Treatment of anicteric acute hepatitis C with peginterferon alpha-2a plus ribavirin

BACKGROUND: Hepatitis C virus (HCV) infection is the most frequent cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma in the world. Acute hepatitis C is the most commonly asymptomatic liver disease with the development of chronic HCV infection in the majority of infected patients. Studies of the natural history of HCV infection suggest that only 15-30% of patients with acute infection recover spontaneously. Others, up to 85% of the infected patients develop chronic hepatitis C. Acute hepatitis C is so uncommon and with the unpredictable occurrence, and of the low frequency, that it is difficult to determine the optimal treatment of this disease. There have been many randomized, controlled trials of the therapy in patients with chronic hepatitis C, but none of an adequate size or rigor in patients with acute hepatitis C. Therefore, the causal treatment of patients with acute hepatitis C aimed at the prevention of chronic liver disease is necessary. CASE REPORT: We have treated a patient with anicteric form of acute hepatitis C after a three-month outpatient follow-up using a combined therapy: pegylated interferon-alpha 2a, 180 microg, subcutaneously, once a week plus ribavirin 1000 mg orally once a day. The treatment lasted 24 weeks. Stable biochemical and virological response was achieved both at the end of the treatment and 6 months after the completion of the therapy. CONCLUSION: We believe that the above mentioned might be one of the approaches to the treatment of acute hepatitis C. However, further prospective studies with significantly larger number of patients are necessary for the definite conclusions about the treatment of HCV infections.     

Therapy of acute hepatitis C infection

BACKGROUND: Hepatitis C viral infection is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. The progression of acute to chronic infection occurs in 50-90% of cases. There is no standard therapy for acute HCV infection. Comparative studies are required to verify the optimal doses, dosage schedules and the treatment duration, and to establish the optimal treatment for acute hepatitis C. Recent reports have demonstrated that early application of interferon alpha was a treatment of choice for acute HCV infection. The addition of ribavirinin in the treatment of acute HCV infection, and HCV genotype, did not improve the end-of-treatment responses. It is important to consider the treatment of acute HCV infection before it progresses to chronic state. CASE REPORT: Beneficial effect of interferon therapy in a patient with acute hepatitis C is presented. Early treatment with 3 MIU interferon alpha, three times a week, within six-months, resulted in the normal serum aminotransferases, and good virological response in our patient. CONCLUSION: Interferon therapy significantly increased the probability of obtaining normal serum aminotransferases and undetectable HCV RNA, following acute HCV infection.     

丙型肝炎病毒逃避宿主固有免疫的分子机制

丙型肝炎病毒(HCV)可引起慢性肝炎、肝硬化和肝癌.80%的新发感染发展为慢性感染,干扰素/利巴韦林联合治疗疗效不尽如人意,这些现象提示HCV已建立了一系列抵抗机制对抗宿主的免疫反应和干扰素的抗病毒活性.近年来研究发现,病毒可通过干扰模式识剐受体TIJR3、RIG-I介导的信号通路和干扰素信号通路以及干扰素刺激基因等多个水平的逃避机制,抵抗宿主的抗病毒反应.本文对HCV封闭模式识别受体介导的信号通路,干扰宿主固有免疫以建立持续感染的分子机制进行了综述.     

Significance of iron reduction for the therapy of chronic hepatitis C

BACKGROUND: It has been established that many patients with chronic hepatitis C have elevated serum iron, feritin levels and iron deposites in the liver. Therefore, the liver damage due to hepatitis C virus may be aggravated with iron overload. In many studies higher levels of iron in the blood and the liver were connected with the decreased response to interferon-alfa therapy for chronic viral hepatitis C. Recent introduction of pegylated interferons plus ribavirin has improved the therapeutic response, so it is now possible to cure more than 50% of the patients. CASE REPORT: Three patients with chronic hepatitis C and iron overload were presented. Iron reduction therapy using phlebotomy or eritrocytapheresis with plasmapheresis was done at different times in regard to specific antiviral therapy or as a sole therapy. CONCLUSION: It has been shown that iron reduction, sole or combined with antiviral therapy, led to the deacreased aminotransferase serum activity and might have slown down the evolution of chronic hepatitis C viral infection.     

