Human monoclonal antibody MBL-HCV1 delays HCV viral rebound following liver transplantation: a randomized controlled study.

Rapid allograft infection complicates liver transplantation (LT) in patients with hepatitis C virus (HCV). Pegylated interferon-α and ribavirin therapy after LT has significant toxicity and limited efficacy. The effect of a human monoclonal antibody targeting the HCV E2 glycoprotein (MBL-HCV1) on viral clearance was examined in a randomized, double-blind, placebo-controlled pilot study in patients infected with HCV genotype 1a undergoing LT. Subjects received 11 infusions of 50 mg/kg MBL-HCV1 (n=6) or placebo (n=5) intravenously with three infusions on day of transplant, a single infusion on days 1 through 7 and one infusion on day 14 after LT. MBL-HCV1 was well-tolerated and reduced viral load for a period ranging from 7 to 28 days. Median change in viral load (log10 IU/mL) from baseline was significantly greater (p=0.02) for the antibody-treated group (range -3.07 to -3.34) compared to placebo group (range -0.331 to -1.01) on days 3 through 6 posttransplant. MBL-HCV1 treatment significantly delayed median time to viral rebound compared to placebo treatment (18.7 days vs. 2.4 days, p<0.001). As with other HCV monotherapies, antibody-treated subjects had resistance-associated variants at the time of viral rebound. A combination study of MBL-HCV1 with a direct-acting antiviral is underway.

Successful algorithm for selective liver biopsy in the right hepatic lobe live donor (RHLD).

Routine versus selective predonation liver biopsy (LBx) remains controversial for assuring the safety of right hepatic lobe live donor (RHLD). Between December 1999 and March 2007, 403 potential RHLD were evaluated; 142 donated. Indications for selective LBx were: abnormal liver function tests or imaging studies, body mass index (BMI) >28, history of substance abuse or family history of immune mediated liver disease. All donors had a LBx at the time of surgery. Of 403 potential RLD, 149(36.9%) were accepted as donors, 25(6.3%) had their recipient receive a deceased donor graft, 94(23.4%) were rejected, 52(12.9%) stopped the evaluation process, 76(18.8%) withdrew from the process and 7(1.7%) are currently completing evaluation. Eighty-seven (21.5%) met criteria and were biopsied. Seventy-three (83.9%) had either normal (n = 24) or macrosteatosis <10% (n = 49); 51 of these donated. Abnormal LBx eliminated 15 potential donors. No significant abnormalities were found in donation biopsies of donors not meeting algorithm criteria. Three of 87 (3.4%) had complications requiring overnight admission (2 for pain, 1 for bleeding; transfusion not required). Use of this algorithm resulted in 78% of potential donors avoiding biopsy and potential complications. No significant liver pathology was identified in donors not meeting criteria for evaluation LBx. Routine predonation LBx is unnecessary in potential RHLD.

Improved survival after live donor adult liver transplantation (LDALT) using right lobe grafts: program experience and lessons learned.

We present our program experience with 85 live donor adult liver transplantation (LDALT) procedures using right lobe grafts with five simultaneous live donor kidney transplants using different donors performed over a 6-year period. After an "early" 2-year experience of 25 LDALT procedures, program improvements in donor and recipient selection, preoperative imaging, donor and recipient surgical technique and immunosuppressive management significantly reduced operative mortality (16% vs. 3.3%, p = 0.038) and improved patient and graft 1-year survival in recipients during our "later" experience with the next 60 cases (January 2001 and March 2005; patient survival: early 70.8% vs. later 92.7%, p = 0.028; graft survival: Early 64% vs. later 91.1%, p = 0.019, respectively). Overall patient and graft survival were 82% and 80%. There was a trend for less postoperative complications (major and minor) with program experience (early 88% vs. later 66.7%; p = 0.054) but overall morbidity remained at 73.8%. Biliary complications (cholangitis, disruption, leak or stricture) were not influenced by program experience (early 32% vs. later 38%). Liver volume adjusted to 100% of standard liver volume (SLV) within 1 month post-transplant. Despite a high rate of morbidity after LDALT, excellent patient and graft survival can be achieved with program experience.

