Interferon therapy following treatment of recurrent hepatocellular carcinoma in an 83-year-old man with hepatitis C virus-related liver cirrhosis

A sustained virological response and improvement of liver function were achieved by low-dose interferon (IFN) therapy following curative treatment of initial and recurrent hepatocellular carcinoma (HCC) in an 83-year-old man with hepatitis C virus (HCV)-related liver cirrhosis (CLC). Although a fourth HCC episode recurred 16 months after IFN therapy, it was successfully treated. The patient is still alive 6 years and 7 months after diagnosis of the initial HCC and has been in a tumor-free state for 19 months following treatment of the last HCC. The results of this case suggest that, given sufficient consideration of adverse effects, IFN therapy for HCV and repeated local treatment for HCC contribute to improving the prognosis even in the case of a CLC patient over 80 years of age whose condition is complicated by recurrent HCC.     

Development of small hepatocellular carcinoma in a patient with chronic hepatitis C after 77 months of a sustained and complete response to interferon therapy

We report a case of hepatocellular carcinoma (HCC) that developed 77 months following sustained and complete response to interferon (IFN) therapy for chronic hepatitis C. A 67-year-old Japanese woman presented with a small mass in the liver that was diagnosed as HCC, 77 months after having completed IFN therapy and having shown a complete response to the therapy with sustained normalization of serum aminotransferases and eradication of serum hepatitis C virus (HCV). Hepatitis C virus RNA was also not detected in the resected tumorous and non-tumorous liver tissues by polymerase chain reaction. This suggests that all patients with chronic HCV infection should be followed closely for as long as possible for the potential development of HCC, even after a complete and sustained response to IFN treatment.     

Development of small hepatocellular carcinoma 80 months after clearance of hepatitis C virus with interferon therapy

We describe a patient who had a complete and sustained response to interferon (IFN) therapy for chronic hepatitis C but developed small hepatocellular carcinoma (HCC) 80 months later. A 55-year-old Japanese man with hepatitis C virus (HCV) infection and histological features of chronic active hepatitis was treated with recombinant IFN alpha-2a, 9,000,000 U daily for 2 weeks followed by three times a week for 22 weeks. He successfully responded to IFN therapy with a normalization of serum alanine aminotransferase and continuous disappearance of serum HCV-RNA. However, 80 months after the cessation of IFN therapy, the patient's alpha-fetoprotein (AFP) level became elevated for the first time and HCC, 12 mm in diameter, was detected by routine ultrasonographic screening. Laparotomy revealed a small HCC with no metastasis, and the nontumorous liver demonstrated chronic inactive hepatitis. This case indicates the need for careful follow-up using ultrasonography and AFP testing for at least 7 years after completing IFN therapy in all patients with chronic hepatitis C, even if the patients have a complete response to the therapy.     

Effect of interferon therapy on first and second recurrence after resection of hepatitis C virus-related hepatocellular carcinoma

Aim: Several investigators have shown that interferon (IFN) therapy can suppress the recurrence of hepatocellular carcinoma (HCC) after curative treatment. We investigated the effect of IFN therapy on the first and second HCC recurrence following hepatic resection of hepatitis C virus (HCV)-related HCC. Methods: Subjects included 166 patients who had undergone curative resection for a single HCV-related HCC. We analyzed the outcome after initial hepatic resection and risk factors of a second HCC recurrence following treatment for the first HCC recurrence. Results: Using multivariate analysis, a non-sustained virological response (non-SVR) was significantly associated with a high incidence of first HCC recurrence. The rate of second HCC recurrence tended to be higher in the non-SVR group than in the SVR group. In the patients with recurrence of multiple tumors or who received non-curative treatment for recurrent HCC, the second HCC recurrence rates were significantly higher. Multivariate analysis demonstrated that non-curative treatment for first HCC recurrence was an independent risk factor for a second HCC recurrence. Among the patients who received curative treatment for their first HCC recurrence, the rates of second recurrence were significantly higher in the non-SVR group than in the SVR group. Multivariate analysis also revealed that SVR was independently associated with prevention of a second HCC recurrence. Conclusions: These results suggest that on first HCC recurrence, a curative treatment should be considered in order to prevent a second recurrence if possible. In addition, IFN therapy contributes to improved prognosis after curative treatment, even in patients with recurrent HCC.     

