Advancement in the diagnosis and treatment of hepatic portal venous gas

Abstract

Hepatic portal venous gas (HPVG) is a rare yet clinically significant radiological manifestation characterized by diverse etiologies, unclear pathophysiology, and nonspecific clinical presentations. Its appearance frequently heralds a severe underlying condition, with a reported mortality rate as high as 75%, earning it the moniker “harbinger of death”. In recent years, with advancements in diagnosis and treatment of HPVG, its mortality rate has been reduced to below 40%. Nevertheless, the infrequency of HPVG, coupled with its complex etiologies and rapid progression, often leaves clinicians failing to provide timely intervention due to a lack of awareness, resulting in the death of patient. Currently, there is no consensus on the standardized diagnosis and treatment strategies for HPVG. The purpose of this review is to synthesize the existing literature on HPVG and to discuss the advancements in understanding its clinical manifestation, etiologies, pathogenesis, diagnostic methods, and treatment strategies, as well as to emphasize the necessity for further research to enhance our comprehension of its pathophysiology and to refine diagnostic and therapeutic approaches.

Key Words: Hepatic portal venous gas; Computed tomography; Advancement; Diagnosis; Treatment

Core Tip: Hepatic portal venous gas (HPVG) represents a rare yet clinically significant radiological finding, underpinned by complex etiologies. Early and comprehensive diagnosis is important, and abdominal contrast-enhanced computed tomography scans can identify the underlying causes and assess the severity of the condition. It is essential to adopt individualized treatment strategies on the basis of the specific etiology of HPVG. Dynamic evaluation of patients’ conditions is important, and timely surgical intervention is warranted when intestinal necrosis occurs. Enterostomy may be considered instead of one-stage anastomosis after bowel resection. Clinicians must enhance their awareness of HPVG to elevate their diagnostic and therapeutic capabilities, ultimately improving patient outcomes.

INTRODUCTION

Hepatic portal venous gas (HPVG) is a rare imaging finding characterized by the accumulation of gas within the portal vein and its intrahepatic branches, typically manifesting as branching or tubular gas distributions extending from the porta hepatis to the liver capsule. First reported by Wolfe and Evans in 1955[1,2], HPVG has traditionally been regarded as a “harbinger of death”, which was indicative of severe underlying pathology and reported to have a mortality rate of up to 75%[3]. However, recent advancement in diagnostic techniques and therapeutic strategies have reduced this mortality rate to below 40%[4]. HPVG is characterized by a low incidence, complex etiology, unclear pathogenesis, diverse treatment approaches and rapid disease progression in most patients. Delayed treatment due to a lack of awareness among clinicians, ultimately resulted in patient’s death[5]. Currently, there are no standardized diagnostic and therapeutic guidelines for HPVG. The purpose of this minireview is to integrate the existing literature and clinical experiences on HPVG to elucidate its clinical characteristics, etiologies, pathophysiological mechanisms, diagnostic methods, and treatment strategies, thereby enhancing clinicians’ understanding of HPVG and improving patient prognosis.

