Gastrointestinal Intervention 2018; 7(3): 167-171  https://doi.org/10.18528/gii180026
Transjugular intrahepatic portosystemic shunt creation for portal hypertension in patients with hepatocellular carcinoma: A systematic review
He Zhao, Jiaywei Tsauo* , Xiaowu Zhang, Tao Gong, Jinggui Li, and Xiao Li
Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
*Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, China. E-mail address: 80732059@qq.com (J. Tsauo). ORCID: https://orcid.org/0000-0002-5655-7989
Received: July 16, 2018; Revised: August 13, 2018; Accepted: August 13, 2018; Published online: October 31, 2018.
© Society of Gastrointestinal Intervention. All rights reserved.

cc This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract

Background

To evaluate the safety and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) creation for the management of portal hypertension in patients with hepatocellular carcinoma (HCC).

Methods

A literature search of the MEDLINE/PubMed and Embase databases was conducted. All articles reporting the outcomes of TIPS creation for variceal bleeding and refractory ascites and hepatic hydrothorax in patients with HCC were included. Exclusion criteria were non-English language, sample size < 5, data not extractable, and data reported in another article.

Results

A total of 280 patients (mean age, 48–58; male gender, 66%) from five articles were included. TIPS creation was performed for variceal bleeding in 79% and refractory ascites and/or hepatic hydrothorax in 26% of patients. Technical and clinical success was achieved in 99% and 64% of patients, respectively. Clinical failure occurred in 36% of patients due to rebleeding or recurrent bleeding (n = 77) or no resolution or improvement of refractory ascites and hepatic hydrothorax (n = 24). One percent of patient had major complications, including accelerated liver failure (n = 1) and multi-organ failure resulting from hemorrhagic shock (n = 1), all of which resulted in early (i.e., within 30 days) death. Hepatic encephalopathy occurred in 40% of patients after TIPS creation. Lung metastasis was found 1% of patient 5 months (n = 1) and 72 months (n = 1) after TIPS creation.

Conclusion

TIPS creation seems to be safe and effective for the management of portal hypertension in patients with HCC.

Keywords: Ascites, Gastrointestinal hemorrhage, Hydrothorax, Liver neoplasms, Portasystemic shunt, transjugular intrahepatic
Introduction

Portal hypertension is most often caused by liver cirrhosis and is associated with a wide range of complications, mainly variceal bleeding, ascites, and hepatic hydrothorax.1,2 Transjugular intrahepatic portosystemic shunt (TIPS) creation is well-established for the management of portal hypertension and its complications.3 Traditionally, this procedure has been considered relatively contraindicated in patients with hepatocellular carcinoma (HCC) due to concerns of tumor rupture, bleeding, accelerated liver failure, and lung metastasis. Nonetheless, since most cases of HCC arise in the setting of liver cirrhosis and therefore, it is not uncommon for cirrhotic patients to present with both portal hypertension and HCC.4 In these patients, the management of the complications of portal hypertension presents a challenge because treatment options besides TIPS creation are very limited after medical therapy.1,2 Over the years, several studies have been conducted to understand the safety and efficacy of TIPS creation in patients with HCC.59 However, the outcomes of TIPS creation in patients with HCC remains controversial due to a paucity of evidence from large studies.8,9 Systematic review is a useful tool to combine the results of multiple studies to obtain more accurate estimates. The purpose of the present systematic review was to evaluate the safety and efficacy of TIPS creation for the management of portal hypertension in patients with HCC.

Methods

Search strategy and selection criteria

Institutional review board approval is not required for review articles at our institution. The present review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.10 A literature search of the MEDLINE/PubMed and EMBASE databases was conducted to identify eligible articles published before May 2018 using pertinent MeSH and Emtree terms (Supplementary Table 1). References of relevant articles were also screened. Duplicates, reviews, case reports, editorials, letters, and abstracts were excluded at outset. Title and abstract screening followed by full-text screening was performed to identify articles that met the selection criteria. All articles reporting the outcomes of TIPS creation for variceal bleeding and refractory ascites and hepatic hydrothorax in patients with HCC were included. Exclusion criteria were non-English language, sample size < 5, data not extractable, and data reported in another article. Two reviewers independently performed the literature search, and discrepancies were resolved by consensus.