Histological recurrence and progression of hepatitis C after orthotopic liver transplantation: influence of immunosuppressive regimens.

Post-orthotopic liver transplantation (OLT) recurrence of hepatitis C is virtually universal, but histological progression of disease is not. This study examines long-term clinical and liver histological features at and after OLT to elucidate factors predictive of hepatitis C recurrence and progression after OLT. A blinded retrospective review of clinical, serological, and histopathologic features of 65 patients who underwent OLT for hepatitis C and Non A Non B hepatitis was conducted. Histological findings of recurrent hepatitis C and progression (fibrosis, >or= grade 2 by last follow-up) were correlated with clinical parameters. Histological recurrence of hepatitis C was seen in 43 of 65 patients, with progression in 19 patients. Histological findings in the native liver and post-OLT biopsy specimen at the time of recurrence showed no correlation with hepatitis C recurrence and progression. Patients treated with azathioprine (AZA)-containing immunosuppressive regimens experienced less recurrence (6 of 17 v 37 of 48 patients; P < .005) and progression (1 of 17 v 18 of 48 patients; P = .014) than those without AZA as part of their immunosuppressive regimen. No difference was seen between patients treated with cyclosporine versus those administered FK506 (P > .05). Histological recurrence of hepatitis C after OLT is seen in 66% of patients with progressive disease and 29% of all patients. The grade of inflammation in the native liver at the time of OLT and time of recurrence is not predictive of progression. AZA-containing regimens reduce histological recurrence and progression of hepatitis C in post-OLT patients.

Adult-to-adult live donor liver transplantation: a short-term clinicopathologic study.

With the success of pediatric live donor liver transplantation (LDLT) and the continued shortage of cadaveric donors, adult-to-adult LDLT has been performed at some centers, including ours. We performed a detailed histologic review of all liver specimens obtained from 9 adult recipients at and after LDLT and correlated these findings with the patients' course and outcome. Five patients had histologic evidence of biliary tract pathology; 3 of 5 required surgical or radiologic intervention. The other 2 had clinically insignificant biliary disease. Diffuse hepatocytic hemorrhagic necrosis secondary to massive portal blood flow after portal venous revascularization resulted in graft failure and retransplantation in a single patient with severe preoperative portal hypertension. Two perioperative deaths were caused by sepsis and multiorgan failure (day 25) and generalized thrombosis related to factor V Leiden (day 6). The preoperative diagnosis, presence of portal vein thrombosis in the native liver, postoperative cholangiopathy, and subcapsular hemorrhagic necrosis in donor liver wedge biopsies did not affect the short-term outcome. In conclusion, biliary tract pathology is common after adult-to-adult LDLT but does not negatively affect graft or patient survival. Infrequent but catastrophic vascular complications related to portal hemodynamics or thrombosis can result in graft loss and/or patient death.

Life-threatening hypophosphatemia after right hepatic lobectomy for live donor adult liver transplantation.

Life-threatening hypophosphatemia (phosphorus < 1.0 mg/dL) has been reported only once after liver resection for tumor and was associated with a significant increase in postoperative complications. Hypophosphatemia is associated with reversible cardiac dysfunction, hypoventilation, and impaired immunity. The purpose of this study was to determine the incidence of hypophosphatemia after elective right hepatic lobectomy for live donor adult liver transplantation (LDALT), investigate the associated complication rate and surgical outcome of live liver donors, and determine the efficacy of prospective treatment with phosphate repletion as part of total parenteral nutrition (TPN). Evaluation of 30 donors who provided 30 right-lobe grafts between December 1998 and January 2000 was performed. Of the initial 18 live liver donors (group 1), 10 donors were treated with TPN that contained slightly more (35 +/- 8 mmol/d) than the recommended daily allowance (RDA) of phosphorus (30 mmol/d) starting on postoperative day 1. The last 12 donors (group 2) were prospectively studied and administered similar TPN with 2 times the RDA for phosphorus (60 mmol/d). All donors in group 1 developed hypophosphatemia that was either life threatening (phosphorus < 1.0 mg/dL) in 70% or severely depleted (phosphorus, 1.5 to 1.1 mg/dL) in 30%. With more aggressive phosphate repletion (group 2), only 8% developed life-threatening (phosphorus < 1.0 mg/dL) hypophosphatemia and 30% developed severe (phosphorus, 1.1 to 1.5 mg/dL) hypophosphatemia. Results suggest that hypophosphatemia is a universal event after LDALT and may have contributed to the observed complications in this study. Repletion of phosphorus at twice the RDA abrogates the incidence of hypophosphatemia and may reduce donor morbidity. Institutions performing LDALT should carefully monitor live liver donors for hypophosphatemia and correct abnormal phosphate levels. Additional studies are needed to determine whether more aggressive parenteral repletion can prevent postoperative hypophosphatemia and thus improve outcomes.

