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Cholangitis and liver abscess after percutaneous ablation therapy for liver tumors: incidence and risk factors.

PURPOSE: To determine the risk factors of cholangitis and liver abscess occurring after percutaneous ablation therapy for liver tumors. MATERIALS AND METHODS: Between October 1995 and September 2002, 358 patients with 455 liver tumors underwent a total of 683 ablation procedures, such as percutaneous ethanol injection (PEI), percutaneous microwave coagulation (PMC), and radiofrequency (RF) ablation therapy. With a retrospective review of medical records, the rates and outcomes of cholangitis and/or liver abscess occurring after ablation therapy were evaluated. The relationship between cholangitis and/or liver abscess and multiple variables (age, disease, Child-Pugh class, size of nodules, multiplicity of nodules, history of transcatheter arterial embolization, presence of bilioenteric anastomosis, and lack of prophylactic antibiotics administration) were statistically analyzed. RESULTS: Cholangitis and/or liver abscess occurred in 10 sessions (1.5%) in 10 patients: six sessions after PEI, three sessions after PMC, and one session after RF ablation. Both cholangitis and liver abscess were noted in seven sessions, cholangitis was noted in two, and liver abscess was noted in one. Six patients recovered, but two developed recurrent cholangitis and liver abscess, one developed lung abscess complicated with liver abscess, and one died of septic shock associated with cholangitis. On stepwise regression analysis, bilioenteric anastomosis was the sole significant predictor of cholangitis and/or liver abscess formation (P <.001; odds ratio = 36.4; 95% CI = 9.67-136.9). CONCLUSION: Bilioenteric anastomosis strongly correlated with the development of cholangitis and/or liver abscess after percutaneous ablation therapy. Close posttreatment attention should be paid to this subgroup of patients.

Adolescent↗

Gene expression analysis identifies novel genes participating in early murine liver development and adult liver regeneration.

Adult liver tissue regeneration may recapitulate molecular events of liver organogenesis. As gaps in our understanding of the fundamental processes that govern development and regeneration of the liver still exist, we studied gene expression in the developing liver at embryonic day 9.5 post coitum (E d9.5 p.c.). Microarray data from E d9.5 p.c. as well as previously published data from embryonic day 11.5 post coitum (E d11.5 p.c.) and embryonic day 13.5 post coitum (E d13.5 p.c.) were subjected to cluster analysis. This led to the identification of 130 genes which were characterized by continuous expression at all stages of liver development with peak expression of 44 genes at E d9.5 p.c. Five of these genes, previously not known to be associated with early liver development or with adult liver regeneration were selected for further analysis. The expression of the genes was studied by real-time polymerase chain reaction at 0, 2, 4, 6, 12, 24 and 48 hr after partial hepatectomy in the adult liver. Two of the genes, growth arrest protein 43 (GAP43) and paired-like homeodomain transcription factor 2 (Pitx2) were exclusively detected at 24 hr, whereas the genes Twist1, Midkine, and zinc finger protein of cerebellum 1 (Zic1) each showed a specific expression profile in the regenerating liver with peak expressions at 4, 24, and 6 hr, respectively. In summary, we were able to identify novel genes, that may act as regulators during liver formation as well as in the regeneration phase of adult liver. This information may contribute to the development of new targets for the treatment of liver diseases in the future.

Animals↗

One hundred liver resections including comparison to non-resected liver-mobilized patients.

