Is serum alanine transaminase level a reliable marker of histological disease in chronic hepatitis C infection?

Background: Approximately 20–30% of patients chronically infected with hepatitis C virus (HCV) have persistently normal alanine transaminase (PNALT) levels. These patients are described to have a mild degree of histological liver damage. We aimed to assess the histological liver changes in HCV patients with PNALT. Patients and methods: Sixty‐five patients with HCV and PNALT (group A) underwent a liver biopsy. PNALT was defined as three or more determinations identified to be within the normal range over 6 months or longer. The demographical features and histological changes were compared with 66 consecutive patients with chronic HCV infection and elevated ALT (group B). All patients had a detectable HCV RNA. Histological disease was scored according to the METAVIR system. Results: Females were more likely to have normal ALT levels (65%). The mean ALT level in Group A and B was 30 and 105 IU/L respectively. No patient in either group had normal histology. The mean necro‐inflammatory scores in groups A and B (2.0±0.68 vs 2.09±0.67) and the mean fibrosis scores (2.11±0.87 vs 2.24±1.04) were not significantly different. Bridging fibrosis in groups A and B was seen in 24.6 and 37.9% patients, respectively, while cirrhosis was seen in 6.2 and 7.6% patients respectively. Hepatic steatosis in groups A and B (0.94±0.86 vs 1.0±1.02 respectively) was also not significantly different and did not show any association with the fibrosis scores across the two groups. In group A, the necro‐inflammatory and fibrosis scores of patients with and without steatosis were not statistically significant. Age was the only predictor of normal ALT levels. However, increasing age did not show a significant increase in histological activity in either group beyond a certain age. Conclusion: This study demonstrates that ALT is a poor surrogate marker for inflammation and fibrosis in HCV patients. Given the presence of significant necro‐inflammation in PNALT patients, the risk/benefit ratio justifies treatment without the need for a liver biopsy.     

Chronic hepatitis C infection in patients with end stage renal disease: characterization of liver histology and viral load in patients awaiting renal transplantation

OBJECTIVES: Hepatitis C virus (HCV) is common in patients with end stage renal disease (ESRD) awaiting renal transplantation (RT). However, few data are available on the liver histology and viral titer in these patients relative to patients with HCV and normal renal function. The aims of this study were to assess liver histology, quantitative HCV-RNA titer, and alanine aminotransferase (ALT) levels in patients with ESRD awaiting RT, and to identify clinical predictors of histological progression to advanced bridging fibrosis and/or cirrhosis. METHODS: A total of 50 consecutive patients (mean age 42 yr, 62% male) with ESRD and HCV, who were awaiting RT, underwent liver biopsy. Two HCV populations, one with persistently normal ALT and another with elevated ALT, both with normal renal function, served as controls. HCV-RNA titer was assessed by quantitative PCR. RESULTS: Of the patients with ESRD, 94% had normal ALT. Log HCV RNA titer was significantly higher in patients with ESRD (5.8+/-0.3) than in either normal ALT (5.4+/-0.1) or elevated ALT (5.3+/-0.1) controls (p < 0.05). Knodell Histological Activity Index (HAI) in patients with ESRD was similar to that observed in control patients with normal ALT (4.8+/-0.4 vs 4.9+/-0.4) but significantly less (p < 0.05) than that observed in control patients with elevated ALT (8.4+/-0.5). The percentage of patients with bridging fibrosis or cirrhosis was similar in patients with ESRD and controls with persistently normal ALT (22% vs 13%) but significantly less (p < 0.001) than that observed in control patients with elevated ALT (48%). No significant differences in ALT, HCV-RNA titer, duration on hemodialysis, or time from first possible exposure was observed between ESRD patients with advance fibrosis (n = 11) and those with mild disease (n = 39). CONCLUSIONS: Our data suggest that liver biopsy is necessary to exclude significant liver pathology in patients with HCV and ESRD, and to help define those patients in whom interferon treatment might be helpful.     

