The lack of transmission of NANB/C hepatitis between acute and chronically infected patients and their heterosexual partners

In order to study the risk of heterosexual transmission of non-A, non-B/C (NANB/C) hepatitis, 34 spouses and/or sexual partners to 34 index patients (13 women, 21 men; median age 39 years) with acute NANB/C hepatitis (anti-HCV positive 13/34) were repeatedly tested for antibodies to hepatitis C virus (anti-HCV) and serum alanine aminotransferase (S-ALAT) values. Spouses and/or sexual partners to 13 patients with chronic NANB/C hepatitis (11/13 anti-HCV positive) were also studied by determining anti-HCV and S-ALAT levels. No conclusive evidence of heterosexual transmission of NANB/C hepatitis was found.     

Decrease in reported posttransfusion hepatitis. Contributions of donor screening for alanine aminotransferase and antibodies to hepatitis B core antigen and changes in the general population.

Blood donor screening for hepatitis B core antibody and elevation of serum alanine aminotransferase level, surrogate markers of hepatitis C/non-A, non-B (NANB) infection, was implemented in 1986. Reported cases of posttransfusion hepatitis (PTH) from 1985 to 1988 were reviewed to ascertain the effect of surrogate testing on the number and character of cases and to compare any changes with those in the incidence of hepatitis in the general population. The reports of all PTH, NANB PTH, and type B PTH decreased 61.5%, 75.4%, and 84.5%, respectively. The rates of reported cases of NANB hepatitis and hepatitis B in the general community also fell during the period of review. The decrease in PTH and background hepatitis was similar between 1985 and 1986. In 1987, the first complete year of surrogate testing, the incidence of PTH decreased at a greater rate, to levels 50% below what would have been projected on the basis of background changes alone for NANB PTH, and to 35% below projected for type B PTH. There appears to have been a substantial decrease in the risk of both type B PTH and NANB PTH in the northeastern United States between 1985 and 1988 due to a combined effect of donor surrogate testing and a decrease in the background rates of hepatitis in the donor population.     

The significance of blood transfusion in non-A, non-B chronic liver disease in Japan

We performed a follow-up study on 70 patients with acute non-A, non-B (NANB) posttransfusion hepatitis and a retrospective study on 283 chronic hepatitis, 70 cirrhosis and 53 hepatocellular carcinoma patients of type NANB. In acute NANB post-transfusion hepatitis, as judged by the transaminase levels, th duration of the disease exceeded 6 months in 46/70 = 65.7% and 1 year in 32/70 = 45.7%. The histological diagnosis of the 32 cases persisting for more than 1 year was chronic active hepatitis in 5, chronic persistent hepatitis in 2 and unresolved hepatitis in 6. The frequency of previous transfusion in chronic hepatitis, cirrhosis and hepatocellular carcinoma of type NANB was 42.8, 37.1 and 15.1%, respectively, whereas the incidence of early posttransfusion hepatitis was 8.5, 8.6 and 7.5%, respectively. in chronic liver diseases with a history of jaundice and/or hepatitis, previous transfusions are more frequently associated with type NANB than with type B disease. The present study demonstrates that NANB posttransfusion hepatitis tends to develop to chronic liver disease when analyzed prospectively as well as retrospectively.     

Prospective controlled study of posttransfusion hepatitis after cardiac surgery in a large referral hospital in India

ABSTRACT— We studied the risk of post-transfusion hepatitis (PTH) in recipients of blood collected from voluntary donors screened for HBsAg. Two hundred and fifty patients without any previous history of liver disease or transfusion were followed up for 12 months subsequent to cardiac surgery. Thirty-five of them had closed-heart surgery without receiving transfusion and served as controls. The remaining 215 patients received single-point transfusions (mean 4 ± 2.4 units). None of the controls and 15 (6.9%) blood recipients developed PTH. Three (20%) patients had hepatitis-B-virus-induced hepatitis while the remainder (80%) had non A, non B (NANB) hepatitis. The number of units of blood transfused and surrogate markers for development of PTH (donor alanine aminotransferase, anti-HBc and anti-HBs antibody) were not associated with the occurrence of PTH (p>0.05). Nine (60%) of the 15 patients developing PTH were asymptomatic. All the patients recovered from the PTH, except one who died of fulminant hepatitis. At the end of 1 year of follow-up, none of the patients had evidence of chronic hepatitis. Only three (25%) of the patients with NANB-PTH developed anti-hepatitis C virus (HCV) antibody during the follow-up. We conclude that the incidence of PTH in India is similar to other parts of the world and NANB virus was the major cause of the PTH. The absence of chronicity and lack of seroconversion to anti-HCV antibody in the majority of the patients after 1 year of follow-up may suggest the possibility of a NANB virus other than HCV as the major cause of PTH in India.     

