Alcohol and hepatitis C

BACKGROUND/AIMS: Alcohol use and hepatitis C are prominent risk factors for liver injury and this review offers the current understanding of each factor's effects on liver disease. METHODS: A Medline database search was preformed for English articles with a focus on alcohol, hepatitis C and liver disease. Article citations were also considered for further applicable articles, and the strongest studies were included in our review. RESULTS: Up to 60% of patients with hepatitis C have a past history of alcohol use. In patients with hepatitis C, chronic alcohol consumption of more than 5 drinks/day increases the rate of liver fibrosis, risk for cirrhosis, hepatocellular carcinoma, and, possibly, death from liver disease. Numerous studies have further found that even moderate amounts of alcohol can be detrimental to hepatitis C patients. The prevalence of hepatitis C is higher in alcoholics with advanced liver disease than in alcoholics without liver disease. Also, recent alcohol use decreases the response rate to interferon treatment. CONCLUSIONS: Hepatitis C and alcohol use are often co-occurring risk factors for liver disease, and though their interaction is not clear, it is known that heavy drinking significantly promotes liver disease progression.     

Recovery of Graft Function Early Posttransplant Determines Long-Term Graft Survival in Deceased Donor Renal Transplants

Introduction

Because kidneys show remarkable resilience and can recover function, we examined the impact on long-term graft survival in deceased donor renal transplants of both immediate graft function (IGF) and the rate of renal function recovery over the first 3 months after transplantation.

Methods

We included all cadaveric renal transplants from 1990 to 2007 (n = 583). Delayed graft function (DGF) was defined as the need for dialysis in the first 7 days posttransplant. Slow graft function (SGF) and IGF were defined by serum creatinine falls of <20% or >20% in the first 24 hours posttransplant respectively. Recovery of renal function was expressed as either the best creatinine clearance (CrCl) in the first 3 months post-renal transplantation (BCrCl-3mos) as calculated using the Cockcroft-Gault formula or as a percentage of actual versus expected value (as calculated from the donors' CrCl at procurement).

Results

There were 140 (23.6%) subjects who received extended criteria donor (ECD) organs. The overall graft survival at 1 and 5 years was 87.8% and 74%, respectively. The 5-year graft survivals for patients with IGF, SGF, and DGF were 85%, 76%, and 54%, respectively (P < .02). ECD kidneys showed twice the DGF rate (49% vs 23%, P < .001). BCrCl-3mos of <30 mL/min displayed a 5-year graft survival of 34%; 30 to 39 mL/min, 72%; 40 to 49 mL/min, 85%; and >50 mL/min, 82% (P < .001). Similarly, a recovery within 90% of expected CrCl in the first 3 months posttransplant correlated with 5-year graft survival of 81%; a recovery of 70% to 90%, with 65%; and a recovery of <70%, with 51% (P < .001).

Conclusion

Early graft function in the first 3 months showed a significant impact on long-term graft survival after deceased donor renal transplantation.     

A novel homozygous missense mutation of the leptin gene (N103K) in an obese Egyptian patient

Congenital leptin deficiency is a rare recessive genetic disorder resulting in severe hyperphagia and early onset obesity. It is caused by mutations in the LEP gene encoding leptin. To date, only two mutations have been identified in the LEP gene, Δ133G and R105W. We present the third reported mutation identified in an Egyptian patient with very low serum leptin levels and severe early onset obesity (BMI = 51). Direct sequencing of the coding region of the LEP gene revealed a novel homozygous missense mutation, N103K. The N103K mutation was not found in 100 alleles from 50 unrelated Egyptian normal-weight control subjects using polymerase chain reaction and restriction fragment length polymorphism analysis. In conclusion, this study presents the third reported mutation of the LEP gene and will provide further insight into the physiologic role of leptin in human obesity.     

Increased prevalence of infectious endocarditis in patients with type II diabetes mellitus

BACKGROUND: Patients with diabetes mellitus (DM) are at increased risk of infection. However, there are controversial reports about DM association with infectious endocarditis (IE). We evaluated the occurrence of IE in DM patients compared to a matched control. METHOD: Treatment files of inpatients' admission that contained discharge diagnosis (ICD-9 codes) from Veterans Health Administration hospitals were used for this study. ICD-9 codes for DM (n=293,124) and a control group with ICD-9 codes for hypertension without DM (n=552,623) were utilized for comparison. The prevalence of IE was studied using ICD-9 codes for IE. Multivariate analysis was performed adjusting for chronic and acute renal failure and aortic and mitral valve disease. Continuous variables were analyzed by unpaired t tests. Binary variables were analyzed using the chi-square test and Fisher's Exact Tests. RESULTS: IE was present in 1340 (0.5%) DM patients versus 1412 (0.3%) patients from the control group (relative increase of 40%). Using multivariate analysis adjusting for renal failure and valvular abnormalities, DM remained independently associated with IE (odds ratio=1.9; 95% confidence interval=1.8-2.1; P<.0001). CONCLUSION: Patients with type II DM have significantly higher prevalence of IE independent of renal failure or valvular abnormalities consistent with increased vulnerability of DM patients for infections.     