Differences in background characteristics of patients with chronic hepatitis C who achieved sustained virologic response with interferon‐free versus interferon‐based therapy and the risk of developing hepatocellular carcinoma after eradication of hepatitis C virus in Japan

We compared the background characteristics of patients with chronic hepatitis C who achieved eradication of hepatitis C virus (HCV), that is sustained virologic response (SVR), with interferon (IFN)‐based versus IFN‐free antiviral therapy in Japan. In addition, we used a previously reported risk assessment model to compare the incidence of hepatocellular carcinoma (HCC) after SVR by treatment type. Pretreatment characteristics of 1533 patients who achieved SVR with IFN‐based therapy and 1086 patients with IFN‐free therapy from five institutions across Japan were compared. The risk of HCC after SVR was assessed based on pretreatment characteristics, and the incidence of HCC after SVR was estimated in both groups. Age and serum alpha‐fetoprotein levels were higher, platelet count was lower, and liver fibrosis was more advanced in patients who achieved SVR with IFN‐free therapy compared with IFN‐based therapy. The incidence of HCC after SVR in the IFN‐free group was estimated to be more than twofold higher than in the IFN‐based therapy group (7.29% vs. 3.09%, and 6.23% vs. 3.01% when excluding patients who have underwent curative treatment for HCC). There are large differences in pretreatment characteristics between patients who achieved SVR with IFN‐based and IFN‐free therapies in Japan, which are associated with differential risk of HCC after SVR. These differences can influence the incidence of HCC after SVR and should be taken into consideration when comparing IFN‐based and IFN‐free therapies in terms of hepatocarcinogenesis suppression with HCV eradication.     

Suppression of hepatocellular carcinoma development in hepatitis C patients given interferon‐based antiviral therapy

The advance of antiviral treatment for chronic hepatitis C has brought a high sustained virological response (SVR) rate. In this review article, the suppressive effect of interferon (IFN)‐based therapy on the development of hepatocellular carcinoma (HCC), risk factors for developing HCC and the characteristics of HCC development after SVR among chronic hepatitis C patients given IFN‐based therapy were studied. The HCC incidence has been revealed to decrease with IFN‐based antiviral therapy, especially in SVR, and the risk factors for developing HCC were older age, advanced liver fibrosis and male sex. α‐Fetoprotein levels at 24 weeks after the end of IFN‐based treatment was associated strongly with HCC incidence irrespective of virological response. In patients with SVR, other risk factors were glucose metabolism disorders, lipid metabolism disorders and alcohol intake. Extra attention to the possibility of HCC incidence should be required for these SVR patients. Antiviral therapy with a combination of HCV‐specific direct‐acting antivirals (DAA) is expected to be utilized in the future. However, it is not known whether DAA‐based treatment can suppress HCC to the level of IFN‐based treatment. Further research is required to clarify this.     

Development of hepatocellular carcinoma in a patient with chronic hepatitis C after 6 years of a sustained and complete response to IFN-alpha.

The authors report a rare case of hepatocellular carcinoma (HCC) that developed 6 years after a sustained and complete response to interferon (IFN) therapy for chronic hepatitis C. A 61-year-old Japanese man presented with a mass in the liver that was diagnosed as HCC. Six years earlier he was treated with IFN-alpha and responded successfully to therapy, with sustained normalization of serum aminotransferases and eradication of serum hepatitis C virus (HCV)-ribonucleic acid (RNA). HCV-RNA was also not detected in the resected tumorous and nontumorous liver tissues. The findings suggest that all patients with chronic HCV infection should be followed closely for as long as possible for the potential development of HCC even after a complete and sustained response to IFN treatment.     

