Pretransplant hepatitis C virus infection and its effect on the post-transplant course of living renal allograft recipients

BACKGROUND: Hepatitis C virus infection (HCV) is a main health problem in end-stage renal disease (ESRD) patients. The effect of pretransplant HCV infection on survival among ESRD patients who have undergone renal transplantation is controversial. We report the results of a large monocenter study that evaluated the effect of hepatitis C on the patient, and on graft survival in renal-transplanted patients who received living donated allograft. METHODS: A historical cohort study, we investigated all 1006 patients who received a living kidney transplant at Baghiatollah Medical Center in Tehran, Iran, between March 1995 and October 2001 (up to 85 months follow up). Patients' sera had been routinely assayed for anti-HCV antibodies and hepatitis B surface antigen (HBsAg) at the time of transplantation. The HBsAg-positive patients were excluded from the survival analysis. Survivals were examined using Kaplan-Meier analysis and compared using the log-rank test. Multivariate analysis was performed using Cox's model. RESULTS: Forty-five patients (4.5%) were anti-HCV-antibody positive. Anti-HCV-antibody-positive patients spent a longer time on dialysis and had a higher rate of retransplantation. There were no differences in recipients' sex and age and donors' age between the two groups. The 7-year patient survival rate was 89.9% in the anti-HCV-antibody-positive group and 95.5% in the HCV-negative group (P = 0.74). Seven-year graft survival was 82.0% and 75.0% in the anti-HCV-antibody-positive and HCV-negative groups, respectively (P = 0.39). In the multivariate analysis, age was the only significant parameter correlated with patient survival (P = 0.02). CONCLUSIONS: HCV infection does not seem to influence patient and graft survival within a medium-time follow up in living allograft recipients, and anti-HCV-antibody positive status (alone) is not a contraindication for renal transplantation. However, further studies are needed to better define the role of HCV infection in long-term prognosis.     

Serum measures of iron status and HFE gene mutations in patients with hepatitis B virus infection

Aim: We tested associations between HFE mutations and hepatitis B virus (HBV) infection. We also explored measures of total body iron status and their association with chronic HBV infection. Methods: Serum measures of iron status and HFE mutations (C282Y, H63D, and S65C) were assessed in 344 Iranian patients with chronic HBV infection (214 asymptomatic carriers, 130 patients with chronic progressive liver disease [CPLD]) and 302 controls. Results: Frequencies of HFE mutations did not differ between patients with chronic HBV infection and controls (C282Y: P=0.9, H63D: P= 0.8, S65C: P=0.9). By logistic regression, advanced hepatic fibrosis was associated with HFE H63D mutation (OR=13.1, P=0.006; 95% CI=2.0-84.1). Higher levels of serum ferritin and transferrin saturation were observed in patients with CPLD than in healthy controls (P=0.0001 and 0.01, respectively, adjusted for age and sex). None of the serum iron measures was related to liver fibrosis stage or necroinflammatory grade. Conclusion: Serum iron measures are associated with chronic progressive hepatitis B. Carriage of HFE mutations is not associated with the presence of chronic HBV infection or values of serum iron measures in this population, although HFE H63D is associated with more advanced hepatic fibrosis.     

Interferon Alpha-2b Therapy in Chronic Hepatitis Delta

Background:

Approximately 5% of hepatitis B virus (HBV) carriers are coinfected with hepatitis D virus (HDV). HBV/HDV coinfection is a major cause of cirrhosis and end stage liver disease in chronic HBsAg carriers. The only approved therapy for chronic hepatitis delta is interferon alpha (IFN α) in either pegylated or conventional forms. Although higher doses and longer durations of IFN α therapy in HBV/HDV coinfected patients are currently applied, yet treatment response is low.

Objectives:

We aimed to determine the efficacy of IFN α-2b therapy in patients with HBV/HDV coinfection.

Patients and Methods:

In this cross sectional study, 20 HBsAg carriers with positive Anti-HDVAb and RT-PCR for HDV RNA were recruited and treated for three year duration with 5 million units (MU) of IFN α-2b, three times weekly or one year with 5 MU of IFN α-2b daily. Sustained virological response (SVR) was defined as a negative qualitative HDV RT-PCR, 6 months after treatment cessation.

Results:

Overall, 3 (15%) subjects achieved SVR, 10 cases (50%) relapsed after treatment cessation and 7 (35%) patients did not clear HDV during the treatment.

Conclusions:

HDV coinfection with HBV had very low response rate to high doses and long durations of IFN α-2b therapy.     

Non-Viral Related Liver Enzymes Elevation After Kidney Transplantation

Background:

Liver enzymes elevations (LEE) can be observed after kidney transplantation due to multifactorial causes.

