Tropical Infections of the Liver

Tropical Infections of the Liver

Tom Heller1,2, Michaëla A.M. Huson3, and Francesca Tamarozzi4

1 Lighthouse Clinic, Lilongwe, Malawi

2 International Training and Education Center for Health, University of Washington, Seattle, WA, United States

3 Radboud University Medical Center, Department of Internal Medicine and Radboud Center of Infectious Diseases (RCI), Nijmegen, The Netherlands

4 Department of Infectious Tropical Diseases and Microbiology, WHO Collaborating Centre on Strongyloidiasis and other Neglected Tropical Diseases, IRCCS Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, Verona, Italy

Ultrasound plays a key role in the diagnosis and management of hepatic infections. It is particularly helpful in resource‐limited, mainly tropical, settings where ultrasound is usually the first tool to screen, diagnose, guide treatment, and follow up cases, as it is often the only imaging modality available besides chest X‐ray [1]. Ultrasound is sensitive in the detection of many infections. However, it lacks specificity, particularly in necrotic abscess‐like infections, which can mimic benign (e.g. haemorrhagic cysts) or malignant (e.g. necrotic tumours) conditions. Like any diagnostic test, it is important to interpret it in the context of epidemiological and clinical details such as age, sex, and area of residence, exposure, presenting history, symptoms, and current immune status to achieve an accurate presumptive diagnosis. Often this needs to be narrowed down further by employing laboratory tests, for instance serology, or by using other diagnostic imaging modalities. Aspiration and biopsy are frequently required to conclude the final diagnosis and ultrasound is an ideal modality to guide this process.

In this chapter, we will summarise the most important infections of the liver, their sonographic presentations, further tests that may be utilised, and potential treatment options. Infections of the liver will be categorised as parasitic, bacterial, fungal, and viral. Viral hepatitis, although prevalent in many tropical areas and probably the most frequent liver infection worldwide, is not included in this chapter as it is discussed in more detail in Chapter 8.

Parasitic Infections of the Liver

Ultrasound can help with the detection of numerous parasitic diseases endemic in tropical regions. As ultrasound is the imaging mode of choice in echinococcosis and plays a key role in amoebic liver abscess (ALA), these topics will be described in more detail. Schistosomiasis is an important cause of portal hypertension in tropical settings and will also be addressed in detail. Other parasitic infections that can be detected by ultrasound will be described briefly, including Fasciola, Toxocara, Opisthorchis, Clonorchis, and Ascaris.

Cystic Echinococcosis

Introduction and Clinical Picture

Cystic echinococcosis (CE) is caused by the larval stage of the tapeworm Echinococcus granulosus sensu lato. CE has a worldwide distribution, and is especially prevalent in livestock‐raising areas. The natural cycle of the parasite develops between dogs and livestock. In humans, after accidental ingestion of parasite eggs from the environment, CE cysts may develop in any organ or tissue, most commonly in the liver (approximately 80% of cases) followed by the lungs (approximately 20% of cases). CE cysts evolve through stages, either spontaneously or as a consequence of treatment. When symptoms occur, they are due either to the growth of the cyst(s) exerting pressure on neighbouring structures, or to the loss of cyst integrity or its rupture, causing local and/or systemic manifestations. Symptoms are non‐specific and depend on the organ affected. For those in the liver, these include poor appetite, right upper quadrant pain, and jaundice. The most common complication is rupture, which can cause jaundice in case of communication with the biliary tree, anaphylactic reaction, or may be further complicated by superinfection or dissemination (secondary echinococcosis).

Ultrasound Features

Ultrasound is the examination of choice for the diagnosis and staging of abdominal CE cysts. The currently accepted international classification of CE cysts, based on hepatic ultrasound features, is the World Health Organization Informal Working Group on Echinococcosis (WHO‐) classification [2]. This includes six stages, each characterised by a pathognomonic sign that, when clearly visible, allows the diagnosis of CE (Figure 7.1):