BACKGROUND: Factors of liver resection associated with postoperative recovery and survival, the modalities that affect survival with resected colorectal carcinoma liver metastases, the comparison of liver function of liver-resected to liver-mobilized but not resected patients, and observation of early liver regeneration volume over time have not been studied prospectively. This study aimed to prospectively analyse these factors. METHODS: Data were collected prospectively on 100 consecutive liver resections, and 10 liver-mobilized but not resected patients by the Hepatobiliary Unit, University of Melbourne, Austin Campus. Follow-up of patients was 100%. RESULTS: The factors associated with blood loss were the type of liver resection (P = 0.0001), the length of the operation (P = 0.0001) and a central venous pressure greater than 5 cm of water (P = 0.0008). An inverse correlation existed between blood loss and long-term survival (P = 0.003). The only predictor for a postoperative complication was the length of the operation (P = 0.03): a correlation of moderate significance existed between blood loss and a complication (P = 0.052; confidence interval 0.19-1.17). The 5-year cumulative survival for hepatic resection for colorectal carcinoma Dukes A + B was 55%; there was a significantly better survival of Dukes A + B compared to Dukes C (P = 0.03) and also for those 50 years or older, but this did not depend on whether there were one or more lesions present. Resected patients had a significantly higher alanine transaminase (ALT), total bilirubin and international normalized ratio than non-resected patients, but not albumin, total protein, alkaline phosphatase or aspartate aminotransferase. The serum albumin fall was similar in both groups, which indicated that loss of liver tissue was not the cause. The re-resection rate was 8% without mortality and with low morbidity. Liver volume was restored by 64% (510 +/- 170 cc) by 7 days postoperatively. CONCLUSIONS: Major hepatic resection can be performed with low mortality, morbidity and short hospital stay, with a 5-year survival for colorectal carcinoma better than 50%. Resection needs to be considered more frequently for curative management. Serum albumin fall is not caused by loss of liver tissue and blood loss can be controlled by central venous pressure manipulation and vascular isolation. Re-resection is a safe and rewarding treatment and needs to be planned at the first resection.

Blood Loss, Surgical↗

Immune responses to liver membrane antigens in patients with cystic fibrosis and liver disease.

Biliary obstruction by viscid mucus, although important, may not be the only factor for the development of liver disease in some patients with cystic fibrosis. In the present study the relationship between immune responses to liver antigens and the presence of liver damage was investigated using the leucocyte migration test and lymphocyte cytotoxicity to isolated rabbit hepatocytes. Inhibition of leucocyte migration by purified liver-specific lipoprotein, derived from hepatocyte plasma membrane, was found in 9 of 11 children with liver disease, but in only 5 of 14 with cystic fibrosis and no overt liver disease (P < 0.025). Lymphocyte toxicity to isolated rabbit hepatocytes was significantly increased in 10 of 13 children with liver disease, but in only 6 of 29 children without liver disease (P < 0.001). Experiments using lymphocyte subpopulations showed that the cytotoxicity was mediated by a non-T-cell population and could be blocked with liver-specific lipoprotein in 7 out of 10 cases, suggesting that the reaction in these patients was specifically directed against liver-specific lipoprotein. The study suggests that sensitisation against liver membrane antigens, whether arising primarily or secondarily in some way to other hepatic lesions, may contribute to the progression of liver damage in cystic fibrosis.

Adolescent↗

Use of precision-cut liver slices as an in vitro tool for evaluating liver function.

Precision-cut liver slices have been developed as an in vitro tool for assessing liver viability and function and for examining hepatotoxicants. Liver slices from a variety of species (including human) are prepared using mechanical slicers that produce reproducible slices of a uniform thickness, which allows optimum exchange of nutrients, waste, and gases. Slices are incubated in dynamic systems that allow the slices to be maintained viable in culture for 1-10 days. The viability of slices can be assessed by ion content (K+, Na+ ATPase status), intermediary metabolism, energy status (ATP), respiration, biosynthetic ability, and biotransformation activity. In addition, liver tissue slices allow the opportunity for extensive microscopic evaluation (light and electron) as well as newer technologies such as confocal microscopy. Assessment of the toxic potential of a chemical can be performed after a short-term or constant exposure by evaluating the viability parameters. Liver slices have been used extensively for rank-ordering the toxicity of chemicals as well as for examining the mechanisms of liver injury. Liver slices in culture also can be used for an examination of the induction of new enzymes such as cytochrome P-450 and the expression of stress proteins or peroxisomal enzymes. Finally, liver slices offer a system for evaluating whole or cryopreserved liver as well as regeneration of liver tissue after toxic insult. Liver slices have been shown to be a valid in vitro system for examining liver function and offer a bridge between in vivo and cell culture systems.