Non-A, non-B hepatitis: evolving epidemiologic and clinical perspective

Evidence for the existence of human hepatitis agents besides HAV and HBV is compelling. Transmitted predominantly by transfusion and percutaneous inoculation, the type of NANB hepatitis encountered most frequently is epidemiologically similar to type B hepatitis. NANB hepatitis accounts for more than 90% of TAH, but can be transmitted by nonpercutaneous routes as well. Approximately 15 to 30% of sporadic hepatitis cases are attributable by serologic exclusion to NANB hepatitis agents, and, in addition, there is an epidemic form of NANB hepatitis that resembles hepatitis A epidemiologically in its transmission by the enteric route. Clinical features of the predominantly percutaneously transmitted forms of NANB hepatitis are similar to those of hepatitis B, but tend to be less severe during acute illness, on the one hand, but to lead more frequently to chronic hepatitis, on the other; 40 to 60% of patients with TAH have chronic elevations of aminotransferase activity, often in an episodic, fluctuating pattern. CAH can be identified histologically in a majority of patients with chronic NANB TAH. Despite a relatively quiescent course, progression of such chronic cases may be quite insidious; cirrhosis occurs in 10 to 20% of patients with chronic hepatitis after acute TAH. The frequency of chronic liver disease after nonpercutaneously acquired sporadic NANB hepatitis tends to be lower, on the order of 10% or less, and chronic hepatitis has not been recorded after the epidemic type of NANB hepatitis. Evidence supports the existence of an asymptomatic chronic NANB hepatitis carrier state that is several-fold more frequent than the chronic HBV carrier state. Neither viruses nor virus markers have been described that fulfill accepted criteria reproducibly for a specific causal association with NANB hepatitis; on the other hand, evidence suggests (but does not prove) the existence of two different blood-borne NANB hepatitis agents and, in addition, an enterically transmitted NANB hepatitis agent. Effective therapy for and immunoprophylaxis against NANB hepatitis are lacking. Until specific screening tests are developed, interim screening based on indirect, nonvirus-specific tests may be the only practical approach to minimizing the frequency of NANB hepatitis after transfusion. Identification of virus-specific serologic markers remains a high priority.     

Acute viral hepatitis in Lebanon: evidence for a HAV-like non-A non-B hepatitis

Ninety-three cases of acute viral hepatitis in adult Lebanese patients were followed-up prospectively for a period ranging from 6 to 18 months. These included 33 hepatitis A (HAV), 32 hepatitis B (HBV) and 21 non-A, non-B hepatitis (NANB) cases. The clinical and seroepidemiologic characteristics of the three types were evaluated. HAV was characterized by a short prodroma (less than 1 week) and a high IgM level. HBV did not differ from similar cases reported in the Western world except for a complete absence of male homosexuals and drug addicts as a possible route of transmission. NANB hepatitis in Lebanon is mainly a sporadic infection similar to HAV except that the prodromal phase is prolonged (greater than 14 days) and IgM levels are within normal limits. The failure to develop chronicity in NANB suggests that the virus of sporadic NANB may be different from that which causes post-transfusional (PTH) NANB.     

