA may be due to an unforeseen selection or ascertainment bias&#44; never-the-less&#44; they are hypothesis-generating and underscore the fact that patients with cirrhosis who have achieved a SVR still need regular surveillance for HCC&#46;</p><p id="p0050" class="elsevierStylePara elsevierViewall">In conclusion&#44; the risk for developing HCC remains&#44; even though SVR has been achieved and these patients should undergo HCC monitoring for the long term&#46; Whether DAAs themselves are associated with an increased risk of HCC remains to be studied and continued long-term observational studies will be needed&#46;</p><p id="p0055" class="elsevierStylePara elsevierViewall">The goal in HCV care needs to go beyond merely achieving an SVR&#46; We should identify in all patients the risk factors for complications&#44; comorbidity&#39;s and we have to know the hepatic damage at the time patients achieve SVR and in this way we can determine the frequency of the medical visits&#46; In this regard&#44; we agree with Jacobson&#44; <span class="elsevierStyleItalic">et al&#46;&#44;</span><a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">11</span></a> who have published a clinical practice update proposing a modulation of surveillance or management of gastroesophageal varices&#44; modification of the use or dosing of medications metabolized by the liver&#44; guidance regarding alcohol consumption&#44; and assessment of patient candidacy for major surgeries&#46;</p></span>"
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        "resumen" => "<span id="abs0010" class="elsevierStyleSection elsevierViewall"><p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">The increase of incidences of Hepatocellular Carcinoma &#40;HCC&#41; will continue in the next decades&#46; The therapies about hepatitis C infection has been questioned as a risk factor&#46; Some authors emphasized that sustained virologic response &#40;SVR&#41; with interferon-based therapy reduced the risk of developing HCC&#46; In contrast&#44; some publications that to suggest an increasing risk of HCC in patients treated with Direct-Acting Antivirals &#40;DAA&#41;&#46; Whether these therapies are associated with an increased risk of HCC remains to be studied and continued long-term observational studies will be needed&#46; The goal in HCV care needs to go beyond merely achieving an SVR&#46;</p></span>"
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                            3 => "Ponciano-Ro-dr&#237;guez G&#46;"
                            4 => "Almeda-Vald&#233;s P&#46;"
                            5 => "Gonz&#225;lez D&#46;"
                            6 => "Uribe M&#46;"
                          ]
                        ]
                      ]
                    ]
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                            4 => "Kotoh K&#46;"
                            5 => "Kajiwara E&#46;"
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                            4 => "Allen S&#46;"
                            5 => "Goldberg D&#46;"
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                            5 => "Lammert F&#46;"
                            6 => "Duarte-Rojo A&#46;"
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Article information
ISSN: 16652681
Original language: English
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