The hepatitis C virus (HCV) causes acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma, as well as extrahepatic manifestations such as malignant lymphoma. Currently, direct-acting antiviral agents (DAAs) against HCV infection can lead to a sustained virological response (SVR) in almost all HCV-infected patients. In this review article, we discuss acute exacerbation and alanine aminotransferase (ALT) flare in patients with chronic HCV infection. Although acute liver failure caused by HCV infection is rare, careful attention should be paid to the cases with ALT elevation during the natural course of chronic HCV infection. HCV genotype 2 infection, the use of rituximab, and a higher dose of corticosteroid are factors associated with HCV acute exacerbation and ALT flare. Treatment regimens for cancer have been interrupted or changed due to ALT flare due to HCV infection in some patients undergoing chemotherapy for cancer. The pathogenesis of HCV acute exacerbation and ALT flare could involve cellular as well as humoral immune responses. In the DAA era, the earlier introduction of DAAs may prevent chronic HCV-infected patients with acute exacerbation and ALT flare from developing into a more severe form, although DAAs may not be effective for all of them.

The majority of patients with hepatitis C virus (HCV) in China were infected via blood transfusion prior to the year 1996. In this systematic retrospective cohort study, disease progression in 804 consecutive patients with transfusion-acquired HCV is investigated. In addition, the occurrence of compensated cirrhosis, decompensated cirrhosis and hepatocellular carcinoma (HCC) is analyzed among these patients, along with the risk factors for disease progression. Patients with cirrhosis or HCC were classified as the serious development group (SD group) and the remaining patients with chronic hepatitis were classified as the hepatitis group (H group). Significant differences were found between the two groups in age at the time of infection, duration of infection and age at the time of observation. SD group patients were significantly older at the time of transfusion (33.73 vs. 23.56 years; P<0.001), with a significantly longer mean duration of HCV infection (21.88 vs. 21.15 years; P=0.029) compared with that in the H group. Male gender and age at the time of transfusion were significant risk factors for HCC (OR=2.48, P=0.031 and OR=1.07, P=0.002, respectively). Age was a significant risk factor for disease progression in older Chinese patients with transfusion-acquired HCV, and there were significant differences in the prevalence of compensated cirrhosis, decompensated cirrhosis and HCC between the age groups (P<0.001), suggesting that more patients with HCV may develop cirrhosis or HCC in their third and fourth decades of infection. Results of the present study will be helpful for predicting disease progression in Chinese patients with HCV infected via blood transfusion.

This review focuses on research findings in the area of diagnosis and pathogenesis of hepatitis C virus (HCV) infection over the last few decades. The information based on published literature provides an update on these two aspects of HCV. HCV infection, previously called blood transmitted non-A, non-B infection, is prevalent globally and poses a serious public health problem worldwide. The diagnosis of HCV infection has evolved from serodetection of non-specific and low avidity anti-HCV antibodies to detection of viral nucleic acid in serum using the polymerase chain reaction (PCR) technique. Current PCR assays detect viral nucleic acid with high accuracy and the exact copy number of viral particles. Moreover, multiplex assays using real-time PCR are available for identification of HCV-genotypes and their isotypes. In contrast to previous methods, the newly developed assays are not only fast and economic, but also resolve the problem of the window period as well as differentiate present from past infection. HCV is a non-cytopathic virus, thus, its pathogenesis is regulated by host immunity and metabolic changes including oxidative stress, insulin resistance and hepatic steatosis. Both innate and adaptive immunity play an important role in HCV pathogenesis. Cytotoxic lymphocytes demonstrate crucial activity during viral eradication or viral persistence and are influenced by viral proteins, HCV-quasispecies and several metabolic factors regulating liver metabolism. HCV pathogenesis is a very complex phenomenon and requires further study to determine the other factors involved.