Histologic recurrence-free outcome after orthotopic liver transplantation for chronic hepatitis B.

Recurrent hepatitis B (HB) following orthotopic liver transplantation (OLT) for chronic disease is common. However, an unpredictable minority of patients follow a recurrence-free course. Clinical, virologic, and pathologic data from patients surviving longer than 60 days (n=24) with pathologically confirmed nonrecurrence of HB following OLT for chronic HB were reviewed to identify factors associated with nonrecurrence of HB. Nine of 24 patients had no histologic and immunohistologic evidence of recurrent HB. In addition to pre-OLT hepatitis B e antigen (HBeAg) negativity, coexisting delta and anti-HB therapy/prophylaxis, other acquired viral infections and their therapy, and severe acute rejection due to noncompliance were considered the possible protective factors against HB recurrence in these 9 patients. Histologic and, particularly immunopathologic, evaluation of liver biopsies must be utilized in definitively diagnosing recurrence of HB.

Live donor adult liver transplantation using right lobe grafts: donor evaluation and surgical outcome.

HYPOTHESIS: Live donor adult liver transplantation (LDALT) is a safe and efficacious treatment for patients with end-stage liver disease. DESIGN: Case-control study. SETTING: Hepatobiliary surgery and liver transplantation unit. PATIENTS: From December 10, 1998, through April 10, 2000, a single team performed 15 LDALT procedures with 2 simultaneous living donor kidney transplants. During this period, 66 potential donors were screened and evaluated. INTERVENTIONS: Potential donors were evaluated with 3-dimensional helical computed tomographic scan, including volume renderings for hepatic lobar volume, vascular anatomy, virtual resection planes, and morphologic features. Suitable donors undergo complete medical and psychiatric evaluation and preoperative arteriography. MAIN OUTCOME MEASURES: Donor demographics, evaluation data, operative data, hospital length of stay, and morbidity. RESULTS: A total of 38 men (58%) and 28 women (42%) were evaluated with 15 donors participating in LDALT. Two additional donors provided kidney grafts for simultaneous transplantation at the time of LDALT. Thirty-two donors (48%) were rejected for either donor or recipient reasons, and 10 patients (15%) elected not to participate after initial screening. Three-dimensional volume renderings by helical computed tomographic scan predicted right lobe liver volume within 92% of actual graft volume. Donor morbidity, including all complications, was 67% with no mortality. Residual liver regenerated to approximately 70% of initial volume within 1 week and 80% within 1 month after surgery. CONCLUSIONS: Donor evaluation is an important component of LDALT. Significant donor morbidity is encountered even with careful selection. To minimize donor morbidity, groups considering initiating living donor programs should have expertise in hepatic resection and vena cava preservation using the "piggyback" technique during liver transplantation.

Hyperdynamic circulation in portal hypertension: a comparative model of arterio-venous fistula.