Increased prevalence of ventricular fibrillation in patients with type 2 diabetes mellitus

Diabetes mellitus (DM) is an independent risk for cardiovascular disease. Furthermore, patients with DM have increased risk for ventricular arrhythmia that is thought to be secondary to coronary artery disease (CAD) or congestive heart failure (CHF). We hypothesized that DM may cause ventricular arrhythmias independent of CAD or CHF. Using a large database, we evaluated the occurrence of ventricular fibrillation in patients with DM adjusting for CAD and CHF. We used patient treatment files (PTF), documents of inpatients' admissions containing discharge diagnoses (ICD-9 codes) from all Veterans Health Administration Hospitals. The patients were stratified in two groups: ICD-9 code for DM (293 124) and a control group with ICD-code for hypertension (HTN) but no DM (552 623). ICD-9 codes for ventricular fibrillation were used for this study. We performed uni- and multivariant analysis adjusting for comorbid conditions. Ventricular fibrillation was present in 563 (0.2%) vs 781 (0.1%) in the control group. Using multivariate analysis, DM remained independently associated with ventricular fibrillation (odds ratio: 1.7; confidence interval: 1.5–1.9; P < 0.000). Patients with DM have significantly higher prevalence of ventricular fibrillation independent of CAD or CHF, which in part may explain the higher risk of sudden death in patients with DM.     

Defining the contribution of renal dysfunction to outcome after traumatic injury

Renal failure is frequently considered an ominous development after injury, but its impact on outcome is poorly understood. Renal dysfunction or failure can be defined in many ways, such as elevated serum creatinine or the need for dialysis. The best method to characterize renal dysfunction however, is not known. To determine which definition of renal dysfunction correlates best with outcome, we retrospectively analyzed all injured patients from 1994 to 2000 who had an Injury Severity Score > or =14 and a hospital length of stay >2 days for the development of renal impairment. One hundred sixty-seven patients (4%) developed a serum creatinine > or =2.0 mg/dL and 49 patients required dialysis. Patients with renal dysfunction were older, suffered from more comorbid medical problems, were more seriously injured, and were more likely to have been in shock. A serum creatinine > or =2.0 mg/dL, the maximum creatinine level, and need for dialysis, were highly correlated with death, and the total number of dialysis treatments was not. All measures of renal dysfunction correlated relatively poorly with length of stay. These data demonstrate that the simple measure of serum creatinine > or =2.0 mg/dL is associated with a significantly increased likelihood of death in injured patients and is a stronger predictor than other common indicators of renal impairment.     

Claudin-2 is selectively enriched in and promotes the formation of breast cancer liver metastases through engagement of integrin complexes

The liver represents the third most frequent site of metastasis in patients with breast cancer. We performed in vivo selection using 4T1 breast cancer cells to identify genes associated with the liver metastatic phenotype. Coincident with the loss of numerous tight-junctional proteins, we observe claudin-2 overexpression, specifically in liver-aggressive breast cancer cells. We further demonstrate that claudin-2 is both necessary and sufficient for the ability of 4T1 breast cancer cells to colonize and grow in the liver. The liver-aggressive breast cancer cells display a claudin-2-mediated increase in their ability to adhere to extracellular matrix (ECM) components, such as fibronectin and type IV collagen. Claudin-2 facilitates these cell/matrix interactions by increasing the cell surface expression of α(2)β(1)- and α(5)β(1)-integrin complexes in breast cancer cells. Indeed, claudin-2-mediated adhesion to fibronectin and type IV collagen can be blocked with neutralizing antibodies that target α(5)β(1) and α(2)β(1) complexes, respectively. Immunohistochemical analyses reveal that claudin-2, although weakly expressed in primary human breast cancers, is readily detected in all liver metastasis samples examined to date. Together, these results uncover novel roles for claudin-2 in promoting breast cancer adhesion to the ECM and define its importance during breast cancer metastasis to the liver.