End-stage renal disease and African American race are independent predictors of mild liver fibrosis in patients with chronic hepatitis C infection

Recipients of haemodialysis for end-stage renal disease (ESRD) have a higher prevalence of hepatitis C virus (HCV) infection relative to the general US population. However, the natural course of HCV infection in patients with renal failure, including African Americans (AAs) and Caucasian Americans (CAs), is not well known. We compared the degree of liver inflammation and fibrosis in AA and CA patients with HCV infection, with and without ESRD. This was a cross-sectional study of 156 HCV patients with ESRD (130 AAs and 26 CAs) with a liver biopsy between 1992 and 2005. The control group consisted of 138 patients (50 AAs; 88 CAs) with HCV infections and a serum creatinine <1.5 mg/dL with a liver biopsy between 1995 and 1998. Specimens were graded for inflammation and fibrosis using Knodell histological activity index. Compared to patients without renal impairment, HCV patients with renal failure were older and more likely to be AA. Patients with renal impairment had lower mean serum transaminases, a higher mean serum alkaline phosphatase levels (all P < 0.0001) and less hepatic necro-inflammation (Knodell histological activity index -I, II and III; P < 0.05) and fibrosis (Knodell histological activity index -IV; P < 0.0001). There were no racial differences in serum liver chemistry and histology scores among patients with renal failure. In a multivariate analysis, younger age, ESRD, AA race and a lower serum alkaline phosphatase were associated with lower odds for advanced liver fibrosis. Thus, HCV patients with ESRD had a lower degree of hepatic inflammation and fibrosis compared to those without renal disease, independent of race.     

What is the reason of elevated alanine aminotransferase level in HBeAg negative patients with low viremia: NAFLD or chronic hepatitis?

Background and study aims: Increased alanine aminotransferase (ALT) levels with negative hepatitis B virus (HBV) DNA by hybridization is a common problem in Turkey where is a mild endemic region. We aimed to evaluate the causes of elevated ALT levels in patients who are negative for hepatitis B e antigen (HBeAg) and HBV DNA (by hybridization) for at least 6 months.Patients-methods: Forty-nine patients were enrolled in this study. Histological changes [histological activity index (HAI), and the extent of fibrosis] were assessed according to the Knodell scoring system and steatosis were graded by Brunt’s classification for NAFLD in all patients.Results: A mean age of the patients was 34.9 ± 12.1 years (16-70). 43 (87.8%) of them were male. Mean ALT level was 95 ± 39.7 IU/L (50258). Hyperglycemia (>100 mg/dL) and hyperlipidemia were found in 12 and 24 patients, respectively. Hepatic steatosis (7 patients grade 1; 5 patients grade 2; and 7 patients grade 3), ground-glass hepatocyte, chronic hepatitis, and Wilson disease were found in liver biopsy in 38.8%, 32.6%, 26.6%, 2%, respectively. Mean HAI was 6.5 ± 3.6 (4-12) in chronic hepatitis. Seven patients (53.9%) were in stage 1 and 2 while 6 patients (46.1%) were in stage 3 and 4.Conclusions: Nonalcoholic fatty liver disease is the most common cause of elevated ALT levels in HBeAg negative/HBV DNA negative patients. Chronic hepatitis B was found in 26.6% of these patients.     

Pentoxifylline for the treatment of non-alcoholic steatohepatitis: a randomized controlled trial

