https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.20466

Prevalence of hepatic steatosis in an urban population in the United States: Impact of ethnicity

https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.20973

Nonalcoholic fatty liver disease: From steatosis to cirrhosis

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1053/jhep.2003.50193

Nonalcoholic steatohepatitis: Summary of an AASLD Single Topic Conference

Background Immunosuppressive regimens with the fewest possible toxic effects are desirable for transplant recipients. This study evaluated the efficacy and relative toxic effects of four immunosuppressive regimens. Methods We randomly assigned 1645 renal-transplant recipients to receive standard-dose cyclosporine, mycophenolate mofetil, and corticosteroids, or daclizumab induction, mycophenolate mofetil, and corticosteroids in combination with low-dose cyclosporine, low-dose tacrolimus, or low-dose sirolimus. The primary end point was the estimated glomerular filtration rate (GFR), as calculated by the Cockcroft–Gault formula, 12 months after transplantation. Secondary end points included acute rejection and allograft survival. Results The mean calculated GFR was higher in patients receiving low-dose tacrolimus (65.4 ml per minute) than in the other three groups (range, 56.7 to 59.4 ml per minute). The rate of biopsy-proven acute rejection was lower in patients receiving low-dose tacrolimus (12.3%) than i...

/pdf/reduced-exposure-to-calcineurin-inhibitors-in-renal-3i5bjd6nsr.pdf

Reduced exposure to calcineurin inhibitors in renal transplantation.

Adiponectin has recently been shown to be a promising candidate for the treatment of obesity-associated metabolic syndromes. Replenishment of recombinant adiponectin in mice can decrease hyperglycemia, reverse insulin resistance, and cause sustained weight loss without affecting food intake. Here we report its potential roles in alcoholic and nonalcoholic fatty liver diseases in mice. Circulating concentrations of adiponectin decreased significantly following chronic consumption of high-fat ethanol-containing food. Delivery of recombinant adiponectin into these mice dramatically alleviated hepatomegaly and steatosis (fatty liver) and also significantly attenuated inflammation and the elevated levels of serum alanine aminotransferase. These therapeutic effects resulted partly from the ability of adiponectin to increase carnitine palmitoyltransferase I activity and enhance hepatic fatty acid oxidation, while it decreased the activities of two key enzymes involved in fatty acid synthesis, including acetyl-CoA carboxylase and fatty acid synthase. Furthermore, adiponectin treatment could suppress the hepatic production of TNF-alpha and plasma concentrations of this proinflammatory cytokine. Adiponectin was also effective in ameliorating hepatomegaly, steatosis, and alanine aminotransferase abnormality associated with nonalcoholic obese, ob/ob mice. These results demonstrate a novel mechanism of adiponectin action and suggest a potential clinical application of adiponectin and its agonists in the treatment of liver diseases.

/pdf/the-fat-derived-hormone-adiponectin-alleviates-alcoholic-and-l2zr96t1cu.pdf

The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice

methods We evaluated the natural history of chronic allograft nephropathy in a prospective study of 120 recipients with type 1 diabetes, all but 1 of whom had received kidney–pancreas transplants. We obtained 961 kidney-transplant–biopsy specimens taken regularly from the time of transplantation to 10 years thereafter. results Two distinctive phases of injury were evident as chronic allograft nephropathy evolved. An initial phase of early tubulointerstitial damage from ischemic injury (P<0.05), prior severe rejection (P<0.01), and subclinical rejection (P<0.01) predicted mild disease by one year, which was present in 94.2 percent of patients. Early subclinical rejection was common (affecting 45.7 percent of biopsy specimens at three months), and the risk was increased by the occurrence of a prior episode of severe rejection and reduced by tacrolimus and mycophenolate therapy (both P<0.05) and gradually abated after one year. Both subclinical rejection and chronic rejection were associated with increased tubulointerstitial damage (P<0.01). Beyond one year, a later phase of chronic allograft nephropathy was characterized by microvascular and glomerular injury. Chronic rejection (defined as persistent subclinical rejection for two years or longer) was uncommon (5.8 percent). Progressive high-grade arteriolar hyalinosis with luminal narrowing, increasing glomerulosclerosis, and additional tubulointerstitial damage was accompanied by the use of calcineurin inhibitors. Nephrotoxicity, implicated in late ongoing injury, was almost universal at 10 years, even in grafts with excellent early histologic findings. By 10 years, severe chronic allograft nephropathy was present in 58.4 percent of patients, with sclerosis in 37.3 percent of glomeruli. Tubulointerstitial and glomerular damage, once established, was irreversible, resulting in declining renal function and graft failure. conclusions Chronic allograft nephropathy represents cumulative and incremental damage to nephrons from time-dependent immunologic and nonimmunologic causes.

