Outbreak of Non-A, Non-B Hepatitis in Centre Haemodialysis Patients: A Retrospective Analysis

We reviewed the medical records of 177 patients who at 31 December1985 had been on dialysis treatment for at least one year. Fifty cases of non-A, non-B hepatitis were found: 33 in 70 patientsdialysed at the centre and 17 in 107 outpatients (P<0.000l).The difference was not related to blood transfusions but tothe high prevalence of non-A, non-B in hospital patients whohad not been transfused. The time on dialysis before the onset of non-A, non-B hepatitisbecame gradually shorter, from an average of 82 months before1980 to 5.7 months in the patients starting haemodialysis after1983. At follow-up, 7% of patients had abnormal hepatic enzymes5 years from the onset of acute illness. The epidemiology of non-A, non-B hepatitis in haemodialysispatients appears to be similar to that of hepatitis B. Apartfrom blood transfusions, contamination of hospital environmentalsurfaces seems to be the major route of transmission. Our results strongly support a preventive programme for non-A,non-B hepatitis similar to that for hepatitis B, and a separatesection for any patient with suspected non-A, non-B hepatitismust be considered.     

Chronic liver dysfunction in heart transplant recipients, with special reference to viral B, C, and non-A, non-B, non-C hepatitis. A retrospective study in 80 patients with follow-up of 60 months

In order to assess the prevalence, causes, and severity of chronic liver dysfunction (LD) in heart transplant patients, 80 transplanted patients followed for 60 months (median; range, 1.5-98 months) were reviewed. Sustained liver dysfunction was found in 50 patients, occurring during the first year after heart transplantation in 42 (84%) of them. Most patients were asymptomatic (80%). Causes for the liver dysfunction included non-A, non-B hepatitis in 16 cases (32%), viral B hepatitis in 13 (26%), delta hepatitis in one (2%), drug-induced hepatitis in six (12%), and cardiac failure in seven (14%). Anti-HCV antibodies were found in 56.2% of patients with non-A, non-B hepatitis and in 22% of patients with HBV hepatitis. It was found neither in patients with drug-induced hepatitis cardiac failure nor in patients with normal liver tests. This study outlines a high prevalence of LD (62.5%) in heart transplant patients, the high frequency of viral-related chronic LD (usually of moderate severity), and high incidence of HCV and HBV hepatitis.     

Hepatitis C virus antibody response in acute and chronic non-A, non-B hepatitis.

Patients with post-transfusion, community-acquired or hemodialysis-acquired non-A, non-B hepatitis (NANBH) were tested for antibody to hepatitis C virus (HCV) during acute-phase and resolving or chronicized illness. HCV appears to be involved in most cases of post-transfusion and hemodialysis-acquired NANBH, but only in 40% of community-acquired NANBH. Second generation HCV antibody assays are more specific and sensitive, favoring early detection of HCV seroconversion and identification of HCV-antibody-positive individuals years after exposure to the virus.     

Incidence and clinical relevance of recurrent hepatitis C infection after orthotopic liver transplantation

Abstract From September 1988 to November 1992 318 liver transplants were performed at our hospital. Of these patients 68 had end-tage cirrhosis due to non-A, non-B, hepatitis, 44 of whom (64.7%) had hepatitis C virus RNA in the serum. Of this subgroup 35 patients (79.5%) were also anti-HCV positive. Postoperatively most recipients remained anti-HCV positive and after 1 year more than 90% had HCV RNA in the serum. About 40% developed a mild, chronic hepatitis and 50% were carriers of HCV without histo-pathological signs. Two patients suffered from a temporary severe acute hepatitis and one patient had a fulminant liver failure due to reinfection. In general, in liver recipients transplanted for end-tage HCV hepatitis there was a high incidence of reinfection with HCV. The clinical course, however, was less severe than in hepatitis B recurrence.     