Introduction. The burden of non-alcoholic steatohepatitis (NASH) is growing and current pharmacologic treatments are limited by side effects and inconsistent efficacy. Pilot studies suggest that pentoxifylline (PTX) can reduce liver injury in patients with NASH.Objective. We sought to determine the tolerability of PTX and its effect on aminotransferases and liver histology in patients with NASH.Material and methods. Thirty patients with biopsy proven NASH were randomized in a 2:1 fashion to receive 1,200 mg PTX or placebo for 12 months. Metabolic parameters, aminotransferases, liver histology and hepatic gene expression changes were compared.Results. At baseline the groups were similar. Adverse events were mild, most frequently headache and abdominal cramps, and did not differ between groups (p = NS). After 12 months, ALT and AST decreased from 92 ± 12 IU/L to 67 ± 13 IU/L and 67 ± 6 IU/L to 47 ± 6 IU/L (p < 0.05), respectively in patients treated with PTX. No significant effect was seen with placebo. Steatosis and cellular ballooning improved in the PTX group (p < 0.05), whereas no histological feature of steatohepatitis improved with placebo. However, between groups comparison of both biochemical and histological features were nonsignificant.Conclusion. Pentoxifylline is safe, well tolerated and improves transaminases and histology in patients with NASH when compared to baseline and may be a reasonable therapeutic modality for the treatment of NASH. However PTX failed to reduce transaminases compared to placebo and did not positively affect any of the metabolic markers postulated to contribute to NASH. Although animal data and small pilot studies in humans have suggested that PTX may be effective as a treatment for NASH, translating this therapy to clinical practice may prove challenging.     

HCV in patients with end-stage renal disease

Chronic hepatitis C virus (HCV) infection remains an important cause of liver disease in patients with end-stage renal disease (ESRD) and conversely, renal failure has a significant impact on morbidity and mortality throughout the natural history of chronic HCV and its treatment. With improved awareness within dialysis units of the potential for spread and the institution of preventative measures, the prevalence of HCV infection in the hemodialysis-dependent population has continued to decline since 1995. Use of HCV (+) donor kidneys is associated with an increase in the prevalence of liver disease, but when compared with continued hemodialysis, transplantation using these kidneys is associated with improved survival. Overall, survival in patients with chronic HCV infection appears to be better after renal transplantation when compared with maintenance hemodialysis, and transplant should be considered for these patients. Data support the use of interferon and the improved efficacy of pegylated interferon formulations for treatment of chronic HCV infection in ESRD patients, although tolerability continues to be troublesome. The newest and most promising data regarding the treatment of HCV in ESRD involve the combination of reduced dose ribavirin with interferon or pegylated interferon suggesting similar enhancements in sustained virologic response (SVR) as seen in non-ESRD patients, but caution is advised, as all studies to date used ribavirin plasma concentration monitoring in patient with ESRD. Finally, with regard to postrenal transplant treatment of HCV infection, there is no evidence to support treatment with interferon-based therapy and pretransplant treatment remains the best option whenever possible.     

Metabolic factors are associated with serum alanine aminotransferase levels in patients with chronic hepatitis C

Background

Although serum alanine aminotransferase (ALT) activity is an important marker for the management of chronic hepatitis C (CHC), the factors associated with serum ALT levels remain to be fully understood. This study aimed to clarify the association between serum ALT levels and clinical, histological, and virological factors in patients with CHC.

Methods

We retrospectively analyzed 256 patients with CHC who underwent liver biopsy, and classified them into three groups according to serum ALT levels: normal to minimal (<40?IU/L), mild (40?C80?IU/L), and moderate to severe elevation (??80?IU/L). All demographic and laboratory data were collected at the time of liver biopsy. All biopsies were evaluated for fibrosis, inflammation, and steatosis. Glucose metabolism was assessed by various indices derived from oral glucose tolerance tests, including the homeostasis model assessment for insulin resistance (HOMA-IR). In 180 patients, visceral fat area was measured at the umbilical level by abdominal computed tomography.

Results

Ordered logistic regression analysis showed that higher serum ALT levels were significantly associated with male sex, lower high-density lipoprotein cholesterol (HDL-C), higher HOMA-IR, and higher grades of histological inflammation and steatosis. HOMA-IR, HDL-C, and hepatic steatosis were associated with visceral fat accumulation.

Conclusions

Metabolic factors, as well as sex and hepatic inflammation, are independent risk factors for serum ALT elevation in hepatititis C virus (HCV)-infected patients. Metabolic factors may offer targets to decrease serum ALT levels.     

