Nonalcoholic Steatohepatitis—A Long-Term Follow-Up Study: Comparison with Alcoholic Hepatitis in Ambulatory and Hospitalized Patients

A previous publication analyzed the clinicopathological characteristics of 105 patients with steatohepatitis: 32 nonalcoholic, 21 ambulatory alcoholics, and 52 hospitalized alcoholics; we now report an up to 12-year follow-up (mean 5.9 ± 4.7). Between 1988 and 1993, all patients with a histological diagnosis of steatohepatitis were included; necrosis, inflammation, Mallory bodies, and fibrosis were graded. Complete follow-up data were obtained in 78%. Survival curves were similar between nonalcoholic and ambulatory alcoholics; they were, however, better in nonalcoholic than hospitalized alcoholics (P < 0.0001), and in ambulatory relative to hospitalized (P = 0.0001) alcoholics. Nonalcoholics had a better prognosis than the combined alcoholic groups (P = 0.001). Patients with moderate to severe Mallory bodies and severe fibrosis had a significantly worse survival (P < 0.01), whereas severity of hepatocellular damage and neutrophil or mononuclear infiltration had no significant impact. In conclusion, alcoholic patients as a whole had a worse prognosis, yet the ambulatory subgroup had a prognosis similar to nonalcoholic patients.     

Innate Immune Reactivity of the Ileum–Liver Axis in Nonalcoholic Steatohepatitis

Background  

Over-proliferation and bacterial translocation of Gram-negative bacilli within the intestinal flora, and increased portal venous levels of endotoxins, are involved in nonalcoholic steatohepatitis (NASH).     

Nonalcoholic Fatty Liver Disease/Non-Alcoholic Steatohepatitis in Childhood: Endocrine-Metabolic “Mal-Programming”

Context:

Nonalcoholic Fatty Liver Disease (NAFLD) is the major chronic liver disease in the pediatric population. NAFLD includes a broad spectrum of abnormalities (inflammation, fibrosis and cirrhosis), ranging from accumulation of fat (also known as steatosis) towards non-alcoholic steatohepatitis (NASH). The development of NAFLD in children is significantly increased.

Evidence Acquisition:

A literature search of electronic databases was undertaken for the major studies published from 1998 to today. The databases searched were: PubMed, EMBASE, Orphanet, Midline and Cochrane Library. We used the key words: "non-alcoholic fatty liver disease, children, non-alcoholic steatohepatitis and fatty liver".

Results:

NAFLD/NASH is probably promoted by “multiple parallel hits”: environmental and genetic factors, systemic immunological disorders (oxidative stress, persistent-low grade of inflammation) as well as obesity and metabolic alterations (insulin resistance and metabolic syndrome). However its exact cause still underdiagnosed and unknown.

Conclusions:

Pediatric NAFLD/NASH is emerging problem. Longitudinal follow-up studies, unfortunately still insufficient, are needed to better understand the natural history and outcome of NAFLD in children. This review focuses on the current knowledge regarding the epidemiology, pathogenesis, environmental, genetic and metabolic factors of disease. The review also highlights the importance of studying the underlying mechanisms of pediatric NAFLD and the need for complete and personalized approach in the management of NAFLD/NASH.     

New Drugs on the Block—Emerging Treatments for Nonalcoholic Steatohepatitis

Patients with nonalcoholic steatohepatitis (NASH) are at higher risk of progression to advanced stages of fibrosis, cirrhosis, hepatocellular carcinoma and othe...     

Cyclooxygenase-2 Promotes Hepatocellular Apoptosis by Interacting with TNF-α and IL-6 in the Pathogenesis of Nonalcoholic Steatohepatitis in Rats

Background and Purpose

The underlying mechanisms of nonalcoholic steatohepatitis (NASH) are poorly understood, and little is known about hepatocellular apoptosis in NASH. Cyclooxygenase (COX)-2, the key enzyme in eicosanoid metabolism, is highly expressed in NASH. COX-2 can also regulate the release of mediators of inflammation, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6. The aim of our study was to evaluate the effects of COX-2 on hepatocellular apoptosis and the mechanism of the action in the pathogenesis of NASH in rats.

