Occult HCV Research Articles

Prevalence of occult hepatitis C in egyptian patients with non alcoholic fatty liver disease

This study aim is to assess the prevalence of occult HCV infection among Egyptian patients with non alcoholic fatty liver disease (NAFLD) with elevated AST and ALT, and to correlate presence of occult HCV with severity of liver disease. Patients and Methods: After informed consent 27 patients with elevateed liver enzymes diagnosed as NAFLD were examined for demographic, clinical, laboratory data and Ultrasonography. Liver biopsy was done and tested for HCV RNA in tissue. Genotyping using RFLP analysis of PCR products in the 5’NCR was done for positive cases. Results: HCV RNA in tissue was positive in 11/27 patients (40.7%); genotype was 4a in all positive cases. AST and ALT values showed significantly lower values in occult HCV than the non HCV NAFLD group. Liver biopsy of studied patients showed no significant difference as regard inflammation and fibrosis according to METAVIR score. Conclusions: Occult HCV is highly prevalent among Egyptian NAFLD patients. It seems to induce a mild liver disease. Patients with elevated ALT and negative HCV RNA in sera might be investigated for tissue HCV RNA. Follow up is recommended for the occult HCV patients to monitor progression to overt disease.

Durability of antiviral therapy for chronic hepatitis C after achieving sustained virological response

See Article on Page 183 Hepatitis C virus (HCV) causes various liver diseases including acute hepatitis, chronic hepatitis, health-holders, liver cirrhosis and hepatocellular carcinoma.1 Acute hepatitis C progresses to chronic hepatitis from 75 to 85% and cirrhosis after 20-25 years later. In patients with HCV-positive cirrhosis, the annual incidence of hepatocellular carcinoma has been reported as 5% approximately.1 The current standard antiviral treatment with peginterferon and ribavirin combination therapy is effective in about 50% of patients with chronic hepatitis C. It is assumed that achievement of sustained virological response (SVR) after the combination therapy, confirmed by means of commercial HCV RNA detection assays is regarded as a cure for chronic hepatitis C (Table 1). It is associated with histological improvement, reduced the risk of hepatocellular carcinoma and liver related mortality, and improved quality of life. Table 1 Commercially available HCV RNA detection assays For the respect of the durability of SVR, several studies have been reported. Marcellin et al2 reported that an SVR after antiviral therapy was associated with long-term biochemical and virological responses as well as histologic improvement. Eighty-patients who had SVR after interferon-alpha monotherapy, mean follow-up of 4 years showed that 96% had undetectable serum HCV RNA. In a large-scale clinical trials, 7 (2%) among 400 sustained virological responder had detectable hepatic HCV RNA during follow-up; 5 have been followed and 2 (0.5%) were reappearance of serum HCV RNA at 12 months after therapy.3 Many other reports including the study of Choi et al4 confirmed that late relapse is rare after achievement of an SVR with completion of interferon without or with ribavirin therapy (Table 2).5-13 On the other hand, earlier reports showed higher rate of late relapse.14-16 These discrepancies may be resulted from use of HCV polymerase chain reaction (PCR) assays with varying degrees of sensitivity and a range of patient populations. As a result, the true durability of the response remains unclear, and the optimal follow-up for patients who have achieved an SVR is unknown. Table 2 Reappearance rates of serum HCV RNA after achieving SVR Even then achievement of an SVR, there are many evidences that HCV can persist and replicate in peripheral blood mononuclear cells, hepatic tissue and other organs including kidney, heart, pancreas, intestine, adrenal gland, lymph node and gallbladder in spite of still undetectable serum HCV RNA.3,17-21 It is so called HCV, which can be reservoir of reappearance HCV RNA in serum3,21 and thus play a role in the persistence and reactivation of infection. Highly sensitive reverse transcription and nested PCR assays detected residual HCV RNA in case of occult HCV. However, these assays are not currently standard diagnostic procedures and whether these findings actually represent a replication-competent virus or have any clinical significance is not clear. The immunologic mechanism of HCV recurrence after SVR is also not well investigated. Quiroga et at22 reported HCV-specific cellular immune responses are stronger in occult HCV infection than in chronic hepatitis C and it would be the cause of the rare incidence of late relapse. For the factors affecting the durability of SVR, no distinct pattern of baseline characteristics could be identified. Several studies with small number of patients reported the transfusion, injection drug use or dose reduction as a risk factor. However, it was unknown whether these cases reflect relapse or re-infection because of the paucity of paired samples. Although there is reappearance of serum HCV RNA in approximate 1% of patients with an SVR, individuals who have achieved an SVR should have a single additional follow-up HCV RNA measurement performed to ensure that the negative HCV RNA result at 6 months posttreatment was not a false negative possibly due to faulty sample collection. If the second posttreatment HCV RNA measurement is negative, the SVR appears to be durable and a reliable sign of cure after antiviral therapy in chronic hepatitis C. However, it is recommended to follow up serum HCV RNA for a long time after an SVR for those individuals who show intermittent viral breakthrough during treatment or who may be considered at risk for reinfection or late relapse.

