Assessment of Prognosis of Cirrhosis

François Durand, M.D.; Dominique Valla, M.D.


Semin Liver Dis. 2008;28(1):110-122. 

In This Article

Prognosis According to Specific Causes of Cirrhosis

A particularity of alcoholic cirrhosis is that the majority of patients with high disease severity indexes do have superimposed alcoholic hepatitis. Alcoholic hepatitis is a potentially reversible condition, which means that some of these patients are likely to improve within the first months following discontinuation of alcohol. Such patients may return to a state of compensated cirrhosis. Accumulated evidence has shown that corticosteroids improve short-term survival in patients with severe alcoholic hepatitis.[51] Therefore, it would be difficult to assess the prognosis of patients with alcoholic cirrhosis without taking into account the existence of alcoholic hepatitis and, in those with severe alcoholic hepatitis, response to steroids.

In most surveys, severe alcoholic hepatitis has been defined by a “discriminant function” above 32 ( Table 4 ).[52] In addition to this discriminant function, generally termed as “Maddrey score” (or Maddrey discriminant function), several specific scores have been created to predict early mortality in patients with severe alcoholic hepatitis.[53,54] The more general MELD score has also been assessed in this setting. MELD score proved to be as efficacious as or even superior to the original Maddrey discriminant function.[55,56] This finding is not surprising since MELD score includes the two variables included in the Maddrey discriminant function (bilirubin and prothrombin). However, none of these scores takes into account the progression over time and the response to steroids which, again, may be determinant.

Recently, an original model termed Lille model was created on the basis of a large series of patients with alcoholic hepatitis treated with steroids.[57] The corresponding score incorporates six objective variables as shown in Table 4 . This score, which includes a dynamic variable corresponding to early response to steroids (change in bilirubin between day 0 and day 7), was more accurate than MELD score, Child-Pugh score, and Maddrey score for predicting 6-month survival in this population. Patients with a score above 0.45 had a 6-month mortality rate of 75%, while those with a score below 0.45 had a mortality rate of only 15%.

It must be noted that these scores have been designed for predicting early mortality. Along with response to steroids, long-term outcome may be related to the residual liver function but also to return to alcohol abuse. As a result, long-term outcome is much more difficult to assess. In addition, long-term survival should necessarily be assessed in view of comorbidities such as cancer, diabetes, or respiratory diseases, which are frequently associated.

In recent years, major advances have been achieved in the treatment of chronic HBV infection with the advent of antinucleot(s)ide analogues. Patients with decompen-sated HBV-related cirrhosis receiving antiviral therapy have a biphasic survival pattern. Mortality rate within the first 6 months after initiation of antiviral therapy is ∼15%.[58] After the first 6 months, mortality rate is 10 times lower. In the subgroup of patients who survive more than 6 months, 3-year survival exceeds 85%. Compared with historical controls, patients with HBV-related decompensated cirrhosis receiving antinucleot(s)ide analogues have better survival rates. Based on a large cohort of patients with decompensated HBV-related cirrhosis receiving lamivudine, a specific prognostic score has been proposed ( Table 4 ). This score incorporates three variables: bilirubin, creatinine, and the presence of HBVDNA before treatment. It is somewhat paradoxical that patients with undetectable HBV-DNA before initiation of antiviral therapy had a better survival. Indeed, it could have been expected that only those with evidence of viral replication (those who are positive for serum HBVDNA) would benefit from antiviral therapy. Nonetheless, other data suggest that 20% of patients initially considered for transplantation can eventually be removed from the waiting list after receiving adefovir-dipivoxil as a result of clinical improvement.[59]

Advances in the treatment of HCV infection have been more limited, although significant. In patients with HVC-related cirrhosis, sustained virological response to interferon was shown to improve long-term outcome by reducing the incidence of liver-related complications.[60] However, the combination of interferon and ribavirin is generally contraindicated in patients with decompen-sated cirrhosis. There is no specific model for predicting the outcome according to viral load, genotype, and response to therapy.

PBC is one of the causes of cirrhosis for which specific prognostic scores were first proposed.[61,62] The aim of scoring was to determine the optimal timing for transplantation. The Mayo risk score for PBC includes four objective variables and one subjective variable (i.e., edema) ( Table 4 ). It has been shown that the probability of survival without transplantation for a risk score of 7.8 is 63% and 39% at 1 and 2 years, respectively. It has also been shown that the risk of post-transplant mortality increases significantly when the risk score exceeds 7.8. Therefore, it is recommended that patients be referred to transplantation centers before reaching this value.

Another prognostic model has been created based upon a large European series.[63] This model includes variables which are relatively close to those included in the Mayo model, which are bilirubin, ascites, albumin, age, and gastrointestinal bleeding. According to this model, the survival benefit from transplantation increases when the probability of survival without transplantation falls below 0.85. In nontransplanted patients, this occurs on average 8 months before death which, in most cases, gives sufficient time to bridge patients to transplantation.

Even though specific scores exist for PBC, there is no evidence that patients with PBC are misclassified with MELD score. Nor there is evidence that specific scores are superior to MELD. However, no discriminant value of MELD score has been established to specifically identify PBC patients who may benefit from transplantation.

The course of PSC is much more variable than that of PBC. Therefore, it is more difficult to create reliable prognostic scores, especially for assessing long-term outcome. It has been shown that the specific risk score (termed Mayo risk score for PSC) shown in Table 4 is more accurate than Child-Pugh for predicting survival, especially in patients with less-advanced disease.[64] This score allows the identification of three groups at low (score < 0), intermediate (0 ≤ score > 2), or high (score ≥ 2) risk. Five-year survival is above 90% in patients at low risk while it is less than 40% in patients at high risk.

MELD score has not been specifically assessed for PSC. However, most patients with advanced PSC have high bilirubin level. In these patients, it is unlikely that disease severity is underestimated by MELD score compared with other chronic liver diseases. However, some patients with relatively low markers of severity have repeated episodes of cholangitis and a rapid deterioration. In this group, bilirubin may be fluctuating. It can be assumed that, independent of the severity of the underlying parenchymal disease, repeated episodes of cholangitis have a deleterious impact on the outcome. Unfortunately, the own influence of the repitition of episodes of cholangitis, response to antibiotics, and the possible selection of resistant strains on prognosis have not been clearly assessed.


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