Epidemic outbreak of acute hepatitis C--clinical course, histology and effectiveness of therapy

An epidemic outbreak of HCV infection was observed in the center of nonconventional therapy, when patients with stable coronary heart disease and arteriosclerosis obliterans were treated. They received drop infusions with chelate therapy with unknown medicine. We diagnosed acute hepatitis C in 15 patients (mean age 61). All were positive for HCV RNA, had known exposure to HCV within the preceding 3 months and elevated serum ALT value 2-10 ULN. 12 out of 15 patients had documented seroconversion to anti-HCV. In 6 patients liver biopsy was performed. Acute viral hepatitis was diagnosed in 4 cases (of mild activity in 2 cases and of moderate activity in the other two cases). In two remaining cases histology required differentiation diagnosis (one with non alcoholic steatohepatitis and one with exacerbation of chronic hepatitis). Different forms of hepatocyte degeneration and steatosis were observed in all cases. Considering the possibility to chronicity we decided to treat 10 patients, while remaining 5 had contraindications to interferon therapy. There was no control group. Patients were treated with pegylated alfa 2b interferon 1.5 mcg/kg/week and ribavirin 1000-1200 mg/d, for 12 weeks. Side effects appear minimal. In no case therapy was interrupted. Sustained viral response (SVR) and normalization of ALT were observed in 6 out of 10 treated patients (1 with jaundice and 5 asymptomatic). Two untreated subjects had spontaneous recovery. We found that administration of pegylated interferon alfa-2b and ribavirin 1-6 months after the appearance of jaundice or significant elevation of ALT activity could prevent progression to chronic infection. This therapy appears to be effective and safe in asymptomatic infection and among others in adult patients with stable coronary heart disease. Our results confirmed the previous observations mentioned by others that treatment of acute hepatitis C with pegylated interferon and ribavirin may lead to cure.     

Combined antiviral treatment in a patient with recurrent chronic hepatitis C after liver transplantation

BACKGROUND: Hepatitis C virus infection persists after liver transplantation and causes recurrent liver injury in the majority of the patients. We report a case of orthotopic liver transplantation with more than five years survival despite the early recurrence of hepatitis C virus. CASE REPORT: A 49-year old woman underwent orthotopic liver transplantation because of liver cirrhosis following chronic hepatitis C virus infection. Twelve years before she received blood-transfusion. The chronic liver disease was diagnosed four years later. However, then it was thought to be a drug induced liver damage. After the liver transplantation hepatitis C chronic hepatitis recurred within one year. The serotype analysis (1b) proved the autoreinfection. The combined antiviral treatment (interferon plus ribavirin) resulted significant improvement. She was asymptomatic nearly for two years. The liver biopsy showed a significant histological improvement. However the virologic response and remission was transient. Four years after the transplantation recurrence occurred again. The liver biopsy proved cirrhosis. Antiviral therapy with pegylated interferon plus ribavirin was started but it had been stopped because of severe cytopenia. Lack of adequate antiviral treatment her condition became progressively worse. Finally, five years after the transplantation she died because of bilateral haemorrhagic ovarian necrosis and severe circulatory insufficiency thanks to the low albumin level. CONCLUSIONS: In the case of liver cirrhosis caused by hepatitis C virus the liver transplantation could prolongs the life with years. The presented case illustrate that the hepatitis C virus injures the transplanted liver by autoreinfection. However, the combined antiviral therapy could result sustained virologic response in these cases as well. Our patient survived five years thanks to the transplantation and the following antiviral therapy.     