Animals↗

Adiponectin and its receptors in rodent models of fatty liver disease and liver cirrhosis.

AIM: To determine circulating and hepatic adiponectin in rodents with fatty liver disease or liver cirrhosis and investigate expression of the adiponectin receptors AdipoR1 on the mRNA and protein level and AdipoR2 on the mRNA level. METHODS: Fat fed rats were used as a model for fatty liver disease and bile duct ligation in mice to investigate cirrhotic liver. Expression of AdipoR1 and AdipoR2 mRNA was determined by real time RT-PCR. AdipoR1 protein was analysed by immunoblot. Adiponectin was measured by ELISA. RESULTS: Systemic adiponectin is reduced in fat-fed rats but is elevated in mice after bile duct ligation (BDL). Hepatic adiponectin protein is lower in steatotic liver but not in the liver of BDL-mice when compared to controls. Adiponectin mRNA was not detected in human liver samples or primary human hepatocytes nor in rat liver but recombinant adiponectin is taken up by isolated hepatocytes in-vitro. AdipoR1 mRNA and AdipoR1 protein levels are similar in the liver tissue of control and fat fed animals whereas AdipoR2 mRNA is induced. AdipoR2 mRNA and AdipoR1 mRNA and protein is suppressed in the liver of BDL-mice. CONCLUSION: Our studies show reduced circulating adiponectin in a rat model of fatty liver disease whereas circulating adiponectin is elevated in a mouse model of cirrhosis and similar findings have been described in humans. Diminished hepatic expression of adiponectin receptors was only found in liver cirrhosis.

Adiponectin↗

New insights into the coagulopathy of liver disease and liver transplantation.

The liver is an essential player in the pathway of coagulation in both primary and secondary haemostasis. Only von Willebrand factor is not synthetised by the liver, thus liver failure is associated with impairment of coagulation. However, recently it has been shown that the delicate balance between pro and antithrombotic factors synthetised by the liver might be reset to a lower level in patients with chronic liver disease. Therefore, these patients might not be really anticoagulated in stable condition and bleeding may be caused only when additional factors, such as infections, supervene. Portal hypertension plays an important role in coagulopathy in liver disease, reducing the number of circulating platelets, but platelet function and secretion of thrombopoietin have been also shown to be impaired in patients with liver disease. Vitamin K deficiency may coexist, so that abnormal clotting factors are produced due to lack of gamma carboxylation. Moreover during liver failure, there is a reduced capacity to clear activated haemostatic proteins and protein inhibitor complexes from the circulation. Usually therapy for coagulation disorders in liver disease is needed only during bleeding or before invasive procedures. When end stage liver disease occurs, liver transplantation is the only treatment available, which can restore normal haemostasis, and correct genetic clotting defects, such as haemophilia or factor V Leiden mutation. During liver transplantation haemorrage may occur due to the pre-existing hypocoagulable state, the collateral circulation caused by portal hypertension and increased fibrinolysis which occurs during this surgery.

Animals↗

[Liver fibrosis indexes in nonalcoholic fatty liver disease].

OBJECTIVE: To assess the clinical utility of liver fibrosis indexes determination in patients with nonalcoholic fatty liver disease. METHODS: Liver fibrosis indexes of 79 patients with fatty liver, diagnosed by B ultrasonic echography, 37 patients with posthepatitic cirrhosis patients and 32 healthy subjects were determined. RESULTS: The level of procollagen III(PC III), hyaluronic acid (HA), collagen IV(C IV), laminin (LN) in the fatty liver cases were significantly higher than those of healthy subjects (P<0.05 - 0.01), but lower than those in the liver cirrhosis cases (P<0.01). The difference of PC III, C IV, LN between the severe and early fatty liver cases was significant (P<0.05 - 0.01). Positive rate of these indexes was higher in severe cases. CONCLUSION: There is a trend of liver fibrosis in severe fatty liver patients. Combined determination of liver fibrosis indexes may help the diagnosis of liver fibrosis in the fatty liver patients.

