Natural history of hepatic sarcoidosis and its response to treatment

BACKGROUND: Liver involvement in sarcoidosis is variable and can occur in the absence of pulmonary disease. Data on the natural history of hepatic sarcoid and response to therapy are lacking. This study investigates hepatic dysfunction complicating lung disease and significant liver involvement presenting independent of pulmonary sarcoid. PATIENTS AND METHODS: One hundred and eighty patients were included in the study. The minimum follow-up was 2 years. RESULTS: Fifty per cent of the study population had derangement of liver function attributable to hepatic sarcoid. Twenty-three patients (13%) had liver involvement without lung disease. Sixty-three patients were administered corticosteroids; approximately one-third had a complete clinical response, one-third a partial response and one-third showed no response. Fourteen patients (8%) were cirrhotic at presentation, and two progressed to cirrhosis despite steroid therapy. Sixteen patients received a second-line immunosuppressive agent; one-half of these showed a response to treatment augmentation (four patients azathioprine, three patients methotrexate, one patient both drugs). Six patients required liver transplantation, with disease recurrence in one recipient. In four patients, sarcoid as the aetiology of end-stage liver disease was diagnosed only on examination of the explanted liver. CONCLUSION: Sarcoidosis can cause end-stage chronic liver disease, which is often unrecognized until examination of the explanted liver. Response to conventional immunosuppression is variable and unpredictable. Transplantation is feasible and safe in this population but recurrence is possible.     

A randomized controlled pilot study of artesunate versus triclabendazole for human fascioliasis in central Vietnam

Human fascioliasis caused by Fasciola hepatica or Fasciola gigantica is an increasing global problem. The mainstay of current treatment is triclabendazole, but resistance in animals has been described, and it is not available in many countries. The antimalarial artesunate has an excellent safety profile, and there is increasing evidence of its efficacy against other parasites both in vitro and in vivo. We performed a study to investigate the usefulness of artesunate in symptomatic human fascioliasis; 100 patients were enrolled. Patients treated with artesunate were significantly more likely to be free of abdominal pain at hospital discharge (50/50 versus 44/50, P = 0.027, relative risk 1.14, 95% confidence interval 1.03-1.26), but the complete response rate at 3 months was lower than for patients treated with triclabendazole (38/50 versus 46/50, P = 0.05, RR 0.83, 95% CI 0.69-0.98, artesunate versus triclabendazole). There may be a role for artesunate in fascioliasis.     

Natural history of acute hepatitis C

To study the short‐ and long‐term outcomes of acute hepatitis C, three groups of patients were enrolled. Of 26 patients with acute hepatitis C, 18 (69%) maintained HCV viraemia and 8 had cleared virus naturally at 12 months after the onset. Normalization of ALT was seen in all 8 patients with acute resolving hepatitis, but in only 1 (5%) of the 18 patients with chronic HCV infection (P < 0.001). Changes in liver histology were analysed in 43 patients with acute hepatitis C who underwent repeated liver biopsy. The mean score of the fibrotic stage was 0.9 within 1 year of the onset, and it increased gradually up to 3.5 at 30 years from the onset (0.1 grade/year). The fibrotic stage increased more rapidly in patients aged more than 50 years. In 115 patients, the mean duration between blood transfusion and the diagnosis of HCC increased significantly (P < 0.001) in accordance with increasing age at blood transfusion; 35 ± 5.3 years in patients aged less than 30 years, 30 ± 4.9 years in those aged between 30 and 40 years, and 25 ± 6.8 years in those aged more than 40 years. In conclusion, approximately 70% of patients with acute hepatitis C develop chronic hepatitis. Once patients develop chronic hepatitic fibrosis of the liver, it progresses over several decades, faster in older patients.     

Radiological evaluation of response to treatment in hepatobiliary fascioliasis

PurposeIn this study, we aimed to evaluate the computed tomography (CT) findings of Fasciola hepatica infestations on initial and follow-up imagings after treatment, and also to describe the role of CT during diagnosis.MethodsIn this retrospective study, patients with a diagnosis of fascioliasis by clinical and laboratory examination who underwent initial and follow-up contrast-enhanced abdominal CT scans after treatment (a single oral dose of 10 mg/kg Triclabendazole) were included. The CT scans were evaluated regarding liver and spleen sizes, portal and splenic vein diameters, involved hepatic segment numbers and involvement patterns, the presence of focal perihepatic hyperdensity, gallbladder wall thickening, dilatation of the intrahepatic biliary tract, periportal-right subdiaphragmatic lymphadenopathy, hepatic subcapsular and intra-abdominal bleeding, and perihepatic/intraabdominal free fluid. Initial (pre-treatment) and post-treatment CT scans (average 25 months after the treatment) were compared with for these features.ResultsA total of 36 patients with a mean age of 39.28 ± 14.64 [15-83] years, were included in this study. After treatment, marked improvement in liver parenchymal involvement, biliary system findings, hepatomegaly-splenomegaly, periportal-peridiaphragmatic lymphadenopathy, and hepatic subcapsular hematoma were detected and focal perihepatic hyperdensity, free intraperitoneal fluid disappeared.ConclusionContrast-enhanced abdominal CT can be used in the diagnosis and post-treatment follow-up of fascioliasis. Awareness of intrahepatic/extrahepatic lesions and all the complications of fascioliasis can greatly aid the diagnosis and also evaluation of the response to treatment.     

