Scholarly article on topic 'The impact and effect of liver insufficiency of HCV infection on patients with chronic obstructive pulmonary diseases'

The impact and effect of liver insufficiency of HCV infection on patients with chronic obstructive pulmonary diseases Academic research paper on "Clinical medicine"

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{"Hepatitis C" / "Chronic obstructive pulmonary disease" / "Extrahepatic manifestation"}

Abstract of research paper on Clinical medicine, author of scientific article — Mahmoud M. El-Habashy, Samy S. Eldahdouh, Anwar A. Mohamed

Abstract Background Hepatitis C virus (HCV) infection is associated with a wide series of extrahepatic manifestations. Pulmonary involvement is one of the extrahepatic manifestations of chronic hepatitis C virus (HCV) infection. The objective of this study was to determine the impact of HCV infection and the degree of liver dysfunction in patients with chronic obstructive pulmonary disease (COPD). Methods This study was conducted on COPD patients. They were selected from outpatient chest clinic in the Menoufia University Hospital. They were classified into 2 groups the first group COPD patients (n =40) without hepatitis C and the second group COPD patients with chronic hepatitis C. Second group (COPD with HCV) classified into 3 subgroups according Child–Pugh classification to determine the degree of liver insufficiency. Group IIA: patients Child–Pugh (A), group IIB: patients Child–Pugh (B) and group IIC: patients Child–Pugh (C). The following pulmonary function parameters were recorded: Forced Expiratory Volume in the first second (FEV1), Forced Expiratory Volume percent (FEV1/FVC%), Forced Expiratory Flow 25–75% (FEF 25–75%) and Maximal Voluntary Ventilation (MVV). Results The study included 80 patients with COPD, 40 patients without chronic HCV infection (group I), and 40 patients with chronic HBV infection (group II).COPD patients with HCV infection have increased deterioration in pulmonary function (FEV1, FEV1/FVC, FEF 25–75% and MVV) than COPD patients without HCV infection. Also there were significant decreases in pulmonary function tests (FEV1, FEV1/FVC, FEF 25–75% and MVV) in group II subgroups IIA, IIB and IIC according to the degree of decompensation. Conclusion Patients with COPD with HCV infection, have increased deterioration in pulmonary function than patients with COPD without HCV infection and the deterioration increases with hepatitis decompensation.

Academic research paper on topic "The impact and effect of liver insufficiency of HCV infection on patients with chronic obstructive pulmonary diseases"

Egyptian Journal of Chest Diseases and Tuberculosis (2014) 63, 81-85

The Egyptian Society of Chest Diseases and Tuberculosis Egyptian Journal of Chest Diseases and Tuberculosis

www.elsevier.com/locate/ejcdt www.sciencedirect.com

ORIGINAL ARTICLE

The impact and effect of liver insufficiency of HCV infection on patients with chronic obstructive pulmonary diseases

Mahmoud M. El-Habashy a *, Samy S. Eldahdouh a, Anwar A. Mohamed b

a Chest Department, Faculty of Medicine, Menoufiya University, Egypt b Hepatology Department, National Liver Institute, Menoufiya University, Egypt

Received 3 October 2013; accepted 10 November 2013 Available online 5 December 2013

KEYWORDS

Hepatitis C; Chronic obstructive pulmonary disease; Extrahepatic manifestation

Abstract Background: Hepatitis C virus (HCV) infection is associated with a wide series of extra-hepatic manifestations. Pulmonary involvement is one of the extrahepatic manifestations of chronic hepatitis C virus (HCV) infection. The objective of this study was to determine the impact of HCV infection and the degree of liver dysfunction in patients with chronic obstructive pulmonary disease (COPD).

Methods: This study was conducted on COPD patients. They were selected from outpatient chest clinic in the Menoufia University Hospital. They were classified into 2 groups the first group COPD patients (n = 40) without hepatitis C and the second group COPD patients with chronic hepatitis C. Second group (COPD with HCV) classified into 3 subgroups according Child-Pugh classification to determine the degree of liver insufficiency. Group IIA: patients Child-Pugh (A), group IIB: patients Child-Pugh (B) and group IIC: patients Child-Pugh (C). The following pulmonary function parameters were recorded: Forced Expiratory Volume in the first second (FEV1), Forced Expiratory Volume percent (FEV1/FVC%), Forced Expiratory Flow 25-75% (FEF 25-75%) and Maximal Voluntary Ventilation (MVV).