Adult↗

Relationship between fatty liver and liver metastasis in rats given injection of rat colon cancer cell line.

BACKGROUND/AIMS: In a previous study we described that colorectal cancer patients with fatty liver had few liver metastases. To clarify whether this clinical finding is correct, we studied whether rats with fatty liver had infrequent liver metastases using experimental colon cancer. METHODOLOGY: Twenty male inbred F344/DuCrj rats (CLEA JAPAN Inc.), 8 weeks of age, were used in this study. These 20 rats were divided into two groups: Fatty liver group (FL group, n = 10) and Non-fatty liver group (NFL group, n = 10). 1.0 ml of tumor-cell suspension containing 1 x 10(7) RCN-9 cells was injected just under the capsule of the spleen. All animals were sacrificed 2 weeks after tumor inoculation. RESULTS: 1) Four rats out of 10 in the FL group (40%) had at least one metastatic nodule on the surface of the liver, while there were 10 rats with metastatic nodules in the NFL group (100%) (p < 0.01). 2) The ratio of the liver metastasis area against the largest section of the left lobe of the lateral segment (RLML) was examined. The average RLML of the FL group was 0.45%, which was significantly lower than that of the NFL group (7.11%) (p < 0.0001). CONCLUSIONS: Rats with fatty liver seldom had liver metastases compared to normal rats. This means that fatty liver itself can possibly bring about situations with infrequent liver metastases.

Animals↗

Anatomical and physiological comparison of liver volumes among three frequent types of parenchyma transection in live donor liver transplantation.

BACKGROUND/AIMS: Adequate venous outflow is a prerequisite for successful live donor liver transplantation. Several techniques of liver transection have been established in both transplant and non-transplant hepatic surgery. The purpose of our study was to define and compare anatomical and physiological characteristics of venous drainage in the three most common types of liver transection techniques (Malagó, Cantlie, Pringle) encountered in live donor liver transplantation METHODOLOGY: Volumes of both graft and remnant livers as well as individual hepatic vein territories were calculated by means of virtual 3-dimensional reconstructions of computed tomography images obtained from 55 potential live liver donors using the software HepaVision (MeVis, Germany). Belonging to the middle hepatic vein (MHV) was assigned according to the largest territorial volume on either right or left hemilivers. Livers from all potential donors were subject to virtual splitting (n=55). Findings were subsequently confirmed intraoperatively in those who underwent donor resection (n=27). RESULTS: There were no statistically significant differences in hemiliver-volumes among the three types of liver partition. There was a predominance of MHV belonging to the right hemiliver: Malagó n=45 (82%) vs. Cantlie n=44 (80%) vs. Pringle n=44 (80%). Dominant right MHV hemiterritory showed a mean volume of 284-296 mL, accounting for 59-61% of total MHV volume. There were no significant differences among the three types of liver partition evaluated. CONCLUSIONS: Our results demonstrate the reliability of virtual 3-dimensional reconstructions based on standard anatomical landmarks for both surgical planning and graft volume calculations. We believe our technique will help prevent small-for-size grafting and liver insufficiency resulting from inaccurate volumetric calculations. Our findings also support the observation that improved venous outflow might be achieved by including the MHV with the right liver graft without disadvantaging the left liver remnant. It is our hope that all these findings will translate into enhanced donor and recipient safety.

Adult↗

Outcome of liver transplantation for children with liver disease.

