Terlipressin improves pulmonary pressures in cirrhotic patients with pulmonary hypertension and variceal bleeding or hepatorenal syndrome.

Terlipressin has been shown to improve both pulmonary and systemic hemodynamics in stable cirrhotic patients with pulmonary hypertension, whereas other vasoconstrictors may cause pulmonary pressures to deteriorate. We investigated the pulmonary and systemic hemodynamic effects of the first terlipressin dose (2 mg) in 7 cirrhotic patients with PH presenting with variceal bleeding (n=4) or hepatorenal syndrome (n=3). Terlipressin decreased pulmonary vascular resistance (158.8+/-8.9 vs 186.5+/-13.9 dynes · sec · cm-5; P=0.003) together with an increase in systemic vascular resistance (2143+/-126 vs 1643+/-126 dynes · sec · cm-5; P<0.001). Terlipressin should be the vasoconstrictor treatment of choice when patients present with variceal bleeding or HRS.

Serum ferritin is a discriminant marker for both fibrosis and inflammation in histologically proven non-alcoholic fatty liver disease patients.

INTRODUCTION: Differentiation between steatosis and non-alcoholic steatohepatitis (NASH) in non-alcoholic fatty liver disease (NAFLD) is important as NASH progress to cirrhosis. No specific laboratory/imaging technique exists either to diagnose NASH or to select patients for liver biopsy. PATIENTS AND METHODS: We evaluated serum ferritin and the features of metabolic syndrome with respect to histological inflammation and/or fibrosis in NAFLD patients. The Kleiner scoring system was used to classify NAFLD in consecutive liver biopsies. One hundred and eleven patients: median age 52.6, 64 males, obesity 62, diabetes mellitus (DM) 58, arterial hypertension 26 and hyperlipidaemia 40%. RESULTS: Histologically, 40.7 had fatty liver, 30.6% had borderline NASH, 28.7% had NASH and 11% had cirrhosis. Multivariate regression showed that diabetes, serum ferritin concentrations, body mass index (BMI) and AST were independently associated with NASH: together, the areas under the receiver operating characteristic (AUROC) was 0.91 (95% confidence interval 0.86-0.96); fibrosis was associated with ferritin concentrations and BMI: AUROC 0.87, portal inflammation with ferritin and DM: AUROC 0.82, while lobular inflammation was associated with BMI, DM and ferritin: AUROC 0.85. CONCLUSION: Serum ferritin concentrations and BMI are strongly associated with fibrosis, portal and lobular inflammation in NAFLD patients. Both ferritin and BMI are potential discriminant markers to select patients for liver biopsy and are associated with inflammation and fibrosis.

Scintigraphic evaluation of intrapulmonary shunt in normoxemic cirrhotic patients and effects of terlipressin.

AIM: The magnitude of intrapulmonary shunt (IPS) in cirrhotic patients without hypoxemia remains undefined. We evaluated the severity and clinical correlations of IPS in normoxemic cirrhotics, and possible IPS alterations after terlipressin treatment. METHODS: Fifteen patients with alcoholic cirrhosis without hypoxemia were studied at baseline and after the administration of 2 mg of terlipressin. The IPS fraction was evaluated by lung perfusion scan after the i.v. injection of technetium-99m-labeled macroaggregated albumin ((99m) Tc-MAA) and calculation of brain uptake (positive value ≥6%). Cardiac output (CO), pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR) were evaluated by Doppler echocardiography. Mean arterial pressure (MAP) was measured and the ratio MAP/CO was calculated as an index of systemic vascular resistance (SVR). Portal vein velocity (PVV) and portal venous flow (PVF) were also assessed by Doppler ultrasonography. RESULTS: Three patients (20%) had an IPS fraction of more than 6%. A significant inverse correlation with platelet count (P = 0.001) and a direct correlation with Child-Pugh score (P = 0.06), PVV (P = 0.07) and PVF (P = 0.07) were noted. IPS fractions decreased significantly after terlipressin administration (P = 0.00001); the IPS fraction fell below 6% in all three patients with positive baseline values. Terlipressin treatment induced a significant decrease in CO (P = 0.003) and significant increases in MAP (P = 0.0003), SVR (P = 0.0003), SPAP (P = 0.001) and PVR (P = 0.01). CONCLUSION: IPS fractions detected by (99m) Tc-MAA lung scan were inversely correlated with platelet count and directly with liver disease severity, and found abnormal in 20% of normoxemic cirrhotic patients. Terlipressin reduced significantly the magnitude of the shunt.

Effects of terlipressin and somatostatin on liver and thorax blood volumes in patients with cirrhosis.