Detection of hepatocellular carcinoma after interferon therapy for chronic hepatitis C: Clinical study of 26 cases

The clinical findings in 26 patients in whom hepatocellular carcinoma (HCC) was detected after the start of interferon (IFN) therapy for chronic hepatitis C were analysed. Histological study before IFN therapy showed that 34.6% of patients were categorized as stage 3 (septal fibrosis with architectural distortion; the 0–4 scale) and 80.8% demonstrated at least some evidence of septal fibrosis or more advanced features. The AFP levels examined before IFN therapy were more than 20 ng/mL in 13 patients (84.6% of those studied). One of 26 patients had a complete response to IFN therapy, while six of 26 patients had only a partial response. HCC was detected within 1 year after the start of IFN therapy in 76.9% of patients. Thus, the possibility of the early occurrence of HCC or its existence at the time of therapy should be seriously considered when IFN therapy is contemplated. Patients with stage 3 or 3–4 histology may already have a small undetectable HCC before IFN therapy. Thus, for this reason, every patient treated with IFN should be examined at short regular intervals for the development of HCC during and after IFN therapy.     

Treatment of chronic hepatitis C virus infection in patients with cirrhosis

Chronic hepatitis C virus (HCV) infection eventually leads to cirrhosis in 20–30% of patients and to hepatocellular carcinoma (HCC) in 1–5% of patients. Rates of sustained virological response with standard interferon-α (IFN-α) are low in patients without cirrhosis (generally < 20%) and are even lower in those with cirrhosis. Combination therapy with IFN and ribavirin improves response rates in patients with chronic hepatitis C without cirrhosis, and the results from subgroups of HCV-infected patients with advanced fibrosis or cirrhosis are encouraging. Importantly, treatment with IFN slows progression of liver fibrosis, regardless of HCV genotype or early response to therapy, and reduces the risk of HCC by two- to fivefold. The risk of development of HCC is also lower in patients who show at least a partial response to IFN therapy compared with those who show no response. There is a clear need for more definitive studies of treatment in patients with chronic hepatitis C and cirrhosis, ideally using therapies with greater efficacy. Nonetheless, based on the potential to slow the progression of liver fibrosis (regardless of treatment response) and to reduce the risk of HCC, a greater number of HCV-infected patients with cirrhosis should be considered as candidates for IFN treatment. Preliminary data indicate that pegylated IFNs have improved virological response rates and may have additional clinical benefits in the prevention or reduction of fibrosis and retardation of progression of cirrhosis and HCC in these patients.     

Long term histological improvement and clearance of intrahepatic hepatitis C virus RNA following sustained response to interferon-ribavirin combination therapy in liver transplanted patients with hepatitis C virus recurrence

BACKGROUND AND AIMS: A proportion of liver transplanted patients with recurrent chronic hepatitis have a sustained virological response to combination therapy with interferon plus ribavirin. However, the long term benefit of antiviral therapy with regard to hepatitis C virus (HCV) RNA clearance remains unknown in patients with HCV recurrence. This study examined the long term biochemical, virological, and histological outcome in transplanted patients with recurrent chronic hepatitis who had a sustained virological response to antiviral therapy. PATIENTS AND METHODS: Fifty four patients with recurrent hepatitis C were treated with antiviral therapy involving induction by combination therapy (interferon (IFN) plus ribavirin) for six months and maintenance ribavirin therapy for 12 months. Fourteen patients who had recurrent chronic hepatitis and sustained virological response to antiviral therapy were followed for three years after the end of antiviral therapy. Serum alanine aminotransferases were assessed every three months during the observation period. Serum hepatitis C RNA detected by polymerase chain reaction was evaluated every six months during follow up, and protocol biopsy procedures were performed routinely every year. Semiquantitative histopathological assessment of allograft hepatitis was performed using the Knodell score and HCV was also detected by polymerase chain reaction on frozen graft tissue samples. RESULTS: At the end of antiviral therapy, the sustained response rate was 26%. A complete response (normal serum alanine aminotransferase level and undetectable serum HCV RNA) was achieved in 13/14 (93%) patients three years after the end of treatment. A comparison of liver histology findings before and after a mean of three years after antiviral therapy showed a clear improvement in 12/14 (86%) patients. In 5/14 (36%) patients, the last biopsy showed normal or near normal histological findings. After three years of follow up, the total Knodell score was 3.2 (range 1-8) versus 8.3 (range 5-12) before treatment (p=0.001). Graft HCV RNA was detectable before treatment in all 14 patients and was undetectable at the end of follow up in 13/14 (93%) patients tested. CONCLUSION: In patients with biochemical and virological responses induced by ribavirin and interferon, a complete response was sustained in 93% for at least three years after cessation of therapy. This long term response was associated with absence of detectable intrahepatic hepatitis C RNA and marked histological improvement.     

