Heart failure (HF) is a condition where the heart cant provide sufficient systemic perfusion to meet body’s metabolic demands. This is due to dysfunction of the cardiac pump.  Patients may show symptoms associated with non-cardiac disorders, such as liver dysfunction. The liver abnormalities seen in HF are due to passive congestion resulting from elevated filling pressures or low cardiac output, both of which impair perfusion. Passive hepatic congestion, can cause elevated liver enzymes and direct and indirect bilirubin levels. Reduced perfusion due to reduced cardiac output may cause acute hepatocellular necrosis, with significant raise in serum aminotransferases. In cases of severe hypotension associated with acute HF, cardiogenic ischemic hepatitis, or "shock liver," may develop.

HF can be divided into systolic and diastolic types. Systolic HF patients show reduced cardiac contractility, and diastolic HF is characterized by impaired relaxation and abnormal ventricular filling.⁽¹⁾ HF can occur due to structural or functional cardiac disorders, whether congenital or acquired, which reduce heart’s ability to properly fill or eject blood.⁽²⁾

HF presents with symptoms of reduced exercise tolerance due to dyspnea and/or fatigue due to impaired cardiac output, or with fluid retention due to increased filling pressure. Liver dysfunctions can occur, especially in right heart failure (RHF). Any condition WHICH impairs right ventricular function can lead to significant hepatic congestion. Patients with hepatic congestion are usually asymptomatic, abnormal LFTs detected during routine screenings can raise suspicion for this issue. Pathophysiology behind hepatic dysfunction in HF includes passive congestion from elevated filling pressures or decreased cardiac output. Passive hepatic congestion, due to increased central venous pressure, can enhance  liver enzymes and bilirubin levels. Reduced cardiac output may cause acute hepatocellular necrosis with significant increase in serum aminotransferases. Cardiogenic ischemic hepatitis or “shock liver” can develop after profound hypotension during acute HF episodes. More hemodynamic disturbances may lead to bridging fibrosis or cardiac cirrhosis, leading to compromised hepatic function. This can affect coagulation, reduce albumin production, and modify metabolism of various cardiovascular medications, causing toxicity. As hepatic dysfunction can affect drug metabolism differently than renal impairment, dose adjustments may be needed, but accuratee guidelines are challenging to frame, as changes in liver drug metabolism are not reflected in standard laboratory markers of liver dysfunction.

AIM AND OBJECTIVES

To study the prevalence of liver function abnormalities in congestive cardiac failure patients.

Objectives:

1.To assess the correlation of liver function tests with etiology, duration and NYHA Class of cardiac failure

2. To study the pattern of elevation of liver enzymes in cardiac failure.

This was a cross-sectional study conducted in the Department of General Medicine, NRI Medical College, Mangalagiri, Andhra Pradesh, India between July 2023 to December 2024. The study population included patients with congestive cardiac failure attending General Medicine department. Among them the patients with history of alcoholism, history of jaundice and those with the usage of any hepatotoxic and/or cholestatic drugs, patients with known presence of viral markers, and patients with history of blood transfusion were excluded from the study. The sample size was calculated using the formula, N=Z2PQ/E2 Where: • n is sample size • Z is Z-score (For 85% confidence level, is 1.44) • p = estimated prevalence (46% or 0.46) (3) • E = margin of error (7% or 0.07) So, the required sample size is approximately 100 The study subjects were selected by consecutive sampling, after fulfilling the inclusion and exclusion criteria. The study was conducted till the target sample size of 100 was achieved. A self-designed, semi-structured questionnaire was used to assess the study subjects. It includes the socio-demographic variables, etiology and duration of heart failure, NYHA Class was assessed. The principal investigator, clinically assess the study subjects for the presence of ascites and hepatomegaly. Biochemical assessment of the bilirubin levels, Seum AST, Serum ALT, ALP, Serum Albumin levels, Prothrombin time, Total protein levels were estimated in the study subjects. Ultrasonography was done among them to identify the presence of ascitic fluid and any hepatomegaly. The data were collected from the selected study subjects after obtaining their written and informed consent. Ethical clearance for this study was obtained from the Institutional Ethics Committee before the study. The collected data was entered in MS Excel 2024 and analysis was done by software, Epi Info version 7.2.6 The results were expressed as frequencies or percentages. Statistical analysis for Chi-square test and ANOVA were done using SPSS V25 and p value of <0.05 was considered statistically significant.