Results: The study included 80 patients with COPD, 40 patients without chronic HCV infection (group I), and 40 patients with chronic HBV infection (group II).COPD patients with HCV infection have increased deterioration in pulmonary function (FEV1, FEV1/FVC, FEF 25-75% and

* Corresponding author. Address: Chest Department, Menoufiya University, Shebin Elkom, Egypt. Mobile: +20 1112143143. E-mail address: habashyica@yahoo.com (M.M. El-Habashy). Peer review under responsibility of The Egyptian Society of Chest Diseases and Tuberculosis.

0422-7638 © 2013 The Egyptian Society of Chest Diseases and Tuberculosis. Production and hosting by Elsevier B.V. All rights reserved. http://dx.doi.Org/10.1016/j.ejcdt.2013.11.003

MVV) than COPD patients without HCV infection. Also there were significant decreases in pulmonary function tests (FEV1, FEV1/FVC, FEF 25-75% and MVV) in group II subgroups IIA, IIB and IIC according to the degree of decompensation.

Conclusion: Patients with COPD with HCV infection, have increased deterioration in pulmonary function than patients with COPD without HCV infection and the deterioration increases with hepatitis decompensation.

© 2013 The Egyptian Society of Chest Diseases and Tuberculosis. Production and hosting by Elsevier

B.V. All rights reserved.

Introduction

Worldwide, HCV is a common cause of chronic liver disease, and a risk factor for liver cirrhosis and hepatocellular carcinoma [1]. This viral infection can also be complicated by a number of extrahepatic manifestations and has been associated with both obstructive and restrictive lung disease [2].

More than 170 million people worldwide are chronically infected by the HCV [3]. The Egyptian Demographic Health Survey (EDHS), a cross sectional survey including hepatitis C virus biomarkers, was conducted in 2008 on a large nationally representative sample. It estimated HCV prevalence among the 15-59 years age group to be 14.7% [4]. Around 30% to 70% of patients with chronic hepatitis C have an extrahepatic manifestation of HCV during the course of the disease [5].

Chronic obstructive pulmonary diseases (COPD 0 is the 4th leading cause of death worldwide; its mortality is rising, while cardiovascular disease's is falling; COPD is expected to be the 3rd leading cause of death in the next 20 years [6].

Chronic infection with hepatitis HCV is to cause intra- and extra-hepatic complications. Among the extra-hepatic complications, the lung is one major target organ [7]. Kanazawa et al reported an accelerated decline of lung function in COPD patients with concomitant hepatitis C infection. They have suggested that the airway disease may be related to the underlying chronic inflammatory disorder [2].

Aim of study

To study the impact and effect of liver insufficiency of HCV infection on patients with chronic obstructive pulmonary diseases.

Patients and methods

This study was conducted on 80 COPD patients. They were selected from outpatient chest clinic in the Menoufiya University Hospital. They were classified into 2 groups the first group COPD patients without chronic hepatitis C group I (n = 40) and the second group COPD patients with chronic hepatitis C group II (n = 40). All study subjects gave their written informed consent for participation in this study.

These patients were conducted through the following:

(I) History: taking history of the patients to clear the presence of hepatitis C infection. Past history of smoking and its duration was documented, DM and hypertension.

(II) Clinical examination: all participants were examined to clear the presence of jaundice, cyanosis, lower limb oedema and ascites.

(III) Laboratory investigations: all participants underwent a group of lab tests:

(1) HCV antibody.

(2) HCV RNA by PCR to document HCV infection in HCV positive patients.

(3) Alanine aminotransferase (ALT).

(4) Aspartate aminotransferase (AST).

(5) Total serum bilirubin.

(6) Serum albumin.

(7) Prothrombin time and concentration, INR (International normalized ratio was calculated for each patient).

(IV) Radiological investigation:

(1) Abdominal ultrasound

(2) Chest X-ray postero-anterior view

(3) Echocardiography and ECG

(V) Pulmonary function tests;

Spirometry was performed in all patients which measured FEV1, FEV1/FVC, FEF 25-75% and MVV.

