Christos Triantos

Infection, coagulation, and variceal bleeding in cirrhosis

Bacterial infections in cirrhotic patients are common. There is a predisposition to intestinal bacterial overgrowth, intestinal dysmotility, and increased intestinal permeability, all leading to an increase in bacterial translocation. Bacterial translocation is the probable mechanism for some of the most common infections in cirrhosis, such as spontaneous bacterial peritonitis, but is also the source of bacterial byproducts such as endotoxin which can cause an increase in portal pressure, impairment of liver function, and worsening of haemostasis. The effects of bacterial infection and bacterial products on portal and systemic haemodynamics in cirrhosis and clinical data on infection, from both retrospective and prospective studies of variceal bleeding and other settings, demonstrate the importance of infection in pathophysiological mechanisms in cirrhosis. This has been followed by recent clinical evidence that antibiotic therapy reverses systemic vasodilation and prevents early variceal rebleeding. In cirrhotic patients there is an increased susceptibility to bacterial infection, related to the degree of liver dysfunction1 leading to several abnormalities of defence mechanisms, all of which increase the susceptibility to infection, including deficiency of bactericidal and opsonic activities, impaired monocyte function, depressed phagocytic activity of the reticuloendothelial system (RES), defective chemotaxis, and low levels of complement in serum. A particularly important role is played by the reduced RES activity, due to the presence of extrahepatic and intrahepatic shunts through sinusoids without Kupffer cells, reduced number of Kupffer cells, and impaired Kupffer cell function. Thus cirrhotics with impaired RES phagocytic activity (as assessed by elimination of 99 m technetium-sulphur colloid) develop acute bacterial infections more frequently than cirrhotics with normal RES phagocytic activity.2 Both community and hospital acquired bacterial infections are frequently diagnosed in cirrhotics, most frequently spontaneous bacterial peritonitis (SBP), urinary tract infections, pneumonia, and skin infections.3 Their incidence rises with worsening liver function.3 Importantly, half of …

Transjugular intrahepatic portosystemic shunt for portal vein thrombosis with and without cavernous transformation

Treatment options for patients with portal vein thrombosis are limited.

Pegylated‐interferon and ribavirin in liver transplant candidates and recipients with HCV cirrhosis: systematic review and meta‐analysis of prospective controlled studies

Summary.  Pegylated interferon with ribavirin (Peg/R) is the most effective therapy for chronic hepatitis C virus (HCV) but its utility and effectiveness after liver transplantation has been difficult to assess. We evaluated efficacy, tolerability, and safety of Peg/R in liver transplant candidates and recipients with HCV cirrhosis. We searched medical databases and conference proceedings between January 1999 and January 2008 selecting randomized and nonrandomized studies. Primary end points meta‐analytically were: (1) sustained viral response (SVR) and (2) histological response. Secondary end points were: (1) treatment discontinuation, (2) mortality, and (3) rejection episodes. Pegylated interferons using either 1–1.5 mcg/kg of pegylated interferon alpha‐2b or 180 μg (pegylated interferon alpha‐2a combined with ribavirin 800–1200 mg/day were the most effective compared to any other regimen or no therapy. In three pretransplant studies the median SVR was 19.6% (19.6–50%). In six postransplant studies where a meta‐analysis was done the cumulative risk difference in SVR was 0.31% (95% CI, 0.18–0.44, p < 0.001). However histological response was not significantly better compared to no therapy or other antiviral regimens. There were no significant differences in discontinuation of therapy, acute or chronic rejection or mortality between optimal Peg/R vs no treatment or other regimens. Hence pegylated interferon plus ribavirin in full doses is effective pre and post transplant but has a low SVR rate. To date no significant histological improvement has been reported.

Transjugular liver biopsy: how good is it for accurate histological interpretation?

Background: A transjugular liver biopsy (TJLB) specimen is often smaller or more fragmented than a percutaneous liver biopsy (PLB) specimen. Recently, for PLB, the minimum requirements to evaluate chronic hepatitis have been set at 20–25 mm length and ⩾11 complete portal tracts. Aim: To evaluate and compare length of TJLB and PLB specimens, portal tract number, fragmentation and adequacy for histopathological diagnosis and staging. Patients and methods: 326 consecutive TJLB specimens in 274 patients (109 who had undergone a transplantation), always using three passes (19-G Tru-cut) and 40 consecutive PLB specimens (15-G Menghini). Results: No technical failures occurred with the TJLB, and histological diagnosis was possible in 98.5%. The median (range) number of fragments was 5 (1–13) and the median total length was 22 (3–46) mm, with 65% of specimens ⩾20 mm and 36% ⩾25 mm; 60% of TJLB specimens were ⩾28 mm long had ⩾11 complete portal tracts. No difference in complete portal tract number or biopsy length was found between PLB and TJLB specimens. Conclusion: A TJLB specimen with three passes is adequate for histological diagnosis, with 89% of specimens being either ⩾15 mm or having ⩾6 complete portal tracts. Although adequate sampling remains a limitation for staging and grading of chronic hepatitis, TJLB is comparable to PLB in this respect.

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 ≥6 mmHg (portal hypertension, PHT), 13% ≥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 ≥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 ≥6 mmHg had fibrosis score ≤3, while 8 patients had normal HVPG but fibrosis stage ≥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. Liver Transpl 13:1305–1311, 2007.