In this study, the mean age of study subjects was 48.1±12.01 years. Among them 39% were between 31-40years of age followed by 24%, 19%, 17% and 1% in 51-60, 61-70, 41-50 and above 70 years respectively. Among the 100 study subjects, 64% were female.

Table 1 Etiology of heart failure among study subjects (n=100)

Among the study subjects, 51% of heart failure was due to Coronary Artery Disease (CAD).

Table 2 Duration of heart failure among study subjects (n=100)

Table 2 shows that 36% had heart failure for 1 to 5 years.

Table 3 NYHA class of the study subjects (n=100)

Among the study subjects, 46% belong to NYHA Class – I followed by 28%, 19% and 7% in NYHA Class II, III and IV respectively.

Table 4 Ultrasound abdomen findings among the study subjects (n=100)

Table 4 shows that ascites was seen among 86% of study subjects while hepatomegaly among 56% in the ultrasound abdomen.

Table 5 Liver function tests among the study subjects

Table 5 represents the liver function tests among the study subjects, which shows that 45% had abnormal prothrombin time, 44% had abnormal serum bilirubin levels, 43% and 42% of them have elevated Serum ALT and Serum Albumin levels respectively.

Table 6 Association between Serum bilirubin levels and NYHA grading

ANOVA

P-value = 0.00000

Table 6 shows that the study subjects in Class IV NYHA had higher levels of S. bilirubin. It was also noted that the serum bilirubin levels were significantly (p<0.01) increasing with increase in the NYHA class.

Table 7 Association between S. ALT and NYHA class among study subjects

ANOVA

P-value = 0.00000

Table 7 represents that there was statistically significant (p<0.05) association between S. ALT and NYHA class among the study subjects.

Table 8 Association between S. ALP and NYHA class among study subjects

ANOVA

P-value = 0.93813

Table 8 shows that there was no statistically significant association observed between S. ALP levels and grade of congestive cardiac failure by NYHA classification.

Table 9 Association between S. Albumin and NYHA class among study subjects

ANOVA

P-value = 0.00000

There was statistically significant association between S. Albumin and grade of congestive cardiac failure among the study subjects.

Table 10 Association between Prothrombin time and NYHA class among study subjects

ANOVA

P-value = 0.00000

Table 10 shows that prolonged prothrombin time was significantly associated with high grade of congestive cardiac failure among the study subjects (p<0.01)

Table 11 Association between AST and NYHA class among study subjects

ANOVA

P-value = 0.00000

Table 11 represents that there was highly significant association seen between the AST and grade of congestive cardiac failure among the study subjects.

