Pulmonary complications in chronic liver disease.

The association of chronic liver disease with respiratory symptoms and hypoxia is well recognized. Over the last century, three pulmonary complications specific to chronic liver disease have been characterized: hepatopulmonary syndrome (HPS), portopulmonary hypertension (POPH), and hepatic hydrothorax (HH). The development of portal hypertension is fundamental in the pathogenesis of each of these disorders. HPS is the most common condition, found in 5%-30% of cirrhosis patients, manifested by abnormal oxygenation due to the development of intrapulmonary vascular dilatations. The presence of HPS increases mortality and impairs quality of life, but is reversible with liver transplantation (LT). POPH is characterized by development of pulmonary arterial hypertension in the setting of portal hypertension, and is present in 5%-10% of cirrhosis patients evaluated for LT. Screening for POPH in cirrhosis patients eligible for LT is critical since severe POPH is a relative contraindication for LT. Patients with moderate POPH, who respond adequately to medical therapy, may benefit from LT, although sufficient controlled data are lacking. HH is a transudative pleural effusion seen in 5%-10% of cirrhosis patients, in the absence of cardiopulmonary disease. Diagnosis of HH should prompt consideration for LT, which is the ultimate treatment for HH. Conservative management includes salt restriction and diuretics, with thoracentesis and transjugular intrahepatic portosystemic shunt (TIPS) as second-line therapeutic options.

The impact of left ventricular hypertrophy on survival in candidates for liver transplantation.

Left ventricular hypertrophy (LVH) occurs in 12% to 30% of patients with cirrhosis; however, its prognostic significance is not well studied. We assessed the association of LVH with survival in patients undergoing a liver transplantation (LT) evaluation. We performed a multicenter cohort study of patients undergoing an evaluation for LT. LVH was defined with transthoracic echocardiography. The outcome of interest was all-cause mortality. LVH was present in 138 of 485 patients (28%). Patients with LVH were older, more likely to be male and African American, and were more likely to have hypertension. Three hundred forty-five patients did not undergo transplantation (212 declined, and 133 were waiting): 36 of 110 patients with LVH (33%) died, whereas 57 of 235 patients without LVH (24%) died (P = 0.23). After LT, 8 of 28 patients with LVH (29%) died over the course of 3 years, whereas 9 of 112 patients without LVH (8%) died (P = 0.007). This finding was independent of conventional risk factors for LVH, and all deaths for patients with LVH occurred within 9 months of LT. No clinical or demographic characteristics were associated with mortality among LVH patients. In conclusion, the presence of LVH is associated with an early increase in mortality after LT, and this is independent of conventional risk factors for LVH. Further studies are needed to confirm these findings and identify factors associated with mortality after transplantation to improve outcomes.

Hepatopulmonary syndrome.

Hepatopulmonary syndrome (HPS) is characterized by an oxygenation defect induced by pulmonary vascular dilatation in the setting of liver cirrhosis or portal hypertension. It is defined by an alveolar-arterial gradient > 15 mm Hg measured at sea level. This syndrome is seen in 15 to 30% of cirrhotic patients and has been associated with worse survival. Most HPS patients are either asymptomatic or develop the insidious onset of dyspnea. The key event in its pathogenesis is the development of intrapulmonary vascular dilatation (IPVD), which has been linked to increased pulmonary levels of nitric oxide. Pulse oximetry is a useful screening test for HPS, which can guide subsequent use of arterial blood gases. Contrast-enhanced transthoracic echocardiography is the most effective test to demonstrate IPVD. Another method for detecting IPVD is the radionuclide lung perfusion scanning, using technetium-labeled macroaggregated albumin particles. Liver transplantation is the only available treatment for HPS, resulting in complete resolution or significant improvement in gas exchange in over 85% of patients.

The natural history of hepatitis C cirrhosis after liver transplantation.

