Pericardiocentesis and pancreatic aspiration needle biopsy in coagulopathic and thrombocytopenic cirrhotic patient.

We report on the case of a 40-year-old patient with coagulopathic alcoholic cirrhosis who underwent ultrasound-directed pericardiocentesis and fine-needle aspiration biopsy of the pancreas after receiving recombinant human factor VIIa (rhFVIIa). The infusion of rhFVIIa rapidly corrected her coagulopathy and made it possible to perform both procedures. The marked changes produced in the prothrombin time and international normalized ratio as a result of the infusion of rhFVIIa are presented. As a result of these changes in coagulation status, both procedures were performed safely, and the patient's clinical management and subsequent care plan were defined.

Small intestinal bacterial overgrowth: a possible risk factor for metabolic bone disease.

Small intestinal bacterial overgrowth (SIBO) is one of the causes of malabsorption syndromes. The prevalence of metabolic bone disease in patients with SIBO is unknown, but a recent prospective case-control study indicated significant contribution of SIBO to the development of metabolic bone disease. We review this and other reports in the literature and discuss the possible mechanisms causing metabolic bone disease in patients with SIBO.

Splenic embolization in a Jehovah's Witness: role of recombinant human factor VIIa.

A case of a 50-year-old Jehovah's Witness with cryptogenic cirrhosis, severe portal hypertension and a coagulopathy, who underwent splenic embolization to improve the platelet count after receiving recombinant human Factor VIIa, is reported. Following the infusion of recombinant human Factor VIIa, the coagulopathy was rapidly corrected and it became possible to safely embolize her spleen. The changes in prothrombin time, international normalized ratio and activated partial thromboplastin time as well as thrombomodulin, tissue factor and plasminogen activator inhibitor after the infusion are presented. As a result of the splenic embolization, her platelet count normalized and she has been listed for liver transplantation.

Prochlorperazine-induced cholestasis in a patient with alpha-1 antitrypsin deficiency.

A case of a 58-year-old woman with history of bilateral lung transplant secondary to alpha-1 antitrypsin deficiency (PIZZ), who presented with a severe drug-induced cholestasis secondary to prochlorperazine is reported. After 27 months of prochlorperazine use, she developed liver failure consisting of jaundice with ascites. Computed tomography of the abdomen, abdominal ultrasonography as well as an endoscopic retrograde cholangiopancreatography showed no evidence for biliary obstruction. Liver biopsy demonstrated diffuse ongoing advanced chronic cholestasis, moderate portal and periportal inflammation as well as bridging fibrosis. During her hospitalization, her total bilirubin increased to 38.6 mg/dL; alkaline phosphatase to 362 IU/L, alanine aminotransferase to 71 IU/L and aspartate aminotransferase to 88 IU/L. After several weeks of ursodiol therapy without clinical improvement the prochlorperazine was discontinued and was followed by a rapid improvement in her measures of liver injury. An immediate decline of her serum total bilirubin and alkaline phosphatase to 21.4 mg/dL and 258 IU/L, respectively, occurred strongly suggesting the idea of a prochlorperazine-induced injury.

Aging Liver. A review.