  • CE1 ‘double‐wall sign’: univesicular cyst with anechoic content, with or without low‐intensity floating echoes on decubitus change and with a visible ‘double‐wall sign’ consisting of an inner hyperechoic and outer hypoechoic wall. Pathognomonic sign: double‐wall sign.
  • CE2 ‘honeycomb sign’: multivesicular cyst with one or more daughter cysts filling the cyst in part or completely, causing a ‘honeycomb’ appearance. Pathognomonic sign: the adjacent walls of juxtaposed daughter cysts are clearly distinguishable, thin, regular, continuous, and avascular.
  • CE3a ‘water lily sign’: univesicular cyst with partial or complete detachment of the inner parasitic layers, visible as a hyperechoic thin and folded membrane floating in the anechoic cyst content. Pathognomonic sign: the whole membrane must be identified as a continuous, regular, hyperechogenic structure.
  • CE3b ‘Swiss cheese sign’: multivesicular cyst with heterogeneous structure, encompassing (i) avascular solid components and hypoechoic folded structures deriving from degenerating membranes, and (ii) one or more daughter cysts with anechoic content. Pathognomonic sign: heterogeneous cyst containing daughter cysts and hypoechoic folded structures.
  • CE4 ‘ball of wool sign’: mass with heterogeneous avascular solid content containing hypoechoic folded structures. Pathognomonic sign: hypoechoic folded structures deriving from degenerating membranes visible in the solid heterogeneous matrix.
  • CE5 ‘eggshell pattern’: a CE4 stage CE cyst (with its visible pathognomonic sign) with complete or nearly complete eggshell‐like peripherally calcified wall.
Six ultrasound scan images are arranged in two rows and three columns. They are titled as follows. C E 1, C E 2, C E 3, C E 4, C E 3a, C E 3b, C E 5. Below the first column labeled Albendazole P A I R + Albendazole. Below the second column labeled Non-P A I R percutaneous treatment + Albendazole Surgery + Albendazole. Below the third column labeled watch and wait.

Figure 7.1 CE cyst stages and suggested stage‐specific clinical management of cystic echinococcosis (CE). PAIR = puncture, aspiration, injection of a scolicidal agent, and re‐aspiration. Non‐PAIR percutaneous treatments include several percutaneous techniques using cutting instruments and large‐bore catheters to evacuate the entire cyst content.

Source: Bélard S et al. (2016), The American Society of Tropical Medicine and Hygiene.

It is important to remember that some calcification in CE cysts can occur at any stage (i.e. presence of calcification alone does not classify a CE cyst as CE5 stage), but these calcifications are always peripheral. CE cysts are also always avascular, therefore the presence of Doppler signal within the cyst excludes the diagnosis of CE.

Further Investigations

Rule‐in/rule‐out diagnosis in case of suspected CE can be achieved by the following:

  • Serology is not standardised and is characterised by false‐positive and false ‐negative results. In general, CE can be confirmed by two concordant positive first‐line tests performed in parallel or at least one positive West Blot test. A negative serology does not rule out CE. Generally, patients with extrahepatic cysts and with single, small hepatic CE1 cysts or CE4–5 cysts are seronegative in a large percentage of cases. Particular care must be taken when interpreting serology for CE in co‐endemic areas for both cystic and alveolar echinococcosis (AE; see the section on AE).
  • Albendazole as a treatment trial (ex juvantibus): in the presence of liquid‐content lesions, albendazole intake for one month followed by visualisation of a response on ultrasound (e.g. CE1 developing into CE3a stage) and/or seroconversion (if previously seronegative).
  • Presence of contrast enhancement rules out CE: CE intracystic components do not enhance, although slight enhancement of the cyst wall may be observed.
  • Diagnostic percutaneous puncture followed by microscopy of the cyst content or polymerase chain reaction (PCR).

Magnetic resonance imaging (MRI) performs better than computed tomography (CT) in defining the pathognomonic features of CE cysts; these techniques are mainly required pre‐operatively to define the relation of the cyst with neighbouring structures.