Successful treatment of hepatitis C reinfection with interferon-alpha2b and ribavirin after liver transplantation.

INTRODUCTION: Recurrence of hepatitis C virus (HCV) infection after orthotopic liver transplantation (OLT) is a virtually universal occurrence, and a significant proportion of patients develop chronic hepatitis and cirrhosis. The aim of this study was to evaluate the safety and efficacy of interferon (IFN)-alpha2b plus ribavirin (RIBA) in the treatment of recurrent HCV after OLT over the long term. MATERIAL AND METHODS: Fifteen patients with recurrent HCV infection (positive serum HCV RNA, elevated serum aminotransferases, histological activity) were started on IFN-alpha2b (3-6 million units administered subcutaneously three times a week) plus RIBA (800-1200 mg/day) 18+/-5 months after OLT. HCV RNA was determined 1, 3, 6, 9, 12 and 18 months after initiation of treatment. Liver biopsy was performed before and after therapy. The patients were followed up for a mean of 33+/-5 months. RESULTS: Thirteen patients (87%) were treated for at least 6 months and nine patients (60%) for 12 months. After 3 months, 11 patients (73%) were free from HCV RNA (<50 copies/ml); the virological end-of-treatment response was 67%. Five patients (33%) remained HCV RNA-negative 6 months posttreatment (sustained response (SR)). During the follow-up period, four patients (27%) died of liver failure, recurrent HCV after virological response, or HCC. The histological activity index improved significantly for both inflammatory activity and fibrosis, from 8.8 to 4.7 and from 7.3 to 4.8, respectively. In none of the patients were signs of rejection observed. CONCLUSION: Combination therapy with IFN and RIBA in transplanted patients with chronic hepatitis C is an effective treatment that results in a high virological SR rate. It is well tolerated and leads to an improvement in histological outcome.     

Secondary prevention of recurrence by interferon therapy after ablation therapy for hepatocellular carcinoma in chronic hepatitis C patients

Chronic hepatitis C is a leading cause of hepatocellular carcinoma （HCC） worldwide. Interferon （IFN） therapy decreases the incidence of HCC in patients with chronic hepatitis C. Prevention of chronic-hepatitisC-related HCC is one of the most important issues in current hepatology. We have previously reported that male gender and high titer of hepatitis C virus （HCV） RNA are predictive factors for the development of HCC in HCV-related cirrhosis. Clinical efforts at eradicating or reducing the viral load may reduce the risk for HCC. Furthermore, because HCC often recurs after ablation therapy, we performed a trial of IFN in patients with chronic liver disease caused by HCV to see whether IFN therapy decreases recurrence after ablation therapy of HCV-related HCC. By using IFN therapy as a secondary prevention, patients with HCC who had received complete tumor ablation showed better survival, primarily as a result of the preservation of liver function and also probably prevention of recurrence. Postoperative IFN therapy appears to decrease recurrence after ablation therapy such as radiofrequency ablation （RFA） therapy of HCV-related HCC. We believe that there is a survival benefit in secondary prevention using IFN therapy. However, a controlled study is essential to obtain conclusive evidence of the efficacy of this strategy.     