丙型肝炎病毒对干扰素治疗的影响及预测

以干扰素为基础的治疗是目前丙型肝炎病毒感染者唯一有效的治疗手段,但干扰素疗效受病毒因素、宿主免疫状态和干扰素剂型等影响,且干扰素价格昂贵,疗程长,又有一定的不良反应。因此,对丙型肝炎患者治疗前或早期治疗过程中进行干扰素疗效的预测,将有助于对临床病例进行合理的干扰素治疗。本文综述了丙型肝炎病毒的基因型、治疗前血清中病毒载量水平、病毒变异率,以及治疗过程中病毒动力学变化等病毒自身因素和干扰素疗效预测的关系。     

Liver damage caused by hepatitis C viral infection and ethyl alcohol consumption

BACKGROUND/AIM: Hepatitis C virus infection (HCV) is a complex disease, most commonly chronicle (80-85%). The aim of this research was to determinate the level of the liver damage in the patients cansed by HCV in conjunction with consuming ethyl alcohol. METHODS: The research included 15 patients with chronic HCV infection supported by the misuse of ethyl alcohol, as well. The diagnosis of C infection hepatitis was proved using the ELISA test and PCR method. RESULTS: The results of the study showed the liver damage by both HCV infection and ethyl alcohol, which was verified by the presence of biochemical changes and patohystological processing of the patients (liver biopsy and prosection). Patohystological changes were at the level of liver cirrhosis and carcinoma (2 patients). There was a signficant difference between the two subgroups (p < 0.001) regarding the examined values gamma-GT, PLT and PTV. The basic therapeutic procedure was to introduce this category of patients into alcohol abstinence, and, in a few patients, to apply the antivirus therapy, as well. CONCLUSION: Based on the number of the examined patients (n = 15), we could conclude that a prolonged ethyl alcohol misuse with the presence of HCV infection was in a correlation with the liver disease progression.     

Treatment of chronic viral hepatitis B in secondary membranoproliferative glomerulonephritis using recombinant alfa-2 interferon

A patient suffering from viral hepatitis B and secondary membranoproliferative glomerulonephritis was presented. He was treated with recombinant alfa-2 interferon. The therapy led to clinical and biochemical remission of the liver and kidney lesions. The example of our patient justifies the use of recombinant alfa-2 interferon in the patients with chronic viral hepatitis B and secondary glomerulonephritis.     

Prediction of therapy response to interferon-alpha in chronic viral hepatitis-B by liver and hepatobiliary scintigraphy

Interferon (IFN) provides effective treatment in some patients with chronic hepatitis. The clarification of factors predictive of therapy response would be helpful in identifying patients who would benefit from treatment. In this study, we evaluated the potential utility of Tc-99m sulfur colloid liver/spleen and Tc-99m-disofenin hepatobiliary scintigraphy to predict therapy response to IFN in patientswith chronic active hepatitis. The study group consisted of ten patients with chronic viral hepatitis B who were treated with 4.5 units of interferon alpha for 12 months. Prior to the start of the therapy, sulfur colloid scintigraphy was obtained by which the liver/spleen ratios were derived. Hepatobiliary scintigraphy was performed on a separate day and time-activity curves were generated from regions of interest drawn over the liver, heart and gall-bladder. The index of blood and liver clearance time was calculated. Histological grading and laboratory values were obtained for clinical correlation. Responders (n = 6) to IFN were defined as those who improved clinically with normalized transaminase levels and had HBeAg seroconversion. On SC scintigraphy, the liver/spleen ratio of non-responders was significantly lower than responders (median values: 0.69 vs. 1.16, p = 0.01) but on hepatobiliary scintigraphy no statistically significant parameters were found to predict response to interferon therapy.     

Evaluation of ribavirin efficacy and tolerance in subjects with chronic hepatitis C virus infection

BACKGROUND: Reports by hepatologists indicated that anti-HCV antibodies might be detected in 71% to 84% of cases of post-transfusion hepatitis and in up to 50% of cases of sporadic non-A non-B hepatitis. Anti-HCV antibodies were detected in 0.05-1% of blood donors with normal alanine transaminase (ALT) levels and negative anti-HBc screening. Anti-HCV antibodies were found in 67% of patients with a history of intravenous drug abuse or autoimmune hepatitis, and in 10-30% of patients with hepatocellular carcinoma. This indicated that hepatitis C virus was a major cause of the acute and chronic hepatitis throughout the world. METHODS: This was a multicenteric, international, double-blind, randomized, placebo-controlled study. After the eight-week screening period, patients were randomized to receive daily ribavirin 1200 mg or placebo, during the 48-week treatment period. Follow-up observations were performed during a 16 week post-treatment period. Up to 80 male and female outpatients with mild to moderate chronic active hepatitis C virus infection were enrolled in this study. RESULTS: During the treatment period ALT values were significantly lower in the ribavirin group. Neither in the ribavirin group, nor in the placebo group significant statistical differences of the HCV RNA values were found. Significantly lower portal inflammation was noticed in ribavirin group after the treatment. Analysis of laboratory data demonstrated that ribavirin therapy was associated with mild to moderate reversible anemia. Investigator's evaluation of the effect of the therapy on patient's well being showed statistically significant differences in the benefit of the ribavirin group. CONCLUSION: In this study ribavirin was more effective than placebo in reducing ALT levels during the treatment period of the applied therapy in patients with chronic active hepatitis C.     