A randomized controlled open study of interferon alpha-2b treatment of chronic non-A, non-B posttransfusion hepatitis: no correlation of outcome to presence of hepatitis C virus antibodies

33 patients with biopsy-proven chronic non-A, non-B posttransfusion hepatitis (NANB PTH) were randomized 2:1 to treatment with interferon alpha-2b (Introna) or to controls. The treatment group received 3 MU interferon 3 times weekly subcutaneously for 36 weeks. 22/33 (67%) patients were reactive for antibodies against hepatitis C virus (anti-HCV). 11/19 (58%) treated patients versus none of the 12 controls had a complete response with normalization of serum alanine aminotransferase levels (p less than 0.001). Another 4/29 (21%) treated patients had a partial response which was also seen in 4/12 (33%) controls; 4 treated patients were nonresponders, all with chronic active hepatitis. Nonresponders had a significantly higher mean weight than responders (p less than 0.05) and tended to have a longer duration of their disease before therapy. During the 6-month follow-up period post treatment 4/11 (36%) complete responders had a sustained response and 7/11 (64%) relapsed. All who were retreated responded again. We conclude that a majority of patients with chronic NANB PTH will respond to 9 months interferon alpha-2b treatment, but that only 1 out of 3 will have a sustained response 6 months post treatment, and that the reactivity for anti-HCV was not correlated to the outcome of therapy.     

Acute viral hepatitis in Lebanon: evidence for an HAV-like non-A non-B hepatitis

ABSTRACT— Ninety-three cases of acute viral hepatitis in adult Lebanese patients were followed-up prospectively for a period ranging from 6 to 18 months. These included 33 hepatitis A (HAV), 32 hepatitis B (HBV) and 21 non-A, non-B hepatitis (NANB) cases. The clinical and seroepidemiologic characteristics of the three types were evaluated. HAV was characterized by a short prodroma (<1 week) and a high IgM level. HBV did not differ from similar cases reported in the Western world except for a complete absence of male homosexuals and drug addicts as a possible route of transmission. NANB hepatitis in Lebanon is mainly a sporadic infection similar to HAV except that the prodromal phase is prolonged (>14 days) and IgM levels are within normal limits. The failure to develop chronicity in NANB suggests that the virus of sporadic NANB may be different from that which causes post-transfusional (PTH) NANB.     

Prospective controlled study of post-transfusion hepatitis after cardiac surgery in a large referral hospital in India.

We studied the risk of post-transfusion hepatitis (PTH) in recipients of blood collected from voluntary donors screened for HBsAg. Two hundred and fifty patients without any previous history of liver disease or transfusion were followed up for 12 months subsequent to cardiac surgery. Thirty-five of them had closed-heart surgery without receiving transfusion and served as controls. The remaining 215 patients received single-point transfusions (mean 4 +/- 2.4 units). None of the controls and 15 (6.9%) blood recipients developed PTH. Three (20%) patients had hepatitis-B-virus-induced hepatitis while the remainder (80%) had non A, non B (NANB) hepatitis. The number of units of blood transfused and surrogate markers for development of PTH (donor alanine aminotransferase, anti-HBc and anti-HBs antibody) were not associated with the occurrence of PTH (p greater than 0.05). Nine (60%) of the 15 patients developing PTH were asymptomatic. All the patients recovered from the PTH, except one who died of fulminant hepatitis. At the end of 1 year of follow-up, none of the patients had evidence of chronic hepatitis. Only three (25%) of the patients with NANB-PTH developed anti-hepatitis C virus (HCV) antibody during the follow-up. We conclude that the incidence of PTH in India is similar to other parts of the world and NANB virus was the major cause of the PTH. The absence of chronicity and lack of seroconversion to anti-HCV antibody in the majority of the patients after 1 year of follow-up may suggest the possibility of a NANB virus other than HCV as the major cause of PTH in India.     

Anti-HCV immunoglobulin M antibody in patients with hepatitis C

Anti-hepatitis C virus (HCV) immunoglobulin M antibody titres were measured by an enzyme-linked immunosorbent assay method in 16 patients with non-A, non-B acute hepatitis (NANB AH), 13 with non-A, non-B fulminant hepatitis (NANB FH) and nine with type C chronic hepatitis. Anti-HCV IgM was positive in one of the 16 patients with NANB AH, six of the 13 with NANB FH, and five of the nine with type C chronic hepatitis. Anti-HCV IgG was positive in eight of the 16 patients with NANB AH and eight of the 13 with NANB FH. Either anti-HCV IgM or anti-HCV IgG were positive in 10 of the 13 patients with NANB FH. All of the five anti-HCV IgM positive patients with type C chronic hepatitis were undergoing an exacerbation of the diseases, while all of the anti-HCV IgM negative patients were in a remission stage which had lasted for more than 6 months. The findings of this study suggest that anti-HCV IgM is useful for the early diagnosis of type C FH and may be a useful marker of diseases activity in type C chronic hepatitis.     

