Relapse rates in chronic hepatitis B naïve patients after discontinuation of antiviral therapy with entecavir.

Registration studies show entecavir (ETV) to be effective and safe in NUC-naïve patients with chronic hepatitis B, but relapse rates after treatment discontinuation have not been well established. Relapse rates and predictors of relapse were evaluated in naïve HBeAg-positive and HBeAg-negative patients treated with ETV. Treatment duration was defined according to international guidelines. Virological relapse was defined as reappearance in serum of hepatitis B virus (HBV) DNA to >2000 IU/mL after discontinuation of treatment. A hundred and sixty-nine consecutive patients were treated for a median 181 weeks. 61% were HBeAg positive, 23% had cirrhosis, and mean HBV DNA level was 6.88 ± 1.74 log10 IU/mL. Ninety-two per cent became HBV DNA negative; 71% of HBeAg+ve patients became HBeAg negative and 68% anti-HBe positive; 14% became HBsAg negative and 13% anti-HBs positive. At the end of the study, 36 patients discontinued treatment: one due to breakthrough associated with resistant variants and 35 (20%) due to sustained virological response; 33 of these patients developed HBeAg seroconversion and 18 HBsAg seroconversion. Median off-treatment time was 69 weeks. Nine patients (26%), all HBeAg positive at baseline, developed virological relapse after a median 48 weeks off-treatment, 3 of them showed HBeAg reversion and 4 lost anti-HBe. No patient with HBsAg seroconversion relapsed. HBeAg clearance after week 48 of treatment was associated with an increase risk of relapse. After ETV discontinuation, HBsAg seroconversion was maintained in 100% of the patients, HBeAg seroconversion maintained in 90%, and virological relapse rate was 24%.

Effectiveness of entecavir in chronic hepatitis B NUC-naive patients in routine clinical practice.

INTRODUCTION: Registration studies showed entecavir (ETV) to be effective and safe in NUC-naïve patients with chronic hepatitis B virus (HBV), but its effectiveness in routine clinical practice is unknown. MATERIALS AND METHODS: Sixty-nine HBeAg positive and negative NUC naïve chronic HBV patients were treated with ETV for 110 weeks. 63% were HBeAg positive, 16% were cirrhotics, mean HBV-DNA was 7.09 log IU/ml and mean ALT was 157 IU/ml. RESULTS: Sixty-one (88%) patients achieved undetectable DNA, with 46%, 77% and 100% virological response rates at week 24, 48 and 96 of treatment, respectively. Thirty-seven (84%) patients in the HBeAg-positive population achieved undetectable DNA, with 67% and 100% virological response rates at week 48 and 96 of treatment, respectively. Twenty-four (96%) patients in the HBeAg-negative population achieved undetectable DNA, with 91% and 100% virological response rates at week 48 and 96 of treatment, respectively. Twenty-three (53%) patients cleared HBeAg and 19 (44%) patients seroconverted to antiHBe positive status; seven (10%) patients cleared hepatitis B surface antigen and five (7%) patients developed antiHBs. At the end of the study, 10 patients successfully stopped therapy: nine HBeAg positive (four developed antiHBs positive) and one HBeAg negative. None of the patients had primary non-response. ETV resistance was not tested. None of the patients developed hepatocellular carcinoma, underwent liver transplantation or died because of liver-related events. No serious adverse events were reported. CONCLUSION: The ETV monotherapy showed high virological response rates, a favourable safety profile for NUC-naive HBeAg-positive and negative patients treated in routine clinical practice.

Hepatitis C virus infection and outcome of renal transplantation.

Chronic hepatitis B and C viruses (HBV and HCV) are common problems in renal transplant patients. There is no uniform agreement regarding their influence on graft outcomes and patient survival. We evaluated the influence of anti-HCV and hepatitis B surface antigen-positive status; gender; age>49 years at the time of transplantation; alanine aminotransferase elevation; acute rejection; type of graft; number of transplants; and maintenance/induction immunosuppressive treatment on both graft and patient survivals among a population transplanted in our center between 1991 and 2004. Univariate analysis showed that anti-HCV-positive status, three-drug immunosuppressive therapy, and one or more episodes of acute rejection were associated with diminished graft survival. Over the age of 49 years at the time of transplantation, anti-HCV-positive status, cadaveric donor, kidney-pancreas transplantation, and three-drug immunosuppressive therapy were associated with diminished patient survival. Upon multivariate analysis, reduced patient survival was associated with the same variables as in the univariate analysis: anti-HCV-positive status, three-drug immunosuppressive therapy, and one or more episodes of acute rejection were associated with diminished graft survival. In our experience, anti-HCV-positive compared with anti-HCV-negative status was associated with a reduced graft (56% vs. 75%; P=.0002) and patient survival (68% vs. 83%; P=.0028).