Hepatitis C after liver transplantation leads to graft cirrhosis in up to 30% of patients within 5 years, but limited data exist regarding the clinical course of cirrhosis after transplantation. The aims of this study were to report the natural history of hepatitis C cirrhosis after liver transplantation and to identify risk factors for decompensation and survival. Hepatitis C patients underwent protocol liver biopsies yearly after liver transplantation. After cirrhosis was identified by biopsy, the outcomes of interest were the development of decompensation, death, or retransplantation for hepatitis C. Kaplan-Meier and Cox regression analysis was used to determine survival and risk factors for decompensation and mortality. Out of 502 liver transplants performed for hepatitis C, 88 patients (18%) had cirrhosis within 3.7 years. Seventy-one patients were compensated at diagnosis. The cumulative probability of decompensation 1 year after cirrhosis was 30%. A Model for End-Stage Liver disease score >or= 16 was predictive of decompensation and poor survival, whereas successful interferon treatment was found to reduce this risk (relative risk = 0.05). Once decompensation occurred, 1-year survival was 46%. In conclusion, the results confirm an accelerated natural history of hepatitis C cirrhosis after liver transplantation and demonstrate poor survival after decompensation. The Model for End-Stage Liver Disease can stratify risk for decompensation and survival, whereas successful antiviral therapy may be protective.

Long-term outcomes of donation after cardiac death liver allografts from a single center.

Organ shortage continues to be a major challenge in transplantation. Recent experience with controlled non-heart-beating or donation after cardiac death (DCD) are encouraging. However, long-term outcomes of DCD liver allografts are limited. In this study, we present outcomes of 19 DCD liver allografts with follow-up >4.5 years. During 1998-2001, 19 (4.1%) liver transplants (LT) with DCD allografts were performed at our center. Conventional heart-beating donors included 234 standard criteria donors (SCD) and 214 extended criteria donors (ECD). We found that DCD allografts had equivalent rates of primary non-function and biliary complications as compared with SCD and ECD. The overall one-, two-, and five-yr DCD graft and patient survival was 73.7%, 68.4%, and 63.2%, and 89.5%, 89.5%, and 89.5%, respectively. DCD graft survival was similar to graft survival of SCD and ECD in non hepatitis C virus (HCV) recipients (p > 0.370). In contrast, DCD graft survival was significantly reduced in HCV recipients (p = 0.007). In conclusion, DCD liver allografts are durable and have acceptable long-term outcomes. Further research is required to assess the impact of HCV on DCD allograft survival.

Factors predicting survival after transjugular intrahepatic portosystemic shunt creation: 15 years' experience from a single tertiary medical center.

PURPOSE: This retrospective analysis was conducted to identify factors predictive of survival after transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS: Patients who underwent TIPS creation between January 1991 and December 2005 at a tertiary-care center were identified. Log-rank tests were used to compare the cumulative survival functions among groups of patients who underwent TIPS creation for various indications. Thirty-day mortality after TIPS creation was examined by logistic regression. Cox proportional-hazards analyses were performed to analyze the cumulative 90-day and 1-year survival. Selected variables such as creatinine, bilirubin, and International Normalized Ratio (INR) were assessed with respect to survival. RESULTS: The study included 352 patients, of whom 229 (65.1%) were male. The mean age at the time of TIPS creation was 53.6 years (range, 21-82 y). A Model for End-stage Liver Disease (MELD) score greater than 15 was significantly associated with poor survival (P < .05) at 30 days, 90 days, and 1 year after TIPS creation. Independently, a serum total bilirubin level greater than 2.5 mg/dL, an INR greater than 1.4 (P < .05), and a serum creatinine level greater than 1.2 mg/dL were predictive of poor survival. Finally, age greater than 70 years was associated with poor survival at 90 days and 1 year after TIPS creation (P < .05). CONCLUSION: The choice to create a TIPS in individuals whose MELD score is greater than 15 and/or whose age is greater than 70 years should involve a careful consideration of risk/benefit ratio, taking into account the finding that such patients have significantly poorer survival after TIPS creation.

