Liver function improvement after human placental extract injections in patients with chronic liver disease: Thirty case reports

Abstract

BACKGROUND

This case report describes a protocol developed by Danaun Medical Clinic for the introduction of a pioneering intervention comprising intravenous human placental extract (HPE) therapy to improve the liver function of patients with chronic liver disease (CLD).

CASE SUMMARY

This study involved data from patients whose chief complaint was reduced quality of life attributable to CLD. The new treatment approach resulted in improvements in the liver function and fatty liver of 30 patients with CLD. Improvements were observed using abdominal ultrasonography. Unlike traditional methods, this protocol provided more sustainable and meaningful results. Treatment with 10 mL of HPE administered intravenously once or twice per week significantly improved liver function. The observed improvements in fatty liver and liver function suggest the utility of this approach for the management of patients with CLD.

CONCLUSION

This case series highlights the potential of innovative treatments for patients with CLD that could improve the quality of life of the patients.

Key Words: Fatty liver; Human placental extract; Liver disease; Liver function; Alanine transaminase; Aspartate aminotransferase; Case report

Core Tip: In this paper, we describe an innovative treatment method that involved the intravenous administration of 10 mL of human placental extract once or twice a week. This is the first case report on the use of placental extract in patients with chronic liver disease (CLD) through an innovative treatment method. This treatment method can be used to improve liver function in patients with CLD.

INTRODUCTION

Cirrhosis and other liver diseases are leading causes of mortality and morbidity worldwide[1]. An estimated 1.5 billion individuals worldwide have chronic liver disease (CLD) with all stages of severity. The most common causes of CLD are metabolic dysfunction-associated steatotic liver disease (MASLD) (59%), hepatitis B virus (29%), hepatitis C virus (9%), and alcoholic liver disease (ALD) (2%)[2]. ALD accounts for approximately 30%–50% of cirrhosis-related deaths worldwide, and unlike viral hepatitis, it cannot be assessed using viral tests. Furthermore, it is a marker of disease trends attributable to the alcohol consumption habits of individuals[3]. MASLD has a global prevalence of 24%[4]. Approximately 59% of MASLD cases include metabolic dysfunction-associated steatohepatitis (MASH), which is a major disease subtype associated with the risk of fibrosis. Studies on MASLD, diabetes, and obesity have predicted that the incidence of MASLD will increase over the next 10 years[5]. Increased alcohol consumption affects obesity-related liver diseases. Both low and moderate alcohol consumption can increase the risk of CLD in obese individuals and worsen MASLD progression[6].

Human placental extract (HPE) has a liver-protective effect against external environmental factors, physical factors, and nutritional disorders that cause liver damage. HPE mainly acts as an antioxidant by activating the nuclear factor erythroid-derived 2-related factor pathway. Besides, HPE increases enzyme activity and second-stage detoxification enzymes and exerts antioxidant effects by reducing the production of reactive oxygen species and malondialdehyde in the liver. Additionally, HPE increases glutathione levels and exerts protective effects on liver cells by activating the endogenous antioxidant system. Furthermore, HPE has antioxidant, anti-inflammatory, and anti-apoptotic properties, improves fibrosis, reduces collagen deposition, and promotes liver regeneration[7]. Therefore, HPE appears to prevent hepatocyte death and promote liver regeneration by suppressing oxidative stress and maintaining cell homeostasis, demonstrating its potential as an alternative treatment option that could regenerate the damaged liver.

Danaun Medical Clinic developed a protocol for an intervention comprising intravenous HPE therapy to improve the liver function of patients with CLD. This treatment was administered to patients with CLD, and the improvement of liver function, ease of administration, and immediate symptom relief experienced by patients, which were different from those resulting from existing treatment protocols, were confirmed.

CASE PRESENTATION

This study, performed at our institution, included 30 patients diagnosed with CLD [alanine transferase (ALT) level ≥ 40 U/L]. The ALT level of each patient varied between 40 U/L and 128 U/L, indicating various disease severities across patients. The treatment protocol created by Danaun Medical Clinic included standardized methods of administering injection therapy. Patients with CLD were administered injections once or twice per week depending on disease severity. The treatment period ranged from a minimum of 4 weeks to a maximum of 8 weeks. A single dose comprised 10 mL of HPE administered intravenously.