Non-A, non-B hepatitis and chronic dialysis--another dilemma

To define the incidence of non-A, non-B (NANB) hepatitis and evaluate possible risk factors, we reviewed records of 163 patients on chronic dialysis during a 3-year period. 23 cases of NANB hepatitis occurred, 13 (27%) in 49 center dialysis, 8 (10%) in 77 home hemodialysis (p less than 0.02) and 2 (5%) in 37 peritoneal dialysis patients (p less than 0.01). Hepatitis patients received significantly more transfusions than controls. Numbers of transfusions and of patients transfused were not significantly different in center patients compared to home and peritoneal. 8 NANB patients received no transfusions. NANB was the most common cause of hepatitis in our unit (68%). Although transfusions were a likely etiologic factor, to explain the increased risk in center dialysis patients, disease in patients not transfused and development of NANB hepatitis without a known parenteral exposure in a physician assigned to the Nephrology Service, we feel another etiologic factor was important, the dialysis center.     

Abnormal alanine aminotransferase activity reflects exposure to hepatitis C virus in haemodialysis patients.

Prospective studies have shown that the annual incidence of non-A, non-B (NANB) hepatitis may be high in haemodialysis patients. To assess whether hepatitis C virus (HCV), the major causative agent of post-transfusion and community-acquired NANB hepatitis, has a role in the pathogenesis of liver disease in dialysed patients, we have studied the prevalence and significance of antibodies to HCV in a cohort of patients with end-stage renal disease on chronic haemodialysis treatment. Seventy-four (30%) had circulating antibodies to HCV. Statistically significant associations with the anti-HCV carrier status were duration of haemodialysis treatment, blood transfusions, and the finding of abnormally elevated ALT on retrospective analysis. In contrast, only one of 103 dialysis staff members showed transient positivity for anti-HCV, suggesting a low risk of professional exposure to HCV. These findings suggests that HCV infection is relatively frequent in haemodialysis patients and may be responsible for a significant proportion of liver disease in this clinical setting.     

Hepatitis C Virus Infection in Dialysis: A Continuing Problem

Patients on chronic dialysis are at increased risk of acquiring parenterally transmitted hepatitis viruses from blood product transfusions or nosocomial transmission in hemodialysis units, and biochemical abnormalities in liver function are seen in 10–44% of patients on chronic hemodialysis. In the past, hepatitis B virus (HBV) was the major cause of parenterally transmitted viral hepatitis in dialysis patients, and the remaining cases were attributed to non-A, non-B hepatitis (NANBH). The discovery of the hepatitis C virus (HCV) has shed light on the cause and clinical course of NANBH in patients on dialysis. The current debate is focused on strategies to reduce the transmission of HCV among dialysis patients and to lessen the consequences of liver disease among patients already infected.     

Hepatitis C: reality of a renal unit.

Hepatitis C virus (HCV) seems to be the most important agent of non-A, non-B hepatitis. This study was undertaken to assess the prevalence of hepatitis C in our renal unit. Twelve patients (29%) had antibodies against HCV (anti-HCV). Seropositive patients were on hemodialysis for a longer period than seronegatives. Statistically significant associations with anti-HCV were: blood transfusions, at least 1 episode of elevated value of transaminases (2-fold) and fluctuations of transaminases. Our findings confirm the high prevalence of anti-HCV in hemodialyzed patients, the importance of parenteral transmission and the high probability of liver disease in anti-HCV-positive patients.     

Hepatitis C virus infection among kidney transplant recipients.

The extent of hepatitis C virus (HCV) infection among kidney recipients was investigated in 67 patients by testing for anti-HCV paired serum samples, collected at time of transplantation and during follow-up (average 32 +/- 20 months). Prevalence of anti-HCV at transplant time was 48%, and was related to the time on dialysis and to the amount of blood transfusions. Following transplantation, nine (28%) seropositive patients lost anti-HCV and five (14%), previously seronegative, seroconverted. Anti-HCV was found to be positive in 92% of the patients with chronic liver disease who were on hemodialysis, but in 56% in kidney recipients with chronic hepatitis. Anti-HCV was positive in 50% of patients with resolving hepatitis before transplantation, but only in 21% of those with acute hepatitis following transplantation. This study confirms the high risk of HCV infection among hemodialysis and kidney recipient populations, and also that HCV is closely related with the length of time the patient is on hemodialysis as well as the number of blood units transfused. HCV is the main cause of acute and chronic liver disease in hemodialysis patients and of chronic liver disease in kidney recipients, but does not clearly influence the survival of the allograft nor that of patients.     

