Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate if any pretreatment characteristics of patients with chronic hepatitis C (HCV) can be used to predict response to the current recommended dose (3 million units three times a week) and higher doses of interferon-alpha (IFN), we retrospectively assessed the response of 37 patients with HCV who were treated with IFN. Sixteen patients (43%) responded to the standard dose of IFN with normalization of ALT. Weight and liver histology were found to be significant factors for response. The responders weighed significantly less than nonresponders (161.8 +/- 35.5 lb versus 200.3 +/- 45.4 lb, P = 0.008). Seventy-five percent of patients with chronic lobular or persistent hepatitis were responders, whereas only 28% of patients with more advanced hepatitis responded (P = 0.01). There was no correlation between the degree of bile duct damage or steatosis and response rate. This study suggests that obesity and severe histologic injury are negative predictive factors of response to the current recommended dose of IFN. The adequacy of the current recommended dose of IFN in overweight patients needs to be investigated.
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PMID:Clinical and histologic predictors of response to interferon-alpha in patients with chronic hepatitis C viral infection. 799 93

We describe three men and two women, aged 18-50, with an occasional finding of increased aspartate and alanine aminotransferase and gamma-glutamyl transpeptidase levels in the absence of any drug treatment and past or current alcohol abuse. Two patients were overweight (body mass index 29 and 32, respectively) and physical examination was normal in all but one case. Tests for hepatitis A, B and C, Epstein-Barr virus, cytomegalovirus, toxoplasma and autoimmune hepatitis were negative and metabolic diseases (Wilson's disease, haemochromatosis, alpha-l-antitrypsin deficiency) were excluded by specific tests. Ultrasound liver scan revealed massive steatosis in all patients. Liver histology showed diffuse steatosis and parenchymal inflammation in all cases, with concomitant fibrosis and Mallory bodies in three of them. Findings were consistent with non-alcoholic steatohepatitis, a rare condition with potential progression to cirrhosis in a minority of cases. This disease, for which no treatment is currently available, must be considered in all subjects with elevated aminotransferases, in the absence of known causes of liver damage.
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PMID:Non-alcoholic steatohepatitis. Report of five cases and review of the literature. 878 33

Recurrence of hepatitis C virus (HCV) after orthotopic liver transplant (OLT) may be mild or may lead to progressive liver disease requiring retransplantation (re-OLT). Results of re-OLT for hepatitis C are not well known. We analyzed outcomes in 14 patients retransplanted for recurrent hepatitis C. All had evidence of recurrent hepatitis on multiple biopsies. Polymerase chain reaction (PCR) was performed in blood or tissue samples from 12 patients when recurrence was suspected; all 12 were positive for HCV-RNA. Explants showed chronic hepatitis with bridging necrosis in 3 patients, hepatitis with transition to cirrhosis in 2, hepatitis and cirrhosis in 3, and cirrhosis alone in 2. In 2 patients, in whom immunosuppression had been withheld for 4 to 6 weeks, there was also evidence of chronic rejection. Four died of sepsis perioperatively (median, 32.5 days; range, 9-59); pre-OLT, 3 of 4 had renal failure, and 1 had fever with no obvious source of infection. Ten patients did well early after OLT and were discharged. One patient was readmitted 6 weeks after discharge and died of cytomegalovirus (CMV) infection 127 days after re-OLT. One patient with concomitant vanishing bile duct syndrome, probably due to chronic rejection, developed recurrent hepatitis and died of progressive liver failure 161 days after re-OLT. Eight patients are well at a median of 926 days (range, 315-1930) after re-OLT. Three have evidence of mild recurrent hepatitis on liver biopsy, one is overweight with severe steatosis on biopsy, and four have no evidence of recurrent hepatitis. Retransplantation for hepatitis C should be considered a viable option for patients who develop end-stage hepatic dysfunction secondary to recurrent disease and should be performed before development of infectious complications and renal insufficiency.
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PMID:Retransplantation for recurrent hepatitis C. 934 26

A 74-year-old man was admitted to hospital because of jaundice and malaise of several weeks' duration. Five years earlier he had sustained a stroke from which he had recovered almost completely. On physical examination he was overweight and had an enlarged liver. Laboratory values were consistent with cholestasis and hepatitis. An abdominal ultrasound showed multiple nodular abnormalities in the liver consistent with a malignancy. Rapidly developing abnormalities in blood coagulation were thought to be a contraindication to hepatic biopsy. The patient deteriorated and sustained a new stroke. The physicians were convinced that he had cancer and could not be cured. They planned further diagnostic studies, but at the same time made an advance directive for non-resuscitation. Three days after admission the patient was found dead; no consent for an autopsy was obtained. If it is suspected that a patient is suffering from a malignant disease, the malignancy should be demonstrated or excluded as quickly as possible in the least uncomfortable way. Also, the patient and his family should be informed of any restriction on the possibilities of treatment.
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PMID:[Clinical thinking and decision making in practice. A severely ill elderly man with icterus]. 1081 73

