We report the clinical case of 23-year-old patient with liver cirrhosis of unknown genesis, significant resistant ascites, and 2 episodes of bleeding from esophageal varices. Evaluation did not find any cause of liver disease, and the patient was placed on the transplant wait list due to subcompensated liver function (Model for End-Stage Liver Disease score of 16, Child-Pugh class B) and poorly controlled severe portal hypertension. After treatment with diuretics, large-volume paracentesis, antibiotics, and vasoconstrictors, hepatorenal syndrome and spontaneous bacterial peritonitis resolved and liver function improved significantly. Because the patient showed consistently good liver function and resistant portal hypertension, liver transplant was delayed with decision to perform transjugular intrahepatic portosystemic shunting instead. During the attempt of shunting, occlusive thrombosis of the iliac veins, inferior vena cavae, and hepatic veins were diagnosed and the procedure was stopped. Therefore, considering preserved liver function and severe portal hypertension, diagnosis of Budd-Chiari syndrome with subsequent development of liver cirrhosis was made. The patient was recommended to undergo evaluation to exclude thrombophilia as a cause of thrombosis.

Key words : Hepatic vein thrombosis, Inferior vena cavae thrombosis, Liver cirrhosis, Portal hypertension, Transjugular intrahepatic portosystemic shunt

Introduction

In November 2015, a 23-year-old Kazakh male patient was admitted with enlargement of the abdomen with hernia, weakness, and feeling of heaviness in the right upper abdominal quadrant. The disease had first manifested itself with asthenia and swelling of the feet in 2012, with later development of ascites and profound weight loss of up to 30 kg in 3 months (initial weight of 91 kg). The ascites was successfully treated with diuretics. Evaluation at a regional hospital found no markers of viral hepatitis and no signs of autoimmune-related, alcohol-induced, or metabolic liver disease. Portal hypertension with esophageal varices and splenomegaly were unlikely to be related to liver cirrhosis due to normal liver function and no signs of decompensation.

In January 2013, the patient experienced the first bleeding from esophageal varices, followed by a second episode in October 2013, both controlled by Sengstaken-Blakemore tube insertion. In March 2014, paracentesis was performed for therapeutic purposes with removal of up to 12 L of ascitic fluid.

At admittance to our inpatient clinic in November 2015, the patient appeared to be well developed, but undernourished, with body mass index of 19 kg/m2. Physical examination was remarkable for significant ascites with reducible umbilical hernia of up to 10 cm in diameter and multiple caput medusae on the abdominal wall (Figure 1). Chronic liver disease stigmata, including telangiectases on chest and palmar erythema, were also present. Contrast-enhanced computed tomography (CT) revealed no signs of vascular thrombosis in portal vein/inferior vena cava and up to 6 L ascitic fluid; we also observed 2 lesions in liver of up to 15 mm in segments V and VI, with wash-out phenomenon in venous phase (Figure 2). We could not obtain a biopsy because of significant ascites and the small size of lesions. A diagnosis of hepatocellular carcinoma (HCC) was made due to characteristic features by CT.

The patient was started on diuretics and paracentesis with removal of up to 5 L of ascitic fluid. The latter was unremarkable for other causes other than portal hypertension at assessment. Hepatorenal syndrome, diagnosed at admittance, and spontaneous bacterial peritonitis were successfully treated with octreotide and ceftriaxone, with subsequent normalization of kidney function (Table 1). Ligation of esophageal varices was performed due to endoscopic stigmata of the risk of bleeding. Because the umbilical hernia was reducible and did not require immediate operation, it was recommended to be addressed later.

Considering the unknown cause of the liver disease, a discrepancy between the severity of the portal hypertension, and the relatively good function of the liver, a diagnosis of idiopathic portal hypertension with subsequent development of liver cirrhosis was made. Repeatedly performed abdominal ultrasonography and CT failed to visualize any cause of portal hypertension in the patient. The subcompensated liver cirrhosis (Model for End-Stage Liver Disease score of 16, Child-Pugh class B) and poorly controlled severe portal hypertension were indications for liver transplant. The patient was subsequently placed on a transplant wait list and discharged in early December 2015.