Data extraction and quality assessment

The following data were extracted: authors, study design, publication year, geographical region, sample size, mean age, gender, liver disease etiology, Child-Pugh class, mean model for end-stage liver disease (MELD) score, variceal bleeding, refractory ascites, hepatic encephalopathy (HE), portal vein tumor thrombus (PVTT), technical success, whether shunt traversed the tumor, stent type, stent diameter, mean portosystemic pressure gradient (PPG), clinical success, major complications, median follow-up, shunt dysfunction, and median survival. Clinical success was defined as no rebleeding and recurrent bleeding and resolution or improvement of refractory ascites and hepatic hydrothorax. Major complications were defined according to the Society of Interventional Radiology (SIR) clinical practice guidelines.11 The quality of the included studies was assessed using the United States National Institutes of Health Quality Assessment of Case Series Studies tool.12 Data extraction and quality assessment were independently performed by two reviewers, and discrepancies were resolved by consensus.

Results

Literature selection and characteristics

A total of 302 non-duplicated articles were identified through the literature search (n = 301) and references (n = 1) (Fig. 1). Title and abstract screening resulted in 16 full-text articles being screened. Of these articles, five met the selection criteria and were included (Table 1).7,8,1315 The remaining 11 articles were excluded due to non-English language (n = 3), sample size < 5 (n = 3), data not extractable (n = 3), and data reported in another article (n = 2) (Supplementary Table 2). All included articles were case series with a sample size ranging from 6 to 209 patients. The quality of these articles ranged from good (n = 3) to fair (n = 2) (Table 2).7,8,1215

Patient demographics and characteristics

A total of 280 patients (mean age [data available for 86% of patients], 48–58 ± 12–13; male gender, 66%) were included. TIPS creation was performed for variceal bleeding in 79% and refractory ascites and/or hepatic hydrothorax in 26% of patients. Data on liver disease etiology, Child-Pugh class, mean MELD score, HE, PVTT were available for 93%, 98%, 0%, 80%, and 98% of patients, respectively. The most common liver disease etiology was hepatitis B virus (73%) followed by alcoholic liver disease (15%). Child-Pugh class was A in 32%, B in 38%, and C in 30% of patients. Thirty-nine percent of patients had HE. PVTT was present in 24% of patients.

Technical success and procedure details

Technical success was achieved in 99% of patients. Technical failure occurred in 1% of patient due to cavernous transformation of the portal vein resulting in inability to puncture the portal vein (n = 4). Data on whether shunt traversed the tumor, stent type, stent diameter, and mean PPG were available for 7%, 95%, 81%, and 79% of patients, respectively. Bare and covered stent was used in 53% and 47% of patients, respectively. Twenty-three percent of patients used 10 mm diameter stent. In the remaining 77% of patients, 8 mm diameter stent was most frequently used (77%). The mean PPG reduced from 29–32 ± 4–5 mmHg before to 12–18 ± 3–4 mmHg after TIPS creation.

Clinical success and complications

Clinical success was achieved in 64% of patients. Clinical failure occurred in 36% of patients due to rebleeding or recurrent bleeding (n = 77) or no resolution or improvement of refractory ascites and hepatic hydrothorax (n = 24). One percent of patient had major complications, including accelerated liver failure (n = 1) and multi-organ failure resulting from hemorrhagic shock (n = 1), all of which resulted in early (i.e., within 30 days) death. No other major complications were reported, in particular tumor rupture and bleeding. HE occurred in 40% of patients after TIPS creation. Lung metastasis was found 1% of patient 5 months (n = 1) and 72 months (n = 1) after TIPS creation.

