Maintenance Therapy With Peginterferon Alfa-2b Does Not Prevent Hepatocellular Carcinoma in Cirrhotic Patients With Chronic Hepatitis C

Bruix, Jordi; Poynard, Thierry; Colombo, Massimo; Schiff, Eugene R.; Burak, Kelly W.; Heathcote, E. Jenny; Berg, Thomas; Poo, Jorge Luis; Mello, C. B.; Guenther, R. Kim; Niederau, Claus; Terg, Rubén; Bédossa, Pierre; Boparai, Navdeep; Griffel, Louis; Burroughs, Margaret; Brass, Clifford A.; Albrecht, Janice K.

doi:10.1053/j.gastro.2011.03.010

Cited by 101 publications

(90 citation statements)

References 21 publications

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“…Portal venous pressure is reduced in HCV-related cirrhotic patients achieving an SVR (15). The EPIC 3 study revealed that low-dose maintenance therapy with peginterferon reduces the frequency of adverse events related to portal hypertension such as ascites and variceal bleeding (8). In addition, in the present case, long-term combined therapy with very-low-dose peginterferon and UDCA decreased the spleen size and increased the peripheral platelet count.…”

Section: Discussionsupporting

confidence: 50%

“…The ability of low-dose maintenance therapy with peginterferon to improve the prognosis in patients who fail to achieve an SVR with interferon (IFN) treatment has been investigated in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial (7) and the Evaluation of PegIntron in Control of Hepatitis C Cirrhosis 3 (EPIC 3 ) program (8). Currently, the efficacy of low-dose maintenance therapy with peginterferon remains controversial.…”

Section: Introductionmentioning

confidence: 99%

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Long-term Combined Therapy with Very-low-dose Peginterferon and Ursodeoxycholic Acid Decreased the Spleen Size in a Patient with Hepatitis C Virus-related Cirrhosis

et al. 2013

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A 42-year-old woman with hepatitis C virus-related cirrhosis underwent peginterferon alpha-2b therapy combined with ribavirin but could not achieve a sustained viral response. Following discontinuation of this combined therapy, the patient's serum transaminase levels suddenly became elevated. Therefore, the administration of very-low-dose peginterferon alpha-2a with ursodeoxycholic acid was introduced. Thereafter, the patient's serum transaminase levels gradually improved. Four years later, enhanced computed tomography showed shrinkage of the spleen and enlargement of the liver. Long-term combined therapy with very-lowdose peginterferon and ursodeoxycholic acid may be effective not only in preventing disease progression, but also in improving portal hypertension in patients hepatitis C virus-related cirrhosis.

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Section: Discussionsupporting

confidence: 50%

Section: Introductionmentioning

confidence: 99%

Long-term Combined Therapy with Very-low-dose Peginterferon and Ursodeoxycholic Acid Decreased the Spleen Size in a Patient with Hepatitis C Virus-related Cirrhosis

et al. 2013

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“…There is currently no available vaccine as in HBV, but preventing the progression of the acute infection to chronic hepatitis and finally cirrhosis with antiviral agents, prevents cancer development; however, the risk of HCC remain higher [37] . In randomized controlled trials, treatment has not been shown to modify disease progression rates or HCC development in patients with chronic HCV and advanced fibrosis [38,39] . There are recent studies showing that elimination of HCV in patients with compensated cirrhosis, decreases the risk of developing the tumor after 10 years [40] .…”

Section: Risk Factors and Preventionmentioning

confidence: 99%

Diagnosis and treatment of hepatocellular carcinoma: An update

Tejeda-Maldonado¹

2015

WJH

110

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Hepatocellular carcinoma (HCC) is one of the most common malignancies leading to high mortality rates in the general population; in cirrhotic patients, it is the primary cause of death. The diagnosis is usually delayed in spite of at-risk population screening recommendations, i.e., patients infected with hepatitis B or C virus. Hepatocarcinogenesis hinges on a great number of genetic and molecular abnormalities that lead to tumor angiogenesis and foster their dissemination potential. The diagnosis is mainly based on imaging studies such as computed tomography and magnetic resonance, in which lesions present a characteristic classical pattern of early arterial enhancement followed by contrast medium "washout" in late venous phase. On occasion, when imaging studies are not conclusive, biopsy of the lesion must be performed to establish the diagnosis. The Barcelona Clinic Liver Cancer staging method is the most frequently used worldwide and recommended by the international guidelines of HCC management. Currently available treatments include tumor resection, liver transplant, sorafenib and locoregional therapies (alcoholization, radiofrequency ablation, chemoembolization). The prognosis of hepatocarcinoma is determined according to the lesion's stage and in cirrhotic patients, on residual liver function. Curative treatments, such as liver transplant, are sought in patients diagnosed in early stages; patients in more advanced stages, were not greatly benefitted by chemotherapy in terms of survival until the advent of target molecules such as sorafenib. Core tip: This paper reviews the most recent evidence on hepatocarcinoma including its molecular pathogenesis and prognosis, with special emphasis on its diagnosis, staging and treatment. The most recent Easter and Western international guidelines are also reviewed.

