Chronic non-A, non-B Hepatitis Research Articles

Genotypic Profile of Hepatitis C Virus (HCV) in Patients Attending the Medical Outpatient Department in Bingham University Teaching Hospital Jos Nigeria for Chronic HCV Infection

INTRODUCTION: HCV is recognized as the major cause of transfusion associated and sexually transmitted sporadic chronic non-A non-B hepatitis. There is a high degree of genetic variability from HCV genomes isolated from infected patients. Currently, HCV isolates are classified into at least six major genotypes and numerous sub- genotypes. The genetic diversity of HCV and the clinical and virological relevance of HCV genetic classification schemes remain important areas of active research. OBJECTIVES: The objective of this study was to determine the genotypic profile of hepatitis C virus (HCV) in patients who are infected with chronic HCV with or without liver cirrhosis and hepatocellular carcinoma, receiving treatment at the medical outpatient department (MOPD) of the Bingham University Teaching Hospital Jos Nigeria with a view to seeing which of these genotypes is more prevalent. METHODS: This prospective cohort study enrolled patients who were clinically diagnosed to have chronic HCV infection and subsequently confirmed by polymerase chain reaction (PCR) using the light cycler. Patients attending the clinic from December 2012 to December 2014 who had all the relevant investigations done were enrolled in the study. This was regardless of whether they were profiled for commencement of treatment or not due to disease stage. RESULTS: A total of 48 patients were enrolled for the study during the period. Out of this figure, genotype 1 patients accounted for 34 (70.8 %) to emerge the leading genotype in the centre. This was followed by genotype 4 with a very low value of 7(14.6 %) as the second while genotype 2 had 6 (12.5 %) and genotype 3 had only 1 (2.1 %) patient. CONCLUSION: The study has revealed that HCV genotype 1 is the most prevalent among the population studied followed by genotype 4 while other genotypes 2 and 3 were also encountered but with lesser prevalence.

Antihepatitis C virus status in hepatocellular carcinoma and the influence on clinicopathological findings and operative results.

Antihepatitis C virus (HCV) status was investigated in 100 patients undergoing hepatectomy for hepatocellular carcinoma (HCC) between 1980 and 1989. The clinicopathological findings and operative results, in patients with or without HCV marker, were compared retrospectively. The positivity rate of anti-HCV was 51 per cent. In this group there was a higher mean age, fewer symptoms, raised alanine aminotransferase level, higher 15-min indocyanine green clearance rate and earlier tumour stage compared with the anti-HCV negative group. Positive tumour margins and vascular invasion were seen less frequently in the anti-HCV positive group. HCC with HCV marker showed characteristic features of chronic non-A non-B hepatitis and of HCC originating from liver cirrhosis. There was a better cumulative 1-year survival rate for anti-HCV positive patients, but 3- and 5-year survival rates after hepatectomy were similar in both groups. Although HCV-related HCC had typical features of chronic non-A non-B hepatitis and a relatively early stage of tumour, biological features and operative results were similar with or without the HCV marker.

Age and platelet count: a simple index for predicting the presence of histological lesions in patients with antibodies to hepatitis C virus. METAVIR and CLINIVIR Cooperative Study Groups.

The aim of this study was to identify clinical and biological factors associated with histological lesions in patients with chronic hepatitis C and to construct a simple diagnostic index. A database consisting of 500 patients with untreated biopsy-proven chronic non-A non-B hepatitis was used. Liver biopsies were reviewed, blind, by a panel of pathologists. Patients were classified according to the presence of necroinflammatory lesions (histological activity) and fibrosis. The diagnostic value of nine clinical and 10 biological factors was assessed using logistic regression analysis, sensitivity, specificity and predictive values, and a score was constructed combining the most significant factors identified. The validation used an independent population of 120 patients. Serum platelet concentration and age were the two main factors significantly and independently correlated with the presence of fibrosis and/or histological activity. A simple score referred to as AP, combining age and platelet count, varied from 0-10. For the presence of significant histological disease (moderate to severe necroinflammatory lesions and/or septal fibrosis to cirrhosis), an AP score of 6 or more had a specificity of 0.93 and a sensitivity of 0.52%. In the validation population, the area under the curve was 0.690 +/- 0.085, not significantly different from that of the first population, 0.763 +/- 0.043. Hence, a simple score combining age and platelet count enabled the accurate prediction of the presence of activity and fibrosis in patients infected with the hepatitis C virus. When this score reached 6, liver biopsy could be avoided owing to its high predictive value. However, the negative predictive value was not high enough to prevent a liver biopsy in patients with a lower score.