Chemoembolization for hepatocellular carcinoma: where does the truth lie?

Hepatocellular carcinoma (HCC) remains one of the most highly lethal cancers in the world. It continues to be plagued by a shortage of effective therapeutic options and consequently is a major cause of death, especially in eastern Asia and sub-Saharan Africa. In the United States, the incidence of HCC has been rapidly and steadily increasing in the past 20 years because of the concomitant epidemic rise in hepatitis C virus infection. Surgical resection and liver transplantation offer the only chance for a cure, but, unfortunately, tumors in most patients are found to be unresectable at presentation and the patients are therefore left with palliative options only. Of those, transcatheter arterial chemoembolization has been the most widely used over the years and has become the mainstay of therapy for patients with unresectable HCC. Yet, controversy has surrounded its efficacy and impact on patient survival. After a period of initial enthusiasm followed by encouraging results from retrospective and prospective studies, several randomized trials failed to show any survival advantage of chemoembolization over supportive care. So where does the truth lie? The publication this year of two separate high-quality randomized trials, one in Hepatology from Hong Kong and the other in Lancet from Spain, should help answer this question and finally establish the usefulness of chemoembolization as an effective palliative therapy against HCC.     

干扰素α-2b治疗HBeAg阳性慢性乙肝疗效及其预测因素分析

目的观察普通干扰素治疗HBeAg阳性慢性乙肝的临床效果及其预测因素。方法选择近年收治的未应用过抗病毒药物的HBeAg阳性慢性乙肝患者,给予普通干扰素抗病毒治疗48周,随访24周,观察其临床疗效及其预测因素。结果持续应答率为23.28%,HBeAg血清转换率为34.48%,持续应答组HBeAg血清转换率为63.04%。性别、是否母婴传播与抗病毒效果无关,基线HBV-DNA、ALT、AST、TBIL、GGT水平与抗病毒效果相关。基线HBV-DNA、ALT、GGT水平可以作为普通干扰素治疗HBeAg阳性慢性乙肝患者抗病毒效果的预测因素。结论普通干扰素治疗HBeAg阳性慢性乙肝疗效确切。持续应答的患者能够获得较高的HBeAg血清转换率。根据患者基线HBV-DNA水平及肝功能情况选择合适的患者是提高应答率的关键。     

Lymphadenopathy resulting from acute hepatitis C infection mimicking metastatic breast carcinoma on FDG PET/CT

We report a case documenting fluorodeoxyglucose (FDG) accumulation in upper abdominal lymph nodes resulting from acute hepatitis C infection. A 42-year-old African-American female with a history of metastatic breast carcinoma was found to have hypermetabolic porta hepatic, peripancreatic, and paraaortic lymphadenopathy and hypermetabolism in the spleen on a surveillance FDG positron emission tomography/computed tomography (PET/CT) scan. Concurrently, she was diagnosed with acute hepatitis C infection. Antiviral therapy was not recommended secondary to the low level of detectable virus at the time of diagnosis. Her breast cancer therapy regimen was continued unaltered. FDG PET/CT scan was repeated 2 months later as a result of concern that the hypermetabolic lymph nodes represented metastatic disease; however, the scan revealed complete resolution of the previously abnormal findings. The resolution of the lymphadenopathy and the patient's clinical course led to the conclusion that the most likely explanation for the FDG PET/CT findings was inflammation secondary to acute hepatitis C infection and not metastatic breast carcinoma. Inflammatory and infectious processes accumulate FDG, occasionally resulting in false-positives for malignancy. Infected macrophages in the lymph nodes draining the liver in this case and stimulation of a cellular immune response by the hepatitis C virus, with resultant cytokine production by cytotoxic and T-helper cells, offer possible explanations for the findings seen on FDG PET/CT in this case. This case highlights the importance of clinical history and laboratory correlation for the proper interpretation of FDG PET scans.     

Viral hepatitis in the U.S. military: a study of hospitalization records from 1974 to 1999

Viral hepatitis remains a health threat for military forces. Most recently, there has been concern about hepatitis C virus transmission during military service because a high prevalence of hepatitis C virus infection has been found in some U.S. veteran populations. In this study, hospitalizations of active duty U.S. military personnel for hepatitis were evaluated using standardized computer records. Only the first hospitalization was assessed during the period January 1, 1989, to December 31, 1999. Among active duty forces, the rate of hospitalization for all types of acute hepatitis declined from 13 to 1.1 per 100,000 personnel from 1989 to 1999. Males, nonwhite racial/ethnic groups, and older troops were more likely to be hospitalized for acute hepatitis. This study's finding of declining rates of acute hepatitis is a continuation of a trend observed since 1974. The decreasing risk of viral hepatitis in the U.S. military is attributable to several factors, including reduced levels of injection drug use because of routine, randomized drug testing.     