This innovative protocol for HPE injection therapy was implemented at our institution. Treatment regimens were carefully designed to achieve rapid therapeutic efficacy for patients with CLD. Standardized methods of injection therapy have been instrumental in ensuring a consistent approach for all patients, while allowing personalized treatment based on the conditions and treatment responses of individual patients. The treatment goals were as follows: (1) To reduce the discomfort and burden of patients caused by subcutaneous injection administration and frequent hospital visits; and (2) To reduce ALT levels while increasing the convenience of treatment comprising the intravenous administration of 10 mL of HPE.

The results were presented as means ± SD. Statistical significance was determined by performing multiple comparisons using the t-test. Significance was considered with P < 0.05 and P < 0.01.

Chief complaints

All patients had a reduced quality of life attributable to CLD.

History of present illness

All patients were diagnosed with CLD at Danaun Medical Clinic between May 2023 and December 2023. The diagnosis of fatty liver was determined more than 6 months before the design of the treatment protocol. These patients experienced constant discomfort attributable to fatty liver.

History of past illness

Most patients had underlying diseases such as hypertension, diabetes, and hyperlipidemia. One patient had latent tuberculosis.

Personal and family history

No specific family history was observed.

Physical examination

A physical examination was not performed.

Laboratory examinations

Liver function tests were performed. The patients scheduled to receive HPE treatment once per week exhibited the following results before treatment: (1) ALT: 59 U/L ± 21.9 U/L; (2) Aspartate aminotransferase (AST): 47 U/L ± 12 U/L; (3) Total bilirubin: 1 mg/dL ± 0.3 mg/dL; (4) Alkaline phosphatase (ALP): 68 U/L ± 14.6 U/L; and (5) Glucose: 95 mg/dL ± 13.3 mg/dL. The patients scheduled to receive HPE treatment twice per week exhibited the following results before treatment: (1) ALT: 61.7 U/L ± 30.4 U/L; (2) AST: 52.2 U/L ± 30.4 U/L; (3) Total bilirubin: 1 mg/dL ± 0.3 mg/dL; (4) ALP: 73 U/L ± 9.9 U/L; and (5) Glucose: 90 mg/dL ± 10.3 mg/dL. HPE was administered for 4 weeks, and the improvement of liver function was significant. After HPE treatment once per week for 4 weeks, the following results were observed: (1) ALT: 29.5 U/L ± 13.4 U/L; (2) AST: 33 U/L ± 13.9 U/L; (3) Total bilirubin: 1 mg/dL ± 0.2 mg/dL; (4) ALP: 67 U/L ± 18.8 U/L; and (5) Glucose: 100 mg/dL ± 7.4 mg/dL. After HPE treatment twice per week for 4 weeks, the following results were observed: (1) ALT: 24 U/L ± 13.3 U/L; (2) AST: 30.4 U/L ± 7.4 U/L; (3) Total bilirubin: 1 mg/dL ± 0.1 mg/dL; (4) ALP: 78 U/L ± 2.6 U/L; and (5) Glucose: 112 mg/dL ± 0 mg/dL.

Imaging examinations

Abdominal ultrasonography was performed at Danaun Medical Clinic. All patients had CLD with fatty liver.

FINAL DIAGNOSIS

CLD with fatty liver.

TREATMENT

One HPE injection was administered once or twice per week for 4–8 weeks. Patients received between four and 16 injections. Of the 30 patients with CLD, 20 received injections once per week and 10 received injections twice per week (Table 1).

Table 1 Age and sex of patients and frequency of injections.

	Male		Female
	Age	n	Age	n
Once a week age	55.7 ± 9.3	7	57.3 ± 9.4	13
Twice a week age	46.2 ± 14.4	6	61.0 ± 5.0	4

OUTCOME AND FOLLOW-UP

The 30 patients with CLD treated with intravenous HPE had positive outcomes. The ALT and AST levels of patients with CLD who received intravenous HPE injections once or twice per week were significantly lower than those observed at baseline (Figure 1).

Figure 1 Alanine transferase and aspartate aminotransferase changes in patients with chronic liver disease who were administered human placental extract once per week and twice per week. A: Alanine transferase level; B: Aspartate aminotransferase level; C: Alanine transferase level; D: Aspartate aminotransferase level. Data were analyzed using the paired samples t-test. ^aP < 0.05. ^bP < 0.01. ALT: Alanine transferase; AST: Aspartate aminotransferase.

