Autoantibody in a patient with chronic hepatitis C virus infection showing complete remission after interferon therapy

A 42-year-old woman was admitted to Kinashi Ohbayashi Hospital for liver dysfunction. She presented with hepatitis C viral infection accompanied by autoimmune hepatitis-like serological manifestations, such as antinuclear antibody (ANA), antismooth muscle cell antibody and especially anti-ribonucleoprotein (RNP) antibody and anti-SSB antibody. After interferon therapy, hepatitis C virus was not detected and ANA, anti-RNP antibody and anti-SSB antibody disappeared. To our knowledge, this is the first reported hepatitis C patient showing anti-RNP antibody and anti-SSB antibody, having complete remission after interferon therapy.     

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.     

Clinical features and prognosis in patients with hepatocellular carcinoma that developed after hepatitis C virus eradication with interferon therapy

Background

We evaluated the clinical features and the prognostic factors of hepatocellular carcinoma (HCC) developed after hepatitis C virus (HCV) eradication with interferon (IFN) therapy.

Methods

Forty-one consecutive patients who developed HCC after HCV eradication with IFN therapy were enrolled. Clinical features were reviewed, and overall survival and associated factors were analyzed. The recurrence rate in 26 patients receiving radical therapy was also analyzed.

Results

Twenty patients developed HCC within 5?years after the end of IFN therapy, 9 patients developed the disease from 5 to 10?years after the end of the therapy, 9 patients developed the disease from 10 to 15?years after the end of the therapy, and 3 patients developed the disease from 15?years after the end of the therapy. Multivariate analysis of independent variables for the development of HCC within 5?years identified age >55?years at HCV eradication (P?=?0.007) and heavy alcohol intake (P?=?0.009). The 5-year survival rate was 64%. On multivariate analysis of overall survival for the 41 patients, the only risk factor with prognostic influence was radical therapy (P?=?0.010), which was associated with a cumulative 5-year survival rate of 91%. The only independent factor for the receipt of radical therapy was regular surveillance for HCC (P?=?0.004). Among patients receiving radical therapy, the 3- and 5-year recurrence rates were 18 and 18%, respectively.

Conclusion

We found that, despite HCV eradication, patients with the risk factors of high age at HCV eradication and heavy alcohol intake might be at heightened risk for the development of HCC within 5 years after HCV eradication. In contrast, risk factors for the development of HCC more than 10?years after HCV eradication were uncertain. These findings indicate the need for long-term surveillance for HCC after HCV eradication.     

Incidence of hepatocellular carcinoma in chronic hepatitis C after interferon therapy

BACKGROUND/AIMS: We investigated the rate of occurrence and the risk factors for hepatocellular carcinoma in chronic hepatitis C patients who received interferon therapy. METHODOLOGY: We followed 413 chronic hepatitis C patients for more than 6 years after interferon therapy and assessed the following patient characteristics: age, sex, platelet count, response to interferon, hepatitis C virus RNA level, hepatitis C virus genotype, liver histology, and changes in serum alanine aminotransferase levels. RESULTS: Hepatocellular carcinoma was found in 21 patients after interferon therapy. The factor most related to the occurrence of hepatocellular carcinoma was changes in serum alanine aminotransferase levels (univariate analysis, P < 0.0001; multivariate analysis, P = 0.0013), followed by age (univariate analysis, P = 0.0003; multivariate analysis, P = 0.0029). A significant difference was observed in the platelet count and response to interferon based on univariate analysis alone (P = 0.0096, P = 0.0241, respectively), however no significant differences were noted in the other factors. The course of serum alanine aminotransferase levels following interferon therapy rather than the eradication of hepatitis C virus was found to be the factor most profoundly involved in liver carcinogenesis. CONCLUSIONS: Even if interferon therapy fails to eradicate the hepatitis C virus, maintaining low serum alanine aminotransferase levels post-interferon therapy would reduce the risk of hepatocellular carcinoma in chronic hepatitis C.     

Immunoglobulin M antibody to hepatitis C virus during interferon therapy for chronic hepatitis C.

Testing for immunoglobulin (Ig) M antibody to hepatitis C virus (anti-HCV) as a predictive factor of therapeutic response to recombinant interferon alfa (rIFN-alpha) in chronic hepatitis C was evaluated in 122 patients with IgG anti-HCV. IgM anti-HCV was present in the pretreatment sample of 88% of patients who responded to treatment, including 20 of 21 (95%) long-term responders and 24 of 29 (83%) responders who had relapses after cessation of therapy. In contrast, IgM anti-HCV was present in only 23 of 39 (59%) nonresponders and 22 of 33 (66%) untreated controls (P less than 0.05). The number of cases with detectable IgM anti-HCV tended to decrease in responder patients, which was more evident for complete responders (42%) than for responders who relapsed (72%). During follow-up, the antibody became undetectable in the majority of long-term responders (28% were still IgM anti-HCV positive) but remained detectable in 69% of responders who relapsed (P less than 0.05). No special changes were noted in nonresponder or control patients. Thus, testing for IgM anti-HCV may help to identify a subset of patients who will benefit from rIFN-alpha therapy in chronic hepatitis C.     