INTRODUCTION: The advent of liver transplantation has revolutionised the outcome of children with both acute liver failure and chronic end-stage liver disease. The aim of this study was to review the outcome of all paediatric liver transplants performed since the National Liver Transplant Programme began in 1990. METHODS: A retrospective review of all paediatric liver transplants from 1990 to December 2004 was performed. RESULTS: 46 liver transplants were performed in 43 children, of whom 23 (53.3 percent) were female. Median age at transplant was 21 months (range 11 months to 14 years). The most common indication for liver transplant was biliary atresia (71.7 percent). Living-related transplants accounted for 63 percent (29). Re-transplant rate was 6.5 percent with allograft loss as a result of hepatic artery thrombosis (two) and hepatic vein thrombosis (one). Tacrolimus was the primary immunosuppressive agent used in 89 percent of patients, with a 19.6 percent incidence of acute allograft rejection within the first six months. There were nine deaths. They were related to portal vein thrombosis (three), chronic rejection (one), sepsis (two), post-transplant lymphoproliferative disease (two) and primary graft non-function (one). Overall actuarial one- and five-year survival rate was 85.7 percent and 81.8 percent, respectively. CONCLUSION: Liver transplantation is an established form of intervention for end-stage liver disease and a variety of liver-related metabolic disease. Our results are comparable to those of well-established liver transplant centres.

Adolescent↗

Effect of phenobarbital and other liver monooxygenase modifiers on dimethylnitrosamine-induced alkylation of rat liver macromolecules.

The effects of phenobarbital (PB) and other liver monooxygenase modifiers on dimethylnitrosamine (DMN)-induced alkylation of rat liver DNA and protein were investigated at different carcinogen doses. In rats given single injections of radioactively labeled DMN, pretreatment with PB (80 mg/kg body weight, administered for 5 days) resulted in a small but significant decrease in the formation of 7-methylguanine and O6-methylguanine per mole of guanine in liver DNA associated with a decrease in the O6/N7-methylguanine ratio. The specific radioactivity of liver protein was also lowered in PB-pretreated rats. The degree of PB interference was independent of DMN dose within a carcinogen dose range of 0.5 microgram to 10 mg/kg body weight. In parallel experiments, the effects of pretreatment with PB, Aroclor 1254, pregnenolone-16 alpha-carbonitrile, butylated hydroxytoluene, beta-naphthoflavone, and ethanol on DMN-induced alkylation of liver DNA were studied at a DMN dose of 5 micrograms/kg body weight. In general, pretreatment with these modifiers of liver monooxygenase resulted in a decrease in specific alkylation of DNA and in the ratio of 7-methylguanine to guanine. If, however, 7-methylguanine levels were related to total liver DNA, these differences in DNA alkylation between controls and pretreated rats became substantially smaller, partially being negligible, since these inducers led to an increase in relative liver weight with concomitant increase in the content of liver DNA. Thus, when expressed per total liver, no significant changes in the overall extent of metabolic activation of DMN were evident. These findings are not consistent with the results of in vitro studies on DMN metabolism in microsomal systems which favored the hypothesis that changes in the metabolism of hepatocarcinogens are responsible for the reduction of liver tumor response in animals treated simultaneously with inducers of the liver monooxygenase system and hepatocarcinogens. Our findings suggest that these effects might rather be related to drug-mediated changes on the cellular level.

Alkylation↗

[Effect of normoxic and anoxic liver perfusion as well as ischemic liver storage on parameters of mitochondrial respiration and swelling].

Using the model of Hb-free perfused rat liver, the influence of normoxic or anoxic perfusion, as well as ischemic storage of the liver on parameters of respiration and on swelling has been studied comparatively. The system used for Hb-free perfusion ensures at normoxic perfusion of the liver the functional integrity of isolated mitochondria for a period of investigation of 180 min. Normothermal ischemia of the liver leads, already after 20 min, to a significant decline of the ADP/O quotient and of the respiration control coefficient of the isolated mitochondria, as well as to mitochondrial swelling. Hypothermal ischemia of the liver (25 degrees C) clearly diminishes the mitochondrial functional loss. As far as the liver disposes of an endogenous glycogen store, the integrity of the mitochondria isolated after anoxic liver perfusion (25 degrees C) is retained and longer than after hypothermal ischemia of the liver. Mitochondria isolated after anoxic perfusion from glycogen-deprived liver swell and uncouple as fast as mitochondria prepared after ischemic storage of the glycogen-containing liver. Normoxic reperfusion of the ischemically pre-damaged liver leads to partial recovery of the mitochondria, if reoxygenation of the liver is started no later than after 80 min of ischemic storagel.

Animals↗

Liver regeneration 4: transcriptional control of liver regeneration.

