Review question
Intrahepatic shunts compared with conventional treatment: which is best for improving the clinical conditions of adults with hepatorenal syndrome?
Key messages
– We did not find enough good-quality evidence on the benefits and harms of intrahepatic shunts to improve clinical conditions in adults with hepatorenal syndrome.
– Larger randomised clinical trials (trials where people are randomly put into one of two or more treatment groups) with more reliable data are needed to better assess the benefits and harms of treating hepatorenal syndrome.
– Future research should also focus on health-related quality of life, and kidney and liver function in adults with hepatorenal syndrome to help guide decision-making.
What is hepatorenal syndrome?
Hepatorenal syndrome is a condition characterised by kidney failure that develops in people who have chronic liver disease, increased portal vein (the main blood vessel that takes blood to the liver) pressure, and fluid in the abdomen as a result of low blood flow to the kidneys. People with hepatorenal syndrome can survive up to six months if they do not undergo liver transplantation.
How is hepatorenal syndrome treated?
The treatment is used to improve clinical conditions and kidney function until liver transplantation. This includes the use of medications, albumin (a protein made by the liver that helps stop fluid leaking out of blood vessels into other parts of the body), removal of abdominal fluid, and placement of transjugular intrahepatic portosystemic shunts (TIPS; non-surgical procedure where a stent (tube) is inserted to create new connections between blood vessels to reduce pressure within the abdomen).
What did we want to find out?
While these treatments appear to be helpful, they have been reported to have some side effects, so information on the beneficial and harmful effects of TIPS remains unclear.
What did we do?
We searched for randomised clinical trials that compared TIPS placement with conventional treatment, no treatment, or other treatments in adults older than 18 years of any sex and ethnicity with hepatorenal syndrome and without previous kidney failure.
We compared and summarised the results of the trials, and rated our confidence in the evidence based on factors such as methods and size.
What did we find?
We found two studies, with 130 adults aged 56 to 61 years, comparing TIPS placement with abdominal cavity fluid removal plus albumin treatment (conventional therapy). One trial was conducted in Spain and the USA, and one in Germany. Participants were monitored for up to 24 months.
Main results
In general, TIPS does not reduce death, the development of other diseases, the development of side effects, and the length of hospitalisation, neither does it provide clear results regarding the improvement of kidney function in the following months compared to conventional therapy.
What are the limitations of the evidence?
We are not confident about the evidence because we found only two small trials, there were few results per outcome, there was a limited number of participants, and there were differences between how the two trials were run.
More research is needed to evaluate whether the placement of TIPS has any effect on death, quality of life, changes in kidney function, and length of hospitalisation in adults with hepatorenal syndrome to improve their clinical condition until they can have a liver transplant. Therefore, further research is likely to change the results of this review.
How up to date is this evidence?
The evidence is up to date to 2 June 2023.
TIPS placement was compared with conventional treatment, with a follow-up of 24 months, in adults with hepatorenal syndrome type 2. Based on two trials with insufficient sample size and trial limitations, we assessed the overall certainty of evidence as low or very low.
We are unsure if TIPS may decrease all-cause mortality, serious adverse events, the number of people who did not receive a liver transplant, and the days of hospitalisation because of the very low-certainty evidence.
We are unsure if TIPS, compared with conventional treatment, has better effects on overall morbidity (bacterial peritonitis, encephalopathy, or refractory ascites). TIPS may improve kidney function, but the certainty of evidence is low.
The trials included no data on health-related quality of life, non-serious adverse events, and liver function associated with the TIPS placement.
We identified one ongoing trial and one study awaiting classification which may contribute to the review when information becomes available.
Hepatorenal syndrome is a condition that occurs in people with chronic liver disease (such as alcoholic hepatitis, advanced cirrhosis, or fulminant liver failure) and portal hypertension. The prognosis is dismal, often with a survival of weeks to months. Hepatorenal syndrome is characterised by the development of intense splanchnic vasodilation favouring ascites and hypotension leading to renal vasoconstriction and acute renal failure. Therefore, treatment attempts focus on improving arterial pressure through the use of vasopressors, paracentesis, and increasing renal perfusion pressure.