Living donor liver transplantation for fulminant hepatic failure

BACKGROUND: Living donor liver transplantation (LDLT) was originally indicated only for elective cases of pediatric patients with end-stage liver disease. In Japan, however, where liver transplantation from brain-dead donor is performed very rarely, this indication has been expanded to emergency cases such as fulminant hepatic failure (FHF). METHODS: Thirty-eight patients with FHF were treated between May 1992 and April 1999. Causes of acute liver failure were non-A, non-B hepatitis in 27 patients, hepatitis B virus in seven, and hepatitis A virus, Epstein-Barr virus, herpes simplex virus, and chrome poisoning in one each. RESULTS: Four patients did not undergo LDLT because of severe brain damage or combined multiple organ failure. The remaining 34 patients underwent a total of 36 LDLTs, including two retransplantations; 16 children received transplants of 17 lateral segments, three children and eight adults transplants of 11 left lobes, and seven adults transplants of eight right lobes. A total of 15 recipients died, four of primary graft dysfunction, three of refractory acute rejection, two of pneumonia, and one each of ductopenic rejection, sepsis, aplastic anemis, recurrence of Epstein-Barr virus hepatitis, multiple organ failure by chrome poisoning, and unknown hepatic failure. Primary graft dysfunction developed in adult recipients with small-for-size graft transplants, whereas refractory acute rejection and ductopenic rejection occurred in six grafts each of children with non-A, non-B FHF. CONCLUSIONS: LDLT can be safely expanded to cases of FHF in adult patients. Primary graft dysfunction in adult recipients with small-for-size left lobe grafts can be overcome by using right lobes. However, refractory acute rejection and ductopenic rejection in children remain a major problem.     

Natural history of acute HCV infection in hemodialysis patients

AIMS: Chronic liver disease develops in the majority of non-uremic patients with hepatitis C virus (HCV) infection. The aim of this study was to analyze the evolution towards chronic hepatopathy in 19 cases of acute hepatitis C observed in hemodialysis patients from 1990 to 2001. METHODS: A prospective follow-up study on HCV infection was conducted in 3 HD units from April 1990 to June 2001 to study clinical outcomes after acute hepatitis C. A total of 781 patients were tested monthly for alanine aminotransferase and anti-HCV in serum. In this period, 19 patients suffered from acute hepatitis C. Evolution to chronic liver disease in the follow-up was evaluated by means of biochemical (increased ALT) and virological criteria (HCV-RNA+). The transmission mechanism, the apparition of anti-HCV, clinical manifestations and mortality were also investigated. RESULTS: In 15 (78.9%) of the 19 patients, the viremia remained positive (chronic viremia) and 11 patients (57.8%) evolved to chronic liver disease (chronic viremia and high transaminase levels) with a median follow-up of 3 years (range 1 - 6). Five of them who underwent liver biopsies had histologic signs of chronic active hepatitis. One of them (5.2%) evolved to liver cirrhosis in the follow-up. In 4 out of 19 patients (21%) the HCV infection resolved. Although 7 (36.8%) of them died in the follow-up, acute hepatitis C infection was not a short-term independent risk factor of death. CONCLUSIONS: Three years after acute hepatitis C, 87.5% of the hemodialysis patients remained HCV-RNA positive and 56.2% evolved to chronic liver disease. It is important to stress that HCV infection spontaneously cleared in 4 out of 19 patients (21%).     

Non-A, non-B hepatitis: clinical laboratory course in patients on hemodialysis and its correlation with the presence of anti-hepatitis C virus antibodies.