Thyrotoxicosis due to long-term therapy with interferon alpha in the patient with mixed chronic active hepatitis B and C

The authors describe a case report of 48-year-old woman treated with Interferon alpha for the chronic active hepatitis B and C. During this therapy thyrotoxicosis occurred. It disappeared after the withdrawal of Interferon alpha and administration of strumigens. Immediately after stopping of the administration of Interferon alpha and three month later antibodies against the thyroid epithelium were found.     

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.     

Hepatocellular carcinoma in patients with chronic hepatitis C virus infection without cirrhosis

AIM:To investigate and characterise patients with chronic hepatitis C virus(HCV) infection presenting with hepatocellular carcinoma(HCC) in the absence of cirrhosis.METHODS:Patients with chronic hepatitis C infection without cirrhosis presenting with HCC over a 2-year period were identified.The clinical case notes,blood test results and histological specimens were reviewed to identify whether additional risk factors for the development of HCC were present.RESULTS:Six patients(five male,one female) with chro...     

Giant negative T waves during interferon therapy in a patient with chronic hepatitis C

Interferon-alpha (IFN-alpha) has been widely used for treatment of chronic hepatitis C in Japan. In general, cardiovascular adverse reactions are rare in association with IFN-alpha therapy. Here, a 64-year-old man with chronic active hepatitis C complained of fatigue, palpitation and depression, and developed atrial fibrillation with prominent negative T waves during IFN-alpha therapy. Echocardiogram showed septal and apical hypertrophy. Three days after discontinuation of IFN-alpha, subjective symptoms and atrial fibrillation subsided. It is unclear whether or not IFN-alpha induced the giant negative T waves with apical hypertrophy. We might observe the developing course of hepatitis C virus (HCV)-related myocardial hypertrophy by chance. Cardiovascular toxicity should be carefully monitored during IFN-alpha therapy even in patients with minor cardiac disease, such as premature ventricular contracture (PVC) and mild hypertension.     

Resected cases of hepatocellular carcinoma detected after interferon therapy for chronic hepatitis C

BACKGROUND/AIMS: Interferon therapy decreases the incidence of hepatocellular carcinoma in patients infected with hepatitis C virus. However, hepatocellular carcinoma was detected after interferon therapy in some patients. METHODOLOGY: Of the 167 patients who underwent liver resection for hepatitis C virus-related hepatocellular carcinoma between 1993 and September 1998, the carcinoma was detected after interferon therapy in 11 patients. The clinicopathologic findings in these 11 patients were studied. RESULTS: The response to interferon was complete (n = 4), partial (n = 4), or no response (n = 3). Hepatocellular carcinoma was detected 2 months to 3 years 9 months, after interferon therapy. The interval period from the end of interferon therapy to the detection of the carcinoma were significantly correlated with the longest diameter of the main tumor (P = 0.0043), indicating that most carcinomas have already developed before the end of interferon therapy. In one non-responder, multicentric carcinogenesis occurred after liver resection for primary hepatocellular carcinoma. Another patient with advanced hepatocellular carcinoma died of the recurrence. CONCLUSIONS: Surveillance for hepatocellular carcinoma must be performed even in patients successfully treated with interferon because occult carcinoma may have developed before or during the therapy.     

Oropharyngeal pemphigus in a patient with chronic hepatitis C during interferon alpha-2a therapy

There are a few reports in the literature concerning pemphigus induced by interferon given for hepatitis C. We present the case of a 28-year-old woman with post-transfusional chronic hepatitis C who developed ulcers and vesicles on her tongue, cheeks, posterior oropharynx and vocal cords 5 months after beginning treatment with recombinant interferon alpha-2a. The direct and indirect immunofluorescence was diagnostic of pemphigus vulgaris. The drug was promptly withdrawn; the patient was medicated with prednisolone and azathioprine and recovered only 3 months later. Although there are several publications describing the occurrence of other autoimmune diseases in patients receiving interferon alpha therapy, this is the first report of a pemphigus induced by interferon in hepatitis C patients involving oropharyngeal and laryngeal mucosae without cutaneous involvement.     

Interstitial pneumonitis in a patient with chronic hepatitis C and chronic renal failure on interferon therapy

After 4-months of alpha interferon (IFN-α), a 64-year old woman with chronic hepatitis C developed a cough and dyspnea and showed diffuse infiltrative opacities on her chest X-ray. Her symptoms persisted after stopping the IFN-α therapy. Pulmonary function testing revealed a reduced forced vital capacity. High-resolution computed tomography of the lung showed peripheral and peribronchovascular ground glass attenuation and consolidation associated with reticulation. Bronchoalveolar lavage was performed for further evaluation and showed a lymphocyte level of 8.2%, an uncommon finding in IFN-α-induced interstitial pneumonitis. We performed a lung biopsy to diagnose her disease and it suggested interstitial pneumonitis. This was considered to be due to the immunomodulatory effects of INF-α. Although rare, any sign of significant pulmonary involvement should be evaluated.