Treatment and Follow‐Up

Asymptomatic hepatic CE should be managed using a stage‐specific approach:

  • CE1 and CE3a: especially if <5 cm, albendazole for 3–6 months continuously; for larger cysts, percutaneous treatment, if available, associated with albendazole prophylaxis for 1–3 months to prevent dissemination. Surgery associated with albendazole prophylaxis may be indicated for very large or superficial cysts.
  • CE2 and CE3b: surgery associated with albendazole prophylaxis. Medical therapy with albendazole may be attempted, especially if cysts are small, but there is a high recurrence rate. If available, modified percutaneous techniques associated with albendazole prophylaxis may also be envisaged.
  • CE4 and CE5: watch‐and‐wait approach, with only regular follow‐up every 6–12 months by ultrasound imaging to detect possible reactivations. These are rare if the CE4–5 stage was reached spontaneously.

Symptomatic CE should be treated surgically. Some experts also add peri‐operative praziquantel to albendazole in cases of invasive procedures. An alternative, less effective drug than albendazole is mebendazole. During albendazole intake, regular (e.g. monthly) monitoring of blood cell counts and liver enzymes is recommended. Ultrasound follow‐up is indicated yearly for a minimum of five years.

Alveolar Echinococcosis

Introduction and Clinical Picture

AE is caused by the larval stage of the tapeworm Echinococcus multilocularis. Similar to CE, humans acquire infection through accidental ingestion of parasite eggs, but AE infection is much less frequent than CE, it only occurs in the Northern Hemisphere, and its cycle is sylvatic. The natural cycle of the parasite develops between wild canids (especially foxes) and different species of small rodents. AE lesions are infiltrative and metastasising tumour‐like lesions, cholangiocarcinoma being the main differential diagnosis. The primary organ affected is almost invariably the liver. AE lesions grow slowly and the asymptomatic period may last 5–15 years or longer; many infections are diagnosed at a late stage. Jaundice is the most common presenting symptom, often associated with itching, right upper quadrant pain, and fever in case of cholangitis or superinfection of the necrotic centre of the lesion. Loco‐regional extension and distant metastases may cause a variety of symptoms. The WHO‐IWGE classifies AE by PNM staging (P = extent and location of the parasitic lesion; N = invasion of neighbouring organs; M = presence of metastases).

Ultrasound Features

According to ultrasound appearance different AE’s sonographic patterns are described [2, 3] (Figure 7.2):

  • The hailstorm pattern is the most frequent, being observed in approximately half of AE patients. It is characterised by an irregular border and heterogeneous content, often with scattered hyperechoic formations with or without posterior acoustic shadowing.
  • The pseudocystic pattern is characterised by a hyperechoic, irregular and non‐homogeneous rim, with no sign of vascularity at color Doppler or CEUS.
  • The ossification pattern is characterised by solitary or grouped, mostly sharply delineated lesions with posterior acoustic shadowing.
  • The haemangioma‐like pattern is characterised by a relatively clearly demarcated heterogeneous hyperecoic lesion that may be difficult to distinguish from a typical haemangioma.
  • The metastases‐like pattern is mostly characterised by hypoechoic lesion or lesions with a central non‐homogeneous hyperechoic scar. They are very difficult to distinguish from some liver neoplastic metastasis that show a hypoechoic halo.

In comparison to CE, no pathognomonic imaging signs of AE exist and especially the haemangioma‐ and metastasis‐like patterns may pose a diagnostic challenge. However, the presence of calcifications and the pattern of contrast enhancement may suggest the diagnosis of AE.

Five sonographic patterns of different ultrasound images. a. Hailstorm. b. pseudocystic. c. ossification. d. hemangioma. e. metastais. It contains three columns. The first column depicts the five sonographic patterns, and the second and the third column contains their respective ultrasound images.

Figure 7.2 Sonographic patterns of E. multilocularis (a) ‘Hailstorm’, (b) ‘pseudocystic’, (c) ‘ossification’, (d) ‘hemangioma‐like’ and (e) ‘metastais like’ appearance of alveolar echinococcosis lesions.

Source: Courtesy of Dr Claudia Wallrauch.

Further Investigations

Serology is almost invariably positive; however, high cross‐reactivity exists with CE, which makes the differential diagnosis between the two infections at times difficult, especially in co‐endemic areas. Definitive diagnosis may be achieved by biopsy followed by histology or PCR. If untreated, the prognosis of AE is poor.