Aging is characterized by a progressive decline of cellular functions. The aging liver appears to preserve its function relatively well. Aging is associated in human liver with morphological changes such as decrease in size attributable to decreased hepatic blood flow. Ultrastructural analysis of the human liver has revealed that the integrity of mitochondria and enzymatic activity remain mostly unchanged with aging. Reactive oxygen species (ROS) are involved in the aging process and result mainly from nonenzymatic processes in the liver. Endogenous free radicals are generated within mitochondria and suspected to cause severe injury to mitochondrial DNA. This damaged DNA accumulates with aging. In addition, polyunsaturated fatty acids, highly sensitive to ROS, decrease in liver mitochondria from human centenarians, a feature acquired during evolution as a protective mechanism to favor longevity. Diet is considered the main environmental factor having effect on lifespan. It has a major impact on aging liver, the central metabolic organ of the body. The ubiquitin proteolytic pathway in the liver serves to destroy many proteins, among them p21 which is encoded by abundant mRNA in senescent cells, can inhibit cell proliferation and favors DNA repair. Drug therapy in the elderly may be complicated by several factors such as decline in body weight, renal function, liver mass and hepatic blood flow, making adverse drug reactions more frequent. Hepatic drug metabolism is mainly mediated by the cytochrome P(450 )system and drug interactions in the elderly are likely related to the progressive decline of this system after the fifth decade of life and another decrease in individuals aged >70. Antihypertensive therapy in the elderly depends upon either hepatic or renal function and should be adjusted accordingly. Finally, telomerases are the biological clocks of replicative lifespan. Shortening of telomeric ends of chromosomes correlates with aging and decline in the replicative potential of the cell: replicative senescence. Telomere DNA of human somatic cells shortens during each cell division thus leading to a finite proliferation. Transfection of the telomerase reverse transcriptase gene results in elongation of telomeres and extension of lifespan. This also applies to humans. Replicative senescence in human cells evolved as a mechanism to protect them from continuous divisions leading to multiple mutations. Longer-lived species such as humans had to develop replicative senescence to ensure that they would have the increased protection that their longevity necessitates.

Liver transplantation for alcoholic liver disease.

In many patients, long-term heavy drinking leads to chronic liver disease, liver failure, and even death. Orthotopic liver transplantation (OLT) is the only definitive treatment for end-stage liver disease, including alcoholic liver disease (ALD). Because of a shortage of donor organs, OLT for ALD patients remains controversial out of concerns that patients may resume drinking, thereby harming the transplanted organ. Therefore, transplant centers conduct careful screening procedures that assess patients' coexisting medical problems and psychosocial status to identify those patients who are medically most suited for the procedure and who are most likely to remain abstinent after OLT. Studies assessing the outcomes of ALD patients after OLT found that the survival rates of the transplanted organ and the patient were comparable to those of patients with nonalcoholic liver disease and that relapse rates among the ALD patients were low. Similarly, ALD patients and patients with other types of liver disease had comparable rates of compliance with complex medication regimens after OLT. Enhanced efforts to identify risk factors for relapse among OLT candidates with ALD and to target interventions specifically to those patients who are at high risk of relapse may further improve patient outcome and enhance the acceptance of OLT for alcoholic patients in the general population.

Transverse myelitis occurring in association with primary biliary cirrhosis and Sjogren's syndrome.

Transverse myelitis (TM) as a manifestation of an autoimmune disorder is relatively rare. In Sjogren's syndrome (SS), the occurrence of TM is remarkably uncommon. Only three cases have been reported associated with primary biliary cirrhosis (PBC). Here we report the fourth case of TM occurring in association with SS and PBC. Patients with unexplained transverse myelitis require a careful search for an underlying etiology to include the findings of SS and PBC. The precise pathogenesis of TM in patients with SS is unknown. Most show good response to steroids. Cyclophosphamide and chlorambucil may be useful in those who respond poorly to steroids.

Response to treatment of hepatitis C in individuals with a recent history of intravenous drug abuse.

OBJECTIVE: The aim of this study was to determine the rate of sustained response (SR) to high-dose daily interferon (IFN) therapy in prior drug abusers with chronic hepatitis C. This was a retrospective matched cohort study conducted at a tertiary care university hospital in a large urban area. METHODS: The 120 individuals in each cohort were treated by the same physicians at the same facility, using the same treatment protocol and management procedures. Each patient received 5 million units of IFN daily for at least 1 yr and usually longer. RESULTS: Both groups achieved a similar rate of SR (no i.v. drug abuse, 37% vs i.v. drug abuse, 33%). The end of treatment (ET) response rate was unexpectedly higher in the drug-abusing population as compared to that non-drug-abusing control subjects but fell during the follow-up period to achieve an SR similar to that of the non-drug-abusing controls. The side effects of IFN therapy were no greater in the prior drug abusing population than in the controls, although many in the drug-abusing group increased their dose of methadone to counteract IFN side effects. CONCLUSIONS: The SR rate achieved by intravenous drug abusers to high-dose, daily IFN is similar to that in a non-drug-abusing HCV positive population. Recent use of illicit drugs within a 6-month period of starting IFN therapy or continued methadone use during treatment does not seem to impair the response to IFN when the results are compared with those of a matched cohort of non-drug-abusing controls.

