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.     

Hepatitis C virus infection in hemodialyzed patients detected by first and second generation assays.

A prospective study of liver disease has been conducted among patients entering our Dialysis Unit between 1987 and 1990. On entry, 7 patients had a history of blood transfusions but none had clinical or biochemical features of liver disease. During follow-up, 13 further patients were transfused; 1 case developed acute resolving hepatitis B and another acute non-A, non-B hepatitis progressing to chronicity. Eleven other cases showed transient or fluctuating ALT abnormalities. On entry, anti-HCV was negative by both 1st and 2nd generation ELISA assays (Ortho-Diagnostic Systems) in all cases. During follow-up, a positive reaction was detected in 17 cases: 4 patients were positive by both assays and 13 only by 2nd generation test (p less than 0.01). HCV was implicated in 66% of cases with liver disease of the non-A, non-B type and in 50% of transfused as compared to 23% of nontransfused cases (p = n.s.). These findings suggest that HCV could play a major etiological role in liver disease of hemodialysis patients and that anti-C100 reactivity is more affected by immunosuppression associated with chronic uremia.     

Clinicopathologic characteristics of patients with non-B non-C hepatitis virus hepatocellular carcinoma after hepatectomy

BackgroundA substantial population of hepatocellular carcinoma (HCC) patients is negative for markers of hepatitis B virus and hepatitis C virus (HCV) infection (non-B non-C hepatitis virus [NBC]).MethodsClinicopathologic data and outcomes were compared retrospectively for HCC patients with hepatitis B virus, HCV, and NBC who had undergone hepatectomy.ResultsThe TNM stage was significantly higher, and the prevalence of cirrhosis was significantly lower, in the NBC group compared with the HCV group. Among patients with a maximum tumor diameter of 5 cm or less, the survival rates were significantly higher in the NBC group than in the HCV group. Multivariate analysis revealed that preoperative serum des-gamma-carboxy prothrombin (DCP) level was a prognostic factor for survival in NBC–HCC patients. The DCP/tumor size ratio was significantly higher in NBC–HCC patients with normal liver histology than in patients with hepatitis or cirrhosis.ConclusionsNBC–HCC patients had more advanced tumors compared with HCV–HCC patients, but significantly higher survival rates. Measurement of DCP potentially is significant for early diagnosis of NBC HCC, which may increase the chance of curative therapy without recurrence.     

Antibodies against hepatitis C virus in hemodialysis patients in the central Italian region of Umbria: evaluation of some risk factors.

The epidemiology of non-A, non-B hepatitis (NANBH) is still incomplete. To define the prevalence of antibodies against the main causative agent of NANBH, the hepatitis C virus (HCV) and the role of some risk factors, we tested sera from 269 patients on chronic dialysis at the hemodialysis units in our region in central Italy. We utilized the recently developed serological assay. Twenty-nine hemodialysis patients (13.3%) and 3 peritoneal dialysis patients (4.8%) were anti-HCV positive. Of these, 13 (40.6%) had antibodies to hepatitis B core antigen (anti-HBc) indicating prior hepatitis B infection. The anti-HCV seropositive patients had been on dialysis longer than the seronegative ones; they had received more transfusions than the others but without a significant difference. The prevalence rate of anti-HCV was statistically significantly higher among hemodialysis patients utilizing the same dialysis equipment for the previous 12 months.     

Detection of antibody to hepatitis C virus in renal transplant recipients.

Non-A, non-B hepatitis is a significant cause of liver disease among renal allograft recipients. In order to assess the impact and prevalence of hepatitis C in a series of renal allograft recipients, we retrospectively screened 621 consecutive patients transplanted between 1979 and 1989 and 484 cadaver organ donors retrieved in the same interval for serologic evidence of hepatitis C viral (HCV) infection using the enzyme-linked assay for anti-HCV antibody. Of 596 HBsAg negative patients, 180 (30%) were anti-HCV positive at the time of transplant. One-year posttransplant, 117 (22%) had detectable levels of anti-HCV antibody. Chemically significant hepatitis developed in 52/234 (22%) anti-HCV positive patients, and 26 of these followed a clinical course consistent with chronic hepatitis. Significantly more males and patients with antibody to HCV detectable at 1 year posttransplant were in the group experiencing an increase in liver enzymes. Ten-year patient and graft survival was 78% and 50%, respectively, for the anti-HCV positive patients who had an elevation of alanine aminotransferase, and 76% and 57% for the cohort maintaining normal liver function (P = NS). There were also no differences in patient and graft survival among the anti-HCV positive group and the consistently sero-negative patients. Of 484 cadaver organ donors with serum available for analysis (out of 1200 retrieved), 67 (14%) were anti-HCV positive at the time of organ donation. Among 23 anti-HCV negative kidney recipients who received a kidney from an HCV antibody positive donor, only one had seroconverted at 1 year posttransplant. Antibody to HCV appears to be widespread among renal transplant recipients and cadaver organ donors. We were unable to demonstrate any evidence of long-term adverse effects on patient and graft survival among anti-HCV positive patients employing the first generation anti-HCV assay.     