Hungarian consensus guideline for the diagnosis and treatment of B, C, and D viral hepatitis

More than 1% of the Hungarian population is infected with hepatitis B, C, or D viruses. Since 2006 the diagnostics and therapy of these infections are carried out in treatment centers according to national guidelines - since 2010 according to financial protocols. The consensus-based guidelines for 2012 are published in this paper. The guidelines stress the importance of quick and detailed virologic evaluations, the applicability of transient elastography as an acceptable alternative of liver biopsy in this regard, as well as the relevance of appropriate consistent follow up schedule for viral response during therapy. The first choice of therapy in chronic hepatitis B infection is pegylated interferon for 48 weeks or continuous entecavir therapy. The later must be continued for at least 6 months after hepatitis B surface antigen (HBsAg) seroconversion. Tenofovir disoproxil fumarat is not yet reimbursed by the National Health Insurance Fund. Adefovir dipivoxil is recommended mainly in combination therapy. Lamivudine is no longer a first choice; patients currently taking lamivudine must switch if response is inadequate. Appropriate treatment of patients taking immunosuppressive medications is highly recommended. Pegylated interferon based therapy is recommended for the treatment of concomitant hepatitis D infection. Treatment naive chronic hepatitis C patients should initially receive pegylated interferon and ribavirin dual combination therapy. In genotype 1 infection if response is insufficient at 4 or 12 weeks one of the two new direct acting antivirals (boceprevir or telaprevir) should be added. The length of treatment is usually 48 weeks; in cases of extended early viral response shorter courses are recommended. Previous treatment failure patients with genotype 1 infection should receive a protease inhibitor backed triple combination therapy, mostly for 48 weeks. However, relapsers without cirrhosis and with extended rapid viral response, shorter telaprevir based combination therapy is sufficient. Drug-drug interactions as well as emergence of viral resistance are of particular importance. For genotype 2 or 3 HCV infections 24 weeks, for genotype 4 infections 24, 48 or 72 weeks of pegylated interferon plus ribavirin therapy is recommended in general. The guidelines published here become protocols when published as official publications of the Hungarian Health Authority.     

Combined interferon-alfa-2b and ribavirin therapy in patients with recurrent chronic hepatitis c after liver transplantation

Interferon with ribavirin therapy has been proposed for the treatment of hepatitis C recurring in liver transplants. AIM OF THE STUDY: Was to assess the efficacy of standard combination therapy (interferon plus ribavirin) of chronic hepatitis C in transplanted patients with recurrent severe HCV induced chronic hepatitis. METHODS: 12 patients with HCV-PCR positive reaction (genotype 1b) were treated with the therapy of interferon-alpha-2b (3 MU three times a week) and 800-1000 mg ribavirin daily. Liver biopsy had been done in every patients before and after the treatment. Study endpoints were the end of treatment and the 6 month post-therapy sustained virologic response. RESULTS: At the end of treatment 3 patients were negative for HCV-PCR and all of them had negative reaction after 6 month follow-up period. CONCLUSION: The results are in a good accordance with treatment of patients with chronic hepatitis C without liver transplantation.     

Treatment of chronic hepatitis C

Since last 5 years there have been several important advances that significantly impact therapy. The most notable advances have been the availability of sensitive, specific, and standardized tests for identifying hepatitis C virus (HCV) RNA in the serum, the addition of ribavirin to alpha interferon, the pegylation of alpha interferon, and the demonstration that sustained virological response (SR) is the optimal surrogate endpoint of treatment. The combination of high-dose peginterferon and ribavirin is more efficacious than standard interferon and ribavirin in persons infected with HCV genotype 1 (Genotype HCV1 patients may show SR of about 40%.) Compensated HCV cirrhosis patients may also be treated with PEG-IF and ribavirin combination. Decompensated cirrhosis needs liver transplantation. Strategies to enhance response to current therapies include the development of novel interferons, nucleoside analogues, inosine 5' monophosphate dehydrogenase inhibitors, and other immunomodulators that are being evaluated as adjunctive therapy to interferon-based regimens.     

New therapeutic options in chronic hepatitis C virus infection

Chronic hepatitis C virus (HCV) infection is the major etiology and the reason of chronic liver disease, liver cirrhosis, hepatic decompensation, hepatocellular cancer and liver transplantation. Less than half of patients with HCV-related chronic hepatitis achieve sustained viral clearance with current pegylated interferon and ribavirin (P+R) combination therapy. Due to the insufficient treatment success, an extended search for new, direct acting anti-HCV agents (DAAs) is ongoing, already leading to submissions of applications for marketing authorization of the protease-inhibitors boceprevir and telaprevir. Both are effective only in triple combinations with P+R. Studies demonstrate a 50% success rate advantage for triple therapies above current standards. In addition, treatment duration can be shortened, and half of the patients who failed previous therapy with P+R can be cured with triple therapies. A major concern with new DAAs is rapid development of DAA-resistant viral mutants, a reason as well as a consequence of insufficient triple therapy. Clinical studies with boceprevir and telaprevir are reviewed in this paper.     