Antibody to the hepatitis C virus in acute hepatitis and chronic liver diseases in Japan

ABSTRACT— In a 6-month follow-up study of acute hepatitis in Japan, 31 out of 41 (75.6%) cases of post-transfusion non-A and non-B hepatitis (NANB-PTH) and 14 out of 40 (35.0%) cases of sporadic non-A non-B hepatitis (NANB-SPO) were found to be positive for antibody to the hepatitis C virus (HCVAb). After 12 months of follow-up, 30 cases (81.1%) became chronic among 37 HCVAb positive acute NANB hepatitis cases. This figure shows a significantly higher rate of chronicity as compared with HCVAb negative acute NANB hepatitis. The prevalences of HCVAb in hepatitis B surface antigen (HBsAg) negative cases of chronic hepatitis and liver cirrhosis were 76.3% (200/262) and 66.7% (106/159), respectively, which were significantly different from the values of 5.1% (13/255) and 10.6% (13/123) observed in HBsAg positive cases. Of chronic liver disease cases positive for HCVAb, 45.8% (152/332) had a history of blood transfusion, in contrast to the value of 3.7% (13/352) observed in HBsAg positive cases of chronic liver disease that were negative for HCVAb.     

Aetiology and outcome of acute viral hepatitis in pregnancy

The aetiologic types of sporadic acute viral hepatitis in 169 pregnant women were compared with those of 70 non-pregnant women and 287 adult men. The majority of pregnant women (87.6%) came with acute hepatitis in the last trimester of pregnancy. Non-A, non-B (NANB) hepatitis accounted for 81.6% of hepatitis during pregnancy in comparison with 48.6% in non-pregnant women and 57.1% in adult men. Hepatitis A was extremely uncommon during pregnancy. Hepatitis B infection accounted for 17% of all cases in pregnant women compared with 45% in controls. Acute viral hepatitis in pregnancy had a poor outcome as assessed by maternal and/or fetal mortality (28.5%). The outcome was equally bad in hepatitis NANB and hepatitis B. Pregnant women generally had significantly lower immunoglobulin levels in comparison with non-pregnant women. In acute NANB hepatitis during pregnancy, serum IgG and IgM levels were lower and higher, respectively, compared with those in non-pregnant women and pregnant women with acute hepatitis B. It is suggested that an immune suppression during pregnancy might be responsible for increased susceptibility to acute NANB viral hepatitis, which, by itself, seems to induce only a transient acute phase IgM response.     

Non-A, non-B hepatitis: characterization of liver biopsy pathology

We reviewed 40 liver biopsy specimens from 36 patients with non-A, non-B (NANB) hepatitis by light microscopy to characterize the histopathologic features associated with this condition. NANB hepatitis had been acquired from intravenous drug use (6 patients), transfusion (11 patients), sporadic (13 patients), and other routes (6 patients). The major pathologic diagnoses included acute hepatitis, chronic persistent hepatitis, chronic lobular hepatitis, chronic active hepatitis with or without cirrhosis, and hepatocellular carcinoma. Histopathologic changes seen in varied combinations in these specimens included acidophilic degeneration of hepatocytes (100%), fat (85%), formation of portal tract lymphoid aggregates or follicles (52%), bile duct damage (30%), and multinucleate giant hepatocytes (25%). Prominence of sinusoidal cells was variable, but often striking. Hepatocyte atypia (liver cell dysplasia) was noted in 17 specimens. These histologic parameters appear to be diagnostically useful when applied in appropriate clinical settings and will require reevaluation when serologic tests for NANB hepatitis become available.     

Antibody to the hepatitis C virus in acute hepatitis and chronic liver diseases in Japan.