Complications of portal hypertension remain perplexing physiologic phenomena in the understanding of shunt hemodynamics with multiple theories. Hyperdynamic circulation was also found in sepsis, chronic anemia and arterio-venous (A-V) fistula which relate to an increase in nitric oxide. We hypothesize that portosystemic collaterals may mimic an A-V fistula in which the high-pressure portal blood connects with the lower pressure systemic venous circulation. Although these collaterals decompress the portal circulation, a number of secondary hemodynamic phenomena occur which increase portal blood flow and tend to counteract the portal hypotensive effect of the portosystemic shunt. The consequent increases in cardiac output and portal blood flow perfuse the compromised liver. As portal blood flow increases, collateral flow increases and is nearly totally shunted in the systemic circulation. This shunt may eventually introduce a vicious cycle of hyperdynamic circulation into a compromised host. Ultimately, high-output cardiac failure occurs, leading to cirrhotic cardiomyopathy.

Human leukocyte antigen DR markers as predictors of progression to liver transplantation in patients with chronic hepatitis C.

OBJECTIVE: Because many patients with chronic viral hepatitis do not progress to end-stage liver disease, it is possible that host factors such as human leukocyte antigen (HLA) differences are important. Our aims were to determine HLA marker-specific rates of progression to liver transplantation among patients with chronic hepatitis C; and to determine if polymerase chain reaction (PCR)-based HLA DRB1 typing can be performed on stored serum samples. METHODS: Forty-two hepatitis C virus RNA-positive liver transplant patients and 87 untransplanted patients were included in a Cox proportional hazards model to test whether the occurrence of certain HLA DRB1 markers were associated with progression to liver transplantation. HLA DRB1 typing was performed on stored serum samples using a PCR method. RESULTS: There were no differences among the HLA DRB1 markers with regard to the HLA marker-specific rate of progression to transplantation among patients with chronic hepatitis C. CONCLUSIONS: HLA DRB1 markers do not appear to be associated with progression of disease in chronic viral hepatitis C. It is possible to perform PCR-based HLA DRB1 typing on stored frozen serum samples.

Liver transplantation for autoimmune hepatitis: a long-term pathologic study.

Autoimmune hepatitis (AIH) after liver transplantation (LT) may recur and is difficult to diagnose. Our aims were to define the histopathology of and factors related to AIH recurrence. Fourteen of 475 patients received LT for AIH; 2 died perioperatively. Liver specimens (native and post-LT biopsies) from 12 other patients were reviewed and correlated with pre- and post-LT clinical course and outcome. Recurrent AIH was seen in 5 of 12 patients, 35 to 280 days post-LT as lobular hepatitis with acidophil bodies and lymphoplasmacytic infiltrate. Portal/interface hepatitis was seen with disease progression and 2 of 5 patients developed cirrhosis. Of 7 nonrecurrent patients, 1 had acquired hepatitis C with lobular/portal hepatitis and none developed cirrhosis. Histology suggestive of overlap syndrome was seen in 3 of 12 native livers with no effect on post-LT course or pathology. High-grade necroinflammation was present in native livers at LT in 5 of 5 cases with recurrent AIH and in 1 of 7 without recurrence (P <.01). Pre-LT disease duration, donor/recipient gender distribution, HLA studies, and rejection episodes did not correlate with AIH recurrence. We conclude that (1) recurrent AIH is not uncommon and was seen in 42% of patients with lymphoplasmacytic lobular, portal, and interface hepatitis; (2) acidophil bodies with lymphoplasmacytic cells are seen in early recurrent AIH; (3) recurrent AIH appears at variable time periods post-LT, and the progression is slow; and (4) high-grade inflammation in native liver at LT is a strong predictor of recurrent AIH.

A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts.