CLINICAL MANIFESTATION

Koizumi et al[6] reported that the incidence of HPVG was 0.0045%, the average onset age was 79.3 years, the male-to-female ratio was approximately 1.16:1, and the incidence of intestinal ischemia was 53%. Daneshmand et al[7] found that the average age of patients was 65.6 years, with a male-to-female ratio of about 1.2:1. The etiologies were broadly categorized as follows: Intestinal thromboembolic diseases (42.6%), mechanical bowel obstruction (17.9%), inflammatory diseases (22.6%), and other conditions (17.1%). The overall mortality rate stood at 47.5%, varying significantly based on underlying causes (ranging from 14.3% to 72.8%) (Figure 1). In summary, HPVG is characterized by a low incidence, predominantly affecting middle-aged and elderly individuals, with a slight male predominance. It is commonly associated with the following types of conditions[8-11]: (1) Intestinal ischemia, such as mesenteric vascular embolism, vascular spasms, aneurysm formation, etc.; (2) Increased pressure in the gastrointestinal lumen, including bowel obstruction of various causes, gastric distension, abdominal trauma, and gastrointestinal tumors; (3) Abdominal infection, such as inflammatory bowel disease, abdominal abscesses, diverticulitis, pancreatitis, etc; and (4) Iatrogenic interventions, including colonoscopy, endoscopic procedures, and hemodialysis, pharmacotherapy. Among these, intestinal ischemia and increased pressure in the gastrointestinal lumen are most prevalent. Recent advancement in diagnostic technology have led to an increase in the reported incidence of HPVG. The mortality rates were closely linked to underlying etiologies, which were notably higher in ischemic conditions compared to non-ischemic ones[12]. Consequently, we classify the etiologies of HPVG into high-risk, moderate-risk, and low-risk categories based on their severities and threats (Table 1). The clinical manifestations of HPVG are generally non-specific, which depend on the severity of the underlying etiologies. Over 90% of patients presented with varying degrees of nausea, vomiting, abdominal pain, and diarrhea[13]. Some patients may exhibit infectious shock at early stage, indicating a poor prognosis[14].

Figure 1  The comparison of mortality rates across etiologies.

Table 1 Etiological classification of hepatic portal venous gas.

Classification	Etiology
Low-risk	Ulcerative disease: Esophageal ulcer, non-perforated gastric ulcer, non-perforated intestinal ulcer
	Inflammatory disease: Pancreatitis, ulcerative colitis, Crohn’s disease, appendicitis, enteritis, cholangitis, diverticulitis
	Iatrogenic interventions: Liver transplantation surgery, biliary tract surgery, gastrointestinal surgery, colonoscopy, cardiac surgery, spinal surgery, endoscopic procedures, hemodialysis, and interventional operation
	Others: Diving, chronic obstructive pulmonary disease, trauma, poisoning, drugs, etc.
Middle-risk	Perforation: Esophageal perforation, gastric ulcer perforation, duodenal ulcer perforation, jejunal ulcer perforation, intestinal diverticular disease with perforation, intestinal perforation
	Obstruction or dilation: Pyloric stenosis, duodenal obstruction, acute cholelytic intestinal obstruction, paralytic intestinal obstruction
	Tumor: Oral and pharyngeal malignant tumor, esophageal malignant tumor, gastric cancer, small intestinal malignant tumor, colon cancer, rectosigmoid colon malignant tumor, malignant tumors of the anus and anal canal, malignant tumors of the liver and intrahepatic bile ducts, gallbladder cancer, malignant tumors of other unknown parts of the biliary tract, pancreatic cancer, malignant tumors of other digestive organs, lip malignant tumor, lung cancer, breast cancer, malignant tumors of bone and articular cartilage, skin cancer, mesothelial and soft tissue tumors, malignant tumors of reproductive organs, urinary system tumors, lymphoma, leukemia, etc.
	Infectious diseases: Clostridium perfringens infection (hemorrhagic enteritis, necrotizing enteritis, gas gangrene, food poisoning)
	Sepsis: Escherichia coli sepsis, streptococcal sepsis, Listeria sepsis, meningococcal septicemia, Candida sepsis, enterogenous infection, abdominal abscess, anastomotic fistula
High-risk	Intestinal ischemia/necrosis: Mesenteric vascular embolism, vascular spasms, aneurysm formation, bowel obstruction, intestinal volvulus