In a 6-month follow-up study of acute hepatitis in Japan, 31 out of 41 (75.6%) cases of post-transfusion non-A and non-B hepatitis (NANB-PTH) and 14 out of 40 (35.0%) cases of sporadic non-A non-B hepatitis (NANB-SPO) were found to be positive for antibody to the hepatitis C virus (HCVAb). After 12 months of follow-up, 30 cases (81.1%) became chronic among 37 HCVAb positive acute NANB hepatitis cases. This figure shows a significantly higher rate of chronicity as compared with HCVAb negative acute NANB hepatitis. The prevalences of HCVAb in hepatitis B surface antigen (HBsAg) negative cases of chronic hepatitis and liver cirrhosis were 76.3% (200/262) and 66.7% (106/159), respectively, which were significantly different from the values of 5.1% (13/255) and 10.6% (13/123) observed in HBsAg positive cases. Of chronic liver disease cases positive for HCVAb, 45.8% (152/332) had a history of blood transfusion, in contrast to the value of 3.7% (13/352) observed in HBsAg positive cases of chronic liver disease that were negative for HCVAb.     

Acute non-A, non-B hepatitis in Kuwait

In a prospective study of acute hepatitis in Kuwait covering the period February 1983 to January 1984, a total of 1781 cases were diagnosed as having an acute viral hepatitis. 1,384 (77.7%) were found to be due to hepatitis A virus (HAV), 206 (11.5%) hepatitis B virus (HBV), 8 (0.4%) coinfection with HBV and delta virus (HDV), 8 (0.4%) superinfection of HDV on chronic HBsAg carriers and 157 (9%) non-A, non-B virus (NANB). 13 cases of CMV and 5 of EBV infections were also diagnosed. NANB viral hepatitis was a disease of young adults (mean age 29 years) with a male-female ratio of 3:1. A high incidence was noted among males from the Indian subcontinent (29.1/100,000 of population, compared to 5.4/100,000 among local Arabs), the majority of whom gave a history of recent visit to the Indian subcontinent. The clinical features and biochemical findings of acute NANB infection were found to be less severe than those of acute HBV infection and similar to acute HAV infection. Three patients (2.3%) with acute NANB virus infection developed chronic hepatitis (all women), and another 3 patients died because of fulminant hepatitis.     

Prevalence of anti-HCV among Chinese patients with acute and chronic liver disease

To assess whether the hepatitis C virus plays an important role in Chinese patients with acute and chronic liver disease, antibodies to HCV (anti-HCV) were measured by enzyme immunoassay in 67 patients with type A and B acute viral hepatitis, 165 patients with non-A, non-B (NANB) hepatitis, 438 patients with chronic hepatitis, 200 patients with postnecrotic liver cirrhosis, 72 patients with alcoholic liver disease, 55 patients with non-alcoholic fatty liver, 24 patients with toxic and drug-induced hepatitis, and 20 patients with other chronic liver diseases. Anti-HCV was not detected in sera from patients with type A and B acute viral hepatitis, toxic and drug-induced hepatitis, primary biliary cirrhosis, Wilson's disease, or lupoid hepatitis. The anti-HCV prevalence was found to be highest in patients with NANB hepatitis (59% in sporadic and 73.2% in transfusion-associated), 16.4% in non-alcoholic fatty liver, 5.6% in alcoholic liver disease, 6.8% in chronic hepatitis, and 16% in postnecrotic liver cirrhosis. In patients with chronic hepatitis, the anti-HCV prevalence was significantly higher in HBsAg-negative (15/34, 44.1%) than in HBsAg-positive cases (15/404, 3.7%; P less than 0.0001). The results indicate that HCV is a major agent of NANB hepatitis and plays an important role in HBsAg-negative chronic liver disease in Taiwan.     