BACKGROUND: Variceal bleeding in cirrhosis can cause liver ischaemia and deteriorate the hyperdynamic state; thus, the effects of vasoconstrictor therapy on liver blood volume (LBV) and thorax blood volume (ThBV) are important. AIM: To evaluate and compare the effects of terlipressin and somatostatin on LBV and ThBV in stable patients with cirrhosis and portal hypertension. METHODS: Twenty patients were studied (Child-Pugh class A/B/C: 5/8/7). The radioactivities in the liver region (LRR) and the thorax region (ThRR) by single-head gamma camera technique, as indicators of LBV and ThBV, respectively, and systemic haemodynamics were measured at baseline and after intravenous infusion of 2 mg of terlipressin (n=10) or somatostatin 250 mg/h after an initial bolus of 250 mg (n=10). RESULTS: LRR and ThRR decreased significantly with increasing severity of cirrhosis. Thirty minutes after terlipressin infusion, LRR and ThRR increased by 7.8 ± 4.4% (NS) and 14 ± 5.3% (P=0.01) compared with baseline values; the increase in ThRR was significantly related to the increase in LRR (r=0.682, P=0.03). In contrast, somatostatin reduced LRR and ThRR by 13.3 ± 6.5% (P=0.07) and 1 ± 4% (NS) respectively. LRR and ThRR increased significantly in the terlipressin group compared with the somatostatin group (P=0.01 and P=0.02 respectively). Terlipressin reduced cardiac output and heart rate (both P=0.01) and increased the mean arterial pressure (MAP) and systemic vascular resistance (P=0.009 and P=0.002 respectively); MAP decreased after somatostatin infusion (P=0.03). CONCLUSIONS: Terlipressin, but not somatostatin, maintains LBV, increases ThBV and improves the hyperdynamic state in cirrhosis. These effects can be beneficial in variceal bleeding, particularly in patients with advanced liver disease.

A comparison of four- versus three-pass transjugular biopsy using a 19-G Tru-Cut needle and a randomized study using a cassette to prevent biopsy fragmentation.

Recently, it has been shown that transjugular liver biopsy (TJLB) with three passes gives comparable specimens to percutaneous liver biopsy (PLB). The aim of this study was to evaluate the adequacy of TJLB using four passes in a consecutive series of patients, and whether using a supportive cassette can prevent fragmentation. One hundred consecutive TJLBs in 92 patients (48 transplanted), always using four passes (19-G Tru-Cut), were compared to three-pass TJLBs. The four-pass TJLB specimens were randomized at a 1:1 ratio of liver cores placed in a cassette versus not. The four-pass TJLBs, compared to three-pass TJLBs, resulted in better specimens for length (>or=25 mm: 50% vs. 35%; p = 0.026) and number of complete portal tracts (CPTs) (>or=11: 40% vs. 26%; p = 0.027), without a higher complication rate. The four-pass TJLB with >or=11 CPTs had a median length of 27 mm, and 57% of them longer than 28 mm contained >or=11 CPTs. Putting the liver biopsy cores into a cassette did not improve the fragmentation rate or adequacy of the specimen (length and number of CPTs) of TJLB. We conclude that at least four passes with TJLB should be performed when liver specimens are needed for grading and staging. Using a supportive cassette did not reduce fragmentation.

Addison's disease and hypertransaminasemia.

Endocrine diseases, such as diabetes mellitus and thyroid dysfunction, have been rarely associated with increased serum transaminase activity. The association of Addison's disease with abnormal liver function tests has received less attention. Addison's disease as a part of autoimmune polyglandular syndrome-1 may be associated with autoimmune hepatitis. Addison's disease may also coexist with celiac disease, an autoimmune disorder commonly associated with hypertransaminasemia. On the other hand, a number of case reports have suggested hypertransaminasemia to be one of the few diagnostic clues to the underlying adrenal insufficiency, allowing the introduction of steroid replacement and obviation of a potential adrenal crisis. We performed a thorough literature review on the prevalence and pathogenesis of hypertransaminasemia as a feature of Addison's disease in an attempt to highlight an as yet under-recognized association.

Hepatic venous pressure gradient to assess fibrosis and its progression after liver transplantation for HCV cirrhosis.