ETIOLOGY AND PATHOGENESIS

It is indicated that HPVG is not a distinct disease in itself but rather a secondary manifestation resulting from various underlying etiologies, such as intestinal necrosis, bowel obstruction, intra-abdominal abscesses, ulcerative colitis, gastric ulcers, Crohn’s disease, complications from endoscopic procedures, intra-abdominal tumors and so on[15,16]. The pathogenesis of HPVG remains incompletely understood, although two primary hypotheses have been proposed: (1) Mechanical theory posits that high-pressure gas from the intestinal lumen enters the portal venous system when endothelial injury is caused by a variety of factors (such as abdominal trauma or intestinal ischemia) or when mucosal rupture is caused by increased intraluminal gas pressure. Statistics show that 85% of HPVG cases are associated with intestinal mucosal injury, bowel distension, and increased intraluminal pressure; and (2) Bacterial theory, which suggests that gas-producing bacteria escape through damaged intestinal mucosa into the submucosa and vascular system, subsequently entering the portal venous system. The most commonly implicated bacteria include Escherichia coli and Clostridium perfringens. Gas-producing organisms such as Clostridium perfringens, Escherichia coli, Citrobacter, Candida, and anaerobes can be isolated from blood cultures and surgical specimens in some patients with HPVG, which are associated with intestinal ischemia and sepsis. Some patients exhibit favorable prognosis following antibiotic treatment[17,18].

DIAGNOSIS

At early stage, the detection of HPVG primarily relied on X-ray imaging, which typically revealed characteristic branching lucencies closing to the liver capsule, and some patients also displayed crescent-shaped gas bubbles in the bowel wall[19]. However, substantial gas accumulation within the portal vein is essential for the detection via conventional X-ray, making a diagnosis at this stage indicative of a poor prognosis[5]. Computed tomography (CT) has emerged as the standard diagnostic method for HPVG due to its high sensitivity. HPVG is often localized in the left lobe of the liver, with CT findings showing lucent gas shadows within the portal vein and its branches. When the accumulation of gas is minimal, it may present as linear distributions closing to the liver capsule, while larger volumes may exhibit the classic “withered branches” expansion (Figure 2A-C). Additionally, contrast-enhanced abdominal CT can detect the presence of gas in the extrahepatic portal vein and mesenteric veins[20]. Ultrasound is also a reliable diagnostic tool for HPVG, exhibiting different specific manifestations in multiple modes: (1) B-mode: It displays bubble-like and punctate strong echoes within the portal vein, often reaching the liver's edge; (2) M-mode: The air bubbles move in the portal vein, producing linear signals on M-mode ultrasound, which is similar to “meteor shower”; (3) Color Doppler mode: The significant difference in acoustic impedance between portal gas and surrounding blood leads to strong sound reflections and the characteristic “flaming portal sign”; (4) Pulsed-wave Doppler mode: It is the most sensitive detection for HPVG, revealing hyperechoic and sharp vertical peaks over the portal venous wave; and (5) Color M-mode: Microbubbles in HPVG appear as oblique lines that interrupt the color, resembling “tiger stripes”[21,22]. When minimal gas enters the portal venous, the advantages of ultrasound are more obvious. At the same time, it also has many advantages, such as cost-effectiveness, non-invasiveness, and bedside applicability[23]. The main differential diagnosis for HPVG is pneumobilia. Pneumobilia is typically centrally located within the liver due to centripetal bile flow and often accompanied by a history of endoscopic procedures or biliary surgery (Figure 2D and E). HPVG is distributed peripherally along the portal venous flow, and closer to the liver capsule, and the patients with severe HPVG may also be confirmed to have gas presenting in the mesenteric vein and bowel wall[24]. Wang et al[25] reported a patient misdiagnosed as having HPVG, and the abdominal CT detected the presence of gas shadows extending to the liver capsule, which was initially consistent with HPVG. But the patient was ultimately diagnosed with pneumobilia by contrast-enhanced abdominal CT. We also had one such patient with pneumobilia (Figure 2F). Therefore, careful attention is required to the differential diagnosis, and further observation and verification is necessary for the presence of gas closing to the liver capsule. Studies have shown that thromboembolic events accounted for about 48.7% of the causes of HPVG, and patients with HPVG associated with ischemic bowel disease had notably high mortality rates of 75%[26]. Contrast-enhanced abdominal CT can assess primary diseases such as bowel obstruction, ischemia, and necrosis, and is beneficial to the final decision for diagnosis and treatment. In contrast, ultrasound findings may be influenced by the operator’s experience and the presence of intestinal gas. Thus, it is recommended that contrast-enhanced abdominal CT be recognized as the preferred imaging modality for HPVG, with ultrasound serving as a supplement after abdominal CT and assessment after treatment.