Shunt dysfunction and survival

Data on median follow-up, shunt dysfunction, and median survival were available for 93%, 98%, and 98% of patients, respectively. The median follow-up was 53 to 211 days (lower range, 3–56 days; upper range, 391–2,919 days). Shunt dysfunction occurred in 50% of patients. The mean survival was 53 to 180 days (lower range, 5–56 days; upper range, 167–392 days).

Discussion

The present systematic review of five articles involving 280 patients with HCC who underwent TIPS creation for variceal bleeding (79%) and refractory ascites and/or hepatic hydrothorax (26%) showed that: (i) technical and clinical success was achieved in 99% and 64% of patients, respectively; (ii) 1% of patient had major complications, including accelerated liver failure (n = 1) and multi-organ failure resulting from hemorrhagic shock (n = 1), all of which resulted in early death; (iii) lung metastasis was found 1% of patient 5 months (n = 1) and 72 months (n = 1) after TIPS creation; and (vi) shunt dysfunction occurred in 50% of patients during a median follow-up of 53 to 211 days (lower range, 3–56 days; upper range, 391–2,919 days).

TIPS creation has traditionally been considered relatively contraindicated in patients with HCC due to concerns of major complications, mainly tumor rupture and bleeding.3 However, tumor rupture and bleeding were not reported in the present systematic review. In addition, only 1% of patient in our current systematic review had major complications (i.e., early deah due to accelerated liver failure [n = 1] and multi-organ failure resulting from hemorrhagic shock [n = 1]). This rate of major complications is similar to those reported for patients without HCC (accelerated liver failure, 3%; death, 1%) and is within the mortality threshold suggested by the SIR (2%).16 This suggests that TIPS creation may be as safe in patients with HCC as it is in patients without HCC. Another concern with TIPS creation in patients with HCC is the occurrence of lung metastasis after the procedure, particularly if the puncture needle and shunt traversed the tumor. However, in our current systematic review, lung metastasis after TIPS creation was found in only 1% of patient and was found well after the procedure (i.e., 5 months [n = 1] and 72 months [n = 1]). Nonetheless, the rate of lung metastasis after TIPS creation may be underestimated as screening protocols were not well defined in any included articles.

The high technical success rate of TIPS creation in the present systematic review (99%) showed that this procedure is very feasible in patients with HCC. However, the clinical success rate of TIPS creation for in our current systematic review (64%) is fairly low. This is mainly due to the high rate of clinical failure associated with rebleeding and recurrent bleeding (28%), which is higher than those reported for patients without HCC (< 10%).1721 This difference may be attributed to the high shunt dysfunction rate (50%). It is well-established that the use of covered stents and 10 mm diameter stents in the creation of TIPS can significantly reduce the risk of shunt dysfunction compared with the use of bare stents and 8 mm diameter stents, respectively.2226 However, only 47% and 23% of the patients in our current systematic review used covered stents and 10 mm diameter stents, respectively. It is anticipated that, if 10 mm diameter covered stents were exclusively used for TIPS creation, the shunt dysfunction rate would markedly decrease resulting in a lower rate of rebleeding and recurrent bleeding.

The present systematic review has several important limitations. First, all included articles were case series with inherent limitations associated with retrospective data collection (e.g., selection and recall biases and data lost). Second, publication bias and selective analysis reporting bias (e.g., inclusion of only patients who achieved technical success) may have resulted in overly optimistic results. Third, different stent types with varying diameters were used for TIPS creation and therefore our results may not reflect outcomes of standard practice. Forth, the rate of lung metastasis after TIPS creation may be underestimated as screening protocols were not well defined in any included articles. Last, a control group of patients without HCC who underwent TIPS creation was not available for comparison and therefore, whether outcomes of TIPS creation are different between patients with and without HCC were unable to be determined.