Females have a greater susceptibility to ethanol-induced liver injury than males. Females who drink ethanol regularly and have been overweight for 10 years or more are at greater risk for both hepatitis and cirrhosis than males, and females develop ethanol-induced liver injury more rapidly and with less ethanol than males. Female rats on an enteral ethanol protocol exhibit injury more quickly than males and have widespread fatty changes over a larger portion of the liver lobule. Moreover, levels of plasma endotoxin, intracellular adhesion molecule-1, free radical adducts, infiltrating neutrophils and nuclear factor kappa B are doubled in female rat livers compared with male rat livers after enteral ethanol treatment. Additionally, estrogen treatment in vivo increases the sensitivity of hepatic macrophages or Kupffer cells to endotoxin. Evidence has been presented that Kupffer cells are pivotal in the development of ethanol-induced liver injury. Destroying Kupffer cells with gadolinium chloride or decreasing bacterial endotoxin by sterilizing the gut with antibiotics inhibits early inflammation due to ethanol. Similar results have been obtained with anti-tumour necrosis factor-alpha antibody. These data pointed to the hypothesis that ethanol-induced liver injury involves elevations in circulating endotoxin concentrations leading to activation of Kupffer cells, which causes a hypoxia-reoxygenation injury. This theory has been tested using pimonidazole, a 2-nitroimidazole marker, to quantify hypoxia in downstream, pericentral regions of the hepatic lobule. After chronic enteral ethanol treatment, pimonidazole binding doubles. Enteral ethanol also increases free radicals detected with electron spin resonance. Radical adducts, with coupling constants such as alpha-hydroxyethyl radical, have been shown to arise from ethanol. Importantly, hypoxia and radical production detected in bile are also decreased by the destruction of Kupffer cells with gadolinium chloride. These data support the hypothesis that Kupffer cells contribute to the vital sex differences in liver injury caused by ethanol.
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PMID:Sex-related liver injury due to alcohol involves activation of Kupffer cells by endotoxin. 1111 Jun 25

In Switzerland, 6% of men and 5% of women are obese (BMI > 30); 33% of men and 17% of women are overweight (BMI 25-30). Both genetic and environmental factors are responsible for obesity. There is an increased risk of C-V disease, diabetes and steato-hepatitis in abdominal obesity (abdominal circumference > 102 cm for men and > 88 cm for women). There is also an increased level of cortisol, which could be due to a difficulty to cope with psycho-social stress. Leptine and different hormones play a role in fat storage. Menopause and pregnancy are moderate risk factors for obesity. Weight gain may also result from different drugs, smoking cessation and stress. Eating disorders such as boulimia and binge eating must be diagnosed and treated. Beneficial health effect of weight loss is analysed.
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PMID:[Ten questions on the causes and consequences of obesity: stress hormones]. 1123 10

Liver enzyme elevations are common in human immunodeficiency virus (HIV)-infected patients, and their diagnosis or management may be difficult because of the intricacies of the pathogenic mechanisms involved. These include hepatotoxicity related to the highly active antiretroviral therapy (HAART) regimen, idiosyncratic or immunoallergic mechanisms, and direct cytotoxicity enhanced by an underlying liver disease. Liver enzyme abnormalities may also reflect hepatitis B (HBV) or hepatitis C (HCV) infection, which each have their own risks for chronic immune-mediated liver disease (including hepatitis flare after immune reconstitution) and of direct cytotoxicity. Finally, other factors may affect liver deterioration, including alcohol-related liver disease, nonalcoholic steatohepatitis associated with metabolic syndromes (e.g., hyperlipidemia, diabetes, or being overweight) that are potentially HAART related, and use of medication or illicit drugs (e.g., methamphetamine). A better understanding of these complex interactions, including adjustments of dosages of antiretroviral drugs, will probably help in the management of HIV-infected patients with liver enzyme abnormalities.
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PMID:HIV infection and hepatic enzyme abnormalities: intricacies of the pathogenic mechanisms. 1498 77