Progression of fibrosis following recurrent hepatitis C virus (HCV) infection is frequent after liver transplantation (LT). Histology remains the gold standard to assess fibrosis, but the value of hepatic venous pressure gradient (HVPG) is being explored. We evaluated patients with recurrent HCV infection after LT to assess whether HVPG correlates with liver histology, particularly fibrosis. A total of 90 consecutive patients underwent 170 HVPG measurements concomitant with transjugular liver biopsy (TJB), with 31.5 (range, 6-156) months of follow up. Median biopsy length was 22 mm and total portal tract count was 12 (complete 6, partial 6). Median HVPG was 4 mmHg: 38% of patients > or =6 mmHg (portal hypertension, PHT), 13% > or =10 mmHg. HVPG correlated with Ishak stage (r = 0.73, P < 0.001) for mild (0-3) and severe fibrosis (4-6), and grade score (r = 0.47, P < 0.001), but neither correlated with interval from LT nor biopsy length. HVPG was > or =10 mmHg in 15 patients: 12 had stage 5 or 6, and 3 severe portal expansion. HVPG was repeated in 49, between 7 and 60 months with weak correlation to fibrosis score (r = 0.30, P = 0.045). A total of 12 patients with HVPG > or =6 mmHg had fibrosis score < or =3, while 8 patients had normal HVPG but fibrosis stage > or =4. These discrepancies were mostly associated with specific histological features such as perisinusoidal fibrosis rather than errors in measuring HVPG. In 29 with HVPG <6 mmHg at 1 yr, none decompensated compared to 4 of 13 (31%) with PHT. In conclusion, HVPG correlates with fibrosis and its progression, due to recurrent HCV infection, assessed in TJB.

Transjugular liver biopsy--indications, adequacy, quality of specimens, and complications--a systematic review.

Transjugular liver biopsy (TJLB) is considered an inferior biopsy, used when percutaneous liver biopsy (PLB) is contraindicated. According to recent literature, specimens with 6 complete portal tracts (CPTs) are needed for histological diagnosis of chronic liver disease but 11 CPTs to reliably stage and grade. Mean CPT number in PLB series is 7.5; more passes increase complications. Sixty-four series reporting 7649 TJLBs were evaluated for quality of specimen and safety. Major indications were coagulation disorders and/or ascites. Success rate was 96.8%. Fragmentation rate was 34.3%, not correlating with length or diagnostic adequacy. With a mean of 2.7 passes, mean CPT number was 6.8. Histological diagnosis was achieved in 96.1% of TJLBs, correlating with length (p=0.007) and CPT number (p=0.04). Tru-Cut specimens had a mean CPT number of 7.5 and, compared to Menghini specimens, were longer (p<0.008), less fragmented (p<0.001) and more diagnostic (p<0.001). Thinner needles (>16-G) provided significantly longer and less fragmented specimens. Minor and major complication rates were 6.5% and 0.56%, respectively, and increased in children, but not with additional passes. In adults, mortality was 0.09% (haemorrhage 0.06%; ventricular arrhythmia 0.03%). TJLB is safe, providing specimens qualitatively comparable to PLB, and may improve further using > or = 18-G Tru-Cut needle and >3 passes.

Combined HLA-DR and -DQ disparity is associated with a stable course of ulcerative colitis after liver transplantation for primary sclerosing cholangitis.

Combined disparity of human leukocyte antigen (HLA)-DR and -DQ between mother and fetus is associated with less severe ulcerative colitis (UC) during pregnancy. We evaluated whether donor-recipient HLA disparity after liver transplantation (LT) affects UC in patients with primary sclerosing cholangitis (PSC). Sixty-nine consecutive patients with PSC underwent LT; all underwent colonoscopy before LT; 48 had UC before and 3 had de novo UC after LT. Clinical and laboratory data, activity and treatment of UC, post-LT cytomegalovirus infection, and disparity of HLA-A, -B, -DR, and -DQ for each donor-recipient pair were evaluated. Pre-LT quiescent UC was present in 26 patients. Post-LT UC activity was evaluated in 36 of 51 patients with UC who had not undergone pre-LT colectomy and who had >12 months' post-LT survival. Of these, 16 were stable, 17 had worsened, and 3 had de novo UC. Seven required colectomy (4 for dysplasia or cancer) after LT. Post-LT cytomegalovirus viremia was neither associated with worse UC activity (P = 0.58) nor de novo UC. Disparity with respect to HLA-A, -B, -DR, and -DQ was found in 58%, 27%, 44%, and 39% donor-recipient pairs, respectively. Post-LT UC course was similar with respect to single HLA disparity. However, disparity in none or only one HLA-DR or -DQ was significantly associated with worse activity compared with patients with disparity at both (65% vs. 0%, P = 0.009). Logistic regression found that the disparity for both -DR and -DQ was the only factor statistically significantly associated with post-LT UC activity. We conclude that disparity in both HLA-DR and -DQ between donor and recipient is associated with stable UC activity after LT.