Natural history of acute and chronic hepatitis C

Hepatitis C virus (HCV) infection remains a major global health burden. Hepatitis C causes significant liver-related morbidity and mortality due to hepatic decompensation and development of hepatocellular carcinoma. In addition, extra-hepatic manifestations of hepatitis C are frequent. There is a very large interindividual variability in the natural history of both acute and chronic hepatitis C which can be explained in part by a combination of various host, viral and environmental factors. Successful antiviral treatment can prevent short- and long-term complications of HCV infection in many patients. Still, the relative contribution of distinct risk factors for disease progression in different phases of HCV infection needs to be better defined. Personalized treatment approaches for HCV infection should consider individual risk profiles to avoid both under- and over-treatment – which will remain important also in upcoming era of interferon-free treatment of hepatitis C.     

Natural history and therapeutic management of acute aortic syndrome

Acute aortic syndrome, an acute lesion of the aortic wall involving the media, comprises aortic dissection, intramural hematoma and penetrating ulcer. Recent advances in imaging techniques have helped us to understand the natural history and dynamics of this medical condition. Despite considerable advances in surgical treatment, the current high mortality rate in the acute phase can still be reduced by early clinical suspicion and improved surgical expertise. The advent and incorporation of endovascular treatment has opened up new perspectives in the management of this disease, and may improve the long-term prognosis. This article aims to review our current understanding of the natural history and therapeutic management of acute aortic syndrome.     

Natural history of contractile abnormalities after acute myocardial infarction in man: severity and response to nitroglycerin as a function of time

The natural history of contraction abnormalities and their response after acute myocardial infarction in man were studied using radionuclide angiography. Sixteen patients were studied before and after sublingual nitroglycerin within 24 hours, 5-7 days and 4-6 weeks after the onset of chest pain. Within 24 hours, central chord shortening in the zone of infarction was reduced to 13.1 +/- 9.8%, but improved 27.2 +/- 18.4% (p less than 0.001) after nitroglycerin. After 5-7 days, central chord shortening improved similarly, but less markedly, from 12.9 +/- 9.2% to 24.4 +/- 13.2% (p less than 0.001). After nitroglycerin 4--6 weeks after the acute myocardial infarction, the central chord showed no response to nitroglycerin; it was 13.9 +/- 10.9% before and 13.4 +/- 2.5% after nitroglycerin. Changes in the lateral chords paralleled changes in the central chords in the three studies. Nonischemic zone improvement after nitroglycerin in all three studies. Global ejection fraction improved and end-diastolic and end-systolic volumes decreased in all three studies after nitroglycerin. These data indicate that after acute myocardial infarction, there is a significant reduction in hemiaxis shortening in the central and lateral chords that remains essentially unchanged over 4-6 weeks. However, the asynergic ischemic area improves considerably after nitroglycerin within 24 hours and 5-7 days, but fails to improve after 6 weeks.     

Natural history of acute kidney disease in patients with cirrhosis

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Natural history of acute symptomatic hepatitis C in Korea]

BACKGROUND/AIMS: Acute hepatitis C (AHC) has a high chronicity rate of up to 85%. Recently, several studies have demonstrated AHC has a self-limited course in about 50% especially in symptomatic cases. However, there is no investigation about the natural course of AHC in Korea. We intended to define the natural course of AHC and the influential factors on it. METHODS: We enrolled the patients with AHC from 2001 to 2004. The diagnosis of AHC was based on seroconversion to anti-HCV antibodies or the clinical and biochemical diagnostic criteria satisfactory to AHC and on the presence of HCV RNA in first serum sample. The self-limited course of AHC was defined as permanent (>6 months) loss of HCV RNA in serum and normalization of ALT. RESULTS: Eighteen patients presented with AHC. Seventeen out of eighteen was symptomatic. Twelve out of eighteen (66.7%, 95% CI 41.7-84.9%) showed spontaneous remissions. Presence of anti-HCV on first serum samples predicted chronic courses. Antibody to HCV was not detected during follow-up periods in nine patients, who all showed spontaneous viral clearance. CONCLUSIONS: AHC has a high rate of spontaneous viral resolution. Further study is needed to define the influential factors on the viral clearance in AHC.     