An abdominal ultrasound evaluation of patients with fatty liver was performed. When patients received treatment once per week, the imaging evaluation of fatty liver yielded normal results for 80% of the patients, improved results for 10% of the patients, and no improved results for 10% of the patients. When patients received treatment twice per week, the imaging evaluation of fatty liver yielded normal results for 90% of the patients and no improved results for 10% of the patients. Therefore, both treatment groups experienced significantly normalized values (Figure 2A).

Figure 2 Chronic liver disease normalization rates and alanine transferase based on the frequency of human placental extract administration observed using abdominal ultrasonography. A: Chronic liver disease normalization rates; B: Alanine transferase normalization rates. ALT: Alanine transferase.

The ALT normalization rate was confirmed after intravenous HPE injections. When treatment was administered once per week, normal and abnormal ALT levels were observed in 80% and 20% of the patients, respectively. Meanwhile, when treatment was administered twice per week, normal and abnormal ALT levels were observed in 90% and 10% of the patients, respectively. Therefore, both treatment groups exhibited high levels of normalization (Figure 2B).

These results demonstrated that intravenous administration of 10 mL of HPE once or twice per week for CLD effectively reduced liver function levels. Most patients with CLD experienced significant improvement with this innovative treatment. The results of the intravenous administration of HPE once or twice weekly for patients with CLD highlighted the potential of this treatment to improve the overall quality of life of these patients.

DISCUSSION

Symptom management of patients with CLD plays an important role in improving their quality of life and affects prognosis. The effective management of liver function can have a significant effect on patient comfort and activities of daily living.

Alcoholic steatohepatitis (ASH) and MASH, which are common liver diseases experienced by patients with CLD, have different causes but similar pathogeneses. The excessive accumulation of lipids in hepatocytes causes oxidative stress that induces cytokines such as tumor necrosis factor-alpha. Pathological findings of both diseases include inflammatory infiltration of hepatocytes[8,9]. Abstinence from alcohol and metabolic control are integral to the treatment of ASH and MASH.

Corticosteroids, anti-tumor necrosis factor, antioxidants, and pentoxifylline have been introduced as treatments for ASH[10]. Corticosteroids and pentoxifylline are used for the management of ALD; however, at present, their use is limited to severe liver disease[11].

MASH is directly associated with obesity, type 2 diabetes mellitus, hypertension, and high cholesterol levels. Insulin sensitizers, antioxidants, and hepatoprotective agents have been studied to determine their potential to modulate the complex metabolic and hepatotoxic sequence of MASH[12].

In addition, HPE has anti-inflammatory and antioxidant properties. Preclinical studies of a concanavalin A-induced liver injury model showed that HPE protects hepatocytes during chronic inflammation through the inhibition of intercellular adhesion molecule-1 and myeloperoxidase. HPE increases superoxide dismutase and decreases oxidative nitrite oxide and malondialdehyde; therefore, HPE protects liver cells damaged by lipid peroxidation.

In the present study, when treatment was administered intravenously once or twice per week, ALT and AST levels improved significantly compared to those observed at baseline.

Some patients with CLD had underlying diseases such as hypertension, hyperlipidemia, diabetes mellitus, and latent tuberculosis infection; therefore, they were receiving medications for those diseases. However, no adverse reactions or side effects were observed with the use these medications or intravenous HPE.

Intravenous HPE therapy can improve the liver function of patients with CLD. However, this study was limited by its experimental design and small sample size; therefore, the results of this treatment for patients with CLD cannot be generalized. Although additional research is needed to fully understand and validate these findings, the preliminary results of the Danaun Medical Clinic protocol highlight a potential shift in treatment that can improve liver function in patients with CLD.

CONCLUSION

The innovative protocol for intravenous HPE therapy developed by Danaun Medical Clinic represents a significant advancement in the treatment of CLD. This study demonstrated that this new treatment method can effectively improve liver function. Although these preliminary results are promising, further studies are required to fully understand and validate the long-term effects and efficacy of this treatment. Intravenous HPE therapy for patients with CLD could be used to manage disease-related muscle spasticity and provide a more holistic and patient-centered approach to treatment. This study provides a foundation for future investigations and clinical trials that are required to establish the role of HPE injection therapy in the management of CLD.

ACKNOWLEDGEMENTS

I would like to thank all those who helped us to correct the data for this study.