Effect of l-arginine infusion on systemic and renal hemodynamics in hypertensive patients

This study was designed to compare the renal endothelial function in patients with essential hypertension and normal renal function with that in hypertensive patients with renal insufficiency. We studied the effects of l-arginine (500 mg/kg intravenously over 30 min) on renal hemodynamics in 30 normotensive control subjects, 32 patients with mild to moderate essential hypertension who had normal renal function, and seven hypertensive patients with renal insufficiency who had a serum creatinine concentration >2.0 mg/mL and a glomerular filtration rate <50 mL/min/1.48 m². l-Arginine infusion similarly reduced the mean blood pressure between the three groups (normotensive: −9.7% ± 0.7%, hypertensives with normal renal function: −10.2% ± 0.8%, and hypertensives with renal insufficiency: −8.2% ± 1.3%). The l-arginine–induced decrease in renal vascular resistance was smaller in essential hypertensive patients than in normotensive subjects (−11.0% ± 2.2 v −19.8% ± 2.1%, P <.05). However, l-arginine had no effect on the renal vascular resistance in hypertensive patients with renal insufficiency (1.6% ± 4.8%). Urine nitrite/nitrate levels in response to l-arginine significantly increased in the three groups in the following order: patients with renal insufficiency (47% ± 15%), essential hypertensive patients (87% ± 10%), and normotensive subjects (129% ± 12%). The glomerular filtration rate was unaffected by l-arginine in normotensive and essential hypertensive patients (3.1% ± 2.4% and 4.2% ± 2.5%), but significantly decreased in hypertensive patients with renal insufficiency (−13.7% ± 6.1%). These findings suggest that the ability of the l-arginine–nitric oxide–cGMP pathway to relax the renal vascular tone may be impaired in essential hypertensive patients and more markedly blunted in hypertensive patients with renal insufficiency, in parallel with increasing serum creatinine concentrations.     

Comparison of clinical features and liver histology in hepatitis C-positive dialysis patients and renal transplant recipients

Objective: Liver biopsies in hepatitis C virus (HCV)-positive end stage renal disease (ESRD) patients before or after renal transplantation were compared to study the effect of transplant-related immunosuppression. Methods: In this prospective study all patients on the active transplant list and all patients with functioning renal transplants at our hospital were tested for HCV antibody (ELISA-2) over a 30-month period. HCV infection was confirmed by polymerase chain reaction in most patients. All HCV-positive patients were asked to undergo liver biopsy without regard to serum transaminase levels. Patients were interviewed, examined, and had detailed chart review. By protocol, liver histology was evaluated according to stage and inflammatory activity in a blinded fashion. Results: There were 129 HCV-antibody–positive patients, of 795 tested. Sixty-seven agreed to liver biopsy. Of these, 22 patients had never been transplanted and 45 had received transplants. Mean transplant duration before biopsy was 41.2 months (range, 1–204 months). Transplant patients had significantly longer duration of ESRD and estimated duration of HCV infection than patients not transplanted. Dialysis patients had significantly more portal inflammatory activity and lymphoid follicles on biopsy whereas transplant patients had more piecemeal necrosis and steatosis. However, the total histological activity score and stage were similar between groups. Multivariate analysis confirmed the association between transplant and steatosis. But independent variables including transplant duration, HCV infection duration, and ESRD duration were not correlated with histological findings. Conclusion: Renal transplantation may not be associated with an increased risk of progressive liver disease in HCV-positive patients, compared with ESRD patients receiving chronic dialysis. Long-term studies with serial liver biopsies are needed to resolve this issue.     