A novel FRET probe-based approach for identification, quantification, and characterization of occult HCV infections in patients with cryptogenic liver cirrhosis

A novel FRET probe-based approach for identification, quantification, and characterization of occult HCV infections in patients with cryptogenic liver cirrhosis

Occult hepatitis C virus infection and associated predictive factors: The Pakistan experience

The aim of the present study was to determine the presence of HCV RNA in the liver biopsies of patients with abnormal liver tests but without detectable serum HCV RNA and anti-HCV antibodies in sera. Liver biopsies and whole blood of total 31 patients who were negative for anti-HCV antibodies with elevated liver function tests were received at Division of Molecular Diagnostics, University of the Punjab Pakistan from January 2002 to June 2009 for the detection of HCV RNA. HCV RNA status of the subjects was tested by reverse-transcription PCR and quantified using SmartCycler II real-time PCR. HCV genotyping was carried out in HCV RNA positive samples using molecular genotyping method. HCV RNA was found in liver-biopsy specimens from 23 (74.2%) of the total 31 patients negative for anti-HCV antibodies and undetectable serum HCV RNA. HCV RNA of both negative and positive polarity was found in the livers of 8 (25.8%) patients. Genotyping analysis showed that 65% patients were infected with HCV 3a, 17% with 3b, 13% with 1a and 4% patients were found with untypable genotype. In a multivariate logistic regression model, patients having previous history surgeries, male sex and age above 30 years were significantly associated with the presence of occult HCV infection (p<0.05). In conclusion, patients with elevated liver enzymes and negative HCV antibodies and negative serum RNA may have occult HCV infection and its chance increases with previous history of surgeries, in male sex and above 30 years of age.

T1974 Evidence for Considerable Undertreatment of Chronic Hepatitis C Infection in HIV-HCV Coinfected Patients

Among anti-HCV-positive patients with secondary occult HCV infection antibody reactivity was more frequently detected against core21–40 (100%) compared with core5–19 (9/11, 82%) and core101–120 (8/11, 73%) epitopes. All chronic hepatitis C patients had detectable antibodies to all three core epitopes (P< 0.01 vs occult HCV infection). Conclusions: Anti-core is detectable in 53% patients with primary occult HCV infection despite lacking serum anti-HCV and HCVRNA using commercial tests. Multiple core peptides allowed a 12% improvement in the sensitivity of the serodiagnosis of primary occult HCV infection and suggest a distinctive core antibody pattern according to HCV infection outcome.

Hepatitis B and Hepatitis C Prevalence and Treatment Referral Among Asian Americans Undergoing Community-Based Hepatitis Screening

We sought to identify cross-sectional hepatitis B virus (HBV) and HCV prevalence among Asian Americans at a community health fair and to assess referral rates. We determined HBV prevalence with hepatitis B surface antigen (HBsAg), antibodies to hepatitis B core antigen (anti-HBc), and antibodies to hepatitis B surface antigen (anti-HBs). We determined HCV prevalence with hepatitis C antibodies. Successful referral occurred when participants with HBV or HCV were contacted, medically evaluated, and given contact information of liver specialists for care. Of 202 people screened, 118 were Asian Americans (65 Chinese and 39 Vietnamese). Twelve had chronic HBV with positive HBsAg. However, chronic HBV prevalence increased from 10.2% to 13.6% by concomitant HBsAg, anti-HBc, and anti-HBs testing. Prevalence of HCV was 6% overall but 15.4% among Vietnamese. Overall, 83% of patients with chronic HBV and 100% of patients with occult HBV or HCV were successfully referred. Concomitant HBsAg, anti-HBc, and anti-HBs testing permits diagnosis of chronic, occult HBV infections missed by testing with HBsAg alone. Persons identified with HBV or HCV at community health fairs can be successfully referred.