Effect of antiviral chemoprophylaxis on adverse clinical outcomes associated with cytomegalovirus after liver transplantation.

OBJECTIVE: To assess t he association be tweencytomegalovirus (CMV) serology of donor and recipient and adverse outcomes afterliver transplantation in the era of effective antiviral chemoprophylaxis. PATIENTS AND METHODS: We performed a retrospective cohort study of 193 consecutive patients undergoing their first liver transplantation between February 1998 and July 2000 with targeted and preemptive ganciclovir chemoprophylaxis. Patients were divided into 4 groups by CMV serology of donor and recipient: donor-/recipient-; donor-/recipient+; donor+/recipient+; and donor+/recipient-. Survival to the end points of retransplantation, death, or survival to 1 year after transplantation (whichever occurred first) was assessed. Rates of bacterial, fungal, and CMV Infection and of CMV disease were recorded and compared. RESULTS: No significant differences were observed in the rates of retransplantation, death, or survival to 1 year among the 4 groups of patients. Despite significantly higher rates of CMV infection in the donor+ groups, there were no differences in the rates of bacterial or fungal Infection or of CMV disease. Rejection occurred least frequently in the donor-/recipient- group. CONCLUSION: The adverse effects of CMV on outcomes after liver transplantation have been diminished in the era of effective antiviral chemoprophylaxis.

Donor age affects fibrosis progression and graft survival after liver transplantation for hepatitis C.

BACKGROUND: The use of liver allografts from an older donor (OD) (age>50 years) is a widespread strategy to manage the disparity between supply and demand of organs for liver transplantation. This study determines the effect of OD allografts on fibrosis progression and graft survival after liver transplantation in patients with and without infection caused by hepatitis C virus (HCV). METHODS: All patients undergoing liver transplantation at our center from March 1998 to December 2001 were analyzed. Protocol liver biopsies were performed at 1, 16, and 52 weeks after transplantation and yearly thereafter. One liver pathologist scored all biopsy specimens for modified hepatic activity index (0-18) and fibrosis (0-6). RESULTS: A total of 402 patients (167 with HCV and 235 without HCV) underwent liver transplantation during the study period. Among patients with HCV, baseline characteristics of OD recipients were similar to younger donor (YD) (age<50 years) recipients. In patients with HCV, graft survival was shorter in OD graft recipients than in YD recipients (P<0.001). In patients without HCV, graft survival was independent of donor age. In patients with HCV, a fibrosis score of 3 or greater was present in 17% of OD recipients at 4 months and in 26% at 12 months after transplantation, compared with 8% of YD recipients at 4 months and 13% at 12 months (P<0.001). CONCLUSIONS: Liver transplantation with OD grafts is associated with rapid progression of fibrosis and decreased graft survival in patients with HCV, but not in patients without HCV. OD grafts should be considered preferentially for patients without HCV.

Gender preference for the endoscopist among Hispanics: the results of a prospective study.

We aim to assess the gender preferences for endoscopists among Hispanics and factors influencing such preferences. Cross-sectional study in prospectively enrolled Hispanic patients using a pre-endoscopy questionnaire regarding their gender preferences for the endoscopist and the reasons for such preferences. Multivariate logistic regression model was used for the statistical analysis. We enrolled total 200 Hispanic patients (100 males, 100 females) in our study. Their mean age was 51 ± 14 years. 30 % of Hispanics expressed a gender preference for the endoscopist. Gender preference was more common among Hispanic women than men (38 % vs. 22 %, p = 0.014). Gender preference for primary care provider was independently associated with the gender preference for the endoscopist (odds ratio 66, 95 % CI 25-182, p < 0.0001). We found significant number of Hispanic patients with gender preference for the endoscopist (female more than male). The odds of such preferences were strongly associated with the gender preference for the primary care physician.