Disease Markers in Blood Donors at King Fahad Hospital, AL BAHA

A total of 4683 donated blood units were screened for HCV-Ab, HBs-Ag, VDRL, malaria parasites and ALT between January 1993 and April 1994. Of the blood units, 7.7% were positive for one or two hepatitis markers (HCV-Ab, HBs-Ag), while 4.6% were positive for HCV antibody, and 3.3% of the 4.6% were accounted for by Egyptian blood donors. Thus, 73% of all positive blood units for HCV-Ab were from Egyptian donors, while the rate of positive blood units for Saudi blood donors was 0.9%. Three and one-tenth percent of the total blood units were positive for HBs antigen, 2.3% from the Saudi population. Thus, 75% of all positive blood units were from Saudi donors. The percentage for HBs-Ag blood units for Egyptians was 0.3%. The exact prevalence of HCV-Ab-positive blood units among Saudis was 1.2% and HBs-Ag-positive units was 3.3%. Prevalence of HCV-Ab-reactive blood units among Egyptians was 34% and HBs-Ag-positive units was 3.3%. HCV-RNA using PCR was detected in a total of 86% of the individuals reactive to HCV antibody. Forty-three percent of hepatitis-B- and/or C-reactive blood donors had elevated alanine aminotransferase (ALT). Elevated ALT was observed in a higher percentage among HCV-Ab-reactive blood donors as compared to HBs-Ag-reactive donors.

A comparison of hepatitis C virus (HCV) RNA and – antibody as markers of infection and predictors of infectivity

The diagnosis of hepatitis C virus (HCV) infection currently relies on the detection of antibody to HCV (anti-HCV). However, anti-HCV positivity may indicate past infection, current infection or possibly non-specific reactivity. For confirmation of current infection the virus needs to be assayed directly and this is possible by the polymerase chain reaction (PCR). The aims were to compare HCV RNA and anti-HCV as markers of infection in two groups of individuals: (i) a heterogeneous group with suspected HCV infection and (ii) a small group of blood and bone marrow donors, and their respective recipients. Serum samples were tested for alanine aminotransferase (ALT) as part of a liver function screen, for anti-HCV by ELISA II, and HCV RNA was detected by PCR. Single round and nested PCR was performed using primers designed from the sequence of the 5'-untranslated region of the HCV genome. Of the 36 subjects in the heterogeneous group, 19/22 anti-HCV-positive patients with chronic non-A non-B hepatitis (NANBH) were viraemic, and the majority (17/19) demonstrated elevated ALT. However, HCV RNA was undetected in seven anti-HCV-positive patients, four of whom suffered autoimmune hepatitis Type I and three were low risk blood donors. Of the remaining subjects (seven/36) who were anti-HCV-negative, three/seven were HCV-RNA-positive and included two with acute post-transfusion (PT) NANBH and a recent needlestick victim who contracted HCV. In the second group, four individuals (donors), including a mother with a history of drug use, were implicated in transmission to three recipients. ALT levels were normal in all donors but raised in two of the recipients. PCR determined which of two anti-HCV-negative blood donors was infectious, confirmed transmission between a bone marrow donor and recipient, and indicated that anti-HCV detected in a newborn child represented passive transfer of antibody. Anti-HCV detected by ELISA II is a useful marker of chronic HCV infection, particularly in association with raised ALT. However, HCV RNA is a superior marker of acute HCV infection, a more reliable predictor of infectivity and is more specific.