In conclusion, TIPS creation seems to be safe and effective for the management of portal hypertension in patients with HCC. Future prospective studies using state-of-the-art modalities with rigorous follow-up are necessary to confirm the findings of the present systematic review. In addition, further comparison studies are warranted to determine if the outcomes of TIPS creation are different in patients with and without HCC.

Conflicts of Interest

No potential conflict of interest relevant to this article was reported.

Acknowledgments

This paper was made possible by the Beijing Hope Run Special Fund of Cancer Foundation of China (grant no. LC2015A01 to X.L.).

Supplementary Materials

Supplementary data is available at https://doi.org/10.18528/gii180026.

Supplementary Information
Figures
Fig. 1. Flowchart of article selection process.
Tables

Table 1

Included Articles and Data Extracted

Wallace and Swaim13 (2003) Jiang et al14 (2004) Zhao et al15 (2014) Bettinger et al7 (2015) Qiu et al8 (2015) Total
Study design Case series Case series Case series Case series Case series -
Geographical region USA China China Germany China -
Sample size (n) 6 14 11 40 209 280
Age (yr) 58 ± 12 56 ± 13 54 ± 13 64 (40–83) 48 ± 13 -
Gender, M/F (%) 100/0 93/7 100/0 88/12 58/42 66/34
Liver disease etiology, HBV/ALD/others (%) - - 100/0/0 0/63/37 86/6/8 73/15/12
Child-Pugh class, A/B/C (%) - 0/0/100 27/27/46 7/73/20 40/34/26 32/38/30
MELD score - - - 13 (7–22) - -
VB (%) 50 79 82 43 87 79
RA/HH (%) 50 21 18 65 19 26
Pre-HE (%) - 36 - - 39 39
PVTT (%) - 100 100 28 15 24
Technical success (%) 100 71 100 100 100 99
Shunt traversed tumor (%) 100 7 - - - 35
Stent type, bare/covered (%) 100/0 - 0/100 60/40 54/46 53/47
Stent diameter, 10 mm/others (%) 0/100 - 0/100 - 25/75 23/77
PPG (mmHg) -
 Before - - 32 ± 5 20 (13–33) 9 ± 4 -
 After - - 12 ± 4 8 (2–16) 18 ± 3 -
Clinical success (%) 83 100 100 83 56 64
Major complications (%) 17 0 0 3 0 1
Post-HE (%) 50 36 55 40 39 40
Median follow-up (day) 53 (5–391) - 168 (56–504) 211 (3–2,919) - -
Lung metastasis (%) 17 0 0 3 0 1
Shunt dysfunction (%) 50 - 0 20 58 50
Median survival (day) 53 (5–167) 132* 168 (56–392) 180* 50* -

Values are presented as number only, mean ± standard deviation, or median (range).

M/F, male/female; HBV, hepatitis B virus; ALD, alcoholic liver disease; MELD, model for end-stage liver disease; VB, variceal bleeding; RA/HH, refractory ascites/hepatic hydrothorax; Pre-HE, preprocedure hepatic encephalopathy; PVTT, portal vein tumor thrombus; PPG, portosystemic pressure gradient; Post-HE, postprocedure hepatic encephalopathy.

*

Mean value.

Table 2

Quality Assessment of Included Articles

NIH Quality Assessment Tool for Case Series Studies Criteria12 Wallace and Swaim13 Jiang et al14 Zhao et al15 Bettinger et al7 Qiu et al8
1. Was the study question or objective clearly stated?
2. Was the study population clearly and fully described, including a case definition?
3. Were the cases consecutive?
4. Were the subjects comparable?
5. Was the intervention clearly described?
6. Were the outcome measures clearly defined, valid, reliable, and implemented consistently across all study participants?
7. Was the length of follow-up adequate?
8. Were the statistical methods well-described?
9. Were the results well-described?
Quality rating Good* (8/9) Fair (4/9) Good* (8/9) Good* (9/9) Fair (6/9)

NIH, National Institute of Health.

*

Met 7–9 criteria;

Met 4–6 criteria.

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