Non-A, non-B hepatitis after open-heart surgery in Stockholm: declining incidence after introduction of restrictions for blood donations due to the human immunodeficiency virus

In 1979 the incidence of non-A, non-B (NANB) posttransfusion hepatitis (PTH) in Stockholm was 19%. After the discovery of HIV the Swedish Board of Health put forward new regulations for blood donations and since 1985 has enforced testing for HIV on all blood units. To find out if these measures have had any impact on the incidence of NANB PTH, 316 patients transfused during open-heart surgery from December 1985 to November 1986 were followed prospectively. PTH due to the NANB agent(s) developed in 4.4% (14/316). A significantly higher mean number of blood units had been given to patients undergoing coronary artery bypass surgery in whom NANB PTH developed than in those who did not develop the infection. The mean number of blood units transfused during open-heart surgery in Stockholm had decreased from 16 in 1979 to 10 in 1985-1986. The number of NANB PTH cases/1,000 blood units transfused declined from 12 to 4 during the same period. Thus, both the reduced number of blood units given during open-heart surgery and the new restrictions for blood donors seem to have been effective in reducing the risk for NANB PTH in Stockholm during the 1980s.     

Evaluation of the specificity of an immunoprecipitin test for non-A, non-B hepatitis

The specificity of a new antigen-antibody system (devised at the International Center for Medical Research and Training [ICMRT], San José, Costa Rica) for non-A, non-B (NANB) hepatitis was evaluated. ICMRT antigen was found in eight (21%) of 38 patients with acute NANB hepatitis; 22 patients (58%) seroconverted, including three who were positive for ICMRT antigen. Five patients with chronic NANB hepatitis were persistently positive for ICMRT antigen and negative for ICMRT antibody during several years of observation. Neither ICMRT antigen nor seroconversion was found among 11 patients with hepatitis A and 19 with hepatitis B occurring concomitantly with NANB hepatitis; only two of 56 patients with other liver diseases had ICMRT antigen, both presumably with chronic antigenemia. Seven of 128 household contacts of patients with NANB hepatitis had ICMRT antigen; 27 had antibody initially, and 35 (37% of susceptible contacts) seroconverted during the observation period. Less than 4% of household contacts of patients with hepatitis A or B seroconverted.     

Incidence of post-transfusion hepatitis in Taiwan before and after introduction of anti-HCV testing

Abstract: The effectiveness of second-generation anti-hepatitis C virus antibody (anti-HCV) screening of blood donations for the prevention of non-A, non-B post-transfusion hepatitis (NANB PTH) was assessed. A prospective study of 192 transfusion recipients was performed to compare the incidence of NANB PTH after the introduction of the second-generation anti-HCV test with the incidence before its introduction. We used a polymerase chain reaction to detect HCV-RNA and HBV-DNA in the sera of patients with NANB PTH. The incidence of acute post-transfusion hepatitis C was 11% (8 of 71) before the screening for anti-HCV as compared with 2.5% (3 of 121) after the screening (p<0.05). Viremia was detected within the first five weeks of infection in 10 patients with acute post-transfusion hepatitis C. However, there was no significant difference in the incidence of non-A, non-B, non-C (NANBNC) PTH before screening (3 of 71, 4.2%) compared with after screening (3 of 121, 2.5%). Usually, NANBNC PTH was not clinically important. Anti-HCV screening of blood donors significantly reduces the incidence of post-transfusion hepatitis C, but not the incidence of NANBNC PTH.     

Serum markers of hepatic fibrogenesis in chronic hepatitis type C treated with alfa-2A interferon

Hepatic fibrogenesis is a dynamic process which characterizes the course of chronic hepatitis. It has stimulated interest in the possible effect of interferon therapy on liver fibrosis. We have evaluated a panel of serum markers of fibrogenesis, namely N-terminal procollagen III peptide (PII-INP), C-terminal procollagen I peptide (PICP), laminin and hyaluronate in 35 patients with chronic hepatitis type C, before, during and after interferon treatment. Before treatment, PIIINP was elevated in 8.5%, 44% and 71% of patients with chronic persistent hepatitis, chronic active hepatitis and cirrhosis, respectively, while the corresponding figures for PICP were 0%, 50% and 46%, and for laminin 16.5%, 70% and 71%; hyaluronate was elevated in only five out of seven patients with cirrhosis. Patients with high PIIINP levels at presentation and a persistent response to treatment showed persistent normalization of this parameter, which was not observed in non-responders. In contrast, the other markers showed no significant correlation with interferon response. These results indicate that PIIINP correlates with interferon response in chronic hepatitis type C.