Hepatocellular carcinoma in renal transplant patients.

INTRODUCTION: Chronic liver diseases, especially those related to hepatitis B (HBV) and C viruses (HCV), are a common problem in renal transplant patients. Hepatocellular carcinoma (HCC) is a complication of chronic liver diseases, incidence in the renal transplant cohort is higher than in the general population (1.4% to 4% vs 0.005% to 0.015%). METHODS: We retrospectively evaluated the incidence of HCC, its clinical presentation, the treatments, and the relation to chronic viral hepatitis among the population transplanted at our center between January 1980 and December 1998 and followed to August 2003. RESULTS: During the study period, six recipients among 534 renal transplants displayed HCC (incidence 1.12% of the entire population and 2.29% of patients with chronic viral hepatitis). Among the cohort five were men, and all had chronic viral hepatitis: three HBV, one HCV, and 2, a coinfection. HCC was diagnosed 124.1 (range 45 to 244) months after transplantation. All patients presented with abnormal liver function tests and tumors larger than 5 cm. Four had more than three tumors and three had an alpha-fetoprotein level higher than 400 IU/mL. Three patients received no treatment (survivals 1, 1, and 4 months); two patients, chemoembolization (survival 6 and 12 months); and one, surgical ethanol injections (survival 4 months). The overall survival was 4.5 months. CONCLUSION: HCC in renal transplant recipients is a common complication among patients with chronic viral hepatitis. The outcome was poor because HCC was detected at an advanced stage. Screening strategies for early diagnosis must be prospectively evaluated.

[Fatal acute hepatic failure with hepatocarcinoma presentation in a patient with renal transplant with asymptomatic chronic B and C hepatitis]. / Descompensación aguda fatal como forma de presentación de un hepatocarcinoma en un transplantado renal con hepatitis crónica B y C asintomática.

Hepatocellular carcinoma is a primary tumor complicating liver disease, associated with cirrhosis in 80-90% of the cases. A kidney transplant recipient with chronic B and C viral hepatitis was admitted because of general malaise, renal function impairment and positive AST, ALT and alkaline phosphatase tests, and very high alpha-fetoprotein levels. Ascites, spontaneous bacterial peritonitis and renal failure developed. A CT showed multiple liver masses. Renal failure required hemodialysis. The patient died 17 days after the initial symptoms with hepatic encephalopathy. A postmortem liver biopsy confirmed the diagnosis of cirrhosis and hepatocellular carcinoma (HCC). This report, as well as a few others, shows the accelerated evolution of chronic viral hepatitis in kidney transplant patients and questions the convenience of kidney transplantation and the adequate follow up in chronic viral hepatitis.

Descompensación aguda fatal como forma de presentación de un hepatocarcinoma en un transplantado renal con hepatitis crónica B y C asintomática. / [Fatal acute hepatic failure with hepatocarcinoma presentation in a patient with renal transplant with asymptomatic chronic B and C hepatitis]

Hepatocellular carcinoma is a primary tumor complicating liver disease, associated with cirrhosis in 80-90

of the cases. A kidney transplant recipient with chronic B and C viral hepatitis was admitted because of general malaise, renal function impairment and positive AST, ALT and alkaline phosphatase tests, and very high alpha-fetoprotein levels. Ascites, spontaneous bacterial peritonitis and renal failure developed. A CT showed multiple liver masses. Renal failure required hemodialysis. The patient died 17 days after the initial symptoms with hepatic encephalopathy. A postmortem liver biopsy confirmed the diagnosis of cirrhosis and hepatocellular carcinoma (HCC). This report, as well as a few others, shows the accelerated evolution of chronic viral hepatitis in kidney transplant patients and questions the convenience of kidney transplantation and the adequate follow up in chronic viral hepatitis.