Development of hepatocellular carcinoma in patients with chronic hepatitis C who had a sustained virological response to interferon therapy: a multicenter, retrospective cohort study of 1124 patients.

BACKGROUND: Interferon (IFN) improves hepatic inflammation/fibrosis and reduces the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CH-C). However, HCC develops in some patients who have a sustained virological response (SVR) to IFN therapy. We designed this study to establish a follow-up protocol for patients with CH-C who have SVR to IFN therapy. METHODS: We retrospectively studied 1124 patients with CH-C who received IFN. RESULTS: HCC developed in 3.5% of patients with SVR to IFN. As compared with SVR patients without HCC, SVR patients with HCC were predominantly male (P=0.003), older at the initiation of IFN therapy (P=0.002), and at a more advanced histologic stage of disease (P<0.001). However, three of the 13 SVR HCC patients had mild fibrosis. The mean interval from IFN therapy to the detection of HCC in SVR HCC patients was 5.8 years and did not differ significantly from that in non-SVR HCC patients (P=0.304). Although most patients with HCC received curative therapy, the prognosis of some SVR HCC patients was poor, probably because of insufficient follow-up, resulting in delayed detection of HCC. CONCLUSIONS: SVR patients with CH-C who are elderly, male, or have an advanced histologic stage are at a high risk for the development of HCC after IFN therapy. We recommend that SVR patients should be observed carefully for more than 10 years after the completion of IFN therapy, even if they only have early fibrosis.     

De novo hepatitis B virus infection in hepatocellular carcinoma following eradication of hepatitis C virus by interferon therapy

Epidemiological studies have revealed that hepatocellular carcinoma (HCC) is still observed in hepatitis C virus (HCV)‐positive patients with a sustained response to interferon (IFN) treatment, although a substantial decrease in the incidence of hepatocellular carcinoma (HCC) has been achieved in those patients. Why HCC develops in patients who have a complete clearance of HCV remains unclear. Here, we provided evidence of latent hepatitis B virus (HBV) infection in an initially HCV‐positive chronic hepatitis patient who developed HCC after the complete eradication of HCV by IFN therapy. Although he was initially negative for anti‐hepatitis B surface antigen (HBsAg) or circulating HBV DNA but positive for anti‐hepatitis B core antigen (anti‐HBc) in his sera, he developed HBsAg and HBV DNA during the course of the management of a series of cancers. HBV DNA was detectable in the liver tissues before HBV reactivation and the viral sequences derived from his anti‐HBc‐positive liver showed 100% homology to that from the serum after HBsAg appearance. These findings indicates that HCV‐positive individuals who are positive for anti‐HBc in the absence of HBsAg could have latent HBV infection in their liver tissues and intrahepatic HBV infection may play a pivotal role in the development of HCC after the IFN‐mediated eradication of HCV.     

Occult hepatitis B virus infection as a risk factor for hepatocellular carcinoma in patients with chronic hepatitis C in whom viral eradication fails.

Aim: Recent studies have suggested that an occult hepatitis B virus (HBV) infection negative for HBsAg but positive for HBV-DNA contributes to hepatocellular carcinoma (HCC) development in patients with chronic hepatitis C. Some follow-up studies have suggested the clinical importance of occult HBV infections in HCC development even after interferon (IFN) therapy, but a recent study denies the significance of the impact of occult HBV infection. Focusing on HCC development in patients in whom hepatitis C virus (HCV) eradication by interferon (IFN) therapy had failed, we conducted this study in order to assess the impact of occult HBV infections on HCC development in these patients. Methods: We enrolled 141 patients with chronic hepatitis C (histological stage F2 or F3) who were seropositive for HCV-RNA even after IFN therapy. Serum HBV-DNA was assayed using the real-time polymerase chain reaction. During follow-up, ultrasonography and/or computed tomography (CT) were performed at least every 6 months to monitor HCC development. Results: The cumulative incidence rates of HCC were 8.9%, 25.7% and 53.7% at 5 years, 10 years and 15 years, respectively, after IFN therapy. Multivariate analysis indicated that low platelet counts (<12 x 10(4)/mm(3)), occult HBV infection, high ALT levels (>/=80 IU/L) after IFN therapy and the staging of liver fibrosis were important independent factors affecting the appearance of HCC. Conclusions: Occult HBV was a risk factor for HCC development in patients with chronic hepatitis C in whom HCV eradication had failed. Therefore, patients with chronic hepatitis C with occult HBV should be monitored carefully for HCC after IFN therapy.     