Clinical significance of activity of ALT enzyme in patients with hepatitis C virus

AIM： TO investigate serum alanine aminotransferase （ALT） levels in relation to the clinical, biochemical, ultrasonographic and histological characteristics of patients with hepatitis C virus.
METHODS： Duration of disease, HCV-RNA, liver steatosis, and the hepatitis activity index （HAI） were correlated with serum ALT in 36 patients with HCV. ALT values were also investigated in 16 control subjects without any liver diseases.
RESULTS： In bivariate analyses, ALT levels correlated with duration of HCV infection （P 〈 0.01）, HCV-RNA （P 〈 0.05）, and the HAI （P 〈 0.01）. Among the components of the HAI, ALT concentrations were significantly associated with periportal bridging/necrosis （P 〈 0.01） and fibrosis （P 〈 0.05）. In multivariate analysis, periportal bridging/ necrosis （β = 0.508; P 〈 0.01）, duration of HCV infection （β = 0.413; P 〈 0.01）, and HCV-RNA （β = 0.253; P 〈 0.05） were independently associated with ALT activity. The normal ALT activity for men and women was 〈 23 IU/L and 〈 22 IU/L, respectively.
CONCLUSION： In patients with HCV, alterations in the liver tissue as reflected by ALT elevation are mainly associated with periportal bridging/necrosis, viral load and duration of disease. A cut-off value 〈 23 IU/L distinguished with high diagnostic accuracy healthy controls from patients with HCV.     

Validation and comparison of simple noninvasive models for the prediction of liver fibrosis in chronic hepatitis C

Introduction. Although it is standard procedure in the evaluation of liver diseases, biopsy is an invasive method subject to sampling error and intra or inter-observer variability. Thus, surrogate markers of liver fibrosis have been proposed, with variable availability and accuracy.Aim. Validate and compare the performance of APRI and FIB-4 as predictors of liver fibrosis in HCV patients.Material and methods. Cross-sectional study including patients with HCV-RNA (+) who underwent liver biopsy. Significant fibrosis was defined as METAVIR stage ≥ 2. The diagnostic performance of the models in predicting significant fibrosis were evaluated and compared by ROC curves.Results. The study included 119 patients, mean age 43.7 ± 10.6 years and 62% males. Significant fibrosis was identified in 41 patients. The AUROCs observed were: APRI = 0.793 ± 0.047, FIB-4 = 0.811 ± 0.045 and AST/ALT = 0.661 ± 0.055 (P = 0.054 for APRI vs. AST/ALT, and P = 0.014 for FIB-4 vs. AST/ALT). Considering classic cutoffs, the PPV and NPV for APRI and FIB-4 were, respectively, 77% and 92% and 83% and 81%. Thirteen (19%) patients were misdiagnosed by APRI and 16 (18%) by FIB-4. By restricting the indication of liver biopsy to patients with intermediate values, it could have been correctly avoided in 47% and 63% of the patients with APRI and FIB-4, respectively.Conclusion. The models APRI and FIB-4 were superior to AST/ALT ratio in the diagnosis of significant fibrosis in chronic HCV infection. Even though the overall performance of APRI and FIB-4 was similar, a higher proportion of patients may be correctly classified by FIB-4.     

Correlation between serum HCV RNA and aminotransferase levels in patients with chronic HCV infection

Cross-sectional studies on the correlation between serum hepatitis C virus (HCV) RNA and alanine aminotransferase (ALT) levels in patients with chronic hepatitis C have yielded conflicting results. We conducted a longitudinal study to examine the correlation between HCV viremia and serum ALT levels in individual patients over time. Serial samples (mean 9) from 25 patients with chronic HCV infection, including interferon-treated and untreated immunocompetent and immunosuppressed patients, collected over a period of 1–4.8 years (mean 2.6 years) were tested for HCV RNA and ALT levels using a highly reproducible quantitative (bDNA) assay. A significant correlation was found between serum HCV RNA and ALT levels in the patients who received IFN therapy, but no correlation was observed in the untreated patients. Among the untreated patients, the immunosuppressed patients had significantly higher HCV RNA levels (39±4 vs 3.6±8 Meq/ml,P<0.0001) but significantly lower ALT (56±11 vs 97±12 units/liter,P=0.03) levels when compared to the immunocompetent ones. In summary, we found no correlation between serum HCV RNA and ALT levels in chronic hepatitis C patients who are not receiving interferon therapy. Immunosuppression results in higher HCV RNA but lower ALT levels.     