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.     

Clinical characteristics of hepatitis B core antibody-positive hepatocellular carcinoma

The pathology and prognosis of hepatitis B surface antigen (HBsAg)-positive hepatocellular carcinoma (HCC) and hepatitis C virus antibody (HCVAb)-positive HCC is well documented. However, patients with HBsAg-negative/hepatitis B core antibody (HBcAb)-positive HCC are included with non-B non-C disease and have been characterized independently. A series of 125 patients who had undergone hepatectomy for HCC were divided into three groups and compared. The HBsAg group comprised 25 HBsAg-positive patients, the HCV group comprised 70 HCVAb-positive patients, and the HBcAb group comprised 22 HBcAb-positive/HBsAg-negative patients. Eight patients of negative virus markers were excluded in this study. Tumors were larger in the HBcAb group (6.2 cm) than in the HBsAg (4.4 cm) and HCV (3.7 cm) groups. Disease-free 1-, 3-, and 5-year survival rates were, respectively, 75.0%, 57.1%, and 57.1% in the HBcAb group; 60.9%, 41.8%, and 41.8% in the HBsAg group; and 88.0%, 54.0%, and 37.8% in the HCV group. HBcAb-positive HCC patients had larger tumors, but their prognosis was relatively good. Although HBsAg and HCVAb are used for conventional screening of patients with hepatic disorders, we believe that screening is also necessary in patients with positive HBcAb titers for early detection of HCC.     

丙型肝炎病毒感染对肾移植受者排斥反应及人/肾存活率的影响

目的 研究丙型肝炎病毒(HCV)感染是否影响移植肾急性和慢性排斥反应的发生率,以及受者和移植肾的存活率.方法 对1992年6月至2004年6月所行肾移植的495例受者进行了随访,其中术前HCV抗体阳性受者27例(HCV阳性组),随机抽取HCV抗体阴性受者27例作为对照组,行组间配对研究,分析HCV感染状态对肾移植受者急性和慢性排斥反应发生率以及人/肾存活率的影响.结果 HCV阳性组受者急性排斥反应的发生率显著高于对照组(19.14%和6.38%,P<0.01),HCV阳性组慢性排斥反应的发生率也明显高于对照组(23.40%和12.76%,P<0.01),对照组肾移植后1、3、5年人/肾存活率显著高于HCV阳性组,差异有统计学意义(P<0.01).结论 HCV感染可以明显增加肾移植受者急性和慢性排斥反应的发生率,降低人/肾存活率.     

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.     

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.     

Retrospective study on the prevalence of B and non-A, non-B hepatitis in a dialysis unit: 17-year follow-up.

To evaluate the prevalence of HBV, non-A, non-B hepatitis (NANBH) and HCV, their evolution and the route of transmission, we performed a retrospective study (17 years) on 65 hemodialyzed patients (mean dialytical age 5 years, range 1-16) who developed acute viral hepatitis. Twenty-six percent of them were affected by HBV; 5 of them (29%) became chronic. Fourty-eight of 65 patients were affected by NANBH; in 1990, 42 of them were tested for antibody to HCV with the C-100 Elisa assay: 27 patients (64%) were positive. Seven of 27 patients demonstrated normal values of ALT. The evaluation of intrafamiliar transmission of HBV showed 8 sexual partners infected. In the family, no one was anti-HCV positive. In agreement with the current literature, we have observed: (1) a decrement in HBV infection; (2) that HCV is the major cause of NANBH; its rate of chronicity is over 50%; (3) that the prevalent mode of HCV transmission is the parenteral route while the sexual route seems to be negligible.     