Therapeutic vaccine IC41 as late add-on to standard treatment in patients with chronic hepatitis C

We examined the effect of the hepatitis C virus (HCV) peptide vaccine IC41 on HCV-specific T-cell responses and virological relapse rates in patients with chronic HCV genotype 1 infection when added to pegylated interferon plus ribavirin standard therapy. 35 patients received 6 vaccinations with IC41 from weeks 28 to 48 of standard antiviral treatment and were followed-up for another 6 months. IC41 vaccination did not prevent HCV-RNA relapse in patients with ongoing interferon standard treatment but HCV-specific T-cell responses were inducible and were associated with lower relapse rates. An increase of HCV-specific T-cell responses occurred in 73% of patients, responses were more frequent and stronger in patients with sustained virologic response than in patients who relapsed. Optimized vaccine responses may enhance sustained virologic response rates obtained with standard treatment of chronic hepatitis C.     

Pathogenesis of hepatitis C virus infection

The hepatitis C virus (HCV) is the leading cause of chronic liver disease worldwide. Chronic hepatitis C is a mayor cause of cirrhosis and hepatocellular carcinoma and HCV-related end-stage liver disease is, in many countries, the first cause of liver transplantation. HCV infection is characterized by its propensity to chronicity. Because of its high genetic variability, HCV has the capability to escape the immune response of the host. HCV is not directly cytopathic and liver lesions are mainly related to immune-mediated mechanisms that are characterized by a predominant type 1 helper cell response. Co-factor influencing the outcome of the disease including age, gender and alcohol consumption are poorly understood and other factors such as immunologic and genetic factors may play and important role. Recent studies have shown that the combination therapy with alpha interferon and ribavirin induces a sustained virological response in about 40% of patients with chronic hepatitis C. The lack of animal models and of in vitro cultures systems hampers the understanding of the pathogenesis of chronic hepatitis C and the development of new antivirals. The conjugation of polyethyleneglycol improved the pharmacodynamics and the efficacy of alpha interferon. The development of an effective vaccine remains the most difficult challenge. Because of the high protein variability of HCV, protective vaccines could be extremely difficult to produce and therapeutic vaccines seem more realistic. Considerable progress has been made in the field of HCV since its discovery 10 years ago but a major effort needs to be made in the next decade to control HCV-related disease.     

丙型肝炎病毒职业暴露处理与追踪随访

目的了解临床医务人员发生丙型肝炎病毒(HCV)职业暴露后处理过程及感染情况,为HCV职业暴露的防护提供经验。方法调查5例发生HCV职业暴露医务人员的暴露环节、暴露后处理方法及追踪随访结果。结果5例发生HCV职业暴露的医务人员均为临床护士,1例确诊为职业暴露后急性感染HCV。发生HCV暴露后,均给予常规心理支持和咨询,4例排除感染者很快恢复正常的工作和生活;确诊被感染者暂时调离临床一线岗位,加强心理支持,坚持完成1年聚乙二醇干扰素联合利巴韦林的抗病毒治疗后痊愈。结论医务人员发生HCV职业暴露后及时上报、进行HCV RNA感染监测;确诊感染HCV后尽早联合聚乙二醇干扰素及利巴韦林抗病毒治疗,是治愈HCV急性感染的关键措施。     

Liver transplantation in patients with cirrhosis secondary to hepatitis B virus and hepatitis C virus infections