Relationships between serum aminotransferase levels, liver histologies and virological status in patients with chronic hepatitis C in Taiwan

In patients with chronic hepatitis C, the relationships between serum alanine aminotransferase (ALT) levels, histological liver injury and serum hepatitis C virus (HCV) RNA titres remain controversial. To evaluate these relationships, 93 Chinese patients with histological diagnosis of chronic hepatitis C were enrolled for this study. Serum ALT levels, HCV-RNA titres and HCV genotypes were examined. The histology was evaluated according to a modified histological activity score based on the degree of periportal necro-inflammation, intralobular necro-inflammation, portal inflammation, total necro-inflammation and fibrosis. The mean serum ALT level was significantly higher in patients with severe intralobular necro-inflammation activity than in patients with mild or no activity (P= 0.013). However, scores of intralobular activity were only weakly correlated with serum ALT levels (r= 0.27) and could not be used to adequately predict ALT values. Serum ALT levels showed no significant correlation with the scores of portal inflammation, periportal necro-inflammation, total necro-inflammation and fibrosis. Also, there was no significant difference in the mean serum ALT level among different serum HCV-RNA levels and HCV genotypes. Serum HCV-RNA titres and genotypes showed no significant correlation with liver histology and serum HCV-RNA titres were only weakly correlated with the total necro-inflammatory score (r= 0.27). In conclusion, although serum ALT levels were higher in patients with more severe intralobular necro-inflammatory activity, the correlation was not strong enough to adequately predict ALT values. Serum HCV-RNA titres and genotypes also showed no significant correlation with serum ALT levels and liver histologies.     

Low prevalence of hepatitis c virus infection in porphyria cutanea tarda in Germany

Previous studies from Spain, Italy, and France have demonstrated a high prevalence (71% to 91%) of antibodies against hepatitis C virus in patients with porphyria cutanea tarda (PCT). To determine the role of hepatitis C virus (HCV) in PCT in Germany, we have assessed the prevalence of antibodies against HCV and hepatitis B virus (HBV) in 106 patients (mean age, 60 ± 14 years) with the disease. Eight of 106 patients (8%) were positive for HCV antibodies and HCV RNA using second-generation enzyme-linked immunosorbent assay (ELISA), recombinant immunoblot assay, and polymerase chain reaction. Antibodies against HBV core antigen were found in 14 patients (13%). Of the patients with antibodies against HCV alanine transaminase (ALT) (aspartate transaminase [Ast]) levels above normal occurred in 71% (86%). Because elevated ALT (AST) levels were also found in 51% (64%) of 88 patients without markers of HCV or HBV, we suggest that liver damage in PCT may exist in absence of these viruses. This is supported by the finding that in patients without HCV or HBV markers, higher serum ALT and AST activities were found in patients with overt disease or relapse (ALT, 59 ± 44 U/L; AST, 37 ± 21 U/L), whereas patients in remission displayed significantly lower serum enzyme activities (ALT, 16 ± 8 U/L; AST, 16 ± 7 U/L), (P < .001). These results indicate that HCV infection does not play a major role in the pathogenesis of PCT in Germany.     

Aspirin,beta-blocker,and angiotensin-converting enzyme inhibitor therapy in patients with end-stage renal disease and an acute myocardial infarction

