**4. Discussion**

According to different authors, cirrhosis caused by alcohol and HCV are more frequent in the fifth and sixth decades of life, and in males. (Safdar K, 2004; Sagnelli E, 2005; Benvegnù L, 2004) Recent series described that the most common causes of liver cirrhosis are due to HCV, HBV, and alcoholism. These causes can vary between them by geographic area. (Dehesa-Violante M, 2007; Fattovich G, 2008)

These conclusions coincide in this series, since the average age was 47.8 ± 12.95 years. The group more frequent were in patients between 40 to 60 years, male sex and the most frequent causes of cirrhosis were HCV and alcohol.

Cirrhosis is often manifested as a silent disease. In the compensated phase the diagnosis can be made by nonspecific manifestations or laboratory findings, whereas in later stages the disease may debut by its complications. (Heidelbaugh JJ, 2006) At the beginning of the study 27.8% of patients were in compensated phase and 72.2% had developed complications.

In the analysis of the survival curves of Kaplan-Meier, categorical variables that had significantly lower survival were male gender (56.4%, average 43.69, 47.56-61.0), the history of ascites (51.1%, average 41.3 months; 35,06-47.53) hepatic encephalopathy (38.1%, mean 30.85 months, 17.67, 44.04), the development of hepatocellular carcinoma (0%, average 11.42, 4.09-18.76) and Child-Pugh stages with 80.8% survival for stage A, 69.9% for B and 31% for C (Table 8). Upper gastrointestinal bleeding for varicose veins was not associated with

> **Median (months)**

**Sex:** Female 74% 54.28 47.56- 61.0 0.033 Male 56,4 43.69 37.52- 49.87 **Ascites:** No 82.7 57.722 51.75- 63.69 0.001 Yes 51.1 41.300 35.06- 47.53

Yes 38.1 30.85 17,67- 44.04

Yes 65.7 47.68 38.62- 56.73 **HCC:** No 65.7 49.92 45.07-54.77 <0.001 Yes 0 11.42 4.09-18.76 **Child- Pugh:** A 80.8 58,04 52.28-63.81 <0.001 B 69.6 51.71 44.30-59.13 C 31.0 26.42 17.88-34.97

**Exp(β) p** 

Age 1.024 0.029 HCC 2.377 <0,001 Child-Pugh 1.378 <0,001

According to different authors, cirrhosis caused by alcohol and HCV are more frequent in the fifth and sixth decades of life, and in males. (Safdar K, 2004; Sagnelli E, 2005; Benvegnù L, 2004) Recent series described that the most common causes of liver cirrhosis are due to HCV, HBV, and alcoholism. These causes can vary between them by geographic area.

These conclusions coincide in this series, since the average age was 47.8 ± 12.95 years. The group more frequent were in patients between 40 to 60 years, male sex and the most

Cirrhosis is often manifested as a silent disease. In the compensated phase the diagnosis can be made by nonspecific manifestations or laboratory findings, whereas in later stages the disease may debut by its complications. (Heidelbaugh JJ, 2006) At the beginning of the study 27.8% of patients were in compensated phase and 72.2% had developed complications.

Table 9. Predictors of survival of liver cirrhosis at 3 years follow- up Cox regression

**Encephalopathy:** No 66.7 50.95 45.96- 55.92 0.032

**Variceal bleeding:** No 61.5 47.85 42.23- 53.46 0.639

**CI 95% p** 

**months (%)** 

Table 8. Univariate analysis of categorical variables to three years of survival

survival.

**4. Discussion** 

(Dehesa-Violante M, 2007; Fattovich G, 2008)

frequent causes of cirrhosis were HCV and alcohol.

**Variable Survival at 36** 

Fig. 3. Survival of patients according the Child-Pugh score

Fig. 4. Survival of patients according the diagnosis of hepatocellular carcinoma

The presence of esophageal varices was more frequent in decompensated liver cirrhosis. Ascites was the most common complication followed by gastrointestinal bleeding, which coincides with reports of other authors (Gines P, 1987). As is known, the higher frequency of esophageal varices is also associated with ascites and with the advanced stage of Child-Pugh. (Samada M, 2008; Sarwar S, 2005; Dib N, 2005)

In this series, overall survival at three years follow-up was 62.5%, which approximates to the average values to the review of natural history and survival in cirrhosis of 118 studies conducted by D'Amico. (D'Amico G, 2006) They reported on 32 studies of survival, with median follow-up of 33 months, cumulative survival of 61%.