Determining what factors are responsible for initiating regeneration following partial hepatectomy or toxic damage, and how the liver maintains differentiated functions while the hepatocytes are undergoing cellular proliferation are central issues in understanding the molecular bases of liver regeneration. Examination of the transcriptional milieu in the regenerating liver provides clues to the answers to these questions. Growth factor-generated intracellular signals that trigger liver regeneration result in activation via posttranslational modifications of latent, normally inactive transcription factors that preexist in the liver. Two transcription factors that are activated by this mechanism include posthepatectomy factor/nuclear factor-kappa B) and Stat3. Because cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-l (IL-1), and IL-6 can induce these factors in the liver, the finding of activated Stat3 and PHF/NF-kappa B suggests that these cytokines may play a role in some aspects of growth regulation during liver regeneration. Rapidly induced transcription factors, Stat3, PHF/NF-kappa B, and others are responsible for activation of the primary growth response or immediate-early genes, which play a role in regulating later phases of cell growth in regenerating liver and other mitogen-activated cells. Immediate-early genes encode many members of diverse transcription factor families including the Jun-Fos-LRF-1, nuclear receptor, and myc families to name a few. In this way a transcriptional cascade is established during the G1 phase of liver regeneration. Coexisting with these induced factors are liver-specific transcription factors such as the CAAT enhancer binding proteins and hepatocyte nuclear factors, which may interact with growth-induced factors to help the liver maintain metabolic homeostasis during regeneration. As a result the liver is able to accomplish the goals of reestablishing its mass while it maintains its functional capacity during regeneration.

Animals↗

Follow-up after liver transplantation for protoporphyric liver disease.

Protoporphyria is a genetic disorder in which patients may develop severe protoporphyrin-induced liver damage and require transplantation. Because unique problems occur in the perioperative period and because excess production of protoporphyrin by the bone marrow continues after liver transplantation, the efficacy of this procedure for protoporphyric liver disease is uncertain. We present follow-up of nine patients who underwent liver transplantation. Two patients died within 2 months of transplantation, one from complications of abdominal bleeding and the other from sepsis after bowel perforations. The remaining seven patients had follow-up at 14 months to 8 years after transplantation (mean, 3.8 years). Two of the seven had suffered skin burns from exposure to operating room lights, which healed without scarring. Three had axonal neuropathies in the postoperative period requiring prolonged mechanical ventilation, and motor defects persisted in two. Five patients had normal liver chemistries at follow-up (mean, 3.5 years), with liver biopsy results normal or showing mild portal triad abnormalities, but erythrocyte protoporphyrin levels remained significantly elevated (1,765 +/- 365 mcg/dL; normal, < 65). The other two patients, both of whom had rejection, cytomegalovirus infection, and biliary tract obstruction requiring endoscopic therapy, had a recurrence of protoporphyric liver disease as indicated by liver biopsy features. One died 5 years after transplantation from complications of the liver disease. The other was stable 3.3 years after transplantation and was being monitored for possible retransplantation. Thus, liver transplantation can be performed successfully in patients with protoporphyric liver disease, with intermediate survival rates comparable to the general transplant population. However, disease may recur in the graft, particularly if there are complications that cause cholestasis.

Adolescent↗

Recovery from liver failure after hepatectomy for hepatocellular carcinoma in cirrhosis: meaning of the model for end-stage liver disease.