OBJECTIVES: We sought to examine the use and impact of standard medical therapies in patients with end-stage renal disease (ESRD) faced with an acute myocardial infarction (AMI). BACKGROUND: The poor prognosis of patients in this high-risk population has become increasingly well recognized. METHODS: Using the ESRD database and the Cooperative Cardiovascular Project (CCP) database, we identified AMI patients who were receiving either peritoneal dialysis or hemodialysis before admission. The early administration of aspirin and beta-blockers was compared between ESRD and non-ESRD patients and the effect of these therapies on 30-day mortality was evaluated with logistic regression models. RESULTS: The cohort consisted of 145,740 patients without ESRD and 1,025 patients with ESRD. Aspirin (67.0% vs. 82.4%, p < 0.001), beta-blockers (43.2% vs. 50.8%, p < 0.001), and angiotensin-converting enzyme (ACE) inhibitors (38.5% vs. 60.3%, p < 0.001) were less likely to be administered to ESRD patients than to non-ESRD patients. The benefit of these therapies on 30-day mortality was similar among ESRD patients (aspirin: relative risk [RR] 0.64; 95% confidence interval [CI] 0.50 to 0.80; beta-blocker: RR 0.78; 95% CI 0.60 to 0.99; ACE inhibitor: RR 0.58; 95% CI 0.42 to 0.77) and non-ESRD patients (aspirin: RR 0.57; 95% CI 0.55 to 0.58; beta-blocker: RR 0.70; 95% CI 0.68 to 0.72; ACE inhibitor: RR 0.64; 95% CI 0.63 to 0.66). CONCLUSIONS: End-stage renal disease patients are far less likely than non-ESRD patients to be treated with aspirin, beta-blockers, and ACE inhibitors during an admission for AMI. The lower rates of usage for these medications, particularly aspirin, may contribute to the increased 30-day mortality. These findings demonstrate a marked opportunity to improve care in this population.     

Is hepatitis C more aggressive in renal transplant patients than in patients with end-stage renal disease?

BACKGROUND: The eventual impact of immunosuppression on the natural history of hepatitis C virus (HCV) infection in patients with end-stage renal disease (ESRD) is still unknown because of the lack of comparative data for HCV-infected patients with ESRD and renal transplant patients. The aim of this study was to compare the biochemical and histological characteristics of chronic HCV infection in renal transplants patients and ESRD patients undergoing hemodialysis. METHODS: Thirty-eight renal transplant patients and 38 ESRD patients undergoing hemodialysis who were chronically infected with HCV and were matched for gender, age at infection, and estimated time of infection were included in the study. The groups were compared regarding laboratory and histological variables. RESULTS: Renal transplant patients showed similar alanine aminotransferase and higher gamma-glutamyltransferase levels (P = 0.05) when compared with ESRD patients. Comparative analysis of histological variables revealed a higher proportion of cases with septal fibrosis (P = 0.04) and confluent necrosis (P = 0.01) among transplant-recipient patients. No difference between groups was observed regarding the intensity of portal and periportal inflammatory infiltrates. Steatosis was more prevalent among transplant-recipient patients (P < 0.001). There was no difference between groups regarding the prevalence of lymphoid aggregates or bile duct injury. CONCLUSION: Renal transplant patients had a larger proportion of cases with septal fibrosis and confluent necrosis than did ESRD patients, suggesting that renal transplantation might modify the natural history of hepatitis C in ESRD patients, leading to a more aggressive liver disease.     

Coronary artery disease in renal transplant recipients: an angiographic study

BackgroundCardiovascular disease is the leading cause of mortality in renal transplant recipients (RT). Coronary artery disease (CAD) in such patients is poorly studied.MethodsDuring 2012–2017, 50 patients with a renal graft (functioning for a minimum of 6 months) were subjected to coronary angiography in our institution. They were matched (for age, gender, diabetes, and indication for angiography) with 50 patients with end-stage renal disease (ESRD) undergoing chronic dialysis and 50 patients with normal renal function who were subjected to coronary angiography during the same period. The extent and severity of CAD were assessed by using the SYNTAX score.ResultsRT had a significantly longer duration of ESRD than patients on dialysis (17.5±7.1 vs. 8.5±8.7 years, p<0.01). Mean SYNTAX score was 13.3±12.0 in RT, 20.6±17.5 in patients on dialysis, and 9.4±9.2 in control patients (p<0.01). At least one significantly calcified lesion was present in 75.7% of RT recipients, 92.1% of patients on dialysis, and 15.8% of control patients (p<0.01). Percutaneous coronary intervention (PCI) was successful in 93.8% of the attempted cases in RT, 75% of patients on chronic dialysis, and 100% of control patients (p=0.04). In the RT group, SYNTAX score significantly correlated with smoking (p=0.02) and the total vintage of ESRD (p=0.04).ConclusionsIn this angiographic study, CAD was less severe in RT than in patients on long-term dialysis despite a longer duration of ESRD. Coronary artery calcification was highly prevalent after renal transplantation. PCI in RT had a high rate of angiographic success.     