The natural history of chronic allograft nephropathy.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1053/jhep.2002.30692

NASH and insulin resistance: Insulin hypersecretion and specific association with the insulin resistance syndrome

BACKGROUND The role and burden of cyclosporine (CsA) nephrotoxicity in long-term progressive kidney graft dysfunction is poorly documented. METHODS The authors evaluated 888 prospective protocol kidney biopsy specimens from 99 patients taken regularly until 10 years after transplantation for evidence of CsA nephrotoxicity. RESULTS The most sensitive histologic marker of CsA nephrotoxicity was arteriolar hyalinosis, predicted by CsA dose and functional CsA nephrotoxicity. Striped fibrosis was associated with early initiation of CsA and the need for posttransplant dialysis (both P < 0.05). The 10-year cumulative Kaplan-Meier prevalence of arteriolar hyalinosis, striped fibrosis, and tubular microcalcification was 100%, 88.0%, and 79.2% of kidneys, respectively. Beyond 1 year, 53.9% had two or more lesions of CsA nephrotoxicity. Structural CsA nephrotoxicity occurred in two phases, with different clinical and histologic characteristics. The acute phase occurred with a median onset 6 months after transplantation, was usually reversible, and was associated with functional CsA nephrotoxicity (P < 0.05), high CsA levels (P < 0.05), and mild arteriolar hyalinosis (P < 0.001). The chronic phase of CsA nephrotoxicity persisted over several biopsies, occurred at a median onset of 3 years, and was associated with lower CsA doses and trough levels (both P < 0.05). It was largely irreversible and accompanied by severe arteriolar hyalinosis and progressive glomerulosclerosis (both P < 0.001). A threshold CsA dose of 5 mg/kg/day predicted worsening of arteriolar hyalinosis on sequential histology. CONCLUSIONS Pathologic changes of CsA nephrotoxicity were virtually universal by 10 years and exacerbated chronic allograft nephropathy. CsA is unsuitable as a universal, long-term immunosuppressive agent for kidney transplantation. Strategies to ameliorate or avoid nephrotoxicity are thus urgently needed.

Calcineurin Inhibitor Nephrotoxicity: Longitudinal Assessment by Protocol Histology

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1053/jhep.2002.36370

Hepatitis C virus genotype 3 is cytopathic to hepatocytes: Reversal of hepatic steatosis after sustained therapeutic response

PURPOSE: The aim of this study was to report the prevalence of postoperative complications and mortality of patients with colorectal cancer when treated by conventional surgery. METHODS: Morbidity and mortality following open resection for colorectal cancer were analyzed in 1,846 patients whose clinical, operative, and pathology data were prospectively documented over a 20-year period. RESULTS: Mortality following elective resection of the left and right colon was low, whereas overall morbidity was high (37.2 percent). Respiratory and cardiac complications were especially common. Incidence of clinically significant leakage was similar following right (0.5 percent) or left (1.1 percent) hemicolectomy. Incidence of anastomotic leakage was significantly higher after emergency right hemicolectomy (4.3 percent). Overall morbidity following excision of the rectum was high (40.2 percent). Respiratory and cardiac complications predominated. Incidence of clinically significant anastomotic leakage following anterior resection was low (2.9 percent). Over the years, there has been a decline in the number of patients with tumor demonstrated histologically in a line of resection, suggesting an improved local surgical clearance. CONCLUSIONS: These results following conventional surgery may be useful when evaluating new techniques.

Caroline L.-S. Fung

Papers

The natural history of chronic allograft nephropathy.

NASH and insulin resistance: Insulin hypersecretion and specific association with the insulin resistance syndrome

Calcineurin Inhibitor Nephrotoxicity: Longitudinal Assessment by Protocol Histology

Hepatitis C virus genotype 3 is cytopathic to hepatocytes: Reversal of hepatic steatosis after sustained therapeutic response

Postoperative morbidity and mortality following resection of the colon and rectum for cancer.