Clinical prediction of portopulmonary hypertension (PPHTN) is critical in the preoperative evaluation of candidates for orthotopic liver transplantation (OLT) because of its association with significant morbidity and mortality. To determine the clinical, laboratory, and echocardiographic predictors of PPHTN, we retrospectively evaluated 55 candidates before OLT. From those, 8 candidates had pulmonary hypertension ([HTN] group A) and 47 candidates did not (group B). Pulmonary HTN was defined as a mean pulmonary artery pressure (PAP) of 25 mm Hg or greater and either elevated pulmonary vascular resistance or normal pulmonary artery wedge pressure. The significant predictors of PPHTN were (1) systemic arterial HTN (63% in group A v 9% in group B; P <.001), (2) loud pulmonary component of the second heart sound (38% v 2%; P =. 001), (3) right ventricular (RV) heave (38% v 4%; P =.002), (4) RV dilatation by echocardiogram (63% v 0%; P <.001), (5) RV hypertrophy by echocardiogram (38% v 0%; P =.001), and (6) echocardiogram-estimated systolic PAP (SPAP) greater than 40 mm Hg (63% v 2%; P <.001). The sensitivity of these variables for the detection of pulmonary HTN ranges from 37% to 63%, and their specificity from 91% to 100%. We conclude that several clinical and echocardiographic features are significantly associated with pulmonary HTN in patients with cirrhosis. In particular, echocardiogram-estimated SPAP greater than 40 mm Hg is strongly associated with pulmonary HTN and is specific. These predictors, however, are not sensitive enough to identify all the patients with PPHTN. Therefore, the evaluation of a combination of these variables may be useful for the preoperative identification of pulmonary HTN in liver transplant candidates.
366 With improvement in surgical techniques and the advent of new and more effective immunosuppressive agents, survival rate in liver transplant recipients has dramatically improved. However, weight gain is common and hyperlipidemia frequently develops in long-term patients under cyclosporine-based immunosupression. We studied the effect of conversion to tacrolimus in a cohort of 21 long-term stable liver transplant recipients with hyperlipidemia, as manifested by elevated cholesterol and/or triglycerides. No other drug manipulations were done. Full lipid profiles were monitored in all. (Table) Mean cholesterol, triglycerides, LDL and VLDL all had significant decreases to normal or near-normal levels at 1 and 3 months. HDL did not show a statistically significant change. Conversion was not accompanied by any increased side effects, and patients tolerated the change well. We conclude that conversion from cyclosporine based immunosupression to tacrolimus for hyperlipidemia is safe and achieves the goal of normalization of lipid profiles. This effect can be of great significance in the long-term survival of these patients.Table
Up to 50% of patients with chronic hepatitis C fail to respond to initial therapy with pegylated interferon (PEG-IFN) and ribavirin (RBV). With unsuccessful viral eradication, these patients remain at risk for developing progression of their liver disease. Retreatment with PEG-IFN/RBV yields sustained virologic response (SVR) rates that are under 10%. A wholly synthetic interferon, interferon alfacon-1 or consensus interferon (CIFN) given with RBV, was evaluated in patients who failed initial PEG-IFN/RBV therapy. The intent-to-treat analysis included 487 patients; 245 received CIFN 9 μg/day and RBV, and 242 received CIFN 15 μg/day and RBV. Within this group of patients, 59.3% had documented advanced fibrosis at baseline liver biopsy (stage F3 or F4). SVR rates were 6.9% (17/245 patients) in the 9 μg group and 10.7% (26/242) in the 15 μg group. In the intent-to-treat analysis, SVR rates were higher among patients with a >2-log10 decrease in hepatitis C virus RNA during prior PEG-IFN/RBV therapy: 11% (4/38) in the 9 μg group and 23% (7/31) in the 15 μg group. Among patients with lower baseline fibrosis scores (F0-F3), SVR rates were 7.8% (15/192) in the 9 μg group and 13.1% (23/175) in the 15 μg group. In this same group of patients (F0-F3), if a >2-log10 decrease in hepatitis C virus RNA with previous PEG-IFN/RBV treatment was achieved, SVR rates improved to 10.7% and 31.6% in the 9 μg and 15 μg groups, respectively. CIFN/RBV combination retreatment was safe and well tolerated. Conclusion: Retreatment of PEG-IFN and RBV nonresponders with CIFN and RBV is safe and efficacious and can be considered a retreatment strategy for patients failing previous therapy with PEG-IFN/RBV, especially in interferon-sensitive patients with lower baseline fibrosis scores. (HEPATOLOGY 2009.)