Clinical Course of Lamivudine Monotherapy in Patients with Decompensated Cirrhosis due to HBeAg negative chronic HBV infection

OBJECTIVES:We have evaluated the efficacy of long-term lamivudine monotherapy in patients with decompensated HBeAg-negative/HBV-DNA positive cirrhosis.METHODS:We analyzed the clinical course and outcome of lamivudine treatment in 30 consecutive cirrhotics and compared with 30 HBV untreated historical HBeAg-negative controls matched for age and gender.RESULTS:Significant clinical improvement, defined as a reduction of at least two points in Child-Pugh score was observed in 23 of the 30 treated patients (76.6%) versus none of the 30 patients in the control group (p < 0.0001) after a mean follow-up of 20.6 ± 12.1(±SD) months. There were 10 deaths in the treated group versus 24 in the control group (p= 0.07). Liver-related deaths occurred in five of the eight patients soon after the development of biochemical breakthrough. Patients with clinical improvement had better survival than patients with no improvement (p= 0.04) or those who developed biochemical breakthrough due to YMDD mutants (p= 0.001).CONCLUSIONS:Lamivudine significantly improves liver function in HBeAg-negative decompensated cirrhosis. However, the development of the biochemical breakthrough due to YMDD mutants is associated with fatal outcome.

Meta-analysis: ursodeoxycholic acid for primary sclerosing cholangitis.

Aliment Pharmacol Ther 2011; 34: 901–910

Altered intestinal tight junctions’ expression in patients with liver cirrhosis: a pathogenetic mechanism of intestinal hyperpermeability

Eur J Clin Invest 2012; 42 (4): 439–446

Antiviral therapy reduces portal pressure in patients with cirrhosis due to HBeAg-negative chronic hepatitis B and significant portal hypertension

BACKGROUND/AIMS Lamivudine improves liver histology in patients with chronic hepatitis B (CHB), but its effects on portal pressure remain unknown. We evaluated the effect of lamivudine monotherapy on hepatic venous pressure gradient (HVPG) in CHB-related cirrhosis with significant portal hypertension. METHODS We studied 19 patients with cirrhosis due to HBeAg-negative CHB and HVPG >or=10 mm Hg treated with oral lamivudine (100mg daily). Liver biochemistry, Child-Pugh and MELD score were determined every 3 months, alpha-fetoprotein and HBV DNA every 6 months and HVPG at baseline and at 12 months after lamivudine initiation. Diuretics, beta-blockers, antibiotics and/or endoscopic therapy were used for routine indications. RESULTS At 12 months, a significant reduction was observed in ALT (p=0.001), HBV DNA (p=0.002), Child-Pugh (p=0.012) and MELD score (p=0.006). Four patients developed virological breakthrough during treatment. At 12 months, HVPG decreased in all but one patient [baseline: 14.4+/-3.9 and 12 months: 12.4+/-3.3 mm Hg (p=0.007)]. HVPG decreased >20% or below the 12 mm Hg threshold in 10 of 13 patients with baseline HVPG >or=12 mm Hg. HVPG increased in a patient with hepatic flare after virological breakthrough. CONCLUSION In conclusion, in patients with cirrhosis due to HBeAg-negative CHB, lamivudine monotherapy reduces HVPG, especially when virological suppression and biochemical remission is achieved.

The effects of unfractionated heparin, low molecular weight heparin and danaparoid on the thromboelastogram (TEG): an in-vitro comparison of standard and heparinase-modified TEGs with conventional coagulation assays.

To investigate the effects of unfractionated heparin (UFH), low molecular weight heparin (LMWH) and danaparoid (DPD) added to whole blood in vitro on standard and heparinase-modified thromboelastogram (TEG) parameters compared with conventional assays of coagulation. The effects of UFH, LMWH and DPD on standard TEG parameters were compared with the prothrombin time, activated partial thromboplastin time, thrombin time and anti-activated factor X (anti-FXa) activity, at concentrations of these anticoagulants ranging from 0.025 to 1 U/ml. In the second part of the study, the effects of very low concentrations (0.005–0.05 U/ml) of UFH, LMWH and DPD on the difference between standard and heparinase-modified TEG parameters were compared with the prothrombin time, activated partial thromboplastin time, thrombin time and anti-FXa activity. Standard TEG parameters were outside the reference range at lower concentrations of UFH, LMWH and DPD than most conventional coagulation assays were able to detect. Only anti-FXa activity was more sensitive to the presence of these anticoagulants than the standard TEG alone. The lowest concentration of UFH, LMWH and DPD used in this study (0.005 U/ml) caused significant differences between the standard and heparinase-modified α-angles of the TEG. In addition, the difference between standard and heparinase-modified TEG parameters distinguished between low concentrations (0.005–0.05 U/ml) of UFH with greater sensitivity than anti-FXa activity, but were less sensitive to LMWH and DPD. The standard TEG is more sensitive to UFH, LMWH and DPD than most conventional coagulation tests, with the exception of anti-FXa activity. Calculation of the difference between standard and heparinase-modified TEG parameters greatly increases the sensitivity of the assay for the effects of these anticoagulants, and is more sensitive to very low quantities of UFH than anti-FXa activity.