136 patients on hemodialysis, 89 males and 47 females, were studied; we evaluated the index of hepatic function (SGOT and SGPT) and antibodies against HCV. We observed 42 cases of increased transaminases classified as non-A, non-B (NANB) hepatitis. Antibodies against HCV were present in 40 patients. Among 42 patients with NANB hepatitis. 31 (73.8%) presented anti-HCV antibodies. No significant clinical or laboratory difference exists between anti-HCV-positive and -negative patients with NANB hepatitis. The distribution of patients who present anti-HCV antibodies is similar in post-transfusional and sporadic forms.     

Gamma globulin prophylaxis to reduce post-transfusion non-A, non-B hepatitis after cardiac surgery with cardiopulmonary bypass

A prospective, randomized study of immune serum globulin (ISG) for prevention of post-transfusion hepatitis was performed on 196 patients (100 controls without gammaglobulin or placebo and 96 who received ISG) undergoing valve replacement or coronary artery bypass with extracorporeal circulation. The dose of ISG was 2 ml i.m. at premedication and 2 ml i.m. on postoperative day 3. Probable non-A, non-B hepatitis developed postoperatively in ten of the 100 controls and two of the 96 in the ISG group. Two ISG patients and three controls with non-A, non-B hepatitis still have increased serum aminotransferase values after 3-5 years, but liver biopsy revealed hepatitis, which histologically was very mild, in only two control and two ISG patients. Low-dose gamma globulin thus reduced the incidence of acute, probable non-A, non-B hepatitis in cardiac surgery with cardiopulmonary bypass.     

Prevalence and Causes of Long-Lasting Hepatic Dysfunction after Heart Transplantation: A Series of 80 Patients

The long-term follow-up of 80 heart transplant patients (70 men, 10 women) from January 1982 to July 1985 who had received cyclosporine (CsA) showed a high incidence of mild to severe liver dysfunction. Fifty patients (62.5%) had long-lasting postoperative biological disturbances (alanine amino transferase greater than 2N and/or alkaline phosphatase greater than 1.5N for 3 months or more). Most patients were asymptomatic; eight were icteric, and one had arthralgia. The most common biological feature consisted of isolated elevation of ALAT (27 cases). Assessment of causes led to a definite etiology in 42 patients: 7 cardiac failure, 13 HBsAg-positive liver disease (26%) (chronic persistent hepatitis 8, chronic active hepatitis 2, subacute necrosis 2). Fourteen patients (28%) sustained non-A, non-B (NANB) hepatitis (chronic persistent hepatitis 5, chronic active hepatitis 1, cirrhosis 1), and 7 (14%) sustained a drug-related hepatitis. Liver biopsy and complete virus screening was contributive to the diagnosis in nearly all patients. Additionally, prolonged impairment of liver function tests occurred in 62% of heart transplant recipients, mostly during the first 6 postoperative months. Hepatitis B virus (HBV) and NANB hepatitis accounted for 26% and 28% of the cases of liver dysfunction, respectively; drug-induced hepatitis may have been involved in 14% of the cases. Complete hepatitis virus screening should be performed before heart transplant and in any case of abnormal liver function posttransplantation. HBV vaccination prior to heart transplant is recommended in HBsAg- and HBcAb-negative candidates for heart replacement. Long-term follow-up of these patients is mandatory to assess the severity of these liver dysfunctions.     

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.     

Akute Non-A-non-B-Aortendissektion

The current aortic dissection classifications do not consider the situation when the dissection process involves the aortic arch but not the ascending aorta, so-called non-A non-B aortic dissection. Every tenth patient with an acute aortic dissection has a non-A non-B dissection and one third of these undergo emergency aortic surgery for aortic rupture or organ malperfusion. Almost all patients with non-A non-B aortic dissection require aortic surgery sooner or later. There are several surgical and interventional treatment options. It is crucial to close the entry into the aortic arch and to avoid endovascular treatment of patients in cases of an entry located in the aortic arch due to the risk of retrograde type A dissection.     