The term 'non-alcoholic fatty liver disease' (NAFLD) includes cases with steatosis alone and those with non-alcoholic steatohepatitis (NASH). Usually there are no signs or symptoms, sometimes fatigue or pain, and apart from hepatomegaly the condition is revealed by abnormal liver biochemistry or by abdominal ultrasound. Most cases are associated with overweight or diabetes. Liver enzymes are usually elevated, especially GGT, ASAT and ALAT. Other conditions, including alcohol abuse and autoimmune hepatitis, have to be excluded. The diagnosis of steatosis can be made with ultrasound or CT scan. A liver biopsy is often needed to exclude other disease and to assess inflammation and fibrosis. Cirrhosis can develop. NAFLD is usually caused by two 'hits': the 'first hit' is peripheral insulin resistance, causing steatosis. The 'second hit' is caused by reactive oxygen species, inducing vicious cycles leading to inflammation. Weight loss, metformin or thiazolidinediones can improve NAFLD by increasing insulin sensitivity. Radical scavengers such as vitamin E, betaine and perhaps also urodeoxycholic acid may improve the hepatitis component. Further studies on treatment are needed.
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PMID:Non-alcoholic fatty liver disease: a brief review. 1569 51

Patients with obstructive sleep apnea (OSA) are at risk for the development of fatty liver as a result of being overweight. Several data suggest that OSA per se could be a risk factor of liver injury; ischemic hepatitis during OSA has been reported, and OSA is an independent risk factor for insulin resistance. Therefore, we investigated liver damage and potential mechanisms in 163 consecutive nondrinking patients with nocturnal polysomnographic recording for clinical suspicion of OSA. Serum levels of liver enzymes were measured in all patients. Liver biopsy was offered to patients with elevated liver enzymes. Intrahepatic hypoxia was assessed by the expression of vascular endothelial growth factor (VEGF) on liver biopsy specimens. Severe OSA (apnea-hypopnea index [AHI] > 50/hr) was seen in 27% of patients; 52% had moderate OSA (AHI 10-50/hr), and 21% had no OSA. Overall, 20% had elevated liver enzymes. Independent parameters associated with elevated liver enzymes were body mass index (BMI) (OR: 1.13; CI: 1.03-1.2) and severe OSA (OR: 5.9; CI: 1.2-29). Liver biopsy was performed in 18 of 32 patients with elevated liver enzymes and showed steatohepatitis in 12 cases, associated with fibrosis in 7 cases. Patients with severe OSA were more insulin-resistant according to homeostasis model assessment, had higher percentage of steatosis as well as scores of necrosis and fibrosis, despite similar BMI. Hepatic immunostaining used as an indirect marker of hypoxia was not different between patients with or without severe OSA. In conclusion, severe OSA is a risk factor for elevated liver enzymes and steatohepatitis independent of body weight. Promotion of insulin resistance is probably involved. Further studies are needed to determine whether hypoxia contributes directly to liver injury.
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PMID:Chronic liver injury during obstructive sleep apnea. 1591 59

Antiretroviral medications have significantly improved the prognosis of subjects infected by human immunodeficiency virus (HIV). However, long-term complications of these drugs are increasingly recognized as significant causes of morbidity and mortality. Non-alcoholic fatty liver disease (NAFLD), which can evolve into non-alcoholic steato-hepatitis (NASH), cirrhosis and ultimately hepatic failure is one of the more often observed complications in the current clinical practice and the correlation with liver enzyme elevations is controversial. Multiple factors have been considered as possibly correlated to this event in the HIV-infected population, including metabolic abnormalities (such as hyperlipidaemia, hyperglycaemia and being overweight), chronic inflammation, concurrent infection with hepatitis C and B viruses, and treatment with certain nucleoside reverse transcriptase inhibitors (NRTI). HIV-associated syndromes such as lactic acidosis and lypodystrophy are frequently associated with fatty liver disease and a mitochondrial injury has been considered as its possible pathogenetic factor. In particular, treatment containing stavudine and didanosine have proven to be the most commonly implicated in the occurrence of mitochondrial abnormalities. Epidemiologic data to better define the role of predictive factors and drugs associated with the development of NAFLD are still lacking. Furthermore, it remains unclear the better therapeutic management for this condition, even if the current best therapeutic option for NAFLD is the treatment of the underlying disease. Other studies are mandatory to better elucidate the pathogenesis of NAFLD and the optimal therapeutic strategy for the underlying conditions.
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PMID:Steatohepatitis in HIV-infected subjects: pathogenesis, clinical impact and implications in clinical management. 1789 69


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