Despite recommendations at discharge regarding need for evaluation and consultation of a hepatologist and transplant specialist every 3 months, the patient was not seen at our facility until September 2016. He had undergone another abdominal tapping with removal of 11 L of ascitic fluid in May 2016. The patient was admitted to our inpatient clinic in September 2016 with his 30-year old brother as a potential living liver donor. The appearance of the patient had not changed compared with that of November 2015, with significant resistant ascites, caput medusa, and inguinal hernia still present. Due to no signs of thrombosis and lesions in the liver by abdominal ultrasonography, preserved liver function (Table 2), and resistant ascites, liver transplant was delayed, with the decision to insert a transjugular intrahepatic portosystemic shunt (TIPS) instead.

During the attempt to insert the TIPS, the shunt failed to pass further to the level of confluence of hepatic veins in the inferior vena cava (IVC) (Figure 3). Further attempts to visualize the IVC system via iliac veins revealed signs of thrombosis extending to the IVC and hepatic veins (Figures 4-6). Occlusive thrombosis of the iliac veins, IVC, and hepatic veins were contraindications for TIPS, and the procedure was stopped.

The patient was started on low-molecular-weight heparin (0.6 mL/day) and then switched to rivaroxaban (10 mg/day) for long-term use. Further evaluation did not find any other sites of thrombosis, including legs, chest area, and neck. When we considered the severe portal hypertension without signs of decompensated liver disease and occlusive thrombosis of the hepatic veins, extending to IVC and iliac veins, a diagnosis of Budd-Chiari syndrome with subsequent development of liver cirrhosis was made. The patient has been recommended to undergo evaluation by a hematologist to exclude thrombophilia as a cause of thrombosis.

Discussion

Budd-Chiari syndrome is a rare condition associated with obstruction of the hepatic venous outflow, which could occur anywhere from the hepatic venules up to the junction of the IVC and right atrium. The disease usually progresses, leading to a worsening patient state if no intervention is applied. Because most treatment decisions of patients with Budd-Chiari syndrome are based on an expert opinion and are not evidence-based, a clear management algorithm for this life-threatening condition has not yet been established. Although 4325 publications on Budd-Chiari syndrome have been published up to 2014, only 421 (9.7%) have been cohort studies, 45 (1%) have been case-control studies, and none have been randomized controlled trials.¹ This demonstrates the need for adequately powered cohort studies or controlled trials to determine the natural history of this disease and the optimal intervention strategy.

To stratify patients into subgroups with the subsequent optimal treatment options, several prognostic scores have been applied to patients with Budd-Chiari syndrome, such as Budd-Chiari syndrome-TIPS, Child-Pugh, the Clichy prognostic index, Model for End-Stage Liver Disease, the new Clichy prognostic index, and the Rotterdam index.² None have been able to reach an area under the curve value of more than 0.7, thus being difficult to recommend for treatment of an individual patient.3 Thus, in clinical practice, the optimal strategy would be a step-wise move to a more invasive therapeutic option if there have been no adequate responses to less invasive treatments.⁴

A reasonable step-wise strategy for most cases would be starting anticoagulation, then angioplasty or stenting, followed by vascular decompression (surgical shunting or TIPS), and finally liver transplant in case of hepatic failure. Resistant ascites, persistent encephalopathy, and decompensation of the liver function have been proposed as criteria for stepping up.⁵ Different types of liver lesions have been described in patients with Budd-Chiari syndrome, including large regenerative nodules, mimicking HCC.⁶ Our patient also had liver lesions when first admitted resembling HCC, but follow-up evaluation did not confirm it. Considering the liver cirrhosis in the patient, they were most likely regenerative nodules.

Our patient received anticoagulation therapy, with obvious contraindications for TIPS. Liver transplant was not needed at the patient's current stage due to normal liver function, absence of HCC, and occlusive thrombosis of the IVC and hepatic veins. According to the above-mentioned step-wise strategy, angioplasty/stenting or surgical decompression/shunting might be optimal treatment options for our patient; however, since discharge in October 2016, we have lost contact with this patient.

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