Chronic non-A, non-B hepatitis: role of hepatitis C virus.

Thirty three consecutive children with chronic non-A, non-B hepatitis (NANBH) were studied during a four year period to evaluate clinical and histological features and the role of hepatitis C virus (HCV). All patients were asymptomatic. Thirteen (39%) of them were anti-HCV positive. A history of parenteral exposure was significantly more frequent among anti-HCV positive (69%) than anti-HCV negative patients (15%). Aminotransferase serum values were not statistically different between anti-HCV positive and anti-HCV negative patients. Unlike adults, cirrhosis was never found in the children studied. Our results suggest that chronic NANBH is, during childhood, an asymptomatic disease and that the prevalence of HCV infection is lower than in adults. As the majority of the children with chronic NANBH showed no evidence of HCV infection, it seems unwarranted to identify NANBH with HCV infection in children. The lack of cirrhosis in paediatric patients is probably related to a shorter duration of liver disease.

Hepatitis C virus antibodies in a long-term follow-up of beta-thalassaemic children with acute and chronic non-A non-B hepatitis.

The presence of antibodies toward hepatitis C virus (HCV) was examined in 78 polytransfused beta-thalassaemic children. The anti-HCV status was correlated with acute and chronic non-A non-B (NANB) hepatitis that developed during a follow up of about 13 years. Anti-HCV was present in 83.3% of children with acute NANB hepatitis and in 82.9% of those with chronic NANB hepatitis. The percentage of chronic evolution was 56.7% for acute anti-HCV positive NANB hepatitis and 50.0% for anti-HCV negative NANB hepatitis. The long-term persistence of anti-HCV antibodies did not correlate with chronic evolution of liver infection in thalassaemic patients. Histological features of chronic hepatitis showed little or no difference between HCV associated or non-associated liver disease. The multifactorial liver injury in beta-thalassaemic children explains the high prevalence of cirrhosis (about 30%) observed in these patients with NANB hepatitis. On the other hand, independent of liver disease, some patients never seroconverted during the follow up in spite of the high number of transfusions suggesting the existence of "non-responders".

Detection of hepatitis C virus (HCV) RNA in paraffin embedded tissue sections of human liver of non-A, non-B hepatitis patients by in situ hybridization.

Localization of hepatitis C virus (HCV) RNA was investigated by non-radioactive in situ hybridization in human liver specimens of chronic non-A, non-B (NANB) hepatitis patients who were seropositive for antibodies to HCV (anti-HCV). For in situ hybridization, T-T dimerized synthetic oligodeoxynucleotide probes were used and DNAs hybridized in situ were detected immunohistochemically using specific antibodies against T-T dimer. The data demonstrates that HCV-RNA was localized in the cytoplasm of hepatocytes in human liver biopsies obtained from the patients with chronic NANB hepatitis seropositive for anti-HCV.

INTERACTION BETWEEN FK506 AND CLOTRIMAZOLE IN A LIVER TRANSPLANT RECIPIENT

FK506, a new and powerful immunosuppressant, has become the principal drug in the immunosuppressive regimens of organ transplant recipients at the University of Pittsburgh (1–3). It is well known that transplant patients often receive multiple-drug therapy, and that many of these co-administered agents can alter the kinetics of immunosuppressive drugs, such as cyclosporine and prednisone (4,5). In this communication we report for the first time a potential interaction between FK506 and the antifungal agent clotrimazole in a liver transplant recipient.