Detection of Occult Hepatitis C and Hepatitis B Virus Infections from Peripheral Blood Mononuclear Cells

Purpose: To investigate the problem of occult HCV & HBV infections in patients with persistently longstanding abnormal liver function test results of unknown etiology and to investigate occult HCV in patients with sustained virological response (SVR). Methods: The study included two groups; first group included 40 patients with persistently longstanding abnormal liver function test, in addition to 62 patients with history of hepatitis C who developed SVR. HCV RNA status was tested in serum by conventional RT-PCR and by real-time PCR in Peripheral Blood Mononuclear Cells (PBMCs). HBV DNA in PBMCs was done in first group only. Results: In first group, PCR in PBMCs was positive for HCV RNA in 4 patients with elevated liver enzymes and HBV DNA was positive in PBMCs in 3 patients. In patients with SVR, 7 patients were positive for HCV RNA in PBMCs. Conclusions: Patients with long-standing abnormal results of liver-function tests with unknown etiology may have HCV RNA or HBV DNA in their PBMCs in the absence of anti-HCV antibodies, HBV markers, serum HBV DNA and serum HCV RNA.In Patients with SVR, HCV RNA in PBMCs is recommended to detect residual infection especially in those with high serum HCV RNA levels before treatment.

PP-140 The occult HCV infection

PP-140 The occult HCV infection

Identification of serologically silent occult hepatitis C virus infection by detecting immunoglobulin G antibody to a dominant HCV core peptide epitope

Occult HCV infection has been described among anti-HCV-HCV RNA-negative individuals with abnormal transaminase values in whom HCV RNA is detected in liver. IgG antibody to an HCVcore-derived peptide (anti-HCVcore) was investigated in 145 patients with serologically silent occult HCV infection. At the time of the diagnostic biopsy 45/145 (31%) occult HCV-infected patients tested IgG anti-HCVcore-positive but none of the 140 patients with HCV-unrelated liver disease (P<0.001). Among 23 IgG anti-HCVcore-positive patients at baseline, 22 remained antibody-reactive (one became antibody-negative). Similarly, 17/31 baseline anti-HCVcore-negative patients remained non-reactive whereas 14 seroconverted to IgG anti-HCVcore (although transiently in 10 patients). Thus, a total of 59/145 (40.7%) patients with occult HCV infection showed IgG anti-HCVcore reactivity at any time point analyzed, including 14 initially non-reactive patients. By supplemental immunoblot assay 16 sera reacted weakly with an HCVcore-peptide band (indeterminate result) of which 10 (62.5%) reacted in the IgG anti-HCVcore assay. Occult HCV-infected patients who tested anti-HCVcore-positive showed more frequently signs of necro-inflammation (P=0.035) and greater percentages of HCV RNA-positive hepatocytes (P=0.004) compared with those anti-HCVcore-negative. This work documents that IgG anti-HCVcore testing identifies occult HCV infection among seronegative, non-viremic patients using screening tests and may be useful in tracking anti-HCV-negative infections.

Occult hepatitis B virus and hepatitis C virus infections

Occult HBV infection is a well-recognised clinical entity characterised by the detection of HBV-DNA in serum and/or in liver in the absence of detectable hepatitis B surface antigen (HBsAg). Occult HBV infection has been described not only in patients who have resolved an acute or chronic HBV infection but also in patients without any serological markers of a past HBV infection. Occult HBV infection in patients with chronic HCV infection may induce more severe liver disease and lower response rate to interferon treatment. The existence of occult HCV infections has been also reported more recently. Occult HCV infection is characterised by the presence of HCV-RNA in liver and peripheral blood mononuclear cells in the absence of detectable serum HCV-RNA. Occult HCV infection may occur under two different clinical situations: in hepatitis C antibody-(anti-HCV) negative and serum HCV-RNA-negative patients with abnormal liver function tests and in anti-HCV-positive patients who have no detectable serum HCV-RNA and who have normal liver enzymes. The clinical relevance of occult HCV infections is still under investigation.