Overall survival is less specific because patients are very heterogeneous regarding the presence or absence of complications. In conducting the study it was observed that patients that were at the beginning of the evaluation in compensated and decompensated stage, presented survival rates with significant differences, with 85% and 53.8% respectively. It is reported that the development of hepatocellular carcinoma is a major cause of mortality in patients in compensated phase and the transition to the decompensated stage may be 5 to 7% per year (D'Amico G, 2001). In the present study, HCC was the cause of death in 28.5% of patients who were compensated and the rest died of other cirrhosis complications.

As identified by D'Amico (D'Amico, 2006), compensated cirrhosis by the absence of complications includes two states, patients without varices or ascites (state 1) and patients with varicose veins but without ascites (state 2). Although they have different prognoses, mortality is low (1% per year for state 1 and 3.4% for state 2). On the other hand, decompensated cirrhosis (stages 3 and 4) has a significantly higher mortality (20% per year for the state 3 and up to 57% in 4). This classification was accepted at the Consensus Conference of Portal Hypertension, Baveno IV (De Franchis R, 2000) and modified states Baveno decompensated phase V (D 'Amico G, 2011)

Many factors have been studied in relation to the survival of patients with liver cirrhosis and to improve forecasting models. In the study by D'Amico (D'Amico, 2006), it was reported that the Child-Pugh was the best predictor of mortality in cirrhosis, followed by the five components measured individually. Age was the only variable that was predictive of survival in more than 10 studies, and that was not part of the Child-Pugh score. These data are consistent with those presented by the authors of this paper. The univariate analysis showed that in addition to Child-Pugh, MELD, age, sex and liver cancer were associated with lower survival of the five variables of Child-Pugh, bilirubin, albumin, INR from prothrombin time, ascites and encephalopathy.

In our series, creatinine was not a factor associated with survival, which corresponds with other authors. (Degre D, 2004; Ruf AE, 2005) In relation to sex as a prognostic factor, we must consider that the United States 56 409 deaths related to hepatitis C in the period 1995- 2004, there was an increase in mortality from 1.09 to 2.44 per 100 000 inhabitants. This represented an increase of 123% in the period studied, a male predominance with 144% and 81% in females. Alcohol was a cofactor related and could be underestimated. These data confirm the higher male mortality by the two leading causes of cirrhosis, hepatitis C and alcohol (Wise M, 2008)

Ascites is one of the earliest and most frequent complications of liver cirrhosis. Approximately 50% of patients with compensated cirrhosis, can develop ascites within 10 to

The presence of esophageal varices was more frequent in decompensated liver cirrhosis. Ascites was the most common complication followed by gastrointestinal bleeding, which coincides with reports of other authors (Gines P, 1987). As is known, the higher frequency of esophageal varices is also associated with ascites and with the advanced stage of Child-

In this series, overall survival at three years follow-up was 62.5%, which approximates to the average values to the review of natural history and survival in cirrhosis of 118 studies conducted by D'Amico. (D'Amico G, 2006) They reported on 32 studies of survival, with

Overall survival is less specific because patients are very heterogeneous regarding the presence or absence of complications. In conducting the study it was observed that patients that were at the beginning of the evaluation in compensated and decompensated stage, presented survival rates with significant differences, with 85% and 53.8% respectively. It is reported that the development of hepatocellular carcinoma is a major cause of mortality in patients in compensated phase and the transition to the decompensated stage may be 5 to 7% per year (D'Amico G, 2001). In the present study, HCC was the cause of death in 28.5%

of patients who were compensated and the rest died of other cirrhosis complications.

As identified by D'Amico (D'Amico, 2006), compensated cirrhosis by the absence of complications includes two states, patients without varices or ascites (state 1) and patients with varicose veins but without ascites (state 2). Although they have different prognoses, mortality is low (1% per year for state 1 and 3.4% for state 2). On the other hand, decompensated cirrhosis (stages 3 and 4) has a significantly higher mortality (20% per year for the state 3 and up to 57% in 4). This classification was accepted at the Consensus Conference of Portal Hypertension, Baveno IV (De Franchis R, 2000) and modified states

Many factors have been studied in relation to the survival of patients with liver cirrhosis and to improve forecasting models. In the study by D'Amico (D'Amico, 2006), it was reported that the Child-Pugh was the best predictor of mortality in cirrhosis, followed by the five components measured individually. Age was the only variable that was predictive of survival in more than 10 studies, and that was not part of the Child-Pugh score. These data are consistent with those presented by the authors of this paper. The univariate analysis showed that in addition to Child-Pugh, MELD, age, sex and liver cancer were associated with lower survival of the five variables of Child-Pugh, bilirubin, albumin, INR