Interferon alpha 2B is effective in chronic non-A non-B hepatitis

Interferon alpha 2B is effective in chronic non-A non-B hepatitis

Treatment of chronic non-A, non-B hepatitis with interferon

The efficacy of interferon therapy (IFN) was investigated in 46 patients with chronic non-A, non-B (NANB) hepatitis, of would 40 (87.0%) were positive for anti-HCV antibody (Ab) (C-100-3). Three kinds of IFN were used; human lymphoblastoid interferon (HLBI), interferon alpha-2b and interferon beta. Total doses of IFN ranged from 1 million units (MU) to 10 MU and treatment duration ranged from 2 weeks to 144 weeks. Of 46 patients 34 (73.9%) responded to IFN. Nine patients have maintained normal ALT levels and 5 patients have maintained near-normal ALT levels for more than 6 months after cessation of IFN treatment. In these cases the titers of anti-HCV Ab had decreased significantly at the end of IFN therapy and 6 months after IFN therapy respectively. The mean age was young and the mean disease duration was short in effective cases. As for doses and treatment duration of IFN, low doses of IFN requires long treatment duration to acquire continuous efficacy and high doses of IFN requires rather short treatment durations. Therefore, early IFN treatment, higher doses and longer periods of IFN treatment may improve the response rate of patients with chronic NANB hepatitis.

Therapy of chronic viral hepatitis

Chronic infection with hepatitis B virus (HBV), the delta agent (HDV) or hepatitis C virus (HCV) carries high risks of chronic liver disease which can result in cirrhosis and hepatocellular carcinoma. Many antiviral agents have been tried to inhibit viral replication and thereby limit infectivity and the risks of eventual serious liver disease. Interferon offers a 30–40% chance of viral clearance to the hepatitis B carrier, offers a good chance of clinical response in parenterally acquired chronic non-A non-B hepatitis and may be of benefit for some patients with chronic delta infection.

Hepatitis C virus RNA genome in plasma of patients with non-A, non-B hepatitis

Recently, the assay system of anti-hepatitis C virus antibody (HCV-Ab) was developed. However, there is no clinically useful method to detect hepatitis C virus (HCV) itself. The authors recently developed a method to detect the HCV-RNA genome in plasma using polymerase chain reaction (PCR). In the present study, the specificity of this assay in detecting HCV infection was investigated. Freshly obtained 1 ml plasma specimens from 100 patients with various liver diseases and from 11 control subjects were studied. In patients with non-A, non-B (NANB) hepatitis-related liver diseases, HCV-RNA was detected in 2 out of 7 cases of acute hepatitis, in 29 out of 31 cases of chronic hepatitis, in 17 out of 21 cases of cirrhosis and in 2 out of 6 cases of hepatocellular carcinoma. On the other hand, no HCV-RNA was detected in 15 cases of various types of alcoholic liver diseases, in 12 cases of hepatitis B related liver diseases, and in 11 controls. HCV-RNA was detected in 2 of 6 drinkers with chronic hepatitis. The prevalence of HCV-RNA was not closely related to a history of blood transfusions. These results suggest that our method for HCV-RNA is specific for HCV infection and HCV infection is the likely etiology of most chronic NANB hepatitis cases. The clinical usefulness of our method is illustrated by the fact that we were able to study 100 patients and needed only 1 ml plasma per HCV-RNA assay.

Hepatitis C Virus Antibody in Poland

To assess the epidemiology of hepatitis C virus (HCV) in Poland, anti-HCV was studied in patients with acute and chronic non-A, non-B (NANB) hepatitis, in healthy adults, and in subjects at risk. Anti-HCV prevalence was 2% in 152 blood donors, 78% in 95 parenteral drug addicts, 21% in 112 alcoholics, and 86% in 42 patients with chronic NANB hepatitis. Among 34 prospectively followed patients with acute NANB hepatitis 17 (50%) developed anti-HCV. It seems that HCV infection is responsible for the majority of NANB hepatitis in Poland and is common in parenteral drug abusers and alcoholics.