The mean age of patients was 48.1 years in the current study. 39% of the patients were aged 31 to 40 years. 17% of the patients were aged 41 to 50 years. 24% of the patients were aged 51 to 60 years. 19% of the patients were aged 61 to 70 years. 1% of the patients were aged above 70 years and 64% of the patients were males in the current study. CAD was seen in 51% of the patients. Cardiomyopathy was seen in 5% of the patients. 12% of the patients had cor pulmonale. 15% of the patients had hypertensive heart. 17% patients had RHD in the current study. 36% of the patients had HF for 1 to 5 years. 32% of the patients had HF for above 5 years. 32% of the patients had HF for below 1 year. 28% of the patients belonged to NYHA class II. 46% of the patients belonged to NYHA class I. 28% of the patients belonged to NYHA class III. 7% of the patients belonged to NYHA class IV in the current study. INDRAJIT STUDY(4) reported most common cause of CCF was coronary artery disease followed by rheumatic heart disease (24.8%). Hypertension is least common cause. In the current study also, CAD is the most common cause. In present study 44% of the patients had jaundice; 44% of the patients had hepatomegaly in USG. Ascites was seen in 14% patients. Mean bilirubin was 1.293 mg/dl. 56% of the patients had normal serum bilirubin. 44% of the patients had abnormal serum bilirubin. 60% of the patients had normal serum AST levels. 40% of the patients had abnormal serum AST levels; 57% of the patients had normal ALT levels; 43% of the patients had abnormal ALT levels; 62% of the patients had normal ALP levels; 38% of the patients had abnormal ALP levels; 42% had low albumin levels; 42% of the patients had abnormal albumin levels; 45% of the patients had more prothrombin time; 55% of the patients had normal prothrombin time; 36% of the patients had low total protein; 64% of the patients had normal protein in the current study. It was more in patients with severe heart failure. Mean serum bilirubin of patients with NYHA class I was 46 mg/dl. Mean serum bilirubin of patients with NYHA class II was 28 mg/dl. Mean serum bilirubin of patients with NYHA class III was 19 mg/dl. Mean serum bilirubin of patients with NYHA class IV was 7 mg/dl in the current study. There is significant association between serum ALT levels and NYHA class. Mean ALT levels of patients with NYHA class I was 35.17. Mean ALT levels of patients with NYHA class II were 35.25 IU/L. Mean ALT levels of patients with NYHA class III was 105.21 IU/L Mean ALT levels of patients with NYHA class IV was 100.4 IU/L. There is no significant association between ALP levels and NYHA class. Mean ALP levels of patients with NYHA class I was 39.18. Mean ALP levels of patients with NYHA class II was 39.7 IU/L. Mean ALP levels of patients with NYHA class III was 39.63. Mean ALP levels of patients with NYHA class IV was 38.4 IU/L. In the current study, there is significant association between albumin levels and NYHA class. Mean albumin value of patients with NYHA class I was 3.5 g/dl. Mean albumin value of patients with NYHA class II was 3.4 g/dl. Mean albumin value of patients with NYHA class III was 2.7 g/dl. Mean albumin value of patients with NYHA class IV was 2.6 g/dl. There is significant association between prothrombin time and NYHA class. Mean prothrombin time of patients with NYHA class I was 13.89 sec. Mean prothrombin time of patients with NYHA class II was 14.07 sec . Mean prothrombin time of patients with NYHA class III was 17.8 sec. Mean prothrombin time of patients with NYHA class IV was 19.2 sec. There is significant association between serum AST levels and NYHA class. Mean AST levels of patients with NYHA class I was 34.02. Mean AST levels of patients with NYHA class II was 64.1 IU/L. Mean AST levels of patients with NYHA class III was 165.26 IU/L. Mean AST levels of patients with NYHA class IV was 166.28 in the current study. SANER STUDY(2009) (5) showed that among 202 admissions between May 2003 and December 2007, all with acute liver failure. Among those, 13 cases were due to congestive heart failure, which had a 54% mortality rate. Major cause of death was underlying heart failure. Major cause of death was underlying heart failure. Liver function tests, like AST bilirubin, and INR didn’t significantly differ between patients who survived and those who did not. Both groups showed signs of cardiogenic shock, cardiac index (CI) at admission was significantly higher in survivors compared to non-survivors. Central venous pressure(CVP) and pulmonary wedge pressure did not show significant differences. Significant improvement in liver function was observed in patients who recovered from cardiogenic shock. Their study stressed that an appropriate diagnostic approach is important for patients with acute liver failure, and CCF should be considered as a main cause. SAMSKY STUDY (2016)(6) Authors wanted characterize abnormal liver function tests (LFTs) in patients with heart failure. They used data from ASCEND-HF trial to know association with baseline LFTs. Each LFT was analyzed as both a continuous and dichotomous variable (normal vs. abnormal; bilirubin >1.0 mg/dL, AST and ALT >35 mmol/L). Logistic regression was used to assess the association of LFTs with 30-day all-cause mortality and heart failure rehospitalization, and Cox proportional hazards models assessed the association with 180-day all-cause mortality among patients alive at a 30-day landmark. In ASCEND-HF study, 59% patients had complete admission LFT data. Of these, 42% had abnormal bilirubin, 22% had abnormal ALT, and 30% had