Anticarcinogenic impact of interferon therapy on the progression of hepatocellular carcinoma in patients with chronic viral infection

Hepatocellular carcinoma (HCC) is mainly caused by a persistent infection due to the hepatitis B or hepatitis C virus. The number of HCC cases is increasing in Asian and African countries, as well as in European and American countries. Interferon (IFN) therapy, used for type B chronic liver diseases, inhibits hepatic carcinogenesis in patients with compensated cirrhosis. However, there is insufficient evidence that IFN therapy inhibits hepatic carcinogenesis in patients with chronic hepatitis B. There are few cases of HCC due to chronic hepatitis B, and long-term follow-up periods verifying the inhibitory effect of IFN on hepatic carcinogenesis have not been obtained. To improve the prognosis of type B chronic liver diseases, it is important that hepatitis treatment follows guidelines in which a patient's age and the extent of hepatic fibrosis are taken into account. As for chronic hepatitis C, since a sustained virological response (SVR) in IFN therapy inhibits hepatic carcinogenesis and improves prognosis, treatment that aims for an SVR while taking into consideration host-sided and virus-sided factors is recommended for patients with type C chronic liver diseases. In areas with low incidence of HCC (e.g. USA), a large number of cases and a long-term follow-up period are needed before it can be accepted that IFN therapy inhibits hepatic carcinogenesis. After locally curative treatment of HCC, IFN therapy suppresses recurrence and improves survival rates.     

Efficacy of interferon in treating chronic hepatitis C in children with a history of acute leukemia

Interferon (IFN) is effective in treating adults as well as children with chronic hepatitis C. We investigated the efficacy of IFN therapy in 13 children with underlying acute leukemia who had chronic hepatitis C (age range, 5 to 17 years; mean age, 9.9 years). Natural IFN- alpha was administered at a dose of 0.1 mega unit (MU)/kg (maximum dose, 6.0 MU) daily for 2 weeks and then three times per week for an additional 22 weeks (total dose, 8 MU/kg). IFN treatment was initiated at least 2 years after the completion of treatment for acute leukemia. A complete response was obtained in 5 children (38%). The serum level of anti- hepatitis C virus core antibody was closely related to the response to IFN. IFN therapy was well tolerated by all but 1 of the children, who developed mild transient heart failure 4 months after the initiation of therapy. IFN therapy for children with chronic hepatitis C who had underlying acute leukemia was beneficial. However, further trials are required to confirm the safety and improve the dosage schedule of IFN therapy.     

Long-term follow-up of alpha-interferon treatment of patients with chronic hepatitis B