Objectives:

We performed a retrospective study on 1589 kidney transplants, 971 male and 618 female, who were hepatitis B surface antigen (HBsAg) and hepatitis C virus-antibody (HCV Ab) negative, and had no other liver diseases, to detect the prevalence of LEE and its risk factors in these patients between May 2008 and May 2010.

Patients and methods:

Liver enzymes and other biochemical parameters were measured in all recipients. Patients were divided into three groups, according to laboratory test time since transplantation: Group I, less than 3 months, Group II, 4 - 12 months after transplantation, and Group III, more than one year post-transplantation.

Results:

The highest LEE was more frequent in older patients (P < 0.001) and male individuals (P < 0.001). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were higher in patients who received kidneys from deceased donors (10.4% and 23.8%, respectively) as compared to living donor transplants (5.6% and 14.8%, respectively) (P < 0.001). The elevation of ALT was the liver enzyme abnormality after kidney transplantation with the highest prevalence (34.3%). The levels of ALT and AST were significantly elevated within the first 3 months after transplantation, followed by the 4-12 months period (P < 0.001). There was a reverse correlation between liver enzyme levels and renal allograft function in both univariate and linear regression analyses. This correlation increased over time. There was also a significant relation between cyclosporine blood levels and liver enzyme values in the univariate analysis. However, this relationship was attenuated over time. Elevated liver enzymes also correlated with anemia.

Conclusions:

The LEE is a common finding among kidney transplant recipients. Serial monitoring of aminotransferases, particularly ALT, should be performed in all patients after kidney transplantation.     

Occult Hepatitis C Virus Infection in Patients With Autoimmune Hepatitis

Background:

Occult hepatitis C virus infection (OCI) is recognized by finding hepatitis C virus (HCV) RNA in hepatocytes without detectable anti-HCV antibodies and viral RNA in plasma. Autoimmune hepatitis (AIH) is a chronic and generally progressive disease without exactly-identified etiology.

Objectives:

This study aimed to determine the prevalence of OCI among patients with AIH and to evaluate the tests used to rule out HCV infection in diagnosing AIH.

Patients and Methods:

Between July 2012 to February 2013, 35 Iranian patients with AIH who attended Tehran Hepatitis Center were investigated. For identifying OCI, detection of HCV RNA in both ultracentrifuged serum samples and peripheral blood mononuclear cells (PBMCs) was used. Data analysis was performed using SPSS.

Results:

Six males and 29 females with mean disease duration of 77.1 ± 39.5 month and mean age of 43.62 ± 12.67 years were investigated. All cases were negative for anti-HCV antibody and we could not find any HCV RNA in ultracentrifuged serum samples and PBMCs.

Conclusions:

With our laboratory diagnostic method, it seems that there are no cases of OCI in patients with AIH. However, we recommend further studies with more samples and more precise laboratory method.     

The Therapeutic Use of Analgesics in Patients With Liver Cirrhosis: A Literature Review and Evidence-Based Recommendations

Context:

Pain management in cirrhotic patients is a major clinical challenge for medical professionals. Unfortunately there are no concrete guidelines available regarding the administration of analgesics in patients with liver cirrhosis. In this review we aimed to summarize the available literature and suggest appropriate evidence-based recommendations regarding to administration of these drugs.

Evidence Acquisition:

An indexed MEDLINE search was conducted in July 2014, using keywords “analgesics”, “hepatic impairment”, “cirrhosis”, “acetaminophen or paracetamol”, “NSAIDs or nonsteroidal anti-inflammatory drugs”, “opioid” for the period of 2004 to 2014. All randomized clinical trials, case series, case report and meta-analysis studies with the above mentioned contents were included in review process. In addition, unpublished information from the Food and Drug Administration are included as well.

Results:

Paracetamol is safe in patients with chronic liver disease but a reduced dose of 2-3 g/d is recommended for long-term use. Non-steroidal anti-inflammatory drugs (NSAIDs) are best avoided because of risk of renal impairment, hepatorenal syndrome, and gastrointestinal hemorrhage. Most opioids can have deleterious effects in patients with cirrhosis. They have an increased risk of toxicity and hepatic encephalopathy. They should be administrated with lower and less frequent dosing in these patients and be avoided in patients with a history of encephalopathy or addiction to any substance.

Conclusions:

No evidence-based guidelines exist on the use of analgesics in patients with liver disease and cirrhosis. As a result pain management in these patients generates considerable misconception among health care professionals, leading under-treatment of pain in this population. Providing concrete guidelines toward the administration of these agents will lead to more efficient and safer pain management in this setting.