Hepatitis C in hemodialysis: the contribution of injection drug use

BackgroundHepatitis C virus (HCV) infection is the most common cause of acute or chronic hepatitis in patients on hemodialysis (HD). The purpose of this study was to describe the prevalence of positive HCV RNA and investigate injection drug use as an emerging risk factor in patients with chronic renal disease on HD.MethodsThis was a multicenter cross-sectional study with 325 patients with chronic renal disease on HD in the period between August 1, 2005 to August 30, 2006, receiving care at four institutions in the city of Porto Alegre, Southern Brazil. Epidemiological data were collected by means of a structured questionnaire. The following laboratory tests were performed: alanine aminotransferase (ALT), anti-hepatitis C virus antibodies (anti-HCV), and qualitative polymerase chain reaction (PCR).ResultsOf 325 patients, 68 had positive HCV RNA results. The comparison between patients with positive and negative PCR results revealed signifi cant differences in duration of HD (mean = 71 versus 52.4 months; p = 0.02); previous blood transfusion (92% versus 72%; p < 0.01); injection drug use (13% versus 0.7%; p < 0.01); anti-HCV positivity at start of HD therapy (60% versus 4%; p < 0.01); and mean ALT value (39 versus 26.5; p < 0.01). Logistic regression analysis showed a positive HCV RNA independently associated to being on HD for more than five years [OR: 2.1 (95% CI 1.2 - 3.8)]; previous blood transfusion [OR: 3.7 (95% CI 1.4 - 9.5)]; and injection drug use [OR: 22.6 (95% CI 4.2 - 119.6)].ConclusionInjection drug use was an independent risk factor for HCV infection among chronic renal disease patients on HD.     

Hepatitis C infection in potential recipients with normal liver biochemistry does not preclude renal transplantation

The hepatitis C virus (HCV) may be an important cause of chronic liver disease in renal transplant recipients. We investigated retrospectively the incidence and outcome of HCV infection in long-term renal transplant recipients and patients on hemodialysis. Stored, pretransplant sera of transplant recipients with normal liver biochemistry at surgery were tested for hepatitis C by a second-generation enzyme immunoassay. Hemodialysis patients were tested by a first-generation enzyme-linked immunosorbent assay (ELISA) against c100-3. We studied 252 renal transplant recipients and 58 hemodialysis patients followed for 65±10 months and 26±6 months, respectively. Fifteen percent (38/252) of the transplant recipients were HCV positive as were 3/58 (5%) of the hemodialysis patients. Over liver disease occurred in 22/252 (8.7%) transplant recipients and none in the hemodialysis group. Thirty-six percent (8/22) of transplant recipients with overt liver disease were HCV positive. No HCV-positive patients died of liver failure. Of six biopsies in the HCV-positive transplant group, two had histological evidence of CAH. CAH was seen in six of eight biopsies in the HCV-negative transplants and two of these latter patients progressed to cirrhosis. No hemodialysis patients had clinical or histological evidence of chronic liver disease. Two HCV-negative transplant patients died of liver failure, while no deaths related to liver disease occurred in hemodialysis patients regardless of HCV status. We conclude that hepatitis C may cause chronic hepatitis in renal transplant patients. However, chronic liver disease in HCV-positive renal transplant recipients appears to be a clinically and histologically benign entity. HCV-positive potential renal allograft recipients with normal liver biochemistry should not be excluded from renal transplantation.