Liver cirrhosis main related to hepatitis C virus constitutes the main indication of liver transplantation in Europe and the USA, representing as many as 50% of the indications in adults, while cirrhosis associated with hepatitis B virus represents around 10%. The indications for transplantation in patients with infection by both viruses are fulminant hepatitis, decompensated cirrhosis and hepatocellular carcinoma. Both injections may relapse after transplantation. The evolution of the relapse in the graft is variable and can include non-significant alterations of the liver junction tests, chronic active hepatitis and cirrhosis. Less frequently, a particularly severe form called "fibrosing cholestatic hepatitis" can develop, which rapidly evolve to graft failure. The immunoglobin against the B virus and lamivudine reduce the risk of reinfection. The principal factor associated with reinfection is active viral replication before the transplantation, thus it is considered a contraindication for liver transplantation. INF-alpha has been used in the treatment of hepatitis B virus reinfection with discouraging results. More recently, lamivudine and adefovir have been used. Post-transplantation recurrence of hepatitis C is universal and its evolution towards cirrhosis is more rapid than in immunocompetent patients, with graft dysfunction being the most frequent cause of mortality and of indication for retransplantation. Different factors have been related to the severity of the recurrence including factors related to the donor, the recipient, the virus, immunosuppression and surgery. There are no preventive treatments against recurrence of post-transplantation hepatitis C. In the treatment of the hepatitis C virus recurrence, INF-alpha and rivabirin have been used in single form or in combination with variable results, with the combined therapy being more effective. Recently, encouraging results have been described with the combination of pegylated interferon and rivabirin without a higher incidence of rejection. Finally, the results of retransplantation in patients with recurrent hepatitis B or C have not been encouraging.     

Retreatment strategies for the patients with HCV infection

Despite recent advances in the treatment of chronic hepatitis C, especially introduction of combined therapy with pegylated interferons with ribavirin, significant number of patients fails to achieve sustained virologic response. Such patients may be divided into relapsers and non-responders.. Pegylated interferon-based retherapy appear to induce sustained response in 40-68% of relapsers and only in 11% of non responders. New therapeutic approaches are needed for treatment of these group of patients. Current retreatment strategies includes administration of pegylated interferon and ribavirin, maintenance therapy with pegylated interferon for prevention of liver fibrosis and daily administration of consensus interferon and ribavirin. In the work the initial results of 3 clinical investigation (HALT-C, EPIC 3 and COPILOT) are presented, in which beneficial efficacy of pegylated interferon in non responders was observed.     

Hepatitis C infections in dialyzed patients

The prevalence of hepatitis C virus (HCV) infection in dialyzed patients (pts) with end stage renal disease (ESRD) is higher than that of the general population. Generally it is thought that the course of hepatitis C is milder then in pts with normal renal function, but there is no agreement about natural history of HCV infection in dialyzed. Immunosuppressive therapy after renal transplantation (RTx) worsens the prognosis for pts with HCV infection. Additionally, actually available anti-HCV treatment is contraindicated after RTx due to the high risk of the graft rejection. That is the reason why antiviral therapy should be given before RTx and indications for treatment should be wider (treatment of HCV infection not only of hepatitis). The biggest number of papers addressed to anti-HCV treatment in dialyzed pts considers monotherapy with standard interferon. One out of two pegylated interferons was approved for dialyzed pts--but up to date there is no data about efficacy and safety of this compound in this group of pts. The use of ribavirin in ESRD pts is contraindicated due to the high risk of anemia.     

Of lives and livers: emerging responses to the hepatitis C virus

Hepatitis C is an infectious disease affecting the liver, caused by the hepatitis C virus (HCV). HCV is an etiological agent of acute and chronic liver disease that exists throughout the world. The high genetic variability of the HCV genome is reflected by six genotypes (1 to 6). Each genotype has a characteristic geographical distribution, which is important epidemiologically. HCV is a blood-borne virus that generally circulates in low titers in the serum of infected individuals. Epidemiologic studies show that the most efficient transmission of HCV is through the transfusion of blood or blood products, the transplantation of organs from infected donors, and the sharing of contaminated needles among injection-drug users. However, fewer than half of patients with acute hepatitis C report a history of such exposure. A small number of epidemiologic studies demonstrate that perinatal, sexual, household, and occupational transmission occurs, but our understanding of the risks of transmission in these settings has been limited. The therapy for chronic hepatitis C has evolved steadily since alpha interferon was first approved for use. At present, the optimal regimen appears to be a 24- or 48-week course of a combined pegylated alpha interferon and ribavirin regimen. Currently, the combination of RNAi (LV-shIRES) with IFN-α has been proposed to prevent therapeutic resistance, and to promote enhanced antiviral activity against HCV. However, any RNAi based therapy may be years away due to off-target effects.     