The present manuscript represents an updated review on different aspects of immunology involved during hepatitis C virus infection in human beings. This includes a brief mention of HCV structure, presentation of viral components to host immune system, and ensuing immune response and immunopathogenesis occurring during HCV infection. The present article also highlights immunodiagnosis of HCV infection and the current status of immunotherapy available for HCV eradication. Its envelope protein, E2, is the primary mediator of virus attachment and cell entry. CD81 molecule on cell surface acts as a major receptor for viral entry into the host cells. Mature dendritic cells play an important role in presenting viral antigen, activate T-cells, and initiate anti-viral immune response. Relative T-cell populations and release of different cytokines from activated T-cells ultimately determine the clearance or persistence of HCV viremia through cellular and humoral immune responses. Natural killer (NK) cells constitute the first line of host defense against invading viruses by recruiting virus-specific T-cells and inducing antiviral immunity in liver. Diagnosis of acute or chronic hepatitis C virus (HCV) infection is established by serological assays for presence of antibodies against different sets of viral proteins during varied periods post infection. An effective immunotherapy and vaccine against HCV is still awaited.

Hepatitis C virus (HCV) causes a persistent infection, chronic hepatitis, and hepatocellular carcinoma. Since there are several reports indicating that some viruses influence the tumor suppressor p53 function, we determined the effects of HCV proteins on p53 function and its mechanism determined by use of a reporter assay. Among seven HCV proteins investigated (core, NS2, NS3, NS4A, NS4B, NS5A, and NS5B), only core protein augmented the transcriptional activity of p53 and increased the expression of p21(waf1) protein, which is a major target of p53. Core protein increased both DNA-binding affinity of p53 in electrophoretic morbidity shift assay and transcriptional ability of p53 itself in a reporter assay. The direct interaction between core protein and C terminus of p53 was also shown by glutathione S-transferase fusion protein binding assay. In addition, core protein interacted with hTAF(II)28, a component of the transcriptional factor complex in vivo and in vitro. These results suggest that HCV core protein interacts with p53 and modulates p53-dependent promoter activities during HCV infection.

Interferon therapy has a beneficial effect in patients with chronic hepatitis C who have a low viral load. The aim of this study was to compare the core protein level with HCV RNA levels and to analyze whether virus quantitation predicts the efficacy of interferon therapy.

HCV core protein level assessed by the recently developed assay was compared with HCV RNA levels measured by three different methods (Amplicor-HCV monitor, competitive RT(CRT)-PCR, and bDNA probe assay) in 352 patients with chronic hepatitis C in relation to viral serotype.

From 91% (320/352) to 93% (299/322) of patients with viremia were detected by Amplicor-monitor and CRT-PCR, in contrast to 60% (187/312) and 74% (191/258) by bDNA and HCV core protein assay, respectively. The HCV core protein level was positively correlated with HCV RNA levels measured by the three assays (r = 0.680 to 0.731). Serum HCV RNA and core protein levels were significantly lower in patients with serotype 2 than in those with serotype 1. Viral eradication after interferon therapy was observed in 60-70% of the patients with < 1 x 10(4) copies/ml of HCV RNA by Amplicor-monitor assay, < 2 x 10(5) copies/ml by CRT-PCR, < 0.5 Meq/ml by bDNA assay, and < 20 pg/ml of core protein by HCV core protein assay. Viral eradication was uncommon (< 11%) among the patients with higher viral loads. Bivariate analysis revealed that the outcome of interferon therapy was more closely associated with both HCV core protein and RNA levels than the HCV serotype.

Quantitation of HCV core protein and HCV RNA in useful for prediction of the interferon response.

There have been few prospective studies of hepatitis C virus (HCV) infection after needlestick accidents in hospital employees. In the present study, the prevalence and features of HCV infection after needlestick accidents were evaluated prospectively measuring serum HCV-RNA. Subjects were 56 employees who had HCV needlestick accidents. To monitor the development of hepatitis, the serum ALT levels and HCV-related seromarkers, such as first generation anti-HCV (RIA), second generation anti-HCV (PHA) and HCV-RNA (RT-PCR) were measured every month for at least 12 months after the accidents. Three of 56 (5.4%) recipients developed HCV infection. HCV-RNA was detected in all three recipients within 4 months after the exposure, and second-generation HCV antibody was detected in two of three recipients. The detection of HCV-RNA was earlier than that of HCV antibody. Two of three HCV-infected recipients developed type C acute hepatitis and one of two received interferon therapy; however, the other case received no medication. The detection of HCV-related seromarkers and the elevation of ALT levels were transient in these three recipients: thus, none developed chronic hepatitis. In conclusion, HCV infection developed in 5.4% of recipients within 4 months after HCV accidents. All of these HCV-infected recipients showed fair prognosis. HCV-RNA was a beneficial parameter for early detection of HCV infection.