Several authors have reported that the placement of transjugular intrahepatic portosystemic shunts (TIPS) may be a therapeutic option because it decreases portal pressure and improves arterial and renal pressures. However, the evidence is not clearly documented and TIPS may cause adverse events. Accordingly, it is necessary to evaluate the evidence of the benefits and harms of TIPS to assess its value in people with hepatorenal syndrome.
To evaluate the benefits and harms of transjugular intrahepatic portosystemic shunts (TIPS) in adults with hepatorenal syndrome compared with sham, no intervention, conventional treatment, or other treatments.
We used standard, extensive Cochrane search methods. The latest search date was 2 June 2023.
We included only randomised clinical trials with a parallel-group design, which compared the TIPS placement with sham, no intervention, conventional therapy, or other therapies, in adults aged 18 years or older, regardless of sex or ethnicity, diagnosed with chronic liver disease and hepatorenal syndrome.
We excluded trials of adults with kidney failure due to causes not related to hepatorenal syndrome, and we also excluded data from quasi-randomised, cross-over, and observational study designs as we did not design a separate search for such studies.
We used standard Cochrane methods. Our primary outcomes were 1. all-cause mortality, 2. morbidity due to any cause, and 3. serious adverse events. Our secondary outcomes were 1. health-related quality of life, 2. non-serious adverse events, 3. participants who did not receive a liver transplant, 4. participants without improvement in kidney function, and 5. length of hospitalisation.
We performed fixed-effect and random-effects meta-analyses using risk ratio (RR) or Peto odds ratio (Peto OR), with 95% confidence intervals (CI) for the dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) for the continuous outcomes. We used GRADE to assess certainty of evidence.
We included two randomised clinical trials comparing TIPS placement (64 participants) versus conventional treatment (paracentesis plus albumin 8 g/L of removed ascites) (66 participants). The co-interventions used in the trials were dietary treatment (sodium less than 60 mmoL/day), spironolactone (300 mg/day to 400 mg/day), and furosemide (120 mg/day). Follow-up was up to 24 months. Both were multicentre trials from Spain and the USA, and Germany, conducted between 1993 and 2002. Most participants were men (aged 18 to 75 years).
We are uncertain about the effect of TIPS placement compared with conventional treatment, during the first 24 months of follow-up, on all-cause mortality (RR 0.88, 95% CI 0.55 to 1.38; 2 trials, 130 participants; I2 = 58%; very low-certainty evidence) and on the development of any serious adverse event (RR 1.60, 95% CI 0.10 to 24.59; 2 trials, 130 participants; I2 = 78%; very low-certainty evidence).
The use of TIPS may or may not result in a decrease in overall morbidity such as bacterial peritonitis, encephalopathy, or refractory ascites, during the first 24 months of follow-up, compared with the conventional treatment (RR 0.95, 95% CI 0.77 to 1.18; 2 trials, 130 participants; I2 = 0%; low-certainty evidence).
We are uncertain about the effect of TIPS placement versus conventional treatment on the number of people who did not receive a liver transplant (RR 1.03, 95% CI 0.93 to 1.14; 2 trials, 130 participants; I2 = 0%; very low-certainty evidence) or on the length of hospitalisation (MD −20.0 days, 95% CI −39.92 to −0.08; 1 trial, 60 participants; very low-certainty evidence). Kidney function may improve in participants with TIPS placement (RR 0.53, 95% CI 0.27 to 1.02; 1 trial, 70 participants; low-certainty evidence).
No trials reported health-related quality of life, non-serious adverse events, or number of participants with improvement in liver function associated with the TIPS placement.
Funding
No trials reported sources of commercial funding or conflicts of interest between researchers.
Ongoing studies
We found one ongoing trial comparing TIPS with conventional therapy (terlipressin plus albumin) and listed one study as awaiting classification as no full-text article could be found.