聚乙二醇干扰素α-2a联合病毒唑治疗自身免疫抗体阳性慢性丙型肝炎的临床研究

目的探讨聚乙二醇干扰素（IFN）α-2a联合病毒唑治疗自身免疫抗体阳性慢性丙型肝炎的临床疗效。方法慢性丙型肝炎患者93例,筛查自身免疫抗体;然后分为试验组（自身免疫抗体阳性）和对照组（自身免疫抗体阴性）,均给予聚乙二醇IFNα-2a联合病毒唑治疗。观察治疗前丙型肝炎病毒（HCV）RNA载量和肝功能、治疗过程中血丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平变化以及病毒学应答情况。结果93例慢性丙型肝炎患者中,共检出自身免疫抗体阳性28例,其中抗线粒体抗体阳性17例,抗平滑肌抗体阳性8例,1型抗肝肾微粒体抗体阳性3例。两组治疗前HCVRNA载量,以及治疗后快速和持续病毒学应答率比较差异均无统计学意义（P〉0．05）。治疗前及治疗中试验组患者血ALT和AST水平均高于对照组,但仅治疗第36,48周两组比较差异有统计学意义（P〈0．05）。结论聚乙二醇IFNα-2a联合病毒唑可有效治疗自身免疫抗体阳性和阴性慢性丙型肝炎患者;但自身免疫抗体阳性的患者肝功能恢复情况不如自身免疫抗体阴性患者效果好。     

Hepatitis C virus infection--after 12 years. Advances in the management of chronic hepatitis C

Therapy of different manifestations of HCV infection is discussed--after 12 years of the discovery of HCV. In acute hepatitis C the antiviral treatment of the early phase is debated, but if 3 months after the onset the HCV viremia persists, interferon (IFN) therapy may be recommended. Asymptomatic HCV carriers with normal alanine aminotransferase (ALT) do not need antivirals. However, their serum ALT, GGT, gammaglobulin values and liver ultrasound findings should be monitored, to disclose an underlying liver disease, and biopsy is considered, if suspicion of hepatitis raises. In patients with chronic hepatitis C biopsy is mandatory, it may prove mild, moderate or severe histological activity (HAI). Moderate or severe active hepatitis C (> 2 x normal ALT, HAI > 7) should be treated. In the first period of the antiviral treatment for HCV, a standard IFN monotherapy (3 x 3 MU s.c. IFN weekly for 6-12 months) has been used, which resulted in 15-20% sustained response (SR) rate. In the second half of nineties, combination of IFN with an oral nucleoside analogue ribavirin increased the SR to 30-30%, by means of decrease in relapse rate. Recently, pegylated IFN (PEG-IFN) in combination with ribavirin can lead to 60% SR. (Genotype HCV1 patients may show SR of about 40%, HCV 2.3 ones about 80%, respectively). Compensated HCV cirrhosis patients may also be treated with this type of combination, which can possibly inhibit progression. Decompensated cirrhosis needs liver transplantation. In the prevention of HCV infection, screening of blood donors, viral inactivation of blood products, disposable needles and education of risk populations are of basic importance, HCV vaccination, however is not on the horizon yet. Thus, antiviral treatment remains of great significance. Searches for new therapeutic modalities, such as multiple antiviral combinations (e.g amantadin + ribavirin + IFN), protease- and helicase inhibitors, ribozymes and cytokines may result further advances.     