Gastric antral vascular ectasia and its clinical correlates in patients with early diffuse systemic sclerosis in the SCOT trial.

OBJECTIVE: To describe the prevalence and clinical correlates of endoscopic gastric antral vascular ectasia (GAVE; "watermelon stomach") in early diffuse systemic sclerosis (SSc). METHODS: Subjects with early, diffuse SSc and evidence of specific internal organ involvement were considered for the Scleroderma: Cyclophosphamide Or Transplant (SCOT) trial. In the screening procedures, all patients underwent upper gastrointestinal endoscopy. Patients were then categorized into those with or without endoscopic evidence of GAVE. Demographic data, clinical disease characteristics, and autoantibody data were compared using Pearson chi-square or Student t tests. RESULTS: Twenty-three of 103 (22.3%) individuals were found to have GAVE on endoscopy. Although not statistically significant, anti-topoisomerase I (anti-Scl70) was detected less frequently among those with GAVE (18.8% vs 44.7%; p = 0.071). Similarly, anti-RNP antibodies (anti-U1 RNP) showed a trend to a negative association with GAVE (0 vs 18.4%; p = 0.066). There was no association between anti-RNA polymerase III and GAVE. Patients with GAVE had significantly more erythema or vascular ectasias in other parts of the stomach (26.1% vs 5.0%; p = 0.003). CONCLUSION: Endoscopic GAVE was present on screening in almost one-fourth of these highly selected patients with early and severe diffuse SSc. While anti-Scl70 and anti-U1 RNP trended toward a negative association with GAVE, there was no correlation between anti-RNA Pol III and GAVE. Patients with GAVE had a higher frequency of other gastric vascular ectasias outside the antrum, suggesting that GAVE may represent part of the spectrum of the vasculopathy in SSc.

Current use of hepatitis B immune globulin for prevention of de novo hepatitis B in recipients receiving anti-HBc-positive livers.

Livers from donors positive for antibody against anti-HBc can potentially transmit de novo hepatitis B (DNH) to their recipients. Despite a good outcome, prophylaxis is usually offered to such recipients. There is no consensus on the standard prophylactic regimen and hence prophylaxis varies among different transplant centres. Nonetheless, hepatitis B immune globulin (HBIG) is considered the mainstay of such prophylaxis, either alone or in combination with an oral antiviral treatment. We aim to provide a concise review of the current use of HBIG in prevention of DNH. We also address a few important questions regarding HBIG use.

Vanishing bile duct syndrome in human immunodeficiency virus: nevirapine hepatotoxicity revisited.

Vanishing bile duct syndrome (VBDS) refers to a group of disorders characterized by prolonged cholestasis as a result of destruction and disappearance of intrahepatic bile ducts. Multiple etiologies have been indentified including infections, neoplastic disorders, autoimmune conditions and drugs. The natural history of this condition is variable and may involve resolution of cholestasis or progression with irreversible damage. VBDS is extremely rare in human immunodeficiency virus (HIV)-infected patients and anti-retroviral therapy has never been implicated as a cause. We encountered a young pregnant female with HIV and VBDS secondary to anti-retroviral therapy. Here, we report her clinical course and outcome.

Liver retransplantation of patients with hepatitis C infection is associated with acceptable patient and graft survival.

Infection with hepatitis C virus (HCV) is the leading cause of liver transplantation (LT), while liver retransplantation (RT) for HCV is controversial as a result of concerns over poor outcomes. We sought to compare patient and graft survival after RT in patients with and without HCV. We performed a retrospective chart review of all patients undergoing RT at our center between February 1998 and April 2004. Indications for RT, HCV status, patient, and donor characteristics, laboratory values, and hospitalization status at RT were collected. A total of 108 patients (48 HCV and 60 non-HCV) underwent RT during the study period, with mean post-RT follow-up of 1,096 days (range, 0-2,888 days). Grafts from donors aged>60 years were used less frequently in HCV patients at RT (6%) compared with LT (47%), P<0.001. There was no difference between HCV vs. non-HCV patients in 1- and 3-year patient survival (respectively, 79% vs. 63%, and 71% vs. 63%) and graft survival (respectively, 67% vs. 66%, and 59% vs. 56%). Post-RT mortality and graft failure in HCV patients occurred within the first year in 89% of patients, and 83% were unrelated to HCV recurrence. We conclude that patients should not be excluded from consideration for retransplantation solely on the basis of a diagnosis of HCV.