Mesohepatectomy for centrally located hepatocellular carcinoma: an appraisal of a rare procedure

BACKGROUND: For centrally located hepatocellular carcinoma (HCC), extended major hepatectomy is usually recommended, but the risk of postoperative liver failure is high when liver function is not sound. Mesohepatectomy (en bloc resection of Goldsmith and Woodburne's left medial and right anterior segments or Couinaud's segments IV, V, and VIII) is a rare procedure, so its role in treating HCC is unclear. STUDY DESIGN: We retrospectively reviewed 364 patients who underwent a curative resection for HCC. Among them, 15 patients were treated by mesohepatectomy. Their nontumorous liver revealed cirrhosis in 11 and chronic hepatitis in 4. The mean tumor diameter was 12.8 cm. In 10 of the 15 patients, HCC also invaded adjacent organs. The operative results of another 25 patients with different disease extent who underwent extended major hepatectomy were compared. RESULTS: The hepatic inflow occlusion time for mesohepatectomy was longer than for extended hepatectomy (p = 0.01). The mean operative blood loss, amount of blood transfusion, operating time, and postoperative hospital stay in the mesohepatectomy group were 2,450 mL, 1,100 mL, 7.9 hours, and 14.9 days, respectively. In the extended-hepatectomy group, the values were 1,863mL, 768mL, 5.8 hours, and 16.8 days, respectively (all p>0.05 compared with mesohepatectomy). No patient died after mesohepatectomy, but after extended hepatectomy there was one death from liver failure. The Union Internationale contre le cancer (UICC) TNM stages of patients who underwent mesohepatectomy were as follows: stage II in 1, stage III in 4, and stage IVA in 10. All patients who underwent extended hepatectomy presented with stage IVA disease. The 6-year disease-free and actuarial survival rates after mesohepatectomy were 21% and 30%, respectively. The 6-year disease-free survival rate after extended hepatectomy was 9% (p = 0.11 compared with mesohepatectomy). CONCLUSION: Although mesohepatectomy is time-consuming, it is justified for selected patients with centrally located large HCC in a diseased liver.     

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.     

Antibodies against hepatitis C virus (anti-HCV) in haemodialysis patients: association with hepatitis B serological markers.

Hepatitis C virus (HCV) seems to be the main causative agent of the parenterally transmitted non-A, non-B hepatitis and the detection of anti-HCV may be a marker of ongoing infection with this virus. This study was undertaken to determine the frequency of anti-HCV in 51 haemodialysis patients of our renal unit. In addition association of these antibodies to sex, history of blood transfusions, and duration on haemodialysis, as well as to serological markers of hepatitis B virus infection, was applied. Enzyme-linked immunosorbent assay (ELISA), were used for the detection of all serological markers. Nine of the 51 (17.6%) haemodialysis patients had anti-HCV. The presence of anti-HCV was related to male sex. Although seropositive patients were transfused more often than seronegatives, this difference is not statistically significant. The presence of anti-HCV was associated with the duration of haemodialysis. The majority of anti-HCV patients had serological markers of previous HBV infection, in contrast to seronegative patients.     

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.     

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.     

Prognostic factors and survival after hepatic resection for hepatocellular carcinoma without cirrhosis

BACKGROUND: Detailed follow-up of patients with chronic hepatitis has resulted in increased diagnosis of hepatocellular carcinoma (HCC) in patients without cirrhosis. Despite numerous studies on hepatic resection, the prognostic factors for intrahepatic recurrence and survival are not well known for patients with HCC without cirrhosis. METHODS: Among 349 patients with HCC treated in the past 13 years, cirrhosis was absent in 126 patients (36 per cent). Curative hepatic resection was carried out in 100 (79 per cent) of these patients. Risk factors for intrahepatic recurrence and prognostic factors for survival were evaluated by univariate and multivariate analyses. RESULTS: Postoperative morbidity and mortality rates were 22 and 3 per cent respectively. The 5- and 10-year disease-free and overall survival rates were 31 and 50 per cent, and 22 and 47 per cent respectively. Blood loss, surgical resection margin, intrahepatic metastasis, portal vein invasion and extent of hepatic resection were independently associated with overall survival. However, the only risk factors for intrahepatic recurrence were portal vein invasion and hepatitis C virus (HCV) infection. The former was related to early recurrence while the latter was related to later recurrence. The 5-year disease-free survival rate was 58 per cent in patients with hepatitis B virus infection while it was 6 per cent in patients with HCV infection (P < 0.001). CONCLUSION: In the treatment of HCC without cirrhosis, major hepatectomy is advocated to prevent early recurrence. Liver transplantation may be required for patients with HCV infection.     