In our series, creatinine was not a factor associated with survival, which corresponds with other authors. (Degre D, 2004; Ruf AE, 2005) In relation to sex as a prognostic factor, we must consider that the United States 56 409 deaths related to hepatitis C in the period 1995- 2004, there was an increase in mortality from 1.09 to 2.44 per 100 000 inhabitants. This represented an increase of 123% in the period studied, a male predominance with 144% and 81% in females. Alcohol was a cofactor related and could be underestimated. These data confirm the higher male mortality by the two leading causes of cirrhosis, hepatitis C and

Ascites is one of the earliest and most frequent complications of liver cirrhosis. Approximately 50% of patients with compensated cirrhosis, can develop ascites within 10 to

Pugh. (Samada M, 2008; Sarwar S, 2005; Dib N, 2005)

Baveno decompensated phase V (D 'Amico G, 2011)

from prothrombin time, ascites and encephalopathy.

alcohol (Wise M, 2008)

median follow-up of 33 months, cumulative survival of 61%.

15 years after diagnosis, with a mortality of 15% per year and 44% within five years followup (Planas R, 2006). In this study, the survival at three years follow-up was 51.1%, indicating that all patients with ascites should be evaluated for liver transplantation, preferably before they develop renal dysfunction, and worsening prognosis.

Encephalopathy is a complication involving low survival. Bustamante et al. (Bustamante J, 1999), followed for 12 ± 17 months 111 patients with cirrhosis who had a first episode of acute encephalopathy, and found that 74% died during follow-up, with a survival rate of 42% per year. In this series the survival at three years was 38.1%.

Hepatocellular carcinoma was the complication that had lower survival; within 11.4 months mean follow-up there was no survivor. This complication can occur at any stage of cirrhosis and is associated with increased frequency in viral causes, so it is very important to increase surveillance programs for early diagnosis and thereby obtain prolonged survivals rates. (Capocaccia R, 2007; Perz JF, 2006) In studies of cirrhosis caused by HBV and HCV has been the leading cause of mortality, especially in patients with HCV. (Perz JF, 2006)

In the survival analysis of MELD and Child-Pugh, it was observed that as they grow, the rate decreases in relation to time tracking. Although the MELD system is the outcome of choice to give priority to patients on the waiting list for liver transplantation in the Consensus Document of the Spanish Society for Liver Transplantation published in 2008, it is argued that currently there are not available data for the Child-Pugh classification no longer used in favor of the MELD system and recommend to apply both models with their advantages and limitations in the future to decide which method is most convenient. Spanish Society for Liver Transplantation. (Spanish Society for Liver Transplantation, 2008)

In the work developed in short and long term, the Child-Pugh score has proven to be a good predictor of mortality. In a review by Cholongitas (Cholongitas E, 2006) on studies that compare the MELD and Child-Pugh, performed with patients on the waiting list for liver transplantation that included 12 532 cirrhotic patients, only 4 of 11 studies showed that the MELD is superior to Child-Pugh in predicting short-term mortality and Gotthardt et al (Gotthardt D, 2009) from the results of their work, consider that for the prediction of longterm mortality (estimated at one year) and removal from the waiting list of patients awaiting transplantation, monitoring should be better by Child-Pugh score than by MELD. This might have implications for the development of new improved scoring systems

In this series, we found on univariate analysis similar significance of Child-Pugh and MELD index as predictors of survival at three years follow-up. But the Child-Pugh acted as an independent predictor of survival.

The prediction of MELD can rise to associate other factors such as clinical or biochemicals. Some studies have shown the prognostic contribution of the addition of sodium to MELD (Ruf AE 2005, Biggins SW 2005), as well as ascites and encephalopathy. (Somsouk M, 2009, Stewart CA, 2007) It has been shown that patients with severe ascites and low sodium, low MELD even have very poor prognosis and suggest incorporating these two elements to the MELD (Heuman DM, 2007).

In another review of prognostic models for priority to liver transplantation, with numerous suggestions for additions to the MELD concluded that the MELD-sodium store is better able to predict survival on the waiting list than the Standard MELD score. (Cholongitas E, 2010)

Biselli M et al (Biselli M 2010) evaluated the survival of patients with advanced liver cirrhosis, liver transplant candidates at 3, 6 and 12 months. Six scoring systems used, included the modified Child Pugh (MCTP) and the standard MELD, and four of its modifications. The modified CTP (Huo TI, 2006) was obtained by assigning an additional point in patients whose serum bilirubin was > 8 mg/dL, prothrombin time prolongation >11 seconds, or albumin <2.3 g/dL, accordingly a mCTP score of 16-18 was defined as class D, which identifies severely decompensated cirrhosis. In this study population, the prognostic power of mCTP did not differ from that of MELD, MELD-sodium and integrated MELD were the best prognostic models.

Although these models are used to assess the short-term survival and give priority for liver transplantation, it would be interesting to determine their behavior in pursuit of longer than one year.