753 INSULIN RESISTANCE IS INDEPENDENTLY ASSOCIATED WITH ADVANCED LIVER FIBROSIS AND HIGH BODY MASS INDEX IN HIV/HCV-COINFECTED PATIENTS

Results: Among 145 patients with serologically silent occult HCV infection 45 (31%) tested anti-HCVcore-positive at the time of the diagnostic biopsy. Anti-HCVcore was detected in 143/145 (98.6%) chronic hepatitis C patients but in none of the 140 patients with HCV-unrelated liver disease (P< 0.001). A serological follow-up was conducted in occult HCV-infected patients (every 3−6 months for at least 12 months). Among 23 anti-HCVcorepositive patients at baseline, 18 remained antibody-reactive on all occasions tested; anti-HCVcore fluctuated in 4 (from positive to negative and viceversa) and was lost in one patient. Similarly, among 31 anti-HCVcorenegative at baseline, 17 remained antibody non-reactive; however, 4 patients seroconverted to anti-HCVcore and remained so whereas antiHCVcore became reactive in 10 patients on at least one occasion. Thus, a total of 59/145 (40.7%) patients with occult HCV infection reacted in the anti-HCVcore assay at any time-point analyzed, including 14 initially non-reactive patients. By supplemental anti-HCV immunoblot assay 16/83 (19.2%) sera reacted weakly with a single core-peptide band (indeterminate test result) of which 10/16 (62.5%) reacted in the anti-HCVcore ELISA. According to anti-HCVcore status, occult HCV-infected patients who tested anti-HCVcore-positive showed significantly greater scores of necroinflammation (P = 0.046) and percentages of HCVRNA-positive hepatocytes (P = 0.004) compared with the anti-HCVcore-negative counterparts. Conclusion: Anti-HCVcore is detectable in 40% patients with serologically silent occult HCV infection. Anti-HCVcore testing improves serodiagnosis of HCV infection in patients lacking serum anti-HCV and HCVRNA using commercial tests. This anti-HCVcore assay may be useful in tracking subclinical HCV infections.

Molecular Diagnosis of Occult HCV and HBV Infections

Occult HCV and HBV infections are recently identified entities whose existence became evident when nucleic acid amplification assays of enhanced sensitivity were employed for the detection of viral genomes and their replicative intermediates. These long-term silent infections are consequences of persistent low-level viral replication progressing in hepatocytes as well as in cells of the immune system. Detection of these new forms of HCV and HBV persistence requires a thorough testing approach in which analysis of serial serum and peripheral blood lymphoid cell samples and, when feasible, liver tissue samples is performed under strict contamination-controlled conditions using nucleic acid amplifications targeting different regions of viral genomes. This review focuses on the identification and general characteristics of occult HCV and HBV infections, and also acknowledges data from experimental occult infection in the woodchuck model of hepatitis B.

527 Persistent hepatic alterations in individuals with occult HCV infection following sustained virological response to antiviral therapy

527 Persistent hepatic alterations in individuals with occult HCV infection following sustained virological response to antiviral therapy

Delayed treatment of acute hepatitis HCV? Yes, but when, who, and how?

Delayed treatment of acute hepatitis HCV? Yes, but when, who, and how?

Occult viral hepatitis: What is the significance?

Occult viral hepatitis: What is the significance?

High frequency of occult HCV infection in HD patients

Occult HCV infection in liver and peripheral blood mononuclear cells (PBMC) of patients with cryptogenic chronic hepatitis (anti‐HCV, serum HCV RNA negative) and no renal diseases, has been reported (1). In this work we studied the existence of occult HCV infection in PBMC of HD patients. Inclusion criteria: high ALT (&gt;28 IU/l) and/or gamma‐GPT levels, negative serological HCV and HBV markers (anti‐HCV, serum HCV‐RNA and HBsAg negative), and exclusion of other causes of liver damage. Four Spanish HD units participated in the study and 40 patients were enrolled; 40 (25 males) fulfilled the inclusion criteria. HCV‐RNA in PBMC was tested by RT‐PCR and by in situ hybridization. Occult HCV infection was found in 24/40 (60%) patients by RT‐PCR and all cases were confirmed by in situ hybridization. No differences were found regarding gender, etiology of renal disease, or fluctuant or persistent abnormal liver enzymes values. Among patients with occult HCV infection, 4/24 (16.7%) had only increased ALT levels; 7/24 (29.2.%) GGTP values; and both enzymes were elevated in 13/24 (54.2%).In our population, 60% HD patients with persistent or fluctuant ALT and/or GGTP values of unknown etiology and negative for serological viral markers (including serum HCV‐RNA) have an occult HCV infection in PBMC and these patients could be potentially infectious.(1)J Infect Dis 2004;189: 7–14.