Disease Management Programs for Hepatitis C

Hepatitis C is an important target for the development of disease management programs. Hepatitis C virus (HCV) infection is common and most infected individuals develop persistent infection. Although this is usually associated with chronic liver injury (chronic hepatitis C), the infection and liver disease may be unrecognized for years. Most patients are relatively asymptomatic and their illness remains clinically silent for at least 20 years after onset. In a substantial proportion of such individuals, the most widely available tests of the presence of liver injury, the serum aminotransferases, may be persistently normal. If unrecognized and untreated, chronic hepatitis C may lead to unfavorable outcomes including cirrhosis, the complications of end-stage liver disease, and hepatocellular carcinoma. These in turn sharply reduce health-related quality of life, lead to debilitating symptoms, decrease life expectancy by increasing premature death, and result in very high costs of care including the most expensive form of treatment — liver transplantation. In fact, end-stage liver disease due to chronic hepatitis C is now the single most common indication for liver transplantation in the US and Western Europe.Based on available data, the future illness and economic burden of chronic hepatitis C is likely to increase dramatically during the next few decades as currently infected, untreated individuals progress toward advanced liver disease. Unfortunately, treatment with the current agent of choice — the combination of interferon alfa and ribavirin — is difficult, expensive, and effective in only a proportion of patients. Nonetheless, computer-generated modeling studies indicate that current treatment diminishes the reduction in life expectancy expected in chronic hepatitis C and that cost-effectiveness ratios either fall within the bounds of other widely accepted medical interventions or are cost saving.Disease management programs in hepatitis C need to be designed to reduce unhealthy high risk behavior by education of the uninfected, promote health-seeking behavior such as the avoidance of alcohol in those infected, institute disease screening for those at risk with early confirmation of diagnosis, and initiate appropriate and effective treatment regimens, including actions designed to support adherence to treatment and appropriate follow-up. Advances in treatment such as the development of long-acting pegylated interferons which may enhance response rates, may be effective in advanced disease, and are well-tolerated should be incorporated into disease management programs when available. Disease management program design will require a multidisciplinary team approach and careful assessment of the effectiveness of these programs is needed.     

Possible role of angiotensin-converting enzyme polymorphism on progression of hepatic fibrosis in chronic hepatitis C virus infection

Many functional polymorphisms in the rennin-angiotensin system (RAS) have been described; these polymorphisms have been postulated to contribute to fibrosis in several diseases. Our aim was to study the frequency of ACE I/D polymorphism in chronic hepatitis C virus (HCV) infection and its association with liver fibrosis and response to treatment. This study included 90 patients with chronic hepatitis C. All patients received antiviral therapy in the form of pegylated interferon and ribavirin. Patients were grouped according to the stage of liver fibrosis by biopsy into: group 1 (fibrosis: 0 or 1); group 2 (fibrosis: 2 or 3) and group 3 (fibrosis: 4 or 5). The study included also 170 healthy subjects, as a control group. Polymerase chain reaction was carried out to detect the different ACE genotypes. The D/D genotype was significantly more prevalent among HCV patients compared to controls (65.6% vs 48.2%, P = 0.006). Degree of necroinflammation was significantly higher among patients with I/I genotype when compared to patients with D/D genotype (P = 0.04). No significant difference in the distribution of the ACE I/D genotypes between the fibrosis groups and between responders and non responders to interferon therapy. The D/D genotype may increase the susceptibility to infection with hepatitis C.     

The influence of HCV infection and immunomodulating therapy (interferon-alpha and ribavirin) on the condition of minor salivary glands and oral mucosa

The aim of the study was to determine an influence of HCV infection and combination therapy with interferon - alpha and ribavirin on the condition of oral mucosa and minor salivary glands in patients with chronic hepatitis C in comparison to subjects without liver pathology on 12-month follow-up. Patients with chronic hepatitis C more commonly develop pathological changes on the oral mucosa than patients without liver pathology. Combination therapy affects the amount of pathological lesions in the oral cavity of patients suffering from chronic hepatitis C and B. The occurrence of oral lichen planus on the oral mucosa may be associated with chronic hepatitis C as well as with concomitant alpha-interferon and antiviral therapy.     