Demonstration of viraemia patterns in haemophiliacs treated with hepatitis-C-virus-contaminated factor VIII concentrates

Sequential serum samples from previously untreated haemophiliacs in whom non-A, non-B hepatitis (NANBH) developed after they received factor VIII concentrate contaminated with hepatitis C virus (HCV) were tested by a commercial assay for the presence of antibodies to the C100 protein of HCV (anti-C100) and by "nested" PCR for the presence of HCV RNA sequences. Three temporal patterns of viraemia were observed: transient viraemia in acute resolving NANBH; viraemia lasting for several years in chronic NANBH; and intermittent viraemia in chronic NANBH, with an initial transient phase followed by recurrence after many months. In three of five cases the initial detection of serum HCV RNA was made before the onset of liver function test abnormality, many weeks or months before anti-C100 seroconversion. Diagnosis of acute HCV infection may therefore be possible much earlier by PCR than by existing serological techniques, but the timing of samples may be critical.

Does hepatitis C virus play a role in “non‐viral” chronic liver disease?

It has recently been suggested that the hepatitis C virus may play a significant role in chronic liver diseases, such as autoimmune chronic active hepatitis, which are usually attributed to non-viral causes. We tested for antibodies to hepatitis C virus (anti-HCV) in sera from 140 patients with well characterised "non-viral" chronic liver diseases as well as sera from 51 patients thought to have chronic non-A, non-B (NANB) hepatitis (acting as positive controls) and 25 patients with non-hepatic autoimmune disorders. As expected, 45 of 51 patients (88%) diagnosed as having chronic NANB hepatitis were anti-HCV seropositive. Among 26 patients with cryptogenic cirrhosis, 8 were anti-HCV seropositive; in 5 patients (22%) there was no apparent risk factor for parenteral transmission. In the remaining 114 patients with chronic liver disease, 10 patients (9%) were seropositive for anti-HCV. However, 5 of these patients had a significant risk factor for parenteral transmission of hepatitis C virus, leaving only 5 of 106 (4.7%) with unexplained positive anti-HCV test results. Among patients with high titres of circulating autoantibodies but no liver disease, no positive results occurred. It is concluded that hepatitis C virus infection may account for some cases of cryptogenic cirrhosis. Although anti-HCV occurs more commonly in patients with other "non-viral" chronic liver diseases than has been reported in the community (0.5%-1.2%), the low prevalence of the antibodies indicates that hepatitis C virus infection is unlikely to be important in the aetiology or pathogenesis of autoimmune chronic active hepatitis and other poorly understood chronic liver diseases.

A human T-cell clone cytotoxic for hepatocytes from patients with chronic non-A, non-B hepatitis

A human T-cell clone (TA-NB-2) which could lyse hepatocytes from patients with chronic non-A, non-B (NANB) hepatitis was established (Proc Natl Acad Sci USA 1989;86:2883-2887). TA-NB-2 cells belonged to CD3+ CD8+ cytotoxic T lymphocytes, and recognized the target hepatocytes by T-cell receptor without restriction by major histocompatibility complex (MHC) antigens. TA-NB-2 cells significantly lysed hepatocytes from 22 of 23 patients with chronic NANB hepatitis, whereas they lysed hepatocytes from only one of 17 control patients with chronic type B hepatitis, acute hepatitis B or acute hepatitis A. TA-NB-2 cells also significantly lysed hepatocytes from 4 of 5 patients with autoimmune liver disease. The results suggest that TA-NB-2 cells specifically recognize a NANB hepatitis-related antigen expressed on NANB hepatitis virus-infected hepatocytes by T-cell receptor in non-MHC-restricted manner. The results also suggest that most, if not all, cases of chronic NANB hepatitis are caused by one agent and that a portion of cases of autoimmune liver disease may be induced by infection with a NANB hepatitis virus.

Is the response to recombinant alpha interferon related to the presence of antibodies to hepatitis C virus in patients with chronic non-A,non-B hepatitis?

