Abstract

Abnormal liver functions are caused by a number of causes which include viral hepatitis, alcohol intake, nonalcoholic fatty liver disease, autoimmune liver diseases, hereditary diseases, hepatobiliary malignancies and infections, gallstones and drug-induced liver injury. However, the liver may be involved in systemic diseases that mainly affect other organs. Therefore, in a patient without etiology of the liver injury by screening serology and diagnostic imaging, but who have systemic diseases, the abnormal liver function tests may be caused by the systemic disease. In most of these patients, the systemic disease should be treated primarily. The chronic obstructive pulmonary disease (COPD) is one of the most important systemic disease resulting in hepatitis mainly due to hypoxia. COPD patients may present with hypoxic hepatitis and the liver functions return to normal with the treatment of the primary disease.

A case of hepatitis in a case of chronic obstructive pulmonary disease (COPD) is described here.Pulmonary complications of chronic liver disease such as hepatopulmonary syndrome, portopulmonary hypertension and hepatic hydrothorax are well-known, and have been described extensively in literature. Conversely, hepatobiliary manifestations of primary pulmonary disease also occur with high-frequency, but have been studied less frequently. Abnormal liver functions are caused by a number of causes which include viral hepatitis, alcohol intake, nonalcoholic fatty liver disease, autoimmune liver diseases, hereditary diseases, hepatobiliary malignancies and infections, gallstones and drug-induced liver injury. However, the liver may be involved in systemic diseases that mainly affect other organs. Therefore, in a patient without etiology of the liver injury by screening serology and diagnostic imaging, but who have systemic diseases, the abnormal liver function tests may be caused by the systemic disease. In most of these patients, the systemic disease should be treated primarily. 

Case Report

An 85-year-old female with history of COPD presented to the emergency department of Gian Sagar Medical College, Ramnagar, Patiala, Punjab with history of an episode of breathlessness. She was a diagnosed case of COPD with forced expiratory volume in 1 second/ forced vital capacity (FEV1/FVC) ratio of 52%. She presented with an acute exacerbation of COPD with breathlessness, cough and expectoration. 

On examination, the pulse rate was 92/min, regular and a blood pressure (BP) of 130/86 mmHg. She was cyanosed with pursed lip breathing and asterixis was present. 

Chest examination revealed bilateral rhonchi, cardiovascular system (CVS) and abdomen examination was unremarkable. There was no pedal edema, jugular venous pressure (JVP) was not raised.

On investigations, her hemogram revealed a hemoglobin level of 15 g/dL and erythrocyte count was 6 million/mm³, total leukocyte count (TLC) was 11,200/mm³, platelet count was 70,000. Chest radiograph was consistent with COPD. Arterial blood gas (ABG) analysis was done and showed pCO₂ of 90.6% and PaO₂ of 67.0 with a pH of 7.210 diagnosed as type 2 respiratory failure. Renal function tests (RFTs) were normal and liver function tests (LFTs) revealed a serum bilirubin level of 0.8 and raised transaminases i.e., serum glutamic oxaloacetic transaminase (SGOT) was 3,020 and serum glutamic-pyruvic transaminase (SGPT) was 2,016, alkaline phosphatase was 199, her serum albumin was 3.5. After 2 days of treatment for COPD and of invasive ventilation and oxygen therapy, SGOT was 1,000, SGPT was 876, lactate dehydrogenase (LDH) was 658. 

The pressure-time integral (PTI) was 56.8% and international normalized ratio (INR) was 1.76, which after 2 days of treatment of COPD was 90%. The LFT pattern suggested the presence of liver injury. Viral markers for hepatitis A, B, C and E were negative. The antinuclear antibody (ANA) was negative. 

The ultrasound for hepatobiliary system was normal. There was no history of any joint pains and/or any features suggestive of autoimmune hepatitis. There was also no history of intake of any hepatotoxic drugs or herbal/indigenous drugs. Serum LDH was evaluated and it was 1,000 units. 

Discussion

Pulmonary complications of chronic liver disease such as hepatopulmonary syndrome, portopulmonary hypertension and hepatic hydrothorax are well-known, and have been described extensively in literature. Conversely, hepatobiliary manifestations of primary pulmonary disease also occur with high-frequency, but have been studied less frequently.¹ 

In our case report, we are reporting such a case in which hypoxic hepatitis was due to the hypoxia, which is not a very commonly labeled entity. As we observed that the LFT started declining as the treatment of the COPD was started and on Day 7 of the admission, the LFT were all normalized except LDH, which was 350 units that was typical of the hypoxic hepatitis. 