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“…Regarding liver decompensation and mortality, we have observed a significant association between virological response and the occurrence of liver events in both patients with and without EV, although the formers maintained a risk to develop liver decompensation and to die in consequence of liver events even after SVR achievement. Further evidences were provided from three randomized controlled trials -HALT-C [34], COPILOT [35] and EPIC-3 [36] -that investigated the effectiveness of a longterm maintenance therapy with pegylated-IFN in nonresponder HCV patients with advanced fibrosis or cirrhosis. The outcomes assessed were death, hepatic decompensation, HCC development and an increase in hepatic fibrosis for noncirrhotic patients: overall, a poor benefit of maintenance therapy on clinical outcomes -including HCC -was observed, despite the reduction of viral load and the improvement of inflammatory Cardoso et al…”

Section: Koreamentioning

confidence: 99%

Residual Risk of Hepatocellular Carcinoma After HCV Eradication: more than meets the eye

Macaluso

Calvaruso

2015

Future Microbiol.

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Eradication of HCV in patients with advanced liver fibrosis or cirrhosis reduces, but does not altogether abolish, the risk of development of hepatocellular carcinoma. The reasons underlying this residual risk remain elusive. Even if HCV clearance eliminates its direct and indirect carcinogenic effects, the persistence of cirrhosis and the possible coexistence of metabolic factors (diabetes, obesity and insulin resistance) and of alcohol abuse can promote the development of hepatocellular carcinoma acting as autonomous, nonviral carcinogenic factors. Lessons learned in the IFN era may still assist in predicting the forthcoming scenario, when IFN-free regimens will obtain high rates of viral clearance even at the most advanced stages of liver disease. KeywordsHepatocellular carcinoma (HCC) is a challenging malignancy of global importance, being the second cause of cancer-related death worldwide [1]. The majority of HCCs occur in the context of chronic infection with HBV and HCV, and the cancer risk is directly related to the histological and clinical stage of the underlying liver disease [2]. In particular, HCV infection stands today as the leading risk factor for HCC in many industrialized countries [3], occurring at a rate between 3 and 8%, according to the geographic area, in patients with HCV-related cirrhosis [4]. On these assumptions, prevention of population exposure to HCV can be regarded as the most effective tool to reduce liver-related mortality from HCC due to chronic HCV infection. In the HCV scenario, where an effective vaccine is not currently available, antiviral treatments have stood as the real backbone of prophylaxis strategy in the prevention of HCC, of course together with all procedures implemented to prevent HCV transmission [5].However, the evidence that patients with chronic hepatitis C (CHC) are completely protected against occurrence of HCC by successful IFN-based treatments is controversial, mainly due to methodological limitations of available literature. All in all, HCC risk seems to be sharply attenuated, although not completely eliminated -especially in patients with advanced fibrosis -following eradication of HCV infection, and the causes for this residual HCC risk in patients who achieved a sustained virological response (SVR) remain receding. Moreover, the intrinsic limitations of the use of IFN to patients with less advanced liver disease have curtailed the potential benefit, due to the fact that HCC in HCV cirrhosis becomes more prevalent at the more advanced stages of liver disease.In this review, we discuss the available clinical evidence of the role of antiviral treatment against chronic HCV infection for the prevention of HCC, and the residual risk existing in patients successfully treated. In addition, we focus on the molecular mechanisms that might explain the pathophysiological rationale of the reduction, but not elimination, of HCC risk after HCV eradication. The lesson from the IFN era may be extremely useful to predict the near-future scenario, when For repri...

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Maintenance Therapy With Peginterferon Alfa-2b Does Not Prevent Hepatocellular Carcinoma in Cirrhotic Patients With Chronic Hepatitis C

Cited by 101 publications

References 21 publications

Long-term Combined Therapy with Very-low-dose Peginterferon and Ursodeoxycholic Acid Decreased the Spleen Size in a Patient with Hepatitis C Virus-related Cirrhosis

Long-term Combined Therapy with Very-low-dose Peginterferon and Ursodeoxycholic Acid Decreased the Spleen Size in a Patient with Hepatitis C Virus-related Cirrhosis

Diagnosis and treatment of hepatocellular carcinoma: An update

Residual Risk of Hepatocellular Carcinoma After HCV Eradication: more than meets the eye

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