COPD patients with chronic hepatitis C patients were classified to three groups according to Child-Pugh classification to determine the degree of liver insufficiency [8]: group IIA: patients Child-Pugh A 16 patients, group IIB: patients Child-Pugh B 10 patients and group IIC: patients Child-Pugh C 14 patients. The score employs five clinical measures of liver disease. Each measure is scored 1-3, with 3 indicating most severe derangement.

Child-Pugh score.

Measure 1 Point 2 Points 3 Points

Total bilirubin, <34 (< 2) 34-50 (2-3) >50 (>3)

imol/l (mg/dl)

Serum albumin >35 28-35 <28

PT INR <1.7 1.71-2.30 >2.30

Ascites None Mild Moderate to

severe

Hepatic None Grade I-II (or Grade III-IV

encephalopathy suppressed with (or refractory)

medication)

Exclusion criteria:

(1) Patients with cardiac diseases for example valvular heart disease.

(2) COPD in exacerbation.

(3) Patients with a history of alcohol intake or active consumption of alcohol.

(4) Patients with focal hepatic lesions or with malignancy anywhere.

(5) Pregnancy and lactation.

(6) Patients with pleural effusion.

(7) Patients with renal failure.

Statistical analysis: statistical analyses were performed by SPSS ver 13.0 for Windows® (SPSS Inc, Chicago IL, US). Univariate methods included a Student's t test to compare means of groups for continuous variables, and |c|2 analysis for categorical variables unless the Fisher's exact test was required for contingency tables-when more than 20% of the expected values were less than five. P < 0.05 was considered statistically significant [9].

Result

This study included 80 patients with COPD, 40 COPD patients without chronic HCV infection (group I), and 40 COPD patients with chronic HBV infection (group II). Group II was classified into subgroups according to Child-Pugh score (IIA, IIB and IIC). Table 1 shows demographic features of COPD patients without chronic HCV infection (group I) and COPD patients with chronic HCV infection (group II) according to sex, smoking, DM and hypertension, no significant difference between the two groups (P > 0.05).

Table 2 shows that there was a statistically significant difference between groups I and II regarding FEV1, FEV1/FVC (p < 0.05) but there was high significant difference between them regarding FEF25-75 and MVV (p < 0.001).

Table 3 and Fig. 1 show that there was a statistically significant difference between groups II subgroups (IIA, IIB and IIC) according to Child score regarding FEV1%, FEF 2575% and MVV but there was no significant difference between group IIA to IIC and IIB to IIC regarding FEV1 /FVC% and

there was significant difference between IIA and IIB according FEVi/FVC%.

Discussion

It is well-known that patients with HCV infection are at higher risk for development of some extrahepatic conditions. While the association of some extrahepatic conditions with HCV is very clear, for some conditions, the association is strongly suspected and for other conditions it is based only on some anecdotal data [10].

Our study revealed that COPD patients associated with chronic HCV infection have significant decrease in pulmonary function compared with COPD patients. These findings suggest that chronic HCV infection is associated with accelerated decline of lung function in patients with COPD. This agrees with study by Saetta et al., they found a decline of pulmonary function in COPD patients associated with HCV infection [11]. Also Kanazawa et al., [2] reported an accelerated decline of lung function in COPD patients with concomitant hepatitis C infection. They have suggested that the airway disease may be related to the underlying chronic inflammatory disorder. It is also possible that the number and importance of different inflammatory hits may change as the airway disease evolves. Severe COPD is associated with the development of lymphoid follicles in the small airways, implying the presence of an adaptive immune response. This immune response could be due to chronic infection or the exposure of auto-antigens as a result of increasing tissue damage. The extent to which the coexistence of more than one acute or chronic inflammatory stimulus produces additive or synergistic effects [12].

The general principle that the coexistence of multiple inflammatory stimuli produces a more severe inflammatory response might also apply to acute inflammatory stimuli. This

Table 1 Demographic features of patients with COPD (group I) and COPD with chronic HCV infection (group II).