High prevalence of and risk factors for hepatitis C in haemodialysis patients in Saudi Arabia: a need for new dialysis strategies

Non-A, non-B is a major form of hepatitis in haemodialysis (HD)patients. Hepatitis C virus (HCV) has been recently identifiedas the leading cause of non-A, non-B hepatitis in HD. A variableprevalence of hepatitis in HD has appeared in the literature,ranging between 1% and 29% in the Western world, and between30% and 54% in Saudi Arabia, but all these reports used first-generationELISA. Using second-generation enzyme immunoassay, we conducteda multi-centre study involving 22 HD centres all over SaudiArabia in order to establish the prevalence and risk factorsfor HCV in HD patients in Saudi Arabia. A total of 1147 patientswere studied, with a mean age of 43.4±15.3 years. Fivehundred and eighty were males and 567 were females. The overallprevalence rate of positive anti-HCV was 68%, with a range fromas low as 14.5%, to 94.7%. To our knowledge, this is the highestvalue reported among dialysis patients world-wide. A positivecorrelation was found between anti-HCV positivity and male sex(P=0.005), longer duration on dialysis (P=0.002) and blood transfusion(P=0.003). However, interestingly 62.6% of the patients whohad not had blood transfusion had anti-HCV antibodies. HCV antibodieswere also found more frequently in Egyptians, Pakistanis andYemenis than in Saudis. A comparison between those centres withlow prevalence of positive HCV and those with high prevalenceregarding risk factors was carried out, and it was found thatthe major difference between them was the adherence of the staffto universal infection precautions. In conclusion, HCV is amajor health problem in HD patients in Saudi Arabia. Identifiablerisk factors are longer duration in dialysis, blood transfusion,male sex, nationality and most importantly the lack of adherenceto universal infection precautions.     

Significance of HBV DNA in the Hepatic Parenchyma from Patients with Non-B, Non-C Hepatocellular Carcinoma

Introduction The etiologic and prognostic factors for non-B, non-C hepatocellular carcinoma (HCC), which is defined by its seronegativity for both hepatitis B surface antigen and hepatitis C virus (HCV) antibody, remain unclear. Methods Nonneoplastic liver tissue from 46 patients with non-B, non-C HCC were examined for hepatitis B virus (HBV) DNA and HCV RNA using in situ hybridization. Recurrence-free survival rates were compared between patients showing high or low HBV DNA expression. Other potential prognostic factors were examined as well. Results HBV DNA was detected in nonneoplastic liver specimens from 35 patents (76.1%), whereas HCV RNA was not detected in any case. In patents with high HBV DNA group expression, recurrence-free survival rates at 1 and 5 years after onset were 68.8% and 13.8%, respectively; those with low expression had higher rates of 89.2% and 59.2%, respectively. Multivariate analysis identified high tumor stage (P = 0.042) and high HBV DNA expression (p = 0.014) as independent negative prognostic factors. Conclusions In many patients with non-B, non-C HCC, HBV DNA in the liver appears to be involved in the carcinogenesis, with intense HBV DNA expression predicting poor outcome for patients with these cancers.     

Surgical Results in Patients with Hepatitis B-related Hepatocellular Carcinoma and Positive Hepatitis B Early Antigen

Hepatitis B virus (HBV) infection is the major risk factor in the pathogenesis of hepatocellular carcinoma (HCC). Patients who are positive for hepatitis B early antigen (HBeAg) have active liver disease. The present study aimed to evaluate the possible role of HBeAg in patients with resectable HCC. A series of 249 HCC patients with complete preoperative hepatitis marker who had undergone potentially curative resection were enrolled. Patients with hepatitis C virus infection were excluded. Of these patients, 27 were positive for hepatitis B surface antigen (HBsAg) and HBeAg (group I), 171 were positive for HBsAg and negative for HBeAg (group II), and 51 were negative for hepatitis B markers (group III). The clinicopathologic features and postoperative survivals were compared among the three groups. The prevalence of HBeAg was 10.8%. Group I patients were significantly younger and had worse liver function, smaller tumors, and a higher incidence of liver cirrhosis and chronic active hepatitis than those in groups II and III. No increase in tumor invasiveness was noted in group I patients. The operative morbidity, mortality, and postresection survival were comparable among the three groups. Our findings indicated that HBeAg positivity is not a negative factor for resection in HCC patients and has no significant influence on postresection survival.