Correlation of 99mTc-GSA hepatic scintigraphy with liver biopsies in patients with chronic active hepatitis type C.

99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA) liver scintigraphy was performed in 230 patients with chronic active hepatitis type C, and its quantitative indices were compared with histological findings. 99mTc-GSA findings correlated well with four indices of the histology activity index (HAI), especially with the fibrosis score. Ninety patients were given interferon treatments, and 99mTc-GSA findings were compared with the results of the treatments. We classified the effects of interferon treatment into three groups according to clinical outcome: group 1: good effect (HCV-RNA negative, n = 34), group 2: moderate effect (HCV-RNA positive, but the value of GPT was normal for six months after the end of treatment, n = 19) and group 3: no effect (n = 37). Quantitative indices of 99mTc-GSA showed significant differences between groups. Follow-up study with 99mTc-GSA scintigrams was obtained in eight patients. The results of 99mTc-GSA improved in three patients in group 1 and deteriorated in five patients in group 3. There is a possibility that 99mTc-GSA scintigraphy can be used to predict the clinical outcome of chronic active hepatitis type C after interferon treatment.     

99mTc-GSA SPECT analysis was clinically useful to evaluate the effect of interferon in a patient with interferon non-responsive chronic hepatitis C

We describe a 62-year-old woman with advanced chronic hepatitis C who showed no response to low-dose long-term interferon-beta monotherapy (3?MU, three times a week). The interferon monotherapy was continued for 2?years and 9?months. Despite this lack of response to interferon, the patient's clinical course was good and liver function assessed by (99m)Tc-galactosyl human serum albumin single photon emission computed tomography ((99m)Tc-GSA SPECT) analysis improved significantly. Improvement of the data obtained by (99m)Tc-GSA SPECT analysis justified continuation of the treatment. (99m)Tc-GSA SPECT analysis was clinically useful to evaluate the effect of interferon in a patient with interferon non-responsive chronic hepatitis C, despite a lack of reduction of the ALT level and HCV-RNA titer.     

"Ecstasy"-induced hepatitis in an active duty soldier

3,4-Methylenedioxymethamphetamine, or "Ecstasy," is a drug commonly used at "rave" parties to heighten energy and intimacy. Although its complications have been well described in Europe, including less common side effects such as hepatic failure and rhabdomyolysis, physicians in the United States have less experience with this drug because of the shorter duration of its use in this country. We present a case of an active duty soldier who was admitted for acute hepatitis secondary to Ecstasy ingestion and describe its proposed pathophysiology. We believe that with the increased use of Ecstasy in the United States, especially among younger patients, including soldiers, military physicians will need to be more familiar with this potentially deadly drug.     

New nonsurgical therapies in the treatment of hepatocellular carcinoma

The last decade has seen a rapid increase in the incidence of hepatocellular carcinoma in the United States, mostly because of the increased incidence of hepatitis C. Surgical therapy remains limited to the few patients who are surgical candidates at presentation. In addition, surgery has been plagued by high recurrence rates, which can reach 80% at 3 years. Systemic chemotherapy has been found to be ineffective, with response rates approaching 10% to 20%. Nonsurgical percutaneous therapies, including percutaneous locoregional ablative procedures (ethanol or acetic acid injection, radiofrequency ablation, microwave coagulation therapy, chemotherapy infusion, laser photocoagulation, and high-intensity ultrasound) and intra-arterial procedures (radioembolization with yttrium-90 microspheres or transcatheter intra-arterial chemoembolization) are gaining popularity because they are less invasive than surgery and can be nearly as effective in prolonging survival. Multiple studies have shown good response rates with high technical success rates, as well as significant survival advantages for nonresectable disease. Furthermore, they can be performed repeatedly without compromising liver function and at a considerably lower morbidity and cost than surgery.     

Hepatocellular carcinoma with sarcomatous change arising after eradication of HCV via interferon therapy

A patient was diagnosed with chronic hepatitis C at the age of 63 years. He achieved eradication of HCV via interferon (IFN). Eight years after, a hepatocellular carcinoma (HCC) was detected and treated through transarterial embolization and percutaneous ethanol injection therapy. After about 1 year, a large hypovascular tumor was detected. This tumor was surgically resected and diagnosed as an HCC with sarcomatous change. This is the first case of an HCC with sarcomatous change arising after a sustained response to IFN therapy.