Viral hepatitis in HBsAg-positive renal transplant patients treated with cyclosporin and steroids

This study reports clinical, serological and immunomorphological observations on viral hepatitis in 14 HBsAg-positive renal transplanted patients treated with cyclosporin and steroids. Eleven patients who were HBsAg positive before transplantation developed signs of hepatitis. This was due to HBV in six cases and progressed into a mild chronic disease. The remaining five subjects lacked signs of HBV reactivation. The hepatitis, attributed to non-A non-B agents, recovered completely. Two more patients became HBsAg positive after transplantation both developed acute hepatitis, respectively drug and HBV related. Transition into chronicity occurred only in the latter case. The results seem to indicate: (1) the possibility of a high incidence of non-B virus hepatitis in HBsAg-positive transplanted patients under cyclosporin treatment; (2) a good prognosis in non-B hepatitis as compared to hepatitis B for the same patient group; and (3) a mild degree of disease activity in cases who develop chronic hepatitis.     

Prevalence of hepatitides in our hemodialyzed population.

We evaluated the prevalence of hepatitis in our hemodialysed population (65 patients, 37 M and 28 F). Screening for A and B hepatitis was tested with the RIA method and research of the anti-HCV with the immunoenzymatic method (Ortho HCV ELISA test of 2nd generation). 15 patients (23.07%) were anti-HCV positive (anti-HCV+); 23 (35.38%) showed positivity for 1 or more markers of B hepatitis (HBV+). A meaningful greater prevalence of B virus infections in anti-HCV+ patients (86.66%), compared to negatives, (20.00%) resulted. All non-A, non-B hepatitides are anti-HCV+. The dialytic treatment of the anti-HCV+ patients was meaningfully longer than in the negatives (p less than 0.05). The prevalence of the seropositive patients to B and C virus is not correlated to the number of transfusions, while it is to the number of surgical operations carried out in the predialytic period. This information suggests common pathogenetic mechanisms between the 2 forms of hepatitis and increased probability to find anti-HCV+ with a longer dialytic treatment.     

Hepatitis C virus antibodies in patients with liver disease. The western Cape experience.

Hepatitis C virus (HCV) is a recently characterised non-A, non-B hepatitis (NANBH) agent, which appears to be important in both parenteral and sporadic NANBH. HCV infection has been associated with the development of chronic liver disease, cirrhosis and hepatoma. Groups of patients in the western Cape with chronic liver disease and hepatoma were screened for antibodies to HCV and the results were confirmed by standard neutralisation tests. Three of 19 patients with cirrhosis secondary to alcohol abuse or classic auto-immune chronic active hepatitis were considered to have antibodies to HCV at initial screening. All of these were false-positive results. Five of 20 patients with presumptive chronic NANBH were considered possibly to have antibodies to HCV. Only 1 patient with post-transfusional NANBH was confirmed to have specific HCV antibodies. Two of 30 patients with hepatoma had specific anti-HCV antibodies in contrast to 11 others with serum HBsAg positivity. One hundred blood transfusion donors and 25 antenatal patients were tested concurrently and shown to be negative for anti-HCV. Specific antibodies to HCV were present in very few patients with cirrhosis, presumptive NANBH and hepatoma tested in this local survey. False-positive reactions appeared to occur at a higher rate than true-positive results.     

Antibody responses to hepatitis C virus and its modes of transmission in dialysis patients.

Five of 72 patients dialysed at the same dialysis unit developed elevated alanine aminotranspherase (ALT) levels attributed to acute non-A, non-B hepatitis (NANBH). Histopathologic findings consistent with NANBH were present in four of them. Serological screening for antibodies to hepatitis C virus (anti-HCV) was performed in all 72 cases. Three of the patients with NANBH and 2 of the other 67 patients had positive tests. Low and transient levels of anti-HCV were noted in 2 patients with NANBH in spite of chronic hepatitis. Only 1 of 5 patients with NANBH was known to have had blood transfusions indicating other, as yet undefined, modes of transmission of HCV for the others. Although antibody responses to HCV might be transient or low, testing for anti-HCV should be considered in dialysis populations.