Figure 2 Contrast-enhanced abdominal computed tomography. A: Hepatic portal venous gas (HPVG) is localized in the left lobe of the liver, and closer to the liver capsule (the arrow shows the gas); B: HPVG exhibits the classic “withered branches” expansion (the arrow shows the gas); C: HPVG involves the superior mesenteric vein and portal vein (the arrow shows the gas); D and E: Pneumobilia is typically centrally located within the liver (the arrow shows the gas); F: The rare presence of gas shadows closing to the liver capsule in the Pneumobilia (the arrow shows the gas).

TREATMENT

Currently, there is no consensus on the standardized treatment strategies for HPVG. The management for HPVG is dependent on patient’s clinical manifestation, imaging findings, and state analysis, including surgical approach and conservative approach. The progression of patients with HPVG often is acute and rapid, with some patients succumbing within 24 hours of onset. However, HPVG is not an indication for surgery. The treatment strategies should focus on the underlying etiology, and patient’s disease severity determines whether surgery is necessary. The consensus on surgical indications has not yet been reached[27]. Moser et al[28] found that the mortality rate exceeded 50% when HPVG coexisted with intestinal necrosis. A retrospective study involving 182 patients with HPVG reported an overall mortality rate of 39%, which was soaring to 75% among those with intestinal necrosis. Thus exploratory laparotomy was recommended for such patients[2]. Bani Hani et al[29] used logistic regression to analyze the data of 209 HPVG patients, from multiple centers in the United States, and found that age over 60 years, signs of peritoneal irritation, and creatinine levels exceeding 25 mg/dL were independent risk factors for intestinal ischemia or intestinal necrosis, advocating for aggressive surgical treatment in these patients. Gonda et al[30] proposed a scoring system indicating that surgery should be promptly performed if two or more of the following indicators were present: CT indicated ascites, physical examination revealed peritoneal irritation, and unstable vital signs were indicative of shock. These may serve as indications for surgery, but need further validation in large cohorts. Timely surgical intervention has been shown to significantly benefit patients with intestinal thromboembolic diseases, reducing overall mortality from 72.8% to 40.6%[7]. Approximately 13% of patients with HPVG may present with altered consciousness as chief complaints, and a large portion of them exhibit severe shock early in the disease course, complicating the assessment of peritoneal irritation. In such cases, elevated lactate levels and decreased base excess may serve as important predictors of intestinal ischemia[31]. Furthermore, the following four CT findings, including unenhanced bowel wall, gas present in the bowel wall, mesenteric artery embolism, and free gas within the abdominal cavity, can indicate intestinal necrosis or perforation[32]. Because of the complexity of HPVG, mortality rates still reached 50% in the patients treated with timely surgical intervention. Anastomotic leaks after one-stage bowel resection and anastomosis was the main cause of death[5]. The relationship between the number of liver segments involved and prognosis remains controversial. Moussa et al[33] proposed that more than three liver segments affected with HPVG was associated with poor prognosis. Kinoshita et al[2] also found that involvement of three or more liver segments by portal venous gas was a significant marker of potential fatal outcomes, correlating with adverse prognoses in 75% of cases, suggesting that such patients should be approached with caution regarding surgical intervention. However, other studies argued that prognosis is not related to the volume of HPVG or the number of liver segments containing HPVG[26]. This correlation remains unproven and needs to be further demonstrated. In summary, surgery should be performed as soon as intestinal necrosis is found. Compared with exploratory laparotomy, laparoscopic surgery is not recommended, because of its limitations in assessing acute mesenteric artery embolism and high abdominal pressure affecting portal venous flow and bowel perfusion. Enterostomy is recommended instead of one-stage anastomosis after bowel resection[5]. Recent studies have suggested the use of near-infrared fluorescence angiography to assess bowel perfusion, which has potentially reduced the rate of postoperative intestinal fistula, although its effectiveness warrants further investigation[34].