Use of activated recombinant human factor VII (rhFVIIa) for colonic polypectomies in patients with cirrhosis and coagulopathy.

The prevalence of colonic polyps in patients with cirrhosis appears to be higher than that of the general population. The current practice for a polypectomy in a coagulopathic cirrhotic patient involves the reversal of the coagulopathy using fresh frozen plasma (FFP) prior to the polypectomy, usually at a second colonoscopy. The use of FFP is associated with many problems, particularly that of volume overload. Here we report four cases with advanced cirrhosis and severe coagulopathy that underwent polypectomies by snare cautery after an intravenous bolus infusion of recombinant human factor VIIa (rhFVIIa). The dose used was 120 microg/kg, which provided normalization of the coagulation parameters for 10-16 hr. The immediate use of rhFVIIa reduced the utilization of resources and enabled the performance of the polypectomies at the initial colonoscopy. No postpolypectomy bleeding was noted. The high cost of the drug is the only obstacle to a wider use of rhFVIIa for this purpose. The cost of the drug, however, is offset substantially by the cost of hospitalization for the administration of FFP, the cost of a second colonoscopy, and the charges associated with a second utilization of the endoscopy suite.

Bone mineral density among cirrhotic patients awaiting liver transplantation.

Osteoporosis is an important and common complication in patients with chronic liver disease. The goal of this study was to determine the bone mineral density (BMD) in different subgroups among pretransplant cirrhotic patients. BMD of the lumbar vertebrae (L) and femoral neck (F) were obtained in 104 consecutive cirrhotic patients. Descriptive and inferential statistics were used to compare the BMD among various groups. The mean BMD in males (n = 54) and females (n = 50) at L were 1.28 +/- 0.25 g/cm(2) and 1.13 +/- 0.20 g/cm(2), respectively (P =.001); at F they were 1.03 +/- 0.14 and 0.91 +/- 0.17, respectively (P <.0001). Among males, BMD at L in Child-Turcotte-Pugh class B and C were 1.40 +/- 0.21 and 1.13 +/- 0.20, respectively (P =.001); at F they were 1.11 +/- 0.10 and 0.93 +/- 0.13, respectively (P <.0001). Among females, BMD at L in Child-Turcotte-Pugh class B and C were 1.27 +/- 0.18 and 1.05 +/- 0.16, respectively (P =.0003); at F they were 1.02 +/- 0.16 and 0.83 +/- 0.12, respectively (P =.001). The BMD in premenopausal females (n = 15) and postmenopausal females (n = 35) at L were 1.20 +/- 0.19 and 1.11 +/- 0.20, respectively (P =.15); at F they were 0.97 +/- 0.17 and 0.88 +/- 0.16, respectively (P =.12). The BMD in postmenopausal females on hormone replacement therapy (n = 19) and on no hormone replacement therapy (n = 16) at L were 1.07 +/- 0.17 and 1.14 +/- 0.23, respectively (P =.29); at F they were 0.85 +/- 0.15 and 0.91 +/- 0.18, respectively (P =.33). The BMD values between etiologic groups were not significantly different. The overall prevalence of osteopenia and osteoporosis were 34.6% and 11.5%, respectively, being significantly higher in females than in males. In conclusion, significant difference in BMD values exists between males and females, as well as between Child-Turcotte-Pugh class B and C patients with cirrhosis. In addition, there is no significant influence of menopausal status, hormone replacement therapy, and etiology of cirrhosis on BMD.