Transjugular intrahepatic portosystemic shunts (TIPS) may worsen liver function and decrease survival in some patients. The Child-Pugh classification has several drawbacks when used to determine survival in such patients. The survival of 231 patients at 4 medical centers within the United States who underwent elective TIPS was studied to develop statistical models to (1) predict patient survival and (2) identify those patients whose liver-related mortality post-TIPS would be 3 months or less. Among these elective TIPS patients, 173 had the procedure for prevention of variceal rebleeding and 58 for treatment of refractory ascites. Death related to liver disease occurred in 110 patients, 70 within 3 months. Cox proportional-hazards regression identified serum concentrations of bilirubin and creatinine, international normalized ratio for prothrombin time (INR), and the cause of the underlying liver disease as predictors of survival in patients undergoing elective TIPS, either for prevention of variceal rebleeding or for treatment of refractory ascites. These variables can be used to calculate a risk score (R) for patients undergoing elective TIPS. Patients with R > 1.8 had a median survival of 3 months or less. This model was superior to both the Child-Pugh classification, as well as the Child-Pugh score, in predicting survival. Using logistic regression and the same variables, we also developed a nomogram that indicates which patients survive less than 3 months. Finally, the model was validated among an independent set of 71 patients from the Netherlands. This Mayo TIPS model may predict early death following elective TIPS for either prevention of variceal rebleeding or for treatment of refractory ascites.

Recurrent hepatitis B, hepatitis C, and combined hepatitis B and C in liver allografts: a comparative pathological study.

Although recurrence of viral hepatitis in liver transplants is common, data comparing recurrent hepatitis B (HB), hepatitis C (HC), and co-existing dual hepatitis B and C (HB&C) are sparse. Posttransplantation liver biopsies, along with molecular, serological, immunohistochemical, and clinical data from 27 patients with pretransplantation diagnosis of chronic viral hepatitis, were reviewed. The patients were placed into 4 groups: Group I, with pretransplantation HB (n = 8); group II, with pretransplantation HC (n = 10); group III with pretransplantation HC and anti-HB surface or core antibody (n = 4); and group IV, with pretransplantation HB&C (n = 5). The histopathologic findings and patient outcome were compared in the 4 groups. A high rate of recurrence of viral hepatitis was seen for all 4 groups: Group I = 100%, group II = 90%, Group III = 100%, and group IV = 80%, with the mean (median) recurrence time of 308 (224), 82 (52), 61 (64), and 125 (70) days, respectively. The number of deaths (their median survival times) were: group I = 4 (374 days), group II = 4 (794 days), group III = 1 (1,143 days), and group IV = 5 (448 days). The earliest histological findings of lobular injury was the presence of acidophil bodies and Kupffer cell hyperplasia, the latter being more prominent in recurrent HC cases. Recurrent HB presented in 2 forms: early (before 150 days) with poor survival and with either severe necroinflammatory histology or with features of fibrosing cholestatic hepatitis, and delayed (after 150 days), with mild necro-inflammatory activity and prolonged survival. HC with or without anti-HB antibodies had early recurrence, but the course was slowly progressive. Patients with HB&C had recurrence of both viruses; however, the course was dictated by HB virus.

Transjugular intrahepatic portosystemic shunt for treatment of bleeding ectopic varices with portal hypertension.

PURPOSE: In the setting of hepatic failure and portal hypertension, hemorrhage from stomal and rectal varices is a well-described problem. It has recently been suggested that transjugular intrahepatic portosystemic shunting may be useful in the therapy of bleeding from parastomal or anorectal varices in patients unresponsive to conservative therapy. METHODS: We retrospectively review our institution's experience of five patients with parastomal varices and seven patients with anorectal varices who underwent transjugular intrahepatic portosystemic shunting for hemorrhage refractory to conservative management between 1994 and 1998. RESULTS: The study group consisted of four Child's A, five Child's B, and three Child's C patients. The mean age of the patients was 60.3 (range, 37-85) years. Mean follow-up was 15 (range, 5-27) months. The mean portosystemic pressure gradient before transjugular intrahepatic portosystemic shunting was 17.4+/-3.1 mm Hg. After transjugular intrahepatic portosystemic shunting, the mean portosystemic pressure gradient was reduced to 5.8+/-1.8 mm Hg (P<0.05). Transjugular intrahepatic portosystemic shunting were successful in complete resolution of bleeding in all patients. Three patients had encephalopathic changes after transjugular intrahepatic portosystemic shunting. Two patients died within 30 days of transjugular intrahepatic portosystemic shunting of causes unrelated to the procedure. Four patients required shunt revision within one year of placement. CONCLUSION: The transjugular intrahepatic portosystemic shunting procedure is an effective modality in the therapy of cirrhotic patients with bleeding stomal or anorectal varices unresponsive to conservative management. There is an acceptable procedure-related morbidity and mortality.