abnormal AST. Patients with abnormal LFTs are likely to be younger, with low BMI and a lower LVEF. After multivariable adjustment, elevated total bilirubin was associated with increased 30-day mortality or HF rehospitalization but was not associated with an increase in 180-day mortality per 1 mg/dL increase. When compared with normal bilirubin levels, abnormal bilirubin was associated with both increased 30-day mortality or HF rehospitalization and 180-day mortality. No significant associations were found between AST or ALT levels and outcomes. More than 40% of patients hospitalized with acute heart failure had abnormal liver function tests. Raised bilirubin was independently associated with worse clinical outcomes, making it an important prognostic marker in these patients. MARIA STUDY (2013)(3) was done to evaluate the prevalence of abnormal LFTs among patients with acute decompensated heart failure and to assess clinical profile and outcomes. Post hoc analysis was don using data from SURVIVE trial, which included ADHF patients treated with legomena or dobutamine. Baseline LFT data were there for 1134 patients. Abnormal LFTs were seen in 46% of ADHF patients: 11% had isolated abnormal alkaline phosphatase (AP), 26% had isolated abnormal transaminases, and 9% had both. Abnormal AP was associated with systemic congestion and more right-sided filling pressures but did not correlate with 31-day mortality. Abnormal AP was associated with worse 180-day mortality Abnormal transaminases, were associated with clinical signs of hypoperfusion and higher 31-day and 180-day mortality. No additional prognostic value was found for patients with both abnormal AP and transaminases. Abnormal LFTs were seen in about half of the ADHF patients treated with inotropes. Specific clinical and biological features were associated with abnormal AP and abnormal transaminases, with transaminase elevations linked to short-term mortality. These findings indicate that there is a need for careful monitoring of liver function in ADHF patients. INDRAJIT STUDY(4) shows that liver biochemical abnormalities were seen in HF patients, correlated with the severity of heart failure. The study showed the importance of early detection of liver function abnormalities, mainly in acute cases or during hypotensionn. Low serum protein and albumin levels were common, with various contributing factors discussed. Authors reported significant modifications in LFTs in patients with acute heart failure, mainly during hypotension, compared to those with chronic HF. There is a need for early identification and monitoring of liver dysfunction in heart failure patients. DUERSEN STUDY:(2010)(7) was aimed to know the relationship between liver function abnormalities and hemodynamic profiles in HF patients. Among 323 HF patients, liver function was assessed through AST, ALT, alkaline phosphatase, GGT, LDH, and direct and total bilirubin (Bili dir, Bili tot). Measures assessed were CVP and cardiac index (CI). Follow-up involved tracking all-cause mortality. The mean age of patients was 53 years, and 60% were male subjects. LFTs were associated with CVP. More CVP was correlated with GGT and direct bilirubin. Elevated AST, ALT and total bilirubin were linked to low CI and elevated CVP. Prognostic value of abnormal liver function tests appeared to be related to their interaction with CI and CVP. LFTs mainly more GGT and direct bilirubin, are indicative of higher CVP. Presence of elevated AST, ALT, or total bilirubin may reflect low CI. Absence of prognostic information when invasive hemodynamic measurements are available suggests implies that liver function abnormalities in HF are reflective of poor hemodynamic status rather than prognostic indicators. In the current study, GGT was not assessed. Finally, liver dysfunction is common in patients with CHF.(8) Hepatic injury in these patients can occur due t hypoperfusion, and decreased cardiac output, and congestion caused by volume and pressure overload.(9) Patients experience poor outcomes,(10) and prognostic significance is unclear. Some studies showed more serum aminotransferase levels act as prognostic markers in CHF patients(11,12) and other studies have linked worse clinical outcomes to increases in cholestatic markers, like total bilirubin, alkaline phosphatase, and γ-glutamyl transferase. (13,14) Patterns of abnormal LFTs were associated with liver congestion and hypoperfusion in the context of heart failure, implying that alterations in LFTs could reflect hemodynamic disturbances in CHF. Some studies showed differences in hemodynamic changes between HFpEF and HFrEF.(15,16) Vyskocilova et al. (17) found that ALT and AST patterns were more common in left-sided forward acute heart failure (AHF), associated with reduced EF, and cholestatic profile was predominantly observed in bilateral and right-sided AHF. In one post-hoc analysis of PARADIGM-HF trial, ALT was shown to be linked to a worse prognosis in chronic HFrEF patients, along with total bilirubin (TBIL), but not AST.(18)

The current study was done on 100 subjects with heart failure. Liver function was assessed among them. Prevalence of abnormal liver function tests was found to be high and associated with the severity of heart failure as per NYHA class. Continued research and more detailed characterization of hepatic dysfunction in heart failure is important understand its pathophysiology. Patients with significant hepatic dysfunction in the context of HF should be considered high-risk and treated aggressively.

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