Demographic data HCV—ve COPD HCV + ve COPD Fisher's exact test P value

No % No %

Sex Male 33 41.3 34 42.5 0.009 >0.05

Female 7 8.8 6 7.5

Smoking Positive 30 37.5 27 33.8 0.001 >0.05

Negative 10 12.5 13 16.3

DM Positive 16 20.0 19 23.8 0.002 >0.05

Negative 24 30.0 21 26.3

HTN Positive 25 31.3 18 22.5 2.46 >0.05

Negative 15 18.8 22 27.5

Age (mean ± SD) 46.2 ± 7.9 44.6 ± 7.5 t test -0.4 >0.05

Table 2 Comparison between group I and group II according to pulmonary function tests.

HCV—ve COPD (mean ± SD) HCV + ve COPD (mean ± SD) t Test P value

FEV1/FVC% pred. FEV1% pred. FEF 25-75% pred. MVV% pred. 66.80 ± 4.32 56.46 ± 7.49 66.96 ± 3.72 54.69 ± 7.00 48.16 ± 3.17 46.23 ± 3.87 68.04 ± 6.3 54.7 ± 3.9 —6.06 —7.766 — 1.943 11.37 <0.05 <0.05 <0.001 <0.001

Table 3 Comparison between group II subgroups (IIA, IIB and IIC) according to pulmonary function tests.

Group II HCV + ve COPD LSD test P value

IIA IIB IIC

FEV1/FVC. 64.2 ± 1.8 56.7 ± 2.7 62.8 ± 6.06 112.890 P1 6 0.05

P2 P 0.05

P3 P 0.05

FEV1% pred. 60.94 ± 3.67 51.33 ± 5.43 50.78 ± 5.09 13.506 P1 6 0.01

P2 6 0.01

P3 6 0.05

FEF 25-75% pred. 48.33 ± 3.14 45.5 ± 4.03 43.92 ± 3.2 4.046 P1 6 0.05

P2 6 0.001

P3 6 0.05

MVVl% pred. 57.42 ± 3.23 55.45 ± 2.33 50.8 ± 1.45 18.664 P1 6 0.05

P2 6 0.001

P3 6 0.001

P1 fi IIA-IIB, P2 fi IIA-IIC and P3 fi IIB-IIC.

□ Group IIA

□ Group IIB

□ Group IIC

70 60 50 40 30 20 10 0

FEV1/FVC%F EV1.%pred FEF%pred MWl.%pred

Figure 1 Comparison between group II subgroups (IIA, IIB and IIC) according to pulmonary function tests.

mechanism might be particularly important in the development of exacerbations of asthma and COPD [13]. Chronic liver disorder decreases glutathione synthesis in the liver, and an inadequate supply of glutathione in the lung would render the lung vulnerable to oxidative damage [14].

Our study showed that there was a statistically significant difference between groups II subgroups (IIA, IIB and IIC) according to Child score regarding FEV1%, FEF 25-75% and MVV but there was no significant difference between group IIA to IIC and IIB to IIC regarding FEV1/FVC% and this is due to a decrease in FVC(due to presence of ascites which impairs diaphragmatic movement decreasing lung volumes) more than a decrease in FV1 and this leads to preservation of the FEV1/FVC% ratio so they were not affected as in group II A and B. and there was a significant difference between IIA and IIB according to FEV1/FVC%. This agrees with Yigit et al., they found that among the PFT parameters, FEV1/FVC and FEF 25-75% values were found to be lower in patients with ascites than those without (P < 0.05) [15].

A previous study reported that numbers of lymphocytes in bronchoalveolar lavage (BAL) fluid are increased in patients with chronic HCV infection, suggesting that HCV infection might be a trigger of the development of lymphocyte alveolitis [16]. These findings suggest that cytotoxic T lymphocytes induced by chronic HCV infection may contribute to the development of parenchymal lung destruction.

Conclusion

Lung complications may occur as a result of hepatic disease from any cause and represent a highly heterogeneous group of conditions. Early recognition of such complications may be challenging but is crucial both in forming a meaningful differential diagnosis and in avoiding severe sequelae and irreversible damage. Patients with COPD with HCV infection, have increased deterioration in pulmonary function than patients with COPD without HCV infection and the deterioration increases with hepatitis decompensation.

Conflict of interest

The authors have declared no conflict of interest.

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