Sarcoidosis with selective involvement of a second liver allograft: report of a case and review of the literature.

A case of sarcoidosis recurrent in a patient's second liver allograft is described. There was no granulomatous disease seen in the patient's first liver allograft. After the second orthotopic liver transplantation (OLT), the patient was successfully treated for acute rejection, aspergillus infection, and cytomegalovirus viremia. Approximately 2 months after the second OLT, the patient was treated with long-term interferon-alpha for recurrent hepatitis C. Five years after the operation, he experienced liver failure secondary to recurrent hepatitis and underwent a third OLT. This is only the second reported case of sarcoidosis recurrent in the liver parenchyma of a transplanted organ and the first in which interferon-alpha might have played a role.

Cost-effectiveness of screening patients for hepatitis C.

This review discusses the benefits and drawbacks of public health screening for hepatitis C, its cost effectiveness, and the various strategies to identify individuals infected with the hepatitis C virus (HCV). Of the estimated 4 million people infected with hepatitis C in the United States, approximately 50% are unaware of their infection. Both the high incidence and recent improvements in the treatment of hepatitis C make it likely that a screening program for this disease would be beneficial to patients, their families, and to the public. Testing for anti-HCV antibody is now widely available, automated, sensitive (>95%), and relatively inexpensive (approximately $80 per test). Interferons and the introduction of ribavirin into the treatment armamentarium have improved the effectiveness of therapy. Lifestyle modifications can be made to decrease the risk of transmission, and patients can be counseled to avoid alcohol consumption and receive hepatitis A and hepatitis B vaccinations, if appropriate. An additional benefit of early detection is that family members can be alerted to the risk factors for hepatitis C. Such education increases overall public awareness of the disease and may improve prevention efforts. Several national agencies within the United States and in Europe have issued guidelines for hepatitis C screening. Each of these calls for screening of high-risk populations, which include individuals who have received blood products and intravenous drug users. Targeted screening and improved treatment outcomes will likely show identification of those with hepatitis C to be cost effective in the future.

Lung abcess complicating Legionella micdadei pneumonia in an adult liver transplant recipient: case report and review.

Legionella micdadei (Pittsburgh pneumonia agent) is the second most common cause of Legionella pneumonia, and occurs predominantly in immunocompromised hosts. L micdadei is the cause of nosocomial pneumonia in renal transplant recipients, but has not been described in other adult solid organ transplant recipients. This report describes the first case of L micdadei pneumonia in an adult liver transplant recipient on immunosuppressive therapy. Importantly, this case highlights the difficulties in establishing the diagnosis, as the Legionella urinary antigen is negative, and special culture conditions are required. Furthermore, this case illustrates several atypical clinical features of L micdadei pneumonia in a transplant recipient, including a community acquired mode of transmission, occurrence several years after organ transplantation, and lung abcess formation. The patient was successfully treated with limited surgical resection and quinolone antimicrobial monotherapy.

AST/ALT ratio predicts cirrhosis in patients with chronic hepatitis C virus infection.

OBJECTIVE: A liver biopsy is necessary to grade and stage chronic hepatitis C virus (HCV) infection. In a previous study of patients with nonalcoholic liver disease, an aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio >1 suggested cirrhosis. We sought to examine the value of the AST/ALT ratio in distinguishing cirrhotic patients with chronic HCV infection from noncirrhotic patients and to correlate the ratio with the grade and stage of hepatitis and other biochemical indices. METHODS: We retrospectively studied 139 patients with chronic HCV infection. Routine biochemical indices were determined, and the histological grade of necroinflammatory activity and the stage of fibrosis of the liver biopsy specimens were scored. RESULTS: The mean AST/ALT ratio in the cirrhotic patients (n = 47) was higher than in the noncirrhotic patients (n = 92) (1.06 +/- 0.06 vs 0.60 +/- 0.09; p < 0.001). A ratio > or =1 had 100% specificity and positive predictive value in distinguishing cirrhotic from noncirrhotic patients, with a 53.2% sensitivity and 80.7% negative predictive value. The ratio correlated positively with the stage of fibrosis but not with the grade of activity or other biochemical indices. Of the cirrhotic patients, 17% had no clinical or biochemical features suggestive of chronic liver disease except for an AST/ALT ratio > or =1. CONCLUSION: The AST/ALT ratio is a dependable marker of fibrosis stage and cirrhosis in patients with chronic HCV infection.