The purpose of this study was to determine whether the response of serum alanine aminotransferase (ALT) to recombinant α-interferon was related to the presence or absence of antibodies to hepatitis C virus (anti-HCV) in patients with chronic non-A, non-B hepatitis. A group of 65 patients with chronic non-A, non-B hepatitis was studied. The source of contamination was blood transfusion or administration of blood products in 32, intravenous drug addiction in 14 and unknown in 19. The patients received 1, 3 or 5 MU of recombinant α-interferon, three times a week, for 6 months. A complete response was defined as normal ALT by the end of recombinant α-interferon treatment. Sera collected before treatment were tested for anti-HCV with an enzyme immunoassay. The overall percentage of anti-HCV positive patients in the study group was 75%. There was no difference between the anti-HCV positive and the anti-HCV negative patients before the treatment with respect to age, sex ratio, source of contamination, serum albumin, prothrombin, bilirubin, ALT or prevalence of cirrhosis. In the anti-HCV positive and the anti-HCV negative groups, there was no difference in the proportion of patients receiving the 1, 3 or 5 MU dosage. The percentage of patients with complete response was not different in anti-HCV positive patients (48%) and in anti-HCV negative patients (50%). There was also no difference in the kinetics of the decrease of mean serum ALT levels between the two groups. Conclusion: the response of ALT to recombinant a-interferon administration is not different in anti-HCV positive and anti-HCV negative patients with chronic non-A non-B hepatitis. This observation is consistent with the view that hepatitis C virus or a closely related virus is responsible for the liver disease in anti-HCV negative patients with chronic non-A, non-B hepatitis.

Orthotopic liver transplantation in a patient with combined hemophilia A and B

A 38-year-old man with severe factor IX and mild factor VIII deficiencies complicated by cirrhosis secondary to chronic non-A non-B hepatitis underwent orthotopic liver transplantation as treatment for both the cirrhosis and his congenital coagulopathy. Intraoperative hemostasis was obtained with factor VII-depleted prothrombin complex concentrate and fresh frozen plasma. Factor VIII and factor IX levels were assayed frequently in the perioperative period, and both returned to normal within 24 hr and remained normal postoperatively. Liver transplantation can be considered as definitive therapy for hemophilia A and/or B with transfusion-related liver disease.

Hepatis C Virus: A Giant Leap Forward

A random–primed complementary DNA library was constructed from plasma containing the uncharacterized non–A, non–B hepatitis (NANBH) agent and screened with serum from a patient diagnosed with NANBH. A complementary DNA clone was isolated that was shown to encode an antigen associated specifically with NANBH infections. This clone is not derived from host DNA but from an RNA molecule present in NANBH infections that consists of at least 10,000 nucleotides and that is positive–stranded with respect to the encoded NANBH antigen. These data indicate that this clone is derived from the genome of the NANBH agent and are consistent with the agent being similar to the togaviridae or flaviviridae. This molecular approach should be of great value in the isolation and characterization of other unidentified infectious agents. A specific assay has been developed for a blood–borne non–A, non–B hepatitis (NANBH) virus in which a polypeptide synthesized in recombinant yeast clones of the hepatitis C virus (HCV) is used to capture circulating viral antibodies. HCV antibodies were detected in six of seven human sera that were shown previously to transmit NANBH to chimpanzees. Assays of ten blood transfusions in the United States that resulted in chronic NANBH revealed that there was at least one positive blood donor in nine of these cases and that all ten recipients seroconverted during their illnesses. About 80 percent of chronic, post–transfusion NANBH (PT–NANBH) patients from Italy and Japan had circulating HCV antibody; a much lower frequency (15 percent) was observed in acute, resolving infections. In addition, 58 percent of NANBH patients from the United States with no identifiable source of parenteral exposure to the virus were also positive for HCV antibody. These data indicate that HCV is a major cause of NANBH throughout the world.