Conservative management is suitable for HPVG patients with stable vital signs, non-ischemic disease, and mild or no signs of peritonitis[35]. Combining with literature review and clinical experience, we summarize the following insights: (1) Aggressive treatment of underlying etiologies is important. HPVG is a secondary phenomenon arising from primary diseases, and therefore treatment should aim at the primary etiology. Successful management of the underlying etiology can lead to the spontaneous resolution of HPVG and improved prognosis[36]; (2) Antibiotics should be administered in the early stage. Timely and appropriate antibiotic therapy is crucial in preventing the occurrence of infectious shock and necrotizing enterocolitis[37]. Patients with HPVG are at risk of bacteremia, and a recent study reported that approximately 42.8% of patients were tested positive in blood cultures[13]. According to the characteristics of the most commonly implicated bacteria, we can employ broad-spectrum antibiotics empirically, including piperacillin-tazobactam, cefperazone-sulbactam and imipenem[17,18]. It is necessary to collect blood and ascitic samples for bacterial culture and drug sensitivity detection, and tailor antibiotic therapy accordingly in the subsequent treatment process[13]; (3) Aggressive anti-shock therapy should be administered. Early signs of shock often include tachycardia, which is an independent risk factor for mortality in adult patients with HPVG[38]. Nearly all critical patients with HPVG exhibit severe shock early in their course[39]. Therefore, it is imperative to monitor for early signs of shock such as heart rate and urine output and implement corrective measures before shock occurs, utilizing a combination of crystalloids and colloids; (4) Anticoagulation therapy is necessary. Many patients with HPVG have underlying conditions such as hypertension and diabetes, which elevate thrombotic risk, and the occurrence of thrombosis can worsen the clinical condition[13]. Intestinal ischemia, especially acute mesenteric vascular thrombosis, is a major indication for anticoagulation treatment. It has also been suggested that thromboprophylaxis with low-molecular-weight heparin should be started early in HPVG patients[40]. For severe patients, anticoagulant therapy can improve blood flow and reduce the incidence of thrombosis. Unfractionated heparin or low-molecular-weight heparin can also be administered because of their lower risk of inducing bleeding when surgery is considered[41]. Effective use of the thromboembolic risk assessment tool such as Caprini assessment scale and Padua assessment scale are emphasized and we should remain vigilant for potential bleeding during anticoagulation. When bleeding occurs, the anticoagulant treatment should be stopped immediately; and (5) Clinical status should be dynamically assessed. It is essential to evaluate patients’ conditions dynamically, including the primary disease and its severity, rather than applying a one-size-fits-all treatment option. If intestinal necrosis occurs, timely surgical intervention is warranted. However, it is crucial to avoid overly aggressive expansions of surgical indications to prevent unnecessary harm. According to a recent retrospective analysis, including 25 consecutive adult patients with HPVG between 2009 and 2019, approximately 47.1% of surgical patients do not require bowel resection upon intraoperative evaluation[42]. Zhang et al[12] developed a multidisciplinary diagnostic and therapeutic pathway for HPVG mainly based on the classification of disease severity and supplemented by the classification of etiology, which offers valuable reference and application potential.