The successful treatment of symptomatic, refractory hepatic hydrothorax with transjugular intrahepatic portosystemic shunt.

Hepatic hydrothorax is a rare complication of portal hypertension. Conservative therapy may be successful but refractory hepatic hydrothorax is not uncommon. Management of refractory hydrothorax is usually ineffective and can result in a worsened clinical status. Transjugular intrahepatic portosystemic shunts (TIPS) lower portal pressure and have been used in the treatment of refractory ascites. The aim of this study was to determine the efficacy of TIPS in the treatment of symptomatic refractory hepatic hydrothorax. A TIPS was placed in 24 consecutive cirrhotic patients with symptomatic refractory hepatic hydrothorax. Five patients (20.8%) were Child's/Pugh class B and 19 (79.2%) were class C. All had undergone multiple thoracenteses and were hypoalbuminemic. Mean follow-up was 7.2 months (range, 0.25-49 months). Fourteen (58.3%) of 24 patients had complete relief of symptoms after shunt placement and did not require further thoracentesis. Five (20.8%) additional patients required fewer thoracenteses. Five (20.8%) patients developed worsening liver function and died within 45 days. In eight (66.7%) of 12 patients with > or = 60 days of follow-up, the serum albumin increased by a mean of 1.2 g/dL (range, 0.1-2.2 g/dL). The Child's-Pugh score improved in 7 (58.3%) of these 12 patients and two patients improved from class C to class A. These two patients no longer require liver transplantation. This study shows that TIPS can be effective in the management of symptomatic, refractory hepatic hydrothorax. Clinical and laboratory improvement may be seen and liver transplantation may become unnecessary.

Relationship between hepatitis C genotype and severity of recurrent hepatitis C after liver transplantation.

BACKGROUND: Recurrence of hepatitis C virus (HCV) infection after liver transplantation is universal, but the relationship between hepatitis C genotype and posttransplant outcome has been controversial. The aim of this study was to assess the relationship between hepatitis C genotype on posttransplant frequency of recurrent hepatitis, histologic severity of recurrence, and progression to cirrhosis. METHODS: We studied 42 HCV RNA positive patients who received transplants between 1985 and 1994. Sera were tested for HCV RNA and protocol liver biopsies were in obtained the posttransplant period. Biopsies were scored according to the histologic activity index (HAI) and staged in a blinded fashion. RESULTS: The distribution of hepatitis C genotypes distribution was as follows: 1a, 19 (45%); 1b, 17 (40%); 2b, 3 (7%); and 1 each of 2a, 3a, and 4a. There was histologic evidence of hepatitis in 38 of 42 (90.4%) of patients. Hepatitis C was mild, moderate, or severe (HAI>3) in 38% of grafts and minimal (HAI 0-3) in 62%. Overall HAI scores and histologic stage were higher in the genotype 1b group. Six of 17 (35%) genotype 1b patients had cirrhosis compared with 2 of 25 (8%) in the non-1b genotype group. CONCLUSIONS: (1) Histologic evidence of recurrent hepatitis C is seen in 90% of liver allografts; (2) Histologic hepatitis C recurs with similar frequency in genotype 1b and non-1b recipients; (3) Genotype 1b is associated with more severe histologic disease recurrence than non-1b genotypes; (4) Genotype 1b appears to be associated with a higher degree of posttransplant fibrosis and cirrhosis than non-1b genotypes.