Treatment and Follow‐Up

After assessment of the extension of the disease, the options may be curative resection (partial debulking should be avoided) followed by two years of albendazole, or prolonged, often life‐long, albendazole administration, with interventional radiology or endoscopic procedures if complications occur. In some cases, liver transplant followed by albendazole may be an option. Regular follow‐up with serology, imaging, and monitoring of blood cell counts, aminotransferases, and albendazole‐sulfoxide blood levels is required. Discontinuation of albendazole treatment may be possible in case of seronegativity and negative fluorodeoxyglucose–positron emission tomography (FDG‐PET; delayed imaging acquisition).

Amoebic Liver Abscess

Introduction and Clinical Picture

Amoebic liver abscess (ALA) is the most common extraintestinal manifestation of Entamoeba histolytica infections and around 8% of patients with intestinal amoebiasis develop hepatic abscesses. In tropical settings they are far more common than bacterial abscesses. After ingestion of the amoebic cysts through contaminated food or water, amoeba trophozoites develop in the bowel and cause amoebic colitis, although the infection is often asymptomatic. In some cases the parasites invade the mucosa and travel via the mesenteric and portal veins to the liver. Here substantial liquefaction necrosis of hepatocytes is induced 5–7 days after arrival of the amoeba in the liver, explaining the abrupt clinical onset with fever, right upper quadrant pain, and leucocytosis in previously healthy individuals. For unknown reasons ALAs are more frequent in adults than in children and more frequent in male than in female patients.

Ultrasound Features

ALAs are more frequently seen in the right liver lobe (77%); the most common location is the posterior segment of the right lobe. In the majority of patients a single lesion is found; nevertheless, about 40% of patients have two or more lesions. On ultrasound, typically a hypoechoic lesion measuring about 4–10 cm is seen (Figure 7.3). Inside the lesion there are often fine internal echoes. The shape is round and regular; due to the reduced echogenicity, mild distal acoustic enhancement is seen. The lesion usually lacks significant wall echoes. All of these features may also occur in pyogenic abscesses and are thus not sufficient to make a distinction between the two.

An ultrasound scan image of round hypoechoic amoebic liver abscess without significant walls in the dorsal segments of the right lobe.

Figure 7.3 Round hypoechoic amoebic liver abscess without significant wall in the dorsal segments of the right lobe.

Rarely, ALAs can present with atypical patterns like echogenic nodules, thick echogenic walls, mural nodules, and septations, causing difficulties in the differential diagnosis of solid masses and other lesions.

Further Investigations

Sonographic findings need to be combined with clinical information and serological results to reach the correct diagnosis. Diagnostic aspiration is an option and produces an ‘anchovy sauce’–like product, but it is rarely indicated. Serology for anti‐amoebic antibodies will be positive in more than 90% of patients with ALA and in combination with the history and the ultrasound findings it is usually diagnostic.

Treatment and Follow‐Up

The treatment of choice is metronidazole. Usually a very rapid clinical response is seen within days – sonographically lesions shrink far more slowly. Initially the lesions tend to lose echogenicity with effective treatment and can become anechoic. For uncomplicated ALA there is no strong evidence for percutaneous aspiration or drainage over medical treatment only. Indications for percutaneous drainage are lack of response to metronidazole therapy, multiple or very large lesions, and continuing diagnostic uncertainty. ALAs may rupture into the pericardium, pleural cavity, or peritoneal cavity if they are located superficially. Prevention of these complications is another reason for initial drainage.

Time to complete resolution depends on the initial size of the lesion; it may take up to 3–6 months. In approximately 5% of ALA patients the resolution is not complete and post‐ALA residual lesions may be found. These are usually hypo‐ to isoechoic compared to liver tissue and show a hyperechoic wall. The residual lesions were found to persist for more than a decade and may pose differential diagnostic problems.

Liver Schistosomiasis

Introduction and Clinical Picture

While genito‐urinary schistosomiasis is caused by infection with the trematode Schistosoma haematobium, all other Schistosoma species affecting humans, mainly S. mansoni and less frequently S. japonicum and other species, cause intestinal and hepato‐splenic schistosomiasis. S. mansoni

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Feb 17, 2024 | Posted by in CARDIOVASCULAR IMAGING | Comments Off on Tropical Infections of the Liver

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