Hypoxic injury to liver is a largely reversible condition occurring in at least 1% of critically-ill patients and accounting for more than 50% large increase in serum aminotransferases identified in hospital admissions.² 

In recent years, various mechanisms of the hypoxic liver injury have been identified such as the noncardiogenic shock and the respiratory failure giving rise to the more inclusive term ‘hypoxic hepatitis (HH)’.¹

Hypoxic hepatitis may be grouped on the basis of the primary pathophysiology: (1) decreased oxygen uptake (e.g., respiratory failure); (2) reduced oxygen delivery (e.g., hypotension); (3) decreased oxygen availability (e.g., sepsis) and (4) increased oxygen consumption (e.g., hypothermia). Our patient had massive increase in SGOT and SGPT and serum LDH with normal serum bilirubin levels, which further supported the hypoxic hepatitis as laboratory testing in a case of hypoxic hepatitis shows a characteristic increase in serum transaminases 10-100 times the upper limit of the normal. Serum LDH is significantly increased as well. Hyperbilirubinemia is characteristically mild and rarely exceeds 5 mg/dL.^2,3

The PTI in our patient was initially 56.8%, which after 2 days was normalized. In hypoxic hepatitis, coagulopathy is usually not significant and the serum prothrombin time peaks within the initial 24-48 hours of the insult with subsequent normalization.^2-4

Initially in our patient, we thought of the presence of viral hepatitis. The serological viral markers were all negative, the transaminases showed a declining trend with treatment of the respiratory failure, which was suggestive of the hypoxic hepatitis. Important distinguishing features of hypoxic hepatitis from toxin-induced liver injury and viral hepatitis include rapid reversal of the increased transaminase levels, lower alanine transaminase (ALT)/LDH ratio, low-degree of coagulopathy and bilirubinemia, and lower incidence of renal dysfunction.^1,4 

Ultrasonography in our patient showed a normal liver and biliary system, had it been due to congestive heart failure, there would have been congestive hepatomegaly. Imaging study may be normal or may show hypoechoic areas on ultrasonography that resolve completely in time.⁴ 

Moreover, our patient clinically had no signs of heart failure, JVP was not raised, no pedal edema was there. Close correlation between enzymatic changes and severity of arterial hypoxemia, and lack of correlation between enzymatic changes and clinical signs of right heart failure, appear to indicate that severe hypoxia per se plays a major role in the development of liver injury rather than mechanical factors due to increased venous pressure.⁵ 

Since, our patient was a female, so the possibility of autoimmune hepatitis was also considered but there was no feature suggestive of autoimmune diseases and also the ANA and the anti-LKM antibodies were negative.

Hypoxic hepatitis is the most common cause of sharp, transient increase in serum transaminases in hospitalized patients and 15-20% of these patients may have respiratory failure as the underlying cause. The overall prognosis in these cases is poor because of the comorbidities and poor clinical condition, and management involves the treatment of the underlying cause and supportive care.¹ Thus, the treating physician must be aware of the association of the liver injury with the respiratory failure as the treatment of the underlying cause is the only remedy in these cases.

REFERENCES

1. Kochar R, Fallon MB. Pulmonary diseases and the liver. Clin Liver Dis 2011;15(1):21-37.
2. Birrer R, Takuda Y, Takara T. Hypoxic hepatopathy: pathophysiology and prognosis. Intern Med 2007;46(14):1063-70.
3. Henrion J, Schapira M, Luwaert R, Colin L, Delannoy A, Heller FR. Hypoxic hepatitis: clinical and hemodynamic study in 142 consecutive cases. Medicine (Baltimore)  2003;82(6):392-406.
4. Ebert EC. Hypoxic liver injury. Mayo Clin Proc 2006;81(9):1232-6.
5. Refsum HE. Arterial hypoxaemia, serum activities of GO-t, GP-t and LDH, and centrilobular liver cell necrosis in pulmonary insufficiency. Clin Sci 1963;25:369-74.
6. Henrion J, Colin L, Schapira M, Heller FR. Hypoxic hepatitis caused by severe hypoxemia from obstructive sleep apnea. J Clin Gastroenterol 1997;24(4):245-9.
7. Liver ischemia was initially thought to be the main mechanism responsible for hypoxic hepatitis. But more recently, Henrion et al found that arterial hypoxemia when severe may lead to hypoxic hepatitis even in the absence of cardiac and circulatory failure.6 

About the Authors

VARUN VIJAY MAHAJAN, Senior Resident, Dept. of Medicine, Chintpurni Medical College, Pathankot, Punjab

IESHA PARGAL, Senior Resident, Dept. of Forensic Medicine and Toxicology, Government Medical College, Jammu