Ovarian carcinoma as a cause of Zollinger-Ellison syndrome. Natural history, secretory products, and response to provocative tests

Zollinger-Ellison syndrome is usually caused by a gastrin-secreting tumor in or near the pancreas. We describe a patient in whom an ovarian cystadenocarcinoma was the cause of the syndrome. The patient presented with a short history of peptic ulceration and development of a large pelvic mass. Investigations demonstrated a basal acid output of 37.8 mEq/h and a maximal acid output of 36.0 mEq/h, and the plasma concentration of gastrin was 830 pg/ml (normal less than 100). Secretin and calcium infusion tests were positive, and a meal test was compatible with Zollinger-Ellison syndrome. Imaging studies demonstrated a normal liver and pancreas but a large cystic right ovarian mass. Resection of the mass resulted in a marked reduction in gastric acid output, a fall in plasma gastrin concentration to normal, negative calcium and secretin tests, and a normal (positive) meal test. Histology of the mass showed it to be a mucinous cystadenocarcinoma. The tumor stained with immunoperoxidase technique was positive for gastrin, and the cyst fluid contained high concentrations of gastrin and calcitonin. One year later, the patient has no biochemical or imaging evidence of tumor. Ovarian, gastrin-producing tumors and pancreatic gastrinomas cannot be distinguished by provocative tests, and negative imaging studies do not exclude a pancreatic tumor. Patients with an ovarian mass and Zollinger-Ellison syndrome should have a bilateral oophorectomy and a careful exploration of the pancreatic area.     

Balloon angioplasty. Natural history of the pathophysiological response to injury in a pig model

The restenosis or occlusion that frequently follows balloon angioplasty is poorly understood. Thus, the pathophysiological response to angioplasty of the common carotid artery in 38 heparinized normal pigs was investigated by quantification of the 111In-labeled platelet deposition and histological and electron microscopic examination from 1 hour to 60 days after angioplasty. At 1 hour, the following findings were noted: complete endothelial denudation in all arteries, marked platelet deposition (44.7 +/- 20.7 X 10(6)/cm2), mural thrombus in seven of 10 pigs, and a medial tear extending through the internal elastic lamina in nine of 18 arteries. All nine arteries with tears had associated mural thrombus and severe platelet deposition (76 X 10(6)/cm2); in contrast, the nine arteries without a tear had no mural thrombus and much lower platelet deposition (6 X 10(6)/cm2). Necrosis of medial smooth muscle cells was evident at 24 hours. Platelet deposition remained high at 24 hours (40.5 +/- 20.6 X 10(6)/cm2), but was markedly reduced at 4 days (4.4 +/- 1.5 X 10(6)/cm2), coincident with partial regrowth of endothelium or periluminal lining cells. No significant platelet deposition was noted at 7 days, when the endothelial cell type of regrowth was largely complete. Intimal proliferation of smooth muscle cells was mild and patchy at 7 days, significantly greater and more uniform at 14 days, and unchanged at 30 and 60 days after angioplasty. Complete thrombotic occlusion occurred in four (11%) of the 38 pigs. A significant stenosis present at 30 days after angioplasty was shown by histological examination to be due to organization of mural thrombus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Natural history of acute pancreatitis and the role of infection.

Bacterial infection of pancreatic necrotic tissue is a frequent complication of severe acute pancreatitis. Infected pancreatic necrotic tissue is observed in 30-70% of all patients suffering from necrotizing pancreatitis. It is the leading cause of deaths in severe acute pancreatitis, with mortality rates ranging from 15 to 30%. The incidence of infection increases with the extent of the necrotic areas and with the time after onset of pancreatitis. Compared to patients with sterile necrosis, those with infection of the necrotic areas have an increased mortality, and systemic complications occur more frequently. Standard treatment for infected pancreatic necrotic tissue is surgical debridement, whereas conservative management is feasible in approximately 30% of the patients with sterile necrosis. As bacterial infection of pancreatic necrotic tissue has a tremendous impact on the prognosis of the disease and on the patient's clinical course, efforts have been made to prevent it. Although clinical and experimental data provide evidence that prophylactic antibiotics have beneficial effects on the outcome and course of patients with severe acute pancreatitis, this topic has to be investigated further. General recommendations concerning the early use of antibiotics have to await the results of larger, double-blind studies.     

Natural history of pertussis antibody in the infant and effect on vaccine response

To better characterize the transplacental transfer and persistence of pertussis antibodies and their role in the immune response to vaccine, concentrations of pertussis agglutinins and antibodies to lymphocytosis promoting factor (LPF) and filamentous hemagglutinin (FHA) were measured in three distinct groups of serum. Transplacental pertussis IgG antibody concentrations in newborns were found to be comparable to corresponding maternal concentrations and to decline with a half-life of approximately 6 weeks. By the age of 4 months, most infants had no detectable antibodies to LPF or FHA. Higher concentrations of maternally derived antibody to LPF were associated with a significantly weaker antibody response to conventional vaccine. In contrast, acellular vaccine stimulated superior antibody production, regardless of antecedent concentrations of antibody to LPF. The data support continuation of the current schedule of pertussis immunization and further efforts to develop an acellular vaccine for use in young infants.