43-year-old Caucasian female with end stage renal disease requiring hemodialysis, being evaluated for renal transplant presented for treatment of Chronic Hepatitis C. Her medications included Midodrine, Fludrocortisone, and Phoslo. She was anicteric without stigmata of chronic liver disease. Laboratory tests revealed Hb 10.1g/dl, platelets of 520000, PT/INR 16/1.2.Creatinine 4.5mg/dl. Bilirubin 0.3mg/dl, albumin of 3.7g/dl, AST 74 U/l, ALT 49 U/l, Alkaline phosphatase 479 U/l. ANA, AMA, SMA negative. HCV RNA 14460000 IU/ml. CT scan showed hepatomegaly. Liver biopsy showed chronic hepatitis with dense periportal chronic inflammatory infiltrate, periportal fibrosis, focal interface inflammation and moderate steatosis. In view of her renal failure, she was started on Intron A 3 million Units 3 times a week monotherapy. After 8 weeks of therapy, she decompensated with jaundice and ascites. Her admission labs include Hb 10.8 gm/dl, platelets of 65000, PT/INR 17.1/1.3, Bilirubin 9.3 mg/dl, Albumin of 2.2 g/dl, AST 100 U/l, ALT 55 U/l, Alkaline phosphatase 320 U/l.Repeat autoimmune markers were negative, HCV RNA was negative. Ultrasound revealed enlarged liver, patent portal vein. Transjugular liver biopsy revealed a pressure gradient of 14mmHg consistent with moderate portal hypertension. Biopsy showed grade 3 inflammatory activity, bridging fibrosis (stage 2) and severe, massive steatosis and steatohepatitis. Her decompensation was attributed to interferon therapy in the absence of infectous, drug and autoimmune etiology. Interferon therapy was stopped, and was worked up for possible liver/kidney transplant. During her workup, she continued to deteriorate with worsening jaundice, ascites and eventually expired. Interferon therapy in patients with chronic hepatitis C can cause decompensation of liver disease due to a number of causes including exacerbation of autoimmune disease. In our patient the only reason for decompensation was a severe form of steatohepatitis, a clear worsening of moderate steatosis seen on her liver biopsy 2 years ago. Sub fulminant Steatohepatitis has been described in a few case reports but this is the first case of interferon-induced steaohepatitis reported in the literature. Hence in conclusion, patients with moderate steatosis should be informed of possible worsening of steatohepatitis on Interferon therapy.
Purpose: Hepatitis B (HBV) practice guidelines include viral load, HBeAg (eAg) status, Alanine aminotransferase (ALT) and histology for patient management. Little histological data exists for those with low viral load (LVL), normal ALT, and negative HBeAg since disease progression is felt to be rare. AIM: Compare histological disease in HBV patients. Methods: A cross sectional study of sequential HBV infected patients referred to our center was performed. Inclusion criteria: (1) measurable HBV DNA (Taqman Real Time PCR); (2) no co-infections; (3) immune competent; (4) no prior antiviral treatment; (5) liver biopsy. Low viral load (LVL) was defined as <105 copies/ml and high viral load (HVL) as >105 copies/ml. METAVIR scores were categorized using the following combined histological severity definitions: Normal (grade 0/stage 0); Mild (grade 1 ± stage 1); Moderate (grade 2 ± stage 2); and Severe (grade 3–4 ± stage 3–4). Patients were then categorised into 3 groups based on ALT and Viral load. Group A: normal ALT/LVL; Group B: normal ALT/HVL; Group C: abnormal ALT/HVL. Demographics, Body mass index (BMI), ethanol use and eAg status were determined. Results: 23 patients met inclusion criteria of which 11 were women and 12 men. Race:18 Asians (Vietnamese 13, Korean 1, Combodian 1, Chinese 2, Taiwanese1), Hispanic 2, African Descent 3. Age range 30–71 (mean 50). Groups: A: N = 11 (all HBeAg negative); B: N = 8; C: N = 4. Group histology results by eAg status: B: eAg+ (n = 2) 1/2 mild, 1 moderate, eAg neg. (n = 2) both severe; C: eAg+ (n = 4), ¾ severe, 1/3 moderate, eAg neg. 2/3 severe, 1/3 moderate. Significant alcohol intake in 1 Group C patient with cirrhosis, all others denied significant alcohol use. All patients below 40 years (n = 6) had mild to moderate disease. Conclusions: ALT, viral load and eAg status can be unreliable in predicting HBV disease progression. High rates of histologically worrisome disease was observed in our patients with LVL or HVL and normal ALT regardless of eAg status. Therefore, a liver biopsy should be considered in all HBV infected patients with detectable viremia, even low level viremia. These results need to be confirmed in a larger cohort.Table: Histology vs Viral Load