Cyclosporine suppresses hepatitis C virus in vitro and increases the chance of a sustained virological response after liver transplantation.

Cyclosporine is an immunosuppressive agent widely used in the management of liver transplant recipients. Cyclosporine has been shown to have antiviral activities against HIV, herpes simplex, and vaccinia viruses. The aim of this study was to determine the effect of Cyclosporine in viral clearance in the liver transplant recipients during therapy with combination of interferon and ribavirin, and to determine the anti-viral potential of Cyclosporine in vitro. Immunosuppression consisted of either Cyclosporine or Tacrolimus-based therapy. Both groups received therapy with interferon and ribavirin for 48 weeks when evidence of progressive histologic disease was determined. We found that subjects on Cyclosporine-based immunosuppression (n = 56) had a higher sustained virological response of 46% compared to 27% in the patients on Tacrolimus-based therapy (n = 59, P = 0.03). In vitro studies were performed to evaluate the antiviral effect of Cyclosporine in the replicon system. These studies showed that Cyclosporine inhibits hepatitis C viral replication in a dose-dependent manner. Combination of Cyclosporine with interferon showed additive effect, and its function is independent of interferon signaling pathways. In conclusion, Cyclosporine may offer an advantage to Tacrolimus in those patients undergoing interferon-based therapy and should be studied in a prospective randomized trial.

Impact of implementation of the MELD scoring system on the prevalence and incidence of chronic renal disease following liver transplantation.

The implementation of the model for end-stage liver disease (MELD) score decreased mortality of those awaiting liver transplantation (LT); however, the impact of the MELD allocation system on the risk of chronic renal disease after LT remains unknown. We conducted a non-concurrent single-center cohort study of 174 patients undergoing LT at our center. We compared patients who underwent LT one year prior to MELD implementation (pre-MELD cohort) to those patients who underwent LT 1 year following MELD implementation (MELD cohort). All patients were followed for at least 2 years after LT. Stage 3 chronic renal disease (CRD-3) was defined by an estimated creatinine clearance (CL(Cr)) below 60 ml/min/1.73 m2, and stage 4 chronic renal disease (CRD-4) was defined by an estimated CL(Cr) below 30 mL/min/1.73 m2 according to the validated Modification of Diet and Renal Disease (MDRD) formula. Requirement of kidney transplantation and need for hemodialysis were also evaluated following LT. The pre-MELD cohort (n=97) and the MELD cohort (n=77) were comparable in baseline characteristics, prevalence of diabetes and hypertension, and immunosuppression. Mean calculated MELD score in the pre-MELD cohort was significantly lower than in the MELD cohort (16 vs. 19, P < 0.05). The estimated CL(Cr) at time of LT was lower in the MELD cohort compared with the pre-MELD cohort (75 vs. 95, P < 0.01). However, the incidence and prevalence of CRD-3 and CRD-4 at 6, 12, and 24 months after LT were comparable between the two cohorts. Need for kidney transplantation or hemodialysis after LT was comparable between the groups. In multivariate analysis, serum creatinine at LT was the only variable associated with the development of CRD-3 in the first 2 years after LT. In conclusion, the implementation of the MELD allocation system is not associated with increased mortality or occurrence of CRD-3 or CRD-4 in the first 2 years after LT.

Arterioportal fistula causing acute pancreatitis and hemobilia after liver biopsy.