The clinical manifestations of hepatitis C virus (HCV) infection are generally indistinguishable from other causes of viral hepatitis. HCV infections are usually anicteric, asymptomatic, and rarely cause acute fulminant liver failure. Serological testing for HCV in conjunction with epidemiological studies have verified that HCV was the major cause of parenterally transmitted non-A, non-B hepatitis (NANBH). With the widespread introduction of serological screening of blood products for HCV antibody, the risk of transfusion-associated HCV infection has been dramatically reduced (to < 3 cases per 10,000 units transfused). Despite the virtual elimination of transfusion-associated infections, the diagnosis of HCV remains important because > 50% of infections are sporadic in origin, 50 to 70% of infected individuals develop chronic hepatitis, and these individuals are at risk of developing cirrhosis (> 20%) as well as hepatocellular carcinoma. Although currently available anti-HCV immunoassays function well as blood-donor screening assays, they are poor at detecting acute infection because of the prolonged lag time between infection and detection of seroconversion (approximately 10 to 26 weeks for second-generation immunoassays). In contrast, polymerase chain reaction (PCR)-based detection of HCV RNA in serum can detect infection in as little as 1 to 2 weeks after exposure. This review focuses on the impact of modern serologic and nucleic acid-based HCV detection methodology on the clinical understanding of HCV infection, its associated illnesses, and its transmissability. Quantitative and reproducible nucleic acid-based detection assays will be required to provide additional insights into the clinical spectrum of HCV infections as well as to assess the efficacy of antiviral agents.

Non-A, non-B acute hepatitis progresses to a higher incidence of chronicity and hepatocellular carcinoma. To avoid the development of chronic liver disease, resolution of acute hepatitis C might be most effective. The aim was to establish the effect of interferon in disturbing progression to chronicity and to determine the most appropriate treatment protocol.

Ninety-seven acute non-A, non-B hepatitis cases were randomly assigned to six different protocols and treated with 8.4-336 MU of interferon; 90 cases were finally completely analyzed. Titers of hepatitis C virus (HCV) RNA and HCV genotypes were determined.

Seventy-four cases were positive for second-generation anti-HCV. Of these, 65 (89%) were positive for HCV RNA. In these 65 cases, the resolution rate was 32%, and this rate was dependent on the total treatment dosage. Only the group treated with 336 MU showed a high (83%; 10/12) resolution rate; the other five groups had 0%-38% resolution.

Interferon treatment for acute hepatitis C could be regarded as a "vaccinelike" therapy by preventing the development of the virus carrier state.

The aim of the study was to evaluate the specificity and sensitivity of detection of hepatitis C virus (HCV)-RNA in formalin-fixed paraffin-embedded (FFPE) liver biopsies by polymerase chain reaction (PCR). Routinely processed FFPE diagnostic needle liver biopsies as well as stored serum samples from 43 patients with liver disease were tested for HCV-RNA by reverse transcription-nested PCR using the same sets of primers and following strict anticontamination measures. Twenty-nine cases were positive and 14 were negative for serum HCV-RNA. Tissue HCV-RNA was detected in 17 out of the 29 serum HCV-RNA-positive cases but not in any of the 14 serum HCV-RNA-negative cases. Compared to serum-PCR, tissue-PCR was 100% specific, 58.6% sensitive, and 72% efficient. HCV-RNA was detected more frequently in biopsies stored for less than 1 year, than in those stored for more than 1 year (P = 0.046). In biopsies stored for up to 1 year detection of HCV-RNA by PCR was 81.8% sensitive and 90.9% efficient. Short (< 0.5 cm) liver biopsies were as sufficient for nucleic acid extraction and amplification as long (> 0.5 cm) ones. It is concluded that following strict anticontamination measures, HCV-RNA detection by PCR in routinely fixed, processed, and stored diagnostic liver biopsies provides a valuable adjunct to diagnosis of HCV infection. In this study, this option was free from contamination problems, even though routine batch histological processing schedules were used.