Soft technique, hard end-points Jaume Bosch⇑ Hepatic Hemodynamic Laboratory, Hospital Clínic-IDIBAPS, University of Barcelona and CIBERehd, Barcelona, Spain See Article, pages 1017–1024
Increased portal pressure is the major factor driving the clinical course of cirrhosis . This concept seems obvious as most (severe) clinical consequences of chronic liver disease are related to portal hypertension – including varices, bleeding from varices or from portal hypertensive gastropathy/colopathy, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, hepatic encephalopathy, hepatopulmonary syndrome, and porto-pulmonary hypertension . However, it has not been until very recently demonstrated by longitudinal studies assessing the natural history of portal hypertension in patients with cirrhosis and more important [3,4], its reversion by effective portal pressure reduction by medical treatment [5,6]. The best predictor of development of these complications (or clinical ‘‘decompensation’’) so far detected is an increase of the hepatic venous pressure gradient (HVPG) of at least 10 mmHg, which represents the threshold value for the complications of portal hypertension to occur [1,3,4]. In this issue of the Journal of Hepatology, Rotic and his coworkers from Toulouse  go a step further by showing that one can detect these patients with poor prognosis – who therefore are candidates to portal hypotensive therapy – just by looking at something so simple and ‘‘clean’’ as transient elastography (TE), that had the same predictive value as HVPG, which is a much more invasive, sophisticated, and expensive measurement. Bravo! Certainly the study has limitations. These include: (a) a small number of patients (100, and only 65 of them had cirrhosis, which is the relevant population as only three non-cirrhotic had any event during follow-up), (b) it is likely to have some selection bias, as suggested by the high percentage of patients who already had varices (72% of the compensated cirrhotics) and their unusually high risk of decompensation (55% at 2 year; as compared with the 40% prevalence of varices and 29% incidence of decompensation in a larger study in totally compensated cirrhotics with an 8-year follow-up [3,4]), (c) the potential impact of treatments for portal hypertension offered to these patients on the incidence of events, (d) the lack of explanation on the method of imputation of TE values in the patients where this measurement was not possible, and (e) the role of different etiologies rais-
DOI of original article: 10.1016/j.jhep.2011.01.051. Address: Hepatic Hemodynamic Lab, Hospital Clínic, C.Villarroel 170, 08036, Barcelona, Spain. Tel.: +34 932 275 5790; fax: +34 932 275 9348. E-mail address: [email protected]
ing the cut off value of TE to detect a HVPG P10 mmHg. Indeed, a key issue is that the 21.1 kPa cut off value to detect patients with clinically signiﬁcant portal hypertension (deﬁned by an HVPG P10 mmHg) has not been conﬁrmed by other investigators using the same equipment. Thus, Vizzutti et al.  showed this cut off to be much lower (13.6 kPa) in a study done in patients with chronic liver disease due to hepatitis C, and we do have very similar data at our institution (Berzigotti et al., unpublished data). Also, Kazemi et al. showed that French patients with hepatitis C related cirrhosis could have oesophageal varices (and therefore very signiﬁcant portal hypertension) with TE values well below 21.1 kPa,  something that was also found by Vizzutti et al. . Therefore, if we were to use the results of this study as a guide, we would classify as low risk some of the high risk patients with cirrhosis due to hepatitis C infection, which would diminish the predictive value of the test (and its clinical applicability). In summary, the results of the study that apparently are so clear-cut and robust – which in practice would overcome all its limitations – are not so rock hard as the livers from which the information was drawn . This does not mean that the study is not useful. On the contrary, I think this study makes a lot of sense; actually I would be very surprised if such study would have yielded opposite results. This is because many studies have shown that TE correlates well with HVPG, especially when HVPG is <10–12 mm Hg [8,11,12]. Given this correlation, it is logical that TE can predict patients with HVPG above threshold, as already demonstrated by the same group back in 2008 . The only point in discussion is which the optimal cut off value is and to what extent it is disease speciﬁc or may be inﬂuenced by other factors. What is undeniable is the prognostic value of TE in cirrhosis. It is now clear that the harder your liver is, the harder your life will be. . . and the harder will be the task for the attending physician that shall face the problem of ameliorating this poor prognosis. On the other hand, the ﬁnding that TE predicts the occurrence of events during the follow up may appear obvious if TE can predict a marked HVPG elevation. It can further be argued that if something is obvious, then there is no need of demonstrating it. However, medicine is not (totally) an exact science and taking the pain of demonstrating what at ﬁrst glance may seem obvious is wise and reassuring. The study under consideration has the merit of showing the right path for what would be a big step forward. Actually, two independent studies suggest that increased
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Editorial TE values (again with different cut off values) predict an increased risk of hepatocellular carcinoma during the follow-up of patients with chronic liver disease due to hepatitis C  and hepatitis B , which is also correlated with the degree of HVPG elevation . It is debatable whether measurement of TE by Fibroscan will be the right technique to use. Fibroscan has been widely used in Europe, but there is large room for technological advances that can make elastography measurements more applicable and reliable. Actually, it has been shown that magnetic resonance elastography  is more accurate and applicable than transient elastography by Fibroscan (but much more costly), and more recently, virtual touch elastography using acoustic radiation force impulse imaging (ARFI) is emerging as a reliable technique without the practical limitations inherent to MR elastography [17,18]. Finally, whether measuring TE can substitute measurements of HVPG in other situations, for example in assessing the feasibility of liver resection surgery in patients with cirrhosis , or in assessing the response to the medical treatment of portal hypertension  would have to be speciﬁcally investigated, as essentially there is no solid data on these points. The same hold true for the question on whether new serum ﬁbrosis markers may also be used to non-invasively detect when a patient with chronic liver disease is at risk of clinical complications aggravating his prognosis.
Conﬂict of interest The author declared that he does not have anything to disclose regarding funding or conﬂict of interest with respect to this manuscript. References  Garcia-Tsao G, Bosch J. Management of varices and variceal hemorrhage in cirrhosis. N Engl J Med 2010;362:823–832.  Bosch J. Vascular deterioration in cirrhosis. The big picture. J Clin Gastroenterol 2007;41:S247–S253.  Groszmann RJ, Garcia-Tsao G, Bosch J, Grace ND, Burroughs AK, Planas R, et al. Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis. N Engl J Med 2005;353:2254–2261.  Ripoll C, Groszmann R, Garcia-Tsao G, Grace N, Burroughs A, Planas R, et al. Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated cirrhosis. Gastroenterology 2007;133:481– 488.
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