We report the case of a 49-year-old patient who developed hemobilia and acute pancreatitis from an arterioportal fistula after a percutaneous liver biopsy, and we analyze diagnostic testing and management based on a concise review of the available literature. Hemobilia can present as late as 10 days after liver biopsy. Acute pancreatitis is a rare complication of hemobilia. To our knowledge, this is the first documented case of an arterioportal fistula after percutaneous liver biopsy with the late manifestation of hemobilia and acute pancreatitis.

Esophageal sarcoidosis: an unusual diagnosis.

We report a 48-year-old patient who developed secondary achalasia because of esophageal sarcoidosis. Sarcoidosis can involve many gastrointestinal tract organs and can affect the esophagus in different ways. We describe how achalasia was diagnosed and treated in our patient and provide a review of the presentations of esophageal sarcoidosis.

Colonoscopy in octogenarians: a prospective outpatient study.

OBJECTIVES: The number of octogenarians (age > or =80 yr) referred for colonoscopy is increasing. Reported success rates regarding colonoscopy completion and adequacy of colonic preparation are poor overall in this group. This may be the result of age-related differences or biases due to retrospective data. The aims of this study were to prospectively determine differences between octogenarians and nonoctogenarians in adequacy of colonic preparation, success in completing colonoscopy, and complications of conscious sedation. METHODS: Prospective cohort study of 250 consecutive outpatients (150 nonoctogenarians and 100 octogenarians) referred for colonoscopy. Colonic preparation tolerance was assessed before colonoscopy, and the success rate and preparation were evaluated after the procedure. Conscious sedation complications were compared. RESULTS: In octogenarians and nonoctogenarians preparation tolerance (86% and 90%, respectively) was similar. Endoscopic success rate was slightly lower in octogenarians (90% vs 99%, p = 0.002). Preparation was poor in 16% of octogenarians compared with 4% of nonoctogenarians (p = 0.001). This was independent of the type of preparation used. Oxygen desaturation was more common in octogenarians (27% vs 19%, p = 0.0007) and associated with a higher meperidine dose (1.05 vs 0.75 mg/kg). No adverse outcomes occurred in either study group. CONCLUSIONS: Colonic preparations were well tolerated and colonoscopic success rates were high in octogenarians and nonoctogenarians. However, poor colonic preparation was four times as likely in octogenarians and was the most important impediment to adequate colonoscopy.

Hepatitis C recurrence is not associated with allograft steatosis within the first year after liver transplantation.

The natural history of allograft steatosis in hepatitis C (HCV)-infected patients after liver transplantation (LT) is poorly understood. The aim of our study was to determine the relationship of allograft steatosis to HCV recurrence after LT. All patients undergoing LT at our center from March 1998 to December 2001 were included in the study. Explanted liver tissue and liver biopsies performed at 1 week, 4 months, and 12 months were scored for degree of allograft steatosis (0-4), fibrosis (0-6), and modified histological activity index (0-18). One hundred sixty-seven HCV and 235 non-HCV-infected patients (control group) underwent LT. Of these patients, 122 HCV and 154 non-HCV patients had a viable graft at 1 year and were analyzed. Allograft steatosis was present in 40% of HCV patients at 4 months and 36% at 1 year. The incidence of allograft steatosis after LT was similar in HCV-infected and non-HCV-infected patients (P not significant). Age of the donor (P =.041), or higher recipient body mass index (BMI) at the time of LT (P =.015) or at 12 months after LT (P =.041) predicted a higher degree of allograft steatosis at 12 months in the HCV group. Degree of allograft steatosis was not associated with higher fibrosis or necroinflammatory score. In conclusion, there is a similar high incidence of allograft steatosis in HCV and non-HCV-infected patients after LT. A high BMI of the HCV-infected recipient is the best predictor for high degree of allograft steatosis after LT. Allograft steatosis does not predict the severity of HCV recurrence in the first 12 months after LT.