Methods

Sprague-Dawley rats were fed a high-fat diet (HFD) or standard diet for 8 and 12 weeks. COX-2 and cytokines expression in hepatic tissue and TNF-α and IL-6 levels in serum were measured at 8 and 12 weeks. Moreover, celecoxib (10 mg/kg body weight once a day) was administered to rats for 4 weeks to inhibit the expression of COX-2. Liver pathology was assessed by hematoxylin and eosin (H&E) stain and electron microscopy. Hepatocyte apoptosis was evaluated by TUNEL staining.

Results

COX-2 messenger RNA and protein were highly expressed in livers of HFD rats and were correlated with the severity of steatohepatitis (R = 0.82, p < 0.01). COX-2 upregulation was preceded by increases in TNF-α and IL-6. The level of hepatocellular apoptosis was significantly higher in HFD rats than in the control rats. The hepatocellular apoptosis was suppressed by the inhibition of COX-2.

Conclusions

COX-2 may promote hepatocellular apoptosis by interacting with TNF-α and IL-6 in NASH in rats.     

Resistant Hypertension in Pregnancy: How to Manage?

Purpose of Review

The concept of resistant hypertension may be changed during pregnancy by the physiological hemodynamic changes and the particularities of therapy choices in this period. This review discusses the management of pregnant patients with preexisting resistant hypertension and also of those who develop severe hypertension in gestation and puerperium.

Recent Findings

The main cause of severe hypertension in pregnancy is preeclampsia, and differential diagnosis must be done with secondary or primary hypertension. Women with preexisting resistant hypertension may need pharmacological therapy adjustment. Several drugs can be used to treat severe hypertension, with exception of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists. The most used drugs are methyldopa, beta-blockers, and calcium channel antagonists. There is a general agreement that severe hypertension must be treated, but there are still debates over the goals of the treatment. Delivery is indicated in viable pregnancies in which blood pressure control is not achieved with three drugs in full doses. Resistant hypertension may arise in postpartum.

Summary

The management of resistant hypertension in pregnancy must regard the possible etiology, the fetal well-being, and the mother’s risk. Good care is mandatory to reduce maternal mortality risk.

     

Will dietary restriction work in primates?

This issue of Biogerontology addresses whether dietary restriction (DR) “... can increase longevity in all species, particularly in human beings.” The possibility that DR can increase longevity in all species seems a trivial issue compared to that of DR’s potential efficacy in people. The striking phylogenetic breadth of DR’s longevity increasing effect supports the notion of human translatability. The available evidence in primates (human and nonhuman) suggests that it is highly probable that DR will increase the span of good health (and the average lifespan) but the magnitude of this predicted increase is unknown. Robust survival data for monkeys subjected to highly controlled DR will be available in ∼ ∼25 years; similar data for large numbers of human practitioners of DR appear to be many decades away.     

Animal Models in Alcoholic Pancreatitis — What Can We Learn?

Although the majority of patients with chronic pancreatitis present a history of excessive alcohol consumption, the pathophysiology underlying chronic alcoholic pancreatitis remains poorly defined. Since experimental animal models represent helpful tools in understanding human disease, numerous laboratory studies have been designed to study the effects of alcohol on the pancreas. In the present article we summarize the existing animal models that have been used to investigate the effects of acute and chronic alcohol application on the development of morphological alterations and pancreatic injury. Despite considerable experimental effort, acute or chronic ethanol feeding alone failed to cause acute or chronic pancreatitis in animals. However, ethanol-feeding and the combination with other procedures has demonstrated several mechanisms that play a role in ethanol-induced pancreatic injury. Among these ethanolinduced alterations and mechanisms are the reduction of pancreatic blood-flow and microcirculation, damaging effects of ethanol metabolites, increased pancreatic acinar cell expression of digestive and lysosomal enzymes, increased glandular enzyme content, additional nutritional factors, pancreatic duct obstruction, and limitations of pancreatic regeneration. Although no satisfactory animal model for alcoholic pancreatitis has been developed, these animal models have provided insights in several factors that predispose the pancreas to development of pancreatic injury and contribute to alcoholic pancreatitis.