The role and possibilities of natural interferon treatment in chronic hepatitis C: experience with natural interferon treatment for patients barred from combined antiviral therapy because of the STOP rule

The first choice, and the most efficient therapy for chronic hepatitis C is the pegylated interferon + ribavirin treatment. The introduction and application of the STOP rule (pegylated interferon + ribavirin treatment should be stopped in cases without sufficient virological answer for the therapy at the 12th or 24th week of the treatment) is motivated by the very high cost of this treatment. Aims: The greatest problem of the application of the STOP rule is that these patients are not coming in for the proven advantages of one-year interferon treatment (arrest or decrease the inflammation, decrease or prevent the progression to liver cirrhosis, decrease probability or prevent the development of hepatocellular carcinoma), which were observed almost in virologically slow-, partial-, or non-responder patients who received one-year interferon therapy. Based on these data, the official Hungarian treatment protocol allows and recommends the continuation of the antiviral treatment by natural interferon for patients whose pegylated interferon + ribavirin treatment should have been stopped because of the STOP rule. Patients and methods: 15 patients whose pegylated interferon + ribavirin treatment should have been stopped because of the STOP rule (8 men, 7 women, age: 35-63, mean: 48.8 years, HCV genotype: 1b, HAI mean: 6.7, SD: +/-5.03; stage: mean: 1.75 SD: +/-0.9) treatment was continued with natural IFN for further 16-36 (mean 23.7) weeks. The total treatment duration was 48-52 weeks. The duration of follow-up was at least 6 months. Control group: 18 patients whose pegylated interferon + ribavirin treatment should have been stopped because of the STOP rule (7 men, 11 women, age: 32-63, mean: 48.7 years, HCV genotype: 1b, HAI mean: 10.1, SD: +/-4.8; stage mean: 2.0 SD: +/-0.6). The duration of follow-up was at least 6 months. Results: There is no significant difference between the two groups. The ALT level significantly decreased (73.4 U/l SD: +/-25.5 versus 45.9 U/l SD: +/- 22.1) due to pegylated interferon + ribavirin treatment, and remained at this level during the natural interferon treatment and the follow up (45.7 U/l SD: +/-15.1, and 49.3 U/l SD: +/-19.4 U/l; p < 0.001). The difference is significant. The ALT level decreased (108.5 U/l SD: +/-69.8 versus 86.0 U/l SD: +/-82.8) due to pegylated interferon + ribavirin treatment, but increased after the cessation of the therapy (99.7 U/l SD: +/-60.9) in the control group. The biochemical response (significant reduction of ALT level) which was detected during the pegylated interferon + ribavirin treatment remained permanent during the continuation and after the cessation of the therapy in the natural interferon treated group, while relapse occurred in every case in the control group. The viral load increased at least 1 log 10 after cessation of the therapy in pegylated interferon + ribavirin treatment non-responder patients. The natural interferon treatment was able to control the viral replication (prevent the increasing of the viral load), but after the termination of natural interferon dosage, similar elevation of viral load was observed. The subjective side effects of natural interferon treatment were rarely and milder. Leucopenia and thrombopenia occurs rarely and was milder than that during the pegylated interferon + ribavirin therapy. Conclusions: The patients have no difficulty in the application of natural interferon; probably the positive psychic effect of the fact that they have not been barred from treatment compensated the technical hardness (three injections weekly). A wide range of the application of this therapeutic possibility, and further studies with larger number of patients are suggested.     

Hepatitis C viral infection and depression

About 170 million individuals can be found with chronic hepatitis C viral infection all over the world. The occurrence of depression is more frequent among the persons than in the healthy population, this depression can be found in 58 per cent of patients with chronic hepatitis C. On the basis of the literature the authors review the aetiology of depression in liver diseases, examining the neuropathogenic effect of HCV. They demonstrate the scientific results which are evidences of hepatitis C viral infection for the alterations in the central nerve system. The depression is one of the side effects of the alpha-interferon treatment used in the therapy of HCV. The authors demonstrate the biological basis, development, consequences of depression produced by interferon and they give a review of the protocol in the diagnostic procedure of a patient with depression. They summarize the steps of psychiatric drug therapy in chronic liver diseases. That is also important whether the chronic HCV infected patient with depression can be treated with interferon. The loss of interferon treatment can lead to the fatal outcome of liver disease. In order to have the correct decision a collaboration between internist and psychiatric specialist is necessary.