BACKGROUND: Hepatectomy for hepatocellular carcinoma in cirrhosis is followed by an impairment of liver function that can lead to patient death. The model for end-stage liver disease (MELD) is considered an index of hepatic functional reserve, and its assessment on postoperative course may properly identify individuals at risk of liver failure. STUDY DESIGN: Two hundred hepatectomies for hepatocellular carcinoma in cirrhosis were reviewed. Irreversible postoperative liver failure was defined as an impairment of liver function after hepatectomy that led to patient death or required transplantation. The MELD scores at postoperative days (POD) 1, 3, 5, and 7 were calculated and kinetics of changes investigated with t-test; logistic regression was applied to identify predictive variables of postoperative liver failure. RESULTS: Kinetics of postoperative MELD score showed an impairment of liver function between PODs 1 and 3; 185 patients in whom postoperative liver failure did not develop showed a considerable decrease in MELD score between PODs 3 and 5 (11.9+/-2.8 and 10.6+/-2.4, respectively, p<0.001). On the contrary, 15 patients, who experienced the event, showed an increase in MELD score between PODs 3 and 5 (18.2+/-3.9 and 18.3+/-3.6, respectively; p=0.845). Multivariate analysis showed preoperative MELD score (p<0.001), major hepatectomy (p=0.028), and MELD score increase between PODs 3 and 5 (p=0.011) as independent predictors of irreversible postoperative liver failure. Scores are reported as mean+/-SD. CONCLUSIONS: Recovery from liver impairment after hepatectomy for hepatocellular carcinoma in cirrhosis starts from POD 3; MELD scores increasing between PODs 3 and 5 may identify patients at risk of liver failure and represents the trigger for beginning intensive treatment or evaluating salvage transplantation.

Aged↗

Is liver biopsy useful in the evaluation of patients with chronically elevated liver enzymes?

STUDY OBJECTIVE: To determine the diagnostic usefulness of percutaneous liver biopsy in evaluating patients with chronically elevated liver-associated enzymes. DESIGN: Comparison of diagnosis made before biopsy by one physician on the basis of a noninvasive work-up (history, physical examination, laboratory values, and imaging studies) and final diagnosis made after biopsy by a second physician formulated after review of all available noninvasive information and study of the biopsy specimen. SETTING: Referral-based gastroenterology clinic at a U.S. Navy medical center. PATIENTS: Sequential sample of 107 patients with elevated liver-associated enzymes for a minimum of 3 months. Ninety patients were eligible for study. INTERVENTIONS: The final diagnosis made by the second physician blinded to the first clinician's diagnosis served as the criterion standard. MEASUREMENTS AND MAIN RESULTS: Four diagnostic groups were selected for analysis: Alcoholic liver disease, fatty liver, chronic necroinflammatory diseases, and miscellaneous. The positive predictive value of the prebiopsy diagnosis ranged from 88% (CI, 75% to 100%) for alcoholic liver disease to 56% (CI, 37% to 75%) for fatty liver. Higher elevations of transaminase values (greater than three times the upper limit of normal) correlated positively with increased prebiopsy diagnostic accuracy. Fatty liver was present in 19% of the cohort. Liver diseases requiring specific therapy other than alcohol abstinence were overlooked and diagnosed only after review of the biopsy in five cases. Conversely, four cases of liver disease, thought to require specific therapy on the basis of noninvasive work-up, were ruled out by biopsy. CONCLUSION: The cause of chronic liver disease is best elucidated when the noninvasive work-up is complemented by review of a biopsy specimen.

Adult↗

Liver transplantation for alcoholic liver disease.

BACKGROUND: Alcoholism is the leading cause of end-stage liver failure in the United States, but the application of liver transplantation to the treatment of alcoholic liver disease remains controversial because of medical and ethical concerns. Information about the outcome of patients who undergo transplantation for alcoholic cirrhosis would help to resolve these concerns. METHODS: The results of 41 patients (Group 1) with alcoholic liver disease were compared with those of patients who underwent liver transplantation for other medical problems (group 2) at this center. Thirty of the 32 survivors from group 1 and 30 matched subjects from group 2 were interviewed to assess substance dependence, recidivism, and activity level. RESULTS: Compared with control subjects, patients with alcoholic liver disease had equivalent patient and graft survival rates and achieved an equal level of postoperative health. These results were achieved even though patients with alcoholic liver disease had significantly worse liver failure and more morbidity before surgery, and one third of the patients in this group were not abstinent before transplantation. CONCLUSIONS: We conclude that patients with alcoholic liver disease merit equal consideration for liver transplantation compared with other causes of liver failure. Treatment of the addictive disorder should be included before and after surgery.

Actuarial Analysis↗