It is worth noting that perioperative management plays a crucial role in improving patient survival, and it often runs through the entire treatment process of the patient. We summarize the key points in perioperative management as follows: (1) Fluid resuscitation protocols: The administration of balanced crystalloid over normal saline is suggested in the initial resuscitation of shock, as administering a large dose of normal saline may lead to hyperchloremic metabolic acidosis and increase the risk of acute kidney injury[43]. Balanced crystalloid fluids, whose chloride concentration is similar to plasma, should be used instead of normal saline in adult patients with sepsis or septic shock. For patients who do not respond to the standard treatment with crystalloid fluids, isotonic albumin solutions may be considered[44]; (2) Antibiotics selection criteria: Broad-spectrum antibiotics, such as piperacillin-tazobactam, cefperazone-sulbactam and imipenem, should be empirically employed on the basis of the features of most commonly implicated bacteria[17,18]. In the subsequent treatment process, bacterial culture and drug sensitivity detection are able to guide the use of antibiotic therapy[13]. Metronidazole can be used for the treatment of anaerobic bacterial infections. Another proposed alternative therapy is hyperbaric oxygen, which can reduce the partial pressure of gas in the venous system and act as a toxin for anaerobic bacteria[45]. When there is a concern about fungal sepsis, a reliable approach is to increase empirical antifungal coverage and perform a beta-d-glucan testing[46]; (3) Vasopressor strategies for septic shock complicating HPVG: We recommend early administration of vasopressors with resuscitation fluids during the initial resuscitation of septic shock complicating HPVG. Norepinephrine is used as a first-line vasopressor for septic shock, and vasopressin is used as a second-line vasopressor for septic shock. Patients with septic shock who do not respond to initial fluid resuscitation are given low-dose hydrocortisone (200-300 mg/day) and vasopressors for recovery from shock[44]; and (4) Differentiating between infectious and thrombotic causes: A retrospective study involving 21 patients with HPVG found that C-reactive protein, procalcitonin (PCT), and D-dimer (DD-I) in patients with HPVG were higher than normal levels. The levels of PCT and C-reactive protein can indicate the degree of inflammation in patients[47]. As a degradation product of cross-linked fibrin, DD-I mainly reflects the fibrinolytic function and is used in the diagnosis of venous thromboembolism, deep vein thrombosis and pulmonary embolism. These biomarkers appear to be useful in distinguishing infectious cause from thrombotic cause. DD-I is more prone to thrombotic causes, while PCT is more prone to infectious causes. However, as the disease progresses, ischemia is often complicated with infection, which is easy to be confused. Therefore, they should be used in combination to improve the differential efficiency, but the final diagnosis depends on imaging and clinical evaluation[26].

In recent years, with the improvement of imaging techniques and treatment methods, the mortality rate has decreased from 75% to 40%[4]. Nevertheless, HPVG still has the characteristics of insidious onset, rapid progression and high mortality rate[48]. Many aspects such as exploration of biomarkers related to intestinal necrosis, artificial intelligence-assisted CT interpretation and prognostic related factors (age, comorbidities, and etiology) still require further research and verification. More prospective multicenter clinical studies should be conducted to provide reliable evidence for the diagnosis and treatment of HPVG in the future, thereby improving the prognosis of patients.

CONCLUSION

In summary, HPVG is a rare yet clinically significant imaging manifestation characterized by diverse etiologies, unclear pathophysiology, and nonspecific clinical presentations. Recent advancements in imaging technology have markedly improved the early diagnosis rates of HPVG and contributed to a reduction in mortality. However, it remains a perilous condition. Comprehensive imaging examinations, particularly contrast-enhanced abdominal CT, contribute to the early identification of underlying causes and thorough assessment of the clinical status. Treatment for HPVG should involve an adequate evaluation of the primary disease and its severity, and individualized therapeutic strategies while dynamically evaluating the patients’ conditions. Timely surgical intervention is warranted when intestinal necrosis occurs. Enterostomy may be considered instead of one-stage anastomosis after bowel resection. Clinicians must enhance their understanding of HPVG to improve diagnostic and therapeutic capacity, ultimately improving patient outcomes. Currently, there is still a lack of consensus on the diagnosis and treatment, surgical indications, surgical methods and prognosis evaluation for HPVG. Therefore, it is essential to conduct more prospective multicenter clinical studies to provide more reliable evidence for the diagnosis and treatment of HPVG in the future.