Data on the long-term effects of interferon alfa (IFN) treatment on disease progression and mortality in patients with chronic hepatitis B (CHB) are limited. To evaluate factors that influence clinical outcome and survival, we performed a follow-up study on 165 hepatitis B e antigen (HBeAg) positive CHB patients treated with IFN between 1978 and 2002. The median IFN dose was 30 megaunits (MU)/week (range, 2-70 MU/week), and the median duration of therapy was 16 weeks (range, 1-92 weeks). Response to treatment was defined as HBeAg loss within 12 months after the end of IFN therapy. Median follow-up was 8.8 years (range, 0.3-24 years). Fifty-four patients (33%) responded to IFN treatment. Relapse (HBeAg reactivation) occurred in 7 of the 54 (13%) responders. Fifty-two percent of the responders lost hepatitis B surface antigen (HBsAg) as compared with 9% of the nonresponders (P <.001). Liver histology showed a decreased necroinflammatory activity and less progression of fibrosis in responders. Twenty-six patients died during follow-up. Hepatocellular carcinoma (HCC) was found in 8 patients, 6 of whom were nonresponders. Of the two responders who developed HCC, one patient had relapsed after discontinuation of therapy. Multivariate analysis showed significantly improved survival (relative risk (RR) of death 0.28, 95% CI 0.10-0.78) and reduced risk of developing HCC (RR 0.084, 95% CI 0.09-0.75) in responders. In conclusion, response to IFN therapy results in a prolonged clinical remission with an increased rate of HBsAg seroconversion and improved liver histology. Our results indicate that after correction for baseline factors, response to IFN therapy increases survival and reduces the risk of developing HCC.     

Intrahepatic cholangiocellular carcinoma and hepatocellular carcinoma developed after a 6-year sustained virological response to interferon therapy for chronic hepatitis C

A 67-year-old male patient presenting with chronic hepatitis C (CHC) achieved a sustained virological response (SVR) following 6 months of treatment with 6 million units of beta-interferon (IFN). The SVR state continued for 6 years. Hepatocellular carcinoma (HCC) developed in liver segments 4 and 5, and was treated with transcatheter arterial chemoembolization, followed by radiofrequency ablation of the tumors. A recurrence of HCC occurred in segment 4 one and a half years after the initial treatment for HCC and a new tumor also developed in segment 8. These tumors were diagnosed to be recurrent HCC, and the three hepatic segments were resected. The pathological examination and immunostaining of the tumors revealed the tumor in segment 4 to be a well to moderately differentiated typical HCC. On the other hand, the tumor in segment 8 was a moderately to poorly differentiated adenocarcinoma and was diagnosed as an intrahepatic cholangiocellular carcinoma (ICC). HCC developed from CHC in a patient who achieved a 6-year SVR after IFN therapy, followed one and a half years later by the development of a heterochronous ICC at a different site, thus indicating the presence of HCC–ICC double cancer. This was an exceedingly rare and clinically important case in terms of the carcinogenic mechanism of HCC and ICC from a post-SVR CHC patient. We have to be aware of the possible development not only of HCC but of ICC after SVR in CHC patients.     

Effect of long-term interferon therapy for refractory chronic hepatitis c: preventive effect on hepatocarcinogenesis

BACKGROUND/AIMS: Effect of interferon (IFN) therapy for refractory chronic hepatitis C is not sufficient. For patients with persistent hepatitis C virus (HCV) infection, one of the clinical goals is prevention of progression to liver cirrhosis (LC) and hepatocellular carcinoma (HCC). In this study, we evaluated effect of long-term IFN administration for refractory chronic hepatitis C. METHODOLOGY: The patients who were positive for HCV of genotype lb in high viral load and failed in HCV elimination by standard IFN therapy were retrospectively analyzed. The patients were divided into three groups according to administration duration of IFN therapy. The patients in group 1, 2 and 3 received IFN therapy for 6 months, 6-24 months and more than 24 months, respectively. RESULTS: The normalization rate of alanine aminotransferase (ALT) levels less than twice that of the normal limit 6 months after the treatment was highest in group 3 (85%). The platelet counts in group 1 gradually decreased more than 3 x 10(4)/microL from the pretreatment levels at 100 months after the start of treatment. Cumulative hepatocarcinogenesis rate in groups 1, 2 and 3 were 34.7%, 5.9% and 0%, respectively. We found distinct improvement in both ALT levels and histopathological findings in the case that received the longest term of IFN therapy (91 months). CONCLUSIONS: Long-term IFN therapy is effective in preventing hepatocarcinogenesis through reduction of chronic necroinflammation and accumulation of fibrosis in the liver and may be a good indication even for refractory chronic hepatitis C.